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Global Guidelines for the Prevention of Surgical Site Infection. Geneva: World Health Organization; 2018.

Cover of Global Guidelines for the Prevention of Surgical Site Infection

Global Guidelines for the Prevention of Surgical Site Infection.

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4Evidence-Based Recommendations on Measures for the Prevention of Surgical Site Infection

Preoperative Measures

4.1. Preoperative bathing

Recommendations

It is good clinical practice for patients to bathe or shower prior to surgery.

The panel suggests that either a plain or antimicrobial soap may be used for this purpose.

(Conditional recommendation, moderate quality of evidence)

The panel decided not to formulate a recommendation on the use of chlorhexidine gluconate (CHG)-impregnated cloths for the purpose of reducing SSI due to the limited and very low quality evidence.

Rationale for the recommendation

  • The GDG considers it good clinical practice to bathe or shower before surgery to ensure that the skin is as clean as possible and to reduce the bacterial load, especially at the site of incision. Moderate quality evidence shows that preoperative bathing with antimicrobial soap containing CHG has neither benefit nor harm compared to plain soap in reducing the SSI rate. As no study was available using antimicrobial agents other than CHG, the GDG unanimously agreed that either plain or antimicrobial soap may be used.
  • Evaluation of the evidence from 3 observational studies showed that preoperative bathing with 2% CHG-impregnated cloths may have some benefit in reducing the SSI rate when compared to bathing with CHG soap or no preoperative bathing. However, in 2 of these studies, the comparison group was inadequate as it included patients who did not comply with instructions to use the cloths preoperatively. This limited and very low quality evidence was considered as insufficient to make any recommendation regarding the use of CHG cloths. All GDG members agreed not to formulate a recommendation on this topic, apart from one member who would have preferred to have a recommendation discouraging the use of CHG-impregnated cloths due to concerns about the waste of resources if these products are purchased, especially in developing countries.

Remarks

  • Although no study including paediatric patients was retrieved, the GDG believes that the good practice statement on the importance of patient bathing applies also to paediatric patients. However, if performed with antimicrobial soap, the manufacturer’s instructions should be followed regarding the suitability for this age category.
  • The GDG identified possible harm associated with the use of CHG-containing solutions, although it was stressed that this is a rare occurrence. Two studies (1, 2) found that CHG solutions may cause skin irritation, delayed reactions, such as contact dermatitis and photosensitivity, and hypersensitivity reactions in very rare cases, such as anaphylactic shock. Some of these potential adverse events may be induced also by ingredients of regular soap, such as fragrances. A concern of the GDG was the possible development of reduced susceptibility to CHG, particularly when using CHG-impregnated cloths (3).
  • The GDG also expressed concern about the cost of CHG-impregnated cloths, in particular in settings with limited resources where other interventions may have a higher priority.

Background

Preoperative whole-body bathing or showering is considered good clinical practice to make the skin as clean as possible prior to surgery in order to reduce the bacterial load, especially at the site of incision. This is generally done with an antimicrobial soap (usually CHG 4% combined with a detergent or in a triclosan preparation) in settings where this is available and affordable (4, 5).

Preoperative showering with antiseptic agents is a well-accepted procedure for reducing skin microflora (68), but it is less clear whether this procedure leads to a lower incidence of SSI (7, 8). Although rare, patient hypersensitivity and allergic reactions to CHG can occur (1).

When considering the available evidence, the most relevant question is whether preoperative bathing or showering with an antimicrobial soap is more effective than plain soap to reduce SSI. The GDG also considered it relevant to investigate whether using CHG-impregnated cloths rather than bathing with CHG soap is more effective.

Several organizations have issued recommendations regarding preoperative bathing (Table 4.1.1). Most recommend bathing with soap the day of the operation or the day before. Only the US Institute of Healthcare Improvement bundle for hip and knee arthroplasty recommends CHG soap for preoperative bathing. Others state that the use of an antimicrobial soap instead of plain soap is an unresolved issue.

Table 4.1.1. Recommendations on preoperative bathing according to available guidelines.

Table 4.1.1

Recommendations on preoperative bathing according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the effectiveness of preoperative bathing or showering with antimicrobial soap (including CHG-impregnated cloths) compared to plain soap and to determine if the former should be recommended for surgical patients to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 2) was to evaluate whether preoperative bathing using an antimicrobial soap is more effective in reducing the risk of SSI than bathing with plain soap. The review evaluated also whether preoperative bathing with CHG-impregnated cloths is more effective than using an antimicrobial soap. The target population included patients of all ages undergoing a surgical procedure. The primary outcome was occurrence of SSI and SSI-attributable mortality.

A total of 9 studies (7 RCTs and 2 observational studies) including a total of 17 087 adult patients (2, 1623) investigated preoperative bathing or showering with an antimicrobial soap compared to plain soap.

There is a moderate quality of evidence that bathing with CHG soap does not significantly reduce SSI rates compared to bathing with plain soap (OR: 0.92; 95% CI: 0.80–1.04).

Three observational studies (2426) examined the effectiveness of bathing with CHG-impregnated cloths on SSI rates. One prospective cohort study (24) compared bathing with CHG 2% cloths vs. CHG 4% antiseptic soap. Two other prospective studies (25, 26) compared bathing twice preoperatively with CHG 2%-impregnated cloths to no preoperative bathing among orthopaedic surgery patients. In the latter studies, the comparison group was inadequate as it comprised patients who did not comply with instructions to use the cloths preoperatively (and therefore most likely did not bathe). No RCTs meeting the specified inclusion criteria were identified.

There is only very low quality evidence that preoperative bathing with CHG-impregnated cloths may reduce SSI rates when compared to either bathing with CHG soap or no bathing. The body of retrieved evidence focused on adult patients and no studies were available in the paediatric population. No studies reported SSI-attributable mortality rates.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG acknowledged that most people with access to water would bathe prior to surgery. It was highlighted that patients wish to be informed of best clinical practice and they will tend to carry out the procedures that they were told to do by the professional health care worker. Some GDG members highlighted that patients may value CHG-impregnated cloths if access to clean water is limited. However, others emphasized that the evidence on the use of CHG-impregnated cloths is very low quality and their use could contribute to CHG resistance.

Resource use

The GDG pointed out that the availability of and access to clean water can be a problem in rural areas in LMICs and preoperative bathing may be neglected. In addition, antimicrobial soap will place an additional financial burden on the health care facility and/or patients in many of these countries. Similarly, CHG-impregnated cloths will pose an additional important financial burden and availability might be very limited in LMICs. Plain soap is more widely available and cheaper than antimicrobial soap.

A cost-effectiveness study (16) found that preoperative whole-body washing with a CHG solution is not a cost-effective intervention for reducing SSI. However, it is important to note that this study predominantly consisted of clean surgical procedures for which the risk of SSI is low. Findings from 2 additional studies suggested that the use of CHG-impregnated cloths could lead to reducing health care costs, mainly by decreasing the incidence of SSI (27, 28).

Research gaps

GDG members highlighted that the available evidence compared only CHG as the antiseptic agent to bathing with plain soap. Further research is needed to compare different antiseptic agents to each other and to plain soap for preoperative bathing. Well-designed RCTs and cost-effectiveness analyses are also needed to examine the timing and duration of bathing and its importance in the context of different types of surgery and wound classes, especially in LMICs. In addition, microbiological studies of contamination levels could be of interest. Finally, well-designed RCTs are needed to produce better quality results on the effectiveness of CHG-impregnated cloths to reduce SSI and their cost implications, in particular in low-resource settings. The long-term impact of the use of CHG on the possible induction of CHG resistance should also be studied, particularly CHG-impregnated cloths. Further research is also needed to clarify the effect of soap or antiseptics on the skin microbiome.

References

1.
Krautheim AB, Jermann TH, Bircher AJ. Chlorhexidine anaphylaxis: case report and review of the literature. Contact Dermatitis. 2004;50(3):113–6. [PubMed: 15153122]
2.
Byrne DJ, Napier A, Cuschieri A. Prevention of postoperative wound infection in clean and potentially contaminated surgery. A prospective, randomised, double-blind, placebo-controlled clinical trial. Surg Res Comm. 1992;12:43–52.
3.
Horner C, Mawer D, Wilcox M. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter? J Antimicrob Chemother. 2012;67(11):2547–59. [PubMed: 22833635]
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Derde LP, Dautzenberg MJ, Bonten MJ. Chlorhexidine body washing to control antimicrobial-resistant bacteria in intensive care units: a systematic review. Intensive Care Med. 2012;38(6):931–9. [PMC free article: PMC3351589] [PubMed: 22527065]
5.
Koburger T, Hubner NO, Braun M, Siebert J, Kramer A. Standardized comparison of antiseptic efficacy of triclosan, PVP-iodine, octenidine dihydrochloride, polyhexanide and chlorhexidine digluconate. J Antimicrob Chemother. 2010;65(8):1712–9. [PubMed: 20551215]
6.
Garibaldi RA. Prevention of intraoperative wound contamination with chlorhexidine shower and scrub. J Hosp Infect. 1988;11(Suppl. B):5–9. [PubMed: 2898503]
7.
Kaiser AB, Kernodle DS, Barg NL, Petracek MR. Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers. Ann Thorac Surg. 1988;45:35–8. [PubMed: 3337574]
8.
Seal LA, Paul-Cheadle D. A systems approach to preoperative surgical patient skin preparation. Am J Infect Control. 2004;32:57–62. [PubMed: 15057196]
9.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
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Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337:a1924. [PubMed: 18957455]
11.
Surgical site infection: evidence update 43 (June 2013). London: National Institute for Health and Care Excellence (NICE); 2013 (http://www​.nice.org.uk​/guidance/cg74/evidence​/evidence-update-241969645, accessed 21 July 2016)..
12.
Targeted literature review: What are the key infection prevention and control recommendations to inform a surgical site infection (SSI) prevention quality improvement tool? Edinburgh: Health Protection Scotland; version 3.0, February 2015 (http://www​.documents​.hps.scot.nhs.uk/hai​/infection-control/evidence-for-care-bundles​/literature-reviews​/ssi-review-2015-02.pdf, accessed 21 July 2016).
13.
Owens P, McHugh S, Clarke-Moloney M, Healy D, Fitzpatrick F, McCormick P, et al. Improving surgical site infection prevention practices through a multifaceted educational intervention. Ir Med J. 2015;108(3):78–81. [PubMed: 25876299]
14.
How-to guide: prevent surgical site infection for hip and knee arthroplasty: Cambridge (MA): Institute for Healthcare Improvement; 2012 (http://www​.ihi.org, accessed 21 July 2016).
15.
High impact intervention: care bundle to prevent surgical site infection. London: Department of Health; 2011 (http://webarchive​.nationalarchives​.gov.uk​/20120118164404/http://hcai​.dh.gov.uk/files​/2011/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL.pdf, accessed 21 July 2016).
16.
Lynch W, Davey PG, Malek M, Byrne DJ, Napier A. Cost-effectiveness analysis of the use of chlorhexidine detergent in preoperative whole-body disinfection in wound infection prophylaxis. J Hosp Infect. 1992;21(3):179–91. [PubMed: 1353510]
17.
Rotter ML. A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on postoperative wound infection rates. J Hosp Infect. 1988;12:137–8. [PubMed: 2905721]
18.
Earnshaw JJ, Berridge DC, Slack RC, Makin GS, Hopkinson BR. Do preoperative chlorhexidine baths reduce the risk of infection after vascular reconstruction? Europ J Vasc Surg. 1989;3(4):323–6. [PubMed: 2670608]
19.
Hayek LJ, Emerson JM. Preoperative whole body disinfection--a controlled clinical study. J Hosp Infect. 1988;11(Suppl. B):15–19. [PubMed: 2898499]
20.
Randall PE, Ganguli LA, Keaney MG, Marcuson RW. Prevention of wound infection following vasectomy. Br J Urology. 1985;57:227–9. [PubMed: 3986461]
21.
Veiga DF, Damasceno CA, Veiga-Filho J, Figueiras RG, Vieira RB, Garcia ES, et al. Randomized controlled trial of the effectiveness of chlorhexidine showers before elective plastic surgical procedures. Infect Control Hosp Epidemiol. 2008;30:77–9. [PubMed: 19046051]
22.
Ayliffe GA, Noy MF, Babb JR, Davies JG, Jackson J. A comparison of pre-operative bathing with chlorhexidine-detergent and nonmedicated soap in the prevention of wound infection. J Hosp Infect. 1983;4:237–44. [PubMed: 6195236]
23.
Leigh DA, Stronge JL, Marriner J, Sedgwick J. Total body bathing with ‘Hibiscrub’ (chlorhexidine) in surgical patients: a controlled trial. J Hosp Infect. 1983;4:229–35. [PubMed: 6195235]
24.
Graling PR, Vasaly FW. Effectiveness of 2% CHG cloth bathing for reducing surgical site infections. AORN J. 2013;97(5):547–51. [PubMed: 23622827]
25.
Johnson AJ, Daley JA, Zywiel MG, Delanois RE, Mont MA. Preoperative chlorhexidine preparation and the incidence of surgical site infections after hip arthroplasty. J Arthroplasty. 2010;25(6;Suppl.):98–102. [PubMed: 20570089]
26.
Johnson AJ, Kapadia BH, Daley JA, Molina CB, Mont MA. Chlorhexidine reduces infections in knee arthroplasty. J Knee Surg. 2013;26(3):213–8. [PubMed: 23288739]
27.
Bailey RR, Stuckey DR, Norman BA, Duggan AP, Bacon KM, Connor DL, et al. Economic value of dispensing home-based preoperative chlorhexidine bathing cloths to prevent surgical site infection. Infect Control Hosp Epidemiol. 2011;32(5):465–71. [PMC free article: PMC3386002] [PubMed: 21515977]
28.
Kapadia BH, Johnson AJ, Daley JA, Issa K, Mont MA. Pre-admission cutaneous chlorhexidine preparation reduces surgical site infections in total hip arthroplasty. J Arthroplasty. 2013;28(3):490–3. [PubMed: 23114192]

4.2. Decolonization with mupirocin ointment with or without chlorhexidine gluconate body wash for the prevention of Staphylococcus aureus infection in nasal carriers undergoing surgery

Recommendations

  1. The panel recommends that patients undergoing cardiothoracic and orthopaedic surgery with known nasal carriage of S. aureus should receive perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash.
    (Strong recommendation, moderate quality of evidence)
  2. The panel suggests considering to treat also patients with known nasal carriage of S. aureus undergoing other types of surgery with perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash.
    (Conditional recommendation, moderate quality of evidence)

Rationale for the recommendation

  • Moderate quality evidence shows that the use of mupirocin 2% ointment with or without a combination of CHG body wash in surgical patients with S. aureus nasal carriage has significant benefit when compared to placebo/no treatment in reducing the S. aureus SSI rate, as well as the overall S. aureus HAI rate.
  • The GDG carefully considered this evidence and the additional subgroup analysis conducted by the systematic review team. The GDG concluded that the evidence is most solid for the cardiothoracic and orthopaedic patient population and that recommending the intervention with the same strength for all surgical patients would pose cost and feasibility constraints, including diagnostic implications to identify carriers among all surgical patients.
  • As a result, the GDG agreed to recommend that cardiothoracic and orthopaedic surgical patients with known nasal carriage of S. aureus should receive perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash. The strength of this recommendation was considered to be strong. Although the risk and consequences of postoperative S. aureus infection are more relevant in cardiothoracic and orthopaedic surgery, the GDG noted that the data from the meta-analysis and meta-regression show that patients with known S. aureus nasal carriage undergoing other types of surgery might also benefit from perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash. The strength of this recommendation was considered to be conditional and the GDG proposed to use the terminology “The panel suggests considering…” to highlight the need for careful local evaluation about whether and how to apply this recommendation, in particular regarding feasibility of carriers’ identification in a broader surgical patient population and cost effectiveness.
  • In patients undergoing other types of surgery to be targeted with this intervention, it is advisable to take other factors into account, such as the local rates of S. aureus and methicillin-resistant S. aureus (MRSA) and patient-related factors. Among the latter, the most important are past S. aureus infection, known carrier status of community-acquired MRSA, and patients colonized by S. aureus in sites other than the nose.
  • The GDG emphasized that the recommendation to use mupirocin with or without a combination of CHG body wash is derived from the available evidence as CHG 4% soap was used for full body wash in combination with mupirocin nasal ointment in 2 of the included 6 studies. Moreover, in one study CHG 2% soap body wash was used as standard preoperative clinical practice.
  • The GDG highlighted that the studies identified as the evidence base for these recommendations did not assess screening for S. aureus as part of the intervention. Consequently, no recommendation can be formulated on the role of screening in this context or the surgical patient population that should undergo screening for S. aureus carriage. The GDG noted also that standard operating procedures should be agreed upon according to national recommendations and the decision based on the local epidemiology, the patient’s risk factors for S. aureus acquisition, the microbiological capacity and financial resources available at the health care facility. The GDG emphasized that this recommendation applies to facilities where screening for S. aureus is feasible. The GDG strongly believes also that decolonization with mupirocin ointment with or without a combination of CHG body wash should be performed on known S. aureus carriers only in order to avoid unnecessary treatment and the spread of resistance.

Remarks

  • Included studies were performed in adult patients undergoing cardiac, orthopaedic, general, gynaecological, neurological, Mohs micrographic, vascular and gastrointestinal surgery. Based on this evidence, this recommendation is not applicable to paediatric patients.
  • The available evidence focused on the nasal carriage of S. aureus. Other body sites of frequent and/or known colonization could be considered for decolonization. However, due to the lack of substantial evidence, no recommendation can be made in this direction.
  • Studies were performed mostly in high-income countries.
  • Mupirocin nasal ointment at a concentration of 2% was used in all included studies. In 2 of the included 6 studies (1, 2) CHG 4% soap was used for full body wash in combination with the mupirocin nasal ointment. In one study (3) CHG 2% soap body wash was used as standard preoperative clinical practice.
  • The application of mupirocin varied from 2 times a day for 5 days (2, 4, 5) to 7 days (3) before surgery or from the day of hospital admission until the day of surgery (6). Daily administration was continued after surgery for a total of 5 days only in one trial (1). In all studies, at least one administration took place in the immediate preoperative period. Given the variability of treatment protocols, the GDG was unable to give specific instructions about the frequency and duration of mupirocin administration.
  • The GDG identified AMR as an important possible harm associated with the use of mupirocin (7). It was emphasized that an approach to treat all patients, regardless of their carriage status, instead of carriers only increases the likelihood of resistance to mupirocin (8, 9). Consequently, monitoring of AMR is recommended in facilities where mupirocin is used (1012). The available evidence (3, 5, 6) and additional studies (13, 14) showed no trend towards an increasing prevalence of mupirocin resistance following its short-term use in surgical patients. However, there is evidence that the increased short-term use of mupirocin leads to an increase of resistance to mupirocin and other antibiotics (15). Moreover, in settings known to have a high prevalence of mupirocin resistance, the recommendation to use perioperative intranasal mupirocin ointment may not apply.
  • Potential allergic reactions to mupirocin should be accounted for.
  • One recent study (16) showed a reduction in mortality at one year in patients receiving mupirocin compared to patients receiving placebo. The present review of the evidence based on 3 studies (1, 3, 5) did not find an effect on short-term mortality (up to 8 weeks follow-up).
  • The GDG identified a possible harm associated with the use of CHG-containing solutions, although it was stressed that this is a rare occurrence. Two studies (17, 18) found that CHG solutions may cause skin irritation, delayed reactions (such as contact dermatitis and photosensitivity) and hypersensitivity reactions in very rare cases, such as anaphylactic shock. Some of these potential adverse events may be induced also by ingredients of regular soap, such as fragrances. A concern of the GDG was the possible development of reduced susceptibility to CHG (19).

Background

S. aureus is the leading health care-associated pathogen in hospitals worldwide. These infections are associated with substantial morbidity and mortality and this trend is increasing due to the widespread dissemination of MRSA (20).

Staphylococcal infections occur regularly in hospitalized patients and can have severe consequences, including postoperative wound infections, nosocomial pneumonia and catheter-related bacteraemia (2125). A recent study of over 7 million hospital admissions in the USA estimated that the annual national impact was 2.7 million additional days in hospital, US$ 9.5 billion excess costs and at least 12 000 in-patient deaths (26). Given the high burden of these infections for the patient and the health system, effective prevention strategies are essential.

Traditionally, the control of S. aureus has been focused on preventing cross-transmission between patients (27). However, it has been shown repeatedly that a large proportion (approximately 80% after surgery) of HAI due to S. aureus originate from the patients’ own flora (23, 28, 29). Nasal carriage of S. aureus is now considered a well-defined risk factor for subsequent infection in various patient groups (22, 30).

Mupirocin nasal ointment (usually applied to the nose 2 times daily for 5 days) is an effective, safe and relatively cheap treatment for the eradication of carriage. Mupirocin can be used for the eradication of both methicillin-sensitive S. aureus (MSSA) and MRSA, although mupirocin resistance has been reported (31). Several interventional studies have attempted to reduce infection rates by eradicating nasal carriage (22). Recently, rapid molecular diagnostics with the capacity to detect S. aureus nasal carriage within hours rather than days have become available (32, 33), thus enabling the prompt pre-emptive treatment of carriers when appropriate.

The SSI prevention guideline published by SHEA/IDSA) (34) recommends screening for S. aureus and decolonizing surgical patients for high-risk procedures. Some SSI prevention bundles, such as the one issued by the US-based Institute for Healthcare Improvement (35) recommend to screen for S. aureus and decolonize prior to surgery, if positive (Table 4.2.1). However, these recommendations are not based upon systematic reviews of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

Table 4.2.1. Recommendations on screening and decolonization of S. aureus according to available guidelines and bundles.

Table 4.2.1

Recommendations on screening and decolonization of S. aureus according to available guidelines and bundles.

Following the in-depth analysis of the sources and strength of evidence in available guidelines, the GDG members decided to conduct a systematic review to assess the available evidence on the effectiveness of decolonization with mupirocin nasal ointment for the reduction of the S. aureus infection rate, including SSI, in patients undergoing surgery with known S. aureus nasal carriage.

Summary of the evidence

The purpose of the evidence review (web Appendix 3) was to determine whether decolonization with intranasal mupirocin ointment with or without a combination with CHG soap body wash reduces S. aureus overall infection rates, including SSI. The target population included patients of all ages with known S. aureus nasal carriage undergoing a surgical procedure. The primary outcomes were the occurrence of SSI and SSI-attributable mortality.

Six RCTs (16) including 2385 patients comparing mupirocin nasal ointment combined with or without CHG soap body wash to placebo or no treatment were identified. Five trials described surgical patients (cardiac, orthopaedic, general, gynaecological, neurological or Mohs micrographic surgery) and one (1) included both surgical (cardiac, vascular, orthopaedic, gastrointestinal or general surgery) and non-surgical patients (internal medicine). According to the selected studies, the following comparisons were evaluated:

  1. mupirocin vs. placebo/no treatment with the following outcomes:
    1. all HAI caused by S. aureus;
    2. health care-associated SSI caused by S. aureus.

Overall, a moderate quality of evidence shows that the use of mupirocin 2% ointment combined with or without CHG soap body wash has a significant benefit for the reduction of the SSI rate caused by S. aureus in surgical patients with nasal carriage when compared to placebo/no treatment (OR: 0.46; 95% CI: 0.31–0.69), including the overall health care-associated S. aureus infection rate (OR: 0.48; 95% CI: 0.32–0.71). It should be noted that most studies included patients undergoing cardiothoracic and orthopaedic surgery, but 2 trials included also other types of procedures. Indeed, in meta-regression analysis, there was no evidence to suggest that the effect on the S. aureus infection rate differed between different types of surgery (P=0.986).

The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that patients with nasal S. aureus colonization would prefer to be treated with mupirocin ointment nasally with or without a combination of CHG body wash in order to reduce the risk of SSI. Conversely, patients could be concerned about the emergence of AMR, as well as the possible development of reduced susceptibility to antiseptics, such as CHG.

Resource use

The use of mupirocin, including screening for S. aureus (“screen-and-treat” strategy), was shown to be cost-effective in 2 studies (1, 39). On average, hospital costs were ú 1911 lower per patient treated with mupirocin and CHG soap (n=210) than the costs of care in the placebo arm (n=205; ú 8602 vs. ú 10 513; P=0.01). A subgroup analysis showed that cardiothoracic patients with S. aureus nasal carriage treated with mupirocin and CHG cost ú 2841 less (n=280; ú 9628 vs. ú12 469; P=0.006) and orthopaedic patients ú 955 less than non-treated patients (n=135; ú 6097 vs. ú 7052; P=0.05). Furthermore, based on a nasal S. aureus carriage rate of 20%, the authors estimated a saving of approximately ú 400 000 per 1000 surgical patients (39).

The GDG highlighted that the access to and availability of nasal mupirocin ointment could be limited for LMICs and pose a financial burden, including also to patients. In addition, antimicrobial soap will pose an additional financial burden to the health care facility and/or patients in many LMICs. The same applies to the technical laboratory capacity and financial burden for the screening process.

Research gaps

Most GDG members emphasized that no further studies are needed on mupirocin. However, given the variability in the timing and duration of mupirocin administration and bathing with CHG across the trials included in this review, additional well-designed RCTs are needed to clarify this issue in surgical patients. GDG members highlighted that other agents for the decolonization of nasal S. aureus carriers scheduled for surgery should be investigated in well-designed double-blind RCTs. It was underlined that the development and implementation of an inexpensive screening process for S. aureus is highly desirable for LMICs. In addition, there is a need for effectiveness and cost-effectiveness studies in these settings.

References

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Tai YJ, Borchard KL, Gunson TH, Smith HR, Vinciullo C. Nasal carriage of Staphylococcus aureus in patients undergoing Mohs micrographic surgery is an important risk factor for postoperative surgical site infection: a prospective randomised study. Austral J Dermatol. 2013;54(2):109–14. [PubMed: 23425142]
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Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. New Engl J Med. 2002;346(24):1871–7. [PubMed: 12063371]
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Poovelikunnel T, Gethin G, Humphreys H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother. 2015;70(10):2681–92. [PubMed: 26142407]
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Talon D, Marion C, Thouverez M, Bertrand X. Mupirocin resistance is not an inevitable consequence of mupirocin use. J Hosp Infect. 2011;79(4):366–7. [PubMed: 21968283]
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Hetem DJ, Vogely HC, Severs TT, Troelstra A, Kusters JG, Bonten MJ. Acquisition of high-level mupirocin resistance in CoNS following nasal decolonization with mupirocin. J Antimicrob Chemother. 2015;70(4):1182–4. [PubMed: 25538164]
11.
Desroches M, Potier J, Laurent F, Bourrel AS, Doucet-Populaire F, Decousser JW. Prevalence of mupirocin resistance among invasive coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (MRSA) in France: emergence of a mupirocin-resistant MRSA clone harbouring mupA. J Antimicrob Chemother. 2013;68(8):1714–7. [PubMed: 23535880]
12.
Lee AS, Macedo-Vinas M, Francois P, Renzi G, Schrenzel J, Vernaz N, et al. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin-resistant Staphylococcus aureus carriage after decolonization therapy: a case-control study. Clin Infect Dis. 2011;52(12):1422–30. [PubMed: 21628482]
13.
Fawley WN, Parnell P, Hall J, Wilcox MH. Surveillance for mupirocin resistance following introduction of routine peri-operative prophylaxis with nasal mupirocin. J Hosp Infect. 2006;62(3):327–32. [PubMed: 16377029]
14.
Hetem DJ, Bonten MJ. Clinical relevance of mupirocin resistance in Staphylococcus aureus. J Hosp Infect. 2013;85(4):249–56. [PubMed: 24144552]
15.
Bathoorn E, Hetem DJ, Alphenaar J, Kusters JG, Bonten MJ. Emergence of high-level mupirocin resistance in coagulase-negative staphylococci associated with increased short-term mupirocin use. J Clin Microbiol. 2012;50(9):2947–50. [PMC free article: PMC3421826] [PubMed: 22760047]
16.
Bode LG, Rijen MM, Wertheim HF, Vandenbroucke-Grauls CM, Troelstra A, Voss A, et al. Long-term mortality after rapid screening and decolonization of Staphylococcus aureus carriers: observational follow-up study of a randomized, placebo-controlled trial. Ann Surgery. 2016;263(3):511–15. [PubMed: 26565136]
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Krautheim AB, Jermann TH, Bircher AJ. Chlorhexidine anaphylaxis: case report and review of the literature. Contact Dermatitis. 2004;50(3):113–6. [PubMed: 15153122]
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Byrne DJ, Napier A, Cuschieri A. Prevention of postoperative wound infection in clean and potentially contaminated surgery. A prospective, randomised, double-blind, placebo-controlled clinical trial. Surg Res Comm. 1992;12:43–52.
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Horner C, Mawer D, Wilcox M. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter? J Antimicrob Chemother. 2012;67(11):2547–59. [PubMed: 22833635]
20.
National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32(8):470–85. [PubMed: 15573054]
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Kaplowitz LG, Comstock JA, Landwehr DM, Dalton HP, Mayhall CG. Prospective study of microbial colonization of the nose and skin and infection of the vascular access site in hemodialysis patients. J Clin Microbiol. 1988;26(7):1257–62. [PMC free article: PMC266588] [PubMed: 3410944]
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Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997;10(3):505–20. [PMC free article: PMC172932] [PubMed: 9227864]
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Kluytmans JA, Mouton JW, Ijzerman EP, Vandenbroucke-Grauls CM, Maat AW, Wagenvoort JH, et al. Nasal carriage of Staphylococcus aureus as a major risk factor for wound infections after cardiac surgery. J Infect Dis. 1995;171(1):216–9. [PubMed: 7798667]
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Yu VL, Goetz A, Wagener M, Smith PB, Rihs JD, Hanchett J, et al. Staphylococcus aureus nasal carriage and infection in patients on hemodialysis. Efficacy of antibiotic prophylaxis. New Engl J Med. 1986;315(2):91–6. [PubMed: 3523240]
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Yzerman EP, Boelens HA, Tjhie JH, Kluytmans JA, Mouton JW, Verbrugh HA. Delta APACHE II for predicting course and outcome of nosocomial Staphylococcus aureus bacteremia and its relation to host defense. J Infect Dis. 1996;173(4):914–9. [PubMed: 8603971]
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Noskin GA, Rubin RJ, Schentag JJ, Kluytmans J, Hedblom EC, Smulders M, et al. The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database. Arch Int Med. 2005;165(15): 1756–61. [PubMed: 16087824]
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Pittet D, Hugonnet S, Harbarth S, Mourouga P, Sauvan V, Touveneau S, et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Lancet. 2000;356(9238):1307–12. [PubMed: 11073019]
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von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. New Engl J Med. 2001;344(1):11–6. [PubMed: 11136954]
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Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004;364(9435):703–5. [PubMed: 15325835]
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Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27(2):97–132; quiz 3–4; discussion 96. [PubMed: 10196487]
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How-to guide: prevent surgical site infection for hip and knee arthroplasty. Cambridge (MA): Institute for Healthcare Improvement; 2012.
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4.3. Screening for extended-spectrum beta-lactamase colonization and the impact on surgical antibiotic prophylaxis

Recommendation

The panel decided not to formulate a recommendation due to the lack of evidence.

Rationale for the recommendation

The literature search did not identify any relevant studies comparing the tailored modification of SAP for the prevention of SSI in areas with a high prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriacae (including patients with rectal colonization of ESBL) to no modification of standard antibiotic prophylaxis. Furthermore, no studies comparing routine screening for ESBL (irrespective of ESBL prevalence prior to surgery) with no screening that could inform a recommendation for this question were identified.

Remarks

  • The prevalence of ESBL-producing Enterobacteriacae was considered to be high when demonstrating a prevalence of >10% on the total number of all samples submitted to the laboratory for investigation, including both infection and/or colonization.
  • The GDG believes that routine screening for ESBL prior to surgery might increase the widespread use of broad-spectrum antibiotics (particularly carbapenems) pre-surgery in ESBL-colonized patients. This practice may be harmful as it is likely to further increase the emergence of resistance in gram-negative bacteria, especially carbapenem-resistant Enterobacteriacae. The WHO global surveillance report on AMR has already highlighted concerns about the emergence of antibiotic-resistant bacteria due to the inappropriate use of antimicrobial agents. Importantly, the options for the treatment of infections are now extremely limited due to the lack of development of a new class of antimicrobial agents over the past decades (1).

Background

In recent years, the prevalence of patients colonized with ESBL-producing bacteria has increased globally both in health care facilities and in the community. Similar to most gram-negative bacteria, ESBL resides in the gastrointestinal tract and decolonization is very difficult to achieve. The most frequent infections caused by ESBL concern the urinary tract and, to a lesser extent, bloodstream infections. Current SSI prevention guidelines do not address the screening, decolonization and modification of SAP in patients who are colonized with these organisms prior to surgery or the effect of these procedures for the prevention of SSI. The GDG decided to conduct a systematic review to assess the effectiveness of these measures.

Summary of the evidence

The purpose of the evidence review (web Appendix 4) was to evaluate whether the tailored modification of SAP in areas with a high prevalence of ESBL-producing Enterobacteriaceae (>10%), including patients known to be colonized with ESBL, is more effective in reducing the risk of SSI than no modification of prophylaxis. A further objective was to investigate whether routine screening for ESBL in both low and high ESBL prevalence areas has an impact on reducing the risk of SSI compared to no screening. The target population included patients of all ages undergoing a surgical operation. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

The literature search did not identify any studies comparing the tailored modification of SAP for the prevention of SSI in areas with a high prevalence of ESBL-producing Enterobacteriaceae (including patients with rectal colonization of ESBL) to no modification of standard prophylaxis. Similarly, no studies were identified comparing routine patient screening for ESBL with no screening as a preventive measure prior to surgery.

Additional factors considered

Resource use

In the absence of evidence, the implementation of routine screening for ESBL to detect faecal colonization prior to surgery would have major cost implications, especially in LMICs. For example, this would include clinical staff who have to take a swab and competent microbiology laboratory services to detect ESBL, perform antibiotic susceptibility tests and then communicate the results to the surgical team in a timely manner. This may be difficult as most laboratories are under-resourced and may lack good quality control programmes, particularly in LMICs. In addition, when the screening swab is positive for ESBL, it is very tempting for a clinical team to use carbapenems on colonized patients. This generates additional costs as they have to be given by the intravenous route, which is costly and time-consuming, notably in settings with low resources where there are already a shortage of nursing and medical power.

Research gaps

The GDG members highlighted that although there is an increase in the emergence of ESBL-producing Enterobacteriacae worldwide, no controlled trials or good quality observational studies have been published to answer the questions of this review, even in countries where ESBL-producing Enterobacteriaceae are endemic. Well-designed, RCTs and good quality observational studies are urgently needed to give guidance to the surgical team and prevent the inappropriate use of broad-spectrum antibiotics and the emergence of multidrug-resistant organisms on a global basis. As a priority, these studies should investigate whether the tailored modification of SAP in areas with a high prevalence of ESBL-producing Enterobacteriacae, including patients known to be colonized with ESBL, is more effective in reducing the risk of SSI than no modification of the standard prophylaxis.

References

1.
Antimicrobial resistance: global report on surveillance. Geneva: World Health Organization; 2014 (http://apps​.who.int/iris​/bitstream/10665​/112642/1/9789241564748_eng.pdf, accessed 17 May 2016).

4.4. Optimal timing for preoperative surgical antibiotic prophylaxis

Recommendations

The panel recommends the administration of SAP prior to the surgical incision when indicated (depending on the type of operation).

(Strong recommendation, low quality of evidence)

The panel recommends the administration of SAP within 120 minutes before incision, while considering the half-life of the antibiotic.

(Strong recommendation, moderate quality of evidence)

Rationale for the recommendations

  1. Overall low quality evidence shows that the administration of SAP after the incision causes harm with a significant increase of the SSI risk compared with administration of SAP prior to incision. Adequate tissue concentrations of the antibiotic should be present at the time of incision and throughout the procedure for SAP to be effective. This necessitates administration prior to incision. Further evidence shows that a low tissue concentration of antibiotics at the time of wound closure is associated with higher SSI rates (1, 2). As a result, the GDG unanimously agreed to recommend the administration of SAP prior to incision and decided that the strength of this recommendation should be strong, although the overall quality of evidence is low. It is unlikely that higher quality evidence will be available in the future and indeed it would be unethical to perform a study where SAP is only administered post-incision because of the risk to cause significant harm.
  2. A moderate quality of evidence comparing different time intervals prior to incision shows significant harm when SAP is administered before 120 minutes compared to within 120 minutes pre-incision. Given the significant increase of SSI with SAP administration more than 120 minutes before incision, the GDG decided to recommend SAP administration within 120 minutes pre-incision. A further analysis of data from studies assessing the effect of SAP administration on SSI at different time intervals within the 120-minute pre-incision period was performed, that is, 120–60 minutes vs. 60–0 minutes and 60–30 minutes vs. 30–0 minutes. No significant difference was found. Therefore, based on the available evidence, it is not possible to establish more precisely the optimal timing within the 120-minute interval.
    Several GDG members expressed concern that serum and tissue concentrations of antibiotics with a short half-life may be less effective than administration closer to the time of incision if given early in this time interval. For this reason, the GDG recommends to take into account the half-life of the administered antibiotics in order to establish the exact time of administration within 120 minutes pre-incision (for example, administration closer to the incision time [<60 minutes] for antibiotics with a short half-life, such as cefazolin, cefoxitin and penicillins in general). The same attention should be paid to the single antibiotic half-life when considering re-dosing during prolonged surgery. Concerns about antibiotic protein binding may arise when choosing highly-bound antimicrobials, such as ceftriaxone, teicoplanin or ertapenem. Under particular pathophysiological conditions (for example, patients with a low level of serum proteins, such as the critically ill or very elderly individuals), such drug disposition may indeed be affected. In addition, malnourishment, obesity, cachexia or renal disease with protein loss may result in suboptimal antibiotic exposure through increased antibiotic clearance in the presence of normal or augmented renal function, including overexposure and potential toxic effects in the presence of severely impaired renal function.

Remarks

  • It is not within the scope of these guidelines to provide recommendations on what type of operations require SAP and the antibiotics, doses and intraoperative redosing rules that should be used. Separate specific guidelines will be made available by WHO on this topic. Examples of procedures that do not require SAP are clean orthopaedic operations not involving implantation of foreign materials or low-risk elective laparoscopic procedures.
  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. However, the GDG considers this recommendation valid also for paediatric patients.
  • In the included studies, the information was generally unclear regarding the duration of the procedure, re-dosing protocol, exact timing of the administration, infusion time and whether the half-life of the administered antibiotics was taken into account.
  • Studies on caesarean section were not included in this review as they compared pre-incisional administration of SAP vs. administration after cord clamping. A recent systematic review on caesarean section indicated that SAP should be administered prior to incision in order to reduce maternal infectious morbidities (3). This aligns with the recommendations in other surgical procedures where SAP is indicated.
  • The guidelines of the American Society of Health-System Pharmacists (ASHSP) (4) recommend that intraoperative re-dosing is needed if the duration of the procedure exceeds 2 half-lives of the drug or if there is excessive blood loss during the procedure. While the benefit of this approach seems reasonable from a drug pharmacokinetic aspect, the reviewed studies have not addressed in SAP protocols the duration of surgical procedures or re-dosing in relation to SSI. No recommendation could be concluded on the benefit or harm of this approach.
  • Some guidelines distinguish that some antibiotics require administration over 1–2 hours, such as fluoroquinolones and vancomycin. Therefore, the administration of these agents should begin within 120 minutes before the surgical incision. The literature search has not identified studies with SSI as an outcome that differentiate between the timing of administration of antibiotics requiring a longer period and those with a shorter administration timing. Clinicians should consider the half-life and protein binding as the most important pharmacokinetic parameters of any single SAP agent in order to ensure adequate serum and tissue concentration at the time of incision and during the entire surgical procedure.

Background

SAP refers to the prevention of infectious complications by administering an effective antimicrobial agent prior to exposure to contamination during surgery (4). Successful SAP requires delivery of the antimicrobial agent in effective concentrations to the operative site before contamination occurs (5). Microbial contamination of the wound during the procedure can be of exogenous or endogenous origin. The benefit of the routine use of SAP prior to non-clean and implant surgery to prevent SSI has long been recognized. Further evidence of its benefit for other clean procedures where the consequences of an infection would be devastating (for example, cardiac and neurosurgery) is also an important research topic. Of note, the effect of SAP does not concern the prevention of SSI caused by postoperative contamination. Within these guidelines, the recommendations have been developed with a focus on the optimal timing of SAP administration and the indication and type of SAP depending on the type of surgery is outside the scope of the document. Some experimental and clinical studies have demonstrated an effect of SAP timing on SSI (6, 7), but the optimal timing is still under debate.

The administration of SAP prior to surgery has been specified in many clinical practice guidelines issued by professional societies or national authorities (Table 4.4.1). Several of these guidelines, such as those published by the ASHP (4), SHEA/IDSA) (8), the Royal College of Physicians of Ireland (9) or Health Protection Scotland (10), recommend administration within 60 minutes prior to incision (120 minutes for vancomycin and fluoroquinolones due to prolonged infusion times) (3). However, these recommendations are not based on systematic reviews of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

Table 4.4.1. Recommendations on SAP according to available guidelines.

Table 4.4.1

Recommendations on SAP according to available guidelines.

Following the in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the available evidence on the correct timing of SAP administration.

Summary of the evidence

The purpose of the evidence review (web Appendix 5) was to compare the effect of different timings of SAP administration on the risk of SSI and to identify the optimal timing to effectively prevent SSI. The target population were patients of all ages undergoing surgical interventions where SAP was indicated. The primary outcomes were the occurrence of SSI and SSI-attributable mortality. A total of 13 observational studies (7, 1425) including a total of 53 975 adult patients were identified; 2 were from multiple centres. No RCTs were identified. The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality. Despite substantial heterogeneity in reporting time intervals between the selected studies, separate meta-analyses were performed to evaluate the following comparisons of SAP timing administration: pre- vs. post-incision within 120 minutes vs. more than 120 minutes prior to incision; more than 60 minutes vs. within 60 minutes prior to incision; and 30–60 minutes vs. 0–30 minutes.

Moderate quality evidence shows that SAP administration before 120 minutes pre-incision is associated with a significantly higher risk of SSI when compared to administration within 120 minutes (OR: 5.26; 95% CI: 3.29–8.39). Furthermore, there is low quality evidence that administration of SAP after incision is associated with a significantly higher risk of SSI compared to administration prior to incision (OR: 1.89; 95% CI: 1.05–3.4). In addition, low quality evidence shows that administration within 60 minutes prior to incision has neither benefit nor harm for the reduction of SSI rates compared to administration between 60 to 120 minutes prior to incision. Similarly, SAP administration within 30 to 0 minutes prior to incision has neither benefit nor harm for the reduction of SSI rates when compared to administration within 60 to 30 minutes prior to incision.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG concluded that all patients, health care providers and policy-makers will favour the intervention for both recommendations. Due to logistic and practical considerations, anaesthesiologists tend to administer SAP in the operating room. This is often close to the start of incision, but it still lies within the 120-minute interval recommended by the GDG.

Resource use

There are no extra costs related to an optimized timing interval for SAP. However, the GDG believes that it is important to define responsibility for timely SAP administration and organizational resources may be required. In-service training including best practices for SAP administration should be provided. Feasibility and equity are not identified as significant issues for both recommendations.

Research gaps

The GDG highlighted the limited evidence available on optimal SAP timing to prevent SSI and the need for further studies on this topic. In particular and as a high priority, RCTs comparing the effect of different time intervals within the 120 minutes prior to incision are needed, that is, 120–60 minutes vs. 60–0 minutes and 60–30 minutes vs. 30–0 minutes. These should clearly state the duration of the procedure, the re-dosing protocol according to the drug chosen, as well as the infusion time and best exact timing of administration, while taking into account the half-lives of the antibiotics. Research is warranted also to identify the best timing according to specific types of surgical procedures. Furthermore, well-designed RCTs are necessary to investigate the relation between the pharmacokinetic and pharmacodynamic parameters of the antimicrobial agents used for SAP, including tissue levels at the incision site and SSI rates. The GDG noted that there are no high quality data examining the effect of dose adjustments or intraoperative re-dosing on SSI rates. Thus, it would be important to conduct RCTs comparing optimal doses of antibiotics and redosing protocols.

References

1.
Goldmann DA, Hopkins CC, Karchmer AW, Abel RM, McEnany MT, Akins C, et al. Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens. J Thorac Cardiovasc Surg. 1977;73(3):470–9. [PubMed: 402508]
2.
Zelenitsky SA, Ariano RE, Harding GKM, Silverman RE. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother. 2002;46(9):3026–30. [PMC free article: PMC127433] [PubMed: 12183263]
3.
Mackeen AD, Packard RE, Ota E, Berghella V, Baxter JK. Timing of intravenous prophylactic antibiotics for preventing postpartum infectious morbidity in women undergoing cesarean delivery. Cochrane Database Syst Rev. 2014;12:CD009516. [PubMed: 25479008]
4.
Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt). 2013;14(1);73–156. [PubMed: 23461695]
5.
Dellinger EP, Gross PA, Barrett TL, Krause PJ, Martone WJ, McGowan JE, Jr., et al. Quality standard for antimicrobial prophylaxis in surgical procedures. Infect Control Hosp Epidemiol. 1994;15(3):182–8. [PubMed: 8207176]
6.
Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961;50:161–8. [PubMed: 16722001]
7.
Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326(5):281–6. [PubMed: 1728731]
8.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
9.
Preventing surgical site infections. Key recommendations for practice. Dublin: Joint Royal College of Surgeons in Ireland/Royal Colleges of Physicians of Ireland Working Group on Prevention of Surgical Site Infection; 2012 (https://www​.rcsi.ie/files​/surgery/docs/20140318021114​_Sample​%20Audit%20Surgical%20site%20Inf.pdf, accessed 21 July 2016).
10.
Scottish Intercollegiate Guidelines Network. Antibiotic prophylaxis in surgery. July 2008, updated April 2014. Edinburgh: Healthcare Improvement Scotland; 2014 (http://www​.sign.ac.uk/pdf/sign104.pdf., accessed 10 May 2016).
11.
A summary of selected new evidence relevant to NICE clinical guideline 74 “Prevention and treatment of surgical site infection” (2008). Evidence update 43. June 2013. Manchester: National Institute for Health and Care Excellence; 2013. (http://www​.nice.org.uk​/guidance/cg74/evidence, accessed 21 July 2016).
12.
How-to guide: prevent surgical site infections. Cambridge (MA): Institute for Healthcare Improvement; 2012 (http://www​.ihi.org, accessed 21 July 2016).
13.
High impact intervention bundle: care bundle to prevent surgical site infection. London: Department of Health; July 2010 (http://webarchive​.nationalarchives​.gov.uk​/20120118164404/http://hcai​.dh.gov.uk/files​/2011/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL.pdf, accessed 21 July 2016).
14.
van Kasteren ME, Mannien J, Ott A, Kullberg BJ, de Boer AS, Gyssens IC. Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. Clin Infect Dis. 2007;44(7):921–7. [PubMed: 17342642]
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Weber WP, Marti WR, Zwahlen M, Misteli H, Rosenthal R, Reck S, et al. The timing of surgical antimicrobial prophylaxis. Ann Surg. 2008;247(6):918–26. [PubMed: 18520217]
16.
Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, et al. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg. 2009;250(1):10–6. [PubMed: 19561486]
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Ho VP, Barie PS, Stein SL, Trencheva K, Milsom JW, Lee SW, et al. Antibiotic regimen and the timing of prophylaxis are important for reducing surgical site infection after elective abdominal colorectal surgery. Surg Infect (Larchmt). 2011;12(4):255–60. [PubMed: 21790479]
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Koch CG, Nowicki ER, Rajeswaran J, Gordon SM, Sabik JF, III, Blackstone EH. When the timing is right: Antibiotic timing and infection after cardiac surgery. J Thorac Cardiovasc Surg. 2012;144(4):931–7. [PubMed: 22608676]
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Koch CG, Li L, Hixson E, Tang A, Gordon S, Longworth D, et al. Is it time to refine? An exploration and simulation of optimal antibiotic timing in general surgery. J Am Coll Surg. 2013;217(4):628–35. [PubMed: 23849901]
20.
El-Mahallawy HA, Hassan SS, Khalifa HI, El-Sayed Safa MM, Khafagy MM. Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery. J Egypt Natl Canc Inst. 2013;25(1):31–5. [PubMed: 23499204]
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Munoz PE, Jimenez Antolin JA, Brea ZS, Bravo GP. [The effect of surgical antibiotic prophylaxis and the timing of its administration on the risk of surgical wound infection]. Rev Clin Esp. 1995;195(10):669–73. [PubMed: 8532921]
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Lizan-Garcia M, Garcia-Caballero J, Sensio-Vegas A. Risk factors for surgical-wound infection in general surgery: a prospective study. Infect Control Hosp Epidemiol. 1997;18:310–5. [PubMed: 9154472]
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Trick WE, Scheckler WE, Tokars JI, Jones KC, Reppen ML, Smith EM, et al. Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2000;119(1):108–14. [PubMed: 10612768]
24.
Garey KW, Dao T, Chen H, Amrutkar P, Kumar N, Reiter M, et al. Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections. J Antimicrob Chemother. 2006;58(3):645–50. [PubMed: 16807254]
25.
Kasatpibal N, Norgaard M, Sorensen H, Schonheyder H, Jamulitrat S, Chongsuvivatwong V. Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand. BMC Infect Dis. 2006;6(1):111. [PMC free article: PMC1553447] [PubMed: 16836755]

4.5. Mechanical bowel preparation and the use of oral antibiotics

Recommendations

  1. The panel suggests that preoperative oral antibiotics combined with mechanical bowel preparation (MBP) should be used to reduce the risk of SSI in adult patients undergoing elective colorectal surgery.
    (Conditional recommendation, moderate quality evidence)
  2. The panel recommends that MBP alone (without administration of oral antibiotics) should not be used for the purpose of reducing SSI in adult patients undergoing elective colorectal surgery.
    (Strong recommendation, moderate quality evidence)

Rationale for the recommendations

  1. Overall moderate quality evidence shows that preoperative oral antibiotics combined with MBP reduce the SSI rate compared to MBP alone. Of note, none of the included studies investigated the effect of oral antibiotics alone, that is, without combining their administration with MBP. All studies also applied standard intravenous antibiotic prophylaxis. Furthermore, the available evidence shows that there is no difference between the intervention and control groups in the occurrence of anastomotic leakage. This result is important because concerns can be raised about the possible higher frequency of leakage if MBP is not performed. Considering the moderate quality of the evidence and the demonstrated effect, the GDG decided to suggest that preoperative oral antibiotics in combination with MBP should be used to reduce the risk of SSI in addition to routine standard intravenous antibiotic prophylaxis, when appropriate.
  2. A moderate quality of evidence shows that preoperative MBP alone has no benefit in reducing the SSI rate when compared to performing no MBP. Moreover, the meta-analysis indicates that no MBP has a non-significant beneficial effect in reducing the risk of SSI. In addition, the available evidence shows that there is no difference in the occurrence of anastomotic leakage with or without MBP. Therefore, the GDG unanimously agreed to recommend that MBP alone, without administration of oral antibiotics, should not be used for the purpose of reducing SSI in elective colorectal surgery.

Remarks

  • MBP refers to the preoperative administration of substances to induce voiding of the intestinal and colonic contents. Polyethylene glycol and/or sodium phosphate were the agents of choice for MBP in most studies. However, the protocols differed between the trials in terms of dosage, timing of the application and fasting. It was emphasized that suboptimal cleaning of the colon may be more problematic than no bowel preparation at all.
  • All studies included adult patients undergoing colorectal surgical procedures; therefore, the effectiveness of these interventions is not proven for paediatric patients.
  • Apart from the MBP regimen, the oral antibiotics and the drug of choice for intravenous antibiotic prophylaxis varied across the studies. In 8 trials, oral aminoglycosides were combined with anaerobic coverage (metronidazole (15) or erythromycin (68)) and 3 studies (911) applied a gram-negative coverage only.
  • The GDG acknowledges that is difficult to provide a universal statement on the choice of drugs for oral antibiotics to be used for MBP. The combination of the drugs used should guarantee an activity against both facultative gram-negative and anaerobic bacteria. The choice of antimicrobials should be made ideally according to local drug availability, updated resistance data within institutions and the volume of surgical activity.
  • The GDG identified possible harms of the intervention of MBP with varying levels of severity. These include patient discomfort, electrolyte abnormalities and potentially severe dehydration at the time of anaesthesia and incision.
  • The GDG pointed out that there is an alert issued by the US Food and Drug Administration highlighting that acute phosphate nephropathy (a type of acute renal failure) is a rare but serious adverse event associated with oral sodium phosphate bowel cleansing (12).
  • Concerns were also raised with regard to the potential adverse effects of the oral antibiotics used (for example, high risk of idiosyncratic reaction with erythromycin). A further concern was AMR as a potential unintended consequence of this intervention. The effectiveness of oral antibiotics may decrease due to their widespread use, thus triggering the emergence of resistant strains. The GDG noted that there was a widespread belief that non-absorbable antibiotics should be preferably used. In the corresponding comparisons, a combination of non-absorbable and absorbable antibiotics was administered in 8 of 11 RCTs (18). Two studies (9, 10) applied non-absorbable and one study (11) absorbable antibiotics only.
  • The GDG emphasized that the intervention of oral antibiotics with MBP is for preoperative use only and should not be continued postoperatively. This intervention should not be referred to as “selective digestive decontamination” (SDD) in order to avoid any confusion with SDD used for the prevention of ventilator-associated pneumonia in the intensive care setting.

Background

The optimal preparation of the bowel of patients undergoing colorectal surgery has been a subject of debate for many years. The main focus has been on whether or not mechanical cleansing of the bowel should be part of the standard preoperative regimen. MBP involves the preoperative administration of substances to induce voiding of the intestinal and colonic contents. The most commonly used cathartics for MPB are polyethylene glycol and sodium phosphate. It was assumed that cleaning the colon of its contents was necessary for a safe operation and could lower the risk of SSI by decreasing the intraluminal faecal mass and theoretically decreasing the bacterial load in the intestinal lumen. Furthermore, it was believed that it could prevent the possible mechanical disruption of a constructed anastomosis by the passage of hard faeces. Finally, MBP was perceived to improve handling of the bowel intraoperatively.

Another aspect of preoperative bowel preparation that has evolved over the last decades concerns the administration of oral antibiotics. Since the 1930s, orally administered antibiotics have been used with the aim to decrease the intraluminal bacterial load. However, these drugs had typically poor absorption, achieved high intraluminal concentrations and had activity against (anaerobic and aerobic) species within the colon. The addition of oral antibiotics that selectively target potentially pathogenic microorganisms in the digestive tract, predominantly gram-negative bacteria, S. aureus and yeasts, is known also as “selective digestive decontamination”. This term originates from intensive care medicine and usually refers to a regime of tobramycin, amphotericin and polymyxin combined with a course of an intravenous antibiotic, often cefotaxime. Originating from the belief that oral antibiotics would work only when the bowel had been cleansed of its content, a regime of oral antibiotics was frequently combined with MBP.

A few organizations have issued recommendations regarding preoperative MBP and the administration of oral antimicrobials (Table 4.5.1). For example, SHEA/IDSA recommend to use MBP for colorectal procedures, but only combined with oral antibiotics. However, these recommendations are not based on systematic reviews of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

Table 4.5.1. Recommendations on MBP and the administration of oral antimicrobials according to available guidelines.

Table 4.5.1

Recommendations on MBP and the administration of oral antimicrobials according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess the available evidence on the effectiveness of preoperative oral antibiotics and MBP for the prevention of SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 6) was to evaluate whether preoperative MBP is more effective in reducing the risk of SSI than no MBP at all. The review evaluated also whether combining the preoperative administration of oral antibiotics with MBP in addition to the standard preoperative intravenous antibiotic prophylaxis is more effective than MBP alone. The population targeted were patients of any age undergoing elective colorectal surgery. The primary outcome was the occurrence of SSI and SSI-attributable mortality. Data on anastomotic leakage were analysed separately as a secondary outcome. The body of retrieved evidence focused on adult patients and no study was available in the paediatric population.

A total of 24 RCTs (111, 1527) were identified. They compared either MBP with no MBP or the combined intervention of MBP and oral antibiotics with MBP and no oral antibiotics.

A total of 11 RCTs (111) including a total of 2416 patients and comparing preoperative MBP combined with the administration of oral antibiotics vs. MBP and no oral antibiotics were identified. Moderate quality evidence shows that preoperative MBP combined with oral antibiotics reduces the SSI rate when compared to MBP only (OR: 0.56; 95% CI: 0.37–0.83). Using this intervention, there is neither benefit nor harm in the occurrence of anastomotic leakage (OR: 0.64; 95% CI: 0.33–1.22).

A total of 13 RCTs (1527) including a total of 4869 patients and comparing MBP with no MBP were identified. Moderate quality evidence shows that preoperative MBP has neither benefit nor harm for the reduction of SSI rates when compared to no MBP at all (OR: 1.31; 95% CI: 1.00–1.72). The available evidence shows also that there is no difference in the occurrence of anastomotic leakage with or without MBP (OR: 1.03; 95% CI: 0.73–1.44).

Among the studies comparing MBP combined with oral antibiotics vs. MBP alone, only 2 (8, 11) reported specifically on SSI-attributable mortality. Both studies reported a lower mortality rate when oral antibiotics were administered, although they failed to report any test for statistical significance. Of the 13 trials comparing MBP with no MBP, 3 reported specifically on SSI-attributable mortality (18, 23, 27), but they did not find any statistical difference in the mortality rate.

None of the identified RCTs specifically evaluated the role of oral antibiotics without a MBP regimen, but some observational studies (2830) using registry databases suggested that oral antibiotics may be effective in reducing the risk of SSI, irrespective of being combined with MBP. In addition, a prospective, randomized study (31) strongly supports the use of oral antibiotics as part of a bundled intervention, but in combination with MBP. In this study, the combination of the preoperative administration of oral antibiotics and MBP was omitted in one group and compared with a standard regimen of oral antibiotics and MBP, while both arms received intravenous antibiotics prior to the surgical incision.

Additional factors considered when formulating the recommendation

Values and preferences

One study (9) found a higher incidence of diarrhoea when oral antibiotics were administered. Another study (1) assessed patient tolerance with 3 different oral antibiotic regimes. Patients reported more gastrointestinal symptoms (that is nausea and vomiting) at the time of preoperative preparation when given 3 doses of oral antibiotics compared to no oral antibiotics or one dose only. Among the studies comparing MBP with no MBP, 4 reported on patient discomfort. Berrera and colleagues (15) reported that half of all patients (50%) receiving MBP reported fair or poor tolerance. The main causes were nausea (56%), vomiting (23%) and cramping abdominal pain (15%). In another study (16) including 89 patients with MBP, 17–28% complained of similar disorders which led to a stop of preoperative MBP in 11% of cases. In one study (17), MBP was associated with discomfort in 22% of patients, including difficulty in drinking the preparation, nausea, vomiting and abdominal pain. Zmora and colleagues (27) found that diarrhoea in the early postoperative period was more common in the MBP than the non-MBP group and reached statistical significance. The GDG acknowledged that some patients, for example, the elderly or disabled, might prefer not to undergo MBP, regardless of the outcome.

Resource use

It was acknowledged that MBP, including the administration of oral antibiotics, involves an additional workload as this intervention requires organizational resources to ensure its appropriate administration (for example, clear written instructions to patients and staff education). Furthermore, the initial cost is higher compared to not undertaking this intervention, but none of the included studies reported on costs and cost-effectiveness. However, the GDG concluded that the benefits of administering oral antibiotics outweigh these aspects. The antibiotics commonly used for the intervention (erythromycin, metronidazole and an aminoglycoside) are generally inexpensive and readily available, including in LMICs.

Research gaps

The GDG highlighted that there is enough evidence available on MBP alone. However, further research is needed on the effects of using oral antibiotics without MBP for the prevention of SSI. In particular, well-designed RCTs are needed to compare oral antibiotics and adequate intravenous prophylactic antibiotics vs. adequate intravenous prophylactic antibiotics only. The GDG noted also that there is limited evidence on the role of these interventions for patients undergoing laparoscopic procedures. However, some observational studies of mixed populations who underwent open and laparoscopic procedures suggested benefits for MBP across all groups. A RCT was recently published on this topic and showed a significant reduction of SSI in laparoscopic patients receiving oral antibiotics in addition to MBP and standard intravenous antibiotic prophylaxis (32). However, this study could not be included in the systematic review due to the time limits determined for study inclusion.

References

1.
Espin-Basany E, Sanchez-Garcia JL, Lopez-Cano M, Lozoya-Trujillo R, Medarde-Ferrer M, Armadans-Gil L, et al. Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics? Int J Colorectal Dis. 2005;20(6):542–6. [PubMed: 15843938]
2.
Lewis RT. Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s. Can J Surg. 2002;45(3):173–80. [PMC free article: PMC3686946] [PubMed: 12067168]
3.
Oshima T, Takesue Y, Ikeuchi H, Matsuoka H, Nakajima K, Uchino M, et al. Preoperative oral antibiotics and intravenous antimicrobial prophylaxis reduce the incidence of surgical site infections in patients with ulcerative colitis undergoing IPAA. Dis Colon Rectum. 2013;56(10):1149–55. [PubMed: 24022532]
4.
Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamata H, Ozaki T, et al. Comparison between oral antibiotics and probiotics as bowel preparation for elective colon cancer surgery to prevent infection: prospective randomized trial. Surgery. 2014;155(3):493–503. [PubMed: 24524389]
5.
Takesue Y, Yokoyama T, Akagi S, Ohge H, Murakami Y, Sakashita Y, et al. A brief course of colon preparation with oral antibiotics. Surg Today. 2000;30(2):112–6. [PubMed: 10664331]
6.
Ishida H, Yokoyama M, Nakada H, Inokuma S, Hashimoto D. Impact of oral antimicrobial prophylaxis on surgical site infection and methicillin-resistant Staphylococcus aureus infection after elective colorectal surgery. Results of a prospective randomized trial. Surg Today. 2001;31(11):979–83. [PubMed: 11766085]
7.
Kobayashi M, Mohri Y, Tonouchi H, Miki C, Nakai K, Kusunoki M. Randomized clinical trial comparing intravenous antimicrobial prophylaxis alone with oral and intravenous antimicrobial prophylaxis for the prevention of a surgical site infection in colorectal cancer surgery. Surg Today. 2007;37(5):383–8. [PubMed: 17468819]
8.
Stellato TA, Danziger LH, Gordon N, Hau T, Hull CC, Zollinger RM, Jr., et al. Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis. Am Surg. 1990;56(4):251–4. [PubMed: 2194417]
9.
Horie T. Randomized controlled trial on the necessity of chemical cleaning as preoperative preparation for colorectal cancer surgery. Dokkyo J Med Sci. 2007;34.
10.
Roos D, Dijksman LM, Oudemans-van Straaten HM, de Wit LT, Gouma DJ, Gerhards MF. Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery. Br J Surg. 2011;98(10):1365–72. [PubMed: 21751181]
11.
Taylor EW, Lindsay G. Selective decontamination of the colon before elective colorectal surgery. West of Scotland Surgical Infection Study Group. World J Surg. 1994;18(6):926–31; discussion 31–2. [PubMed: 7846921]
12.
Postmarket drug safety information for patients and providers. Silverspring (MD): Food and Drug Administration; 2015 (http://www​.fda.gov/Drugs​/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/default​.htm, accessed 21 July 2016).
13.
Anderson DJ, Podgorny K, Berr›os-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control. 2014;35(06):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
14.
Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337:a1924. [PubMed: 18957455]
15.
Barrera E A, Cid B H, Bannura C G, Contreras R J, Z‡niga T C, Mansilla E J. Utilidad de la preparacifin mecanica anterfigrada en cirug›a colorrectal electiva. Resultados de una serie prospectiva y aleatoria [Usefulness of anterograde mechanical bowel cleansing in colorectal surgery.]. Rev Chil Cir. 2012;64:373–7.
16.
Bretagnol F, Panis Y, Rullier E, Rouanet P, Berdah S, Dousset B, et al. Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial. Ann Surg. 2010;252(5):863–8. [PubMed: 21037443]
17.
Bucher P, Gervaz P, Soravia C, Mermillod B, Erne M, Morel P. Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery. Br J Surg. 2005;92(4):409–14. [PubMed: 15786427]
18.
Burke P, Mealy K, Gillen P, Joyce W, Traynor O, Hyland J. Requirement for bowel preparation in colorectal surgery. Br J Surg. 1994;81(6):907–10. [PubMed: 8044619]
19.
Contant CM, Hop WC, van’t Sant HP, Oostvogel HJ, Smeets HJ, Stassen LP, et al. Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial. Lancet. 2007;370(9605):2112–7. [PubMed: 18156032]
20.
Fa-Si-Oen P, Roumen R, Buitenweg J, van de Velde C, van Geldere D, Putter H, et al. Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery. Dis Colon Rectum. 2005;48(8):1509–16. [PubMed: 15981065]
21.
Jung B, Pahlman L, Nystrom PO, Nilsson E. Multicentre randomized clinical trial of mechanical bowel preparation in elective colonic resection. Br J Surg. 2007;94(6):689–95. [PubMed: 17514668]
22.
Miettinen RP, Laitinen ST, Makela JT, Paakkonen ME. Bowel preparation with oral polyethylene glycol electrolyte solution vs. no preparation in elective open colorectal surgery: prospective, randomized study. Dis Colon Rectum. 2000;43(5):669–75; discussion 75–7. [PubMed: 10826429]
23.
Pena-Soria MJ, Mayol JM, Anula R, Arbeo-Escolar A, Fernandez-Represa JA. Single-blinded randomized trial of mechanical bowel preparation for colon surgery with primary intraperitoneal anastomosis. J Gastrointest Surg. 2008;12(12):2103–8; discussion 8–9. [PubMed: 18820977]
24.
Ram E, Sherman Y, Weil R, Vishne T, Kravarusic D, Dreznik Z. Is mechanical bowel preparation mandatory for elective colon surgery? A prospective randomized study. Arch Surg. 2005;140(3):285–8. [PubMed: 15781794]
25.
Santos JC, Jr., Batista J, Sirimarco MT, Guimaraes AS, Levy CE. Prospective randomized trial of mechanical bowel preparation in patients undergoing elective colorectal surgery. Br J Surg. 1994;81(11):1673–6. [PubMed: 7827905]
26.
Young Tabusso F, Celis Zapata J, Berrospi Espinoza F, Payet Meza E, Ruiz Figueroa E. [Mechanical preparation in elective colorectal surgery, a usual practice or a necessity?]. Rev Gastroenterol Peru. 2002;22(2):152–8. [PubMed: 12098743]
27.
Zmora O, Mahajna A, Bar-Zakai B, Rosin D, Hershko D, Shabtai M, et al. Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial. Ann Surg. 2003;237(3):363–7. [PMC free article: PMC1514315] [PubMed: 12616120]
28.
Cannon JA, Altom LK, Deierhoi RJ, Morris M, Richman JS, Vick CC, et al. Preoperative oral antibiotics reduce surgical site infection following elective colorectal resections. Dis. Colon Rectum. 2012;55(11):1160–6. [PubMed: 23044677]
29.
Morris MS, Graham LA, Chu DI, Cannon JA, Hawn MT. Oral Antibiotic bowel preparation significantly reduces surgical site infection rates and readmission rates in elective colorectal surgery. Ann Surg. 2015;261(6):1034–40. [PubMed: 25607761]
30.
Scarborough JE, Mantyh CR, Sun Z, Migaly J. Combined mechanical and oral antibiotic bowel preparation reduces incisional surgical site infection and anastomotic leak rates after elective colorectal resection: an analysis of colectomy-targeted ACS NSQIP. Ann Surg. 2015;262(2):331–7. [PubMed: 26083870]
31.
Anthony T, Murray BW, Sum-Ping JT, Lenkovsky F, Vornik VD, Parker BJ, et al. Evaluating an evidence-based bundle for preventing surgical site infection: a randomized trial. Arch Surg. 2011;146(3):263–9. [PubMed: 21079110]
32.
Hata H, Yamaguchi T, Hasegawa S, Nomura A, Hida K, Nishitai R, et al. Oral and parenteral versus parenteral antibiotic prophylaxis in elective laparoscopic colorectal surgery (JMTO PREV 07-01): a phase 3, multicenter, open-label, randomized trial. Ann Surg. 2016;263:1085–91. [PubMed: 26756752]

4.6. Hair removal

Recommendation

The panel recommends that in patients undergoing any surgical procedure, hair should either not be removed or, if absolutely necessary, it should be removed only with a clipper. Shaving is strongly discouraged at all times, whether preoperatively or in the operating room (OR).

(Strong recommendation, moderate quality of evidence)

Rationale for the recommendation

  • For the formulation of the recommendation, the GDG considered the meta-analysis comparing clipping and no hair removal vs. shaving to be the most relevant. Moderate quality evidence shows a clear benefit of either no hair removal or clipping when compared to shaving with a significant decrease of the SSI risk.
  • As a result, the GDG unanimously agreed to recommend that hair should either not be removed or, if absolutely necessary, it should be removed only with a clipper and the strength of this recommendation should be strong.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. However, the GDG considers this recommendation valid also for paediatric patients.
  • When analysed separately, there was no significant difference between clipping and shaving compared to no hair removal, but clipping was found to be significantly beneficial when compared to shaving. The GDG decided that no hair removal and clipping should be compared to shaving in the same group as they are both similar in nature.
  • It was noted that only one study (1) compared different times of hair removal (night before vs. day of surgery for both shaving and clipping). This study showed no clear evidence favouring any of the times for either method. Therefore, the GDG agreed that no recommendation regarding the timing of hair removal could be given. However, it was acknowledged that if hair is removed, removal shortly before surgery could be the most practical and safest approach.
  • No studies were identified evaluating the effect of settings where hair removal is performed (OR vs. ward or home) with the outcome of SSI. Thus, the GDG agreed that no recommendation could be developed regarding the location of hair removal with clippers when this is necessary.
  • The GDG did not identify any possible harm associated with no hair removal or using clippers.

Background

Removal of hair from the intended site of surgical incision has traditionally been part of the routine preoperative preparation of patients undergoing surgery. Hair removal may be necessary to facilitate adequate exposure and preoperative skin marking. Furthermore, suturing and the application of wound dressings can be complicated by the presence of hair. Apart from these practical issues, hair has been associated with a lack of cleanliness and the potential to cause SSI. There is also the belief that hair removal inversely increases the risk of SSI by causing microscopic trauma of the skin. To minimize the potential of skin trauma, the use of clippers instead of razors has been proposed for preoperative hair removal. In contrast to razors that involve a sharp blade drawn directly over the skin, clippers cut the hair close to the skin without actually touching it. A third method for hair removal is the application of depilatory creams containing chemicals. Drawbacks of the use of these creams are the necessity to leave them in place for approximately 15–20 minutes for the hair to be dissolved and the potential for allergic reactions. A Cochrane review published in 2009 and updated in 2011 found no statistically significant difference in SSI rates between hair removal and no hair removal interventions.

However, a significant harm was observed when hair removal with razors was compared with clipping (2).

Among available guidelines, 4 explicitly recommend to avoid routine hair removal as a part of preoperative measures to prevent SSI (36).

All other guidelines recommend not using razors. If electric clippers are used, a single-use head should be used (Table 4.6.1). Only a few guidelines provide an evaluation of the quality of the evidence.

Table 4.6.1. Recommendations on hair removal according to available guidelines.

Table 4.6.1

Recommendations on hair removal according to available guidelines.

Following the in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the available evidence on the need and correct method for hair removal.

Summary of the evidence

The purpose of the evidence review (web Appendix 7) was to investigate whether the method and timing of hair removal (using clippers, depilatory cream or shaving with razors) or no hair removal affect the incidence of SSI. The target population was patients of all ages undergoing a surgical procedure. The primary outcomes were the occurrence of SSI and SSI-attributable mortality.

A total of 15 RCTs or quasi-randomized trials (1, 922) comparing the effect of preoperative hair removal vs. no hair removal or different methods of hair removal (shaving, clipping and depilatory cream) were identified. Meta-analyses were performed to evaluate the following comparisons: shaving, clipping and depilatory cream individually vs. no hair removal, shaving vs. clipping and shaving vs. depilatory cream. As no hair removal and clipping are similar in terms of reduced potential to cause microscopic skin trauma, an additional analysis was performed combining no hair removal and clipping vs. shaving.

A low to very low quality of evidence shows that shaving, clipping or the use of depilatory cream has neither benefit nor harm related to the reduction of the SSI rate when compared to no hair removal (OR: 1.78; 95% CI: 0.96–3.29; OR: 1.00;95% CI: 0.06–16.34; and OR: 1.02; 95% CI: 0.42–2.49, respectively).

However, when hair is removed, there is a low quality of evidence showing that clipping has a significant benefit in reducing the SSI rate compared to shaving (OR: 0.51; 95% CI: 0.29–0.91). A very low quality of evidence shows that the use of depilatory cream has neither benefit nor harm when compared to shaving for the prevention of SSI (OR: 2.78; 95% CI: 0.86–9.03). When clipping and no hair removal were combined in the meta-analysis, a moderate quality of evidence showed that both are associated with a significantly lower risk of SSI when compared to shaving (OR: 0.51; 95% CI: 0.34–0.78).

A moderate quality of evidence shows that hair removal the day before surgery does not affect the SSI rate compared to hair removal on the day of surgery (OR: 1.22; 95% CI: 0.44–3.42).

The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

Studies evaluating surgeon or patient preferences for hair removal show variable results. Ilankovan and colleagues investigated patient and surgeon preferences before maxillofacial surgery and showed that patients prefer no hair removal over shaving, while the surgeons’ assessment of the difficulty of wound closure did not differ between the two methods (18).

The GDG acknowledged that the preferences of both patients and surgeons may differ according to the body area. Some members expressed the following opinions.

  • Surgeons may be hesitant to use clippers in the male genitalia area.
  • Women may prefer shaving for surgery in the genital area or even come to the hospital already shaved because of cultural norms.
  • Surgeons may prefer to remove hair because of concerns that long hair would interfere with surgery and stick to the drapes.

While acknowledging this variability of approaches and cultural issues, the GDG emphasized that these preferences could be changed with an awareness-raising campaign to highlight the benefits of the recommendation and the harms of shaving practices, together with strong implementation strategies. Furthermore, the GDG was confident that the typical values of the target population regarding the SSI outcome would most probably favour the intervention.

Resource use

The GDG observed that avoiding hair removal has no cost and puts no burden on staff. Clippers are expensive and it might be difficult to procure them in LMICs. It is generally advisable to use single-use clippers/clipper heads, which may again be difficult to procure in LMICs. Of note, when reused, clipper heads can be very difficult to clean and decontaminate. When required for reuse, the GDG suggests that local infection prevention procedures are followed for clipper/clipper head decontamination, taking into account the following basic instructions for the general process: carefully disassemble the blades; clean with soap and water using a cloth and wearing appropriate personal protective equipment; dry with a fresh cloth and wipe with alcohol, again using a fresh cloth. Following the procedure, dispose of cloths and personal protective equipment, cleanse hands and store the clipper in a clean, covered dry storage space to avoid contamination.

Research gaps

Although the evidence to support the recommendation appears to be sufficient, the GDG provided the following directions for additional research on this topic. Studies are needed to evaluate the optimal timing and the most appropriate setting (ward vs. home) for the hair removal procedure when it is considered necessary by the surgeon. It would be important also to conduct surveys on the acceptability of patients and surgeons regarding hair removal (or not) prior to surgery, particularly for body areas where preferences may vary, for example, genitalia for females and the maxillofacial area for males. The best and most acceptable methods of hair removal in settings with limited resources need to be investigated, including low-cost solutions. In particular, studies with a focus on the use of clippers in LMICs are needed to stimulate research on the design and production of an affordable clipper for these settings, including a cost-effectiveness analysis. For all settings, research is required to develop and test evidence-based procedures on how to decontaminate clippers.

References

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Alexander JW, Fischer JE, Boyajian M, Palmquist J, Morris MJ. The influence of hair-removal methods on wound infections. Arch Surg. 1983;118(3):347–52. [PubMed: 6824435]
2.
Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011(11):CD004122. [PubMed: 22071812]
3.
Mangioni C, Bianchi L, Bolis PF, Lomeo AM, Mazzeo F, Ventriglia L, et al. Multicenter trial of prophylaxis with clindamycin plus aztreonam or cefotaxime in gynecologic surgery. Clin Infect Dis. 1991;13(Suppl.7):S621–5. [PubMed: 2068470]
4.
Hemsell DL, Bernstein SG, Bawdon RE, Hemsell PG, Heard MC, Nobles BJ. Preventing major operative site infection after radical abdominal hysterectomy and pelvic lymphadenectomy. Gynecol Oncol. 1989; 35(1):55–60. [PubMed: 2792903]
5.
Friese S, Willems FT, Loriaux SM, Meewis JM. Prophylaxis in gynaecological surgery: a prospective randomized comparison between single dose prophylaxis with amoxycillin/clavulanate and the combination of cefuroxime and metronidazole. J Antimicrob Chemother. 1989;24 (Suppl. B):213–6. [PubMed: 2691483]
6.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
7.
Yildiz B, Abbasoglu O, Tirnaksiz B, Hamaloglu E, Ozdemir A, Sayek I. Determinants of postoperative infection after laparoscopic cholecystectomy. Hepatogastroenterology. 2009; 56(91–92):589–92. [PubMed: 19621660]
8.
Neri V, Fersini A, Ambrosi A, Tartaglia N, Valentino TP. Umbilical port-site complications in laparoscopic cholecystectomy: role of topical antibiotic therapy. JSLS. 2008;12(2):126–32. [PMC free article: PMC3016169] [PubMed: 18435883]
9.
Thur de Koos P, McComas B. Shaving versus skin depilatory cream for preoperative skin preparation. A prospective study of wound infection rates. Am J Surg. 1983;145:377–8. [PubMed: 6837864]
10.
Goëau-Brissonnière O, Coignard S, Merao AP, Haicault G, Sasako M, Patel JC. [Preoperative skin preparation. A prospective study comparing a depilatory agent in shaving]. Presse Med. 1987;16(31):1517–9. [PubMed: 2958817]
11.
Abouzari M, Sodagari N, Hasibi M, Behzadi M, Rashidi A. Re: Nonshaved cranial surgery in black Africans: a short-term prospective preliminary study (Adeleye and Olowookere, Surg Neurol 2008;69–72) Effect of hair on surgical wound infection after cranial surgery: a 3-armed randomized clinical trial. Surg Neurol. 2009;71(2):261–2. [PubMed: 18440617]
12.
Adisa AO, Lawal OO, Adejuyigbe O. Evaluation of two methods of preoperative hair removal and their relationship to postoperative wound infection. J Infect Dev Ctries. 2011;5(10):717–22. [PubMed: 21997940]
13.
Balthazar ER, Colt JD, Nichols RL. Preoperative hair removal: a random prospective study of shaving versus clipping. South Med J. 1982;75(7):799–801. [PubMed: 7089645]
14.
Celik SE, Kara A. Does shaving the incision site increase the infection rate after spinal surgery? Spine. 2007;32(15):1575–7. [PubMed: 17621202]
15.
Court-Brown CM. Preoperative skin depilation and its effect on postoperative wound infections. J R Coll Surg Edinb. 1981;26(4):238–41. [PubMed: 7021812]
16.
Grober ED, Domes T, Fanipour M, Copp JE. Preoperative hair removal on the male genitalia: clippers vs. razors. J Sex Med. 2013;10(2):589–94. [PubMed: 22908852]
17.
Horgan MA, Kernan JC, Schwartz MS, Kellogg JX, McMenomey SO, Delashaw JB. Shaveless brain surgery: safe, well tolerated, and cost effective. Skull Base Surg. 1999;9(4):253–8. [PMC free article: PMC1656773] [PubMed: 17171113]
18.
Ilankovan V, Starr DG. Preoperative shaving: patient and surgeon preferences and complications for the Gillies incision. J R Coll Surg Edinb. 1992;37(6):399–401. [PubMed: 1283411]
19.
Kattipattanapong W, Isaradisaikul S, Hanprasertpong C. Surgical site infections in ear surgery: hair removal effect; a preliminary, randomized trial study. Otolaryngol Head Neck Surg. 2013;148(3):468–74. [PubMed: 23283828]
20.
Powis SJ, Waterworth TA, Arkell DG. Preoperative skin preparation: clinical evaluation of depilatory cream. BMJ. 1976;2(6045):1166–8. [PMC free article: PMC1689580] [PubMed: 791444]
21.
Rojanapirom S, Danchaivijitr S. Pre-operative shaving and wound infection in appendectomy. J Med Assoc Thai. 1992;75(Suppl. 2);20–3. [PubMed: 1402495]
22.
Seropian R, Reynolds BM. Wound infections after preoperative depilatory versus razor preparation. Am J Surg. 1971;121(3):251–4. [PubMed: 5546329]

4.7. Surgical site preparation

Recommendation

The panel recommends alcohol-based antiseptic solutions based on CHG for surgical site skin preparation in patients undergoing surgical procedures.

(Strong recommendation, low to moderate quality of evidence)

Rationale for the recommendation

  • Moderate quality evidence shows that the use of alcohol-based antiseptic solutions for surgical site skin preparation is more effective compared to aqueous solutions in reducing SSI. A meta-analysis of available studies (low quality of evidence) showed that alcohol-based CHG is beneficial in reducing SSI rates compared to alcohol-based povidone-iodine (PVP-I). As a result, the GDG agreed to recommend the use of an alcohol-based antiseptic solution preferably based on CHG for surgical site preparation on intact skin. The strength of this recommendation was considered to be strong.
  • The GDG discussed whether to formulate the recommendation for adult patients only or to make a recommendation for all patients. The body of evidence focused on adult patients. The paediatric population was not represented as most commercially-available products have no indications for use in these patients due to the lack of studies in this population. By contrast, the GDG emphasized that it is unlikely that high quality evidence will be available in the future on paediatric patients, mainly due to ethical reasons.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, the effectiveness of this intervention is not proven for paediatric patients.
  • Although the systematic review time limits for inclusion were set to a publication date between 1 January 1960 and 15 August 2014, a relevant trial published on 4 February 2016 was exceptionally included after discussion with the WHO Guidelines Review Committee and the GDG. The GDG was confident that no additional relevant trial had been published since the systematic review set date and therefore the search was not fully updated.
  • According to the available studies, a sub-analysis of the comparison of alcohol-based antiseptic solutions vs. aqueous solutions was performed. A significant benefit in reducing the risk of SSI was observed with CHG in an alcohol-based solution compared to PVP-I in an aqueous solution. No significant difference was found between alcohol-based vs. aqueous PVP-I solutions. Most of the included studies used isopropyl alcohol at a concentration of 70–74%. Concentrations of the iodophor compound ranged from 0.7–10% and from 0.5–4% for CHG. Due to this heterogeneity and the lack of data to confirm any one direction, the GDG did not feel comfortable to include a statement about the concentration of the antiseptic compound in the recommendation.
  • Washing the patient’s skin with detergents or antiseptics is dealt with in chapter 4.1 and should be performed separately outside of the OR, whereas surgical site skin preparation is done prior to surgery within the OR.
  • The GDG identified possible harms associated with the use of alcohol-based solutions and it was highlighted that they should not be used on neonates or be in contact with mucosa or eyes. CHG solutions must not be allowed to come into contact with the brain, meninges, eye or middle ear. As alcohol is highly flammable, alcohol-based antiseptic preparations may ignite if used in the presence of diathermy and they must be allowed to dry by evaporation. Therefore, it is advisable to ensure that the drapes are not saturated with alcohol or that the alcohol-based solution has not formed a pool underneath the patient before operating. While possible allergies should be accounted for (for example, to PVP-I), it should be noted that CHG has a potential risk of causing skin irritation. OR staff should be trained and informed about the potential harms associated with the solutions used for surgical site preparation.

Background

Surgical site preparation refers to the preoperative treatment of the intact skin of the patient within the OR. Preparation includes not only the immediate site of the intended surgical incision, but also a broader area of the patient’s skin. The aim of this procedure is to reduce the microbial load on the patient’s skin as much as possible before incision of the skin barrier. The most widely used agents include CHG and PVP-I in alcohol-based solutions, which are effective against a wide range of bacteria, fungi and viruses. However, aqueous solutions, particularly those containing iodophors, are also widely used, notably in developing countries.

Application techniques for preoperative surgical site preparation are also a topic of interest.

However, 3 trials investigating the effect of the application technique with comparable antiseptic compounds showed no difference in surgical site infection (SSI) rates (13). Despite current knowledge of the antimicrobial activity of many antiseptic agents and application techniques, it remains unclear what is the best approach to surgical site preparation (4, 5).

Several guidelines, such as those published by SHEA/IDSA) (6), NICE (7) or the Royal College of Physicians of Ireland (8), recommend the use of an alcohol-based solution for surgical site preparation (Table 4.7.1). However, these recommendations are not based upon systematic reviews of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

Table 4.7.1. Recommendations on surgical site skin preparation according to available guidelines.

Table 4.7.1

Recommendations on surgical site skin preparation according to available guidelines.

Following the in-depth analysis of the sources and strength of evidence in available guidelines, the GDG decided to conduct a systematic review to assess the available evidence on the efficacy of solutions and antiseptic agents used for surgical site skin preparation.

Summary of the evidence

The purpose of the evidence review (web Appendix 8) was to compare the effect of different solutions (alcohol-based vs. aqueous preparations) and antiseptic agents (CHG vs. PVP-I) used for surgical site skin preparation in order to prevent SSI. The target population included patients of all ages undergoing a surgical procedure. The primary outcomes were the occurrence of SSI and SSI-attributable mortality.

A total of 17 RCTs (2, 1227) comparing antiseptic agents (PVP-I and CHG) in aqueous or alcohol-based solutions were identified. According to the selected studies, the following comparisons were evaluated:

  1. Alcohol-based antiseptic solutions vs. aqueous solutions
    a)

    CHG in an alcohol-based solution vs. PVP-I in an aqueous solution

    b)

    PVP-I in an alcohol-based solution vs. PVP-I in an aqueous solution

  2. CHG vs. PVP-I - both in alcohol-based solutions

Moderate quality evidence shows that alcohol-based antiseptic solutions are overall more effective compared to aqueous solutions in reducing the risk of SSI (OR: 0.60; 95% CI: 0.45–0.78). More specifically, a low quality of evidence shows a significant reduction of the SSI risk with the use of alcohol-based CHG compared to PVP-I in alcohol-based solutions (OR: 0.58; 95% CI: 0.42–0.80). Moderate quality evidence shows also a significant benefit in using CHG alcohol-based solutions compared to aqueous PVP-I for the reduction of SSI rates (OR 0.65; 95% CI: 0.47–0.90). However, very low quality evidence suggests that there is no significant difference between PVP-I alcohol-based solutions and PVP-I aqueous solutions (OR 0.61; 95% CI: 0.19–1.92).

The literature search did not identify any studies that used aqueous CHG for surgical site skin preparation. The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Furthermore, most commercially available products have no indications for use in paediatric patients due to the lack of studies in this population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patients’ values and preferences with regards to this intervention. The GDG concluded that most patients wish to receive this intervention in order to reduce the risk of SSI.

However, the use of alcohol might be refused by patients and/or health care workers because of religious reasons. This issue was addressed as part of the WHO Clean Care is Safer Care programme of work and a chapter on this topic is included in the WHO guidelines on hand hygiene in health care (28), which recommends the preferred use of alcohol-based handrub (ABHR) for hand cleansing. The engagement of cultural and religious leaders (for example, in the hand hygiene campaign in health care facilities) proved useful to overcome such barriers and positive solutions were found. Indeed, an encouraging example is the statement issued by the Muslim Scholars’ Board of the Muslim World League during the Islamic High Council’s meeting held in Mecca, Saudi Arabia, in January 2002: “It is allowed to use medicines that contain alcohol in any percentage that may be necessary for manufacturing if it cannot be substituted. Alcohol may be used as an external wound cleanser, to kill germs, and in external creams and ointments.” There may be a necessity to resume the discussion with religious leaders and individual patients with regards to the recommendation to use alcohol-based solutions for surgical site skin preparation.

Resource use

The GDG highlighted that the availability of alcohol-based solutions is limited in LMICs, particularly when combined with an antiseptic compound. These commercial products may represent a financial burden to health care facilities and patients if they are required to provide care supplies. The GDG discussed the implementation of this recommendation in LMICs and argued that local production may be a more affordable and feasible option in these settings, provided that adequate quality control is put in place. As an example, in the context of the Surgical Unit-based Safety Programme, instructions for the local production of an alcohol- and CHG-based preparation were produced and implemented by WHO in 5 African hospitals (29). A cost-effectiveness study (30) found that although CHG is more expensive, its effectiveness to reduce SSI makes it up to 36% more cost-effective than PVP-I.

Research gaps

GDG members highlighted that the use of alcohol-based solutions in surgical site skin preparation per se is no longer a research topic. There is a need for well-designed RCTs comparing specific preparations containing CHG, PVP-I and other antiseptics in alcohol-based and other solutions, taking into consideration their effectiveness, toxicity and costs. The GDG remarked that studies should focus on SSI as the critical endpoint and defined according to the CDC criteria. Furthermore, there is a need to compare commercial products with locally-produced solutions in health facilities in LMICs in effectiveness and cost-effectiveness studies. As there are no studies investigating the use of these solutions in paediatric patients, studies in this population would be particularly welcome. Currently, a few alcohol-based or aqueous solutions with antiseptic compounds contain colouring agents. Adding these agents to preparations can be helpful to indicate where surgical site preparation products have been applied on the patient’s skin, but further studies would be needed if new colouring agents are proposed in order to ascertain effectiveness and tolerability.

References

1.
Ellenhorn JD, Smith DD, Schwarz RE, Kawachi MH, Wilson TG, McGonigle KF, et al. Paint-only is equivalent to scrub-and-paint in preoperative preparation of abdominal surgery sites. J Am Coll Surg. 2005;201(5):737–41. [PubMed: 16256917]
2.
Segal CG, Anderson JJ. Preoperative skin preparation of cardiac patients. AORN J. 2002;76(5):821–8. [PubMed: 12463081]
3.
Shirahatti RG, Joshi RM, Vishwanath YK, Shinkre N, Rao S, Sankpal JS, et al. Effect of pre-operative skin preparation on postoperative wound infection. J Postgrad Med. 1993;39(3):134–6. [PubMed: 8051642]
4.
Lowbury EJ. Prevention of postoperative infection. Injury. 1985;16(9):583–4. [PubMed: 4086094]
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Mishriki SF, Law DJ, Jeffery PJ. Factors affecting the incidence of postoperative wound infection. J Hosp Infect. 1990;16(3):223–30. [PubMed: 1979572]
6.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
7.
A summary of selected new evidence relevant to NICE clinical guideline 74 “Prevention and treatment of surgical site infection” (2008). Evidence update 43. June 2013. Manchester: National Institute for Health and Care Excellence; 2013. (http://www​.nice.org.uk​/guidance/cg74/evidence, accessed 21 July 2016).
8.
Preventing surgical site infections. Key recommendations for practice. Dublin: Joint Royal College of Surgeons in Ireland/Royal Colleges of Physicians of Ireland Working Group on Prevention of Surgical Site Infection; 2012 (https://www​.rcsi.ie/files​/surgery/docs/20140318021114​_Sample​%20Audit%20Surgical%20site%20Inf.pdf, accessed 21 July 2016).
9.
How-to guide: prevent surgical site infection for hip and knee arthroplasty. Cambridge (MA): Institute for Healthcare Improvement; 2012 (http://www​.IHI.org, accessed 21 July 2016).
10.
Targeted literature review: What are the key infection prevention and control recommendations to inform a surgical site infection (SSI) prevention quality improvement tool? Version 3.0. February 2015. Edinburgh: Health Protection Scotland; 2015 (http://www​.documents​.hps.scot.nhs.uk/hai​/infection-control/evidence-for-care-bundles​/literature-reviews​/ssi-review-2015-02.pdf, accessed 21 July 2016).
11.
High impact intervention: care bundle to prevent surgical site infection. London: Department of Health; 2011 (http://webarchive​.nationalarchives​.gov.uk​/20120118164404/http://hcai​.dh.gov.uk/files​/2011/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL.pdf, accessed 21 July 2016).
12.
Rodrigues AL, Simoes Mde L. Incidence of surgical site infection with pre-operative skin preparation using 10% polyvidone-iodine and 0.5% chlorhexidine-alcohol. Rev Col Bras Cir. 2013;40(6):443–8. [PubMed: 24573620]
13.
Sistla SC, Prabhu G, Sistla S, Sadasivan J. Minimizing wound contamination in a ‘clean’ surgery: comparison of chlorhexidine-ethanol and povidone-iodine. Chemotherapy. 2010;56(4):261–7. [PubMed: 20693796]
14.
Srinivas A, Kaman L, Raj P, Gautam V, Dahiya D, Singh G, et al. Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries. Surg Today. 2014;45:1378–84 [PubMed: 25381486]
15.
Paocharoen V, Mingmalairak C, Apisarnthanarak A. Comparison of surgical wound infection after preoperative skin preparation with 4% chlohexidine and povidone iodine: A prospective randomized trial. J Med Associ Thai. 2009;92(7):898–902. [PubMed: 19626807]
16.
Bibbo C, Patel DV, Gehrmann RM, Lin SS. Chlorhexidine provides superior skin decontamination in foot and ankle surgery: a prospective randomized study. Clin Orthop Rel Res. 2005;438:204–8. [PubMed: 16131892]
17.
Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL. Efficacy of surgical preparation solutions in shoulder surgery. J Bone Joint Surg (Am). 2009;91:1949–53. [PubMed: 19651954]
18.
Roberts A, Wilcox K, Devineni R, Harris R, Osevala M. Skin preparation in CABG surgery: A prospective randomized trial. Complications Surg. 1995;14(6):741–7.
19.
Howard R. Comparison of a 10-minute aqueous iodophor and 2-minute water-insoluble iodophor in alcohol preoperative skin preparation. Complications Surg. 1991;10.
20.
Hort KR, DeOrio JK. Residual bacterial contamination after surgical preparation of the foot or ankle with or without alcohol. Foot Ankle Int. 2002;23(10):946–8. [PubMed: 12398148]
21.
Gilliam DL, Nelson CL. Comparison of a one-step iodophor skin preparation versus traditional preparation in total joint surgery. Clin Orthop Rel Res. 1990;(250):258–60. [PubMed: 2293938]
22.
Darouiche RO, M. J. Wall J, Itani KMF, Otterson MF, Webb AL, Carrick MM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. New Engl J Med. 2010;362:18–26. [PubMed: 20054046]
23.
Savage JW, Weatherford BM, Sugrue PA, Nolden MT, Liu JC, Song JK, et al. Efficacy of surgical preparation solutions in lumbar spine surgery. J Bone Joint Surg (Am). 2012;94:490–4. [PubMed: 22437997]
24.
Veiga DF, Damasceno CA, Veiga-Filho J, Figueiras RG, Vieira RB, Florenzano FH, et al. Povidone iodine versus chlorhexidine in skin antisepsis before elective plastic surgery procedures: a randomized controlled trial. Plast Reconstr Surg. 2008;122(5):170e-1e. [PubMed: 18971711]
25.
Cheng K, Robertson H, Mart JPS, Leanord A, McLeod I. Quantitative analysis of bacteria in forefoot surgery: a comparison of skin preparation techniques. Foot Ankle Int. 2009;30:992–7. [PubMed: 19796594]
26.
Berry AR, Watt B, Goldacre MJ, Thomson JW, McNair TJ. A comparison of the use of povidone-iodine and chlorhexidine in the prophylaxis of postoperative wound infection. J Hosp Infect. 1982;3(1):55–63. [PubMed: 6177735]
27.
Tuuli MG, Liu J, Stout MJ, Martin S, Cahill AG, Odibo AO, et al. A randomized trial comparing skin antiseptic agents at cesarean delivery. New Engl J Med. 2016;374(7):647–55. [PMC free article: PMC4777327] [PubMed: 26844840]
28.
WHO guidelines on hand hygiene in health care. Geneva: World Health Organization; 2009 (http://apps​.who.int/iris​/bitstream/10665​/44102/1/9789241597906_eng.pdf, accessed 21 July 2016).
29.
Allegranzi B, Aiken AM, Zeynep Kubilay N, Peter Nthumba, Jack Barasa, Gabriel Okumu, et al. A multimodal infection control and patient safety intervention to reduce surgical site infections in Africa: a multicentre, before/after, cohort study. Lancet Infect Dis. 2018;18(5):507–515. [PubMed: 29519766]
30.
Lee I, Agarwal RK, Lee BY, Fishman NO, Umscheid CA. Systematic review and cost analysis comparing use of chlorhexidine with use of iodine for preoperative skin antisepsis to prevent surgical site infection. Infect Control Hosp Epidemiol. 2010;31(12):1219–29. [PMC free article: PMC3833867] [PubMed: 20969449]

4.8. Antimicrobial skin sealants

Recommendation

The panel suggests that antimicrobial sealants should not be used after surgical site skin preparation for the purpose of reducing SSI.

(Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Overall very low quality evidence from eight RCTs and one quasi-randomized trial shows that the preoperative application of antimicrobial skin sealants, in addition to standard surgical site skin preparation, produces neither benefit nor harm in reducing the SSI rate. The GDG unanimously agreed that there is no advantage in using antimicrobial sealants and suggested not using them. Given the quality of the evidence, the GDG decided that the strength of this recommendation should be conditional.

Remarks

  • The body of retrieved evidence mainly focused on adult patients, but one study also included children. This recommendation is valid for both patient populations.
  • The GDG observed that most studies investigating cyanoacrylate-based antimicrobial sealants were funded by manufacturers of commercial sealants.
  • All included studies investigated the use of antimicrobial sealants on the skin of the surgical site before incision.
  • Although the type and concentration of the antiseptics used for skin preparation varied among the included studies, the GDG underlined that the intervention and control groups in each of the studies received the same skin preparation technique, while antimicrobial sealants were added in the intervention group.
  • The GDG identified skin irritation and allergic reactions as possible harms associated with the use of antimicrobial sealants.

Background

The endogenous bacteria on a patient’s skin is believed to be the main source of pathogens that contribute to SSI (1). Surgical site skin preparation commonly includes scrubbing or applying alcohol-based preparations containing antiseptic agents prior to incision, such as CHG or iodine solutions. Additional technologies are being researched and developed to reduce the rate of contamination at the surgical site and subsequent SSI.

Antimicrobial skin sealants are sterile, film-forming cyanoacrylate-based sealants commonly applied as an additional antiseptic measure after standard skin preparation of the surgical site and prior to skin incision. The sealant is intended to remain in place and block the migration of flora from the surrounding skin into the surgical site by dissolving over several days postoperatively. As an antimicrobial substance, sealants have been shown to reduce bacterial counts on the skin of the operative site (2). However, most studies reported only changes in bacterial colonization and did not investigate SSI rates. Therefore, the use of antimicrobial sealants for the purpose of preventing SSIs is still under debate.

Currently available SSI prevention guidelines do not address the use of antimicrobial skin sealants and their effect to prevent SSI. The GDG decided to conduct a systematic review to assess the effectiveness of their use.

Summary of the evidence

The purpose of the evidence review (web Appendix 9) was to evaluate whether the use of antimicrobial skin sealants in addition to standard surgical site skin preparation is more effective in reducing the risk of SSI than standard surgical site skin preparation only. The target population were patients of all ages undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

A total of nine studies including a total of 1974 patients and comprising 8 RCTs (310) and one prospective quasi-randomized trial (11) were identified. The studies compared the effect of the addition of antimicrobial skin sealants to standard skin preparation in the intervention group vs. standard skin preparation only in the control group.

Very low quality evidence shows no benefit or harm for the reduction of SSI rates when using the addition of antimicrobial sealants compared to standard surgical site skin preparation only (OR: 0.69; 95% CI: 0.38–1.25).

The body of retrieved evidence mainly focused on adult patients, but one study also included children. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was retrieved on patient values and preferences with regards to this intervention. However, the GDG observed that some studies (8, 12) reported that patients may suffer skin irritation due to the antimicrobial sealants as they remain on the skin for some time. Therefore, patients may prefer not to experience skin irritation, particularly when there is no evidence of benefit in using antimicrobial sealants to prevent SSI.

Resource use

The GDG pointed out that the availability of antimicrobial sealants may be limited in LMICs and their cost was a potential major resource concern. Lipp and colleagues observed that no studies included in a meta-analysis reported the cost of cyanoacrylate sealants as a preoperative preparation of the surgical site and no benefit was shown in preventing SSI (13).

In addition to economic concerns, the availability of these commercial products may be an added barrier in LMICs. Furthermore, training in the proper technique and resources for their use would need to be available for surgical staff.

Research gaps

GDG members highlighted that many of the available RCTs have a high risk of bias and potential conflicts of interest. Several studies were excluded because they reported only bacterial colonization and not SSI as the primary outcome. Further studies are needed to identify evidence associated with important outcomes, including SSI rates (rather than microbial data), length of stay, cost-effectiveness and adverse effects on skin.

Most of the included studies investigated the use of cyanoacrylate-based sealants in contaminated procedures and the use of these agents may be more or less effective in other procedures. Importantly, the protocol for standard surgical site skin preparation with antiseptics varied across studies, thus making it difficult to discern the actual effect of the sealant alone. The GDG considers that more well-designed RCTs with adequate power are needed. These should focus on SSI as the primary outcome, rather than a reduction in the microbial load. Conducting trials with a more diverse surgical patient population will also further support evidence-based guidance on the use of antimicrobial sealants. For example, more evidence is needed in paediatric surgical patients.

References

1.
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27(2):97–132; quiz 3–4; discussion 96. [PubMed: 10196487]
2.
Dohmen PM. Impact of antimicrobial skin sealants on surgical site infections. Surg Infect (Larchmt). 2014;15(4):368–71. [PubMed: 24818521]
3.
Daeschlein G, Napp M, Assadian O, Bluhm J, Krueger C, von Podewils S, et al. Influence of preoperative skin sealing with cyanoacrylate on microbial contamination of surgical wounds following trauma surgery: a prospective, blinded, controlled observational study. Int J Infect Dis. 2014;29:274–8. [PubMed: 25449258]
4.
Doorly M, Choi J, Floyd A, Senagore A. Microbial sealants do not decrease surgical site infection for clean-contaminated colorectal procedures. Tech Coloproctol. 2015;19(5):281–5. [PubMed: 25772684]
5.
Dromzee E, Tribot-Laspiere Q, Bachy M, Zakine S, Mary P, Vialle R. Efficacy of integuseal for surgical skin preparation in children and adolescents undergoing scoliosis correction. Spine. 2012;37(21):e1331–5. [PubMed: 22814302]
6.
Falk-Brynhildsen K, Soderquist B, Friberg O, Nilsson U. Bacterial growth and wound infection following saphenous vein harvesting in cardiac surgery: a randomized controlled trial of the impact of microbial skin sealant. Europ J Clin Microbiol Infect Dis. 2014;33(11):1981–7. [PubMed: 24907853]
7.
Iyer A, Gilfillan I, Thakur S, Sharma S. Reduction of surgical site infection using a microbial sealant: a randomized trial. J Thorac Cardiovasc Surg. 2011;142(2):438–42. [PubMed: 21440263]
8.
Towfigh S, Cheadle WG, Lowry SF, Malangoni MA, Wilson SE. Significant reduction in incidence of wound contamination by skin flora through use of microbial sealant. Arch Surg. 2008;143(9):885–91; discussion 91. [PubMed: 18794427]
9.
Vierhout BP, Ott A, Reijnen MM, Oskam J, Ott A, van den Dungen JJ, et al. Cyanoacrylate skin microsealant for preventing surgical site infection after vascular surgery: a discontinued randomized clinical trial. Surg Infect (Larchmt). 2014;15(4):425–30. [PubMed: 24840774]
10.
von Eckardstein AS, Lim CH, Dohmen PM, Pego-Fernandes PM, Cooper WA, Oslund SG, et al. A randomized trial of a skin sealant to reduce the risk of incision contamination in cardiac surgery. Ann Thorac Surg. 2011;92(2):632–7. [PubMed: 21704290]
11.
Waldow T, Szlapka M, Hensel J, Plotze K, Matschke K, Jatzwauk L. Skin sealant InteguSeal(R) has no impact on prevention of postoperative mediastinitis after cardiac surgery. J Hosp Infect. 2012;81(4):278–82. [PubMed: 22705297]
12.
Roy P, Loubiere A, Vaillant T, Edouard B. [Serious adverse events after microbial sealant application in paediatric patients]. Ann Pharm Fr. 2014;72(6):409–14. [PubMed: 25438651]
13.
Lipp A, Phillips C, Harris P, Dowie I. Cyanoacrylate microbial sealants for skin preparation prior to surgery. Cochrane Database Syst Rev. 2013;8:CD008062. [PubMed: 23963766]

4.9. Surgical hand preparation

Recommendation

The panel recommends that surgical hand preparation be performed either by scrubbing with a suitable antimicrobial soap and water or using a suitable ABHR before donning sterile gloves.

(Strong recommendation, moderate quality of evidence)

Rationale for the recommendation

  • The GDG noted that surgical hand preparation is vitally important to maintain the lowest possible contamination of the surgical field, especially in the event of sterile glove puncture during the procedure. Appropriate surgical hand preparation is recommended in the WHO guidelines on hand hygiene in health care (1) issued in 2009 and in all other existing national and international guidelines on the prevention of SSI.
  • Moderate quality evidence shows the equivalence of handrubbing with an ABHR and handscrubbing with antimicrobial soap and water for surgical hand preparation for the prevention of SSI.

Remarks

  • The available evidence on SSI as an outcome is limited to three RCTs. The trials compared handrubbing (with alcohol-based preparations) vs. handscrubbing (with PVP-I, CHG or plain soap) for surgical hand preparation and showed no significant difference between the two methods.
  • Evidence from additional studies using the bacterial load on participants’ hands as the outcome demonstrated that some ABHR formulations are more effective to reduce colony-forming units than scrubbing with water and antimicrobial or plain soap. The relevance of this outcome to the risk of SSI remains uncertain and the GDG considered this as indirect evidence and concluded that the recommendation could not be developed based on this surrogate outcome. Only evidence from RCTs with an SSI outcome was taken into account for the recommendation development.
  • The WHO hand hygiene guidelines recommend preferably using “a product ensuring sustained activity”. It was assumed that the sustained activity ensured by certain products (for example, CHG) was desirable, but there was no evidence that these products were more effective in directly reducing the risk of SSI. In the absence of such evidence, the GDG decided not to make any recommendations on specific products with or without a sustained effect and it emphasized the need to define what is considered a “suitable” product.
  • The hands of the surgical team should be clean upon entering the OR by washing with a non-medicated soap. Once in the operating area, repeating handrubbing or scrubbing without an additional prior handwash is recommended before switching to the next procedure.
  • It should be kept in mind that the activity of ABHRs may be impaired if hands are not completely dried before applying the product or by the handwashing itself. Hence, surgical handscrub and surgical handrub with alcohol-based products should not be combined sequentially (1).
  • When choosing ABHR, health care facilities should regularly procure products with proven efficacy (that is, complying with European norms or those of the American Society for Testing and Materials or equivalent international standards) to implement this recommendation and position no-touch or elbow-operated dispensers in surgical scrub rooms. Alternatively, antimicrobial soap, clean running water and disposable or clean towels for each health care worker should be available in the scrub room.
  • In LMICs where ABHR availability is limited, WHO strongly encourages facilities to undertake the local production of an alcohol-based formulation according to WHO guidance, which has been demonstrated to be a feasible and low-cost solution (1, 2).
  • Skin irritation, dryness, dermatitis and some rare allergic reactions are adverse events that can occur following frequent scrubbing for surgical hand preparation. Although these are less frequent with ABHRs and more frequent with iodophors, even well-tolerated ABHRs containing emollients may cause a transient stinging sensation at any site of broken skin (cuts, abrasions). Allergic contact dermatitis or contact urticaria syndrome caused by hypersensitivity to alcohol or to various additives present in some ABHRs are rare occurrences. ABHR preparations with strong fragrances may be poorly tolerated by a few health care workers with respiratory allergies. Studies of surgeon preferences indicate a primary preference for ABHRs with a higher tolerability and acceptability, due mostly to the shorter application time required and fewer skin reactions.
  • Care must be taken to avoid contact with the eyes when using preparations with CHG 1% or greater as it may cause conjunctivitis or serious corneal damage. Ototoxicity precludes its use in surgery involving the inner or middle ear. Direct contact with brain tissue and the meninges should be avoided. The frequency of skin irritation is concentration-dependent, with products containing 4% most likely to cause dermatitis when used frequently for antiseptic handwashing. True allergic reactions to CHG are very uncommon (1).
  • Alcohols are flammable and health care workers handling alcohol-based preparations should respect safety standards.

Background

The purpose of routine hand hygiene in patient care is to remove dirt, organic material and reduce microbial contamination from transient flora. In contrast to hygienic hand hygiene through handwash or handrub, surgical hand preparation must eliminate the transient flora and reduce the resident flora. In addition, it should inhibit the growth of bacteria under the gloved hand (1). Despite the limited scientific evidence on the effect of surgical hand preparation (usually called “handscrubbing”) in reducing SSIs, the aim of this preventive measure is to reduce the release of skin bacteria from the hands of the surgical team to the open wound for the duration of the procedure, particularly in the case of an unnoticed puncture of the surgical glove. A rapid multiplication of skin bacteria occurs under surgical gloves if hands are washed with a non-antimicrobial soap, whereas it occurs more slowly following preoperative scrubbing with a medicated soap. The skin flora, mainly coagulase-negative staphylococci, Propionibacterium spp. and Corynebacteria spp., are rarely responsible for SSI, but in the presence of a foreign body or necrotic tissue, even inocula as low as 100 colony-forming units can trigger such infections (3).

The spectrum of antimicrobial activity for surgical hand preparation should be as broad as possible against bacteria and fungi. Viruses are rarely involved in SSI and are not part of test procedures for licensing in any country. Similarly, activity against spore-producing bacteria is not part of international testing procedures. According to the European Committee for Standardization (4, 5) and the American Society for Testing and Materials (6), antiseptic preparations intended for use as surgical hand preparations are evaluated for their ability to reduce the number of bacteria released from hands for immediate and persistent activity, thus targeting both transient and resident flora. Therefore, to be considered efficacious, antiseptic preparations should comply with either the European norm 12791 (7) or the American Society for Testing and Materials E-1115 standards (8).

The WHO guidelines on hand hygiene in health care (1) (Table 4.9.1) recommend to keeping nails short and to remove all jewellery, artificial nails or nail polish before surgical hand preparation. If hands are visibly soiled, the guidelines recommend to wash hands and remove debris from underneath fingernails using a nail cleaner (not brushes), preferably under running water (sinks should be designed to reduce the risk of splashes). Surgical hand antisepsis should be performed using either (but not combined) a suitable antimicrobial soap or ABHR, preferably with a product ensuring sustained activity, before donning sterile gloves. Hands and forearms should be scrubbed with antimicrobial soap for the length of time recommended by the manufacturer, usually 2–5 minutes. The guidelines stipulate that if the quality of water is not assured in the OR, surgical hand antisepsis using ABHR is recommended. A sufficient amount of ABHR should be applied to dry hands and forearms for the length of time recommended by the manufacturer, typically 1.5 minutes, and hands and forearms allowed to dry before donning sterile gloves. Several organizations have issued recommendations regarding surgical hand preparation and these are summarized in Table 4.9.1.

Table 4.9.1. Summary of recommendations on surgical hand preparation according to available guidelines.

Table 4.9.1

Summary of recommendations on surgical hand preparation according to available guidelines.

A Cochrane systematic review was published in 2008 (12) and very recently updated in 2016 (13). The update included 14 RCTs; four trials reported rates of SSIs as the primary outcome, while the other studies measured the numbers of colony-forming units on participants’ hands. The main finding was that that there is no firm evidence that one type of hand antisepsis (either ABHRs or aqueous scrubs) is better than another in reducing SSIs, but the quality of the evidence was considered low to very low. However, moderate or very low quality evidence showed that ABHRs with additional antiseptic ingredients may be more effective to reduce colony-forming units compared with aqueous scrubs (12, 13).

Following an in-depth analysis of the sources and strength of the evidence in current guidelines, which are not based on systematic reviews and GRADE methodology, the GDG decided to address the issue of what type of products and scrubbing technique should be used for surgical hand preparation.

Summary of the evidence

The purpose of the evidence review (web Appendix 10) was to compare the effect of different techniques (that is, handrubbing vs. handscrubbing), products (that is, different ABHR formulations and plain or medicated soap) and application times for the same product. The primary outcome was the occurrence of SSI and SSI-attributable mortality. The target population included patients of all ages undergoing a surgical procedure.

Only six studies comprising 3 RCTs (1416) and three observational studies (1719) were identified with SSI as the primary outcome. All studies compared handrubbing to handscrubbing for surgical hand preparation. Handrubbing was performed by using either Sterilium® (Bode Chemie GmbH, Hamburg-Stellingen, Germany; 75% aqueous alcohol solution containing propanol-1, propanol-2 and mecetronium), the WHO-recommended formulation II (75% (volume/volume [v/v]) isopropyl alcohol, 1.45% (v/v) glycerol, 0.125% (v/v) hydrogen peroxide), Avagard® (3M, Maplewood, MN, USA; 61% ethanol plus CHG 1% solution) or Purell® (Gojo Industries Inc., Akron, OH, USA; 62% ethyl alcohol as an active ingredient; water, aminomethyl propanol, isopropyl myristate, propylene glycol, glycerine, tocopheryl acetate, carbomer and fragrance as an inactive ingredient). Handscrubbing products contained either CHG or PVP-I and/or plain soap. Five studies compared ABHR to handscrubbing with an antimicrobial soap containing either PVP-I 4% or CHG 4% and showed no significant difference in SSI. The same result was found in a cluster randomized cross-over trial comparing ABHR to handscrubbing with plain soap (15). It was not possible to perform any meta-analysis of these data as the products used for handrubbing and/or handscrubbing were different.

The systematic review also identified 58 studies conducted either in laboratory or hospital settings, which evaluated participants’ hand microbial colonization following surgical hand preparation with different products and techniques. There was a high variability in the study setting, microbiological methods used, type of product and time of sampling. The GDG decided not to take this indirect evidence into consideration to formulate the recommendation. Evidence from RCTs with only a SSI outcome was taken into account for the development of the recommendation, which is rated as moderate due to inconsistency. The overall evidence shows no difference between handrubbing and handscrubbing in reducing SSI.

The systematic review did not identify any studies comparing different durations of the technique for the same product with an SSI outcome. Only studies assessing the bacterial load on hands were found. After evaluation of this indirect evidence, the GDG decided not to develop any recommendation on the duration of surgical hand preparation and to continue to recommend following the manufacturer’s instructions for each product.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. Given that surgical hand preparation has been considered to be best clinical practice since almost 200 years and is recommended in all surgical guidelines, the GDG is confident that the typical values and preferences of the target population regarding the outcome would favour the intervention.

Studies of surgeon preferences indicate a primary preference for ABHR. In general, studies show that ABHRs are more acceptable by surgeons compared to handscrubbing, due mainly to the reduced time required for surgical hand preparation and fewer skin reactions. The included studies provided some data on acceptability and tolerability of the products. According to a user survey in a study conducted in Kenya (15), OR staff showed a preference for ABHR as it was faster to use, independent of the water supply and quality and did not require drying hands with towels. No skin reactions were reported with either ABHR or plain soap and water. Parienti and colleagues (14) assessed 77 staff for skin tolerance and found that skin dryness and irritation was significantly better in the handrubbing periods of the study. Although Al-Naami and colleagues (16) failed to show a significant difference, a survey of OR staff in a Canadian surgical hand preparation intervention study (18) showed that 97% of responders approved of the switch to handrubbing and four persons even noted an improvement in their skin condition. All studies reported fewer (one or none) episodes of substantial dermatitis with ABHR compared to handscrubbing. In one study, some surgeons noted the occasional reversible bleaching of the forearm hair after the repeated use of handrub (15).

Resource use

Observational studies with SSI outcome show a significant cost benefit of handrubbing. A Canadian study (18) showed that the standard handscrub-related costs of direct supplies were evaluated to be around Can$ 6000 per year for 2000 surgical procedures, not including the cost of cleaning and sterilizing surgical towels. The actual expenses incurred after a full year of handrub use were Can$ 2531 for an annual saving of approximately Can$ 3500. A dramatic decrease in surgical towel use (an average of 300 fewer towels per week) added to the savings. Two other studies (17, 19) from the USA and Cote d’Ivoire showed lower costs with Avagard® and Sterilium® when compared to the use of antiseptic-impregnated hand brushes and a PVP-I product, respectively. One RCT (15) also supported these findings and showed that the approximate total weekly cost of locally-produced ABHR according to the modified WHO formula was just slightly higher than plain soap and water (€ 4.60 compared with € 3.30; cost ratio: 1:1.4).

Despite this evidence on the cost-effectiveness of ABHRs, they may still have a high cost and limited availability in LMICs, even if local production is promoted. The barriers to local production may include the difficulty to identify staff with adequate skills, the need for staff training, constraints related to ingredient and dispenser procurement and the lack of adequate quality control. However, the GDG strongly emphasized that local production still remains a promising option in these circumstances. A WHO survey (20) of 39 facilities from 29 countries demonstrated that the WHO ABHR formulations can be easily produced locally at low cost and are very well tolerated and accepted by health care workers. Although the contamination of alcohol-based solutions has seldom been reported, the GDG emphasized the concern that top-up dispensers, which are more readily available, impose a risk for microbial contamination, especially in LMICs. According to the survey, the reuse of dispensers at several sites helped to overcome difficulties caused by local shortages and the relatively high costs of new dispensers. However, such reuse may lead to handrub contamination, particularly when empty dispensers are reprocessed by simple washing before being refilled, and the “empty, clean, dry, then refill” strategy to avoid this risk may require extra resources.

The feasibility and costs related to the standard quality control of locally-produced products is another consideration. In the WHO survey (20), 11/24 assessed sites could not perform quality controls locally due to lack of equipment and costs. However, most sites were able to perform basic quality control with locally-purchased alcoholmeters. The use of soap and water will require disposable towels, which adds to the cost. Towel reuse is not recommended in the health care setting and towels should be changed between health care workers, thus resulting in resource implications.

Research gaps

The GDG noted that there are major research gaps and heterogeneity in the literature regarding comparisons of product efficacy, technique and duration of the scrubbing methods with SSI as the primary outcome. In particular, it would be useful to conduct RCTs in clinical settings to compare the effectiveness of various antiseptic products with sustained activity to reduce SSI vs. ABHR or antimicrobial soap with no sustained effect. Well-designed studies on the cost-effectiveness and tolerability/acceptability of locally-produced formulations in LMICs would be also helpful. Furthermore, research is needed to assess the interaction between products used for surgical hand preparation and the different types of surgical gloves, in relation to SSI outcome.

References

1.
WHO guidelines on hand hygiene in health care. Geneva: World Health Organization; 2009 (http://apps​.who.int/iris​/bitstream/10665​/44102/1/9789241597906_eng.pdf, accessed 24 July 2016).
2.
Guide to local production; WHO-recommended handrub formulations. Geneva: World Health Organization; 2009 (http://www​.who.int/gpsc​/5may/Guide_to_Local_Production.pdf, accessed 24 July 2016).
3.
Elek SD, Conen PE. The virulence of Staphylococcus pyogenes for man; a study of the problems of wound infection. Br J Exper Pathol. 1957;38(6):573–86. [PMC free article: PMC2083292] [PubMed: 13499821]
4.
European standard EN 1499. Chemical disinfectants and antiseptics. Hygienic handwash. Test method and requirements. Brussels: European Committee for Standardization; 1997.
5.
European standard EN 1500. Chemical disinfectants and antiseptics. Hygienic handrub. Test method and requirements. Brussels: European Committee for Standardization; 1997.
6.
Standard test method for evaluation of the effectiveness of health care personnel or consumer handwash formulations. (designation: E 1174). American Society for Testing and Materials (ASTM International); 1999.
7.
European standard EN 12791. Chemical disinfectants and antiseptics. Surgical hand disinfection. Test method and requirements. Brussels: European Committee for Standardization; 2004.
8.
Test method for evaluation of surgical handscrub formulations; (designation: E 1115). American Society for Testing and Materials (ASTM International); 2002.
9.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
10.
Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337:a1924. [PubMed: 18957455]
11.
Surgical site infection: evidence update 43 (June 2013). London: National Institute for Health and Care Excellence (NICE); 2013 (http://www​.nice.org.uk​/guidance/cg74/evidence​/evidence-update-241969645, accessed 24 July 2016).
12.
Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008(1):CD004288. [PubMed: 18254046]
13.
Tanner J, Dumville JC, Norman G, Fortnam M. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2016;1:CD004288. [PMC free article: PMC8647968] [PubMed: 26799160]
14.
Parienti JJ, Thibon P, Heller R, Le Roux Y, Von Theobald P, Bensadoun H, et al. Hand-rubbing with an aqueous alcoholic solution vs traditional surgical hand-scrubbing and 30-day surgical site infection rates: A randomized equivalence study. JAMA. 2002;288(6):722–7. [PubMed: 12169076]
15.
Nthumba PM, Stepita-Poenaru E, Poenaru D, Bird P, Allegranzi B, Pittet D, et al. Cluster-randomized, crossover trial of the efficacy of plain soap and water versus alcohol-based rub for surgical hand preparation in a rural hospital in Kenya. Br J Surg. 2010; (11):1621–8. [PubMed: 20878941]
16.
Al-Naami MY, Anjum MN, Afzal MF, Al-Yami MS, Al-Qahtani SM, Al-Dohayan AD, et al. Alcohol-based hand-rub versus traditional surgical scrub and the risk of surgical site infection: a randomized controlled equivalent trial. EWMA J. 2009;9(3):5–10.
17.
Weight CJ, Lee MC, Palmer JS. Avagard hand antisepsis vs. traditional scrub in 3600 pediatric urologic procedures. Urology. 2010;76(1): 15–7. [PubMed: 20363495]
18.
Marchand R, Theoret S, Dion D, Pellerin M. Clinical implementation of a scrubless chlorhexidine/ethanol pre-operative surgical handrub. Can Oper Room Nurs J. 2008;26(2):21–2, 6, 9–2231. [PubMed: 18678198]
19.
Adjoussou S, Konan Ble R, Seni K, Fanny M, Toure-Ecra A, Koffi A, et al. Value of hand disinfection by rubbing with alcohol prior to surgery in a tropical setting. Med Trop. 2009;69(5):463–6. [PubMed: 20025174]
20.
Bauer-Savage J, Pittet D, Kim E, Allengranzi B. Local production of WHO-recommended alcohol-based handrubs: feasibility, advantages, barriers and costs. Bull World Health Organ. 2013;91:963–9. [PMC free article: PMC3845264] [PubMed: 24347736]
Image ch4f1

Preoperative and/or Intraoperative Measures

4.10. Enhanced nutritional support

Recommendation

The panel suggests considering the administration of oral or enteral multiple nutrient-enhanced nutritional formulas for the purpose of preventing SSI in underweight patients who undergo major surgical operations.

(Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Multiple nutrient-enhanced nutritional formulas contain any combination of arginine, glutamine, omega-3 fatty acids and nucleotides.
  • After careful appraisal of the included studies, the research team and the GDG decided to perform meta-analysis comparisons including only studies in which the oral and enteral routes were used and excluding those where the parenteral route was used. The main reason was that the parenteral route is very different and the experts considered it inappropriate to administer enhanced nutritional formulas only for the purpose of preventing SSI when considering the infectious risk related to intravenous access.
  • Overall very low quality evidence from eight RCTs and two observational studies shows that multiple nutrient-enhanced formulas demonstrate a benefit in reducing the risk of SSI compared to standard nutritional support. The population studied were adult patients undergoing major surgical procedures (mainly cancer and cardiac patients).
  • Overall low quality evidence from five RCTs and one observational study (very low quality) shows that a single nutrient-enhanced formula (containing either arginine or glycine or omega-3 fatty acids) produces neither benefit nor harm when compared to standard nutritional support in reducing the risk of SSI.
  • As a result of these evaluations and comparisons, the GDG agreed to suggest that underweight patients who are undergoing major surgical operations (particularly oncology and cardiovascular procedures) may benefit from the administration of oral or enteral multiple nutrient-enhanced nutritional formulas for the purpose of preventing SSI. Given the very low quality of the evidence, the strength of this recommendation was considered to be conditional and the GDG proposed to use the terminology “The panel suggests considering…” to highlight the need for careful local and patient-by-patient evaluation about whether and how to apply this recommendation, in particular depending on the availability of nutritional formulas and costs.
    Note: “underweight” is a term describing a person whose body weight is considered too low to be healthy. The definition usually refers to people with a body mass index of under 18.5 or a weight 15–20% below the norm for their age and height group.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, the effectiveness of the intervention is not proven for paediatric patients and is valid for adult patients only.
  • There is little evidence as to whether the timing of administration of multiple nutrient-enhanced nutritional formulas modifies the effect on the prevention of SSI. Therefore, the GDG was unable to identify an optimal timing and duration of the administration of these formulas.
  • The GDG emphasized that most patients included in the studies were receiving enteral feeding through a tube for other reasons than the prevention of SSI. When inserting a feeding tube solely to administer multiple nutrient-enhanced nutritional formulas for the purpose of SSI prevention, it is important to be aware of the possible discomfort and harm ranging from mucosal irritation and the development of sinusitis to perforation. The GDG does not encourage the insertion of a feeding tube for the sole purpose of preventing SSI. In particular, it considers that improving nutritional status should not in any way lead to a delay in surgery.
  • The GDG identified contaminated preparations as a potential harm, especially due to contaminated water and/or a break in the aseptic technique during preparation. This risk is increased when the feeding takes place at the patient’s home. It is good practice to follow clinical and IPC guidelines and aseptic precautions when preparing nutritional formulas.

Background

Malnutrition, including protein-energy and micronutrient deficiencies, continues to be a major public health problem, particularly in developing countries. It affects also the rapidly growing elderly population in high-income countries (1, 2). Nutritional status can have a profound impact on the immune system (3) as documented by some studies (24). These alterations in host immunity may make patients more susceptible to postoperative infections and malnutrition was reported as a threat to surgical outcome, such as delayed recovery, higher rates of morbidity and mortality, prolonged hospital stay, increased health care costs and a higher early readmission rate (27).

Some studies showed that early nutritional support can improve the outcome following major surgery and decrease the incidence of infectious complications in selected malnourished or severely injured patients. The hypothesis is that the immune system may be modulated by the use of specific types of nutritional support (2, 3, 6, 8).

Surgery also induces an altered metabolism of protein, marked by a negative nitrogen balance and changes in amino acid patterns in blood. In addition, inflammation is integral to the recovery after stress, such as a surgical procedure. Therefore, nutritional support is being used more and more as a means to increase protein and caloric intake during the perioperative period, particularly by using formulas high in specific amino acids, antioxidants and anti-inflammatory nutrients (9, 10).

Given the role of nutrition in the host response to surgery, many researchers believe that nutritional interventions would reduce SSI and the related morbidity. However, an epidemiological association between incisional SSI and malnutrition has been difficult to demonstrate consistently for all surgical subspecialties. There is very little consensus on the optimal timing and dosage of multiple nutrient-enhanced nutrition, especially for the prevention of SSI.

At present, there are no formal recommendations for nutrition supplementation for SSI prevention. Recent recommendations from SHEA/IDSA state that the preoperative administration of parenteral nutrition should not delay surgery (11). Following an in-depth analysis of the resources and limited recommendations from other guidelines, the GDG members decided to conduct a systematic review on the effectiveness of nutrition supplementation for SSI prevention.

Summary of the evidence

The purpose of the evidence review (web Appendix 11) was to evaluate the effect of enhanced nutritional support compared to standard nutrition for the prevention of SSI. The population targeted were patients of all ages undergoing surgical procedures. The primary outcomes were the occurrence of SSI and SSI-attributable mortality.

A total of 23 studies comprising 19 RCTs (1230) and four observational studies (3134) were identified with SSI as a reported outcome. Studies included adult patients undergoing cardiac surgical procedures (one study) or undergoing elective surgical procedures for head and neck, gastrointestinal, colorectal or gynaecological cancer. No study was available in the paediatric population. There was a substantial variation in the route of administration, nutritional formulas used and the definition of SSI. After careful appraisal of the included studies, the research team and the GDG decided to perform meta-analysis comparisons including only studies in which the oral and enteral routes were used and excluded those using the parenteral route.

Despite the above-mentioned heterogeneity, two meta-analyses were performed to evaluate the following comparisons: a multiple nutrient-enhanced nutritional formula vs. standard nutrition and a single nutrient-enhanced nutritional formula vs. standard nutrition, administered through either oral or enteral routes.

A total of 10 studies were identified. They comprised eight RCTs (15, 1921, 23, 26, 28, 29) and two observational studies (31, 33) including a total of 1434 patients and comparing the use of multiple nutrient-enhanced nutritional formulas (containing any combination of arginine, glutamine, omega-3 fatty acids and nucleotides) to standard nutrition. One study (19) involved data from multiple centres. Very low quality evidence shows that a multiple nutrient-enhanced nutritional formula has a significant benefit when compared to a standard nutritional formula in reducing the risk of SSI. The combined OR was 0.53 (95% CI: 0.30–0.91) for the RCTs and 0.07 (95% CI; 0.01–0.53) for the observational studies.

Furthermore, six studies including 397 patients and comprising of five RCTs (14, 1618, 29) and one observational study (32) compared the use of nutritional supplements enhanced with a single nutrient (either arginine, glycine or branched chain amino acids) to standard nutrition. These studies included adult patients undergoing elective surgical procedures with head and neck cancer, hepatocellular carcinoma and cardiac disease. Low quality evidence shows that a single nutrient-enhanced formula has neither benefit nor harm for the reduction of SSI when compared to standard nutrition (RCTs: OR: 0.61; 95% CI: 0.13–2.79; observational study: OR: 0.29; 95% CI: 0.06–1.39).

The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. It was acknowledged that although patients may value measures to prevent SSI, they do not wish to be exposed to discomfort or possible harm due to a feeding tube inserted solely for that purpose. The GDG is confident that patients would very likely accept the administration of multiple nutrient-enhanced nutritional formulas if they are already receiving enteral feeding. Moreover, if oral feeding is possible, this would be an alternative likely welcomed by most patients. Some of the formulas were dairy-based, which may represent a problem for individuals who avoid dairy products for dietary, ethical or cultural reasons.

Resource use

No cost-effectiveness studies were identified. However, the use of enhanced nutrition support is expensive and requires additional work for clinical staff. In facilities where these formulas are used, there is a special need for dieticians and pharmacists, including the training of staff on their appropriate use and preparation. It is essential that all oral feeds be prepared in a clean dedicated area using an aseptic technique. Furthermore, the availability of enhanced nutrition formulas may be limited, particularly in LMICs, including the availability of ingredients for the preparation of the formulas (for example, clean drinking water). IPC measures for the preparation of the formulas need to be implemented. Given the very low quality of evidence for a benefit, the GDG was uncertain whether the benefits outweigh the costs of multiple nutrient-enhanced nutritional formulas.

Research gaps

The GDG highlighted that the few trials studying the efficacy of enhanced nutritional support for the prevention of SSI are small and generally of low quality. In addition, they are often conducted in populations that are at a high risk of malnutrition (for example, gastrointestinal cancer), which limits their generalizability. Many studies were funded by manufacturers of proprietary formulas and this could increase the potential for bias.

Future well-designed RCTs should be independent of manufacturers and performed in larger populations of individuals undergoing a variety of general surgical procedures. The impact of nutritional support should be investigated further in LMICs. Studies should investigate the benefit of other nutritional elements (for example, iron, zinc) and vitamins. Finally, the optimal timing and duration of the administration of nutritional support in relation to the time of surgery should be further assessed by well-designed RCTs.

References

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Fry DE. Fifty ways to cause surgical site infections. Surg Infect (Larchmt). 2011;12(6):497–500. [PubMed: 22142318]
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Mazaki T, Ishii Y, Murai I. Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a multiple-treatments meta-analysis. Ann Surg. 2015;261(4):662–9. [PubMed: 25405556]
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Yue C, Tian W, Wang W, Huang Q, Zhao R, Zhao Y, et al. The impact of perioperative glutamine-supplemented parenteral nutrition on outcomes of patients undergoing abdominal surgery: a meta-analysis of randomized clinical trials. Am Surg. 2013;79(5):506–13. [PubMed: 23635587]
11.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
12.
Beattie AH, Prach AT, Baxter JP, Pennington CR. A randomised controlled trial evaluating the use of enteral nutritional supplements postoperatively in malnourished surgical patients. Gut. 2000;46(6):813–8. [PMC free article: PMC1756438] [PubMed: 10807893]
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Burden ST, Hill J, Shaffer JL, Campbell M, Todd C. An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients. J Human Nutr Diet. 2011;24(5):441–8. [PubMed: 21699587]
14.
Casas-Rodera P, Gomez-Candela C, Benitez S, Mateo R, Armero M, Castillo R, et al. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Nutr Hosp. 2008;23(2):105–10. [PubMed: 18449445]
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Çelik JB, Gezginç K, Özçelik K, Çelik Ç. The role of immunonutrition in gynecologic oncologic surgery. Europ J Gynaecol Oncol. 2009;30(4):418–21. [PubMed: 19761135]
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de Luis DA, Aller R, Izaola O, Cuellar L, Terroba MC. Postsurgery enteral nutrition in head and neck cancer patients. Europ J Clin Nutr. 2002;56(11):1126–9. [PubMed: 12428179]
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de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Europ J Clin Nutr. 2004;58(11):1505–8. [PubMed: 15138461]
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De Luis DA, Izaola O, Cuellar L, Terroba MC, Martin T, Aller R. High dose of arginine enhanced enteral nutrition in postsurgical head and neck cancer patients. A randomized clinical trial. Europ Rev Med Pharmacol Sci. 2009;13(4):279–83. [PubMed: 19694342]
19.
Falewee MN, Schilf A, Boufflers E, Cartier C, Bachmann P, Pressoir M, et al. Reduced infections with perioperative immunonutrition in head and neck cancer: exploratory results of a multicenter, prospective, randomized, double-blind study. Clin Nutr. 2014;33(5):776–84. [PubMed: 24182765]
20.
Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y, et al. Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg. 2012;99(5):621–9. [PubMed: 22367794]
21.
Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology. 2002;122(7):1763–70. [PubMed: 12055582]
22.
Klek S, Kulig J, Sierzega M, Szybinski P, Szczepanek K, Kubisz A, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg. 2008;248(2):212–20. [PubMed: 18650630]
23.
Klek S, Sierzega M, Szybinski P, Szczepanek K, Scislo L, Walewska E, et al. The immunomodulating enteral nutrition in malnourished surgical patients - a prospective, randomized, double-blind clinical trial. Clin Nutr. 2011;30(3):282–8. [PubMed: 21074910]
24.
Oguz M, Kerem M, Bedirli A, Mentes BB, Sakrak O, Salman B, et al. L-alanin-L-glutamine supplementation improves the outcome after colorectal surgery for cancer. Colorectal Dis, 2007;9(6):515–20. [PubMed: 17573745]
25.
Roth B, Birkhauser FD, Zehnder P, Thalmann GN, Huwyler M, Burkhard FC, et al. Parenteral nutrition does not improve postoperative recovery from radical cystectomy: results of a prospective randomised trial. Europ Urol. 2013;63(3):475–82. [PubMed: 22695241]
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Snyderman CH, Kachman K, Molseed L, Wagner R, D’Amico F, Bumpous J, et al. Reduced postoperative infections with an immune-enhancing nutritional supplement. Laryngoscope. 1999;109(6):915–21. [PubMed: 10369282]
27.
Suzuki D, Furukawa K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, et al. Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy. Surgery. 2010;148(3):573–81. [PubMed: 20227099]
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Tepaske R, Velthuis H, Oudemans-van Straaten HM, Heisterkamp SH, van Deventer SJ, Ince C, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet. 2001;358(9283):696–701. [PubMed: 11551575]
29.
Tepaske R, te Velthuis H, Oudemans-van Straaten HM, Bossuyt PM, Schultz MJ, Eijsman L, et al. Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients. J Parenter Enteral Nutr. 2007;31(3):173–80. [PubMed: 17463141]
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Wei Z, Wang W, Chen J, Yang D, Yan R, Cai Q. A prospective, randomized, controlled study of ω-3 fish oil fat emulsion-based parenteral nutrition for patients following surgical resection of gastric tumors. Nutr J. 2014;13(1);25–31. [PMC free article: PMC3974447] [PubMed: 24655407]
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Horie H, Okada M, Kojima M, Nagai H. Favorable effects of preoperative enteral immunonutrition on a surgical site infection in patients with colorectal cancer without malnutrition. Surg Today. 2006;36(12):1063–8. [PubMed: 17123134]
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4.11. Perioperative discontinuation of immunosuppressive agents

Recommendation

The panel suggests not discontinuing immunosuppressive medication prior to surgery for the purpose of preventing SSI.

(Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Very low quality evidence shows that the perioperative discontinuation of methotrexate (MTX) might be harmful or have no effect on the risk of SSI compared to its continuation. Furthermore, very low quality evidence from two observational studies showed that the perioperative discontinuation of tumour necrosis factor (TNF) inhibitors (anti-TNF) might have a benefit for the reduction of the SSI rate when compared to the continuation of anti-TNF. Taking into consideration (1) the very limited evidence (for anti-TNF) or lack of evidence and even potential harm (for MTX) to support a discontinuation of treatment, and (2) the risk associated with the discontinuation of treatment on the patient’s underlying disease/s, the GDG unanimously agreed to suggest that immunosuppressive medication should not be discontinued for the purpose of preventing SSI.

Remarks

  • The GDG emphasized that the decision to discontinue immunosuppressive medication may be made on an individual basis, involving the prescribing physician, the patient and the surgeon.
  • No relevant evidence was found on the perioperative discontinuation of long-term corticosteroid therapy.
  • The population investigated in the studies on MTX included patients with rheumatoid arthritis (15) and Crohn’s disease (6). Studies on anti-TNF investigated a population with rheumatoid arthritis (7) and other inflammatory rheumatic diseases (8).
  • The time point and time interval of discontinuation of the immunosuppressive agent were very heterogeneous across studies or not specified.
  • The GDG identified the occurrence of a flare-up of the underlying disease as a potential harm associated with discontinuation of immunosuppressive therapy. The risk of major adverse events associated with discontinuation is high in patients taking immunosuppressive therapy after organ transplantation or for rheumatoid arthritis, whereas it might be lower in those taking immunosuppressive agents for inflammatory bowel disease (4, 5, 914).

Background

Immunosuppressive agents are drugs that inhibit or prevent activation of the immune system. They are commonly prescribed to prevent rejection of transplanted organs or for the treatment of inflammatory diseases, such as rheumatoid arthritis or inflammatory bowel disease. Some observational studies indicate that the immunosuppressive effect of the drugs could lead to impaired wound healing and increased risk of infection in patients treated with these agents (8). Conversely, the discontinuation of immunosuppressive treatment could induce flares of disease activity and long-term interruptions of therapy might induce the formation of anti-drug antibodies and subsequently decrease the effect of the immunosuppressives (15).

To date, only one SSI prevention guideline has issued a recommendation regarding the administration of immunosuppressive agents in the perioperative period. This guideline was published by SHEA/IDSA and recommends avoiding the use of immunosuppressive agents in the perioperative period if possible (16). However, this recommendation is not based on systematic reviews of the literature and meta-analyses or a rigorous evaluation of the quality of the available evidence. Of note, several other SSI prevention guidelines do not address this topic.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess the influence of immunosuppressive agents on the incidence of SSI and whether a discontinuation of immunosuppressive medication in the perioperative period is effective to prevent SSI in surgical patients.

Summary of the evidence

The purpose of the evidence review (web Appendix 12) was to evaluate whether a discontinuation of immunosuppressive medication in the perioperative period is more effective in reducing the risk of SSI than continuation of the medication. The target population was patients of all ages taking immunosuppressive agents and undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

A total of eight studies comparing the perioperative discontinuation of immunosuppressive medication vs. continuation were identified and included a total of 2461 patients. They comprised one RCT (5), one quasi-RCT (3) and six observational studies (1, 2, 4, 68). Six studies comprising one RCT (5), one quasi-RCT (3) and four observational (1, 2, 4, 6) investigated MTX and two observational studies (7, 8) investigated anti-TNF. The time point and time interval of discontinuation of the immunosuppressive agent were as follows: seven days before surgery (5); one week prior to surgery and the week of surgery (2); two weeks before surgery until two weeks after surgery (3); within four weeks prior to surgery (6); four weeks before surgery (1); and one, four or eight weeks before and reintroduced one week after surgery (8). The remaining two studies gave a rather unspecific description of the time point and time interval of discontinuation, that is, more than four times the half-life of the agent (7) or more than one week during the perioperative period (4).

According to the selected studies the following comparisons were evaluated:

Discontinuation vs. continuation of:

  1. MTX
  2. anti-TNF.

Very low quality evidence shows that the perioperative discontinuation of MTX might be harmful or have no effect on the risk of SSI when compared to continuation of MTX. The combined OR was 7.75 (95% CI: 1.66–36.24) for the controlled trials and 0.37 (95% CI: 0.07–1.89) for the observational studies. Furthermore, there is very low quality evidence from two observational studies (7, 8) that the perioperative discontinuation of anti-TNF might have a benefit in reducing the SSI rate compared to the continuation of anti-TNF (OR: 0.59; 95% CI: 0.37–0.95).

The body of retrieved evidence focused mainly on adult patients, although a few studies also included a paediatric population (6, 8). The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that most patients value the prevention of SSI, but they also do not want to be exposed to the risk of flare-ups or progression of their underlying disease due to the discontinuation of immunosuppressive therapy. Furthermore, most patients would like to be fully informed about the consequences of these decisions and to be involved in the decision making process.

Resource use

No cost-effectiveness data are available on the continuation or discontinuation of immunosuppressive therapy. The GDG pointed out that when making any decision on discontinuation, the physician treating the underlying disease or another senior physician will have to be involved, which may generate additional costs.

Research gaps

GDG members highlighted that well-designed RCTs are urgently needed to clarify this issue. Trials should examine also the optimal time between discontinuation of immunosuppressive agent(s) and time of surgery. In addition, the importance of the optimal dose of the various immunosuppressive therapy agents with regards to the SSI rate should be investigated. Studies should take into account new immunosuppressive agents. The GDG pointed out that surveillance and registry data are very likely to contribute also to the evidence in this field of research.

References

1.
Bridges SL, Jr., Lopez-Mendez A, Han KH, Tracy IC, Alarcon GS. Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? J Rheumatol. 1991;18(7):984–8. [PubMed: 1920333]
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Carpenter MT, West SG, Vogelgesang SA, Casey Jones DE. Postoperative joint infections in rheumatoid arthritis patients on methotrexate therapy. Orthopedics. 1996;19(3):207–10. [PubMed: 8867548]
3.
Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis. 2001;60(3):214–7. [PMC free article: PMC1753573] [PubMed: 11171680]
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Murata K, Yasuda T, Ito H, Yoshida M, Shimizu M, Nakamura T. Lack of increase in postoperative complications with low-dose methotrexate therapy in patients with rheumatoid arthritis undergoing elective orthopedic surgery. Mod Rheumatol. 2006;16(1):14–9. [PubMed: 16622718]
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Sany J, Anaya JM, Canovas F, Combe B, Jorgensen C, Saker S, et al. Influence of methotrexate on the frequency of postoperative infectious complications in patients with rheumatoid arthritis. J Rheumatol. 1993;20(7):1129–32. [PubMed: 8371204]
6.
Colombel JF, Loftus EV, Jr., Tremaine WJ, Pemberton JH, Wolff BG, Young-Fadok T, et al. Early postoperative complications are not increased in patients with Crohn’s disease treated perioperatively with infliximab or immunosuppressive therapy. Am J Gastroenterol. 2004;99(5):878–83. [PubMed: 15128354]
7.
den Broeder AA, Creemers MC, Fransen J, de Jong E, de Rooij DJ, Wymenga A, et al. Risk factors for surgical site infections and other complications in elective surgery in patients with rheumatoid arthritis with special attention for anti-tumor necrosis factor: a large retrospective study. J Rheumatol. 2007;34(4):689–95. [PubMed: 17117492]
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Berthold E, Geborek P, Gulfe A. Continuation of TNF blockade in patients with inflammatory rheumatic disease. An observational study on surgical site infections in 1,596 elective orthopedic and hand surgery procedures. Acta Orthop. 2013;84(5):495–501. [PMC free article: PMC3822136] [PubMed: 24032521]
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Hirano Y, Kojima T, Kanayama Y, Shioura T, Hayashi M, Kida D, et al. Influences of anti-tumour necrosis factor agents on postoperative recovery in patients with rheumatoid arthritis. Clin Rheumatol. 2010;29(5):495–500. [PubMed: 20069328]
10.
Jain A, Witbreuk M, Ball C, Nanchahal J. Influence of steroids and methotrexate on wound complications after elective rheumatoid hand and wrist surgery. J Hand Surg. 2002;27(3):449–55. [PubMed: 12015719]
11.
Kawakami K, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Yano K, et al. Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers: perioperative interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology. 2010;49(2):341–7. [PubMed: 19965973]
12.
Perhala RS, Wilke WS, Clough JD, Segal AM. Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum. 1991;34(2):146–52. [PubMed: 1994911]
13.
Schluender SJ, Ippoliti A, Dubinsky M, Vasiliauskas EA, Papadakis KA, Mei L, et al. Does infliximab influence surgical morbidity of ileal pouch-anal anastomosis in patients with ulcerative colitis? Dis Colon Rectum. 2007;50(11):1747–53. [PubMed: 17704969]
14.
Waterman M, Xu W, Dinani A, Steinhart AH, Croitoru K, Nguyen GC, et al. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease. Gut. 2013;62(3):387–94. [PubMed: 22619367]
15.
Bafford AC, Powers S, Ha C, Kruse D, Gorfine SR, Chessin DB, et al. Immunosuppressive therapy does not increase operative morbidity in patients with Crohn’s disease. J Clin Gastroenterol. 2013;47(6):491–5. [PubMed: 23090048]
16.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]

4.12. Perioperative oxygenation

Recommendation

The panel suggests that adult patients undergoing general anaesthesia with tracheal intubation for surgical procedures should receive an 80% fraction of inspired oxygen (FiO2) intraoperatively and, if feasible, in the immediate postoperative period for 2–6 hours to reduce the risk of SSI.

(Conditional recommendation, moderate quality of evidence)

Rationale for the recommendation

  • A moderate quality of evidence shows that providing high FiO2 (80%) is beneficial in adult surgical patients under general anaesthesia with tracheal intubation and results in a significant decrease of the risk of SSI compared to 30–35% FiO2.
  • There is low quality of evidence regarding no increased risk of major adverse events such as atelectasis, cardiovascular events, ICU admission, and death during the study period, associated with using high FiO2 in adult surgical patients under general anaesthesia with tracheal intubation. As a result, the GDG suggests that patients undergoing surgical procedures under general anaesthesia with tracheal intubation should receive 80% FiO2 intraoperatively and in the immediate postoperative period for 2–6 hours, if feasible, and that the strength of this recommendation should be conditional.
  • This recommendation is based on FiO2 administered, rather than on arterial partial pressure of oxygen (PaO2) or arterial oxygen saturation measured by pulse oximeter, as the clinical trials that led to the recommendation development provided results based only on FiO2 administered.

Remarks

  • This recommendation has been updated in 2018 after the initial guideline publication in 2016 (see section 2 of Methods) (1, 2). The systematic review on the evidence of effectiveness of the use of high FiO2 previously used for the 2016 WHO recommendation was updated to April 2018 and an independent systematic review on adverse effects associated with the recommended intervention has been conducted (3, 4).
  • In the updated review, the evidence for a beneficial effect has become weaker, despite an increased number of patients. In the 2018 update, the exclusion of two studies by Schietroma M and colleagues included in the previous systematic review due to disputed credibility and the net addition of four new trials testing the effectiveness of the use of high FiO2 did not strengthen the evidence for effect modification found in the original review or for a benefit in patients undergoing general anaesthesia with tracheal intubation that led to the strong recommendation in the WHO guidelines.
  • An independent systematic review on safety shows no substantive evidence to discourage the use of high FiO2 in this population. However, adverse events were not the primary focus of the original studies and the evidence is thus limited.
  • Further high-quality RCTs are urgently needed.
  • The body of retrieved evidence focused on adult patients and no study specifically performed in a paediatric population was identified. Therefore, the effectiveness of this intervention is not proven for paediatric patients.
  • After careful appraisal of the included studies, the research team and the GDG decided to perform meta-analysis comparisons including only patients under general anaesthesia with tracheal intubation and mechanical ventilation. Studies using neuraxial anaesthesia with a facemask or nasal cannula were excluded. Indeed, according to a meta-regression analysis introducing general anaesthesia with tracheal intubation as a significant covariate, the type of anaesthesia proved to independently modify the effect of hyperoxygenation. In neuraxial anaesthesia with a nasal cannula or facemask, the control of ventilation (and thereby control of the actual administration of high FiO2 to the lungs) is limited and was therefore considered as different from an intervention with mechanical ventilation.
  • The benefit of hyperoxygenation tended to be greater in open colorectal surgery than in other types of surgery, but no significant association was found between the type of surgery and the effect of hyperoxygenation.
  • The GDG emphasized that reduced SSI was found only in studies of patients intubated for general anaesthesia who received 80% FiO2 during surgery and continued to receive the higher oxygen concentration through a high flux mask in the immediate postoperative period. This should be considered as part of the intervention.
  • Other potential sources of heterogeneity were discussed, including the age of the population (older patients may benefit more) and duration of surgery. It is known that colorectal surgery has a higher risk for SSI compared to other surgical procedures and hyperoxygenation may be beneficial in this group of patients due to the predominance of anaerobic flora in the colonic flora.
  • There was a considerable variation in the exclusion criteria for underlying lung disease, especially chronic obstructive pulmonary disease.
  • The GDG highlighted that the benefits of hyperoxygenation would likely be maximized when normothermia and normovolemia are maintained (see chapters 4.13 and 4.15 for the recommendations on normothermia and normovolemia).
  • The GDG acknowledged also that the studies were performed in high-income countries only.
  • In settings where medical oxygen is scarce, policy-makers may not consider this recommendation as a priority.
  • The GDG pointed out that FiO2 is not the ideal parameter to be measured; PaO2 better reflects the amount of O2 possibly delivered to the tissues and thus could influence the SSI risk more directly.
  • Although monitoring oxygen saturation does not directly reflect the effect of this intervention, it is recommended as good practice, primarily to detect hypoxia in all patients undergoing general anesthesia during surgery and in the postoperative period, regardless of the concentration of inspired oxygen the patient receives.
  • This recommendation is limited to the use of high FiO2 in the perioperative period for the prevention of SSI and does not cover administration of high FiO2 and its effects in other settings and populations.

Background

There is evidence that an optimized blood flow to the surgical incision reduces SSI rates through the avoidance of hypothermia and hypoxia (1214). Since 2000, several trials have been published on the use of high FiO2 concentrations during the perioperative period and the potential association with lower rates of SSI (see Summary of the evidence). These studies include RCTs, meta-analyses and the long-term survival follow-up of original cohorts.

The intervention consists of providing patients with 80% FiO2 compared to the usual administration of 30% FiO2. Patients are routinely given 100% FiO2 for 30 seconds to 2 minutes prior to intubation and then maintained on either “normoxia”, defined as 30% or 35% FiO2, or “hyperoxia”, defined as oxygen at 80% FiO2.

The arguments for providing oxygen levels beyond the standard 30% are largely based on two notions (15). The first is that the surgical incision may not be adequately perfused and therefore might receive substantially higher oxygen if there is a higher partial pressure of oxygen in the blood (16). The other notion is that the host defence systems might be further improved by higher oxygen partial pressures, particularly by enhancing neutrophil oxidative killing (17).

Perioperative oxygenation has been specified in clinical practice guidelines issued by professional societies or national authorities (Table 4.12.1). SSI prevention bundles from both NHS England’s High impact intervention approach and Health Protection Scotland, as well as guidelines from the Royal College of Physicians of Ireland and the UK-based NICE, recommend maintaining a haemoglobin oxygen saturation of at least 95% (6, 8, 9, 18). The SSI prevention guidelines of SHEA/IDSA recommend optimizing tissue oxygenation by administering supplemental oxygen during and immediately following surgical procedures involving mechanical ventilation (5). Following an in-depth analysis of the sources and strength of the evidence in current guidelines, GDG members decided to conduct a systematic review to assess the available evidence on optimal perioperative oxygenation.

Table 4.12.1. Recommendations on oxygenation preparation according to available guidelines on oxygenation preparation according to available guidelines.

Table 4.12.1

Recommendations on oxygenation preparation according to available guidelines on oxygenation preparation according to available guidelines.

A 2015 systematic review assessed the same PICO question as these guidelines (7). However, the conclusions by Wetterslev and colleagues differ substantially from those presented here. The authors did not conduct a subgroup analysis based on the type of anaesthesia (that is, general anaesthesia with tracheal intubation vs. neuraxial with facemask or nasal cannula) as was done here, following the strong suggestion of the GDG. General anaesthesia was therefore not identified as a significant covariate and, consequently, it was not taken into account in the final analysis, thus resulting in a different outcome. The GDG strongly believes that the approach chosen here is superior and that the difference in outcomes is of critical importance for the presented recommendation.

In a recent systematic review (19), Chu and colleagues investigated the effects of liberal oxygen therapy on morbidity and mortality in critically ill patients. Liberal oxygen therapy was defined as any oxygen target higher than that of a more conservative control group. Interventions ranged from 30% up to 100% FiO2, but most did not exceed 30%. Intended exposure duration ranged from one up to 166 hours, but typically exceeded 12 hours. The study population included mostly patients with critical illness, stroke, myocardial infarction or cardiac arrest. Only one trial (0.9% of patients in the meta-analysis) included surgical patients receiving 80% FiO2 perioperatively and showed no increase in mortality (20). Importantly, the intervention and population differed substantially from those targeted in the WHO recommendation. The authors found high quality evidence that liberal oxygen therapy increases mortality in critically ill patients. Although important for the care of critically ill patients, these findings appear to have little relevance to the perioperative use of 80% FiO2 in patients undergoing surgery.

Summary of the evidence

The purpose of the evidence review (3, 4) was to compare the effect of increased (80%) FiO2 with standard (30–35%) FiO2 on the occurrence of SSI, SSI attributable mortality, and other adverse events. The target population included patients of all ages undergoing a surgical procedure. Two systematic reviews were conducted. One on the effectiveness of this intervention, which is an update of the original review performed for the 2016 WHO guidelines, and one on the safety of the use of high FiO2 in surgical patients for the purpose of reducing the risk of SSI. Pre-specified safety outcomes of interest were: 1) mortality; 2) ischaemic vascular events affecting coronary and cerebral circulation; 3) respiratory adverse effects (for example, respiratory failure, acute respiratory distress syndrome, number of ventilator days, and lung complications, such as pneumonia or atelectasis, re-intubation or prolonged intubation); and 4) length of hospital stay. In addition, a hypothesis-generating/scoping approach was used to capture any new or unexpected serious adverse effects that may have been reported in this patient population. The pre-specified effectiveness outcomes were the occurrence of SSI and SSI-attributable mortality.

Both reviews included 17 moderate-good quality RCTs (14, 2135); the safety review also included two non-randomized studies (36, 37). All studies administered 80% FiO2 in the intervention group; 16 studies administered 30% FiO2 in the control group and one study used 35% oxygen. Four RCTs used a gas mixture with nitrous oxide. The other studies used room air or nitrogen (N2). Patients were under general anaesthesia with endotracheal intubation and mechanical ventilation in 12 studies. In the remaining five, patients were anaesthetised, but awake and breathed spontaneously with the allocated gas mixture delivered via a facemask or nasal cannula. Surgical procedures ranged from surgery of the gastrointestinal tract, including five studies on colorectal surgery, to caesarean sections and trauma surgery. In addition to the RCTs, two non-randomized studies with serious-critical risk of bias were included in the safety review.

Effectiveness

Meta-analysis of the included trials showed little evidence of a benefit of perioperative administration of high (80%) FiO2 on the prevention of SSI compared to standard (30–35%) FiO2: Relative risk (RR): 0.89; 95% CI: 0.73–1.07 (Table 2). There was evidence of heterogeneity (tau2=0.055; Chi2 test for heterogeneity: P=0.025; I2 =45.4%). After careful appraisal of the included studies, the research team and the GDG noted that the method of delivery of the intervention (that is, under general anaesthesia with endotracheal intubation and mechanical ventilation vs. oxygen administration via a facemask or nasal cannula without intubation) and the type of procedure could be potential effect modifiers. Meta-regression indicated that the method of oxygen administration modified the effect of the administration of high FiO2 on the incidence of SSI (test of interaction, P=0.048; proportion variance explained, 27%). In patients under general anaesthesia with endotracheal intubation and mechanical ventilation, 80% FiO2 reduced the incidence of SSI (RR: 0.80: 95% CI 0.64–0.99; tau2=0.051; Chi2 test for heterogeneity, P=0.043; I2=46.7%). By contrast, if patients were awake and breathing spontaneously via a facemask or nasal cannula, there was no evidence of a benefit of the intervention (RR: 1.20; 95% CI: 0.91–1.58; tau2=0.000; Chi2 test for heterogeneity, P=0.482; I2=0.0 %). The type of procedure did not affect the effect estimate (test of interaction, P=0.110). Similarly, there was no evidence that the use of nitrous oxide in the gas mixture influenced the effect (test of interaction, P=0.945).

Safety

No evidence of harm with high FiO2 was found for major adverse effects in the meta-analysis of randomized trials: atelectasis RR; 0.91 (95% CI: 0.59–1.42); cardiovascular events RR: 0.90 (95% CI: 0.32–2.54); intensive care admission RR: 0.93 (95% CI: 0.7–1.12); death during the trial RR: 0.49 (95% CI: 0.17–1.37). One non-randomized study reported that high FiO2 was associated with major respiratory adverse effects (RR: 1.99 [95% CI: 1.72–2.31]).

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG concluded that all patients, health care providers and policy-makers will likely favour the intervention. The GDG acknowledged that oxygen administration with a mask might be quite uncomfortable for patients in the postoperative period when they are extubated and waking up from anaesthesia. More research is needed on the use of high FiO2, including qualitative research on patient values and preferences.

Resource use

In LMICs, oxygen availability (procurement and distribution) and the related costs are a problem and a burden on available resources. Nevertheless, the implementation of this recommendation and the need for oxygen for other critical clinical uses should drive an increased access to oxygen, including its local production in hospitals, which should be encouraged. However, it was pointed out that even when it is implemented, the equipment for both the concentration and production of oxygen (that is, oxygen generation tanks/pumps) may not be cost effective or readily available. Lack of quality control (for example, contamination of the tanks with bacteria and fungi can occur, especially during condensation), incorrectly labelled tanks, maintenance of production and infrastructure challenges (for example, electricity) are other considerations in resource-limited settings. It was noted also that a high flux mask would be needed to maintain high-flow oxygen in the postoperative period in extubated patients, which would be an additional cost. Furthermore, as it may be uncomfortable for patients to wear a mask for 2–6 hours after surgery, it could be an additional burden on staff.

Research gaps

The GDG members highlighted the limited evidence available in some areas. More research from high quality RCTs is needed on the effectiveness and safety of the perioperative use of high FiO2, in particular to provide more details on research aspects as follows. New trials should account for the values of PaO2 obtained when high FiO2 is applied, that is, they should standardize (normalize) lung conditions through the application of an optimal perioperative ventilatory management. They should also account for other factors related to delivery of oxygen at the cellular level, such as haemodynamics, fluid management, temperature and anaesthetic agents, and have a more diverse geographical representation that includes settings with limited resources and different surgical interventions, while ensuring that basic IPC measures are in place.

Adverse events should be reliably defined, monitored or reported as the study primary outcome. SSI should be defined according to standardized criteria (for example, CDC or ECDC criteria) and sub-specified as superficial, deep and organ/space occupying.

Research is also needed to investigate the benefit of post-extubation hyperoxemia, including different durations, concentrations and oxygen administration routes. As the underlying mechanism of the effect of hyperoxygenation on the incidence of SSI is not entirely understood, translational research investigating these mechanisms is needed. The possible incidence of “awareness” under general anaesthesia with endotracheal intubation and the use of muscle relaxants was not investigated as a potential adverse event with the use of high FiO2, as well as the consequences of the use of a higher concentration of narcotics, hypnotics or inhalational agents. More research is needed on the use of high FiO2, including qualitative research on patient values and preferences. Studies including children are needed as none included the paediatric population so far.

References

1.
Appendix 13a. Summary of the systematic review on perioperative oxygenation issued in 2016. Superseded by Appendix 13b and 13c.
2.
Global guidelines for the prevention of surgical site infection. Geneva: World Health Organization; 2016. [PubMed: 27929621]
3.
Appendix 13b: Effectiveness of 80% versus 30–35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and meta-analysis. de Jonge S, et al. Br J Anaesth. 2019 (in press). doi:10.1016/j.bja.2018.11.024 [PubMed: 30770050] [CrossRef]
4.
Appendix 13c: Safety of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis. Mattishent K, et al. Br J Anaesth. 2019 (in press). doi:10.1016/j.bja.2018.11.026 [PubMed: 30770049] [CrossRef]
5.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:(Suppl 2):S66–88. [PubMed: 25376070]
6.
Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337(7677):1049–51. [PubMed: 18957455]
7.
Preventing surgical site infections. Key recommendations for practice. Joint Royal College of Surgeons in Ireland/Royal College of Physicians of Ireland Working Group on Prevention of Surgical Site Infection; 2012 (http://www​.rcpi.ie/content​/docs/000001/1005_5_media.pdf, accessed 11 December 2018).
8.
Targeted literature review. What are the key infection prevention and control recommendations to inform a surgical site infection (SSI) prevention quality improvement tool? Edinburgh: Health Protection Scotland (http://www​.documents​.hps.scot.nhs.uk/hai​/infection-control/evidence-for-care-bundles​/literature-reviews​/ssi-review-2015-02.pdf, accessed 11 December 2018).
9.
High impact intervention bundle: care bundle to prevent surgical site infection. London (UK): Department of Health; 2010 (http://webarchive​.nationalarchives​.gov.uk​/20120118164404/hcai​.dh.gov.uk/files/2011​/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL​.pdf, accessed 11 December 2018).
10.
Ban KA, Minei JP, Laronga C, Harbrecht BG, Jensen EH, Fry DE, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224(1):59–74. [PubMed: 27915053]
11.
Berrios-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152(8):784–91. [PubMed: 28467526]
12.
Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med. 1996;334(19):1209–15. [PubMed: 8606715]
13.
Dalfino L, Giglio MT, Puntillo F, Marucci M, Brienza N. Haemodynamic goal-directed therapy and postoperative infections: earlier is better. A systematic review and meta-analysis. Crit Care. 2011;15(3):R154. [PMC free article: PMC3219028] [PubMed: 21702945]
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Greif R, Akca O, Horn EP, Kurz A, Sessler DI, Outcomes Research Group. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med. 2000;342(3):161–7. [PubMed: 10639541]
15.
Rodriguez PG, Felix FN, Woodley DT, Shim EK. The role of oxygen in wound healing: A review of the literature. Dermatol Surg. 2008;34(9):1159–69. [PubMed: 18513296]
16.
Hopf HW, Hunt TK, Rosen N. Supplemental oxygen and risk of surgical site infection. JAMA. 2004;291(16):1956; author reply 8–9. [PubMed: 15113804]
17.
Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 1997;132(9):991–6. [PubMed: 9301612]
18.
Owens P, McHugh S, Clarke-Moloney M, Healy D, Fitzpatrick F, McCormick P, et al. Improving surgical site infection prevention practices through a multifaceted educational intervention. Ir Med J. 2015;108(3):78–81. [PubMed: 25876299]
19.
Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391(10131):1693–705. [PubMed: 29726345]
20.
Schietroma M, Cecilia EM, De Santis G, Carlei F, Pessia B, Amicucci G. Supplemental peri-operative oxygen and incision site infection after surgery for perforated peptic ulcer: a randomized, double-blind monocentric trial. Surg Infect (Larchmt). 2016;17(1):106–13. [PubMed: 26554853]
21.
Kurz A, Fleischmann E, Sessler DI, Buggy DJ, Apfel C, Akca O, et al. Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trialdouble dagger. Br J Anaesth. 2015;115(3):434–43. [PubMed: 25900659]
22.
Bickel A, Gurevits M, Vamos R, Ivry S, Eitan A. Perioperative hyperoxygenation and wound site infection following surgery for acute appendicitis: a randomized, prospective, controlled trial. Arch Surg. 2011;146(4):464–70. [PubMed: 21502457]
23.
Duggal N, Poddatoori V, Noroozkhani S, Siddik-Ahmad RI, Caughey AB. Perioperative oxygen supplementation and surgical site infection after cesarean delivery: a randomized trial. Obstet Gynecol. 2013;122(1):79–84. [PubMed: 23743467]
24.
Williams NL, Glover MM, Crisp C, Acton AL, McKenna DS. Randomized controlled trial of the effect of 30% versus 80% fraction of inspired oxygen on cesarean delivery surgical site infection. Am J Perinatol. 2013;30(9):781–6. [PubMed: 23359237]
25.
Stall A, Paryavi E, Gupta R, Zadnik M, Hui E, O’Toole RV. Perioperative supplemental oxygen to reduce surgical site infection after open fixation of high-risk fractures: a randomized controlled pilot trial. J Trauma Acute Care Surg. 2013;75(4):657–63. [PubMed: 24064879]
26.
Chen Y, Liu X, Cheng CH, Gin T, Leslie K, Myles P, et al. Leukocyte DNA damage and wound infection after nitrous oxide administration: a randomized controlled trial. Anesthesiology. 2013;118(6):1322–31. [PubMed: 23549382]
27.
Thibon P, Borgey F, Boutreux S, Hanouz JL, Le Coutour X, Parienti JJ. Effect of perioperative oxygen supplementation on 30-day surgical site infection rate in abdominal, gynecologic, and breast surgery: the ISO2 randomized controlled trial. Anesthesiology. 2012;117(3):504–11. [PubMed: 22790961]
28.
Gardella C, Goltra LB, Laschansky E, Drolette L, Magaret A, Chadwick HS, et al. High-concentration supplemental perioperative oxygen to reduce the incidence of postcesarean surgical site infection: a randomized controlled trial. Obstet Gynecol. 2008;112(3):545–52. [PubMed: 18757651]
29.
Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Hogdall C, Lundvall L, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302(14):1543–50. [PubMed: 19826023]
30.
Pryor KO, Fahey TJ, 3rd, Lien CA, Goldstein PA. Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial. JAMA. 2004;291(1):79–87. [PubMed: 14709579]
31.
Belda FJ, Aguilera L, Garcia de la Asuncion J, Alberti J, Vicente R, Ferrandiz L, et al. Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial. JAMA. 2005;294(16):2035–42. [PubMed: 16249417]
32.
Mayzler O, Weksler N, Domchik S, Klein M, Mizrahi S, Gurman GM. Does supplemental perioperative oxygen administration reduce the incidence of wound infection in elective colorectal surgery? Minerva Anestesiol. 2005;71(1–2):21–5. [PubMed: 15711503]
33.
Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, et al. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007;107(2):221–31. [PubMed: 17667565]
34.
Fariba F, Loghman G, Daem R, Dina S, Jamal S. Effect of supplemental oxygen on the incidence and severity of wound Infection after cesarean surgery. J Chem Pharm Sci. 2016;9(4):3320–5.
35.
Wasnik N, Agrawa V, P, Yede J, Gupta A, Soitkar S. Role of supplemental oxygen in reducing surgical site infection in acute appendicities: Our experience of sixty four cases. Int J Biomed Adv Res. 2015;6(2):124–7.
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Kurz A, Kopyeva T, Suliman I, Podolyak A, You J, Lewis B, et al. Supplemental oxygen and surgical-site infections: an alternating intervention controlled trial. Br J Anaesth. 2018;120(1):117–26. [PubMed: 29397118]
37.
Staehr-Rye AK, Meyhoff CS, Scheffenbichler FT, Vidal Melo MF, Gätke MR, Walsh JL, et al. High intraoperative inspiratory oxygen fraction and risk of major respiratory complications. B J Anaesth. 2017;119(1):140–9. [PubMed: 28974067]

4.13. Maintaining normal body temperature (normothermia)

Recommendation

The panel suggests the use of warming devices in the operating room and during the surgical procedure for patient body warming with the purpose of reducing SSI.

(Conditional recommendation, moderate quality of evidence)

Rationale for the recommendation

  • Overall moderate quality evidence from two RCTs shows that the maintenance of normothermia has a significant benefit in reducing the risk of SSI when compared to non-warming standard care. The GDG unanimously agreed that warming devices should be used to avoid patient hypothermia in the operating room and during the surgical procedure in order to reduce the risk of SSI and, more importantly, other complications associated with surgery (see below). Considering the quality of the evidence (moderate, but relying only on 2 small RCTs), the GDG did not reach full consensus about the strength of this recommendation and most members (11 vs. 4) voted for a conditional recommendation. The GDG appraised that the available evidence supporting this recommendation is limited. It was noted also that no observational studies investigating body warming with a SSI outcome were identified.
  • However, the GDG emphasized that there are additional relevant benefits of warming strategies, such as a decrease in myocardial events, blood loss and transfusion requirements.
  • The GDG agreed that the evidence was insufficient to identify a target temperature to be reached and maintained or an optimal device for warming the patient (for example, fluid warmers or simple blankets). The generally accepted target is core temperature ›36°C, considering that “hypothermia” (or low body temperature) is defined as a core temperature below 36°C and is common during and after major surgical procedures lasting more than two hours. However, it was not possible to reach an agreement regarding the optimal pre- and postoperative time for warming.

Remarks

  • Included studies were conducted in high-income countries and in adult patient populations. However, the GDG considers this recommendation valid also for paediatric patients.
  • The systematic review team and the GDG decided to exclude the study by Wong and colleagues (1) because the PICO question asks for a comparison of warming vs. non-warming, whereas the study by Wong applies warming procedures in both groups. Nevertheless, the GDG acknowledged that the study showed a tendency towards reduced SSI in the intervention group, which employed more intensive warming.
  • The GDG identified a potential harm of skin burns, depending on the warming device (possible with conductive warming mattresses).
  • It was mentioned also that the increased temperature within the work environment may be a concern for surgical staff. Of note, raising the room temperature is not an option to warm the patient as it causes thermal discomfort for the surgical staff, with an increased risk of dripping sweat onto the surgical site.

Background

Hypothermia (or low body temperature) is defined as a core temperature below 36°C and is common during and after major surgical procedures lasting more than two hours. The human body has a central compartment comprising the major organs where temperature is tightly regulated and a peripheral compartment where temperature varies widely (2). Heat loss is compensated by reducing blood flow through the skin and by increasing heat production, mainly by inducing muscular activity (shivering) and increasing the basal metabolic rate. Typically, the periphery compartment may be 2–4°C cooler than the core compartment (2).

Exposure to a cold operating room environment and anaesthetic-induced impairment of thermoregulatory control are the most common events leading to hypothermia (3, 4). Skin surface exposure during the perioperative period can increase heat loss. Furthermore, cool intravenous and irrigation fluids directly cool patients. Sedatives and anaesthetic agents inhibit the normal response to cold, resulting in improved blood flow to the periphery and increased heat loss (3, 4). During the early period of anaesthesia, these effects are observed as a rapid decrease in core temperature caused by redistribution of heat from the central to the peripheral compartment. This early decrease is followed by a more gradual decline, reflecting ongoing heat loss. With epidural or spinal analgesia, the peripheral blockade of vasoconstriction below the level of the nerve block results in vasodilatation and greater ongoing heat loss.

For the above reasons, inadvertent non-therapeutic hypothermia is considered to be an adverse effect of general and regional anaesthesia (5). Published research has correlated unplanned perioperative hypothermia with impaired wound healing, adverse cardiac events, altered drug metabolism and coagulopathies (57).

It is unclear how the maintenance of normothermia in the core body compartment might reduce the incidence of SSI. All available studies measure core and not peripheral temperature. However, it is highly likely that the reported lower core temperatures result in reduced cutaneous temperature at the operative site. Nonetheless, incisional warming has not been shown to decrease SSI rates (8). A recent Cochrane review of the effect of warmed intravenous fluids found no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids (9), but SSI was not the primary outcome. Another Cochrane review of interventions used for treating inadvertent postoperative hypothermia concluded that active warming reduces the time to achieve normothermia. Several warming devices have been studied, including forced-air warming, circulating hot water devices, radiant blankets, radiant warmers and electric blankets. Again, SSI was not among the primary outcomes of the review (10). Temperature monitoring can be performed non-invasively either orally or by infrared ear temperature measurement, which is inaccurate. Intraoperatively, acceptable semi-invasive temperature monitoring sites are the nasopharynx, oesophagus and urinary bladder (11).

Some of the current health care bundles and guidelines recommend that body temperature be maintained above 35.5–36°C during the perioperative period, although there is no consensus among these recommendations for the lower limit or optimal timing for normothermia (Table 4.13.1).

Table 4.13.1. Recommendations on body temperature control (normothermia) according to available guidelines.

Table 4.13.1

Recommendations on body temperature control (normothermia) according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in available guidelines, the GDG decided to conduct a systematic review to assess the effectiveness of body warming on the prevention of SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 14) was to assess whether perioperative body warming vs. no warming is more effective in reducing the risk of SSI. The target population was patients of all ages undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Two RCTs (16, 17) including a total of 478 patients were identified (one was a multicentre study). Both studies compared the effect of body warming in the intervention group vs. no warming in the control group. Both studies addressed pre- and intraoperative warming; no studies were identified that assessed the effect of postoperative warming on SSI. The population studied were adult patients undergoing elective colorectal, hernia repair, vascular and breast surgical procedures. No study was available in the paediatric population. No observational study with SSI as the primary outcome was identified. The literature search did not identify any studies that reported on SSI-attributable mortality.

Moderate quality evidence shows that body warming has a significant benefit when compared to no warming in reducing the risk of SSI (OR: 0.33; 95% CI: 0.17–0.62).

Additional factors considered when formulating the recommendation

Values and preferences

No study was retrieved on patient values and preferences with regards to this intervention. The GDG emphasized that pain, nausea and shivering are among the most frequently reported adverse events following cooling down of the body temperature in the OR. Therefore, the GDG acknowledged that patients may prefer being kept warm during the surgical procedure and would also favour the intervention in order to reduce the risk of SSI. By contrast, the GDG is confident that patients wish to be protected from skin burns due to temperature and contact pressure (for example, conductive warming mattress).

Resource use

The GDG highlighted that the use of warming devices, such as forced-air warming devices or radiant blankets, increases the space and energy needed to store and run the equipment. The equipment and maintenance costs represent also a substantial financial burden, especially for LMICs. Availability and procurement are additional issues in LMICs. It was pointed out that the use of warming devices may decrease the risk of adverse outcomes and overall hospital costs (1820).

The GDG observed that given the lack of evidence to identify the optimal warming devices, it is arguable that simple blankets might function as efficiently as electrically-run devices in warming the patient, particularly in low-resource settings,

Research gaps

The GDG highlighted that well-designed RCTs are needed to identify the target temperature, the optimal devices (fluid warmers, mattresses, simple blankets, etc.) and the proper timing and duration of warming (pre-/intra-/postoperative). Trials should focus on SSI as the primary outcome and ideally address the cost-effectiveness of the intervention. It was emphasized also that there is no evidence from LMICs or in the paediatric population, which represent important research areas.

References

1.
Wong PF, Kumar S, Bohra A, Whetter D, Leaper DJ. Randomized clinical trial of perioperative systemic warming in major elective abdominal surgery. Br J Surg. 2007;94(4):421–6. [PubMed: 17380549]
2.
Hall JE, Guyton AC, editors. Textbook of medical physiology. 12th edition. London: Elsevier Saunders; 2011.
3.
Sessler DI. Mild perioperative hypothermia. New Engl J Med. 1997;336(24):1730–7. [PubMed: 9180091]
4.
Diaz M, Becker DE. Thermoregulation: physiological and clinical considerations during sedation and general anesthesia. Anesthes Prog. 2010;57(1):25–32; quiz 3–4. [PMC free article: PMC2844235] [PubMed: 20331336]
5.
Sessler DI, Rubinstein EH, Moayeri A. Physiologic responses to mild perianesthetic hypothermia in humans. Anesthesiology. 1991;75(4):594–610. [PubMed: 1928769]
6.
Rajagopalan S, Mascha E, Na J, Sessler DI. The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology. 2008;108(1):71–7. [PubMed: 18156884]
7.
Leslie K, Sessler DI, Bjorksten AR, Moayeri A. Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesthes Analg. 1995;80(5):1007–14. [PubMed: 7726398]
8.
Whitney JD, Dellinger EP, Weber J, Swenson RE, Kent CD, Swanson PE, et al. The effects of local warming on surgical site infection. Surg Infect (Larchmt). 2015;16(5):595–603. [PMC free article: PMC4593881] [PubMed: 26125454]
9.
Campbell G, Alderson P, Smith AF, Warttig S. Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia. Cochrane Database Syst Rev. 2015;4:CD009891. [PMC free article: PMC6769178] [PubMed: 25866139]
10.
Warttig S, Alderson P, Campbell G, Smith AF. Interventions for treating inadvertent postoperative hypothermia. Cochrane Database Syst Rev. 2014;11:CD009892. [PubMed: 25411963]
11.
Torossian A. Thermal management during anaesthesia and thermoregulation standards for the prevention of inadvertent perioperative hypothermia. Best Pract Res Clin Anaesthesiol. 2008;22(4):659–68. [PubMed: 19137809]
12.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
13.
Owens P, McHugh S, Clarke-Moloney M, Healy D, Fitzpatrick F, McCormick P, et al. Improving surgical site infection prevention practices through a multifaceted educational intervention. Ir Med J. 2015;108(3):78–81. [PubMed: 25876299]
14.
Targeted literature review: What are the key infection prevention and control recommendations to inform a surgicalsite infection (SSI) prevention quality improvement tool? Edinburgh: Health Protection Scotland; version 3.0, February 2015 (http://www​.documents​.hps.scot.nhs.uk/hai​/infection-control/evidence-for-care-bundles​/literature-reviews​/ssi-review-2015-02.pdf, accessed 24 July 2016).
15.
High impact intervention: care bundle to prevent surgical site infection. London: Department of Health; 2011 (http://webarchive​.nationalarchives​.gov.uk​/20120118164404/http://hcai​.dh.gov.uk/files​/2011/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL.pdf, accessed 24 July 2016).
16.
Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. New Engl J Med. 1996; 334(19):1209–15. [PubMed: 8606715]
17.
Melling AC, Ali B, Scott EM, Leaper DJ. Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial. Lancet. 2001;358(9285):876–80. [PubMed: 11567703]
18.
Fleisher LA, Metzger SE, Lam J, Harris A. Perioperative cost-finding analysis of the routine use of intraoperative forced-air warming during general anesthesia. Anesthesiology. 1998;88(5):1357–64. [PubMed: 9605697]
19.
Mahoney CB, Odom J. Maintaining intraoperative normothermia: a meta-analysis of outcomes with costs. AANA J. 1999;67(2):155–63. [PubMed: 10488289]
20.
Berry D, Wick C, Magons P. A clinical evaluation of the cost and time effectiveness of the ASPAN hypothermia guideline. J Perianesthes Nurs. 2008;23(1):24–35. [PubMed: 18226782]

4.14. Use of protocols for intensive perioperative blood glucose control

Recommendation

The panel suggests the use of protocols for intensive perioperative blood glucose control for both diabetic and non-diabetic adult patients undergoing surgical procedures to reduce the risk of SSI.

(Conditional recommendation, low quality of evidence)

Rationale for the recommendation

  • Overall low quality evidence shows that a protocol with more strict blood glucose target levels has a significant benefit in reducing SSI rates when compared to a conventional protocol. There was evidence that the effect was smaller in studies that used intensive blood glucose controls intraoperatively only compared to studies that used an intensive protocol postoperatively or both intra- and postoperatively. Among the intensive protocols, the effect was similar in studies with a target blood glucose level of ≤110 mg/dL (6.1 mmol/L) and an upper limit target level of 110–150 mg/dL (6.1–8.3 mmol/L). Similar to meta-regression analysis, there was no evidence that the effect of intensive blood glucose control differed between studies of diabetic and non-diabetic patients. Thus, the GDG unanimously agreed that the recommendation to use protocols for intensive perioperative blood glucose control should apply to both diabetics and non-diabetics. However, the GDG decided that the available evidence did not allow the definition of an optimal target level of blood glucose. The strength of this recommendation was considered to be conditional.

Remarks

  • The GDG observed that most studies were done in intensive care settings, with no studies in paediatric populations. Therefore, the effectiveness of this intervention is not proven for paediatric patients.
  • In general, blood glucose target levels in the intensive protocol group were ≤150 mg/dL (8.3 mmol/L), whereas blood glucose target levels in the conventional protocol group were all <220 mg/dL (12.2 mmol/L).
  • Intravenous insulin administration was performed in the intensive protocol group in all studies and in the conventional protocol group in most studies. Three trials (13) used subcutaneous administration in the conventional group. Some studies used continuous insulin administration, whereas others used intermittent. One study (4) administered a fixed high dose of intravenous insulin with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (“insulin clamp”).
  • Duration and timing of glucose control differed between studies. The definitions of postoperative glucose control varied from 18 hours and “until enteral nutrition” to a maximum of 14 days.
  • Five trials (13, 5, 6) studied diabetic patients, 8 studies (4, 713) included both diabetic and non-diabetic individuals, and 2 studies (14, 15) concerned only non-diabetic patients. The most frequent surgical procedures were cardiac surgery. Some studies focused on patients undergoing other major surgical procedures, including abdominal surgery.
  • The GDG emphasized that hypoglycaemia is a possible harm associated with protocols with strict blood glucose target levels. Hypoglycaemia has a serious risk of life-threatening complications, such as cardiac events. Different definitions for hypoglycaemic events were used in the studies and varied from blood glucose levels ≤ 40 mg/dL (2.2 mmol/L) to ≤ 80 mg/dL (4.4 mmol/L).
  • Data from the available evidence showed no difference in the risk of death and stroke with the use of an intensive protocol compared to a conventional protocol.

Background

Blood glucose levels rise during and after surgery due to surgical stress. Surgery causes a stress response that results in a release of catabolic hormones and the inhibition of insulin. Moreover, surgical stress influences pancreatic beta-cell function, which results in lower plasma insulin levels. Taken together, this relative hypoinsulinaemia, insulin resistance and excessive catabolism from the action of counter-regulatory hormones make surgical patients at high risk for hyperglycaemia, even non-diabetic individuals (16).

Several observational studies (1720) showed that hyperglycaemia is associated with an increased risk of SSI and therefore an increased risk of morbidity, mortality and higher health care costs in both diabetic and non-diabetic patients and in different types of surgery. Conflicting results have been reported regarding the different treatment options to control hyperglycaemia in diabetic and non-diabetic patients, the optimal target levels of blood glucose and the ideal timing for glucose control (intra- and/or postoperative). Moreover, some studies targeting relatively low perioperative glucose levels have highlighted the risk of adverse effects associated with intensive protocols as they may cause hypoglycaemia (2124).

Several organizations have issued recommendations regarding perioperative blood glucose control (Table 4.14.1). While most recommendations focus on the diabetic patient only, those issued by SHEA/IDSA (25) and the American College of Physicians (26) apply to all surgical patients. They recommend either target levels between 140–200 mg/dL (7.8–11.1 mmol/L) or upper limits of 180 mg/dL (10mmol/L) or 198 mg/dL (11mmol/L). Due to the risk of hypoglycaemia, targeting lower levels should be avoided (26, 27).

Table 4.14.1. Recommendations on perioperative blood glucose control according to available guidelines.

Table 4.14.1

Recommendations on perioperative blood glucose control according to available guidelines.

Following an in-depth analysis of the sources and strength of the evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the impact of perioperative blood glucose levels on the risk of SSI and to determine the optimal perioperative target levels in diabetic and non-diabetic surgical patients to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 15) was to evaluate whether the use of protocols for intensive perioperative blood glucose control is more effective in reducing the risk of SSI than conventional protocols with less stringent blood glucose target levels. The population studied were patients of all ages, both diabetic and non-diabetic, and undergoing several types of surgical procedures. The primary outcome was the occurrence of SSI and SSI-attributable mortality. A total of 15 RCTs (115) including a total of 2836 patients and comparing intensive perioperative blood glucose protocols vs. conventional protocols with less stringent blood glucose target levels were identified. Eight studies were performed in adult patients undergoing cardiac surgery (1, 2, 4, 6, 911, 15), 6 in patients undergoing abdominal or major non-cardiac surgery (3, 5, 7, 1214), and one other study in patients undergoing emergency cerebral aneurysm clipping (8). No study was available in a paediatric population. In 2 studies (4, 7), glucose control was performed intraoperatively only. Eight studies (1, 2, 6, 8, 9, 11, 13, 15) investigated intra- and postoperative glucose control and 5 studies (3, 5, 10, 12, 14) focused on postoperative glucose control.

None of the studies had SSI as their primary outcome. Most studies had a combined outcome of postoperative complications. The definition of SSI was also different in most studies.

There was substantial heterogeneity among the selected studies in the population, notably regarding the timing when intensive blood glucose protocols were applied in the perioperative period and intensive blood glucose target levels. For this reason, separate meta-analyses were performed to evaluate intensive protocols vs. conventional protocols in different settings (that is, in diabetic, non-diabetic and a mixed population) with intraoperative, intra- and postoperative glucose control, and in trials with intensive blood glucose upper limit target levels of ≤110 mg/dL (6.1 mmol/L) and 110–150 mg/dL (6.1–8.3 mmol/L) (web Appendix 15).

Overall, there is low quality evidence that a protocol with more strict blood glucose target levels has a significant benefit in reducing SSI rates when compared to a conventional protocol (OR: 0.43; 95% CI; 0.29–0.64). In addition, there was no evidence in meta-regression analyses that the effect of intensive blood glucose control differed between studies of diabetic and non-diabetic patients (P=0.590). There was evidence that the effect was smaller in studies that used intensive blood glucose control intraoperatively only (OR: 0.88; 95% CI: 0.45–1.74) compared to studies that used controls postoperatively or both intra- and postoperatively (OR: 0.47; 95% CI: 0.25–0.55; P=0.049 for the difference between ORs). Among the intensive protocols, the effect was similar in studies with upper limit target blood glucose levels of ≤110 mg/dL (6.1 mmol/L) and 110–150 mg/dL (6.1–8.3 mmol/L) (P=0.328).

Data from the available evidence showed no difference in the risk of postoperative death and stroke with the use of an intensive protocol compared to a conventional protocol (OR: 0.74; 95% CI: 0.45–1.23 and OR: 1.37; 95% CI: 0.26–7.20, respectively). The study by Ghandi and colleagues was the only one that reported more strokes and deaths in the intensive group (11). This study had comparable 24-hour achieved blood glucose levels in the intensive care unit in both groups, although they were significantly lower in the intensive group intraoperatively and at baseline. Other studies showed equal or even less strokes and/or deaths in the intensive group, but these findings were not significant. In meta-regression analyses, there is no evidence for a difference in risk between studies with an upper limit target blood glucose level of ≤110 mg/dL (6.1 mmol/L) and an upper limit level of 110–150 mg/dL (6.1–8.3 mmol/L) (P=0.484 for mortality and P=0.511 for stroke).

Meta-analysis of hypoglycaemic events in the 8 RCTs with a blood glucose upper limit target level of ≤110 mg/dL (6.1 mmol/L) showed an increased risk of hypoglycaemic events with the use of an intensive protocol over a conventional protocol (OR: 4.18; 95% CI: 1.79–9.79). However, 2 of the 8 studies included in this analysis had no hypoglycaemic events (4, 13) and only 3 studies (3, 7, 14) found significantly more hypoglycaemic events with the use of the intensive protocol. A meta-analysis of 4 studies (1, 2, 6, 10) showed an increased risk of hypoglycaemic events with the use of a strict protocol with a blood glucose upper limit target level of 110–150 mg/dL (6.1–8.3 mmol/L) compared to a conventional protocol (OR: 9.87; 95% CI: 1.41–69.20). Two studies included in this analysis had no hypoglycaemic events (1, 2). Among the studies that could not be included in the meta-analysis due to missing data, 2 reported significantly more hypoglycaemic events in the intensive group (8, 12), while no difference in risk was observed in another study (9). Overall, there is an increased risk for hypoglycaemic events with the use of either intensive protocol for blood glucose control (OR: 5.55; 95% CI: 2.58–11.96). In meta-regression analyses, there is no evidence for a difference in the risk of hypoglycaemia between studies with a target blood glucose level of ≤110 mg/dL (6.1 mmol/L) and an upper limit target level of 110–150 mg/dL (6.1–8.3 mmol/L) (P=0.413).

The GDG underlined that there are many observational studies showing a reduction in SSI with intensive blood glucose control in non-diabetic populations. However, after discussion, the GDG agreed not to include the data from the observational studies.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that most patients wish to receive this intervention in order to reduce the risk of SSI. Patients are concerned about hypoglycaemic events, as well as being monitored for the blood glucose target level on a regular (sometimes a few times daily) basis, which might be associated with frequent needle pricks.

Resource use

The GDG members emphasized that apart from in intensive care settings, patients are more likely to receive a conventional protocol because of concerns regarding resources and the ability to monitor blood glucose adequately. The GDG highlighted that the purchase and storage (refrigerator) of insulin is a financial burden in LMICs and the availability of insulin is a concern. The equipment for the application of frequent glucose control is also expensive and may be limited in availability in such settings. In addition, the medical staff has to be carefully trained to correctly monitor the blood glucose level and treat hypoglycaemic events. There are no data available to determine the cost-effectiveness of different protocols.

Research gaps

GDG members highlighted that the available evidence mostly consists of intensive care and cardiac surgery populations. There is a need for studies in the paediatric setting, as well as in non-ICU surgical patients and those undergoing different types of surgical procedures. Adequately-powered RCTs should be performed to compare different blood glucose target levels in order to better define the optimal level for the purpose of SSI prevention, but with only a very limited risk of hypoglycaemia. For a given target level, there should be studies investigating the optimal route of insulin administration, as well as studies on the duration of continued postoperative glucose control. In particular, the GDG noted that research on cost-effectiveness and studies from LMICs are needed.

References

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Cao SG, Ren JA, Shen B, Chen D, Zhou YB, Li JS. Intensive versus conventional insulin therapy in type 2 diabetes patients undergoing D2 gastrectomy for gastric cancer: a randomized controlled trial. World J Surg. 2011;35(1):85–92. [PubMed: 20878324]
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Lazar HL, McDonnell MM, Chipkin S, Fitzgerald C, Bliss C, Cabral H. Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients. Ann Surg. 2011;254(3):458–63; discussion 63–4. [PubMed: 21865944]
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Abdelmalak BB, Bonilla A, Mascha EJ, Maheshwari A, Tang WH, You J, et al. Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized controlled trial. Br J Anaesthes. 2013;111(2):209–21. [PubMed: 23539236]
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Bilotta F, Spinelli A, Giovannini F, Doronzio A, Delfini R, Rosa G. The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome, and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective pilot trial. J Neurosurg Anesthesiol. 2007;19(3):156–60. [PubMed: 17592345]
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Chan RP, Galas FR, Hajjar LA, Bello CN, Piccioni MA, Auler JO, Jr. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial. Clinics (Sao Paulo). 2009;64(1):51–60. [PMC free article: PMC2671976] [PubMed: 19142552]
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Desai SP, Henry LL, Holmes SD, Hunt SL, Martin CT, Hebsur S, et al. Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: a prospective randomized controlled trial. J Thorac Cardiovasc Surg. 2012;143(2):318–25. [PubMed: 22137804]
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Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, O’Brien PC, et al. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Int Med. 2007;146(4):233–43. [PubMed: 17310047]
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Grey NJ, Perdrizet GA. Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. Endocrine Pract. 2004;10(Suppl. 2):46–52. [PubMed: 15251640]
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Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Tokumaru T, Iiyama T, et al. Intensive versus intermediate glucose control in surgical intensive care unit patients. Diabetes Care. 2014;37(6):1516–24. [PubMed: 24623024]
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Cao S, Zhou Y, Chen D, Niu Z, Wang D, Lv L, et al. Intensive versus conventional insulin therapy in nondiabetic patients receiving parenteral nutrition after D2 gastrectomy for gastric cancer: a randomized controlled trial. J Gastrointest Surg. 2011;15(11):1961–8. [PubMed: 21904964]
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Zheng R, Gu C, Wang Y, Yang Z, Dou K, Wang J, et al. Impacts of intensive insulin therapy in patients undergoing heart valve replacement. Heart Surg Forum. 2010;13(5):E292–8. [PubMed: 20961828]
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McAnulty GR, Robertshaw HJ, Hall GM. Anaesthetic management of patients with diabetes mellitus. Br J Anaesthes. 2000;85(1):80–90. [PubMed: 10927997]
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Ata A, Lee J, Bestle SL, Desemone J, Stain SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg. 2010;145(9):858–64. [PubMed: 20855756]
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Kotagal M, Symons RG, Hirsch IB, Umpierrez GE, Dellinger EP, Farrokhi ET, et al. Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg. 2015;261(1):97–103. [PMC free article: PMC4208939] [PubMed: 25133932]
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Richards JE, Hutchinson J, Mukherjee K, Jahangir AA, Mir HR, Evans JM, et al. Stress hyperglycemia and surgical site infection in stable nondiabetic adults with orthopedic injuries. J Trauma Acute Care Surg. 2014;76(4):1070–5. [PubMed: 24662873]
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Blondet JJ, Beilman GJ. Glycemic control and prevention of perioperative infection. Curr Opin Crit Care. 2007;13(4):421–7. [PubMed: 17599013]
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Buchleitner AM, Martinez-Alonso M, Hernandez M, Sola I, Mauricio D. Perioperative glycaemic control for diabetic patients undergoing surgery. Cochrane Database Syst Rev. 2012;9:CD007315. [PubMed: 22972106]
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Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180(8):821–7. [PMC free article: PMC2665940] [PubMed: 19318387]
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4.15. Maintenance of adequate circulating volume control/normovolemia

Recommendation

The panel suggests the use of goal-directed fluid therapy (GDFT) intraoperatively to reduce the risk of SSI.

(Conditional recommendation, low quality of evidence)

Rationale for the recommendation

  • Overall low quality evidence shows that intraoperative GDFT has significant benefit in reducing the SSI rate compared to standard fluid management. This effect is shown also for GDFT in the postoperative period.
  • Considering that both fluid overload and hypovolemia are likely to affect other clinical outcomes, the GDG agreed to emphasize that specific fluid management strategies, such as GDFT or restrictive fluid management, may be used during surgery for purposes other than the reduction of SSI, for example, to support cardiovascular and renal functions.
  • Considering the low quality evidence, as well as the above-mentioned factors, the GDG agreed to suggest the use of GDFT intraoperatively and decided that the strength of this recommendation should be conditional.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, this effectiveness of this intervention is not proven for paediatric patients.
  • GDFT refers to a haemodynamic treatment based on the titration of fluid and inotropic drugs according to cardiac output or similar parameters.
  • Restrictive fluid management refers to the administration of a regimen with a reduced volume of fluids in the bolus and/or over time compared to local standard fluid maintenance.
  • Standard fluid maintenance in the control group refers to the administration of fluid regimens at the discretion of the treating medical team or according to the local standard.
  • Most trials among the included studies compared the efficacy of specific fluid management strategies with standard fluid regimens in the intraoperative period. Fourteen RCTs investigated GDFT (114) and 5 RCTs focused on restrictive fluid management (1519). As the PICO question focused on fluid management during surgery, these comparisons were used to formulate the recommendation.
  • Further trials compared specific fluid management strategies vs. standard fluid management in the preoperative (20) and/or postoperative period (2124).
  • It was discussed that the actual physiological effect of administered fluids may also differ, depending on several other factors, such as surgical stress, normothermia and tissue oxygenation.
  • The GDG argued that both fluid overload and hypovolemia are likely to increase mortality and morbidity (25).
  • Although the optimal strategy for GDFT cannot be identified from the published data due to the heterogeneity of the protocols used in the included studies, the panel suggests administering haemo-dynamic therapy based on a goal-directed approach during the entire surgical procedure. Optimization is preferably based on dynamic pre-load parameters (that is, pulse pressure variation, systolic pressure variation) derived from arterial catheter measurements (when an arterial line is indicated) or minimal invasive alternatives.
  • The GDG felt that using an algorithm is helpful, while taking into account that local resources and expertise may vary and limit possibilities for the optimal strategy. Indeed, the variety of effective algorithms on a multitude of outcomes indicates that having an algorithm for a specific goal is the most important factor, more than any particular algorithm associated with the effect of GDFT.

Background

Wound healing and resistance to infection is dependent on tissue oxygen tension. In addition, sufficient tissue oxygenation is essential for collagen synthesis and wound repair (17) and is improved by adequate arterial oxygenation. Ideally, perioperative fluid therapy prevents tissue hypoxia by maximizing the cardiac output and thus improving arterial oxygenation. However, the optimal perioperative fluid strategy remains a subject of debate. A large variability exists between regimens in daily practice and both fluid overload (hypervolemia) and hypovolemia have been associated with increased mortality and morbidity. Fluid overload leads to a decrease in muscular oxygen tension. Due to surgical trauma, a systemic inflammatory response arises, which leads to a fluid shift to the extravascular space. Following a large fluid shift, generalized oedema may occur, which decreases tissue oxygenation and impedes tissue healing. By contrast, hypovolemia leads to arterial and tissue hypoxia due to a decrease in cardiac output.

The optimal fluid (colloid or crystalloid) or strategy of fluid management (GDFT, liberal or restricted) remains a subject of controversy. GDFT uses cardiac output or similar parameters to guide intravenous fluid and inotropic administration, but the disadvantage of this strategy is the difficulty to adequately assess normovolemia. Liberal and restrictive fluid strategies use standard fluid regimens not based on cardiac output. Nevertheless, an adequate assessment of normovolemia in these strategies remains complicated. In addition, the physiological effects of any given volume of fluid may differ, depending on the magnitude of the surgical stress response and not solely on the volume of fluids administered. At present, there is no universal definition of normovolemia or a standardized method for its assessment. Some studies assess normovolemia by urinary output or serum markers, whereas others use more invasive techniques, such as cardiac output or cardiac index.

Few organizations have issued recommendations regarding the maintenance of normovolemia (Table 4.15.1). The UK-based NICE recommends maintaining adequate perfusion during surgery (26). Based on an evidence update in 2013, it is stated that haemodynamic GDFT appears to reduce SSI rates (27). The SHEA/IDSA guidelines do not formulate a specific recommendation on the maintenance of normovolemia for SSI prevention. However, in a statement on oxygen therapy, it is indirectly recommended to maintain an appropriate volume replacement (28).

Table 4.15.1. Recommendations for the maintenance of normovolemia according to available guidelines.

Table 4.15.1

Recommendations for the maintenance of normovolemia according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the effectiveness of specific fluid management strategies compared with standard fluid regimens and to determine if certain fluid management strategies during surgery might be beneficial to prevent SSI in surgical patients.

Summary of the evidence

The purpose of the evidence review (web Appendix 16) was to evaluate whether specific fluid management strategies for the maintenance of normovolemia are more effective in reducing the risk of SSI than standard fluid regimens administered during surgery. The target population included patients of all ages undergoing a surgical operation. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Twenty-four RCTs (124) including a total of 4031 patients and comparing specific strategies of fluid management with standard fluid management were identified. Types of surgical procedures included were colorectal, abdominal, general, urology, gynaecological, cardiothoracic, vascular, orthopaedic and other surgery.

Due to heterogeneity among the selected studies in the type of specific fluid management strategy used throughout the perioperative period, separate meta-analyses were performed for GDFT or restrictive fluid regimens vs. standard fluid regimens in the pre-, intra- and postoperative periods.

Overall, there is low quality evidence that intraoperative GDFT has a significant benefit in reducing the SSI rate compared to standard fluid management (OR: 0.56; 95% CI: 0.35–0.88). By contrast, very low quality evidence indicated that intraoperative restrictive fluid management has neither benefit nor harm compared to standard intraoperative fluid management in reducing the SSI rate (OR: 0.73; 95% CI: 0.41–1.28).

One study (20) compared GDFT vs. standard fluid management preoperatively and demonstrated no benefit in reducing the risk of SSI (OR: 0.47; 95% CI: 0.13–1.72), whereas a meta-analysis of 2 RCTs (22, 23) comparing GDFT vs. standard fluid management in the postoperative period showed a decrease of the risk of SSI in the GDFT group (OR: 0.24; 95% CI: 0.11–0.52). One study (24) comparing restrictive vs. standard fluid management postoperatively showed no difference in risk (OR: 6.20; 95% CI: 0.68–56.56). Similarly, one RCT (21) compared GDFT vs. standard fluid management pre- and postoperatively combined and demonstrated no benefit (OR: 0.75; 95% CI: 0.16–3.52).

The retrieved evidence focused on adult patients only. No study was available in a paediatric population. Five RCTs reported that either fluid overload or hypovolemia seem to be associated with increased mortality and morbidity (15, 18, 19, 23, 24).

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG pointed out that patients are seldom informed about fluid management.

Resource use

The GDG underlined that there are no studies on the costs or cost-effectiveness of different fluid management strategies during surgery. However, the GDG noted that GDFT might require more resources, including the fact that the medical staff needs to be specifically trained. It was noted that in low-resource settings, anaesthesia is often provided by non-specialized professionals and there may also be a limitation in the type of intravenous fluids available.

Research gaps

The GDG highlighted that a widely-accepted definition for normovolemia is needed. Future studies including large well-designed RCTs with clear definitions should aim at identifying the most accurate and least invasive method of measuring normovolemia and assess its influence with regard to tissue oxygenation and normothermia. In particular, studies should be conducted in LMICs. More research is required to investigate the effectiveness of different fluid management strategies in paediatric populations.

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Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Effect of intraoperative fluid management on outcome after intraabdominal surgery. Anesthesiology. 2005;103(1):25–32. [PubMed: 15983453]
20.
Wilson J, Woods I, Fawcett J, Whall R, Dibb W, Morris C, et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ. 1999;318(7191):1099–103. [PMC free article: PMC27840] [PubMed: 10213716]
21.
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22.
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Silva JM, Jr., de Oliveira AM, Nogueira FA, Vianna PM, Pereira Filho MC, Dias LF, et al. The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study. Crit Care. 2013;17(6):R288. [PMC free article: PMC4057181] [PubMed: 24326085]
26.
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27.
A summary of selected new evidence relevant to NICE clinical guideline 74 “Prevention and treatment of surgical site infection” (2008). Evidence update 43. June 2013. Manchester: National Institute for Health and Care Excellence (http://www​.nice.org.uk​/guidance/cg74/evidence, acccessed 21 July 2016).
28.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]

4.16. Drapes and gowns

Recommendations

  1. The panel suggests that either sterile, disposable, non-woven or sterile, reusable woven drapes and surgical gowns can be used during surgical operations for the purpose of preventing SSI.
    (Conditional recommendation, moderate to very low quality of evidence)
  2. The panel suggests not to use plastic adhesive incise drapes with or without antimicrobial properties for the purpose of preventing SSI.
    (Conditional recommendation, low to very low quality of evidence)

Rationale for the recommendations

  • It is good clinical practice to use sterile drapes and gowns for surgery. To determine what type of surgical drapes and gowns are the most effective for the purpose of preventing SSI, the GDG decided to focus on disposable non-woven and reusable woven drapes, including plastic adhesive incise drapes with or without antimicrobial properties. Non-woven and woven drapes and gowns with antimicrobial properties were not considered a priority and no relevant evidence was found.
  • Available evidence from one RCT, one quasi-RCT and 2 observational studies (moderate quality for RCTs and very low for observational) shows that the use of sterile disposable non-woven drapes and sterile surgical gowns has neither benefit nor harm when compared to sterile reusable woven drapes and surgical gowns in reducing the SSI rate. Considering the quality of the evidence, the GDG unanimously agreed to suggest that either sterile disposable non-woven or sterile reusable woven drapes and surgical gowns can be used. The strength of this recommendation was considered to be conditional.
  • The GDG pointed out that there is no evidence for the potential effect of the timing or usefulness of changing surgical drapes or gowns in the course of a surgical operation for the purpose of preventing SSI.
  • Evidence available from one RCT, one quasi-RCT and 2 observational studies (overall very low quality for both RCTs and observational) shows that the use of adhesive iodophor-impregnated incise drapes has neither benefit nor harm when compared to no adhesive incise drapes in reducing the SSI rate.
  • Available evidence from 2 RCTs (overall low quality) shows that the use of plastic, adhesive, nonimpregnated incise drapes has neither benefit nor harm when compared to no adhesive incise drapes in reducing the SSI rate.
  • Considering the lack of evidence that plastic adhesive incise drapes (with or without antimicrobial properties) prevent SSI, the GDG unanimously agreed that they should not be used. Given the quality of the evidence (moderate to very low), the strength of this recommendation was considered to be conditional.

Remarks

  • The GDG highlighted that if the material of the disposable and reusable surgical drapes and gowns is permeable to liquids, it can expose health care workers to body fluids and also represents a risk for patients. Ideally, the material should be impermeable to prevent the migration of microorganisms. The GDG remarked that both reusable and disposable drapes and gowns commercially available are in permeable or impermeable forms.
  • The GDG identified possible harms associated with the use of disposable drapes in that the adhesive bands of single-use drapes may provoke skin rash or eczema and devices may be dislodged when removing adhesive drapes after the surgical procedure (1).
  • Regarding plastic, adhesive incise drapes, the GDG identified allergic reactions as a possible harm associated with the use of iodophor-impregnated incise drapes (2). The GDG noted also that a further possible harm could be that pieces of the adhesive film might remain in the wound.

Background

Sterile surgical drapes are used during surgery to prevent contact with unprepared surfaces and maintain the sterility of environmental surfaces, equipment and the patient’s surroundings. Similarly, sterile surgical gowns are worn over the scrub suit of the operating team during surgical procedures to maintain a sterile surgical field and reduce the risk of the transmission of pathogens to both patients and staff (3).

Surgical gowns and drapes are fabricated from either multiple- or single-use materials. In addition, there is a considerable variation in design and performance characteristics within each of these two broad categories, which reflects the necessary trade-offs in economy, comfort and degree of protection required for particular surgical procedures (4).

During surgical procedures, the risk of pathogen transmission increases if the barrier materials become wet. Consequently, the multiple- or single-use materials of the drapes and gowns used in a surgical procedure should prevent the penetration of liquids. Reusable materials are typically composed of different tightly woven textiles and/or knitted cotton or other fabrics possibly blended with polyester and/or chemically treated. These products have to be durable and provide protection after many cycles of processing and treatment. Disposable surgical drapes and gowns are typically composed of non-woven material of synthetic and/or natural origin, possibly combined with chemical treatment (3).

Adhesive plastic incise drapes, either plain or impregnated with an antimicrobial agent (mostly an iodophor), are used on the patient’s skin after completion of the surgical site preparation. The film adheres to the skin and the surgeon cuts through the skin and the drape itself (5). Such a drape is theoretically believed to represent a mechanical and/or microbial barrier to prevent the migration of microorganisms from the skin to the operative site (6). However, some reports have shown an increased recolonization of the skin following antiseptic preparation underneath adhesive drapes compared to the use of no drapes (7).

A Cochrane review (8) and its updates (5, 9) of the effect of adhesive incise drapes to prevent SSI found that there is no evidence that plastic adhesive drapes reduce SSI. No recommendation is available on the use of sterile disposable or reusable drapes and surgical gowns for the purpose of SSI prevention.

This topic is addressed in a few of the recent available guidelines, but with conflicting recommendations. The recent SHEA/IDSA guidelines issued in 2014 recommend that plastic adhesive drapes with or without antimicrobial properties should not be used routinely as a strategy to prevent SSI (10). However, the UK-based NICE issued a guideline in 2008 recommending that an iodophor-impregnated drape should be used if a plastic adhesive drape is required (11).

Following an in-depth analysis of the available resources and given the limited recommendations from other guidelines, the GDG decided to conduct a systematic review to assess the effect of the use of sterile disposable or reusable drapes and surgical gowns, including plastic adhesive incise drapes, for the purpose of SSI prevention.

Summary of the evidence

The purpose of the evidence review (web Appendix 17) was to evaluate 3 important questions: (1) whether sterile disposable non-woven drapes and gowns or sterile reusable woven drapes and gowns should be used to prevent SSI; (2) whether changing drapes during operations affect the risk of SSI; and (3) whether sterile, disposable, adhesive incise drapes should be used to reduce the risk of SSI. The target population included patients of all ages undergoing a surgical procedure, with the presence of postoperative drainage. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

A total of 11 studies (1, 1221) related to these topics with SSI as the primary outcome were identified and included 4 RCTs (12, 17, 20, 21).

Regarding the first question, five studies including a total of 6079 patients and comprising one RCT (12), one quasi-RCT (13) and three observational (1, 14, 15) were identified. Studies included clean and clean-contaminated (for example, general, cardiothoracic, orthopaedic, neurosurgery and plastic surgery) procedures. Four studies (1, 12, 13, 15) compared the use of sterile, disposable non-woven drapes and gowns vs. sterile, reusable woven drapes and gowns. One study (14) compared the use of sterile, disposable fenestrated drapes designed originally for cardiac catheterization with traditional draping that involved the use of multiple reusable cloth drapes. There was a substantial variation among studies in the definition of SSI and the type and material of the single-use and reusable drapes and gowns.

After careful appraisal of the retrieved studies, a meta-analysis including the studies evaluating sterile, disposable non-woven vs. sterile, reusable woven drapes and gowns was performed. A moderate (RCTs) and very low (observational studies) quality of evidence showed that the use of sterile disposable non-woven drapes and gowns has neither benefit nor harm compared to sterile reusable woven items (OR: 0.85; 95% CI: 0.66–1.09 for RCTs; OR: 1.56; 95% CI: 0.89–2.72 for observational studies).

Regarding the second question, no studies assessing whether changing drapes during operations affects the risk of SSI were identified.

Regarding the third question, 6 studies (3 RCTs (17, 20, 21), one quasi-RCT (16) and 2 observational (18, 19)) including a total of 1717 adult patients with SSI as an outcome were identified. Studies included clean and clean-contaminated (for example, cardiac, hip fracture fixation, open appendectomy, hernia repair and liver resection for hepatocellular carcinoma) surgical procedures. There was a substantial variation in the definition of SSI among studies.

Two separate meta-analysis comparisons were performed to evaluate sterile, disposable, antimicrobial-impregnated adhesive incise drapes vs. sterile non-adhesive incise drapes, and sterile, non-antimicrobial-impregnated adhesive incise drapes vs. sterile non-adhesive incise drapes. There is a very low quality of evidence suggesting that the use of sterile, disposable, antimicrobial-impregnated adhesive incise drapes has neither benefit nor harm compared to sterile non-adhesive incise drapes in reducing the risk of SSI (OR: 2.62; 95% CI: 0.68–10.04 for RCTs; OR: 0.49; 95% CI: 0.16–1.49 for observational studies). There is a low quality of evidence from 2 RCTs that the use of sterile, disposable non-antimicrobial-impregnated adhesive incise drapes has neither benefit nor harm compared to sterile non-adhesive incise drapes in reducing the risk of SSI (OR: 1.10; 95% CI: 0.68–1.78).

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to the interventions addressed in the recommendations. The GDG is confident that most patients would not want to be involved in the decision of whether to use disposable or reusable drapes and surgical gowns as long as the risk of SSI is minimized. It was acknowledged also that although patients may value measures to prevent SSI, they do not wish to be exposed to discomfort or possible harm due to skin irritation or allergic reactions to drapes (for example, associated with some adhesive disposable drapes or adhesive incise drapes).

Resource use

The GDG acknowledged that many different aspects need to be taken into account when evaluating the resource implications for the use of sterile disposable vs. sterile reusable drapes and surgical gowns. These include (but are not limited to) direct purchase costs and costs related to laundry and sterilization, labour required for reprocessing and waste disposal (22). Two studies (23, 24) showed lower costs associated with the use of disposable drapes and gowns, whereas a cost-benefit analysis (22) found costs for sterile disposable drapes and gowns to be relatively higher compared with reusable ones. Other authors reported that costs were similar for disposable and reusable items (25, 26). The heterogeneous findings of the available data on resource implications suggest that disposable and reusable surgical drapes and gowns are probably similar in costs.

In LMICs, the availability of disposable drapes and gowns and adhesive incise drapes may be limited and costs may represent a high financial burden, whereas labour costs for reprocessing reusable items may be less of an issue. The disposal of single-use drapes and gowns and the ecological impact should be considered as their use generates additional clinical waste. Taking into account the lack of evidence of any benefit for the prevention of SSI, the additional cost for plastic adhesive incise drapes is not justified, irrespective of the setting.

Research gaps

The GDG highlighted that the available evidence regarding the interventions addressed in the recommendations is limited and comes mainly from high-income countries. More well-designed RCTs investigating the use of sterile disposable compared to sterile reusable drapes and surgical gowns in terms of SSI prevention are needed, particularly in LMICs. A cost-effectiveness analysis is highly recommended, especially in low-resource settings. Further research should focus also on different types of materials (including permeable and impermeable materials) and address environmental concerns (water, energy, laundry, waste, etc.). Another research priority is to investigate whether drapes should be changed during the operation and if this measure has an effect on SSI rates. The GDG highlighted that the use of adhesive incise drapes is not considered a high priority topic in the field of SSI prevention research. Nevertheless, well-designed RCTs should be encouraged to further investigate the potential benefits of these products, which are aggressively promoted by the manufacturing companies.

References

1.
Castro Ferrer MJ, Maseda Alvarez AM; Rodr›guez Garc›a JI. Comparison of sterile, disposable surgical drapes. Enferm Cl›n. 2004;14(01):3–6.
2.
Zokaie S, White IR, McFadden JD. Allergic contact dermatitis caused by iodophorimpregnated surgical incise drape. Contact Dermatitis. 2011;65(5):309. [PubMed: 21985088]
3.
Rutala WA, Weber DJ. A review of single-use and reusable gowns and drapes in health care. Infect Control Hosp Epidemiol. 2001;22(4):248–57. [PubMed: 11379716]
4.
Selection of surgical gowns and drapes in healthcare facilities. AAMI Technical Information Report TIR No. 11-1994; Arlington (VA); Association for the Advancement of Medical Instrumentation; 1994.
5.
Webster J, Alghamdi A. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst Rev. 2013;1:CD006353. [PubMed: 23440806]
6.
French ML, Eitzen HE, Ritter MA. The plastic surgical adhesive drape: an evaluation of its efficacy as a microbial barrier. Ann Surg. 1976;184(1):46–50. [PMC free article: PMC1344305] [PubMed: 938118]
7.
Falk-Brynhildsen K, Friberg O, Soderquist B, Nilsson UG. Bacterial colonization of the skin following aseptic preoperative preparation and impact of the use of plastic adhesive drapes. Biol Res Nurs. 2013;15(2):242–8. [PubMed: 22278031]
8.
Webster J, Alghamdi AA. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst Rev. 2007(4):CD006353. [PubMed: 17943905]
9.
Webster J, Alghamdi A. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst Rev. 2015;4:CD006353. [PMC free article: PMC6575154] [PubMed: 25901509]
10.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
11.
Daeschlein G, Napp M, Assadian O, Bluhm J, Krueger C, von Podewils S, et al. Influence of preoperative skin sealing with cyanoacrylate on microbial contamination of surgical wounds following trauma surgery: a prospective, blinded, controlled observational study. Int J Infect Dis. 2014;29:274–8. [PubMed: 25449258]
12.
Bellchambers J, Harris JM, Cullinan P, Gaya H, Pepper JR. A prospective study of wound infection in coronary artery surgery. Europ J Cardiothorac Surg. 1999;15(1):45–50. [PubMed: 10077372]
13.
Belkin NL. Are “barrier” drapes cost effective? Today’s Surg Nurse. 1998;20(6):18–23. [PubMed: 9875008]
14.
Gallagher MM, Santini L, Magliano G, Sgueglia M, Venditti F, Padula M, et al. Feasibility and safety of a simplified draping method for pacing procedures. Europace. 2007;9(10):890–3. [PubMed: 17566013]
15.
Treggiari M, Benevento A, Caronno R, Dionigi R. [The evaluation of the efficacy of drapes and gowns of nonwoven fabric versus drapes and gowns of cotton in reducing the incidence of postoperative wound infections]. Minerva Chir. 1992;47(1–2):49–54. [PubMed: 1553053]
16.
Al-Qahtani SM, Al-Amoudi HM, Al-Jehani S, Ashour AS, Abd-Hammad MR, Tawfik OR, et al. Post-appendectomy surgical site infection rate after using an antimicrobial film incise drape: a prospective study. Surg Infect (Larchmt). 2015;16(2):155–8. [PubMed: 25126720]
17.
Segal CG, Anderson JJ. Preoperative skin preparation of cardiac patients. AORN J. 2002;76(5):821–8. [PubMed: 12463081]
18.
Swenson BR, Camp TR, Mulloy DP, Sawyer RG. Antimicrobial-impregnated surgical incise drapes in the prevention of mesh infection after ventral hernia repair. Surg Infect (Larchmt). 2008;9(1):23–32. [PubMed: 18363465]
19.
Yoshimura Y, Kubo S, Hirohashi K, Ogawa M, Morimoto K, Shirata K, et al. Plastic iodophor drape during liver surgery operative use of the iodophor-impregnated adhesive drape to prevent wound infection during high risk surgery. World J Surg. 2003;27(6):685–8. [PubMed: 12732986]
20.
Chiu KY, Lau SK, Fung B, Ng KH, Chow SP. Plastic adhesive drapes and wound infection after hip fracture surgery. Aust N Z J Surg. 1993;63(10):798–801. [PubMed: 8274123]
21.
Ward HR, Jennings OG, Potgieter P, Lombard CJ. Do plastic adhesive drapes prevent post caesarean wound infection? J Hosp Infect. 2001;47(3):230–4. [PubMed: 11247684]
22.
Baykasoglu A, Dereli T, Yilankirkan N. Application of cost/benefit analysis for surgical gown and drape selection: a case study. Am J Infect Control. 2009;37(3):215–26. [PubMed: 19216004]
23.
Murphy L. Cost/benefit study of reusable and disposable OR draping materials. J Healthc Mat Manage. 1993;11(3):44–8. [PubMed: 10124965]
24.
Lizzi AM, Almada GC, Veiga G, Carbone N. Cost effectiveness of reusable surgical drapes versus disposable non-woven drapes in a Latin American hospital. Am J Infect Control. 2008;36(5):e125.
25.
Overcash M. A comparison of reusable and disposable perioperative textiles: sustainability state-of-the-art 2012. Anesth Analg. 2012;114(5):1055–66. [PubMed: 22492184]
26.
McDowell J. An environmental, economic, and health comparison of single-use and reusable drapes and gowns. Asepsis. 1993:1–15.

4.17. Wound protector devices

Recommendation

The panel suggests considering the use of wound protector (WP) devices in clean-contaminated, contaminated and dirty abdominal surgical procedures for the purpose of reducing the rate of SSI.

(Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Overall very low quality evidence shows that a single- or double-ring WP device has benefit in reducing the rate of SSI compared with regular wound protection. Meta-regression analysis showed no strong evidence for a difference in the effect between single- and double-ring WPs. There was also no evidence that the effect differed between clean-contaminated or contaminated or dirty surgery and other surgery.
  • The GDG agreed to suggest the use of either WP device in abdominal surgery with laparotomy for the purpose of reducing SSI. Given the very low quality evidence, the strength of the recommendation was considered to be conditional and the GDG proposed to use the terminology “The panel suggests considering…” to highlight the need for careful local evaluation about whether and how to apply this recommendation, in particular regarding the availability of these devices and associated costs.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, the effectiveness of this intervention is not proven for paediatric patients.
  • Two differently designed types of commercially-available WP devices have been used as an intervention in the included studies, that is, single- (16) and double-ring WPs (711).
  • With regard to the degree of wound contamination in abdominal surgery, 5 studies included clean-contaminated (37), 5 studies included contaminated (26) and 6 studies investigated dirty procedures (26, 9).
  • The GDG identified possible harms associated with the use of WP devices, particularly in patients with abdominal adhesions. In these cases, the insertion of a WP device may be difficult and lead to the need to enlarge the incision, to injuries to the small bowel and to the prolongation of the procedure. A further concern is the limited space to access the surgical field after insertion of the WP.
  • Although poorly assessed by the studies included, no serious adverse effects have been reported.
  • The GDG emphasized that the operating surgeon needs to be familiar with handling a WP device during placement, in the operative phase and upon removal to avoid wound contamination at these critical time points, particularly when WP is used in patients with a high intra-abdominal bacterial load, such as diffuse peritonitis.
  • The GDG highlighted that these are single-use devices that must not be reused.

Background

Although surgeons have progressively paid more attention to the control of operative wound contamination during surgical procedures, incisional SSI is still a frequent postoperative adverse event jeopardizing patient safety and increasing health care costs.

Conventional surgical drapes are commonly used by surgeons to limit the aseptic surgical area and to cover the freshly-made wound edges. Nevertheless, this non-fixed mechanical barrier may become dislodged or potentially contaminated.

To better reinforce the aspects related to wound edge isolation, surgical WP devices have been fabricated and marketed, unlike new developed drugs that need different controlled studies before approval by regulatory bodies. These new surgical devices comprise a non-adhesive plastic sheath attached to a single or double rubber ring that firmly secures the sheath to the wound edges. The device is intended to facilitate the retraction of the incision during surgery without the need for additional mechanical retractors and cloths. Theoretically, commercially-available WPs are intended to reduce wound edge contamination to a minimum during abdominal surgical procedures, including contamination from outside (clean surgery) and inside the peritoneal cavity (clean-contaminated, contaminated and dirty surgery). Although these surgical devices are already on the market, their real usefulness and cost-effectiveness warrants additional evidence-based analysis.

Few organizations have issued recommendations regarding the use of WP devices (Table 4.17.1).

The UK-based NICE states that wound edge protection devices may reduce SSI rates after open abdominal surgery, but no recommendation is given due to the lack of further high quality evidence (12). However, SHEA/IDSA guidelines recommend the use of impervious plastic WPs for gastrointestinal and biliary tract surgery (13).

Table 4.17.1. Recommendations on the use of WP devices according to available guidelines.

Table 4.17.1

Recommendations on the use of WP devices according to available guidelines.

Following the in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess the effectiveness of WP devices compared with standard wound edge protection and to determine if they might be beneficial to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 18) was to evaluate whether the use of a WP device is more effective in reducing the risk of SSI than conventional wound protection, which is mainly through placing wet towels between the wound edge in combination with steel retractors. The target population included patients of all ages undergoing either elective or urgent abdominal surgery through conventional open access. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Eleven trials comparing the use of a WP device with conventional wound protection in abdominal surgical procedures with laparotomy were identified. These included a total of 2949 patients and comprised 10 RCTs (1, 311) and one prospective controlled trial (2). There is very low quality evidence for the benefit of either a single- or double-ring WP device in reducing the SSI rate when compared with standard wound protection (OR: 0.42; 95% CI: 0.28–0.62).

This beneficial effect was observed both for single-(OR: 0.51; 95% CI; 0.34–0.76) and double-ring WPs (OR: 0.25; 95% CI: 0.13–0.50). Similarly, meta-regression analysis showed no strong evidence for a difference in the effect between single- and double-ring WPs (P=0.107). There was also no evidence that the effect differed between clean-contaminated (P=0.244), contaminated (P=0.305) or dirty (P=0.675) surgery and other surgery. The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that most patients wish to receive this intervention in order to reduce the risk of SSI. Patients will prefer also to be treated by surgeons who are familiar with the use of WP devices in order to reduce the risk of complications.

Resource use

In LMICs, the availability of WP devices may be limited and represent a high financial burden. The GDG pointed out that this intervention may not be prioritized in resource-limited settings compared to other interventions to reduce SSI. It was highlighted that there is a need for staff training, irrespective of the setting. Few studies addressed the cost-effectiveness of the intervention. Two small studies found the use of WP to be cost-effective (6, 9), while one larger trial did not (14).

Research gaps

The GDG highlighted that the available evidence consists mainly of low quality small studies. There is a need for properly designed multicentre RCTs. The SSI outcome should be defined according to the CDC criteria and sub-specified as superficial, deep and organ/space occupying infections. Specific and relevant surgical procedures should be reported regarding the level of wound contamination and the rate of incisional SSI (for example, colorectal surgery and laparotomy for peritonitis). Investigators should consider comparing single-with double-ring WP devices. Trials should report adverse events related to the intervention. Finally, cost-effectiveness studies are also needed.

References

1.
Baier P, Kiesel M, Kayser C, Fischer A, Hopt UT, Utzolino S. Ring drape do not protect against surgical site infections in colorectal surgery: a randomised controlled study. Int J Colorectal Dis. 2012;27(9):1223–8. [PubMed: 22584293]
2.
Brunet P, Bounoua F, Bugnon PY, Gautier-Benoit C, Intérêt des champs à anneau en chirurgie abdominale. Lyon Chir. 1994;90(6):438–41.
3.
Mihaljevic AL, Schirren R, Ozer M, Ottl S, Grun S, Michalski CW, et al. Multicenter double-blinded randomized controlled trial of standard abdominal wound edge protection with surgical dressings versus coverage with a sterile circular polyethylene drape for prevention of surgical site infections: a CHIRNet trial (BaFO; NCT01181206). Ann Surg. 2014;260(5):730–7; discussion 7–9. [PubMed: 25379844]
4.
Pinkney TD, Calvert M, Bartlett DC, Gheorghe A, Redman V, Dowswell G, et al. Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI Trial). BMJ. 2013;347:f4305. [PMC free article: PMC3805488] [PubMed: 23903454]
5.
Redmond HP, Meagher PJ, Kelly CJ, Deasy JM. Use of an impervious wound-edge protector to reduce the postoperative wound infection rate. Br J Surg. 1994;81(1811).
6.
Sookhai S, Redmond HP, Deasy JM. Impervious wound-edge protector to reduce postoperative wound infection: a randomised, controlled trial. Lancet. 1999;353(9164):1585. [PubMed: 10334259]
7.
Cheng KP, Roslani AC, Sehha N, Kueh JH, Law CW, Chong HY, et al. ALEXIS O-Ring wound retractor vs conventional wound protection for the prevention of surgical site infections in colorectal resections (1). Colorectal Dis. 2012;14(6):e346–51. [PubMed: 22568647]
8.
Horiuchi T, Tanishima H, Tamagawa K, Matsuura I, Nakai H, Shouno Y, et al. Randomized, controlled investigation of the anti-infective properties of the Alexis retractor/protector of incision sites. J Trauma. 2007;62(1):212–5. [PubMed: 17215757]
9.
Lee P, Waxman K, Taylor B, Yim S. Use of wound-protection system and postoperative wound-infection rates in open appendectomy: a randomized prospective trial. Arch Surg. 2009;144(9):872–5.
10.
Reid K, Pockney P, Draganic B, Smith SR. Barrier wound protection decreases surgical site infection in open elective colorectal surgery: a randomized clinical trial. Dis Colon Rectum. 2010;53(10):1374–80. [PubMed: 20847618]
11.
Theodoridis TD, Chatzigeorgiou KN, Zepiridis L, Papanicolaou A, Vavilis D, Tzevelekis F, et al. A prospective randomized study for evaluation of wound retractors in the prevention of incision site infections after cesarean section. Clin Exper Obstet Gynecol. 2011;38(1):57–9. [PubMed: 21485728]
12.
Surgical site infection: evidence update 43 (June 2013) London: National Institute for Health and Care Excellenc (NICE); 2013 (http://www​.nice.org.uk​/guidance/cg74/evidence​/evidence-update-241969645, accessed 24 July 2016).
13.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
14.
Gheorghe A, Roberts TE, Pinkney TD, Bartlett DC, Morton D, Calvert M. The cost-effectiveness of wound-edge protection devices compared to standard care in reducing surgical site infection after laparotomy: an economic evaluation alongside the ROSSINI trial. PloS One. 2014;9(4):e95595. [PMC free article: PMC3991705] [PubMed: 24748154]

4.18. Incisional wound irrigation

Recommendations

The panel considers that there is insufficient evidence to recommend for or against saline irrigation of incisional wounds before closure for the purpose of preventing SSI.

The panel suggests considering the use of irrigation of the incisional wound with an aqueous PVP-I solution before closure for the purpose of preventing SSI, particularly in clean and clean-contaminated wounds.

The panel suggests that antibiotic incisional wound irrigation before closure should not be used for the purpose of preventing SSI.

(Conditional recommendations/low quality of evidence)

Rationale for the recommendation

  • RCTs comparing wound irrigation vs. no wound irrigation or wound irrigation using different solutions with SSI as an outcome were evaluated. Evidence was available on intraperitoneal, incisional wound and mediastinal irrigation in patients undergoing various surgical procedures.
  • Considering the substantial heterogeneity in the available evidence, the GDG decided to focus only on incisional wound irrigation. In particular, the GDG agreed not to consider intraperitoneal irrigation for the formulation of recommendations as the identified studies described contaminated and dirty intra-abdominal procedures (for example, peritonitis). Therefore, wound irrigation was likely to represent a therapeutic intervention, rather than a prophylactic measure.
  • Very low quality evidence shows that incisional wound irrigation with saline solution has neither benefit nor harm compared to no irrigation.
  • Low quality evidence shows that the irrigation of the incisional wound with an aqueous PVP-I solution is beneficial with a significant decrease of the risk of SSI when compared to irrigation with a saline solution.
  • Very low quality evidence shows that the irrigation of the incisional wound with antibiotic solutions has neither benefit nor harm compared to irrigation with a saline solution or no irrigation.
  • The GDG agreed that there is insufficient evidence to issue a recommendation for or against the saline solution irrigation of incisional wounds for the purpose of preventing SSI. The GDG also decided to suggest considering the use of irrigation of the incisional wound with an aqueous PVP-I solution. The term “considering” was proposed to highlight that a decision-making process is needed, especially focusing on clean and clean-contaminated wounds. Finally, the GDG agreed to suggest that antibiotic incisional wound irrigation should not be used for the purpose of preventing SSI. The strength of these recommendations should be conditional due to the low quality of the evidence.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, the effectiveness of irrigation of the incisional wound with an aqueous PVP-I solution is not proven for paediatric patients.
  • The available evidence from 7 RCTs (17) (10 estimates) showed that irrigation of the incisional wound with an aqueous PVP-I solution was beneficial in reducing the risk of SSI when compared to irrigation with a saline solution. Stratification of the evidence by contamination showed that the effect was attributable to incisional wound irrigation in clean and clean-contaminated procedures rated as wound classes I and II according to the CDC system (8).
  • The evidence on irrigation of incisional wounds with aqueous PVP-I is available from studies investigating PVP-I 10% in open abdominal surgery (CDC wound classes I-IV; 3 RCTs), PVP-I 1% in appendectomies (CDC wound classes II-IV; one RCT) and PVP-I 0.35% in orthopaedic spine surgery (CDC wound class I; 3 RCTs). There was no evidence for a dose-response effect with regard to the concentration of the PVP-I solution used.
  • Two RCTs showed that the pulse pressure irrigation of incisional wounds with a normal saline solution was beneficial in reducing the risk of SSI in CDC wound classes I and II-III compared to normal irrigation with a saline solution. One RCT showed that irrigation with a normal saline solution applied with pressure to the incisional wound was beneficial compared to no irrigation. Nevertheless, the GDG considered that there is insufficient evidence to issue a recommendation for or against the saline solution irrigation of incisional wounds as one RCT investigating regular irrigation with a saline solution showed neither benefit nor harm when compared to no irrigation. When saline solution irrigation is used, the use of pulse pressure irrigation may be considered.
  • The available evidence from 5 RCTs shows that the antibiotic irrigation of the incisional wound has neither benefit nor harm in reducing SSI when compared to no or saline solution irrigation.
  • Of the included studies, 3 RCTs (5, 9, 10) described sterility of the irrigation fluid. The other studies did not report whether the irrigation fluid was sterile or not.
  • The GDG discussed allergic reactions and metabolic adverse events as potential harms of iodine uptake. However, clinical signs of iodine toxicity were not reported in the included studies (5). In the case of known or presumed allergy to iodine, other products (for example, chlorhexidine) should be used if incisional wound irrigation is performed. PVP-I must not be allowed to come into contact with exposed meninges and neural tissues, such as the brain or spinal cord (11). Based on in vitro studies (12, 13), the GDG also raised concerns about the potential toxic effects of PVP-I on fibroblasts, the mesothelium and the healing of tissue. No study assessed undesirable outcomes for pulse pressure irrigation.
  • The GDG highlighted the risk of emergence of AMR associated with the use of antibiotics for wound irrigation. Considering that the evidence shows that this procedure has no benefit with regard to SSI prevention, the GDG strongly emphasized that this practice is associated with an unnecessary risk of contributing to AMR. Furthermore, the GDG underlined that there is no standardized procedure to prepare an antibiotic solution for wound irrigation and no certainty of target attainment by using this method.

Background

Intraoperative wound irrigation is the flow of a solution across the surface of an open wound to achieve wound hydration and it is widely practised to help prevent SSI (1416). It is intended to act as a physical cleaner by removing cellular debris, surface bacteria and body fluids, to have a diluting effect on possible contamination, and to function as a local antibacterial agent when an antiseptic or antibiotic agent is used. Up to 97% of surgeons state that they use intraoperative irrigation (14).

However, practices vary depending on the patient population, the surface of application and solutions used. Similar variations in methodology and results can be observed in studies investigating the effect of wound irrigation (17). Some experimental studies have also raised concerns about the cytotoxicity of some bactericidal additives, but the clinical relevance of these findings is unclear. Moreover, most of the literature investigating wound irrigation dates from an era when infection prevention measures were incomparable to practice today.

Two clinical practice guidelines issued by professional societies and a national authority have included contradictory recommendations regarding intraoperative wound irrigation (Table 4.18.1). The SHEA/IDSA guideline recommends performing intraoperative antiseptic wound lavage (grade II level of evidence) (18). The UK-based NICE guideline states that there is only limited evidence suggesting a benefit for intraoperative wound irrigation with PVP-I. However, although wound irrigation with PVP-I may reduce SSI, PVP-I is not licensed for open wounds by the US Food and Drug Administration (19). Therefore, the NICE guideline recommends that wound irrigation should not be used to reduce the risk of SSI (20).

Table 4.18.1. Recommendations on wound irrigation according to available guidelines.

Table 4.18.1

Recommendations on wound irrigation according to available guidelines.

Following the in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the available evidence on wound irrigation.

Summary of the evidence

The purpose of the evidence review (web Appendix 19) was to investigate whether intraoperative wound irrigation (with or without active agents or pressured application) affects the incidence of SSI. The population studied were adult patients undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality. Only studies investigating wound irrigation (flow of solution across the surface of an open wound, with or without active additives) were included. Studies investigating the topical application of antibiotics or antiseptics (powder, gels, sponges, etc.) other than intraoperative wound irrigation were not included. To ensure that only evidence relevant to the current standard of infection prevention measures was included in our analyses, studies where SAP was not administered appropriately (that is, preoperatively and intravenous) were excluded. In addition, studies where wound irrigation represented a therapeutic intervention for a pre-existent infection rather than a prophylactic measure were also excluded.

A total of 21 RCTs comparing (active) wound irrigation vs. no (active) wound irrigation in patients undergoing various surgical procedures were identified with SSI as the outcome (web Appendix 19). There was substantial heterogeneity in the available evidence. The main differences were related to the irrigated surface, the composition of the irrigation fluid and the surgical procedure with the associated wound contamination level. After careful appraisal of the included studies, the research team and the GDG decided to restrict the recommendation to incisional wound irrigation as too little (and heterogeneous) evidence was available to address other applications of irrigation (that is, intraperitoneal or mediastinal irrigation). In particular, the GDG agreed not to consider intraperitoneal irrigation for the formulation of recommendations as the identified studies described contaminated and dirty intra-abdominal procedures (for example, peritonitis). Therefore, wound irrigation was likely to represent a therapeutic intervention, rather than a prophylactic measure.

Meta-analyses were performed to evaluate the following comparisons in incisional wound irrigation: saline solution vs. no irrigation; syringe pressure irrigation with saline solution vs. no irrigation; pulse pressure irrigation with saline solution vs. normal saline solution; aqueous PVP-I vs. saline solution; and antibiotic vs. saline solution or no irrigation.

One study (21) compared irrigation of the incisional wound with normal saline solution to no irrigation in women undergoing a caesarean section (CDC wound class II). The study demonstrated no significant difference between wound irrigation and no irrigation on the incidence of incisional wound infection (OR: 1.09; 95% CI: 0.44–2.69; P=0.85). The quality of evidence was very low due to risk of bias and imprecision. When different methods of irrigation were compared, a low quality of evidence from 2 studies (22, 23) demonstrated a significant benefit for pulse pressure irrigation in preventing SSI compared to normal irrigation with a saline solution (OR: 0.30; 95% CI: 0.08–0.86; P=0.0003). A moderate quality of evidence from another study (24) demonstrated a significant benefit for irrigation with a normal saline solution applied with force compared to no irrigation (OR: 0.35; 95% CI: 0.19–0.65; P=0.0009).

Seven RCTs (17) compared irrigation of the incisional wound with aqueous PVP-I solutions in different concentrations to irrigation with a saline solution. Meta-analysis of these studies demonstrated a significant benefit for incisional wound irrigation with an aqueous PVP-I solution (OR: 0.31; 95% CI: 0.13–0.73; P=0.007). However, the quality of evidence was low due to risk of bias and imprecision. Stratification for wound contamination and PVP-I solution showed that the effect was attributable to incisional wound irrigation in clean and clean-contaminated procedures with PVP-I 10% and PVP-I 0.35%.

Five studies (2529) compared irrigation of the incisional wound with an antibiotic solution to irrigation with a normal saline solution or no irrigation in CDC wound classes I-IV. A meta-analysis of the 5 RCTs demonstrated no significant difference between antibiotic irrigation of the incisional wound and no irrigation or only with a saline solution (OR: 1.16; 95% CI: 0.64–2.12; P=0.63). The quality of evidence was very low due to risk of bias and imprecision.

Factors considered when formulating the recommendation

Values and preferences

Patient values and preferences were not assessed by the studies, but the GDG argued that the recommendation was in line with the values and preferences of most patients.

Resource use

The GDG pointed out that there is a lack of data on costs or the cost-effectiveness of interventions using wound irrigation. Although the GDG recognized that saline and PVP-I solutions are usually readily available in most settings, the availability of sterile products may be limited in LMICs. In many settings, the availability and costs of pulse pressure devices, including their purchase, waste disposal, procurement, energy and machine maintenance, represent a high financial burden, especially in LMICs. Moreover, the use of pressure devices introduces the need for staff protection, such as gowns and face shields.

Research gaps

The GDG highlighted that the available evidence comes from old studies mainly conducted in the 1980s. This represents a serious limitation as IPC measures have changed significantly since that period. New well-designed RCTs using standard of care protocols for SAP are needed to evaluate and compare the most commonly-used irrigation practices with a special emphasis on the agent used and a focus on the prevention of SSI in different surgical procedures. In particular, it is unclear as to what is the best alternative agent to PVP-I in the case of an adverse event with this solution. These studies should be conducted in both high-income and LMICs. In addition, trials should address also the cost-effectiveness of the intervention and the harm associated with irrigation and the agents used for irrigation.

References

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Cheng MT, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. Efficacy of dilute betadine solution irrigation in the prevention of postoperative infection of spinal surgery. Spine. 2005; 30(15):1689–93.. [PubMed: 16094267]
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Chang FY, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. Can povidone-iodine solution be used safely in a spinal surgery? Europ Spine J. 2006;15(6):1005–14. [PMC free article: PMC3489437] [PubMed: 16133077]
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Kokavec M, Fristákováa M. Efficacy of antiseptics in the prevention of post-operative infections of the proximal femur, hip and pelvis regions in orthopedic pediatric patients. Analysis of the first results. [Article in Czech]. Acta Chir Orthop Traumatol Cech. 2008; 75(2):106–9. [PubMed: 18454914]
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Rogers DM, Blouin GS, O’Leary JP. Povidone-iodine wound irrigation and wound sepsis. Surg Gynecol Obstet. 1983;157(5):426–30. [PubMed: 6635913]
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Sindelar WF, Brower ST, Merkel AB, Takesue EI. Randomised trial of intraperitoneal irrigation with low molecular weight povidone-iodine solution to reduce intra-abdominal infectious complications. J Hosp Infect. 1985;6(Suppl. A):103–14. [PubMed: 2860153]
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Sindelar WF, Mason GR. Irrigation of subcutaneous tissue with povidone-iodine solution for prevention of surgical wound infections. Surg Gynecol Obstet. 1979;148(2):227–31. [PubMed: 419426]
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Lau WY, Fan ST, Chu KW, Yip WC, Chong KK, Wong KK. Combined topical povidone-iodine and systemic antibiotics in postappendicectomy wound sepsis. Br J Surg. 1986;73(12):958–60. [PubMed: 3790957]
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Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27:97–132. [PubMed: 10196487]
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Tanaka K, Matsuo K, Kawaguchi D, Murakami T, Hiroshima Y, Hirano A, et al. Randomized clinical trial of peritoneal lavage for preventing surgical site infection in elective liver surgery. J Hepatobiliary Pancreat Sci. 2015; 22(6):446–53. [PubMed: 25611190]
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Silverman SH, Ambrose NS, Youngs DJ. The effect of peritoneal lavage with tetracycline solution of postoperative infection. A prospective, randomized, clinical trial. Dis. Colon Rectum. 1986;29(3):165–9. [PubMed: 3510839]
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Akcay E, Ersahin Y, Ozer F, Duransoy YK, Camlar M, Atci I, et al. Neurotoxic effect of povidone-iodine on the rat spine using a laminectomy-durotomy model. Child’s Nerv Syst. 2012;28(12):2071–5. [PubMed: 22885709]
12.
Kaysinger KK, Nicholson NC, Ramp WK, Kellam JF. Toxic effects of wound irrigation solutions on cultured tibiae and osteoblasts. J Orthop Trauma. 1995;9(4):303–11. [PubMed: 7562152]
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Lineaweaver W, McMorris S, Soucy D, Howard R. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg. 1985;75(3):394–6. [PubMed: 3975287]
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Whiteside OJ, Tytherleigh MG, Thrush S, Farouk R, Galland RB. Intra-operative peritoneal lavage--who does it and why? Ann R Coll Surg Engl. 2005;87(4):255–8. [PMC free article: PMC1963932] [PubMed: 16053685]
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Diana M, Hubner M, Eisenring MC, Zanetti G, Troillet N, Demartines N. Measures to prevent surgical site infections: what surgeons (should) do. World J Surg. 2011;35(2):280–8. [PubMed: 21088838]
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Pivot D, Tiv M, Luu M, Astruc K, Aho S, Fournel I. Survey of intraoperative povidone-iodine application to prevent surgical site infection in a French region. J Hosp Infection. 2011;77(4):363–4. [PubMed: 21257229]
17.
Mueller TC, Loos M, Haller B, Mihaljevic AL, Nitsche U, Wilhelm D, et al. Intra-operative wound irrigation to reduce surgical site infections after abdominal surgery: a systematic review and meta-analysis. Langenbeck’s Arch Surg. 2015;400(2):167–81. [PubMed: 25681239]
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Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
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Barnes S, Spencer M, Graham D, Johnson HB. Surgical wound irrigation: a call for evidence-based standardization of practice. Am J Infect Control. 2014;42(5):525–9. [PubMed: 24773788]
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Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337:a1924. [PubMed: 18957455]
21.
Al-Ramahi M, Bata M, Sumreen I, Amr M. Saline irrigation and wound infection in abdominal gynecologic surgery. Int J Gynaecol Obstet. 2006;94(1):33–6. [PubMed: 16730011]
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Hargrove R, Ridgeway S, Russell R, Norris M, Packham I, Levy B. Does pulse lavage reduce hip hemiarthroplasty infection rates? J Hosp Infect. 2006;62(4):446–9. [PubMed: 16488057]
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Nikfarjam M, Weinberg L, Fink MA, Muralidharan V, Starkey G, Jones R. Pressurized pulse irrigation with saline reduces surgical-site infections following major hepatobiliary and pancreatic surgery: randomized controlled trial. World J Surg. 2014; 38(2):447–55. [PubMed: 24170152]
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Cervantes-Sánchez CR, Gutiérrez-Vega R, Vázquez-Carpizo JA, Clark P, Athié-Gutiérrez C. Syringe pressure irrigation of subdermic tissue after appendectomy to decrease the incidence of postoperative wound infection. World J Surg. 2000; 24(1):38–41. [PubMed: 10594201]
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Pitt HA, Postier RG, MacGowan AW, Frank LW, Surmak AJ, Sitzman JV, et al. Prophylactic antibiotics in vascular surgery. Topical, systemic, or both? Ann Surg. 1980;192(3):356–64. [PMC free article: PMC1344917] [PubMed: 6998390]
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Freischlag J, McGrattan M, Busuttil RW. Topical versus systemic cephalosporin administration in elective biliary operations. Surgery. 1984; 96(4):686–93. [PubMed: 6435272]
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Moesgaard F, Nielsen ML, Hjortrup A, Kjersgaard P, Sorensen C, Larsen PN, et al. Intraincisional antibiotic in addition to systemic antibiotic treatment fails to reduce wound infection rates in contaminated abdominal surgery. A controlled clinical trial. Dis Colon Rectum. 1989;32(1):36–8. [PubMed: 2642790]
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Ruiz-Tovar J, Cansado P, Perez-Soler M, Gomez MA, Llavero C, Calero P, et al. Effect of gentamicin lavage of the axillary surgical bed after lymph node dissection on drainage discharge volume. Breast. 2013; 22(5):874–8. [PubMed: 23602424]

4.19. Prophylactic negative pressure wound therapy

Recommendation

The panel suggests the use of prophylactic negative pressure wound therapy (pNPWT) in adult patients on primarily closed surgical incisions in high-risk wounds, for the purpose of the prevention of SSI, while taking resources into account.

(Conditional recommendation, low quality of evidence)

Rationale for the recommendation

  • Overall low quality evidence shows that pNPWT has a benefit in reducing the risk of SSI in patients with a primarily closed surgical incision following high-risk wounds (for example, in case of poor tissue perfusion due to surrounding soft tissue/skin damage, decreased blood flow, bleeding/hematoma, dead space, intraoperative contamination) when compared to conventional postoperative wound dressings.
  • The GDG emphasized that the devices used for pNPWT are expensive and may not be available in low-resource settings. Thus, the prioritization of this intervention should be carefully considered according to resources available and other priority measures for the prevention of SSI.
  • It was also noted that there were no trials comparing different levels of negative pressure or different durations of applying negative pressure to the wound. In addition, studies did not report subgroup analyses by type of surgery or the degree of wound contamination. In stratified meta-analyses, there was little evidence that the effects differed by type of surgery, wound class or the level and duration of applying negative pressure. The GDG concluded that the effect appears to be independent of these factors and that no recommendations can be made on the optimal level of pressure or duration of application.
  • As a result of the low quality evidence and the other above-mentioned factors, the majority of GDG members agreed to suggest the use of pNPWT on primarily closed surgical incisions in high-risk procedures, but taking resources into account. One GDG member disagreed with the recommendation because he considered the evidence insufficient to support it. The GDG decided that the strength of this recommendation should be conditional.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. Therefore, this recommendation is not proven for paediatric patients. The GDG pointed out that all RCTs were performed in clean surgery (4 in orthopaedic and trauma surgery), apart from one study that also included abdominal procedures. By contrast, the included observational studies were performed in clean, clean-contaminated, contaminated and dirty procedures. As pNPWT devices are commonly used in abdominal surgery, the GDG considered that observational studies should be included.
  • Negative pressure devices were set between 75 mm Hg and 125 mm Hg with the postoperative duration ranging from 24 hours up to 7 days. The control group used sterile dry gauze, tape, occlusive or absorbent dressings.
  • The overall quality of evidence was low for the RCTs due to risk of bias and imprecision and low for the observational studies.
  • The GDG discussed potential mechanisms for the observed benefit of pNPWT, including less wound dehiscence, better removal of fluids and protection against microorganisms entering the wound from the surrounding environment.
  • The GDG identified the appearance of blisters (1) or maceration as possible harms associated with the use of use of negative pressure devices. No other relevant adverse event was identified through the available evidence.

Background

Negative Pressure Wound Therapy consists of a closed sealed system connected to a vacuum pump, which maintains negative pressure on the wound surface. pNPWT is used on primarily closed surgical incisions to prevent SSI. Although negative pressure wound therapy has been used since the late 1990s for several purposes, such as open bone fractures (2), diabetic ulcers (3) and management of open abdomen wounds (4), its use for the prevention of SSI is relatively new. After the first report of its use in orthopaedic surgery in 2006 (5), several studies have followed.

Current SSI prevention guidelines do not offer a recommendation on the use of pNPWT. Only the UK-based NICE addresses this topic in a recent evidence update of its guidelines, but without formulating a recommendation. These guidelines state that “NPWT appears to reduce SSI rates after the invasive treatment of lower limb trauma, but may be less effective in other patient groups, such as those with multiple comorbidities. Further research is needed.” (6).

Following discussion about the interest in this topic and the lack of recommendations in other guidelines, the GDG decided to conduct a systematic review to assess the effectiveness of the use of pNPWT to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 20), was to evaluate whether the use of pNPWT is more effective in reducing the risk of SSI than the use of conventional wound dressings without negative pressure therapy. The target population included patients of all ages undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Nineteen articles describing 21 studies that compared the use of pNPWT with conventional wound dressings were identified. These included a total of 6122 patients and comprised six RCTs (1, 5, 79) and 15 observational studies (1023) (RCTs, 562; observational studies, 5560). One article (5) described two separate studies and another article assessed and analysed separately two different patient populations (breast and colorectal) (20).

Due to heterogeneity among the selected studies regarding the type of surgical procedure or wound contamination class, as well as the level and duration of applying negative pressure, additional separate meta-analyses were performed. These concerned the type of surgical procedure, wounds classified as clean and clean-contaminated, the duration of pNPWT for <5 days vs. >5 days and a pressure level of <100 mmHg vs. >100 mmHg (web Appendix 20).

Overall, there is low quality evidence from RCTs and observational studies that pNPWT has a significant benefit in reducing the risk of SSI in patients with a primarily closed surgical incision when compared to conventional postoperative wound dressings (RCTs: OR: 0.56; 95% CI: 0.32–0.96; observational studies: OR: 0.30; 95% CI: 0.22–0.42). When stratified by the type of surgery (web Appendix 20), the most relevant meta-analyses results showed no statistically significant benefit in the reduction of the risk of SSI in orthopaedic and/or trauma surgery. By contrast, a significant benefit was observed in reducing SSI rates with the use of pNPWT compared to conventional wound dressings in abdominal (9 observational studies; OR: 0.31; 95% CI: 0.19–0.49) and cardiac surgery (2 observational studies; OR: 0.29; 95% CI: 0.12–0.69).

In the stratification by wound contamination class (web Appendix 20), the most relevant meta-analyses results showed a significant benefit in reducing SSI rates with the use of pNPWT compared to conventional wound dressings in clean surgery (8 observational studies; OR: 0.27; 95% CI: 0.17–0.42) and in clean-contaminated surgery (8 observational studies; OR: 0.29; 95% CI: 0.17–0.50).

When considering different durations of pNPWT (for either < or > 5 days) and a pressure level (of either < or > 100 mmHg), the significant benefit observed with the use of pNPWT remained unchanged (web Appendix 20).

The body of retrieved evidence focused on adult patients only. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that most patients would wish to receive this intervention in order to reduce the risk of SSI. However, there are concerns about comfort and convenience as some devices can be noisy and may disturb sleep. The GDG pointed out that the use of pNPWT may prolong hospital stay, but this could be prevented by the use of portable suction systems.

Resource use

The availability and costs of these devices and the potential extension of hospital stay are major concerns, mainly in LMICs, but also in high-resource settings. The GDG remarked that patients are generally more likely to receive a conventional dressing instead of pNPWT due to lack of material and evidence of cost-effectiveness. However, studies in gynaecological patients showed that the intervention may be cost-effective (2426). The GDG acknowledged that it may be possible to construct a non-portable, locally-made device at low cost for LMICs. It was highlighted also that there is a need to train staff in handling these devices, regardless of the setting.

Research gaps

The GDG highlighted that additional well-designed RCTs investigating the use of pNPWT for SSI prevention are needed, especially in LMICs. Future research is likely to have an important impact on our confidence in the estimate of effect. The main research priority is to identify the groups of patients in whom this intervention is cost-effective, including those undergoing contaminated and dirty procedures. Further research is also needed to identify the optimal level of negative pressure and duration of application.

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Masden D, Goldstein J, Endara M, Xu K, Steinberg J, Attinger C. Negative pressure wound therapy for at-risk surgical closures in patients with multiple comorbidities: a prospective randomized controlled study. Ann Surg. 2012;255(6):1043–7. [PubMed: 22549748]
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Stannard JP, Volgas DA, McGwin G, 3rd, Stewart RL, Obremskey W, Moore T, et al. Incisional negative pressure wound therapy after high-risk lower extremity fractures. J Orthop Trauma. 2012;26(1):37–42. [PubMed: 21804414]
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Adogwa O, Fatemi P, Perez E, Moreno J, Gazcon GC, Gokaslan ZL, et al. Negative pressure wound therapy reduces incidence of postoperative wound infection and dehiscence after long-segment thoracolumbar spinal fusion: a single institutional experience. Spine J. 2014;14(12):2911–7. [PubMed: 24769401]
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Bonds AM, Novick TK, Dietert JB, Araghizadeh FY, Olson CH. Incisional negative pressure wound therapy significantly reduces surgical site infection in open colorectal surgery. Dis Colon Rectum. 2013;56(12):1403–8. [PubMed: 24201395]
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Chadi SA, Kidane B, Britto K, Brackstone M, Ott MC. Incisional negative pressure wound therapy decreases the frequency of postoperative perineal surgical site infections: a cohort study. Dis Colon Rectum. 2014;57(8):999–1006. [PubMed: 25003295]
14.
Conde-Green A, Chung TL, Holton LH, 3rd, Hui-Chou HG, Zhu Y, Wang H, et al. Incisional negative-pressure wound therapy versus conventional dressings following abdominal wall reconstruction: a comparative study. Ann Plast Surg. 2013;71(4):394–7. [PubMed: 22868327]
15.
Gassman A, Mehta A, Bucholdz E, Abthani A, Guerra O, Maclin MM, Jr., et al. Positive outcomes with negative pressure therapy over primarily closed large abdominal wall reconstruction reduces surgical site infection rates. Hernia. 2015;19(2):273–8. [PubMed: 25337870]
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Grauhan O, Navasardyan A, Hofmann M, Muller P, Stein J, Hetzer R. Prevention of poststernotomy wound infections in obese patients by negative pressure wound therapy. J Thorac Cardiovasc Surg. 2013;145(5):1387–92. [PubMed: 23111014]
17.
Grauhan O, Navasardyan A, Tutkun B, Hennig F, Muller P, Hummel M, et al. Effect of surgical incision management on wound infections in a poststernotomy patient population. Int Wound J. 2014;11(Suppl. 1):6–9. [PMC free article: PMC7950457] [PubMed: 24851729]
18.
Matatov T, Reddy KN, Doucet LD, Zhao CX, Zhang WW. Experience with a new negative pressure incision management system in prevention of groin wound infection in vascular surgery patients. J Vasc Surg. 2013;57(3):791–5. [PubMed: 23312938]
19.
Pauli EM, Krpata DM, Novitsky YW, Rosen MJ. Negative pressure therapy for high-risk abdominal wall reconstruction incisions. Surg Infect (Larchmt). 2013;14(3):270–4. [PubMed: 23590852]
20.
Pellino G, Sciaudone G, Candilio G, De Fatico GS, Landino I, Della Corte A, et al. Preventive NPWT over closed incisions in general surgery: does age matter? Int J Surg. 2014;12(Suppl. 2):S64–8. [PubMed: 25159226]
21.
Reddix RN, Jr., Leng XI, Woodall J, Jackson B, Dedmond B, Webb LX. The effect of incisional negative pressure therapy on wound complications after acetabular fracture surgery. J Surg Orthop Adv. 2010;19(2):91–7. [PubMed: 20727304]
22.
Selvaggi F, Pellino G, Sciaudone G, Corte AD, Candilio G, Campitiello F, et al. New advances in negative pressure wound therapy (NPWT) for surgical wounds of patients affected with Crohn’s disease. Surg Technol Int. 2014;24:83–9. [PubMed: 24700216]
23.
Soares KC, Baltodano PA, Hicks CW, Cooney CM, Olorundare IO, Cornell P, et al. Novel wound management system reduction of surgical site morbidity after ventral hernia repairs: a critical analysis. Am J Surg. 2015;209(2):324–32. [PubMed: 25194761]
24.
Echebiri NC, McDoom MM, Aalto MM, Fauntleroy J, Nagappan N, Barnabei VM. Prophylactic use of negative pressure wound therapy after cesarean delivery. Obstet Gynecol. 2015;125(2):299–307. [PubMed: 25569006]
25.
Lewis LS, Convery PA, Bolac CS, Valea FA, Lowery WJ, Havrilesky LJ. Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions. Gynecol Oncol. 2014;132(3):684–9. [PubMed: 24440649]
26.
Tuffaha HW, Gillespie BM, Chaboyer W, Gordon LG, Scuffham PA. Cost-utility analysis of negative pressure wound therapy in high-risk cesarean section wounds. J Surg Res. 2015;195(2):612–22. [PubMed: 25796106]

4.20. Use of surgical gloves

Recommendation

The panel decided not to formulate a recommendation due to the lack of evidence to assess whether double-gloving or changing of gloves during the operation or using specific types of gloves is more effective in reducing the risk of SSI.

Remarks

  • Gloving refers to the use of sterile gloves by the surgical team during the operation.
  • During the operation, glove decontamination with alcohol or other products for the purpose of reuse should never be performed.
  • Sterile surgical gloves (as well as medical examination gloves) are single-use items and should not be reused.
  • The literature search failed to identify relevant studies on the following topics of interest that ultimately could inform a recommendation for these questions with regard to the prevention of SSI: a comparison of double-gloving vs. using a single pair of gloves; the intraoperative changing of gloves vs. retaining gloves; and latex gloves vs. other types of gloves.
  • The GDG emphasized that most surgeons prefer to double-glove because it is plausible that bacterial contamination of the surgical field may occur in the event of glove perforation. Moreover, most surgeons prefer to wear double gloves for their own protection against injury from sharps and/or bloodborne infections. In the case of double-gloving, a routine change of the outer gloves during long surgeries is often recommended by health care practitioners. However, no evidence was found to support these practices.

Background

The invasive nature of surgery introduces a high risk for the transfer of pathogens that may cause bloodborne infections in patients and/or the surgical team, as well as SSI. This risk may be reduced by implementing protective barriers, such as wearing surgical gloves.

A Cochrane review (1) published in 2009 investigated whether additional glove protection reduces the number of SSIs or bloodborne infections in patients or the surgical team and the number of perforations to the innermost pair of surgical gloves. There was no direct evidence that additional glove protection worn by the surgical team reduces SSI in patients. However, the review had insufficient power for this outcome as only two trials were found with the primary outcome of SSI, both of which reported no infections. No trials were found with transmitted bloodborne infections as an outcome in surgical patients or the surgical team in relation to the gloving method. Thirty-one RCTs were identified with the outcome of glove perforation, leading to the result that the use of a second pair of surgical gloves, triple gloving, knitted outer gloves and glove liners significantly reduces perforations to the innermost gloves.

Few organizations have issued recommendations regarding the use of gloves (Table 4.20.1). The latest WHO guidelines for safe surgery published in 2009 (2) recommend that the operating team should cover their hair and wear sterile gowns and sterile gloves during the operation, but without any indication on single or double-gloving. The SHEA/IDSA guidelines (3) recommend that all members of the operative team should double-glove and change gloves when perforation is observed. However, the modalities and frequency of changing gloves have not been included in any guidelines or recommendations (24).

Table 4.20.1. Recommendations on gloving according to available guidelines.

Table 4.20.1

Recommendations on gloving according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess the effectiveness of double-gloving and the changing of gloves at a specific time during the operation to reduce SSI. The question of whether a specific type of gloving is beneficial in reducing the risk of SSI was also addressed.

Summary of the evidence

The purpose of the evidence review (web Appendix 21) was to evaluate whether double-gloving or the changing of gloves during the operation is more effective in reducing the risk of SSI than single-glove use or no change of gloves. In a third approach, it was evaluated whether specific types of gloving (that is, glove liners, coloured perforation indicator systems, cloth/steel outer gloves, triple gloves) are more effective in reducing the risk of SSI than the use of latex gloves. The target population included patients of all ages undergoing a surgical operation. The primary outcome was the occurrence of SSI and SSI-attributable mortality. Bacterial contamination of the gloves was considered as a surrogate outcome.

Ten studies comprising 8 RCTs (512) and 2 observational studies (13, 14) were identified. Among these, one observational study compared the efficacy of double-gloving with the use of a single pair of gloves with an SSI outcome (13) and another (observational) with a cerebrospinal fluid shunt infection outcome (14). Six studies compared the changing of gloves during the operation with the retaining of gloves (3 RCTs with an SSI outcome (6, 7, 10), 2 RCTs (5, 11) focusing on bacterial contamination and one RCT (12) reporting on both). Two RCTs with an SSI outcome compared specific types of gloving with the use of latex gloves (8, 9). Types of surgery included were neurosurgery, hernia repair, caesarean section, orthopaedic and vascular surgery.

Due to heterogeneity among the selected studies regarding comparison, design and outcome, quantitative meta-analyses were not performed.

Whereas one observational study (14) showed that the cerebrospinal fluid shunt infection rate was significantly higher in the single-glove group compared to the double-glove group, another observational study (13) found no difference in the risk of SSI between double- vs. single-gloving in patients undergoing hernia repair. Three RCTs (6, 7, 10) showed no difference in risk for post-caesarean SSI or endometritis when comparing changing of gloves or removal of the external second pair of gloves after delivery of the placenta or fetus to retaining the gloves during the entire procedure. One RCT (12) reported a reduction of superficial SSI when changing of gloves was performed vs. no change of gloves before the first contact with the vascular prosthesis in synthetic vascular graft surgery. Three RCTs (5, 11, 12) and one additional non-comparative observational study (15) showed that changing of the external second pair of gloves in the course of the operation significantly decreases the incidence of bacterial contamination of the gloves. Two RCTs (8, 9) showed no difference in SSI when comparing different types of gloves (double-gloving) in orthopaedic surgery.

The methodological quality of most of the selected studies was poor as most trials did not provide sufficient details of their process of randomization, allocation, sample size calculation and blinding. SSI definitions varied across the studies. There were few studies with SSI as the primary outcome. Included studies with bacterial contamination as a surrogate outcome showed a great heterogeneity in the setting, design and outcome measures. There is no direct evidence demonstrating the link between bacterial contamination and SSI rates.

The body of retrieved evidence focused on adult patients and no study was available in a paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered

Resource use

The availability of surgical gloves could be limited in LMICs, particularly specific types, such as glove liners, coloured perforation indicator systems, cloth steel outer gloves. In limited resource settings, an acceptable quality of gloves needs to be ascertained as patients are often asked to purchase surgical gloves themselves, which could be of substandard quality.

Research gaps

GDG members highlighted that well-designed RCTs investigating the effectiveness of double-gloving compared to the use of a single pair of gloves would be welcome, especially in LMICs. In addition, RCTs evaluating whether a change of gloves during the operation is more effective in reducing the risk of SSI than no change of gloves are needed, including an assessment of the criteria for changing gloves during the surgical procedure. It would be interesting also to compare different types of gloving to address the question of the optimal type of gloves to be used. All studies should focus on SSI as the primary outcome and be defined according to the CDC criteria and sub-specified as superficial, deep and organ space-occupying.

References

1.
Tanner J, Parkinson H. Double gloving to reduce surgical cross-infection. Cochrane Database Syst Rev. 2009(4). [PubMed: 12137673]
2.
Guidelines for safe surgery. Geneva: World Health Organization; 2009 (http://apps​.who.int/iris​/bitstream/10665​/44185/1/9789241598552_eng.pdf, accessed 25 July 2016).
3.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
4.
Alexander JW, Solomkin JS, Edwards MJ. Updated recommendations for control of surgical site infections. Ann Surg. 2011;253(6):1082–93. [PubMed: 21587113]
5.
Al-Maiyah M, Bajwa A, Mackenney P, Port A, Gregg PJ, Hill D, et al. Glove perforation and contamination in primary total hip arthroplasty. J Bone Joint Surg Br. 2005;(4):556–9. [PubMed: 15795210]
6.
Atkinson MW, Owen J, Wren A, Hauth JC. The effect of manual removal of the placenta on post-cesarean endometritis. Obstet Gynecol. 1996;87(1):99–102. [PubMed: 8532276]
7.
Cernadas M, Smulian JC, Giannina G, Ananth CV. Effects of placental delivery method and intraoperative glove changing on postcesarean febrile morbidity. J Matern Fetal Med. 1998;7(2):100–4. [PubMed: 9584823]
8.
Sanders R, Fortin P, Ross E, Helfet D. Outer gloves in orthopaedic procedures. Cloth compared with latex. J Bone Joint Surg Am. 1990;72(6):914–7. [PubMed: 2195035]
9.
Sebold EJ, Jordan LR. Intraoperative glove perforation. A comparative analysis. Clin Orthop Rel Res. 1993(297):242–4. [PubMed: 8242939]
10.
Ventolini G, Neiger R, McKenna D. Decreasing infectious morbidity in cesarean delivery by changing gloves. J Reprod Med. 2004;49(1):13–6. [PubMed: 14976789]
11.
Ward WG, Cooper JM, Lippert D, Kablawi RO, Neiberg RH, Sherertz RJ. Glove and gown effects on intraoperative bacterial contamination. Ann Surg. 2014;259(3):591–7. [PubMed: 24045444]
12.
Zdanowski Z, Danielsson G, Jonung T, Norgren L, Ribbe E, Thorne J, et al. Intraoperative contamination of synthetic vascular grafts. Effect of glove change before graft implantation. A prospective randomised study. Europ J Vascular Endovasc Surg. 2000;19(3):283–7. [PubMed: 10753692]
13.
Dodds RD, Barker SG, Morgan NH, Donaldson DR, Thomas MH. Self protection in surgery: the use of double gloves. Br J Surg. 1990;77(2):219–20. [PubMed: 2317684]
14.
Tulipan N, Cleves MA. Effect of an intraoperative double-gloving strategy on the incidence of cerebrospinal fluid shunt infection. J Neurosurg. 2006;104(Suppl. 1):5–8. [PubMed: 16509473]
15.
Beldame J, Lagrave B, Lievain L, Lefebvre B, Frebourg N, Dujardin F. Surgical glove bacterial contamination and perforation during total hip arthroplasty implantation: when gloves should be changed. Orthop Traumatol Surg Res. 2012;98(4):432–40. [PubMed: 22578871]

4.21. Changing of surgical instruments

Recommendation

The panel decided not to formulate a recommendation on this topic due to the lack of evidence.

Remarks

  • Surgical instruments are tools or devices that perform functions such as cutting, dissecting, grasping, holding, retracting or suturing. Most surgical instruments are made from stainless steel.
  • The literature search failed to identify relevant studies comparing wound closure using new, sterile surgical instruments with wound closure with previously-used instruments in contaminated surgery for the purpose of preventing SSI.
  • The GDG believes that changing instruments for wound closure in contaminated surgery is common practice. A change of instruments prior to wound closure after contaminated surgical procedures seems logical, particularly after colorectal surgery or in patients operated on for diffuse peritonitis. Nevertheless, there is no evidence to support this practice.

Background

SSI is caused by microorganisms either from the patient’s own skin flora or from the environment surrounding the patient. In both cases, there is a potential for microorganisms to adhere to surgical instruments and consequently contaminate the incisional wound, particularly during contaminated surgical procedures. Therefore, it is common practice to exchange surgical instruments used in contaminated surgical procedures for a new sterile set of surgical instruments before wound closure.

Current SSI prevention guidelines do not address the exchange of surgical instruments prior to wound closure and its effect to prevent SSI. The GDG decided to conduct a systematic review to assess the effectiveness of this practice.

Summary of the evidence

The purpose of the evidence review (web Appendix 22) was to evaluate whether wound closure employing new, clean surgical instruments is more effective in reducing the risk of SSI than wound closure with previously-used surgical instruments. The target population included patients of all ages undergoing contaminated surgical operations. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

The literature search did not identify any studies comparing wound closure using new, sterile surgical instruments and wound closure with previously-used surgical instruments in contaminated surgery.

Two studies, one RCT (1) and one observational study (2), investigated the change of instruments in colorectal surgery in combination with other interventions performed before wound closure, including the change of drapes, gowns and gloves, wound lavage and rescrubbing (not homogeneous in terms of interventions). Both studies showed no benefit for the prevention of SSI.

Research gaps

The GDG highlighted that well-designed RCTs investigating the change of instruments prior to wound closure would be welcome. SSI outcome should be defined according to CDC criteria and studies should be conducted in LMICs and high-income countries and include different surgical procedures. However, several GDG members pointed out that such trials are unlikely to be done. In the future, it is more likely that further studies of combined interventions will be conducted.

References

1.
Ortiz H, Armendariz P, Kreisler E, Garcia-Granero E, Espin-Basany E, Roig JV, et al. Influence of rescrubbing before laparotomy closure on abdominal wound infection after colorectal cancer surgery: results of a multicenter randomized clinical trial. Arch Surg. 2012;147(7):614–20. [PubMed: 22430092]
2.
Ghuman A, Chan T, Karimuddin AA, Brown CJ, Raval MJ, Phang PT. Surgical site infection rates following implementation of a colorectal closure bundle in elective colorectal surgeries. Dis Colon Rectum. 2015;58(11):1078–82. [PubMed: 26445181]

4.22. Antimicrobial-coated sutures

Recommendation

The panel suggests the use of triclosan-coated sutures for the purpose of reducing the risk of SSI, independent of the type of surgery.

(Conditional recommendation, moderate quality of evidence)

Rationale for the recommendation

Overall low to moderate quality evidence shows that antimicrobial-coated sutures have significant benefits in reducing SSI rates in patients undergoing surgical procedures when compared to non-coated sutures. The effect seems to be independent of the type of suture, procedure or wound contamination classification. In meta-regression analysis, there was no evidence that the effect of antimicrobial-coated sutures differed between braided and monofilament sutures, clean, cardiac or abdominal surgery, and other surgeries. However, the GDG highlighted that the available trials examined triclosan-coated, absorbable sutures only. There were no studies identified that investigated other antimicrobial agents. Considering the low to moderate quality of the evidence and the low quality of comparisons in the subgroups of the RCTs included in the meta-regression analyses, the GDG agreed that the strength of the recommendation should be conditional.

Remarks

  • The body of retrieved evidence mostly focused on adult patients and only one study was available in a paediatric population. This recommendation can be applied to paediatric patients, but the manufacturer’s instructions should be checked to evaluate any contraindication for paediatric patients.
  • The GDG discussed the available evidence and agreed to consider only studies comparing the same type of suture in order to prevent confounding by type of suture (monofilament or braided).
  • The overall quality of evidence was moderate for the RCTs due to risk of bias and low for the observational studies. The GDG discussed whether or not to consider indirectness for the overall comparison of antimicrobial-coated vs. non-coated sutures. The agreement was that indirectness does not apply because the PICO question is very broad.
  • Included studies were performed in high- and middle-income countries.
  • Types of surgical procedures included were colorectal, abdominal, breast, head and neck, lower limb, spinal, cardiac, vascular and other surgery.
  • The types of sutures investigated in the included studies were triclosan-coated polydioxanone suture vs. polydioxanone suture featuring a monofilament suture construction (3 RCTs (13)); triclosan-coated polyglactin 910 suture vs. polyglactin 910 suture featuring a braided (multifilament) suture construction (7 RCTs (410) and 4 observational studies (1114)); and polyglactin 910 and poliglecaprone 25 (both triclosan-coated) sutures vs. polyglactin 910 and poliglecaprone 25 sutures featuring a braided (polyglactin 910) and a monofilament (poliglecaprone 25) suture construction (3 RCTs (1517) and one observational study (18)).
  • No adverse events have been associated in the included studies with the use of antimicrobial-coated sutures. However, the GDG pointed out that there is limited evidence that triclosan may have negative effects on wound healing (19) or lead to contact allergy (20). Although the development of resistance is mentioned as a concern, the daily absorption of triclosan from consumer products (for example, commercially-available hand soap) is higher than a single triclosan suture (2123).

Background

Surgical suture material is used to adequately adapt the wound edges and thus it is in direct contact with the wound itself. To prevent microbial colonization of the suture material in operative incisions, sutures with antibacterial activity have been developed. Triclosan (5-chloro-2-[2.4-dichlorophenoxy] phenol) is a broad-spectrum bactericidal agent that has been used for more than 40 years in various products, such as toothpaste and soaps. Higher concentrations of triclosan work as a bactericide by attacking different structures in the bacterial cytoplasm and cell membrane (24). At lower concentrations, triclosan acts as a bacteriostatic agent binding to enoyl-acyl reductase, a product of the Fab I gene and thus inhibiting fatty acid synthesis (25, 26).

Several trials have shown that the use of triclosan-coated sutures leads to a reduction of the number of bacteria in vitro and also of wound infections in animal and clinical studies (2729). Of note, this effect is not confined to any particular tissue or organ system (23). Apart from triclosan, several novel antimicrobial coatings are now becoming available (30, 31), but there are still no reported clinical studies comparing the efficacy of novel antibacterial sutures with non-coated ones. Triclosan-coated polyglactin 910, triclosan-coated polydioxanone, and triclosan-coated poliglecaprone 25 are commercially-available sutures with antimicrobial properties. Commonly-used non-coated sutures are polyglactin 910, polydioxanone, poliglecaprone 25, polyglycolic acid and polyglyconate sutures.

Few organizations have issued recommendations regarding the use of antimicrobial-coated sutures (Table 4.22.1). The UK-based NICE suggests that antimicrobial-coated sutures may reduce the SSI risk compared to non-coated sutures, although this effect may be specific to particular types of surgery, such as abdominal procedures (32). The SHEA/IDSA guidelines indicate that antiseptic-impregnated sutures should not be used routinely as a strategy to prevent SSI (33).

Table 4.22.1. Recommendations on the use of antimicrobial-coated sutures according to available guidelines.

Table 4.22.1

Recommendations on the use of antimicrobial-coated sutures according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess if the use of antimicrobial-coated sutures might be beneficial for surgical patients to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 23) was to evaluate whether the use of antimicrobial-coated sutures is more effective in reducing the risk of SSI than the use of non-coated sutures. The target population included patients of all ages undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Eighteen studies (13 RCTs (110, 1517) and five cohort studies (1114, 18)) including a total of 7458 patients (RCTs, 5346; observational studies, 2112) and comparing the use of antimicrobial-with non-coated sutures were identified.

Seven studies compared the efficacy of antimicrobial-coated sutures with non-coated sutures in mixed wounds (5 RCTs (25, 8) and 2 observational studies (12, 14)). A further 7 studies (5 RCTs (6, 10, 1517) and 2 observational studies (11, 18)) made the same comparison in clean wounds, mainly cardiac and breast cancer surgery, and 4 studies (3 RCTs (1, 7, 9) and one observational study (13)) concerned clean-contaminated wounds in abdominal surgery.

Due to heterogeneity among the selected studies regarding the type of suture used, type of surgical procedure or wound contamination class, additional separate meta-analyses were performed for triclosan-coated polydioxanone suture vs. polydioxanone suture, triclosan-coated polyglactin 910 suture vs. polyglactin 910 suture, and polyglactin 910 and poliglecaprone 25 (both triclosan-coated) sutures vs. polyglactin 910 and poliglecaprone 25 sutures, as well as in clean, clean-contaminated and mixed types of wounds (web Appendix 23).

Overall, there is moderate to low quality evidence that antimicrobial-coated sutures have significant benefit in reducing SSI rates in patients undergoing surgical procedures when compared to non-coated sutures (moderate quality for RCTs: OR: 0.72; 95% CI: 0.59–0.88; low quality for observational studies: OR: 0.58; 95% CI: 0.40–0.83).

In meta-regression analysis, there was no evidence that the effect of antimicrobial-coated sutures differed between braided and monofilament sutures (P=0.380), or between clean (P=0.69), cardiac (P=0.900) or abdominal (P=0.832) and other types of surgery. According to these analyses, the effect seems to be independent of the type of suture, procedure or wound contamination classification.

Regarding the comparisons of specific types of sutures (web Appendix 23), only the meta-analyses of the studies comparing triclosan-coated polyglactin 910 suture vs. polyglactin 910 suture featuring a braided suture construction showed that the use of antimicrobial-coated sutures has significant benefit compared to non-coated sutures in reducing SSI rates (OR: 0.62; 95% CI: 0.44–0.88 for RCTs; OR: 0.58; 95% CI: 0.37–0.92 for observational studies).

Some limitations of the included studies should be noted. The quality of the included RCTs was moderate to low. Indeed, some studies had an unclear or high risk of blinding of participants, care-providers and outcome assessors, and/or a high risk of incomplete outcome data. Furthermore, some studies had industrial sponsorship or conflicts of interest with a commercial company.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that most patients wish to receive this intervention in order to reduce the risk of SSI, but patients must be informed about the small and unconfirmed risk of allergy to triclosan. The GDG emphasized that patients would like to be part of the process by being involved and informed.

Resource use

The GDG emphasized that sutures are expensive in general. Moreover, the availability of antimicrobial-coated sutures is limited in LMICs. In settings where patients have to pay for the material themselves, an increase in costs would represent an additional personal financial burden. At the time of formulating this recommendation, the GDG noted that manufacturers sold the antimicrobial-coated and non-coated sutures for approximately the same price. However, the GDG is not aware of the future pricing policy of manufacturers. The use of antimicrobial-coated sutures could increase the cost per patient, but it might reduce the mean length of hospital stay and reduce potential costs to the health care system due to the avoidance of the risk of SSI (5, 8, 34).

The body of retrieved evidence mostly focused on adult patients and only one study (4) was available in a paediatric population. The literature search did not identify any studies that reported on SSI attributable-mortality.

Research gaps

The GDG highlighted the limited evidence available in some areas and the need for further research on the effects of antimicrobial-coated sutures in reducing SSI rates. In particular, studies should be conducted in LMICs and include different surgical procedures. Comparisons between antimicrobial-coated and non-coated sutures should be performed with the same type of suture material, including non-absorbable sutures. In particular, comparisons with an alternative antimicrobial agent to triclosan would be welcome. More research is required to investigate the effectiveness of antimicrobial-coated sutures in the paediatric population and in various types of settings. All studies should be designed as a RCT with the SSI outcome defined according to CDC criteria and sub-specified as superficial, deep and organ space occupying. Adverse events related to the intervention should be clearly reported, including the need to assess the risk of allergy. Importantly, possible emerging AMR to the antimicrobial agent should be monitored. Moreover, cost-effectiveness studies are also needed. Of note, research investigating the effectiveness of antimicrobial-coated sutures should be independently funded with a limited influence of industry sponsorship.

References

1.
Baracs J, Huszar O, Sajjadi SG, Horvath OP. Surgical site infections after abdominal closure in colorectal surgery using triclosan-coated absorbable suture (PDS Plus) vs. uncoated sutures (PDS II): a randomized multicenter study. Surg Infect (Larchmt). 2011;12(6):483–9. [PubMed: 22142314]
2.
Diener MK, Knebel P, Kieser M, Schuler P, Schiergens TS, Atanassov V, et al. Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial. Lancet. 2014;384(9938):142–52. [PubMed: 24718270]
3.
Justinger C, Slotta JE, Ningel S, Graber S, Kollmar O, Schilling MK. Surgical-site infection after abdominal wall closure with triclosanimpregnated polydioxanone sutures: results of a randomized clinical pathway facilitated trial (NCT00998907). Surgery. 2013;154(3):589–95. [PubMed: 23859304]
4.
Ford HR, Jones P, Gaines B, Reblock K, Simpkins DL. Intraoperative handling and wound healing: controlled clinical trial comparing coated VICRYL plus antibacterial suture (coated polyglactin 910 suture with triclosan) with coated VICRYL suture (coated polyglactin 910 suture). Surg Infect (Larchmt). 2005;6(3):313–21. [PubMed: 16201941]
5.
Galal I, El-Hindawy K. Impact of using triclosan-antibacterial sutures on incidence of surgical site infection. Am J Surg. 2011;202(2):133–8. [PubMed: 21600552]
6.
Isik I, Selimen D, Senay S, Alhan C. Efficiency of antibacterial suture material in cardiac surgery: a double-blind randomized prospective study. Heart Surg Forum. 2012;15(1):e40–5. [PubMed: 22360905]
7.
Mingmalairak C, Ungbhakorn P, Paocharoen V. Efficacy of antimicrobial coating suture coated polyglactin 910 with tricosan (Vicryl plus) compared with polyglactin 910 (Vicryl) in reduced surgical site infection of appendicitis, double blind randomized control trial, preliminary safety report. J Med Assoc Thai. 2009;92(6):770–5. [PubMed: 19530582]
8.
Nakamura T, Kashimura N, Noji T, Suzuki O, Ambo Y, Nakamura F, et al. Triclosan-coated sutures reduce the incidence of wound infections and the costs after colorectal surgery: a randomized controlled trial. Surgery. 2013;153(4):576–83. [PubMed: 23261025]
9.
Rasic Z, Schwarz D, Adam VN, Sever M, Lojo N, Rasic D, et al. Efficacy of antimicrobial triclosan-coated polyglactin 910 (Vicryl* Plus) suture for closure of the abdominal wall after colorectal surgery. Coll Antropol. 2011;35(2):439–43. [PubMed: 21755716]
10.
Seim BE, Tonnessen T, Woldbaek PR. Triclosan-coated sutures do not reduce leg wound infections after coronary artery bypass grafting. Interact Cardiovasc Thorac Surg. 2012;15(3):411–5. [PMC free article: PMC3422962] [PubMed: 22691378]
11.
Chen SY, Chen TM, Dai NT, Fu JP, Chang SC, Deng SC, et al. Do antibacterial-coated sutures reduce wound infection in head and neck cancer reconstruction? Europ J Surg Oncol. 2011;37(4):300–4. [PubMed: 21296544]
12.
Hoshino S, Yoshida Y, Tanimura S, Yamauchi Y, Noritomi T, Yamashita Y. A study of the efficacy of antibacterial sutures for surgical site infection: a retrospective controlled trial. Int Surg. 2013;98(2):129–32. [PMC free article: PMC3723176] [PubMed: 23701147]
13.
Okada N, Nakamura T, Ambo Y, Takada M, Nakamura F, Kishida A, et al. Triclosan-coated abdominal closure sutures reduce the incidence of surgical site infections after pancreaticoduodenectomy. Surg Infect (Larchmt). 2014;15(3):305–9. [PubMed: 24797228]
14.
Ueno M, Saito W, Yamagata M, Imura T, Inoue G, Nakazawa T, et al. Triclosan-coated sutures reduce wound infections after spinal surgery: a retrospective, nonrandomized, clinical study. Spine J. 2015;15(5):933–8. [PubMed: 23992939]
15.
Thimour-Bergstrom L, Roman-Emanuel C, Schersten H, Friberg O, Gudbjartsson T, Jeppsson A. Triclosan-coated sutures reduce surgical site infection after open vein harvesting in coronary artery bypass grafting patients: a randomized controlled trial. Europ J Cardiothorac Surg. 2013;44(5):931–8. [PMC free article: PMC3794438] [PubMed: 23435526]
16.
Turtiainen J, Saimanen EI, Makinen KT, Nykanen AI, Venermo MA, Uurto IT, et al. Effect of triclosan-coated sutures on the incidence of surgical wound infection after lower limb revascularization surgery: a randomized controlled trial. World J Surg. 2012;36(10):2528–34. [PubMed: 22618956]
17.
Williams N, Sweetland H, Goyal S, Ivins N, Leaper DJ. Randomized trial of antimicrobial-coated sutures to prevent surgical site infection after breast cancer surgery. Surg Infect (Larchmt). 2011;12(6):469–74 [PubMed: 22142317]
18.
Laas E, Poilroux C, Bezu C, Coutant C, Uzan S, Rouzier R, et al. Antibacterial-coated suture in reducing surgical site infection in breast surgery: a prospective study. Int J Breast Cancer. 2012;2012:819578. [PMC free article: PMC3536044] [PubMed: 23316373]
19.
Deliaert AE, Van den Kerckhove E, Tuinder S, Fieuws S, Sawor JH, Meesters-Caberg MA, et al. The effect of triclosan-coated sutures in wound healing. A double blind randomised prospective pilot study. J Plast Reconstr Aesth Surg. 2009;62(6):771–3. [PubMed: 18450530]
20.
Bhutani T, Jacob SE. Triclosan: a potential allergen in suture-line allergic contact dermatitis. Dermatol Surg. 2009;35(5):888–9. [PubMed: 19389086]
21.
Barbolt TA. Chemistry and safety of triclosan, and its use as an antimicrobial coating on Coated VICRYL* Plus Antibacterial Suture (coated polyglactin 910 suture with triclosan). Surg Infect (Larchmt). 2002;3(Suppl. 1):S45–53. [PubMed: 12573039]
22.
Giuliano CA, Rybak MJ. Efficacy of triclosan as an antimicrobial hand soap and its potential impact on antimicrobial resistance: a focused review. Pharmacotherapy. 2015;35(3):328–36. [PubMed: 25809180]
23.
Leaper D, Assadian O, Hubner NO, McBain A, Barbolt T, Rothenburger S, et al. Antimicrobial sutures and prevention of surgical site infection: assessment of the safety of the antiseptic triclosan. Int Wound J. 2011;8(6):556–66. [PMC free article: PMC7950790] [PubMed: 21854548]
24.
Russell AD. Whither triclosan? J Antimicrob Chemother. 2004;53(5):693–5. [PubMed: 15073159]
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Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, Slabas AR, et al. Molecular basis of triclosan activity. Nature. 1999;398(6726):383–4. [PubMed: 10201369]
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McMurry LM, Oethinger M, Levy SB. Triclosan targets lipid synthesis. Nature. 1998;394(6693):531–2. [PubMed: 9707111]
27.
Marco F, Vallez R, Gonzalez P, Ortega L, de la Lama J, Lopez-Duran L. Study of the efficacy of coated Vicryl plus antibacterial suture in an animal model of orthopedic surgery. Surg Infect (Larchmt). 2007;8(3):359–65. [PubMed: 17635059]
28.
Rothenburger S, Spangler D, Bhende S, Burkley D. In vitro antimicrobial evaluation of coated VICRYL* Plus antibacterial suture (coated polyglactin 910 with triclosan) using zone of inhibition assays. Surg Infect (Larchmt). 2002;3(Suppl. 1):S79–87. [PubMed: 12573042]
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Storch ML, Rothenburger SJ, Jacinto G. Experimental efficacy study of coated VICRYL plus antibacterial suture in guinea pigs challenged with Staphylococcus aureus. Surg Infect (Larchmt). 2004;5(3):281–8. [PubMed: 15684799]
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Matl FD, Zlotnyk J, Obermeier A, Friess W, Vogt S, Buchner H, et al. New anti-infective coatings of surgical sutures based on a combination of antiseptics and fatty acids. J Biomat Sci, 2009;20(10):1439–49. [PubMed: 19622281]
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Obermeier A, Schneider J, Wehner S, Matl FD, Schieker M, von Eisenhart-Rothe R, et al. Novel high efficient coatings for anti-microbial surgical sutures using chlorhexidine in fatty acid slow-release carrier systems. PloS One. 2014;9(7):e101426. [PMC free article: PMC4077814] [PubMed: 24983633]
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Fleck T, Moidl R, Blacky A, Fleck M, Wolner E, Grabenwoger M, et al. Triclosan-coated sutures for the reduction of sternal wound infections: economic considerations. Ann Thorac Surg. 2007;84(1):232–6. [PubMed: 17588420]

4.23. Laminar airflow ventilation systems in the context of operating room ventilation

Recommendation

The panel suggests that laminar airflow ventilation systems should not be used to reduce the risk of SSI for patients undergoing total arthroplasty surgery.

(Conditional recommendation, low to very low quality of evidence)

Rationale for the recommendation

Very low quality evidence shows that in both total hip (THA) and knee (TKA) arthroplasty, laminar airflow ventilation has no benefit when compared to conventional ventilation in reducing the SSI rate. In THA, conventional ventilation had a non-significant beneficial effect in reducing the risk of SSI. Therefore, the GDG unanimously agreed that laminar airflow ventilation systems should not be used as a preventive measure to reduce the risk of SSI for total arthroplasty surgery. The strength of this recommendation was considered to be conditional, considering the very low quality of the supporting evidence. For other types of procedures, the available evidence consisted of single observational studies only and the GDG considered this body of evidence to be insufficient to lead to any specific recommendation. Moreover, laminar airflow ventilation has been of interest mainly as a preventive measure in orthopaedic arthroplasty surgery.

Remarks

  • Conventional ventilation systems pass air with a mixed or turbulent flow into the OR. These systems aim to homogenize the fresh air and the air, aerosols and particles within the room. This leads to an accelerated dilution of the air volume and an irregular movement of the particles. Conventional turbulent ventilation systems are used for any type of surgery. Systems with laminar airflow are frequently used in an environment where a contamination with particles is a highly adverse event, for example, in orthopaedic implant surgery. The goal of laminar airflow is to pass the fresh air unidirectionally with a steady velocity and approximately parallel streamlines to create a zone where the air, aerosols and particles within the room are being driven out.
  • No possible harms associated with the recommendation were identified. However, the cooling effect of the fresh air from a laminar airflow system on the surgical wound and the patient may lead to lower intraoperative tissue temperatures in the surgical wound or systemic hypothermia if the temperature is not monitored intraoperatively (1).
  • The GDG underlined that most data are from national surveillance databases or registries. Although these studies have a large sample size, they are not designed specifically for this comparison. Indeed, comparisons were between hospitals with laminar flow and those with conventional ventilation, rather than comparisons within the same hospital. This may lead to major confounding by factors such as differences in hospital/surgeon volume, characteristics of admitted patients and/or the extent of implementation of other SSI prevention measures.
  • The systematic review investigated also the use of fans or cooling devices and natural ventilation in the operating room compared to conventional ventilation with regards to the risk of SSI. However, the literature search did not identify studies that evaluated these interventions. One observational study (2) that evaluated natural ventilation in the operating room compared to conventional ventilation following THA and TKA found no difference in the SSI risk.
  • Given the very limited evidence on natural ventilation and fans/cooling systems, the GDG decided not to develop a recommendation on these topics. Nevertheless, it is advisable to ensure a proper ventilation rate of the operating room and an adequate maintenance of the components of the installed ventilation system (3).

Background

The ventilation system in the operating room is designed to provide certain functions, primarily to create thermal comfort for the patient and staff and to maintain constant air quality by eliminating aerosols and particles within the room. It serves also to maintain certain air pressure requirements between communicating rooms. Special ventilation systems supplying filtered air at positive pressure are required in the operating room. Ideally, around 20 air changes per hour are necessary to dilute microorganisms generated in the operating room and to exclude ingress from surrounding areas (3).

There are various systems used to ventilate an operating room. Natural ventilation is the most basic way and refers to airflow by natural forces. WHO provides the following definition (4): “use of natural forces to introduce and distribute outdoor air into or out of a building. These natural forces can be wind pressures or pressure generated by the density difference between indoor and outdoor air”. Exploiting natural ventilation may be a suitable solution for settings with limited resources and it is considered as an option for IPC by WHO. However, there is no evidence available for its use in operating rooms (4).

A well-designed ventilation system that takes advantage of natural air movements is still complex to achieve and is limited to a benign local climate (4). If natural ventilation alone is not sufficient to fulfil the desired functions mentioned above, fans and cooling or warming devices are commonly installed, mostly to maintain the air temperature and humidity at a comfortable level. Limitations of these devices might be an inadequate rate of air changes per hour and control of the direction of airflow in the operating room and the spread of particles and dust, thus resulting in an insufficient elimination of aerosols and particles.

In most LMICs, operating rooms do not have a full mechanical ventilation system and the air conditioning used is a recirculating cooling device. If such a system is used, it should be wall-mounted rather than floor standing, and should be maintained regularly, including filters checked, cleaned or changed. The use of fans in the operating room is not recommended and should be used only as a last resort if the lack of air circulation affects the surgeon’s performance. Any fans in the operating room or preparation room should be cleaned on a regular basis.

In well-resourced environments, conventional ventilation systems that pass air with a mixed or turbulent flow into the operating room are the most widely installed. These systems aim to homogenize the fresh air and the air, aerosols and particles within the room. This leads to an accelerated dilution of the air volume and an irregular movement of the particles. Conventional turbulent ventilation systems are used for all types of surgery. Systems with laminar airflow are frequently used in an environment where contamination with particles is a highly adverse event, for example, orthopaedic implant surgery. The goal of passing the fresh air unidirectionally with a steady velocity and approximately parallel streamlines is to create a zone where the air, aerosols and particles within the room are being driven out. Limitations to this principle are all forces disrupting the parallel airflow.

In many countries, the use of high efficiency particulate air filters (at least 99.97% efficient in removing particles ≥0.3 Ìm in diameter) in the operating room ventilation system is mandatory by law. Of note, the utmost importance must be paid to the maintenance of any kind of ventilation system and its components. The operating room ventilation system should be regularly checked and filters changed (the need for this is assessed by monitoring the pressure differential across the filters) according to local standard operating procedures, which should be based on the manufacturer’s instructions and international guidelines.

A systematic review (5) published in 2012 on the influence of laminar airflow on prosthetic joint infections found laminar airflow ventilation to be a risk factor for the development of a severe SSI.

Some guidelines have issued recommendations regarding the ventilation systems in the operating room (Table 4.23.1), but several other SSI prevention guidelines do not address this topic. These range from a technical advice for proper air handling in the operating room (6) to leaving this question as an unresolved issue (3). However, these recommendations are not based on systematic reviews of the literature and meta-analysis or a rigorous evaluation of the quality of the available evidence.

Table 4.23.1. Recommendations on ventilation systems in the operating room according to available guidelines.

Table 4.23.1

Recommendations on ventilation systems in the operating room according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG decided to conduct a systematic review to assess the effectiveness of ventilation systems in the operating room for the prevention of SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 24) was to evaluate whether a laminar airflow ventilation system is more effective in reducing the risk of SSI than a conventional ventilation system. The review investigated also whether fans or cooling devices and natural ventilation are acceptable alternatives to conventional ventilation for the prevention of SSI. The target population was patients of all ages undergoing a surgical procedure. The primary outcome was the occurrence of SSI and SSI-attributable mortality. Definitions in included studies that related to severe SSI, periprosthetic infection and deep infections requiring revision were considered as deep SSI.

Twelve observational studies (2, 717) comparing laminar airflow with conventional ventilation were identified. No RCTs were identified. Most data were obtained from national surveillance systems and registries. Of note, although these sources had a large sample size, the databases were not specifically designed for this comparison. Most studies focused on THA (33 0146 procedures) and TKA (134 368 procedures). Only single studies were available for other types of surgery (appendectomy (7), cholecystectomy (7), colon surgery (7), herniorrhaphy (7), gastric (8) and vascular surgery (9)). The population studied were mostly adult patients. According to the selected studies, the following comparisons were evaluated.

  1. Laminar airflow ventilation vs. conventional ventilation
    1. in THA
    2. in TKA.

Very low quality evidence shows that laminar airflow ventilation has no benefit when compared to conventional ventilation in reducing the SSI rate in THA (OR: 1.29; 95% CI: 0.98–1.71) or TKA (OR: 1.08; 95% CI: 0.77–1.52).

In single observational studies, laminar flow was found to be associated with an increased overall risk of SSI in patients undergoing appendectomy; no significant association was shown in colon surgery, cholecystectomy and herniorraphy. In gastric and open vascular surgery, the absence of laminar flow was found to increase the risk of SSI.

The search did not identify data that evaluated the use of fans or cooling devices in the operating room and their impact on the risk of SSI compared to a normal/conventional ventilation system. One observational study (2) that evaluated natural ventilation in the operating room compared with conventional ventilation and its impact on the risk of SSI following THA and TKA found no difference in the risk of SSI.

The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention. The GDG is confident that the typical values and preferences of the target population regarding the outcome would not favour the intervention and therefore would agree with the recommendation. The GDG believes also that patients would not have an opinion about a hospital ventilation system, as long as other aspects are being taken into account to prevent infections.

Resource use

Cost-effectiveness analyses found laminar airflow to be more expensive compared to a conventional ventilation system. An Italian study (18) evaluated an increase of 24% in building costs and an increase of 36% in annual operating costs. A model calculation study from Australia (19) evaluated additional costs of AUD$ 4.59 million per 30 000 THAs performed. Additional costs of ú 3.24 procedure (1000 procedures per year for 15 years) were calculated by a German study group (20). The GDG highlighted that the implementation of laminar airflow is difficult in low-income settings due to the lack of resources, technical expertise and infrastructure.

Research gaps

The GDG highlighted the very low quality evidence available on the topic and the need for further research on the effects of laminar flow in reducing the SSI rate, particularly well-designed clinical trials in the field of endoprosthetic surgery. The GDG acknowledged that RCTs may not be reasonable as they would require a massive investment with a high sample size to have enough power to see a difference. In addition, cluster trials could be problematic as it would be almost impossible to control for confounding factors, such as different surgeons operating in the same operating room. Nationwide databases may provide the best affordable information, but adherence to international definitions and more information about confounders need to be obtained from country surveillance systems and registries. The lack of evidence on the impact of fans/cooling devices and natural ventilation on the SSI rate compared to conventional ventilation emphasizes the need for further research in this field in order to evaluate whether these systems might be an alternative in resource-limited countries when properly designed and maintained.

References

1.
Yang L, Huang CY, Zhou ZB, Wen ZS, Zhang GR, Liu KX, et al. Risk factors for hypothermia in patients under general anesthesia: Is there a drawback of laminar airflow operating rooms? A prospective cohort study. Int J Surg. 2015;21:14–7. [PubMed: 26184995]
2.
Song KH, Kim ES, Kim YK, Jin HY, Jeong SY, Kwak YG, et al. Differences in the risk factors for surgical site infection between total hip arthroplasty and total knee arthroplasty in the Korean Nosocomial Infections Surveillance System (KONIS). Infect Control Hosp Epidemiol. 2012;33(11):1086–93. [PubMed: 23041805]
3.
Sehulster L, Chinn RY. Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Morbid Mortal Wkly Rep. 2003;52(Rr-10):1–42. [PubMed: 12836624]
4.
Atkinson JYC, Pessoa-Silva CL, Jensen P, Li Y, Seto WH. Natural ventilation for infection control in health-care settings. Geneva: World Health Organization; 2009 (http://www​.who.int/water​_sanitation_health​/publications/natural_ventilation/en/, accessed 25 July 2016). [PubMed: 23762969]
5.
Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(6):605–27. [PMC free article: PMC4267723] [PubMed: 24799638]
6.
Gastmeier P, Breier AC, Brandt C. Influence of laminar airflow on prosthetic joint infections: a systematic review. J Hosp Infect. 2012;81(2):73–8. [PubMed: 22579079]
7.
Brandt C, Hott U, Sohr D, Daschner F, Gastmeier P, Ruden H. Operating room ventilation with laminar airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery. Ann Surg. 2008;248(5):695–700. [PubMed: 18948793]
8.
Jeong SJ, Ann HW, Kim JK, Choi H, Kim CO, Han SH, et al. Incidence and risk factors for surgical site infection after gastric surgery: a multicenter prospective cohort study. Infect Chemother. 2013;45(4):422–30. [PMC free article: PMC3902821] [PubMed: 24475356]
9.
Bosanquet DC, Jones CN, Gill N, Jarvis P, Lewis MH. Laminar flow reduces cases of surgical site infections in vascular patients. Ann R Coll Surg Engl. 2013;95(1):15–9. [PMC free article: PMC3964628] [PubMed: 23317717]
10.
Dale H, Hallan G, Hallan G, Espehaug B, Havelin LI, Engesaeter LB. Increasing risk of revision due to deep infection after hip arthroplasty. Acta Orthop. 2009;80(6):639–45. [PMC free article: PMC2823304] [PubMed: 19995313]
11.
Namba RS, Inacio MC, Paxton EW. Risk factors associated with surgical site infection in 30, 491 primary total hip replacements. J Bone Joint Surg Br. 2012;94(10):1330–8. [PubMed: 23015556]
12.
Namba RS, Inacio MC, Paxton EW. Risk factors associated with deep surgical site infections after primary total knee arthroplasty: an analysis of 56,216 knees. J Bone Joint Surgery Am. 2013;95(9):775–82. [PubMed: 23636183]
13.
Pedersen AB, Svendsson JE, Johnsen SP, Riis A, Overgaard S. Risk factors for revision due to infection after primary total hip arthroplasty. A population-based study of 80,756 primary procedures in the Danish Hip Arthroplasty Registry. Acta Orthop. 2010;81(5):542–7. [PMC free article: PMC3214741] [PubMed: 20860453]
14.
Breier AC, Brandt C, Sohr D, Geffers C, Gastmeier P. Laminar airflow ceiling size: no impact on infection rates following hip and knee prosthesis. Infect Control Hosp Epidemiol. 2011;32(11):1097–102. [PubMed: 22011537]
15.
Hooper GJ, Rothwell AG, Frampton C, Wyatt MC. Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry. J Bone Joint Surg (Br). 2011;93(1):85–90. [PubMed: 21196549]
16.
Kakwani RG, Yohannan D, Wahab KH. The effect of laminar air-flow on the results of Austin-Moore hemiarthroplasty. Injury. 2007;38(7):820–3. [PubMed: 17157847]
17.
Miner AL, Losina E, Katz JN, Fossel AH, Platt R. Deep infection after total knee replacement: impact of laminar airflow systems and body exhaust suits in the modern operating room. Infect Control Hosp Epidemiol. 2007;28(2):222–6. [PubMed: 17265409]
18.
Cacciari P, Giannoni R, Marcelli E, Cercenelli L. [Cost evaluation of a ventilation system for operating theatre: an ultraclean design versus a conventional one]. Ann Ig. 2004;16(6):803–9. [PubMed: 15697009]
19.
Merollini KM, Crawford RW, Whitehouse SL, Graves N. Surgical site infection prevention following total hip arthroplasty in Australia: a cost-effectiveness analysis. Am J Infect Control. 2013;41(9):803–9. [PubMed: 23434381]
20.
Kramer A, Kulpmann R, Wille F, Christiansen B, Exner M, Kohlmann T, et al. [Importance of displacement ventilation for operations and small surgical procedures from the infection preventive point of view]. Zentr Chir. 2010;135(1):11–7. [PubMed: 19960416]

Postoperative Measures

4.24. Surgical antibiotic prophylaxis prolongation

Recommendation

The panel recommends against the prolongation of SAP administration after completion of the operation for the purpose of preventing SSI.

(Strong recommendation/moderate quality of evidence)

Rationale for the recommendation

  • Moderate quality evidence from a high number of RCTs (44 studies included in the overall meta-analysis) shows that prolonged SAP postoperatively has no benefit in reducing SSI after surgery when compared to a single dose. However, there was some evidence (low to very low quality) that a prolonged postoperative administration of antibiotics may be beneficial to reduce the risk of SSI in cardiac, vascular and orthognathic surgery when compared to single-dose prophylaxis. Considering this limited and low to very low quality evidence in support of SAP prolongation in the above-mentioned procedures, as well as the possible harm associated with the prolonged duration of antibiotic administration, the GDG agreed to recommend against the prolongation of antibiotic administration after completion of the operation for the purpose of preventing SSI.
  • Considering the possible adverse events, the risk of generating AMR linked to SAP prolongation and the high number of available studies of moderate quality showing no benefit, the strength of the recommendation was decided to be strong.

Remarks

  • In the included studies, “single dose” usually refers to a preoperative dose with or without intraoperative re-dosing, depending on the duration of the operation and the half-life of the drug. The included studies always compared the same antibiotic agent in the same dose per administration.
  • The guidelines of the American Society of Health-System Pharmacists (1) recommend that intraoperative re-dosing is needed if the duration of the procedure exceeds 2 half-lives of the drug or if there is excessive blood loss during the procedure. While the benefit of this approach seems reasonable from a drug pharmacokinetic aspect, the reviewed studies have not addressed the duration of surgical procedures or re-dosing in relation to SSI in standard antibiotic prophylaxis protocols. No recommendation could be concluded on the benefit or harm of this approach.
  • For cardiac (2 RCTs (2, 3)) and orthognathic surgery (3 RCTs (46)), there was some evidence that prolonging antibiotic administration after completion of the operation may be beneficial in reducing the risk of SSI when compared to single-dose prophylaxis. By contrast, other RCTs (713) showed no benefit of prolonging antibiotic prophylaxis beyond 24 hours compared to prophylaxis for up to 24 hours in these types of surgery.
  • In vascular surgery, there was some evidence from one RCT (14) that prolonging antibiotic prophylaxis until intravenous lines and tubes are removed may be beneficial in reducing the risk of SSI when compared to single-dose prophylaxis.
  • The GDG highlighted the risk of promoting AMR if antibiotics are prolonged in the postoperative period, both in the individual patient and at the health care facility level. In addition, this practice might negatively affect the patient microbiome and lead to short- and long-term gastrointestinal complications. A relevant harm possibly linked to prolonged SAP is the intestinal spread of C. difficile with a higher risk of a clinical manifestation of infection.

Background

The preventive effect of the routine use of SAP prior to non-clean and implant surgery has long been recognized. However, the benefit of continuing SAP after completion of the procedure is unclear. While current guidelines recommend a maximum postoperative SAP duration of 24 hours, increasing evidence shows that there may be non-inferiority of a single preoperative dose (and possible additional intraoperative doses according to the duration of the operation). Despite this, surgeons still have a tendency to routinely continue SAP up to several days after surgery (15, 16).

The use and duration of postoperative prophylaxis have been specified in clinical practice guidelines issued by professional societies or national authorities (Table 4.24.1). Several guidelines, such as those published by SHEA/IDSA (17) and the American Society of Health-System Pharmacists (1), recommend discontinuing SAP within 24 hours after surgery. The 2012 SSI prevention bundle from the US Institute of Healthcare Improvement (18) recommends discontinuing SAP within 24 hours in general and within 48 hours in cardiac surgery. Other guidelines published by the UK-based NICE (19), the Scottish Intercollegiate Guidelines Network (SIGN) (20), the Royal College of Physicians of Ireland (21) and the UK Department of Health (22), recommend a single dose of preoperative SAP and no postoperative continuation with or without exceptions for specific surgical procedures.

Table 4.24.1. Recommendations on SAP according to available guidelines.

Table 4.24.1

Recommendations on SAP according to available guidelines.

Following an in-depth analysis of the sources and strength of evidence in current guidelines, the GDG members decided to conduct a systematic review to assess the available evidence on the effectiveness of prolonged antibiotic prophylaxis to prevent SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 25) was to investigate whether prolonged SAP in the postoperative period is more effective in reducing the risk of SSI than perioperative prophylaxis (single dose before incision and possible intraoperative additional dose/s according to the duration of the operation). The target population included patients of all ages undergoing a surgical procedure for which SAP is indicated. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Sixty-nine RCTs (29, 1114, 2379) including a total of 21 243 patients and investigating the optimal duration of antibiotic prophylaxis in a variety of surgical procedures were identified: appendectomy (2327); colorectal surgery (2830, 6064, 75); upper gastrointestinal tract surgery (3134); cholecystectomy (35, 65); hepatobiliary surgery (76, 80); mixed general surgery (3742, 79); caesarean section (4345); gynaecological surgery (46, 47, 74); orthopaedic and trauma surgery (48, 49); spine surgery (50, 66); cardiac surgery (2, 3, 7, 8, 77); thoracic surgery (51); vascular surgery (14); transplantation surgery (52); head and neck surgery (53, 6769, 78, 81); ear, nose and throat surgery (55, 70); maxillofacial surgery (5659, 71); orthognathic surgery (46, 9, 1113, 72); and others (73). Both intervention and control groups received the same preoperative regimen in all included studies and they only differed in the postoperative continuation of antibiotic prophylaxis. There were variations in the antibiotic regimens and in the duration of SAP prolongation. The first dose of the antibiotic prophylaxis was always administered preoperatively.

Considering the heterogeneity among the selected studies regarding the duration of SAP prolongation postoperatively and the type of surgical procedure, several separate meta-analyses were performed according to the following comparisons (web Appendix 25).

  1. Any prolonged regimen vs. no postoperative dose (44 RCTs).
  2. A prolonged regimen less than 24 hours postoperatively vs. a single postoperative dose (one RCT).
  3. A prolonged regimen more than 24 hours postoperatively vs. a prolonged regimen less than 24 hours postoperatively (23 RCTs).
  4. A prolonged regimen more than 48 hours postoperatively vs. a prolonged regimen less than 48 hours postoperatively (3 RCTs).
  5. Type of procedure with a prolonged antibiotic regimen:
    1. cardiac surgery
    2. vascular surgery
    3. orthognathic surgery.

Overall, there is a moderate quality of evidence that prolonged postoperative antibiotic prophylaxis has no benefit in reducing the SSI rate when compared to a single dose of antibiotic prophylaxis (OR: 0.89; 95% CI: 0.77–1.03).

In cardiac (2, 3) and orthognathic surgery (46), there is some low quality evidence that SAP continuation after completion of the operation may be beneficial in reducing SSI when compared to a single dose of prophylaxis (OR: 0.43; 95% CI: 0.25–0.76 and OR: 0.30; 95% CI: 0.10–0.88, respectively). Conversely, other RCTs (713) showed no benefit in SSI prevention by prolonging SAP beyond 24 hours compared to SAP for up to 24 hours in both cardiac (7, 8) (OR: 0.74; 95% CI: 0.32–1.73; very low quality of evidence) and orthognathic surgery (913) (OR: 0.34; 95% CI: 0.08–1.44; very low quality of evidence). In vascular surgery, there was some evidence from one RCT (14) that prolonging antibiotic prophylaxis until intravenous lines and tubes are removed may be beneficial in reducing the risk of SSI when compared to a single dose (OR: 0.50; 95% CI: 0.25–0.98).

The retrieved evidence focused mostly on adult patients. Only 2 studies (27, 61) addressed specifically the paediatric population. Fifteen studies (4, 6, 1113, 25, 26, 37, 39, 41, 42, 57, 70, 82, 83) included some paediatric patients, but with a majority of adult patients. Among the 69 included studies, 14 (4, 6, 9, 11, 13, 26, 38, 4345, 56, 57, 70, 77) were conducted in LMICs. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

Patient values and preferences were not assessed by the studies. The GDG argued that the recommendation was likely to be similar to the values and preferences of most patients. The GDG pointed out that some patients feel reassured by receiving prolonged antibiotic prophylaxis, while others would prefer to receive the lowest number of drugs possible and, in particular, to discontinue antibiotics as soon as possible.

Resource use

Studies addressing cost-effectiveness reported a cost reduction associated with shorter antibiotic prophylaxis regimens. This varied from US$ 36.90 to US$ 1664 and was attributable to the lower number of antibiotic doses administered and a reduced treatment of side-effects and duration of hospitalization (24, 47, 52, 55, 74, 84). The GDG emphasized that the recommendation may generate cost savings due to reduced expenses in drugs and materials, staff time and reduced costs due to the prevention of adverse events associated with prolonged antibiotic prophylaxis. The GDG highlighted that there is a need to raise awareness and provide education on the rational use of antibiotics and antibiotic stewardship among both health care workers (surgeons in particular, with reference to this recommendation) and patients.

Research gaps

The GDG highlighted that there is a need for further well-designed RCTs in cardiac and vascular surgery, as well as in in the paediatric population. Importantly, it would be crucial that studies include the selection of the most appropriate antibiotic according to the surgical procedure. Future trials should investigate the effect of prolonged antibiotic prophylaxis on the microbiome.

References

1.
Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195–283. [PubMed: 23327981]
2.
Nooyen SM, Overbeek BP, Brutel de la Rivière A, Storm AJ, Langemeyer JJ. Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting. Europ J Clin Microbiol Infect Dis. 1994; 13(12):1033–7. [PubMed: 7889965]
3.
Tamayo E, Gualis J, Florez S, Castrodeza J, Eiros Bouza JM, Alvarez FJ. Comparative study of single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery. J Thorac Cardiovasc Surg. 2008;136(6):1522–7. [PubMed: 19114201]
4.
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4.25. Advanced dressings

Recommendation

The panel suggests not using any type of advanced dressing over a standard dressing on primarily closed surgical wounds for the purpose of preventing SSI.

(Conditional recommendation/low quality of evidence)

Rationale for the recommendation

  • Advanced dressings used in the included studies were of the following types: hydrocolloid; hydroactive; silver-containing (metallic or ionic); and polyhexamethylene biguanide (PHMB) dressings. Standard dressings were dry absorbent dressings.
  • Low quality evidence from 10 RCTs shows that advanced dressings applied on primarily closed incisional wounds do not significantly reduce SSI rates compared to standard wound dressings. The GDG unanimously agreed that advanced dressings should not be used as a preventive measure to reduce the risk of SSI. Given the low quality of the evidence, the GDG decided that the strength of this recommendation should be conditional.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. However, the GDG considered this recommendation valid also for paediatric patients.
  • The GDG identified possible harms associated with the use of silver-containing dressings. Allergic reactions or skin irritations may develop in some patients (1).
  • Regarding ionic silver dressings, the GDG was concerned about the possible exposure of patients and health care workers to nanoparticles. It was also pointed out that microbial resistance to silver and PHMB may develop.
  • The GDG also highlighted that the availability of advanced dressings may be limited in LMICs and their purchase might represent a financial burden.
  • The GDG emphasized that dressings used on primarily closed surgical wounds should be sterile and should be applied with an aseptic technique.
  • The studies included did not investigate negative pressure dressings. pNPWT is dealt with in chapter 4.19 of these guidelines.

Background

The term “surgical wound” used in this document refers to a wound created when an incision is made with a scalpel or other sharp cutting device and then closed in the operating room by suture, staple, adhesive tape, or glue and resulting in close approximation to the skin edges. It is common practice to cover such wounds with a dressing. The dressing acts as a physical barrier to protect the wound from contamination from the external environment until the wound becomes impermeable to microorganisms. The dressing can also serve to absorb exudate from the wound and keep it dry.

A wide variety of wound dressings are available (web Appendix 26). Advanced dressings are mainly hydrocolloid or hydrogels or fibrous hydrocolloid or polyurethane matrix hydrocolloid dressings and vapour-permeable films.

A Cochrane review (2) and its update (3) of the effect of dressings for the prevention of SSI found no evidence to suggest that one dressing type was better than any others.

The UK-based NICE issued a clinical guideline for SSI prevention and treatment in 2008 which recommended covering surgical incisions with an appropriate interactive dressing at the end of the procedure (4). The 2013 evidence update of these guidelines suggests that no particular type of dressing emerges as the most effective in reducing the risk of SSI, although silver nylon dressings may be more effective than gauze.

The update recommends further research to confirm the effectiveness of modern types of dressing (5). Postoperative care bundles recommend that surgical dressings be kept undisturbed for a minimum of 48 hours after surgery unless leakage occurs. However, there are currently no specific recommendations or guidelines regarding the type of surgical dressing (68).

Following an in-depth analysis of the sources and strength of evidence in current guidelines and reviews, the GDG members decided to conduct a systematic review to assess the effectiveness of advanced dressings compared to standard surgical wound dressings for the prevention of SSI.

Summary of the evidence

The purpose of the evidence review (web Appendix 26) was to evaluate whether the use of advanced dressings is more effective in reducing the risk of SSI than standard wound dressings. The target population included patients of all ages undergoing a surgical procedures. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Ten RCTs (1, 917), including a total of 2628 patients, evaluated advanced dressings compared to standard dressings. Patients were adults undergoing sternotomy and elective orthopaedic, cardiac, vascular, plastic, abdominal and colorectal cancer surgical procedures. There were variations in the interventions as some studies used hydrocolloid, hydroactive and silver- or PHMB-impregnated dressings. In addition, there were variations in the definition of SSI and the duration of postoperative follow-up.

Despite the heterogeneity of the types of advanced dressings used in the selected studies, separate meta-analyses were performed to evaluate (1) an overall comparison of advanced vs. standard dressings, and (2) hydrocolloid or silver-impregnated or hydroactive or PHMB dressings vs. standard dressings.

Overall, there is low quality evidence that advanced dressings do not significantly reduce SSI rates compared to standard dressings (OR: 0.80; 95% CI: 0.52–1.23). In particular, compared to standard dressings, very low quality evidence showed neither benefit nor harm for hydrocolloid dressings (OR: 1.08; 95% CI: 0.51–2.28), silver-impregnated dressings (OR: 0.67; 95% CI: 0.34–1.30) and hydroactive dressings (OR: 1.63; 95% CI: 0.57–4.66). There is also low evidence for PHMB-containing dressings (OR: 0.20; 95% CI: 0.02–1.76).

The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. In addition, no studies reported SSI-attributable mortality rates.

Additional factors considered when formulating the recommendation

Values and preferences

There are many factors that may contribute to the preferences of surgeons and/or patients with regard to the use of particular dressings. Although no difference in SSI prevention was shown in the meta-analysis of 10 RCTs, other outcomes were reported in some studies. Two RCTs included in these analyses assessed patient comfort and reported that hydrocolloid dressings were more comfortable than standard dressings (16, 17). Another study reported better cosmetic results in patients whose incisions were dressed with hydrocolloid dressings compared to incisions covered with standard dressings, despite no SSI events in either group (13). It was acknowledged that patients may prefer a low frequency of dressing change.

Resource use

The cost and availability of advanced dressings may be a limitation, particularly in LMICs. The added cost of using hydrogel, hydrocolloid or silver-containing dressings has been investigated by several studies included in this review. Two studies reported fewer dressing changes for hydrogel dressings compared to standard dressings (10, 16). Although the hydrogel dressings were associated with a cost 2 to 5 times higher than standard dressings, they may be beneficial for patients unable to change dressings or requiring a return to hospital for subsequent dressing changes (16). One study attributed increased nursing time with standard dressings, which is a consideration for hospitals with a small nursing staff. Another study reported higher costs for hydrocolloid compared to standard dressings (17). In addition to cost, it may be difficult for some LMICs to acquire and properly use moist or metallic dressings. However, one study reported that hydrocolloid dressings were less complicated to apply (15).

Research gaps

It was emphasized that there are very few large, high-quality trials investigating different types of dressings with SSI prevention as a primary outcome.

Future clinical studies should focus on generating a large sample size and include blind outcome assessment. Well-designed studies conducted in LMICs are needed, as well as in the paediatric population. The GDG highlighted a special interest in investigating the use of silver-containing dressings in orthopaedic and cardiac surgery with regard to SSI prevention. Assessment of adverse events should be considered in the trials, including the possible effects of silver nanoparticles. In addition, it would be interesting to explore the comparison of opaque dressings with transparent ones in terms of postoperative visual examination and the duration of keeping the primary dressing in place, ultimately with regard to SSI prevention.

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Leaper D, Burman-Roy S, Palanca A, Cullen K, Worster D, Gautam-Aitken E, et al. Prevention and treatment of surgical site infection: summary of NICE guidance. BMJ. 2008;337. [PubMed: 18957455]
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Surgical site infection: evidence update 43 (June 2013) London: National Institute for Health and Care Excellence (NICE); 2013 (http://www​.nice.org.uk​/guidance/cg74/evidence​/evidence-update-241969645, accessed 25 July 2016).
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Owens P, McHugh S, Clarke-Moloney M, Healy D, Fitzpatrick F, McCormick P, et al. Improving surgical site infection prevention practices through a multifaceted educational intervention. Ir Med J. 2015;108(3):78–81. [PubMed: 25876299]
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High impact intervention; care bundle to prevent surgical site infection. London: Department of Health; 2011 (http://hcai​.dh.gov.uk​/files/2011/03/2011-03-14-HII-Prevent-Surgical-Site-infection-FINAL.pdf, accessed 25 July 2016).
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Biffi R, Fattori L, Bertani E, Radice D, Rotmensz N, Misitano P, et al. Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver. World J Surg Oncol. 2012;10:94. [PMC free article: PMC3407006] [PubMed: 22621779]
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Martin-Trapero C, Martin-Torrijos M, Fernandez-Conde L, Torrijos-Torrijos M, Manzano-Martin E, Pacheco-del Cerro JL, et al. [Surgical site infections. Effectiveness of polyhexamethylene biguanide wound dressings]. Enferm Clin. 2013;23(2):56–61. [PubMed: 23528546]
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4.26. Antimicrobial prophylaxis in the presence of a drain and optimal timing for wound drain removal

Recommendations

  1. The panel suggests that perioperative antibiotic prophylaxis should not be continued to the presence of a wound drain for the purpose of preventing SSI.
    (Conditional recommendation, low quality of evidence)
  2. The panel suggests removing the wound drain when clinically indicated. No evidence was found to recommend an optimal timing of wound drain removal for the purpose of preventing SSI.
    (Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Overall low quality evidence (from 7 RCTs) indicates that prolonged antibiotic prophylaxis in the presence of a wound drain has neither benefit nor harm in reducing SSI when compared to perioperative prophylaxis alone (single dose before incision and possible intraoperative additional dose/s according to the duration of the operation). Considering the lack of evidence that prolonged antibiotic prophylaxis prevents SSI and the possible associated harms (see below), the GDG unanimously agreed that antibiotic prophylaxis should not be continued in the presence of a wound drain. Given the low quality of the evidence, the strength of this recommendation was considered to be conditional.
  • Very low quality evidence (from 11 RCTs) shows that the early removal of wound drains has neither benefit nor harm in reducing the SSI rate when compared to late removal of drains (at postoperative day 6 or later). In particular, no benefit was shown when comparing early removal (from postoperative days 1 to 5) with removal on or after postoperative day 6. Results were also similar when comparing early removal with removal determined according to the volume of drainage. Considering the very low quality evidence and the finding that the body of evidence does not identify an optimal time point for wound drain removal with regard to the prevention of SSI, the GDG decided to suggest that the wound drain should be removed when clinically indicated. Given the very low quality of evidence, the strength of this recommendation was considered to be conditional.

Remarks

  • The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. However, the GDG considers this recommendation valid also for paediatric patients.
  • The GDG emphasized that the body of evidence does not identify an optimal time point of wound drain removal with regard to the reduction of SSI. Definitions for the early removal of drains varied across the studies from 12 hours to 5 days postoperatively. In addition, the definitions for the late removal of drains varied from removal when the drainage volume became minimal (that is, <30 or <50 mL/day) or at specific time points, such as postoperative days 2 to 10.
  • The GDG pointed out that the evidence on the optimal time for drain removal consists of studies that were done with closed wound drains. Therefore, the related recommendation refers to the use of closed wound drainage systems.
  • The available evidence on the optimal time for drain removal was limited to studies conducted in breast and orthopaedic surgery.
  • It was noted that the great majority of available studies on the topics of these recommendations were conducted in high- and middle-income countries; only one study is available from a low-income country.
  • The GDG identified possible harms associated with the prolonged duration of antibiotic administration, such as the selection and emergence of resistant bacteria, the risk of fungal superinfections and Clostridium difficile infection and side effects of antibiotics. Furthermore, early removal of the wound drain may be associated with possible postoperative complications, such as an increase of the occurrence of seroma and haematoma requiring treatment (1).
  • The GDG highlighted that wound drains are single-use devices and must not be reused.

Background

The use of drainage tubes in surgical wounds has a long history (2). Prophylactic placement postoperatively has been widely practiced since the mid-1800s with the dictum of Lawson Tait, the 19th century British surgeon, “When in doubt, drain”, well known to all surgical trainees. However, some studies have called into question the benefits of routine drainage (3, 4). It is even argued that drains might adversely affect surgical outcomes, for example, affecting anastomotic healing by causing infection in the anastomotic area and the abdominal wound (5, 6). Thirty-four systematic reviews investigating the effect of drains compared to no wound drainage in terms of the related infection risk in surgical patients have been published so far. A meta-review summarizing these reviews (web Appendix 27) demonstrated that most meta-analyses showed a tendency towards a beneficial effect of not using a wound drain with regard to a reduced risk of wound infection, but no significant differences were achieved.

The aim of drainage tubes is to remove any fluid or blood that may collect in the wounds and cavities created by the surgical procedure and thus may cause complications. When used, the optimal time for drain removal after surgery is still unknown. Drains are usually left in place until the amount of fluid draining out of them in a 24-hour period has reduced to a certain volume (typically less than 30 mL to 100 mL). However, some surgeons will remove the drains at a particular time point after surgery, which may vary from hours to more than a week. In most cases, antibiotic prophylaxis is continued postoperatively when a drain is used, but this practice is not evidence based.

With the presence of drainage tubes, the need for perioperative antibiotic prophylaxis and the optimal regimen requires further assessment and investigation given the dramatic increase in AMR worldwide. In recognition of the fact that AMR is now considered a major health problem, the implementation of global and national programmes to optimize the use of antibiotic agents in humans has been strongly urged by WHO (7).

There are currently no formal recommendations for antimicrobial prophylaxis in the presence of a drain or regarding wound drain removal for the prevention of SSI. Following an in-depth analysis of the resources and lack of recommendations from other guidelines, the GDG decided to conduct a systematic literature review on these topics.

Summary of the evidence

The purpose of the evidence review (web Appendix 27) was to evaluate whether prolonged antibiotic prophylaxis in the presence of a wound drain is more effective in reducing the risk of SSI than perioperative prophylaxis alone (single dose before incision and possible intraoperative additional dose/s according to the duration of the operation). The review evaluated also whether the early removal of wound drains is more effective than late removal to prevent SSI. The target population included patients of all ages undergoing a surgical operation with the presence of postoperative drainage. The primary outcome was the occurrence of SSI and SSI-attributable mortality.

Seven RCTs (814) were identified. They included a total of 1670 patients and investigated whether antibiotics should be administered preoperatively as a single dose and possibly re-dosed according to the duration of the operation, or if their administration should be extended to the postoperative period.

Three studies reported a prolonged antibiotic administration until the wound drain was removed (8, 9, 11). In the remaining 4 trials, patients received a 3-day (10, 14) or 5-day intravenous course (13). Patients enrolled in the studies underwent general surgery (810, 14), kidney transplantation (11) and pilonidal sinus surgery (13). One trial (12) determined whether prolonged antibiotic prophylaxis reduced the risk of infectious complications for patients undergoing elective thoracic surgery with tube thoracostomy. The antibiotic was continued for 48 hours after the procedure or until all thoracostomy tubes were removed, whichever came first.

There is low quality evidence that prolonged antibiotic prophylaxis in the presence of a wound drain has neither benefit nor harm in reducing SSI when compared to perioperative prophylaxis alone (OR: 0.79; 95% CI: 0.53–1.20).

Eleven RCTs (1, 1524) including a total of 1051 patients and comparing early vs. late removal of drainage were identified. Nine studies investigated the duration of drains in patients undergoing mastectomy (1, 1522) and 2 studies after hip or knee arthroplasty (23, 24). Study definitions for early drain removal varied from removal at 12 hours, 24 hours and 48 hours to 3, 4 or 5 days postoperatively. Late removal was either defined as removal when the drainage volume became minimal (that is, <30 mL/day or <50 mL/day) or as specific time points, such as postoperative days 2, 6, 8 and 10. One trial (24) compared 3 different time points of drain removal (12 hours, 24 hours and 48 hours).

Despite this heterogeneity, two subgroup analyses were performed based on two main classifications for the indication of late wound drain removal, that is, specific time points with drain removal at postoperative day 6 or later (3 studies (17, 19, 22)) and drainage volume (6 studies (1, 15, 16, 18, 20, 21)). Early removal was considered to be from postoperative days 1 to 5. Therefore, 2 studies that compared drain removal at postoperative day 1 vs. postoperative day 2 (23) and 12 hours/24 hours vs. postoperative day 2 (24) were not included in the subgroup comparisons.

There is very low quality evidence that the early removal of wound drains has neither benefit nor harm in reducing the SSI rate when compared to late removal (OR: 0.86; 95% CI: 0.49–1.50). When this comparison was sub-classified by late removal at specific time points (postoperative day 6 or later) and drainage volume, the results remained unchanged (OR: 0.63; 95% CI: 0.07–5.70 and OR: 0.93; 95% CI: 0.51–1.70, respectively).

The body of retrieved evidence focused on adult patients and no study was available in the paediatric population. The literature search did not identify any studies that reported on SSI-attributable mortality.

Additional factors considered when formulating the recommendation

Values and preferences

The GDG is confident that most patients do not wish to receive prolonged antibiotic prophylaxis to reduce SSI in the absence of good evidence for a benefit, including the possibility of potential harms, such as the development of AMR, antimicrobial-related adverse events and C. difficile infection.

The GDG acknowledged that wound drains are uncomfortable and inconvenient for patients. One survey showed that patients prefer early wound drain removal (15). Even patients who developed seromas requiring aspiration indicated their preference for early removal with a return to hospital for further aspiration if necessary. In one trial on mastectomy, Barton and colleagues (1) reported that early drain removal increased the occurrence of seromas requiring treatment and this trial was even halted because of the significantly higher rate of adverse events in the early removal group.

Resource use

The GDG noted that the availability of antibiotics might be limited, particularly in LMICs. The additional costs of prolonged antibiotic prophylaxis in the presence of a wound drain, including the acquisition of wound drains, may represent not only a financial burden to the health system/medical centre in low-resource settings, but also to the patients themselves. The GDG emphasized that there is a need to raise awareness and education on the rational use of antibiotics and antibiotic stewardship among both health care workers (surgeons in particular, with reference to this recommendation) and patients. Early removal of drains may shorten hospital length of stay and therefore lead to cost savings (22).

Research gaps

GDG members highlighted that the available evidence on the time point of wound drain removal is limited to the fields of breast and orthopaedic surgery only. The GDG observed that the number of studies evaluating specific time points is very limited and there is therefore a need for RCTs to focus on specific time points for drain removal, rather than on drainage volume. All future studies should use SSI as the outcome, defined according to CDC criteria, and report any adverse events related to the time of drain removal. There is a need also for well-designed RCTs, especially in orthopaedic joint replacement and cardiac surgery. All included studies were in adult patients and more research is required to investigate the benefit of early drain removal in paediatric populations and among neonates. The great majority of the available evidence comes from high- and middle-income countries and more studies in low-income countries are required.

References

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Moss JP. Historical and current perspectives on surgical drainage. Surg Gynecol Obstet. 1981;152(4):517–27. [PubMed: 7010645]
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Berliner SD, Burson LC, Lear PE. Use and a buse of intraperitoneal drains in colon surgery. Arch Surg. 1964;89:686–9. [PubMed: 14186803]
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Smith SR, Connolly JC, Crane PW, Gilmore OJ. The effect of surgical drainage materials on colonic healing. Br J Surg. 1982;69(3):153–5. [PubMed: 7066655]
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Tenover FC, Hughes JM. WHO Scientific Working Group on monitoring and management of bacterial resistance to antimicrobial agents. Emerg Infect Dis. 1995;1(1):37. [PMC free article: PMC2626819] [PubMed: 8903156]
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Becker A, Koltun L, Sayfan J. Impact of antimicrobial prophylaxis duration on wound infection in mesh repair of incisional hernia – preliminary results of a prospective randomized trial. Europ Surg. 2008;40(1):37–40.
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Hall JC, Christiansen KJ, Goodman M, Lawrence-Brown M, Prendergast FJ, Rosenberg P, et al. Duration of antimicrobial prophylaxis in vascular surgery. Am J Surg. 1998;175(2):87–90. [PubMed: 9515521]
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Orlando G, Manzia TM, Sorge R, Iaria G, Angelico R, Sforza D, et al. One-shot versus multidose perioperative antibiotic prophylaxis after kidney transplantation: a randomized, controlled clinical trial. Surgery. 2015;157(1):104–10. [PubMed: 25304836]
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Oxman DA, Issa NC, Marty FM, Patel A, Panizales CZ, Johnson NN, et al. Postoperative antibacterial prophylaxis for the prevention of infectious complications associated with tube thoracostomy in patients undergoing elective general thoracic surgery: a double-blind, placebo-controlled, randomized trial. JAMA Surg. 2013;148(5):440–6. [PubMed: 23325435]
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Seker D, Ugurlu C, Ergul Z, Akinci M. Single dose prophylactic antibiotics may not be sufficient in elective pilonidal sinus surgery: An early terminated study. Turk Klin J Med Sci. 2011;31:186–90.
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Suzuki T, Sadahiro S, Maeda Y, Tanaka A, Okada K, Kamijo A. Optimal duration of prophylactic antibiotic administration for elective colon cancer surgery: A randomized, clinical trial. Surgery. 2011;149(2):171–8. [PubMed: 20655559]
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Ackroyd R, Reed MR. A prospective randomized trial of the management of suction drains following breast cancer surgery with axillary clearance. Breast. 1997;6:271–4.
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Baas-Vrancken Peeters MJ, Kluit AB, Merkus JW, Breslau PJ. Short versus long-term postoperative drainage of the axilla after axillary lymph node dissection. A prospective randomized study. Breast Cancer Res Treat. 2005;93(3):271–5. [PubMed: 16172795]
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Clegg-Lamptey JN, Dakubo JC, Hodasi WM. Comparison of four-day and ten-day post-mastectomy passive drainage in Accra, Ghana. East Afr Med J. 2007;84(12):561–5. [PubMed: 18402307]
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Dalberg K, Johansson H, Signomklao T, Rutqvist LE, Bergkvist L, Frisell J, et al. A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer. Europ J Surg Oncol. 2004;30(6):602–9. [PubMed: 15256232]
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Gupta R, Pate K, Varshney S, Goddard J, Royle GT. A comparison of 5-day and 8-day drainage following mastectomy and axillary clearance. Europ J Surg Oncology. 2001;27(1):26–30. [PubMed: 11237488]
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Inwang R, Hamed H, Chaudary MA, Fentiman IS. A controlled trial of short-term versus standard axillary drainage after axillary clearance and iridium implant treatment of early breast cancer. Ann R Coll Surg Engl. 1991;73(5):326–8. [PMC free article: PMC2499493] [PubMed: 1929138]
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Kopelman D, Klemm O, Bahous H, Klein R, Krausz M, Hashmonai M. Postoperative suction drainage of the axilla: for how long? Prospective randomised trial. Eur J Surg. 1999;165(2):117–20; discussion 21–2. [PubMed: 10192568]
22.
Parikh HK, Badwe RA, Ash CM, Hamed H, Freitas R, Jr., Chaudary MA, et al. Early drain removal following modified radical mastectomy: a randomized trial. J Surg Oncol. 1992;51(4):266–9. [PubMed: 1434659]
23.
Strahovnik A, Fokter SK, Kotnik M. Comparison of drainage techniques on prolonged serous drainage after total hip arthroplasty. J Arthroplasty. 2010;25(2):244–8. [PubMed: 19056215]
24.
Zamora-Navas P, Collado-Torres F, de la Torre-Solis F. Closed suction drainage after knee arthroplasty. A prospective study of the effectiveness of the operation and of bacterial contamination. Acta Orthop Belg. 1999;65(1):44–7. [PubMed: 10217001]
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