Traumatic brain injuries (TBI) are reported to have a high mortality and morbidity rate among patients, as 60% of those that have had such injuries will die as a result or live with significant disabilities. It is estimated that TBI has an annual economic burden of more than $60 billion in the United States of America.

One of the goals of care for patients that have sustained TBI is the mitigation of secondary neurological insults such as increased intracranial pressure (ICP). While some patients can be treated through medications such as mannitol, many of those that suffer from increased ICP subsequent to injury remain refractory to treatment. These patients are treated with a surgical procedure- decompressive craniectomy. The objective of the present study was to investigate the efficacy of bi-frontotemporoparietal decompressive craniectomy in patients <60 years of age who have sustained TBIs and have experienced ICP that was not brought below acceptable targets by surgical therapies or intensive care.

The investigators recruited patients over approximately seven years (December 2002-April 2010) from intensive care units (ICU) in Australia, New Zealand, and Saudi Arabia. Patients were included in the study if they were between 15-59 years old and had significant non-penetrating injuries to the brain. The severity of the injuries to the brain was defined as a score of three to eight on the Glasgow Coma Scale or Marshall Class III. Potential participants were excluded from the trial if they were deemed by their care team to be unsuitable for active treatment, had unreactive dilated pupils, had an injury to the spinal cord, had cardiac arrest or if they had mass lesions (unless such masses were too small to operate). 155 patients of the 3478 assessed for eligibility for trial participants were enrolled.

Each patient received care in ICUs that included advanced neurosurgical care and ICP monitoring. Treatment for intracranial hypertension was given if patients achieved a pressure greater than 20 mm Hg. The authors defined ICP early refractory elevation as a non-stimulated increase in ICP that was greater than 15 minutes in length regardless of whether the increase was continuous or intermittent. This increase had to occur within a one-hour period despite patients receiving first-tier treatment such as optimal sedation, mannitol, hypertonic saline, blockage of the neuromuscular junction, external ventricular drainage and the normalization of arterial carbon dioxide pressure. Patients were randomly designated to receive decompressive craniectomy + standard of care or to receive solely the standard of care, 72 hours following the sustainment of injury. Stratification of the randomization was done based on the centre and the method of ICP measurement used (parenchymal catheter vs external ventricular drain). Data collection was performed by research coordinators at the respective sites.

At first, the primary outcome that was assessed by the trial was the poor outcome, which was defined as death, vegetative state, or severe disability. This was assessed based on the extended Glasgow scale, six months following the original injury. The final primary outcome that was measured by investigators was the score patients received on the extended Glasgow scale at 6 months post-injury.

73 patients were randomly assigned to receive early decompressive craniectomy, while 82 received standard care.  The median age of patients undergoing craniectomy or standard of care was 23.7 and 24.6 years respectively. The median ICP 12 hours prior to randomization was 20 mm HG (range 18-22) in both experimental groups. Additionally, prior to the process of randomization, 93% of the two study groups were given similar levels of mannitol or hypertonic saline or both for the treatment of intracranial hypertension. 96% of all patients were administered the assigned trial treatment according to the group they were randomized into. However, 18% of patients (15) allocated to the standard of care group received delayed decompressive craniectomy as a lifesaving procedure.

The investigators found that following randomization, the patients that received the early decompressive craniectomy required fewer interventions to reduce ICP relative to the standard of care group. Moreover, patients of the craniectomy group had a lower average ICP relative to the standard care group (14.4 mm Hg vs. 19.1 mm Hg, P<0.001). Additionally, the researchers found that the median intracranial hypertension index was higher in the standard of care group relative to the craniectomy group (19.9 vs 11.59, P<0.001).

The group that received the surgical procedure spent less time on mechanical ventilation and in the ICU relative to patients that received standard care. However, the investigators observed no significant difference between the groups in total time spent in the hospital. More patients in the craniectomy group (37%) developed medical or surgical complications than those in the standard-of-care group (17%). Of note, hydrocephalus was observed more often in the craniectomy group (10%) than in the standard of care group (1%).

6 months post-injury, the investigators used the Extended Glasgow Scale to determine the primary outcomes. They found that the scores were worse in the craniectomy group relative to the standard of care group (median score, 3 vs. 4; the odds ratio for a worse functional outcome in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03). Moreover, 70% of patients in the craniectomy group (51) developed poor outcomes, as opposed to 51% in the standard of care group (42) (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). The investigators observed that 19% of craniectomy patients (14) passed away, and 18% of standard-of-care patients (15) passed away.

The investigators recognized that their study had limitations. Firstly, the medical and surgical teams were not blinded for the group assignments, as only the assessors were unaware of the assignments. Secondly, one surgical centre was responsible for recruiting more than 33% of the study participants. Furthermore, the investigators noted that there were inequalities in baseline traits of the patients such as the fraction of patients that presented without pupil reactivity at admission into the hospital. Moreover, patients with a Glasgow Coma Scale of 3 have poor prognoses and are not typically considered for this surgical procedure. Therefore, they should not have been included in the study or the investigators should have separately stratified this group of patients. Patients with a very low Glasgow Coma Scale  (3-5) we will do poorly regardless of medical or surgical therapy with very rare occasional surprises.  And it is almost impossible to identify that 1% of patients in this group who may recover. Lastly, the research teams altered the primary outcome measure throughout the trial, while maintaining the groups. Ultimately,  decompressive craniotomy is effective in patients with higher Glasgow Coma Scale 8–11 who deteriorate with increased intracranial pressure and become refractory to medical therapy. In an appropriate selective patient group, this procedure is effective when performed appropriately.

In conclusion, while craniectomy reduced ICP, and time spent on mechanical ventilation and in ICU relative to standard of care, these patients had a lower median score on the Extended Glasgow Scale than standard-of-care patients. Moreso, patients that received craniectomy were found to have a greater risk of having poor outcomes relative to those receiving standard of care. 

Citation:

Cooper, D. J., Rosenfeld, J. V., Murray, L., Arabi, Y. M., Davies, A. R., D’Urso, P., … & Wolfe, R. (2011). Decompressive craniectomy in diffuse traumatic brain injury. New England Journal of Medicine, 364(16), 1493-1502.