Neurocrit Care DOI 10.1007/s12028-014-0048-y

REVIEW ARTICLE

Intracranial Pressure Monitoring: Fundamental Considerations and Rationale for Monitoring Randall Chesnut • Walter Videtta • Paul Vespa • Peter Le Roux • The Participants in the International Multidisciplinary Consensus Conference on Multimodality Monitoring

 Springer Science+Business Media New York 2014

Abstract Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging. The Participants in the International Multidisciplinary Consensus Conference on Multimodality Monitoring are listed in ‘‘Appendix’’ section. R. Chesnut
W. Videtta
P. Vespa
P. Le Roux (&) Brain and Spine Center, Suite 370, Medical Science Building, Lankenau Medical Center, 100 East Lancaster Avenue, Wynnewood, PA 19096, USA e-mail: [email protected]

Keywords Intracranial pressure
Cerebral perfusion pressure
Brain injury
Coma
Multimodality monitoring

Introduction Most clinicians believe that monitoring intracranial pressure (ICP) is fundamental to understanding intracranial hemodynamics and if abnormal and untreated can lead to poor neurological outcome after severe traumatic brain injury (sTBI). ICP monitoring techniques are well described and developed, can be safely performed, and are generalizable in centers across the world. ICP can be used as an index of injury severity and to determine prognosis under select circumstances. The utility of ICP monitoring to direct care is clear, however, the influence of treating ICP on outcome remains unproven due to the absence of natural history studies, lack of standardization in ICP measurement, and specification of techniques used in individual studies and in particular what defines intracranial hypertension or the treatment threshold, irregularities in study population selection (e.g., excluding patients for various and often unclear reasons from the study population [e.g., futility]), management variability, treatment toxicity particularly when intracranial hypertension proves resistant to control, and combining different injury types (e.g., diffuse injuries and surgical mass lesions). Finally, there are few focused prospective studies and randomized controlled trials (RCTs) that limit our ability to derive strong conclusions from the literature. Consequently, whether ICP serves simply as an index of injury severity or is a distinct treatable entity remains poorly defined. The goal of this review is to examine whether knowledge about ICP derived from an ICP monitor in sTBI can provide

123

Neurocrit Care

information about prognosis and guide treatment and whether such management can influence outcome.

Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement [1]. We searched the PubMed, Embase, and Cochrane databases using the search string [(exp Craniocerebral Trauma)] and [(exp Intracranial Pressure) and (exp Intracranial Hypertension)]. Limits included English language, human subjects, adults (C18 years), C5 subjects, inhospital/in-ICU studies, and report type including randomized controlled trials (RCTs), cohort studies, case–control studies, case series, databases, or registries. For mixed population studies, a maximum of 15 % of patients could be 15 % of pediatric patients or >15 % of patients with other pathologies and the data were not reported separately]. A total of 244 articles were reviewed in detail to prepare this report and the evidentiary tables, 84 for ICP and prognosis (37 cited), 42 for the impact of aggressive ICP management on outcome (19 cited), 72 for ICP management and outcome (10 cited), 23 for ICP treatment threshold (12 cited), and 23 for admission predictors of intracranial hypertension (20 cited). Studies critical to the process are included in evidentiary tables published on-line. After selection, the evidence was classified and practical recommendations developed according to the GRADE system [2, 3].

The Principal Methods of ICP and CPP Monitoring Monitoring for intracranial hypertension involves clinical examination, brain imaging, and ICP monitoring. We will focus our discussion on ICP monitoring. ICP is a heart-beat by heart-beat fluctuation of pressure that can be obtained from the intracranial parenchymal tissue or the CSF space (ventricles) with characteristic and reliable morphology for all closed intracranial vault conditions. The morphology of the ICP waveform informs the state of brain compliance and elasticity, and changes in morphology reliably indicate changes in intracranial compliance. Two principal methods of ICP monitoring are in common use, intraparenchymal monitoring and intraventricular monitoring using a ventriculostomy, with the latter being considered the gold standard for ICP, although this is based on tradition rather than on head to head scientific comparison. Both techniques require technical expertise by the operator and the nurse, with attention to calibration, proper zero and level positioning, fluid column patency, catheter/monitor infection control, and waveform display. Consideration for location of monitor insertion, side-to-side ICP gradients, and compartmentalization of ICP need to be taken into account for ICP monitoring. Special care needs to be taken to avoid artifacts or false numbers in the ICP including structured protocols for insertion and nursing competencies for monitor maintenance. Contemporary parenchymal monitors have good agreement with an external ventricular drain (EVD) and suffer from zero drift after several days [4]. Table 1 outlines the core competencies and technical specifications to ensure accurate and reliable ICP and CPP monitoring. New methods of ICP monitoring including non-invasive monitoring using optic nerve sheath diameter,

Neurocrit Care Table 1 Core competencies and technical specifications to ensure accurate and reliable ICP and CPP monitoring Requirements for ICP and CPP monitoring Basic requirements

Advanced options

Indications

BTF guidelines

Suspected elevated ICP

Location

Frontal lobe

Ipsilateral to mass lesion

Device

EVD or parenchymal

EVD for CSF drainage Combination devices with intraparenchymal and EVD features

Device zeroing

Pre-insertion for parenchymal Transducer leveled to tragus for EVD

Device maintenance

Blood pressure transducer leveled to tragus For EVD, maintenance patent fluid column For parenchymal, monitor for drift, use re-zero features

Timing

BTF guidelines

Anticipatory to impending brain edema

Duration

During period of suspected elevated ICP

Prolonged with MMM during period of secondary insults

Frequency

Continuous waveform display; fractionated values q 15 min

Continuous display, trending of values for advanced analytic assessment

Determining the value

Safety

Waveform validation

Mean from continuous data acquisition

Mean value recorded

Mean value from poor waveform in the setting of hemicraniectomy

Normal pre-insertion and pre-removal hemostasis and coagulation markers

Use of antibiotic-coated catheters and probes

Pre-insertion antibiotic prophylactics Threshold values

ICP > 20 mmHg CPP < 60 mmHg

Selected threshold based on compartmental considerations, clinical response, data from other MMM values correlating with lower or higher ICP/CPP

BTF Brain Trauma Foundation guidelines

transcranial Doppler ultrasound pulsatility index, and quantitative EEG are potentially promising techniques that currently remain unvalidated for use in most basic centers and are beyond the scope of consideration for this chapter.

What are the Indications for ICP Monitoring? An ICP monitor is indicated in patients at risk for intracranial hypertension, i.e., patients in coma with CT imaging evidence of mass lesion(s), midline shift, dilatation of the contralateral ventricle, loss of the third ventricle, and obliteration of the perimesencephalic cisterns [5–10]. However, an initial admission head CT scan may be normal in 50 % of patients who later develop increased ICP [8]. For patients with normal initial CT imaging, Narayan et al. [5] developed a predictive model that includes age >40 years, admission systolic blood pressure B90 mmHg, or early uni- or bilateral motor posturing. When two or three of these variables were present, the incidence of intracranial hypertension was 60 %, versus 4 % when none were present. Studies that examine prediction of increased

ICP have also used repeated imaging over the treatment course (final CT diagnosis) [11, 12]. One group of patients who may not require an ICP monitor is those with CT evidence for diffuse axonal injury (DAI). Although episodes of increased ICP are common, need for ICP treatment in these patients is rare in some but not all studies [12, 13]. In summary, sTBI patients in coma with an abnormal admission CT or a normal CT with any combination of admission hypotension, age >40 years, and severe neurological status (GCS motor < 3 or pupillary abnormalities), or a lengthy inability to follow the patient’s exam, should be considered at high risk (incidence > 50 %) of intracranial hypertension and hence be candidates for ICP monitoring. Table 2 summarizes the indications for ICP monitoring.

Safety of ICP Monitoring Complications do occur when using ICP monitors and in particular include: surgically induced brain hemorrhage, infection, technical failure, and iatrogenic harm from interventions based on the ICP readings. Overall these risks

123

123

Single-centre retrospective observational study of predictors of intracranial hypertension

Single-centre retrospective observational study modeling CT characteristics as predictors of intracranial hypertension

Narayan et al. 226 [5]

82

277

Miller et al. [10]

Lobato et al. [11]

Single-centre retrospective observational Low study of outcome of monitored patients

Low

Low

Single-centre retrospective observational Low analysis of correlation of final Marshall CT classification with ICP course

Kishore et al. 137 (47 with [9] normal admission CT)

Mod

753

Eisenberg et al. [8]

Multi-centre, retrospective analysis of prospective observational data on prediction of abnormal ICP

Single-centre retrospective analysis of Low correlation of admission CT parameters and initial ICP

100

Mizutani et al. [7]

Non-standardized CT variable grading system. Small sample size for modeling. No magnitude for ICP elevation Normal CT imaging post evacuation of extracerebral No multivariate statistics for ICP. Examined haematomas did not have ICP problems; normal, nononly admission CT imaging operative scans had 15 % incidence of intracranial hypertension, none severe (>35 mmHg). Other combinations of contusions or brain swelling had much higher incidences

Initial CT ventricle size, basilar cisterns, sulcal size, transfalcine herniation, and gray/white differentiation were associated with, but not predictive of intracranial hypertension

Association with intracranial hypertension for abnormal No magnitude for ICP elevation. No admission CT 53–63 %; for normal admission CT 13 %. prospective verification of normal CT 2+ of predictive variables* with normal CT had 60 % model. Examined only admission CT incidence (*age >40 years, systolic blood pressure imaging. Used only end-hour ICP values B90 mmHg, or motor posturing)

Elevated ICP was present in C55 % of patients with intra- Used only intermittent ICP measurements. or extra-axial haematomas. 17 % of patients with normal Did not separate out patients with admission CT imaging had ICP > 20 mmHg persistently normal CT imaging

For first 72 h, strongest (p < 0.001) independent Used only end-hour ICP values predictors of percent of monitored time that ICP > 20 mmHg were abnormal mesencephalic cisterns, midline shift, and subarachnoid blood. For ICP occurrences >20 mmHg, the strongest (p < 0.001) was cisternal compression, with age, midline shift, and intraventricular blood reaching p < 0.05

Admission CT findings that contributed to predicting initial ICP monitored by subarachnoid catheter. No degree of intracranial hypertension included (in order of data on later development of intracranial predictive power) cisternal compression, subdural size, hypertension ventricular size (III and IV), intracerebral haematoma size, and subarachnoid hemorrhage

Lack of rigorous definition and standardization of cisternal compression

74 % of monitored patients with absent cisterns had ICP > 30 mmHg

Caveats

Single-centre retrospective analysis of Low prospective observational data on correlation of cisterns on admission CT and ICP

Results

Toutant et al. 218 [6]

Grade crit.

No univariate predictors with p < 0.05. Model No admission CT data. No control for discrimination (AUC) = 0.50 (95 % CI 0.41–0.58) and decision to monitor. Subjective calibration (Hosmer–Lemeshow goodness of fit) = 0.18 classification of intracranial hypertension. Used only hourly ICP data

No. of patients Design

Hukkelhoven 134 monitored Single-centre retrospective observational Low et al. [105] patients analysis of admission clinical predictors of ICP elevation

References

Table 2 Indications for ICP monitoring

Neurocrit Care

225

Miller et al. [59]

Little detail on patients with normal admission CT

28 % had no ICP > 20 mmHg, 47 % had ICP values 21–30 mmHg and 25 % had ICP values >30 mmHg. Only 1 patient (3 %) underwent treatment

Low

Used only intermittent ICP measurements. Incomplete description of management methods

Primary ICP monitoring by subdural systems

Are there clinical or CT findings that predict the development of intracranial hypertension and so can guide decision making about ICP monitor placement?

88 % had intracranial hypertension (ICP > 20 mmHg), severe (protracted period C 30 mmHg) in 62 %

Low

No patient with persistently normal admission CT had Examined only admission CT imaging sustained intracranial hypertension. Within the first 24 h, 10 % had transient ICP elevation below 25 mmHg

86 % of their patients with normal admission CT and Examined only admission CT imaging. ICP > 25 mmHg had associated pulmonary Implications of ‘‘secondary’’ ICP complications. Patients with ‘‘normal’’ admission CT did elevation unclear. Normal CT could not develop intracranial hypertension include cisternal compression, slit ventricles

Less than 25 % incidence of persistent ICP > 20 mmHg in patients with normal admission CT imaging

O’Sullivan 22 patients (8 Single-centre retrospective observational et al. [108] with highanalysis of ICP course in patients resolution without signs of ICP elevation on monitoring) admission CT Lee et al. [13] 36 Single-centre retrospective observational analysis of ICP course in patients with CT diagnosis of DAI

Low

Low

Caveats

Development of intracranial hypertension by final Marshall Did not separately report admission CT class Classification: DI I = 0 %; DI II = 28.6 % (10 % as predictive of ICP course. Used only uncontrollable); DI III = 63.2 % (1/3 uncontrollable); intermittent ICP measurements DI IV = 100 % (all uncontrollable); EML = 65.2 % (1/ 2 uncontrollable); NEML = 84.6 % (1/2 uncontrollable)

Results

Low

Single-centre retrospective observational study of ICP course of patients with normal admission CT imaging

Single-centre retrospective observational study of ICP and outcome of consecutive sTBI patients

Low

Grade crit.

46 patients (39 Single-centre retrospective observational monitored) study of ICP course of patients with repeatedly normal CT imaging

Lobato et al. [107]

Holliday et al. 17 [106]

94

Poca et al. [12]

Single-centre retrospective analysis of prospective observational data on correlation of final Marshall CT classification with ICP course

No. of patients Design

References

Table 2 continued

Neurocrit Care

123

123

Refractory ICP = 114.3 [95 %CI 40.5–322.3]

Moderate OR of death: ICP 20–40 = 3.5 [95 %CI 1.7–7.3] ICP > 40 = 6.9 [95 %CI 3.9–12.4]

Grade crit. Design No. of patients References

ICP and CPP monitoring are effective in guiding medical and surgical therapy. This question has been studied using a variety of methodologies including: within-institution protocol studies, center-based studies, analysis of trauma or TBI registries, meta-analysis, and clinical trials. In almost all circumstances, ICP monitoring is used as essential part of a protocol or taken as a surrogate for ‘‘aggressive care’’

Table 3 ICP elevation and outcome

What is the Utility of ICP and CPP Monitoring to Direct Medical and Surgical Therapy for TBI?

Results

For purposes of discussion, we define elevated ICP above a threshold of 20–25 mmHg although this definition does vary in the literature. There is strong evidence that intracranial hypertension is associated with increased mortality [25–38]. When morbidity includes early post-injury deaths, there is a relationship between intracranial hypertension and poor outcome [26, 27, 29, 39–53]. However, when death is excluded intracranial hypertension is not independently predictive of morbidity (Glasgow Outcome Score [GOS]/ GOS-E/neuropsychological measures) [26, 27, 32, 38, 41, 54, 55]. In a systematic review of ICP and outcome published in 2007, Treggiari et al. [56] (Table 3) reported that the risk of unfavorable outcome (including death) increased with degree of ICP elevation, particularly for ICP > 40 mmHg, but this predictive value did not hold for survivors alone [32]. They concluded that the pattern of ICP elevation and refractory ICP were more powerful predictors and that ICP is not an independent outcome predictor. Several other studies also describe that increased ICP (>20 mmHg) refractory to treatment is associated with greater mortality [5, 57–60]. In the systematic review by Treggiari et al. [56], the odds ratio of death versus all other outcomes was 88.0 (95 % CI 33.54 and 231.06) and, for survivors, the odds ratio of poor (GOS 2 and 3) versus good (GOS 4 and 5) outcome were 6.95 (CI 1.13 and 42.83) when increased ICP was refractory to treatment. In summary, increased ICP is frequent after severe TBI and its presence, particularly when refractory to treatment is associated with mortality. The relationship with outcome, i.e., morbidity is less certain and less robust.

Systematic review

Caveats

What is the Utility of ICP and CPP Monitoring for Prognosis in the Comatose Patient?

Treggiari 4 studies (409 pts) for ICP values; 5 studies et al. [56] (677 pts) for of ICP patterns

are very low [14] but almost all studies find a greater risk of complications associated with ventriculostomies than with parenchymal monitors [15]. The propensity to induce harm through treatment based on the ICP has not been substantiated in the literature [16, 17]. Safety can be enhanced through using specific protocols and bundles to reduce the risk of iatrogenic hemorrhage [18, 19], infection [20–24], malplacement, and catheter malfunction.

ICP treated at thresholds; few studies with data available for quantitative analysis

Neurocrit Care

Neurocrit Care

or protocol-driven care. Single center, within-institution protocol studies and large quality assurance studies suggest that the initiation of TBI management protocols based in part on ICP monitoring is associated with improved patient outcome, particularly mortality [37, 61–65]. While some studies cannot separate the specific influence of ICP monitoring from overall TBI protocols [66, 67], Alali et al. [62] demonstrated that higher utilization of ICP monitoring use to guide therapy in Level 1 trauma centers was associated with lower mortality. In multicenter studies and in databases or registries, ‘‘aggressive’’ sTBI management of sTBI often is defined by use of ICP monitoring. However, this is confounded by variable definitions of aggressiveness, inability to control for management decisions (e.g., choice to monitor), and case mix [68–75]. Center-based studies demonstrate different conclusion. For example, Bulger et al. [68] who queried the prospective University Hospitals Consortium database defined centers as aggressive if they monitored C50 % of patients meeting Brain Trauma Foundation criteria for monitoring. ‘‘Aggressiveness’’ was associated with increased neurosurgical consultation, CT imaging, use of ICP treatments, and a decrease in discharge mortality but not functional outcome. By contrast, Cremer et al. [69] who retrospectively studied two trauma centers, only one of which monitored ICP, found that 12-month outcome was similar despite more ICP treatment at the ‘‘aggressive’’ center. The implication of these findings is that ICP monitor use alone may not reliably identify centers with improved outcome from sTBI in toto since it covaries with other related process variables. Population database studies show disparate results with some studies showing that ICP monitoring is associated with reduced risk-adjusted discharge mortality [52] whereas others observe that ICP monitoring is associated with worse risk-adjusted hospital mortality and discharge functional status and increased complications (pneumonia, renal failure, and infections) [76, 77]. Similarly when TBIspecific databases are used both a positive impact of ICP monitoring and no influence on short-term mortality are found [17, 73]. These discrepancies likely are associated with methodological differences and definitions rather than ICP or its management. These studies suffer from many flaws including a lack of granularity to adjust for injury severity, a focus on mortality outcomes and lack of validation of center compliance with best practices [78]. In an RCT, potential confounders, e.g., treatment aggressiveness, protocol compliance, and decision to monitor ICP can be controlled for. Chesnut et al. [79] performed an RCT that included 324 sTBI patients and compared two aggressive treatment protocols, one driven by monitored ICP, the other by serial imaging and clinical examination (i.e., there was no control group). Six-month outcome was similar but the ICP monitor group

experienced more efficient care. The trial has excellent internal validity but lacks external validity. In another RCT, Smith et al. [80] examined mannitol dosing in 77 patients where treatment was triggered by the ICP in one group and provided routinely in the other irrespective of the ICP. Mean ICP was 5.5 mmHg higher in the monitorbased-treatment group but outcome was similar at 1-year in the two groups. Table 4 summarizes the studies that were considered. In summary, the literature suggests that ICP monitoring is routinely used to guide medical and surgery therapy, including reversal of brain herniation, and is a fundamental component of aggressive care for TBI. ICP Management and Outcome Does Successfully Managing Intracranial Pressure Improve Outcome? There is strong evidence that elevated (particularly treatment-resistant) ICP is associated with poor outcome. Hence, it is ethically inconceivable that a natural history study of untreated ICP or an RCT on whether the treatment improves outcome will be conducted. A proxy for such a question is whether ICP treatment response predicts outcome. The response may be observed after ‘‘first tier’’ or ‘‘second tier’’ therapies. Five observational studies describe patients with early ICP elevations that normalized with ‘‘first tier’’ treatment but limited sample sizes preclude differentiating outcomes in this group from patients with normal ICP or refractory intracranial hypertension [5, 57–60]. Treggiari et al. [56] combined data from these papers in a systematic review and observed a response between outcome and treatment response. However, they did not access original study data and so were unable to adjust for confounding variables. Subsequently, Farahvar et al. [29] examined the association between response to therapy and 14 day mortality in 388 patients in a prospective TBI database. Response to treatment was independently associated with less mortality. However, treatment specifics were not specified or described. Implementation of ICP monitoring in the context of a guideline-driven protocol resulted in a reduction in mortality in TBI patients [66, 81]. Further insight into ICP treatment response and outcome is derived from 3 RCTs that examined ‘‘second-tier’’ therapies (barbiturates, hypothermia, and decompressive craniectomy) for intracranial hypertension [82–84]. The trials suffer from methodological limitations but two suggest a relationship between increased mortality and inability to control ICP [82, 83]. By contrast in DECRA [84], an RCT of bifrontal decompressive craniectomy versus maximal medical therapy for early (125,000 patients

Grade Crit.

Results

Caveats

General trauma database lacked important demographic information. No control for centre differences or choice to monitor

Multi-centre retrospective cohort Low- Trend toward reduced 2-week No control for decision to study from prospective mod mortality for monitored monitor or to treat unmonitored database examining correlation patients by multivariate logistic patients for intracranial of ICP monitoring and outcome regression modeling (OR 0.64; hypertension 95 % CI 0.41–1.00; p = 0.05) Did not access original data. Ad Meta-analysis of mortality data Low- ‘‘High-intensity’’ treatment hoc definition of and threshold from 127 studies containing mod associated with a for treatment intensity C90 patients, examining approximately 12 % lower influence of treatment intensity adjusted mortality rate (based on prevalence of ICP (p < 0.001) and a 6 % higher monitoring) on 6-month pooled mean rate of favorable mortality outcomes (p < 0.001)

Chesnut et al. [79]

324

RCT comparing BTF-based protocol based on ICP monitoring to protocol based on imaging and clinical exam without monitoring

Smith et al. [80]

77

Prospective randomized trial of patients treated based on ICP vs scheduled treatment

Mod- Primary outcome = no Generalizability limited by issues high significant difference in surrounding prehospital care, 6-month composite outcome choice of primary outcome measure (OR 1.09; 95 % CI measure, and management 0.74–1.58; p = 0.49). protocols Secondary outcome = no significant difference in 14-day mortality (OR 1.36; 95 % CI 0.87–2.11; p = 0.18), cumulative 6-month mortality OR 1.10; 95 % CI 0.77–1.57; p = 0.60), or 6-month GOS-E (OR 1.23; 95 % CI 0.77–1.96) Low No significant difference in Small sample size. Investigation 1-year GOS by univariate not designed to study ICP analysis. Mean ICP 5.5 mmHg monitor utility higher in monitor-basedtreatment group

refractory intracranial hypertension (ICP > 20 mmHg for >15 min within a 1-h period), mortality was similar but morbidity greater in the surgical group despite mean ICP being less in the craniectomy group. However, this trial is not a trial of ICP treatment or not, the definition of ‘‘refractory intracranial hypertension’’ differs from clinical practice and nor was outcome analyzed according to treatment response.

In summary, successful treatment of intracranial hypertension is associated with better outcome than observed in patients who do not respond to treatment. However, this is not a one-to-one relationship since patients with refractory intracranial hypertension may recover. In addition, the definitions of intracranial hypertension and the degree of ICP lowering critical to this effect are not clear (Table 5).

123

Neurocrit Care Table 5 Does successfully managing intracranial pressure improve outcome? Reference No. of patients

Design

Grade crit.

Results

Caveats

Treggiari et al. [56]

677 five Systematic review of association Mod studies of ICP values and patterns with outcome

Odds of death in responders were 2.2 Did not access original data. times higher (OR 2.2; 95 % CI 1.42 Unable to control for numerous and 3.30) and the odds of poor confounding variables recovery (GOS 2 and 3) were 4 times higher (OR 4.0; 95 % CI 2.27 and 7.04) compared to patients with normal ICP courses (threshold = 20 mmHg).

Farahver et al. [29]

388

Multi-centre retrospective cohort Low study from prospective database examining ICP response to treatment and outcome

Lower risk of 14-day mortality in Results very sensitive to ad hoc patients responding to treatment definitions of intracranial (OR 0.46; 95 % CI 0.23–0.92; hypertension and treatment p = 0.03). 20 % greater likelihood response of treatment response for each 1-h decrease in hours of ICP > 25 mmHg in first 24 h (OR 0.80; 95 % CI 0.71–0.90, p = 0.0003)

Eisenberg et al. [82]

73

Multi-centre RCT of high-dose pentobarbital vs conventional therapy in managing refractory intracranial hypertension

30-day survival was 92 % for patients Survival/recovery not primary who’s ICP responded to treatment outcome. Underpowered vs 17 % in nonresponders. 80 % of all deaths were due to uncontrolled ICP

Shiozaki et al. [83]

33

Single-centre RCT of hypothermia Mod vs conventional therapy in managing refractory intracranial hypertension

For the 17 hypothermia patients, the 5 ICP courses not described in any patients with non-responsive ICP detail. Refractory ICP not well died; 6-month mortality among defined. Underpowered. responders was 27 %. Among the Outcome only analyzed by study 17 controls, 3 patients survived group (18 % mortality)

Cooper et al. [84]

155

Multi-centre RCT of decompressive craniectomy vs maximal medical management of early refractory intracranial hypertension.

6-month mortality was similar (19 vs ICP response vs outcome not 18 %). Adjusted GOS-E scores analyzed independently. No data were marginally worse for the specific to nonresponders craniectomy group (adjusted OR 1.66; 95 % CI 0.94–2.94; p = 0.08)

Mod

Low

Threshold for ICP Treatment Is There an Optimal ICP Treatment Threshold the Maintenance of Which is Critical to Optimize Recovery? There are no natural history studies that relate outcome to non-treated ICP in TBI since the studies that attempt to associate an ICP threshold with outcome are confounded by ongoing threshold-driven treatment administered to study patients. Various thresholds, including 15 mmHg [37, 72, 80], 20 mmHg [47, 58, 85], 25 mmHg [86], and 35 mmHg [87] particularly if the threshold is exceeded for >15 min have been defined or suggested. In large part, this variation in ‘‘optimal threshold’’ depends on study methodology, type of analysis, and patient treatment. In addition, a second threshold of 40 mmHg [47, 58] is observed in some but not all studies [72]. This difference depends in part on the successful (or not) up-escalation of

123

therapeutic intensity at the higher threshold. However, it is difficult to make meaningful conclusions from these data since there is confounding by general protocol effects, the studies are underpowered and very little detail is provided on design or patient management. Once a given ICP threshold is exceeded, particularly with ongoing treatment, it is considered strong evidence for severe injury and thus poor outcome. Per se, this leads to consideration of futility. Therefore, information about patient outcome when ICP treatment fails is valuable. While ICP above threshold that is refractory to treatment is associated with poor outcome, modern studies also demonstrate that up to 40 % of patients, usually younger patients, may survive and have a favorable outcome despite persistent increased ICP (>20–25 mmHg) [82, 88, 89] provided aggressive support is maintained. Almost all studies that examine the relationship between ICP and outcome have used intermittent, manually entered, hourly ICP measurements for analysis and rarely is the

Neurocrit Care

recording method (e.g., precise end-hour value vs. hourly average) specified. Control for rounding or estimation in manually entered data are absent. By contrast, management responses are real time and hence the question may be better answered using higher resolution data or alternate analytic techniques [e.g. trending, area under the curve (AUC)]. Vik et al. [53] used hourly, manually entered ICU data and examined the AUC for ICP > 20 mmHg (‘‘dose’’ of ICP) over the entire monitoring period to account for both level and duration of intracranial hypertension. At 6 months, the ICP ‘‘dose’’ was an independent predictor of death and poor outcome. Kahraman et al. [90] compared automated versus manually recorded data and analyzed AUC (>20 mmHg) and ICP mean values. Total and daily AUC ICP values from automated data (6 s) were associated with 3-month outcome, but comparable calculations from manual data (15 min or every hour) were not. These studies suggest that traditional data collection (manual) data and analysis (mean values or percent of monitored time that ICP is >20 mmHg) are relatively insensitive. This has obvious research and clinical implications. In particular, what defines intracranial hypertension needs to be better elucidated. In summary, the crisis threshold for ICP is unclear. Despite these limitations, it appears that patients who respond to efforts to keep ICP < 15–25 mmHg do better in aggregate, but failure of such efforts does not uniformly preclude a favorable outcome. In addition, attempts to determine values that predict unfavorable outcome when a threshold is violated range more toward 35–40 mmHg. However, the data is largely descriptive, which is inadequate to allow definitive statements on the existence of actual treatment thresholds (Table 6).

Conclusions and Closing Thoughts Intracranial pressure and its management is a fundamental concept in TBI care and is central to the Brain Trauma Foundation Guidelines. ICP monitoring has been available since 1951 but it is important to realize that the monitor per se makes little difference to outcome. Instead it is how the data from the monitor is used and whether effective treatments exist. Efforts to ‘‘prove’’ a relationship between ICP, its management and outcome are limited by many confounding variables. The evidentiary tables for this manuscript were prepared for the International Consensus Conference on Neuromonitoring held on 9/29 and 9/30/ 2013. Since then several subsequent publications that represent clinical series, database analysis, or decision analysis also suggest an association between ICP monitor use and guideline adherence with ‘‘better outcome,’’ usually reduced mortality [17, 62, 81, 91, 92]. However, there are many limitations to the available evidence to make definitive statements and the one RCT that addresses this

question demonstrates that an ICP monitor to guide care improves efficiency of care but that outcome is similar to patients managed without an ICP monitor [79]. It is important to recognize that while this RCT has excellent internal validity it lacks external validity and did not test whether treatment of ICP per se makes a difference but rather compared two management protocols. It is perhaps not surprising that a relationship between ICP, its treatment and outcome when a numerical threshold is breached, has been difficult to prove given the heterogeneity and complex pathophysiology of TBI and may be an oversimplification. Indeed while studies of other physiological markers in TBI demonstrate that brain physiology is adversely affected when ICP is elevated [93], brain physiology often may be abnormal [94–97] when ICP is normal (60 mmHg in population-based studies), it may be better practice to manage ICP and then individualize and target CPP to the patient, i.e., define an optimal CPP for each patient [102]. This too may be the ideal way to manage ICP, i.e., individualize and define an optimal ‘‘threshold’’ for treatment. Moving forward this may come about through better understanding of compliance, ICP waveform analysis, autoregulation, the interaction with other physiologic variables, and an ability to predict an increase in ICP rather than react to it [103, 104]. Recommendations (and see Summary Statement) 1.

2.

3.

ICP and CPP monitoring are recommended as a part of protocol-driven care in patients who are at risk of elevated intracranial pressure based on clinical and/or imaging features (Strong recommendation, Moderate quality of evidence). We recommend that ICP and CPP monitoring be used to guide medical and surgical interventions and to detect life-threatening imminent herniation; however, the threshold value of ICP is uncertain based on the literature (Strong recommendation, High quality of evidence). We recommend that the indications and method for ICP monitoring should be tailored to the specific diagnosis (e.g., SAH, TBI, encephalitis) (Strong recommendation, Low quality of evidence).

123

123

130

100

233

428

207 adults Single-centre retrospective observational study

27

77

Nordby and Gunnerod [47]

Marshall et al. [72]

Saul and Ducker [37]

Marmarou et al. [85]

Chambers et al. [87]

Ratanalert et al. [86]

Smith et al. [80]

Low

Low

Low

Grade crit.

Prospective randomized trial of patients treated based on ICP vs scheduled treatment

Prospective randomized trial of protocolised treatment at two different ICP thresholds (20 vs 25 mmHg) Low

Low

Low

Multi-centre retrospective analysis of Low prospectively collected database

Single-centre retrospective sequential Low case series’ comparing two protocols

Single-centre retrospective case series

Single-centre retrospective case series

Single-centre retrospective case series

160

Miller et al. [58]

Design

No. of patients

Reference

Caveats

All patients treated for elevated ICP. Minimal risk adjustment or multifactorial analysis. Epidural monitoring

No significant difference in 1-year GOS by univariate analysis. Mean ICP 5.5 mmHg higher in monitorbased-treatment group

Small sample size. Investigation not designed to study ICP threshold

No significant difference in 6-month GOS by univariate Very small sample size. Little detail provided on study or multivariate analysis design and management

ROC analysis of maximum ICP from hourly averages of Studied only maximal ICP values automated ICP data found optimal prediction of 6-month dichotomized GOS outcome to be 35 mmHg

The proportion of measurements with ICP > 20 mmHg Confounding by choice of threshold, variable responses was the most powerful predictor of 6-month outcome to supra-threshold values of different magnitudes, the after age, admission GCS motor score, and abnormal beneficial and toxic effects of treatments, and the admission pupils. The full model correctly explained interaction of ICP with other variables in individual patients. Their model assumes equal effect of each 53 % of observed outcomes. ICP proportion modeling descriptor over its entire range power peaked at 20 mmHg

Mortality rate was 46 % for those treated with a Threshold analysis confounded by concomitant general 20–25 mmHg threshold protocol vs 28 % for those protocol effects. Minimal risk adjustment or treated with a 15 mmHg protocol (p < 0.0005 by multifactorial analysis univariate analysis). For those with ICP’s C25 mmHg, respective mortality was 84 vs 69 % (p < 0.05). For those with ICP’s B25 mmHg, respective mortalities were 26 and 15 % (p < 0.025)

For patients without mass lesions with All patients treated for ICP > 15 mmHg. Minimal risk ICP < 15 mmHg, 77 % achieved favorable outcome adjustment or multifactorial analysis (GOS = 4–5) vs those with ICP C 15 mmHg for C15 min, wherein 42 % achieved favorable outcome (p < 0.01 by univariate analysis). Favorable outcomes were achieved in 43 % with ICP C 15 for 15 min and in 42 % with ICP > 40 mmHg for 15 min

Significantly worse outcome in patients whose ICP exceeded 20 mmHg (p < 0.001). ICP C 40 mmHg had high risk of progressing to brain death

All patients treated for elevated ICP. Minimal risk No ICP threshold for outcome in patients with mass adjustment or multifactorial analysis lesion. When ICP was 0–10 mmHg in patients without mass lesions, 85 % made a good recovery (GOS 4–5) and 8 % died. When ICP was 11–20 mmHg, good recovery rate was 64 and 25 % died (v2 = 5.30; p < 0.02)

Results

Table 6 Is there an optimal ICP treatment threshold the maintenance of which is critical to optimize recovery?

Neurocrit Care

Single-centre retrospective observational study of patients with ICP > 25 for C2 h

Single-centre retrospective Low observational trial using prospective data analyzing manual vs automated ICP as AUC vs mean

30

Kahraman et al. [90]

Low

Single-centre retrospective observational trial analyzing ICP as AUC

Low

Low

Grade crit.

Vik et al. [53] 93

9

Young et al. [89]

Design

Single-centre retrospective observational study on patients with ICP > 20 mmHg that persisted for >96 h

No. of patients

Resnick et al. 37 [88]

Reference

Table 6 continued Caveats

Small series. No quantification of ICP or CPP insults. No comparison to those who died

For automated data, total ICU AUC had high predictive power for GOS-E 1–4 (area under the ROC curve = 0.92 ± 0.05) and moderate predictive power for in-hospital mortality (0.76 ± 0.15). The percentage of monitoring time that ICP > 20 mmHg had significantly lower predictive power for 3-month GOS-E compared with AUC using 20 mmHg as the cutoff (p = 0.016)

The dose of ICP was an independent predictor of death No control for monitoring duration or terminal events. (OR 1.04; 95 % CI 1.003–1.08; p = 0.035) and poor Arbitrary stratification of AUC categories outcome (OR 1.05; 95 % CI 1.003–1.09; p = 0.034) at 6 months, by multiple regression

Mortality = 56 %. 44 % survived, with GOS = 4 at rehabilitation discharge

38 % reached GOS 4–5 at C6 months; 43 % GOS 1–2. No detail on the degree of ICP resistance or magnitude of Patients 50 %) of

Neurocrit Care

•

•

•

•

intracranial hypertension unless the CT finding is that of uncomplicated diffuse axonal injury (Low quality of evidence). sTBI patients with a normal admission CT but any combination of admission hypotension, age >40 years, and severe neurological status (GCS motor 50 %) of intracranial hypertension (Low quality of evidence). sTBI patients with a normal admission CT who do not meet the above criteria may be considered at low likelihood of developing intracranial hypertension (Low quality of evidence). sTBI patients with uncomplicated diffuse axonal injury on admission CT may be considered at low likelihood of developing intracranial hypertension (Low quality of evidence). Patients initially managed without monitoring whose exam does not improve should undergo repeat CT imaging (Low quality of evidence).

Conflict of interest Randall Chesnut receives NIH funding. Peter Le Roux receives research funding from Integra Lifesciences, Neurologica, the Dana Foundation, and the NIH; is a consultant for Integra Lifesciences, Codman, Synthes, Neurologica; and is a member of the scientific advisory board of Cerebrotech, Brainsgate, Orsan and Edge Therapeutics. Paul Vespa receives Grant Funding from NIH, DOD; is a consultant for Edge Therapeutics; and has Stock Options with Intouch Health. Walter Videtta receives NIH funding.

Paul Vespa, MD, FCCM, FAAN, FNCS Professor of Neurology and Neurosurgery Director of Neurocritical Care David Geffen School of Medicine at UCLA Los Angeles, CA 90095 USA [email protected] Giuseppe Citerio, MD Director NeuroIntensive Care Unit, Department of Anesthesia and Critical Care Ospedale San Gerardo, Monza. Via Pergolesi 33, Monza 20900, Italy [email protected] Mary Kay Bader RN, MSN, CCNS, FAHA, FNCS Neuro/Critical Care CNS Mission Hospital Mission Viejo CA 92691, USA [email protected] Gretchen M. Brophy, PharmD, BCPS, FCCP, FCCM Professor of Pharmacotherapy & Outcomes Science and Neurosurgery Virginia Commonwealth University Medical College of Virginia Campus 410 N. 12th Street Richmond, Virginia 23298-0533 USA [email protected]

Appendix: Participants in the International Multidisciplinary Consensus Conference on Multimodality Monitoring

Michael N. Diringer, MD Professor of Neurology, Neurosurgery & Anesthesiology Chief, Neurocritical Care Section Washington University Dept. of Neurology, Campus Box 8111 660 S Euclid Ave St Louis, MO 63110 USA [email protected]

Peter Le Roux, MD, FACS, Brain and Spine Center, Suite 370, Medical Science Building, Lankenau Medical Center, 100 East Lancaster Avenue, Wynnewood, PA 19096, USA. Tel: +1 610 642 3005; Fax: 610 642 3057 [email protected]

Nino Stocchetti, MD Professor of Anesthesia and Intensive Care Department of physiopathology and transplant, Milan University Director Neuro ICU Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico Via F Sforza, 35 20122 Milan Italy e-mail [email protected]

David K Menon MD PhD FRCP FRCA FFICM FMedSci Head, Division of Anaesthesia, University of Cambridge Consultant, Neurosciences Critical Care Unit Box 93, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK [email protected]

Walter Videtta, MD ICU Neurocritical Care Hospital Nacional ‘Prof. a. Posadas’ El Palomar - Pcia. de Buenos Aires Argentina [email protected]

123

Neurocrit Care

Rocco Armonda, MD Department of Neurosurgery MedStar Georgetown University Hospital Medstar Health, 3800 Reservoir Road NW Washington DC 20007 USA [email protected] Neeraj Badjatia, MD Department of Neurology University of Maryland Medical Center, 22 S Greene St Baltimore, MD, 21201 USA [email protected] Julian Boesel, MD Department of Neurology Ruprect-Karls University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany [email protected] Randal Chesnut, MD, FCCM, FACS Harborview Medical Center, University of Washington Mailstop 359766 325 Ninth Ave, Seattle WA 98104-2499 USA [email protected] Sherry Chou, MD, MMSc Department of Neurology, Brigham and Women’s Hospital 75 Francis Street, Boston MA 02115 USA [email protected] Jan Claassen, MD, PhD, FNCS Assistant Professor of Neurology and Neurosurgery Head of Neurocritical Care and Medical Director of the Neurological Intensive Care Unit Columbia University College of Physicians & Surgeons 177 Fort Washington Avenue, Milstein 8 Center room 300, New York, NY 10032 USA [email protected] Marek Czosnyka, PhD Department of Neurosurgery University of Cambridge,

123

Addenbrooke’s Hospital, Box 167 Cambridge, CB20QQ United Kingdom [email protected] Michael De Georgia, MD Professor of Neurology Director, Neurocritical Care Center Co-Director, Cerebrovascular Center University Hospital Case Medical Center Case Western Reserve University School of Medicine 11100 Euclid Avenue Cleveland, Ohio 44106 [email protected] Anthony Figaji, MD, PhD Head of Pediatric Neurosurgery University of Cape Town 617 Institute for Child Health Red Cross Children’s Hospital Rondebosch, 7700 Cape Town, South Africa [email protected] Jennifer Fugate, DO Department of Neurology, Mayo Clinic, 200 First Street SW Rochester, MN 55905 [email protected] Raimund Helbok, MD Department of Neurology, Neurocritical Care Unit Innsbruck Medical University, Anichstr.35, 6020 Innsbruck, Austria [email protected] David Horowitz, MD Associate Chief Medical Officer University of Pennsylvania Health System, 3701 Market Street Philadelphia, PA, 19104 USA [email protected] Peter Hutchinson, MD Professor of Neurosurgery NIHR Research Professor Department of Clinical Neurosciences University of Cambridge Box 167 Addenbrooke’s Hospital

Neurocrit Care

Cambridge CB2 2QQ United Kingdom [email protected] Monisha Kumar, MD Department of Neurology Perelman School of Medicine, University of Pennsylvania, 3 West Gates 3400 Spruce Street Philadelphia, PA, 19104 USA [email protected] Molly McNett, RN, PhD Director, Nursing Research The MetroHealth System 2500 MetroHealth Drive, Cleveland, OH 44109 USA [email protected] Chad Miller, MD Division of Cerebrovascular Diseases and Neurocritical Care The Ohio State University 395 W. 12th Ave, 7th Floor Columbus, OH 43210 [email protected] Andrew Naidech, MD, MSPH Department of Neurology Northwestern University Feinberg SOM 710 N Lake Shore Drive, 11th floor Chicago, IL 60611 [email protected] Mauro Oddo, MD Department of Intensive Care Medicine CHUV University Hospital, BH 08-623 Faculty of Biology and Medicine University of Lausanne 1011 Lausanne, Switzerland [email protected] DaiWai Olson, RN, PhD Associate Professor of Neurology, Neurotherapeutics and Neurosurgery University of Texas Southwestern 5323 Harry Hines Blvd. Dallas, TX 75390-8897 USA [email protected] Kristine O’Phelan M.D. Director of Neurocritical Care Associate Professor, Department of Neurology University of Miami, Miller School of Medicine

JMH, 1611 NW 12th Ave, Suite 405 Miami, FL, 33136 USA [email protected] Javier Provencio, MD Associate Professor of Medicine Cerebrovascular Center and Neuroinflammation Research Center Lerner College of Medicine Cleveland Clinic, 9500 Euclid Ave, NC30 Cleveland, OH 44195 USA [email protected] Corina Puppo, MD Assistant Professor, Intensive Care Unit, Hospital de Clinicas, Universidad de la Repu´blica, Montevideo Uruguay [email protected] Richard Riker, MD Critical Care Medicine Maine Medical Center, 22 Bramhall Street Portland, Maine 04102-3175 USA [email protected] Claudia Robertson, MD Department of Neurosurgery Medical Director of Center for Neurosurgical Intensive Care, Ben Taub Hospital Baylor College of Medicine, 1504 Taub Loop, Houston, TX 77030 USA [email protected] J. Michael Schmidt, PhD, MSc Director of Neuro-ICU Monitoring and Informatics Columbia University College of Physicians and Surgeons Milstein Hospital 8 Garden South, Suite 331 177 Fort Washington Avenue, New York, NY 10032 USA [email protected] Fabio Taccone, MD Department of Intensive Care, Laboratoire de Recherche Experimentale

123

Neurocrit Care

Erasme Hospital, Route de Lennik, 808 1070 Brussels Belgium [email protected]

References 1. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration. Br Med J (Clin Res Ed). 2009;339:b2700. 2. Andrews JC, Schu¨nemann HJ, Oxman AD, Pottie K, Meerpohl JJ, Coello PA, Rind D, Montori VM, Brito JP, Norris S, Elbarbary M, Post P, Nasser M, Shukla V, Jaeschke R, Brozek J, Djulbegovic B, Guyatt G. GRADE guidelines: 15 Going from evidence to recommendation-determinants of a recommendation’s direction and strength. J Clin Epidemiol. 2013;66(7): 726–35. 3. Jaeschke R, Guyatt GH, Dellinger P, et al. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. Br Med J. 2008;337:a744. 4. Lescot T, Reina V, Le Manach Y, Boroli F, Chauvet D, Boch AL, Puybasset L. In vivo accuracy of two intraparenchymal intracranial pressure monitors. Intensive Care Med. 2011;37(5): 875–9. 5. Narayan RK, Kishore PR, Becker DP, et al. Intracranial pressure: to monitor or not to monitor? A review of our experience with severe head injury. J Neurosurg. 1982;56(5):650–9. 6. Toutant SM, Klauber MR, Marshall LF, et al. Absent or compressed basal cisterns on first CT scan: ominous predictors of outcome in severe head injury. J Neurosurg. 1984;61(4):691–4. 7. Mizutani T, Manaka S, Tsutsumi H. Estimation of intracranial pressure using computed tomography scan findings in patients with severe head injury. Surg Neurol. 1990;33(3):178–84. 8. Eisenberg HM, Gary HE Jr, Aldrich EF, et al. Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg. 1990;73(5):688–98. 9. Kishore PR, Lipper MH, Becker DP, Domingues da Silva AA, Narayan RK. Significance of CT in head injury: correlation with intracranial pressure. AJR Am J Roentgenol. 1981;137(4): 829–33. 10. Miller MT, Pasquale M, Kurek S, et al. Initial head computed tomographic scan characteristics have a linear relationship with initial intracranial pressure after trauma. J Trauma. 2004;56(5): 967–72; discussion 72–73. 11. Lobato RD, Cordobes F, Rivas JJ, et al. Outcome from severe head injury related to the type of intracranial lesion. A computerized tomography study. J Neurosurg. 1983;59(5):762–74. 12. Poca MA, Sahuquillo J, Baguena M, Pedraza S, Gracia RM, Rubio E. Incidence of intracranial hypertension after severe head injury: a prospective study using the Traumatic Coma Data Bank classification. Acta Neurochir Suppl. 1998;71:27–30. 13. Lee TT, Galarza M, Villanueva PA. Diffuse axonal injury (DAI) is not associated with elevated intracranial pressure (ICP). Acta Neurochir (Wien). 1998;140(1):41–6. 14. Bekar A, Dog˘an S, Abas¸ F, Caner B, Korfali G, Kocaeli H, Yilmazlar S, Korfali E. Risk factors and complications of intracranial pressure monitoring with a fiberoptic device. J Clin Neurosci. 2009;16(2):236–40.

123

15. Kasotakis G, Michailidou M, Bramos A, Chang Y, Velmahos G, Alam H, King D, de Moya MA. Intraparenchymal vs extracranial ventricular drain intracranial pressure monitors in traumatic brain injury: less is more? J Am Coll Surg. 2012;214:950–7. 16. Mendelson AA, Gillis C, Henderson WR, Ronco JJ, Dhingra V, Griesdale DE. Intracranial pressure monitors in traumatic brain injury: a systematic review. Can J Neurol Sci. 2012;39(5): 571–6. 17. Farahvar A, Gerber LM, Chiu YL, Carney N, Ha¨rtl R, Ghajar J. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg. 2012;117(4):729–34. 18. Bauer DF, McGwin G Jr, Melton SM, et al. The relationship between INR and development of hemorrhage with placement of ventriculostomy. J Trauma. 2011;70(5):1112–7. 19. Matevosyan K, Madden C, Barnett SL, et al. Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy. J Neurosurg. 2010;114:3–7. 20. Mayhall CG, Archer NH, Lamb VA, et al. Ventriculostomyrelated infections. A prospective epidemiologic study. N Engl J Med. 1984;310(9):553–9. 21. Muttaiyah S, Ritchie S, John S, et al. Efficacy of antibioticimpregnated external ventricular drain catheters. J Clin Neurosci. 2010;17:296–8. 22. Honda H, Jones JC, Craighead MC, Diringer MN, Dacey RG, Warren DK. Reducing the incidence of intraventricular catheterrelated ventriculitis in the neurology-neurosurgical intensive care unit at a tertiary care center in St Louis, Missouri: an 8-year follow-up study. Infect Control Hosp Epidemiol. 2010;31(10): 1078–81. 23. Leverstein-van Hall MA, Hopmans TE, van der Sprenkel JW, Blok HE, van der Mark WA, Hanlo PW, Bonten MJ. A bundle approach to reduce the incidence of external ventricular and lumbar drain-related infections. J Neurosurg. 2010;112(2): 345–53. 24. Fichtner J, Guresir E, Seifert V, Raabe A. Efficacy of silverbearing external ventricular drainage a retrospective analysis. J Neurosurg. 2010;112:840–6. 25. Andrews PJ, Sleeman DH, Statham PF, et al. Predicting recovery in patients suffering from traumatic brain injury by using admission variables and physiological data: a comparison between decision tree analysis and logistic regression. J Neurosurg. 2002;97(2):326–36. 26. Badri S, Chen J, Barber J, et al. Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med. 2012;38(11): 1800–9. 27. Balestreri M, Czosnyka M, Hutchinson P, et al. Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury. Neurocrit Care. 2006;4(1):8–13. 28. Budohoski KP, Schmidt B, Smielewski P, et al. Non-invasively estimated ICP pulse amplitude strongly correlates with outcome after TBI. Acta Neurochir Suppl. 2012;114:121–5. 29. Farahvar A, Gerber LM, Chiu YL, et al. Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury. J Neurosurg. 2011;114(5):1471–8. 30. Fearnside MR, Cook RJ, McDougall P, McNeil RJ. The Westmead Head Injury Project outcome in severe head injury. A comparative analysis of pre-hospital, clinical and CT variables. Br J Neurosurg. 1993;7(3):267–79. 31. Kostic A, Stefanovic I, Novak V, Veselinovic D, Ivanov G, Veselinovic A. Prognostic significance of intracranial pressure monitoring and intracranial hypertension in severe brain trauma patients. Med Pregl. 2011;64(9–10):461–5.

Neurocrit Care 32. Lannoo E, Van Rietvelde F, Colardyn F, et al. Early predictors of mortality and morbidity after severe closed head injury. J Neurotrauma. 2000;17(5):403–14. 33. Papo I, Caruselli G. Long-term intracranial pressure monitoring in comatose patients suffering from head injuries. A critical survey. Acta Neurochir (Wien). 1977;39(3–4):187–200. 34. Papo I, Caruselli G, Scarpelli M, Luongo A. Intracranial hypertension in severe head injuries. Acta Neurochir (Wien). 1980;52(3–4):249–63. 35. Richard KE, Frowein RA. Significance of intracranial pressure and neurological deficit as prognostic factors in acute severe brain lesions. Acta Neurochir Suppl. 1979;28(1):66–9. 36. Ross AM, Pitts LH, Kobayashi S. Prognosticators of outcome after major head injury in the elderly. J Neurosci Nurs. 1992; 24(2):88–93. 37. Saul TG, Ducker TB. Intracranial pressure monitoring in patients with severe head injury. Am Surg. 1982;48(9):477–80. 38. Vapalahti M, Troupp H. Prognosis for patients with severe brain injuries. Br Med J. 1971;3(5771):404–7. 39. Bremmer R, de Jong BM, Wagemakers M, Regtien JG, van der Naalt J. The course of intracranial pressure in traumatic brain injury: relation with outcome and CT-characteristics. Neurocrit Care. 2010;12(3):362–8. 40. Chamoun RB, Robertson CS, Gopinath SP. Outcome in patients with blunt head trauma and a Glasgow Coma Scale score of 3 at presentation. J Neurosurg. 2009;111(4):683–7. 41. Czosnyka M, Hutchinson PJ, Balestreri M, Hiler M, Smielewski P, Pickard JD. Monitoring and interpretation of intracranial pressure after head injury. Acta Neurochir Suppl. 2006;96:114–8. 42. Feldmann H, Klages G, Gartner F, Scharfenberg J. The prognostic value of intracranial pressure monitoring after severe head injuries. Acta Neurochir Suppl. 1979;28(1):74–7. 43. Hiler M, Czosnyka M, Hutchinson P, et al. Predictive value of initial computerized tomography scan, intracranial pressure, and state of autoregulation in patients with traumatic brain injury. J Neurosurg. 2006;104(5):731–7. 44. Jiang JY, Gao GY, Li WP, Yu MK, Zhu C. Early indicators of prognosis in 846 cases of severe traumatic brain injury. J Neurotrauma. 2002;19(7):869–74. 45. Lobato RD, Rivas JJ, Portillo JM, et al. Prognostic value of the intracranial pressure levels during the acute phase of severe head injuries. Acta Neurochir Suppl. 1979;28(1):70–3. 46. Ng I, Lew TW, Yeo TT, et al. Outcome of patients with traumatic brain injury managed on a standardised head injury protocol. Ann Acad Med Singap. 1998;27(3):332–9. 47. Nordby HK, Gunnerod N. Epidural monitoring of the intracranial pressure in severe head injury characterized by non-localizing motor response. Acta Neurochir (Wien). 1985;74(1–2):21–6. 48. Petridis AK, Dorner L, Doukas A, Eifrig S, Barth H, Mehdorn M. Acute subdural hematoma in the elderly; clinical and CT factors influencing the surgical treatment decision. Cent Eur Neurosurg. 2009;70(2):73–8. 49. Schirmer-Mikalsen K, Moen KG, Skandsen T, Vik A, Klepstad P. Intensive care and traumatic brain injury after the introduction of a treatment protocol: a prospective study. Acta Anaesthesiol Scand. 2013;57(1):46–55. 50. Stein DM, Hu PF, Brenner M, et al. Brief episodes of intracranial hypertension and cerebral hypoperfusion are associated with poor functional outcome after severe traumatic brain injury. J Trauma. 2011;71(2):364–73; discussion 73–4. 51. Stocchetti N, Zanaboni C, Colombo A, et al. Refractory intracranial hypertension and ‘‘second-tier’’ therapies in traumatic brain injury. Intensive Care Med. 2008;34(3):461–7. 52. Tasaki O, Shiozaki T, Hamasaki T, et al. Prognostic indicators and outcome prediction model for severe traumatic brain injury. J Trauma. 2009;66(2):304–8.

53. Vik A, Nag T, Fredriksli OA, et al. Relationship of ‘‘dose’’ of intracranial hypertension to outcome in severe traumatic brain injury. J Neurosurg. 2008;109(4):678–84. 54. Struchen MA, Hannay HJ, Contant CF, Robertson CS. The relation between acute physiological variables and outcome on the Glasgow Outcome Scale and Disability Rating Scale following severe traumatic brain injury. J Neurotrauma. 2001;18(2): 115–25. 55. Levin HS, Eisenberg HM, Gary HE, et al. Intracranial hypertension in relation to memory functioning during the first year after severe head injury. Neurosurgery. 1991;28(2):196–9; discussion 200. 56. Treggiari MM, Schutz N, Yanez ND, Romand JA. Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review. Neurocrit Care. 2007;6(2):104–12. 57. Kobayashi S, Nakazawa S, Yano M, Yamamoto Y, Otsuka T. The value of intracranial pressure (ICP) measurement in acute severe head injury showing diffuse cerebral swelling. In: Ishi S, Nagai H, Brock M, editors. Intracranial pressure V. Berlin: Springer; 1983. p. 527–31. 58. Miller JD, Becker DP, Ward JD, Sullivan HG, Adams WE, Rosner MJ. Significance of intracranial hypertension in severe head injury. J Neurosurg. 1977;47(4):503–16. 59. Miller JD, Butterworth JF, Gudeman SK, et al. Further experience in the management of severe head injury. J Neurosurg. 1981;54(3):289–99. 60. Narayan RK, Greenberg RP, Miller JD, et al. Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure. J Neurosurg. 1981;54(6):751–62. 61. Vukic M, Negovetic L, Kovac D, Ghajar J, Glavic Z, Gopcevic A. The effect of implementation of guidelines for the management of severe head injury on patient treatment and outcome. Acta Neurochir (Wien). 1999;141(11):1203–8. 62. Alali AS, Fowler RA, Mainprize TG, Scales DC, Kiss A, de Mestral C, Ray JG, Nathens AB. Intracranial pressure monitoring in severe traumatic brain injury: results from the American College of Surgeons Trauma Quality Improvement Program. J Neurotrauma. 2013;30(20):1737–46. 63. Clayton TJ, Nelson RJ, Manara AR. Reduction in mortality from severe head injury following introduction of a protocol for intensive care management. Br J Anaesth. 2004;93(6):761–7. 64. Fakhry SM, Trask AL, Waller MA, Watts DD. Management of brain-injured patients by an evidence-based medicine protocol improves outcomes and decreases hospital charges. J Trauma. 2004;56(3):492–9; discussion 9–500. 65. Spain DA, McIlvoy LH, Fix SE, et al. Effect of a clinical pathway for severe traumatic brain injury on resource utilization. J Trauma. 1998;45(1):101–4; discussion 4–5. 66. Arabi YM, Haddad S, Tamim HM, et al. Mortality reduction after implementing a clinical practice guidelines-based management protocol for severe traumatic brain injury. J Crit Care. 2010;25(2):190–5. 67. Haddad S, Aldawood AS, Alferayan A, Russell NA, Tamim HM, Arabi YM. Relationship between intracranial pressure monitoring and outcomes in severe traumatic brain injury patients. Anaesth Intensive Care. 2011;39(6):1043–50. 68. Bulger EM, Nathens AB, Rivara FP, et al. Management of severe head injury: institutional variations in care and effect on outcome. Crit Care Med. 2002;30(8):1870–6. 69. Cremer OL, van Dijk GW, van Wensen E, et al. Effect of intracranial pressure monitoring and targeted intensive care on functional outcome after severe head injury. Crit Care Med. 2005;33(10):2207–13.

123

Neurocrit Care 70. Eddy VA, Vitsky JL, Rutherford EJ, Morris JA Jr. Aggressive use of ICP monitoring is safe and alters patient care. Am Surg. 1995;61(1):24–9. 71. Gelpke GJ, Braakman R, Habbema JD, Hilden J. Comparison of outcome in two series of patients with severe head injuries. J Neurosurg. 1983;59(5):745–50. 72. Marshall LF, Smith RW, Shapiro HM. The outcome with aggressive treatment in severe head injuries. Part I: The significance of intracranial pressure monitoring. J Neurosurg. 1979;50(1):20–5. 73. Mauritz W, Steltzer H, Bauer P, Dolanski-Aghamanoukjan L, Metnitz P. Monitoring of intracranial pressure in patients with severe traumatic brain injury: an Austrian prospective multicenter study. Intensive Care Med. 2008;34(7):1208–15. 74. Murray LS, Teasdale GM, Murray GD, Miller DJ, Pickard JD, Shaw MD. Head injuries in four British neurosurgical centres. Br J Neurosurg. 1999;13(6):564–9. 75. Stocchetti N, Penny KI, Dearden M, et al. Intensive care management of head-injured patients in Europe: a survey from the European brain injury consortium. Intensive Care Med. 2001;27(2):400–6. 76. Lane PL, Skoretz TG, Doig G, Girotti MJ. Intracranial pressure monitoring and outcomes after traumatic brain injury. Can J Surg. 2000;43(6):442–8. 77. Shafi S, Diaz-Arrastia R, Madden C, Gentilello L. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma. 2008;64(2):335–40. 78. Stein SC, Georgoff P, Meghan S, Mirza KL, El Falaky OM. Relationship of aggressive monitoring and treatment to improved outcomes in severe traumatic brain injury. J Neurosurg. 2010;112(5):1105–12. 79. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranialpressure monitoring in traumatic brain injury. N Engl J Med. 2012;367(26):2471–81. 80. Smith HP, Kelly DL Jr, McWhorter JM, et al. Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring. J Neurosurg. 1986;65(6):820–4. 81. Gerber LM, Chiu YL, Carney N, Ha¨rtl R, Ghajar J. Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg. 2013;119(6):1583–90. 82. Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker MD. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988;69(1):15–23. 83. Shiozaki T, Sugimoto H, Taneda M, et al. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg. 1993;79(3):363–8. 84. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011;364(16):1493–502. 85. Marmarou A, Saad A, Aygok G, Rigsbee M. Contribution of raised ICP and hypotension to CPP reduction in severe brain injury: correlation to outcome. Acta Neurochir Suppl. 2005;95:277–80. 86. Ratanalert S, Phuenpathom N, Saeheng S, Oearsakul T, Sripairojkul B, Hirunpat S. ICP threshold in CPP management of severe head injury patients. Surg Neurol. 2004;61(5):429–34; discussion 34–35. 87. Chambers IR, Treadwell L, Mendelow AD. Determination of threshold levels of cerebral perfusion pressure and intracranial pressure in severe head injury by using receiver-operating characteristic curves: an observational study in 291 patients. J Neurosurg. 2001;94(3):412–6. 88. Resnick DK, Marion DW, Carlier P. Outcome analysis of patients with severe head injuries and prolonged intracranial hypertension. J Trauma. 1997;42(6):1108–11.

123

89. Young JS, Blow O, Turrentine F, Claridge JA, Schulman A. Is there an upper limit of intracranial pressure in patients with severe head injury if cerebral perfusion pressure is maintained? Neurosurg Focus. 2003;15(6):E2. 90. Kahraman S, Dutton RP, Hu P, et al. Heart rate and pulse pressure variability are associated with intractable intracranial hypertension after severe traumatic brain injury. J Neurosurg Anesthesiol. 2010;22(4):296–302. 91. Talving P, Karamanos E, Teixeira PG, Skiada D, Lam L, Belzberg H, Inaba K, Demetriades D. Intracranial pressure monitoring in severe head injury: compliance with Brain Trauma Foundation guidelines and effect on outcomes: a prospective study. J Neurosurg. 2013;119(5):1248–54. 92. Whitmore RG, Thawani JP, Grady MS, Levine JM, Sanborn MR, Stein SC. Is aggressive treatment of traumatic brain injury cost-effective? J Neurosurg. 2012;116(5):1106–13. 93. Dias C, Maia I, Cerejo A, Varsos G, Smielewski P, Paiva JA, Czosnyka M. Pressures, flow, and brain oxygenation during plateau waves of intracranial pressure. Neurocrit Care 2014;21(1):124–32. 94. Le Roux P, Lam AM, Newell DW, Grady MS, Winn HR. Cerebral arteriovenous difference of oxygen: a predictor of cerebral infarction and outcome in severe head injury. J Neurosurg. 1997;87:1–8. 95. Vespa PM, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, Glenn T, Hovda DA. Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med. 2007;35(4):1153–60. 96. Stiefel MF, Udoetek J, Spiotta A, Gracias VH, Goldberg AH, Maloney-Wilensky E, Bloom S, Le Roux P. Conventional neurocritical care and cerebral oxygenation after traumatic brain injury. J Neurosurg. 2006;105:568–75. 97. Menon DK, Coles JP, Gupta AK, Fryer TD, Smielewski P, Chatfield DA, Aigbirhio F, Skepper JN, Minhas PS, Hutchinson PJ, Carpenter TA, Clark JC, Pickard JD. Diffusion limited oxygen delivery following head injury. Crit Care Med. 2004;32:1384–90. 98. Adamides AA, Rosenfeldt FL, Winter CD, et al. Brain tissue lactate elevations predict episodes of intracranial hypertension in patients with traumatic brain injury. J Am Coll Surg. 2009;209:531–9. 99. Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M. Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study. Acta Neurochir (Wien). 2008;150:461–9. 100. Robertson CS, Valadka AB, Hannay HJ, Contant CF, Gopinath SP, Cormio M, Uzura M, Grossman RG. Prevention of secondary ischemic insults after severe head injury. Crit Care Med. 1999;27(10):2086–95. 101. Kosty JA, Le Roux PD, Levine J, Park S, Kumar MA, Frangos S, Maloney-Wilensky E, Kofke WA. Brief report: a comparison of clinical and research practices in measuring cerebral perfusion pressure: a literature review and practitioner survey. Anesth Analg. 2013;117(3):694–8. 102. Aries MJ, Czosnyka M, Budohoski KP, Steiner LA, Lavinio A, Kolias AG, Hutchinson PJ, Brady KM, Menon DK, Pickard JD, Smielewski P. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012;40(8):2456–63. 103. Gu¨iza F, Depreitere B, Piper I, Van den Berghe G, Meyfroidt G. Novel methods to predict increased intracranial pressure during intensive care and long-term neurologic outcome after traumatic brain injury: development and validation in a multicenter dataset. Crit Care Med. 2013;41(2):554–64. 104. Feng M, Zhang Z, Guan C, Hardoon DR, King NK, Pang BC, Ang BT. Utilization of temporal information for intracranial pressure development trend forecasting in traumatic brain injury. Conf Proc IEEE Eng Med Biol Soc. 2012;2012:3930–4.

Neurocrit Care 105. Hukkelhoven CW, Steyerberg EW, Habbema JD, Maas AI. Admission of patients with severe and moderate traumatic brain injury to specialized ICU facilities: a search for triage criteria. Intensive Care Med. 2005;31(6):799–806. 106. Holliday PO 3rd, Kelly DL Jr, Ball M. Normal computed tomograms in acute head injury: correlation of intracranial pressure, ventricular size, and outcome. Neurosurgery. 1982;10(1): 25–8.

107. Lobato RD, Sarabia R, Rivas JJ, et al. Normal computerized tomography scans in severe head injury. Prognostic and clinical management implications. J Neurosurg. 1986;65(6):784–9. 108. O’Sullivan MG, Statham PF, Jones PA, et al. Role of intracranial pressure monitoring in severely head-injured patients without signs of intracranial hypertension on initial computerized tomography. J Neurosurg. 1994;80(1):46–50.

123