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: Decompressive craniectomy for the treatment of refractory intracranial hypertension in patients with severe traumatic brain injury reduced mortality but increased rates of vegetative states, lower severe disability, and upper severe disability compared to continued medical management.
SOURCE: Hutchinson PJ, Kolias AG, Timofeev IS, et al. Trial of decompressive craniectomy for traumatic intracranial hypertension.
N Engl J Med 2016;375:1119-30. DOI: 10.1056/NEJMoa1605215
Hutchinson et al conducted a randomized, controlled trial to study the effectiveness of decompressive craniectomy as a last-tier therapy in patients with refractory elevation of intracranial pressure (ICP) after severe traumatic brain injury (TBI).1 The surgical intervention was compared to continued medical therapy in the form of continued prior tiered medical therapy and institution of barbiturate coma. Patients between the ages of 10 and 65 years were randomized after surrogate consent if ICP was greater than 25 mmHg for more than one hour, despite maximal tiered medical therapy short of barbiturate coma. Patients with bilateral unreactive pupils and non-survivable injury were excluded. Patients who had craniotomy for surgical lesions were included if the bone flap had been replaced. Prior tiered medical therapy included head elevation, mechanical ventilation, sedation, analgesia, paralysis, ventriculostomy, hyperosmotics, inotropic support, and hypothermia. Patients with unilateral hemispheric swelling underwent lateral frontotemporoparietal craniectomy, whereas those with diffuse bilateral swelling underwent bifrontal craniectomy within 4-6 hours after randomization. Outcomes were measured using GOS-E at six months and secondarily at 12 and 24 months. The authors recruited 409 patients at 52 centers in 20 countries between 2004 and 2014. Baseline characteristics of the 398 patients included for analysis were similar for age, male sex, Glasgow Coma Scale motor score, pupillary abnormality, hypotension, hypoxia, extracranial injury, and Marshall score. In the surgical group, 92.6% underwent craniectomy and 9.4% still required barbiturate therapy, while in the medical group, 87.2% received barbiturates and 37.2% required further decompressive craniectomy. Surgical and medical group outcomes were as follows: mortality 26.9% vs. 48.9%, vegetative state 8.5% vs. 2.1%, lower severe disability (dependent on others for care) 21.9% vs. 14.4%, upper severe disability (independent at home) 15.4% vs. 8.0%, moderate disability 23.4% vs. 19.7%, and good recovery 4% vs. 6.9%. In pre-defined sensitivity analysis, favorable outcomes were 42.8% in the surgical group vs. 34.6% in the medical group. Based on absolute differences, the authors estimated for 100 patients treated surgically, at six months there were 22 more survivors, of whom 36% had favorable outcomes, whereas at 12 months the number with favorable survivors was 59%.
The results of the RESCUEicp trial have been long awaited. The aim of the trial was to study very specifically the effects of decompressive craniectomy when applied in instances of refractory intracranial hypertension. This was defined as failure to all medical therapy except barbiturate coma. The patient selection, randomization, and follow-up were meticulous. Therapy to the point of randomization was identical. Initiation of barbiturate coma or surgical decompression occurred without any significant delay. Mortality was significantly reduced, while functional outcomes are weighed toward worse outcome in surgical patients, although this improved at 12 months.
The previous randomized, controlled trial of craniectomy in TBI (DECRA) showed no improvement in mortality and worse outcomes in surgical patients.2 In the DECRA trial, patients who had ICP > 20 mmHg for more than 15 minutes received decompressive craniectomy as a second-tier therapy. Patients in RESCUEicp had greater incidence of poor functional outcome while good outcomes were not different. However, there was significant crossover from the medical treatment arm to surgical treatment in one-third of the cases, while the surgical arm patients also required additional medical therapy but in a significantly smaller proportion. It is possible that this minimized the benefits. Meanwhile, reduction in high ICP and low cerebral perfusion pressure were significantly greater in the surgical arm. Effects of decompressive craniectomy on ICP and compensatory mechanisms have been demonstrated in earlier studies.3
Reduction in mortality may be viewed as a first step in demonstrating the benefits of decompressive craniectomy, although timing may need to be explored further to determine if earlier surgery perhaps also may improve functional outcomes. The parallel may be made from stroke trials in which decompressive craniectomy was found useful only when surgery was performed very early, and the benefit was lost after 48 hours.4-6 Therefore, it is important that the trial be interpreted strictly in the sense that decompressive craniectomy as a last-tier treatment for severe refractory intracranial hypertension reduces mortality while increasing incidence of unfavorable outcome at six months. The decision for surgical management must be made with this in mind.
- Hutchinson PJ, Kolias AG, Timofeev IS, et al. Trial of decompressive craniectomy for traumatic intracranial hypertension. N Engl J Med 2016;375:1119-1130.
- Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011;364:1493-1502.
- Timofeev I, Czosnyka M, Nortje J, et al. Effect of decompressive craniectomy on intracranial pressure and cerebrospinal compensation following traumatic brain injury. J Neurosurg 2008;108:66-73.
- Hofmeijer J, Kappelle LJ, Algra A, et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): A multicentre, open, randomised trial. Lancet Neurol 2009;8:326-333.
- Vahedi K, Vicaut E, Mateo J, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke 2007;38:2506-2517.
- Juttler E, Schwab S, Schmiedek P, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): A randomized, controlled trial. Stroke 2007;38:2518-2525.