A Trial of Intracranial Pressure Monitoring in Traumatic Brain Injury — What Do We Do Now?

Abstract & Commentary

By Halinder S. Mangat, MD, Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Mangat reports no financial relationships relevant to this field of study.

Synopsis: Intracranial pressure (< 20 mmHg)-guided therapy in patients with severe traumatic brain injury was not shown to be superior to care based on imaging and clinical examination.

Source: Chesnut RM, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012;367:2471-2481.

Chesnut et al have performed the first randomized, controlled trial to evaluate the benefit of intracranial pressure (ICP) monitoring on outcome after severe traumatic brain injury (TBI). The study compares ICP-guided therapy to therapy based on clinical examination and periodic CT-based brain imaging. It was conducted at five centers in Bolivia and one in Ecuador. Patients were included if they arrived within 24 hours of injury, had a closed head injury, had a Glasgow Coma Scale (GCS) score of ≤ 8, a motor score of ≤ 5 if intubated, and were randomized within 24 hours of injury or within 24 hours of deterioration to a GCS of ≤ 8. Patients were excluded if they had a GCS of 3 with bilateral fixed and dilated pupils. There was a decision to not actively treat before enrollment, if there was no ICU bed or no ICP monitor available, if the patient had a non-survivable injury, if the patient was pregnant or a prisoner, or if there was no informed consent. The treatment protocol included basic nursing monitoring and care measures, prophylaxis, and thresholds for laboratory measures. Routine CT scans were obtained on admission, 48 hours, and 5-7 days after the first scan in the imaging group. Intracranial hypertension was treated by tiered algorithms, which were similar in both groups and were titrated to ICP < 20 mmHg or utilized based on imaging and clinical examination.

Six-month outcome, which was a composite of 21 components including survival and neuropsychological testing, was not different in the two groups. Thirty-day mortality was 21% in the ICP monitoring group and 30% in the imaging-medical examination group. However, this difference was not statistically significant. Six-month mortality was 39% in the ICP monitoring group and 41% in the imaging-clinical exam group.

Commentary

The Brain Trauma Foundation has developed guidelines for the management of severe TBI. ICP (and cerebral perfusion pressure)-guided therapy is a central tenet of the TBI guidelines. As there have not been any randomized, controlled trials demonstrating a direct benefit of ICP monitoring in improving outcomes, it is a level II and III recommendation.1 The recommendation is based on studies showing improved outcome in patients treated utilizing ICP monitoring compared to historical controls, small non-randomized studies, and studies published from prospectively collected observational data. Furthermore, the threshold of 20 mmHg at which ICP must be treated is also a level II recommendation.2 In spite of these recommendations in the TBI guidelines, there has been doubt over the direct benefit from ICP monitoring, and whether elevated ICP is merely a marker of severity of injury.

In a retrospective study, Badri et al demonstrated the prognostic correlation of average ICP in the first 48 hours with mortality, and functional and neuropsychological outcome at 6 months.3 They found that the unadjusted odds ratio for death was 2.33 per 10 mmHg increase in average initial 48-hour ICP. However, within survivors there was no association between average ICP and neuropsychological function.

In separate publications from prospectively collected data from the New York state TBI-trac database, Ghajar and colleagues demonstrated significantly lower mortality in patients who underwent ICP monitoring (19.6%; n = 1084) vs patients who did not undergo ICP monitoring (33.2%, n = 223) following severe TBI.4 These are robust data as the two groups were controlled for covariates that affect outcome: age, GCS, pupillary reactivity, brain CT findings, and hypotension. They further demonstrated that patients with ICP monitoring who responded to ICP-lowering therapy had a significantly lower risk of death at 2 weeks (14.7%, n = 95) than those who did not respond (31.4%, n = 274), after adjustment for independent factors as above.5

The trial by Chesnut et al is very well conceived, executed, and remarkable for the high follow-up rate of 92%. However, there are some shortcomings. Thirty-nine percent of patients screened were excluded from the study. Only 45% of patients were transported by ambulance, likely implying inadequate pre-hospital care. This potentially placed the patients at risk of hypoxia and hypotension, which are both highly important pre-hospital factors that influence outcome. In some cases, arrival at hospitals was several hours after injury, further prolonging this vulnerability and duration of insults. The patients were also a severely injured group, with a median GCS of 4, one or both pupillary abnormalities in 44%, midline shift > 5 mm in 36%, and compressed mesencephalic cisterns in 85% of patients. This may make the findings less applicable to less severely injured patients. The Kaplan-Meier survival plot appeared to show early differences in survival between the two groups at day 14, but this trend was slowly reversed over the period of the study. Mortality almost doubled in the ICP group between the initial 30-day period and 6 months. This is most likely related to post-hospital health care systems or lack thereof. The highest mortality in TBI patients tends to be in the first 2 weeks. Therefore, the initial 30-day mortality difference of 21% vs 30% in the ICP and imaging group, respectively, is important. There appears to be a tendency of benefit in the ICP monitoring group, even if it is not statistically significant. And this lack of significant difference may be influenced by pre-hospital factors such as hypotension and hypoxia, which could have blunted the outcome differences.

In summary, while this is a historic trial, the takeaway message must not be to stop pursuing ICP monitoring in patients with severe TBI. As highlighted above, the results of the trial leave some important unanswered questions. One must contemplate carefully the use of different treatments instituted for ICP-directed therapy. Perhaps the adverse effects of these therapies also offset some benefit that is gained by ICP monitoring. It has been shown that adoption of Brain Trauma Foundation guidelines has decreased overall mortality from TBI. Therefore, this apparent contradiction must be handled with care until further convincing data are available, and ICP monitoring should be continued. Clinical examination and imaging should be performed as often as possible. And we must be circumspect of the targets we set for ICP treatment and the therapies we choose.

Reference

  1. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS. Bratton SL, et al. Guidelines for the management of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma 2007;24(Suppl 1):S37-S44.
  2. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS. Bratton SL, et al. Guidelines for the management of severe traumatic brain injury. VIII. Intracranial pressure thresholds. J Neurotrauma 2007;24(Suppl 1):S55-S58.
  3. Badri S, et al. Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med 2012;38:1800-1809.
  4. Farahvar A, et al. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg 2012;117:729-734.
  5. Farahvar A, et al. Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury. J Neurosurg 2011;114:1471-1478.