Our results do not support the hypothesized superiority of management guided by intracranial-pressure monitoring over management guided by neurologic examination and serial CT imaging in patients with severe traumatic brain injury. Intracranial-pressure monitoring is the cornerstone of treatment for severe traumatic brain injury. The principle guiding additional interventions, such as the monitoring of cerebral perfusion pressure or tissue-perfusion modification, is the maintenance of intracranial pressure below 20 mm Hg.
Most of the data from nonrandomized, controlled trials support the association of treatment based on monitored intracranial pressure with improved recovery, which has led to the recommendation of this approach in successive editions of published guidelines for the management of severe traumatic brain injury4–7
(although there have been calls for a randomized, controlled trial). Dissenting literature does exist. In two retrospective studies, there was no association15
or a negative association16
between monitoring-based treatment and outcome, and in an older, small, low-quality study of the usefulness of monitoring in guiding mannitol dosing, monitoring was not found to be useful.17
Since our study was conducted in Bolivia and Ecuador, the extent to which the findings can be generalized to other patient populations warrants discussion. Our data suggest that the care provided in the study hospitals adhered to the fundamentals of ICU care and was consistent with the study design. Prehospital resuscitation is less developed in Bolivia and Ecuador than in higher-income countries, and the more severely injured patients in those two countries may not survive long enough to reach the hospital. Thus, the study population may have had less severe brain injury than comparable ICU populations in higher-income countries. On the other hand, less advanced prehospital resuscitation may result in secondary insults (e.g., hypoxemia and hypotension), which would serve to increase the severity of the injury. In our study, the initial and subsequent readings of intracranial pressure, findings on CT, and pupillary responses were all consistent with very severe injury. The early outcome curves in our study appear to be consistent with what would be expected for young adults with severe brain injury whose care was being well managed in ICUs in wealthier countries. The results we report on early mortality were also similar to those reported in higher-income countries.14
Survival at 6 months is confounded by high mortality (35% of the deaths) after the first 14 days, which is probably related to the limited resources available after discharge from the ICU. None of the study participants received rehabilitation or extensive medical care after hospital discharge. The elderly population with traumatic brain injury, which is prominent in high-income countries, was not represented in this study.
Between-group differences in the individual treatments delivered (with greater use of hyper-tonic saline, mannitol, and hyperventilation in the imaging–clinical examination group than in the pressure-monitoring group) reflect differences in approaches to treatment: scheduled treatment in the imaging–clinical examination protocol and treatment as indicated in the pressure-monitoring protocol. The quantitative measurement of intracranial pressure and the consequent fixed treatment threshold probably explains the more frequent administration of high-dose barbiturates and high-dose hypertonic saline in the pressure-monitoring group.
There was a need to standardize the type of monitoring used. Intraparenchymal monitoring was chosen for its accuracy,7
ease of insertion, safety profile,18
and low maintenance requirements. The alternative — a transduced ventricular catheter, which is accepted worldwide and was available but rarely used at the study sites before the start of the study — was not believed to be as compatible with our study setting, even though it offers the inherently useful therapeutic option of draining cerebrospinal fluid. Cerebrospinal-fluid drainage was a treatment option that would have required separate ventriculostomy placement — an approach to monitoring that is similar to that specified in the protocol for the ongoing Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (BOOST 2) trial (ClinicalTrials.gov number, NCT00974259). Drainage of cerebrospinal fluid is consistent with guidelines-based management.7
Although it is effective as a means of lowering elevated intracranial pressure temporarily,19
drainage has not been shown to improve the outcome of severe traumatic brain injury.20
At issue here is not the question of whether intracranial pressure is important — both groups were treated for intracranial hypertension. We investigated whether the guidelines-based7
protocol used in this study significantly improved the outcome. Our results do not support the superiority of treatment based on intracranial-pressure monitoring7
over treatment guided by neurologic testing and serial CT imaging in improving short-term or long-term recovery in the general population of patients with severe traumatic brain injury. This finding does not argue against the use of intracranial–pressure monitoring. Only the monitoring-based interventional algorithm was tested here. It is possible that the imaging–clinical examination protocol provided superior control of intracranial pressure.17
Alternatively, the lack of efficacy may be attributable to other factors, such as the use of a universal threshold for intracranial pressure or the efficacies and toxic effects of the therapeutic agents used, individually or in combination. Additional reasons for the lack of efficacy may include the interpretation of the data on intracranial pressure (a focus on instantaneous values rather than trends or on intracranial pressure rather than cerebral compliance), the lack of identification of subtypes of traumatic brain injury requiring different approaches to management (subtype identification may evolve over the course of treatment), the universal primacy of manipulation of intracranial pressure as opposed to consideration of other physiological interventions (e.g., management of cerebral perfusion pressure), or even the consideration of intracranial pressure as a treatment variable rather than merely an indication of disease severity.
The value of knowing the precise intracranial pressure is not being challenged here, nor is the value of aggressively treating severe traumatic brain injury being questioned. Rather our data suggest that a reassessment of the role of manipulating monitored intracranial pressure as part of multimodality monitoring and targeted treatment of severe traumatic brain injury is in order.