Abbreviations

IV

intravenous

SR

systematic review

Literature Search Methods

This report is an update of a literature search strategy developed for a previous CADTH report.⁸ For the current report, a limited literature search was conducted on key resources including MEDLINE, the Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused internet search. No filters were applied to limit the retrieval by study type. The initial search was limited to English-language documents published between January 1, 2015 and January 8, 2020. For the current report, database searches were rerun on September 14, 2020 to capture any articles published since the initial search date. The search of major health technology agencies was also updated to include documents published since January 2020.

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Table 1

Selection Criteria.

Exclusion Criteria

Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to 2015. Systematic reviews in which all relevant studies were captured in other more recent or more comprehensive systematic reviews were excluded. Primary studies retrieved by the search were excluded if they were captured in one or more included systematic reviews. Guidelines with unclear methodology were also excluded. Studies using combination IV and oral or nasogastric tube supplementation, or IV supplementation preceding a different route of administration with no separate results presented for IV supplementation alone were excluded.

Critical Appraisal of Individual Studies

The included publication was critically appraised by one reviewer using A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)⁹ as a guide. Summary scores were not calculated for the included study; rather, the strengths and limitations of the included publication were described narratively.

Quantity of Research Available

A total of 396 citations were identified in the literature search, 382 from the original Reference List search,⁸ and 14 from the updated search. Following screening of titles and abstracts, 390 citations were excluded and six potentially relevant reports from the electronic search were retrieved for full-text review. Of these potentially relevant articles, five publications were excluded for various reasons, and one publication met the inclusion criteria and was included in this report. This comprised one systematic review (SR).¹⁰ Appendix 1 presents the PRISMA¹¹ flowchart of the study selection.

The original CADTH Reference List⁸ included Rehou et al¹² as a potentially relevant article based on screening the abstract alone, however upon review of the full text, it was excluded due to the intervention including an IV supplement preceding a enterally administered supplement, without separate results presented for IV supplementation alone. This enteral supplementation was not clear in the abstract. The inclusion of oral supplementation in the intervention group, initiated after the IV supplementation and not matching the oral supplementation provided to the control group, makes it not possible to determine how much effect was driven by the IV supplementation alone. Therefore, a conclusion regarding IV supplementation was not possible.

Summary of Study Characteristics

Additional details regarding the characteristics of included publications are provided in Appendix 2.

One SR¹⁰ was identified with relevance to the research questions, but did not include any relevant primary studies. It was published in 2016 in the Cochrane Database of Systematic Reviews. The SR is the seventh update of a review first published in 2000 and was published by authors from the UK, including randomized and quasi-randomized trials.¹⁰

The scope of the SR was all nutritional interventions for older patients within the first month of experiencing a hip fracture. This was broader than the scope of this Rapid Response report, but the search and inclusion criteria included IV multivitamin interventions, so it was eligible for this review.¹⁰ In the included SR, the eligible articles focused on older people recovering from any type of hip fracture, not including trials focusing on young populations, people with multiple traumas, or people with pathological fractures.¹⁰ The interventions of interest in the included SR were multi-nutrient supplements given orally, enterally or through IV, or dietetic assistance. The eligible comparators were supplements containing less or none of these components, lower doses, placebo or no treatment.¹⁰ Outcomes that were eligible for inclusion in the relevant SR¹⁰ were mortality, morbidity, complications, length of stay in care, quality of life and functioning, healing of the fracture, care required and carer burden, and economic outcomes. However, none of the included studies in this SR were specific to the intervention of interest for this report, (i.e., none evaluated IV multivitamin supplementation alone).

Summary of Critical Appraisal

Additional details regarding the strengths and limitations of included publications are provided in Appendix 3.

The included SR¹⁰ was a high-quality review following Cochrane SR methods, with a prior published protocol. It had adequate reporting of included studies and methods, a comprehensive and thorough search strategy, and two independent assessors evaluated the data and performed study selection. One methodological limitation of the report was the reasoning for the decision to include only randomized and quasi-randomized trials was not provided.¹⁰

Summary of Findings

Limitations

This review was limited by the scarcity of articles examining IV multivitamin supplementation alone, as it does not appear to be a frequently examined route of administration in the literature in comparison to other routes of administration, such as orally or enterally administrated multivitamins. This may be because nutrient supplementation in patients who can swallow is more likely to be done orally, as IV and nasogastric supplementation is often indicated for severely malnourished patients in which oral supplementation is inadequate.¹⁰ There were some studies identified that examined combination IV and oral therapies. Finally, no evidence-based guidelines were identified.

Conclusions and Implications for Decision or Policy Making

One SR¹⁰ was identified with a scope broad enough to include potentially relevant studies, however this SR did not include any primary studies that met eligibility criteria for this review. Therefore, no conclusion can be provided regarding IV multivitamin or micronutrient supplementation for patients with malabsorption issues, patients who underwent surgery, and patients with burns, trauma, intoxication, or serious infectious diseases in a hospital or outpatient setting.

No evidence-based guidelines were identified with relevance to the research questions. However, one expert consensus paper and one recommendation paper with unclear methodology^2,5 were identified regarding adult patients and regarding alcohol-associated vitamin and electrolyte deficiencies, respectively. One article recommends IV micronutrient supplementation in some specific cases (i.e., specific losses, increased oxidative stress, and insufficient enteral intakes in inflammatory patients)² and one article suggests not providing the classic “banana bag” for patients admitted to the intensive care unit with symptoms either mimicking or masking Wernicke’s encephalopathy, instead suggesting an alternative IV formulation.⁵ However, the methodology for the development of these statements was unclear, and these recommendations were not graded, and therefore the methods were not considered to be rigorous enough to constitute an evidence-based guideline. These statements should be interpreted with caution.

Both this report and the original Reference List published in 2020⁸ specifically examined IV multivitamin supplementation. However, this report differs from the original Reference List published in 2020, as the Reference List included a non-randomized study in the main body that appeared relevant based on the abstract.⁸ Upon examination of the full text, it was determined that this report was not eligible for inclusion in the current review as the results were reported after patients had received both IV supplementation and oral supplementation.¹² This was not clear in the abstract.

Overall, the effectiveness of IV multivitamin or micronutrient supplementation in post-surgical patients or in patients with malabsorption issues, burns, trauma, intoxication, or serious infectious diseases is unclear. Future primary research may include IV supplementation alone for patients who are not on total parenteral nutrition, or reviews that include combination IV and oral therapies, as this may reflect another method of nutrient supplementation that may be more common in clinical practice. Therefore, decision-making and policy changes around the use of IV multivitamin supplementation may need to consider combination therapies as a potential practice of relevance.