INTRODUCTION

Every 15 seconds someone suffers a traumatic brain injury (TBI) in the United States. TBI causes more deaths in males <35 years old than all other diseases combined, and it is estimated that 2% of the U.S. population lives with TBI-associated disability. Despite extensive research and success in animal studies, successful drug therapies have proved elusive in clinical trials.¹ Instead, TBI care focuses on the early identification and removal of mass lesions and on the detection, prevention, and management of secondary brain insults that adversely affect outcome (e.g., hypotension, hypoxia, seizures, elevated intracranial pressure). TBI is a heterogeneous disease in cause, pathology, severity, and prognosis. Consequently, TBI care depends in large part on careful and repeated assessment of clinical and laboratory findings, imaging studies, and bedside physiological data.

A variety of physiological processes can be monitored at the bedside.² Traditionally, monitoring and treating intracranial pressure (ICP) that is also used to quantify cerebral perfusion pressure (CPP) has been the cornerstone of severe TBI (sTBI) management, in large part because ICP is considered an indicator of injury severity. In this chapter, the indications, technique, and safety for ICP monitoring will be discussed. In addition, we will examine the relationship between ICP and outcome, treatment thresholds, ICP management, and how ICP management influences outcome. Finally, though ICP and CPP are important, emerging evidence suggests ICP is better viewed as an indicator of an underlying pathophysiological process that needs treatment rather than an independent target. The chapter will finish with a brief discussion on how a multimodal approach may supplement the information obtained from ICP monitoring to better target and individualize care. The focus of this chapter is on adults with TBI and may not apply to pediatric TBI.

INDICATIONS FOR INTRACRANIAL PRESSURE (ICP) MONITORING

The Guidelines for the Management of Severe TBI recommend an ICP monitor in TBI patients at risk for intracranial hypertension, i.e., patients in coma (Glasgow Coma Scale [GCS] <8) and an abnormal admission head CT scan.³ This includes a mass lesion(s), e.g., hematoma or contusion, swelling (edema), midline shift, and compressed basal cisterns, particularly the perimesencephalic cisterns.^4–6 However, up to 50% of patients who subsequently develop increased ICP may have a normal admission head CT scan.⁷ In these patients, an ICP monitor is recommended if two or more of the following are present at admission: age >40 years, unilateral or bilateral motor posturing, or episodes of systolic blood pressure (BP) <90 mmHg.³ These recommendations however are based on studies that included small numbers of patients and were performed 20–30 years ago using older generation CT scanners that may have been insensitive to pathology that can be identified now.^8,9

The indications for an ICP monitor remain debated in several circumstances, including (a) comatose patients with an initial normal CT scan or only minimal findings, e.g., traumatic subarachnoid hemorrhage (SAH); (b) diffuse axonal injury (DAI); (c) bifrontal contusions in the noncomatose patient; and (d) following surgery such as a decompressive craniectomy or evacuation of a mass lesion. These topics were addressed in a recent consensus conference on ICP with the following conclusions.¹⁰ First, invasive ICP monitoring is not recommended in comatose patients with an initial normal CT scan or only minor changes, e.g., small petechiae, particularly if the scan is obtained early after injury. These patients should undergo a follow-up CT scan, particularly if there is neurologic worsening, and receive an ICP monitor if there is disease progression on the CT scan. Second, an ICP monitor is indicated when the CT shows evidence of brain swelling, e.g., compressed or absent basal cisterns.⁵ Third, an ICP monitor may be considered in patients with large bifrontal contusions independent of the neurological condition.¹¹ Fourth, an ICP monitor is recommended when sedation interruption to check neurological function may be dangerous, e.g., respiratory failure. Similarly an ICP monitor is useful when the neurological examination is not reliable, e.g., maxillofacial trauma or spinal cord injury. Fifth, elevated ICP may occur after a decompressive craniectomy performed in a delayed fashion for intracranial hypertension refractory to medical management.¹² ICP monitoring is recommended in these patients. Finally, intracranial hypertension is common in patients who undergo a craniotomy for a mass lesion, particularly an acute subdural hematoma, and when present, intracranial hypertension aggravates outcome.^13,14 Consequently an ICP monitor is recommended after a craniotomy particularly when there are other associated factors, e.g., hypoxia, hypotension, pupil abnormalities, midline shift >5 mm, brain swelling at surgery, and when patients may require other surgeries for extracranial injuries. However, the role of an ICP monitor in patients whose bone flap is left out at this initial surgery is uncertain but may be clarified by the proposed RESCUE-acute subdural hematoma trial.¹⁵

In the intensive care unit, ICP is best treated guided by an ICP monitor since it is difficult to diagnose elevated ICP by clinical means alone. The introduction of clinical guidelines for sTBI has increased the use of ICP monitoring,¹⁶ however, there still is great variability in care and as many as half the patients who fulfill the criteria for an ICP monitor never receive one.^17,18 Meta-analysis of clinical series or analysis of administrative data suggests that “aggressive care,” including an increase use of ICP monitors is associated with improved outcome.^18–22 Furthermore, use of an ICP monitor improves the efficiency of care²³ and decision analysis indicates that when all the costs of sTBI are considered, aggressive care including multimodal monitoring is cost-effective, even for older patients.²⁴

ICP MONITORING TECHNIQUES

A variety of techniques can be used to monitor ICP including clinical examination, brain imaging, and an ICP monitor, both invasive and noninvasive monitors.² The best results are obtained when all three techniques are used. Technology evaluation is not ideally suited to evidence-based medicine, but the literature suggests that a ventricular catheter connected to an external strain gauge, catheter tip strain gauge devices, or catheter tip fiber optic technology inserted into the ventricles or brain parenchyma are accurate, whereas fluid-coupled or pneumatic devices placed in the subarachnoid, subdural, and epidural compartments are less accurate. Noninvasive methods, e.g., optic nerve sheath diameter or transcranial Doppler ultrasound pulsatility index among others are promising but as yet not robust enough or validated for regular clinical use.²⁵ These noninvasive techniques however may be used in select patients, e.g., those with coagulopathy.

Today, two techniques, an intraparenchymal strain gauge or fiber optic monitor and an intraventricular monitor using a ventriculostomy (EVD), are in common use and the preferred and recommended techniques.²⁶ The EVD is considered the gold standard, but this is more a matter of precedence and tradition since it was the first monitor available and for many years the only technology available rather than the result of scientific comparison or physiology. Proponents for ventricular catheters argue that cerebrospinal fluid (CSF) can be drained and hence ICP reduced. This may be true when there is hydrocephalus, but in other patients CSF drainage may alter compliance with adverse effects. Ventricular catheters are also thought to represent a “global” ICP and not be subject to local variation. While there are gradients between parenchymal and ventricular systems, none of these are of clinical significance.^27,28 Parenchymal monitors are easier to insert, e.g., insertion is not influenced by midline shift or brain swelling, and easier to use, e.g., not subject to blockage by hemorrhage or debris.

The choice of whether to use an EVD or parenchymal monitor is best decided on a case-by-case basis and factors such as pathology, presence of coagulopathy, device accuracy, reliability, complication rates, ease of insertion, and cost among others need to be considered. In the presence of hydrocephalus, however, an EVD is preferred because it can also be used for treatment.^26,29

SAFETY OF ICP MONITORING

There are several potential complications associated with ICP monitors and, in particular, brain hemorrhage, infection, and technical failure. The overall risk of clinically significant complications is low. However, almost all studies describe a greater complication rate when using EVDs rather than parenchymal monitors.^30–33

ICP AND OUTCOME

ICP is a valuable indicator of injury severity after TBI and there is a well-described relationship between intracranial hypertension (although the definition of this varies) and mortality after sTBI (Table 15.1).^8,50–54 This relationship becomes proportionally greater as the value of ICP increases with a sixfold increase risk of death when ICP is greater than 40 mmHg.⁵⁰ While brief episodes of elevated ICP can adversely affect outcome,⁵⁵ the relationship between ICP and mortality is greater when the pattern of elevation, e.g., early vs. late intracranial hypertension,^56,57 the “dose” of intracranial hypertension, and treatment response is included in the analysis.^50,58–60 In particular elevated ICP that is refractory to treatment significantly increases the risk of death.^8,50,61,62 In addition, using continuous dynamic ICP information improves the accuracy of outcome prediction.⁶³ The relationship between ICP and morbidity and overall outcome, however, is less robust and most studies find no association between ICP and morbidity.^{50,52,53,64,65}

TABLE 15.1

Relationship (Odds Ratio and 95% Confidence Interval) between Intracranial Pressure Values and Patterns and Outcome (1-Year Glasgow Outcome Score [GOS]) after Severe TBI

The implication of these various data is that ICP, as a simple numeric value or a single threshold, is not an independent outcome predictor, i.e., when used to predict outcome the ICP data should be interpreted with clinical and demographic characteristics, CT findings, and other physiologic data. It should be remembered, however, that these studies are confounded by treatment and decisions on futility and are not true natural history studies. Furthermore, the analysis frequently includes manually entered end hour values and uses linear statistics that may be insensitive to any potential relationship. Indeed when using more sophisticated analysis techniques, e.g., automated data and area under the curve (AUC) analysis, an independent relationship between ICP and outcome is observed.^58,66 Finally, the relationship between ICP and outcome is based on population-derived targets. Recent studies suggest that individualized or patient-specific targets may provide a more robust relationship. For example, Lazardis et al.⁶⁷ retrospectively analyzed data from 327 sTBI patients and defined individualized ICP thresholds by graphing the relationship between ICP and pressure reactivity index (PRx). They observed that individualized doses of intracranial hypertension were stronger predictors of death than doses derived from universal thresholds of 20 and 25 mm Hg (Table 15.2).

TABLE 15.2

Logistic Regression for ICP Doses and Receiver Operating Characteristic (ROC) Analysis of Predictive Power for Mortality in Severe TBI Patients

WHAT IS THE OPTIMAL ICP TREATMENT THRESHOLD?

Several different ICP thresholds, including 15,^54,68 20,^62,69 25,⁷⁰ and 35 mmHg⁷¹ are described in the literature and used in clinical practice, i.e., what defines intracranial hypertension is uncertain. There are many reasons for this. First, there are no natural history studies that relate outcome to nontreated ICP in TBI. Second, described thresholds are population based rather than individualized. Third, general protocol effects, ongoing threshold-driven treatment, and futility decisions often confound the data. Fourth, sTBI has yet to be categorized on the basis of underlying pathophysiology and phenotype and so ICP treatments are empiric and phenomenological rather than mechanistic. Fifth, much of our current practice stems from research performed in the 1960s to the late 1990s under conditions that are not relevant today. During that time there was concern that systolic blood pressure (SBP) drove intracranial hypertension. Consequently patients were kept “dry,” i.e., with mean arterial blood pressures (MABP) <70 mmHg. The normal autoregulatory breakpoint is at 50 mmHg and hence patients were considered at risk for cerebral ischemia when ICP was >20 mmHg. This then was adopted as a “threshold.” Today however, we usually maintain a higher CPP (>60–70 mmHg) and use sedatives that reduce the risk of cerebral ischemia when CPP is <50 mmHg. Sixth, physiologic monitors in use today, e.g., brain oxygen, microdialysis, and PET among others, demonstrate that brain energy dysfunction may occur when ICP is normal or that the brain is “healthy” despite an elevated ICP.^72–74 This has led to the concept of permissive intracranial hypertension, i.e., does it matter what the ICP is (if mildly elevated, e.g., 25 mmHg) if other measures of brain health or CPP are normal? Consequently, rather than accept a generic or absolute ICP threshold, e.g., 20 mmHg, it may be preferable to individualize thresholds based on patient characteristics, pathology, other physiologic parameters, and on a risk-benefit analysis of treating the specific ICP. Conceptually, ICP values then become an epiphenomenon of cerebral compliance, ischemia, hypoxia, cellular dysfunction, or the likelihood of herniation among other pathophysiological processes. This requires multimodal monitoring that in its simplest form means interpreting the ICP value according to the clinical and CT findings or in a more sophisticated approach using other physiologic parameters as well.^75,76 This can be challenging and requires further research validation, and so for the present, it is reasonable to set the treatment threshold at 20–25 mm Hg at the onset of management but consider altering the threshold when other clinical data support this.⁷⁷

MANAGEMENT OF INCREASED ICP

Severe TBI management is centered on avoiding increased ICP or providing an adequate CPP. An alternative to this treatment is the Lund concept, which emphasizes a reduction in microvascular pressures. However, there is no evidence that the Lund concept is a “better” treatment option.⁷⁸ Central to these approaches is use of an ICP monitor that can help guide medical and surgical therapy for sTBI; the use of which appears to improve the efficiency of care. Traditionally ICP management has followed serial box-and-arrow diagrams or stair step-type protocols.^79,80 This linear approach is based on how a specific therapy alters ICP rather than a specific pathophysiological mechanism, i.e., the treatment is largely empiric and phenomenological. This then assumes all patients with increased ICP are the same and the only difference is the resistance or response to treatment. Deleterious side effects may be observed with all ICP treatments and this linear approach generally starts with what is assumed to be the least deleterious approach and moves along the pathway to potentially more deleterious treatments. However, the propensity to harm through treatment based on the ICP is not well substantiated in the literature.^22,81 More recently, therapy for increased ICP has taken a tiered approach with several therapies grouped together.^82,83

Potential reasons why ICP may be increased after TBI are listed in Table 15.3. The therapies for increased ICP using a tiered approach are empiric and include strategies such as sedation and analgesia, hyperosmolar agents (mannitol or hypertonic saline [HTS]), CSF drainage, induced hypocarbia, barbiturates, temperature modulation, and surgery including evacuation of mass lesion or decompressive craniectomy. These various therapies and guideline adherence, their efficacy, comparisons, and cost effectiveness in lowering ICP have all been well studied, although rigorous Level I evidence is lacking on an outcome effect. The reader is referred elsewhere for recent details and reviews.^{20,79,82–93} Methodological issues and how data is collected need to be considered. For example, manually recorded ICP data can overestimate treatment effectiveness. Instead automated data collection may provide a more accurate assessment of treatment response.⁸⁴ With the advent of multimodality monitoring and better understanding of sTBI pathophysiology, newer therapies such as repeated boluses of HTS, hyperbaric oxygen (HBO2), normobaric hyperoxia (NBH), and lactate infusions have also been used to treat increased ICP in the clinical environment.^94–96

TABLE 15.3

Possible Causes of Increased ICP after TBI

DOES ICP MANAGEMENT INFLUENCE PATIENT OUTCOME?

Clinical studies of whether treating ICP enhances outcome are confounded by many variables, some of which are methodological, e.g., how was ICP recorded, how was ICP data analyzed, what defines intracranial hypertension, how are ICP elevations treated, and how were decisions about futility made among others. TBI also is heterogeneous, and select rather than all patients, e.g., intracranial hematoma vs. diffuse axonal injury, benefit from ICP treatment. Furthermore, since there is good evidence that elevated ICP and mortality is associated, no randomized clinical trial (RCT) in which participants undergo ICP monitoring and some receive targeted treatment and others do not has been performed, and for ethical reasons, will likely never be performed. The BEST TRIP trial was a multicenter RCT conducted in general ICUs in Bolivia and Ecuador that included 324 patients >13 years old who had severe TBI that attempted to examine ICP monitor use.²³ Two strategies of care for severe TBI (and not ICP) were examined. An ICP monitor triggered one strategy, although care varied from established guidelines and the other was a novel strategy developed specifically for the trial that was triggered by CT and clinical examination. A similar outcome was observed in the two groups, which is not unexpected since there is no control group. In addition, many patients never developed increased ICP, i.e., BEST TRIP was not a trial of ICP monitoring or a trial of ICP management. The trial also lacks external validity and so should not alter clinical practice. It has, however, prompted research questions about TBI and ICP management.⁷⁶

Attempts to answer how ICP management influences outcome have been examined using several methodologies, e.g., within-institution protocol studies, center-based studies, analyses of trauma or TBI registries, meta-analysis of clinical series, quality-assurance studies, or comparative effectiveness. In large part, these studies are not studies of ICP treatment per se but rather studies of “aggressiveness of care” that includes ICP treatment or guideline adherence that usually is defined by ICP monitor use. The data then are confounded by variable care and management decisions, e.g., whom to monitor. Despite this and a variable case mix, the vast majority of studies demonstrate a significant benefit to outcome, particularly mortality when TBI management protocols based in part on ICP monitoring are initiated or used.^{18,19–22,93,97–103} For example, Alali et al.¹⁸ analyzed 10,628 adults with severe TBI derived from 155 centers in the American College of Surgeons Trauma Quality Improvement Program (TQIP). There was great variability in ICP monitoring rates. Hospitals with higher rates of ICP monitoring use were associated with lower mortality. The adjusted OR of death was 0.52 (95% CI, 0.35–0.78) in the quartile of hospitals with highest use, compared to the lowest.

Rather than examine ICP monitor use or guideline adherence, several studies have examined outcome based on the response of increased ICP to treatment using either first- or second-tier therapies. This may be a better method to examine whether ICP treatment makes a difference. Treggiari et al.⁵⁰ combined data from several observational studies and observed an association between better outcome and treatment response. Similarly, Farahvar et al.²² in a prospective TBI database of 388 patients observed that a response to treatment was independently associated with less mortality at 14 days. Data from RCTs that examine second-tier therapies, e.g., barbiturates, hypothermia also suggest that a treatment response is associated with reduced mortality.^104,105 However DECRA, an RCT of bifrontal decompressive craniectomy versus maximal medical therapy for early intractable hypertension, observed similar morality despite better control of ICP in the surgical group.¹⁰⁶ However, outcome was not analyzed by response to treatment in DECRA and the definition of intractable hypertension was very different from what is usually used in clinical practice.

A handful of studies have observed similar 12-month outcomes despite more ICP treatment,¹⁰⁷ or that ICP monitoring is associated with worse risk-adjusted hospital mortality or increased complications, e.g., pneumonia, renal failure, and infections.^108,109 These reports and the BEST TRIP trial,²³ although it lacks external validity and is not a trial of ICP per se, have made some clinicians question the usefulness of ICP monitoring. However, when all the data are taken together it appears that use of an ICP monitor is associated with reduced mortality and at least associated with more efficient care. Furthermore, successful treatment of intracranial hypertension is associated with better outcome than observed in patients who are refractory to treatment. The clinical implication of this is that ICP monitoring is necessary (who would treat blood pressure without a blood pressure cuff) and that treatment of increased ICP is beneficial. The few dissenting publications should not lead to questions of ICP monitor use in toto but rather indicate that more research is needed to better define: (a) which patients should be monitored; (b) what is intracranial hypertension and does it vary depending on patient or patient pathology; (c) is there a specific ICP level that is deleterious and is it always harmful; (d) is increased ICP as a numeric threshold simply a marker of an underlying pathophysiological process that requires specific (and mechanistic) treatment rather than an independent target; and (e) how should we best treat increased ICP among others? Perhaps the most important implication of these “negative” studies, given the preponderance of data to the contrary is that ICP treatment when a numerical threshold is breached may be an oversimplification of a complex and heterogeneous pathophysiology and that how we treat ICP requires a conceptual shift.

TOWARD A NEW CONCEPT OF ICP TREATMENT

ICP Is More than a Number

At present ICP is treated primarily for two main reasons: to prevent herniation and to preserve cerebral blood flow (CBF), i.e., prevent ischemia. Simply treating a numeric threshold, which is population derived, does not allow therapy to be targeted to an individual and generally is reactive rather than proactive. The Monro-Kellie doctrine (intracranial volume [v; constant] = v.brain + v.CSF + v.blood + v.mass lesion) provides the conceptual framework on which current ICP treatment is based. However, this doctrine describes more than a threshold since it indicates that the brain is also able to compensate for a volume increase in one of the compartments with volume changes in the others. When these compensatory mechanisms fail, a small volume change can cause a significant ICP increase or even herniation. This compensatory reserve or compliance is important since a patient with poor compliance is at much greater risk than one with good compliance even if their ICP was normal and hence management is potentially different. Compliance can be quantified by a volume challenge through an EVD, i.e., the volume-pressure response (VPR = ICP change/volume change). Logarithmic conversion of the VPR defines the volume that would produce a tenfold ICP increase, i.e., pressure-volume index (PVI). The normal PVI is between 25 and 30 mL.¹¹⁰ Rather than inject fluid through an EVD with its attendant risks, compliance is better estimated from ICP waveform analysis or with derived indices such as the index of pressure-volume compensatory reserve (RAP), defined as the correlation coefficient (R) between the pulse pulsation amplitude (A) and mean ICP (P).¹¹¹ The RAP index varies between −1 and +1; higher values indicate less compliance. There are three prominent wavelets in the normal ICP waveform, labeled P1, P2, and P3. P1 is the largest wavelet but as compliance decreases, the amplitude of P2 increases and can become greater than P1. The ICP waveform then resembles the arterial waveform (Figure 15.1).

FIGURE 15.1

Intracranial pressure waveform. (Reprinted from The Evidenced Based Practice of Critical Care, Neligan P. and Deutschman C.S. (eds.), Oddo M. and Le Roux P., What is the etiology, pathogenesis and pathophysiology of elevated intracranial pressure? 399–405, (more...)

Qualitative estimates of compliance may also be derived from observation of a patient’s response to stimulation. In the ICU, patients often are subjected to noxious stimuli, e.g., suctioning or pain, to determine the level of consciousness; when intracranial compensatory reserve is compromised, the ICP increases rapidly and often remains elevated. By contrast, when compliance is adequate, there may not be an ICP increase or if it does increase it rapidly returns to normal. In addition, in the absence of stimulation, the ICP should be stable and without much variation in pulse amplitude during the respiratory cycle. Calculation of a therapeutic intensity level (TIL), i.e., what and how much treatment is needed to control ICP, also can provide insight into compensatory reserve or treatment response; a greater TIL implies worse compliance and perhaps a greater “ischemic burden.”¹¹² This knowledge of compliance when coupled with the clinical examination and CT findings, in particular the amount of midline shift or compression of the perimesencephalic cisterns, allows herniation risk to be determined and so set an “individualized ICP threshold.” However, how these measures (waveform analysis, TIL, RAP, or PVI) can best be used in TBI management is still being elucidated.

The healthy brain maintains a constant CBF when MABP is between 40 and 160 mmHg through autoregulation (AR). However, AR frequently is compromised and there is great heterogeneity between individuals and over time after TBI. Furthermore, observational studies show an association between poor outcome and compromised AR.^113,114 TCD ultrasonography can be used to calculate AR by analyzing the blood flow velocity (BFV) changes resulting from changes in MABP. Other techniques including brain tissue oxygen (PbtO₂), near-infrared spectroscopy (NIRS), laser Doppler flowmetry (LDF), and thermal dilution regional CBF (td-rCBF) can all be used to calculate AR. These techniques provide intermittent assessments only and given the variability of AR indices over time may miss important information. With recent advances in data processing and computerized bedside monitoring it is now possible to perform online, real-time analysis of AR and in particular the cerebrovascular pressure reactivity index (PRx), which is the linear correlation coefficient between average arterial blood pressure and ICP over 3–4 min.^115,116 PRx is negative with intact AR and positive when AR is compromised or lost, since ICP follows MABP.

Knowledge of the PRx can help identify a CPP that builds on cerebrovascular reactivity (or cerebral autoregulation) as an intrinsic autoprotective mechanism in the brain through calculation of “optimal CPP,”¹¹⁶ i.e., an individualized CPP. This is important since clinical trials that have evaluated CPP-based therapy using a single target that is population-derived demonstrate no outcome benefit in large part because of deleterious effects on the lungs by therapies used to increase CPP.¹¹⁷ Instead optimal CPP values are patient and time dependent, and levels both above and below the patient’s optimal level are associated with worse outcome.¹¹⁸ As of yet there are no prospective studies of ICP or CPP management using “autoregulation-optimal” targets in TBI. However, clinical series suggest that the incidence of favorable outcome after TBI is increased when median CPP is close to optimal CPP. The PRx also may be used to define individualized ICP thresholds.⁶⁷ Further study is required but measurement of ICP and PRx in the future may define a patient specific threshold, allow assessment of ICP associated ischemia risk, and so facilitate targeted care.

Patient and Pathology Targeted ICP Care

An important goal in sTBI management is prevention, identification, and treatment of secondary brain injury, including cerebral ischemia, intracranial hypertension, and energy dysfunction that can occur after the primary injury and are known to aggravate patient outcome. Traditionally, ICP monitoring has been at the center of this approach, but despite much research there is still no level I evidence to support targeting a specific ICP threshold in clinical practice. However, ICP monitoring and management remain critical to the care of sTBI and a prerequisite of other forms of monitoring including MMM.²⁶ More important, converging evidence from diverse areas of research indicate that we should no longer simply treat a generic threshold value (i.e., more or less than 20 mmHg). To do this requires a conceptual shift that already is occurring in many ICUs around the world. The important question to ask is what is the purpose of an ICP monitor; this can then lead to targeted therapy with the realization that an ICP number per se is not a target but rather an indicator of an underlying pathophysiological process that needs treatment.

Looking ahead, successful ICP (and perhaps sTBI) management will require extraction of more information from the ICP signal, rather than just a number, and to use this information to provide patient- and pathology-specific targets and to forecast ICP increases.^{63,67,116,140} In addition, ICP should be regarded as an epiphenomenon of cerebral compliance, herniation tendency, cerebral ischemia, cerebral hypoxia, and cellular dysfunction among others, i.e., ICP care needs to be directed by MMM that includes serial neurological examinations, imaging studies, ICP analysis, and measurements from other bedside physiologic monitors. As the field of bioinformatics grows, further advances in integrating this information can be expected,^141,142 but in its simplest form this currently means dynamic individualization of an ICP treatment threshold. The impact of this is not trivial. For example, threshold adjustment may facilitate extubation if it appears that the ICP increases are associated with the extubation trial and are in themselves not harmful. Similarly, threshold adjustment can avoid therapy escalation and potential deleterious side effects, e.g., optimization of volume and ventilator status in a patient with TBI and acute lung injury. Such an approach may have resulted in a different outcome in an RCT performed many years ago that compared ICP- or CPP-based care, using generic population-based thresholds, since the outcomes in the CPP group were worsened by cardiorespiratory complications even though they had a lower incidence of cerebral ischemia.¹¹⁷

Monitoring by itself does not alter outcome. Instead, it is how the information is used that contributes to patient well-being. In its more advanced form, use of MMM for ICP and sTBI care facilitates therapy that is targeted to patient-specific pathophysiology and as physiologically (and perhaps mechanistically) oriented as possible. Specific therapeutic protocols are still being elucidated,¹⁴³ but early clinical experience suggests that this approach may benefit select patients and enhance outcome.^{118,144–146} For example, several but not all observational series suggest outcome is better when both PbtO₂ and ICP/CPP therapy rather than ICP/CPP-based care alone is used in sTBI, i.e., there still is clinical equipoise. In part, the results may depend on probe location.¹⁴⁷ In the past the driving question has been where to place a monitor. A more important question is where is the monitor, i.e., any data should be interpreted based on postinsertion imaging; simply doing this is MMM. Summary analysis of these various studies suggests that combined ICP/CPP- and PbtO₂-based therapy is associated with better outcome.¹⁴⁵ In addition, initial analysis from BOOST-2, a phase II RCT that compared PbtO₂ and ICP/CPP therapy to ICP/CPP alone in sTBI, demonstrates physiological efficacy, and although not powered for outcome also showed an outcome benefit.¹⁴⁶ Support for use of individualized ICP or CPP thresholds have been demonstrated in several studies using PRx to calculate an “optimal” CPP.^118,144 For example Howells et al.¹⁴⁴ examined the clinical utility of PRx in two ICUs, one that used a CPP-based approach and the other an ICP-based approach to sTBI, and found that a CPP-targeted approach was more successful when pressure reactivity was intact, while an ICP-based strategy was better when pressure reactivity was impaired (Figure 15.2).

FIGURE 15.2

Clinical utility of PRx. Bayesian neural network (BANN) model to predict the likelihood of good or bad clinical outcome using the PRx index among sTBI patients managed using an ICP- or CPP-based treatment strategy. According to this data, the optimal (more...)

In summary, even though there is no level I evidence to support the use of a generic ICP threshold, it is clear that ICP remains important to and a foundation of sTBI care. In particular, research using ICP as part of MMM and investigation of the relationship between pressure, volume, blood flow, and metabolism has improved our understanding of sTBI pathophysiology. This has opened the door on new therapies for ICP.⁹⁴ Today numeric ICP values should no longer be considered a target but rather be regarded as an indicator of targetable pathophysiology. As such, optimal ICP management requires integration of ICP data with MMM, including the clinical examination, clinical imaging, and other physiologic parameters to provide individualized and pathophysiology specific care.

ACKNOWLEDGMENTS AND CONFLICTS OF INTEREST

Dr. Le Roux receives research funding from Integra Lifesciences, Neurologica, the Dana Foundation, and the NIH. He is a consultant for Integra Lifesciences, Codman, Synthes, Neurologica, and a member of the scientific advisory board of Cerebrotech and Edge Therapeutics.

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