30 1 / 2013

Harvard Neurosurgery Resident, Dr. Brian Walcott, Summarizes Landmark Trial from NEJM

Brian Walcott is a senior resident in neurological surgery at the Massachusetts General Hospital/Harvard Medical School, where he specializes in the care of patients suffering from diseases of the brain, cerebral blood vessels, skull base, and spine. His research interest is in vascular biology and he has developed various zebrafish models to study vascular malformations and the vascularity of cancer. He is the author of more than 75 papers in international peer reviewed journals.  He is passionate about medical education and was recently awarded the resident teacher of the year award from the Harvard Medical School class of 2012.  Brian is a Docphin Ambassador.

Title: Decompressive Craniectomy in Diffuse Traumatic Brain Injury

Authors: D. James Cooper, M.D., Jeffrey V. Rosenfeld, M.D., Lynnette Murray, B.App.Sci., Yaseen M. Arabi, M.D., Andrew R. Davies, M.B., B.S., Paul D’Urso, Ph.D., Thomas Kossmann, M.D., Jennie Ponsford, Ph.D., Ian Seppelt, M.B., B.S., Peter Reilly, M.D., and Rory Wolfe, Ph.D. for the DECRA Trial Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group 

Journal: New England Journal of Medicine

Date: April 2011 

URL: https://www.docphin.com/articledetail.aspx?articleID=63538

Study relevance

Traumatic brain injury is a major cause of morbidity and mortality, particularly in the young population.  The current standard of care, outlined in the Brain Trauma Foundation guidelines, is centralized around the management of intracranial pressure (ICP) as a way to prevent “secondary neurological injury.”  In most cases of severe injury, ICP is monitored with an invasive device and escalating tiers of treatment are instituted to maintain normal ICP. Initial measures control ICP include “first-tier” therapies such as sedation, maintenance of normal carbon dioxide level, optimization of blood pressure, use of bolus osmotherapy, and drainage of cerebrospinal fluid in a standardized, escalated manner. When these therapies fail in terms of ICP control, patients are considered for decompressive craniectomy or further escalation of medical care, such as barbiturate coma or hypothermia.  The DECRA trial published in the NEJM is the first randomized study of decompressive craniectomy in patients with diffuse traumatic brain injury.  

Results

Over an eight year period, 155 adults admitted to multiple institutions with severe diffuse traumatic brain injury refractory to initial medical therapies were randomized to either bifrontal craniectomy or continued medical management.  The main outcome measure was the Extended Glasgow Outcome Scale score at six month follow up. 

Major findings of the study included:

·      Patients undergoing craniectomy had lower intracranial pressure and spent less time in the intensive care unit

·      Patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale and greater risk of unfavorable outcome

·      Mortality rates in both groups were similar at six months 

Discussion 

The DECRA trial concluded that despite lower ICP measurements, outcomes were worse in the group randomized to decompressive craniectomy.   This is a surprising finding, since management of ICP is historically viewed as the most effective means of treating traumatic brain injury.  There have been several criticisms of the study design, ranging from surgical technique to inclusion criteria.  Regardless of the validity of the study and its acceptance in the medical community, the controversial aspects raised in the discussion are useful when considering the design of future studies.

Ultimately, it is possible that traumatic brain injury has profound effects on brain systems that are remote from the site of perceived injury and were not able to be accounted for in the study design. These effects may contribute to long-term neurological outcome.  Advanced neuroimaging, such as magnetic resonance tractography analysis, may be able to help more accurately compare patient injuries, thereby reducing these potential confounding factors.  Furthermore, there is not currently an adequate means to evaluate outcomes from regional versus global intracranial pressure crisis, although there is a suggestion in the DECRA results that worse outcomes were associated with temporal lobe brain herniation, (with twice as many patients in the craniectomy group having fixed and dilated pupils). 

Whether one supports the use of craniectomy or not in severe traumatic brain injury, craniectomy itself doesn’t prevent cerebral edema formation and has even been reported to precipitate progressive secondary hemorrhage.  Pharmacological trials underscore the importance of recent advances in understanding the role of the molecular targets in traumatic injury. One active study is a randomized trial of glyburide in patients with moderate-to-severe TBI to prevent cerebral edema and hemorrhage (ClinicalTrials.gov Identifier: NCT01454154).  Animal studies suggest that the vast majority of secondary injury can be prevented with pharmacological therapy directed at specific molecular targets.  Hopefully, the day will come soon when medication can control brain swelling and skull removal operations are not necessary.

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