BTF Guidelines - Inhospital Severe TBI Guidelines - Intracranial Pressure Thresholds

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Recommendations
A. Level I
There are insufficient data to support a Level I recommendation for this topic.
B. Level II
Treatment should be initiated with intracranial pressure (ICP) thresholds above 20 mm Hg.
C. Level III
A combination of ICP values, and clinical and brain CT findings, should be used to determine the need for treatment.
Overview
Quantitative guidelines are needed for ICP management. The impact of ICP on outcome from severe traumatic brain injury (TBI) appears to lie in its role in determining cerebral perfusion pressure (CPP), and as an indicator of mass effect. Since CPP can be managed by manipulation of arterial pressure to a great extent, the issue of herniation is more determinant of the ICP threshold. The goal is to balance the risks of herniation against the iatrogenic risks of overtreatment.
Process
For this update, Medline was searched from 1996 through April of 2006 (see Appendix B for search strategy), and results were supplemented with literature recommended by peers or identified from reference lists. Of 10 potentially relevant studies, 3 were added to the existing table and used as evidence for this question (Evidence Table I).
Scientific Foundation
There remain no large randomized trials that directly compare ICP treatment thresholds. The largest study using prospectively collected, observational data, controlling for a large number of confounding prognostic variables, analyzed the mean ICP in 5 mmHg steps against outcome in a logistic regression model, and found 20 mm Hg to have the optimal predictive value.

These values are in keeping with small, non-controlled reports suggesting a range of 15-25 mm Hg. The report by Saul and Ducker changed the ICP threshold from 25 to 15 mm Hg in two sequentially treated groups of patients and found an associated decrease in mortality from 46% to 28%. However, differences in protocols between the first and second treatment periods confound the determination of the independent influence of lowering the ICP treatment threshold on outcome. Shreiber et al. assessed prospectively collected data from 233 patients regarding the impact on survival for multiple predictive parameters. They found an ICP>=15 mm Hg was one of five independent risk factors associated with death.

The study by Eisenberg et al. is the only prospective, double-blind, placebo-controlled study demonstrating improved outcome attributable to lowering ICP. Their lowest ICP thresholds were 25 mm Hg in patients without craniectomy and 15 mm Hg in patients following craniectomy. However, they defined additional ICP thresholds at higher pressures and shorter durations (for details, see Anesthetics, Analgesics, and Sedatives chapter), and they did not stratify outcome by threshold.

A small prospective trial reported 27 patients assigned to ICP treatment groups of 20 or 25 mm Hg. Identical treatment protocols were used, including maintenance of CPP at >70 and SjO₂ at >54%. The 6-month GOS found no difference between groups.

Patients can herniate at intracranial pressures less than 20-25 mm Hg. The likelihood of herniation depends on the location of an intracranial mass lesion. In the report by Marshall et al., pupillary abnormalities occurred with ICP values as low as 18 mm Hg. Therefore, at all points, any chosen threshold must be closely and repeatedly corroborated with the clinical exam and CT imaging in an individual patient.

The intracranial pressure at which patients begin to show signs of neurological deterioration can also occasionally be greater than 20-25 mm Hg. There is some evidence that ICPs higher than 20 mm Hg may be tolerated in patients that have minimal or no signs of brain injury on their CT scans.
Summary
Current data support 20-25 mm Hg as an upper threshold above which treatment to lower ICP should generally be initiated.
Key Issues for Future Investigation
The critical value of ICP and its interaction with CPP and other measures (e.g., SjO₂, PbtO2, CBF) is a major unanswered question. As the importance of other parameters is recognized and the ability is improved to safely maintain adequate intracranial parameters somewhat independently of ICP, the issue of an absolute value for ICP may become less important. ICP may be most closely related to the risk of herniation, which seems to vary between and within patients over the course of therapy. Two potentially important steps toward identifying more concrete treatment thresholds for ICP are to:
- Develop a method to estimate "herniation pressure"
- Determine the critical values for other parameters

Evidence Tables

Evidence Table I: Intracranial Pressure Thresholds

Reference	Data Class	Description of Study	Conclusion
Andrews et al., 19881	III	Retrospective review of the clinical course and CT scans of 45 patients with supratentorial intracerebral hematomas to determine the effect of hematoma location on clinical course and outcome.	Signs of herniation were significantly more common with temporal or temporoparietal lesions. Clot size of 30 cc was the threshold value for increased incidence of herniation. Factors other than ICP (such as location of mass lesion) must be considered in guiding treatment.
Eisenberg et al., 19883	II	Prospective, multicenter study wherein 73 severe TBI patients, whose ICP was not controllable using "conventional therapy" were randomly assigned to a high-dose pentobarbital vs. placebo-control regimen. Dependent variable was ability to control ICP below 20 mm Hg.	The outcome for study patients whose ICP could be kept below 20 mmHg using either regimen was significantly better than those whose ICP could not be controlled.
Marmarou et al., 19914	III	From a prospectively collected database of 1,030 severe TBI patients, all 428 patients who met ICU monitoring criteria were analyzed for monitoring parameters that determined outcome and their threshold values.	Using logistic regression, the threshold value of 20 mm Hg was found to best correlate with outcome at 6 months. The proportion of hourly ICP reading greater then 20 mm Hg was a significant independent determinant of outcome. The four centers used ICP treatment thresholds of 20-25 mm Hg. The degree to which this confounds the regression statistics is unclear. The incidence of morbidity and mortality resulting from severe TBI is strongly related to ICP control wherein 20 mm Hg is the most predictive threshold.
Marshall et al., 19795	III	Retrospective review of 100 consecutively admitted severe TBI patients.	Patients managed with a regimen including ICP monitoring using a threshold of 15 mm Hg had improved outcome compared to published reports using less ICP-intensive therapy.
Narayan et al., 19827	III	Retrospective analysis of the courses of 207 consecutively admitted severe TBI patients. Management included aggressive attempts to control ICP using a threshold of 20 mm Hg.	Outcome was significantly correlated with the ability to control ICP. ICP control using a threshold of 20 mm Hg as a part of an overall aggressive treatment approach to severe TBI associated with improved outcome.
Saul et al., 19829	III	A series of 127 severe TBI patients whose ICP treatment initiated at 20-25 mm Hg, not using a strict treatment protocol, was compared with a subsequent group of 106 patients with similar injury characteristics who received treatment under a strict protocol at an ICP threshold of 15 mm Hg.	The 46% mortality in the first group was was significantly greater then the 28% mortality in the second group. Suggests an increase in mortality if ICP maintained above a threshold of 15-25 mm Hg.
Chambers et al., 20012	III	Prospective series of 207 adult patients with ICP and CPP monitoring were analyzed using ROC curves to determine if there were significant thresholds for the determination of outcome.	The sensitivity for ICP rose for values >10 mm Hg, but it was only 61% at 30 mm Hg. ICP cut off value for all patients was 35 mm Hg, but ranged from 22 to 36 mm Hg for different CT classifications. It may beinappropriate to set a single target ICP, as higher values may be tolerated in certain CT classifications.
Ratanalert et al., 20048	III	Prospective trial of 27 patients, grouped into ICP treatment thresholds of 20 or 25 mm Hg. Treatment protocols were similar between groups with CPP kept as >70 and SjO₂ at >54%.	No difference in outcome between ICP thresholds of 20 or 25 mm Hg.
Schreiber et al., 200210	III	233 patients with ICP monitoring were analyzed from a prospectively collected database of 368 patients. Potentially predictive parameters were analyzed to determine their impact on survival.	An opening ICP of 15 mm Hg was identified as one of five risk factors associated with higher mortality.