Critical care trailblazers: the DECRA trial


Historically, surgical decompression was employed as a desperate measure to reduce pressure within the skull in life-threatening brain injury. At the turn of the 20th century, Theodor Kocher (Fig. 1) first proposed the potential of decompressive craniotomy to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI). In 1901, he wrote that favorable clinical outcomes might ensue with “decompression of the brain by wide opening of the skull to decrease the intracranial pressure”. The current concept of decompressive craniectomy was proposed by Harvey Cushing, involving the removal of a segment of the skull, enabling reduction in pressure by opening the intracranial compartment (1). 

Figure 1. Theodor Kocher (1841–1917)

In the Proceedings of the Society of British Neurological Surgeons in 1971, Ranashoff and Benjamin presented their experience with decompressive craniectomy as a life-saving intervention in patients with acute subdural hematoma within the first 24 hours of injury (2). In the pre-CT era, diagnosis was by expeditious angiography soon after securing the airway by endotracheal intubation, administration of osmotic agents, and continued resuscitative measures as appropriate. They removed a large fronto-temporo-occipital flap, with the removal of the squamous temporal bone to the base of the skull. Eight of 20 patients who underwent decompressive craniectomy were able to return to their previous level of employment, while two others made a partial recovery. 

Seven years later, Britt and Hamilton reported a series of 42 patients with acute subdural hematoma. Evaluation was based on plain radiography, or angiography. A CT scan, in the early days of its introduction to widespread practice, was performed in five patients. The authors performed a large decompressive craniotomy with evacuation of the hematoma, attainment of hemostasis, and patch-grafting of the dura. Although 14 patients were discharged home, many were left severely disabled with cognitive deficits, motor weakness, and aphasia (3).  

By the late 1970s, decompressive craniectomy was considered a reasonable option to reduce ICP rise associated with severe TBI. A reduction in the ICP resulted in improved cerebral perfusion, thus preventing ischemic injury. If cerebral edema worsened, brain herniation would occur through the craniectomy, thus preventing tentorial herniation and fatal brain stem compression. However, anecdotally, massive cerebral edema was occasionally observed at the craniectomy site. Cooper et al. noted in 1979 that the edema in patients who underwent craniectomy might even be more severe compared to those who were not subjected to decompression, although the ICP decreased dramatically (4). The findings of an experimental model suggested that the removal of a bone segment may lead to a drastic reduction in the interstitial pressure in the brain tissue; the intravascular pressure, acting largely unopposed, may drive excessive edema formation (4). 

The 1980s witnessed a resurgence of interest in decompressive craniectomy following TBI. Gaab et al. conducted a prospective observational study of 37 patients aged 40 years or less with TBI. The ICP could not be controlled despite optimizing conservational measures; rapid clinical deterioration followed. Decompressive craniectomy was performed within 5 hours to 10 days of trauma. Among these patients, 32 (86%) survived with a mild or moderate level of disability. The authors observed that an initial GCS of ≥7 was the best predictor of a favorable outcome (5). 

Background to the DECRA trial 

In more than a decade preceding the DECRA trial, decompressive craniectomies were being carried out extensively in TBI. Between 2009-2010, 143 papers were published on the topic, for different types of neurological disorders (6). However, only a single randomized controlled trial (RCT) including 27 children had been carried out. This small RCT showed that very early decompressive craniectomy combined with medical therapy leads to a better functional outcome and improved quality of life compared to medical therapy alone (7). The DECRA trial was designed to answer the question of whether decompressive craniectomy would improve neurological outcomes in patients with TBI, in whom conventional measures had failed to control ICP. 

Study population and design

The DECRA trial was conducted by the Australian and New Zealand Intensive Care Society Clinical Trials Group between 2002–2012 across 15 ICUs in Australia, New Zealand, and Saudi Arabia. The study included patients aged 15–59 years with severe, non-penetrating TBI (8). Severe TBI was defined as a score of 3–8 on the Glasgow Coma Scale or Marshall class III injury on CT imaging, representing moderate diffuse involvement. Patients in whom continued aggressive treatment was considered unlikely to benefit were excluded. Patients with bilateral dilated, non-reactive pupils, mass lesions, spinal cord injury, and those who suffered cardiac arrest at the scene were also excluded. 

Standard care 

The ICP was monitored through an external ventricular drain or a parenchymal catheter. A rise in the ICP above 20 mm Hg triggered first-tier therapeutic interventions, including optimization of sedation, use of neuromuscular blocking agents,  maintenance of normocapnia, osmotherapy including mannitol or hypertonic saline, and external ventricular drainage as appropriate. A spontaneous, persistent rise in the ICP for more than 15 minutes over a 1-hour period despite these measures, either continuously or intermittently, was considered refractory intracranial hypertension. 


Patients were randomly assigned to undergo continued standard care alone or combined with decompressive craniectomy within the first 72 hours if first-tier therapies failed to control ICP. Randomization was stratified according to center and the ICP monitoring technique, in blocks of two or four patients. In patients randomized to decompressive craniectomy, a standard surgical technique was followed. A large, bifrontotemporoparietal craniectomy with opening of the dura was performed to maximize the impact on ICP reduction. The excised bone segment was preserved at -70°C or placed subcutaneously on the abdominal wall according to the preference of the surgeon. The bone flap was replaced after 2–3 months after local swelling and infection had subsided. 

Interventions for refractory intracranial hypertension

Second-tier interventions were resorted to in both groups if the ICP remained persistently high. Such measures included mild induced hypothermia to 35°C and barbiturate infusions. Among patients receiving standard care, decompressive craniectomy could be performed as a life-saving measure after 72 hours of admission. 

Sample size

The initial sample size of 210 patients was calculated based on a 20% increase in favorable neurological outcomes with decompressive craniectomy, defined as a score of 5–8 on the extended Glasgow Outcome Scale. On interim analysis, the sample size was revised to 150 patients (75 in each group) to detect a difference in the median score of 1.5 between groups by ordinal logistic regression. The reduced sample size was aimed to complete the study within a reasonable time frame. If loss to follow up occurred, an additional 15 patients could be recruited. 


Among the 3478 patients who were eligible, 155 were enrolled; the majority of patients were from Australia and New Zealand (88%). Early decompressive craniectomy was performed in 73 patients, while 82 received standard care. Patients were relatively young, with a median age of 23.7 years in the decompressive craniectomy group and 24.6 in the standard care group. There were more patients with unreactive pupils in the decompressive craniectomy group. Patients were transferred to hospital with minimum delay; the median duration from the time of injury to hospitalization was 1 hour in the decompressive craniectomy group and 1.2 hours in the standard care group. Decompressive craniectomy was performed as a life-saving intervention in 15 patients (18%) who were assigned to the standard care group. 

Intracranial pressure

Decompressive craniectomy resulted in a dramatic fall in the ICP. The mean ICP was 14.4 mm Hg post decompressive craniectomy compared to 19.1 mm in the standard care arm. However, did the reduction in ICP improve functional outcomes?

Primary outcome

The primary outcome was the functional status assessed by the Extended Glasgow Outcome scale. Despite lower ICPs and fewer interventions for ICP control, patients who underwent decompressive craniectomy experienced worse functional outcomes. Unfavorable outcomes, defined as death, vegetative state, or severe disability, representing a score of 1–4 on the Extended Glasgow Outcome scale, occurred more frequently with decompressive craniectomy [51/73 (70%) vs. 42/82 (51%)]; odds ratio, 2.21; 95% CI, 1.14 to 4.26; P = 0.02. The risk of an unfavorable functional outcome with decompressive craniectomy remained high after adjustment for predefined co-variates. 

Secondary outcomes

Mortality at 6 months was similar between the two groups. The duration of mechanical ventilation and ICU stay was significantly shorter in the decompressive craniectomy group. The duration of hospital stay was similar between the two groups. 


The DECRA trial demonstrated that in patients with severe TBI and refractory intracranial hypertension, early decompressive craniectomy resulted in worse functional outcomes at 6 months. The ICP levels were markedly lower following decompressive craniectomy; however, neurological outcomes remained poor compared to the standard care group. Although the duration of mechanical ventilation and ICU stay were shorter among patients who underwent decompressive craniectomy, the duration of hospital stay was similar in both groups. 

Why did the functional outcomes remain poor despite a reduction in the ICP as expected? The authors hypothesized that extension of brain swelling outside the skull, with the resultant axonal stretch may have triggered poor clinical outcomes, as suggested by Cooper et al. (4) several decades ago. The surgical technique employed may also have influenced outcomes. The bilateral approach followed in the DECRA trial has been associated with complications compared with a unilateral procedure (9). The sagittal sinus and the falx cerebri were left intact in contrast to the procedure originally described by Polin et al. (10), although there is a likelihood of complications with both techniques. Thus, the findings of the study may apply to the specific surgical technique employed.  


The investigators were aware of the study groups as blinding was not possible; this may have resulted in bias. Although the trial was multicentric, the majority of patients were recruited from Australia and New Zealand; in fact, one-third of all study patients were from a single center. There were more patients with unreactive pupils in the decompressive craniectomy group at baseline, which may have contributed to poor outcomes; however, adjusted analysis after taking this difference into account did not impact the overall effect size. The sample size was scaled down after the first interim analysis with a view to the completion of the study within a reasonable time frame, which may constitute a suboptimal design. The study took 8 years to complete; changes may have occurred in the overall care of patients over this period that may have impacted outcomes. The performance of decompressive surgery after only 15 minutes of ICP rise above 20 mm Hg over a 1-hour period may have been too early. As allowed by the study protocol, 18% of patients in the standard care group crossed over to undergo decompressive craniectomy after 72 hours, which may have affected outcomes on intention-to-treat analysis. 

The post-DECRA era

The RESCUEicp trial (2016) randomized 408 patients in 52 centres across 20 countries (11). The patients were initially treated with stage 1 measures including head end elevation, sedation, analgesia, and neuromuscular blockade. If the ICP remained high, stage 2 measures were applied, including ventriculostomy, osmotherapy, moderate hypocapnia, and therapeutic hypothermia. If the ICP remained >25 mm Hg for 1-12 hours despite these measures, randomization was carried out to decompressive craniectomy or continued medical therapy. The primary outcome was the Extended Glasgow Outcome Score at 6 months. Mortality at 6 months was lower in the decompressive craniectomy group; however, there was a significantly higher incidence of vegetative state and severe disability compared to standard medical care alone. In contrast to the DECRA trial, the RESCUEicp trial employed decompressive craniectomy as a last-tier treatment. 


Although decompressive surgery had been in widespread use at the time, the DECRA trial was the first large RCT to evaluate its efficacy in severe TBI with refractory intracranial hypertension compared with standard care alone. Although decompressive craniectomy resulted in lower ICP levels as predicted, the reduction in intracranial pressure did not translate to improved functional outcomes. Indeed, early decompressive craniectomy, performed after 15 minutes of ICP rise above 20 mm Hg over a 1-hour period, led to worse functional outcomes at 6 months. The subsequent RESUCEicp trial resorted to a more delayed approach to decompressive craniectomy after the failure of stage 1 and 2 measures to control the ICP. Although mortality was lower at 6 months, neurological disability was more severe among survivors. Both these trials point towards a judicious approach to decision-making in severe TBI with refractory intracranial hypertension, with due consideration of adverse functional outcomes among survivors. 


1.         Cushing H. I. Subtemporal Decompressive Operations for the Intracranial Complications Associated with Bursting Fractures of the Skull. Ann Surg. 1908 May;47(5):641-644.1. 

2.         Ransohoff J, Benjamin V. Hemicraniectomy in the treatment of acute subdural haematoma. J Neurol Neurosurg Psychiatry. 1971 Feb 1;34(1):106. 

3.         Britt RH, Hamilton RD. Large decompressive craniotomy in the treatment of acute subdural hematoma. Neurosurgery. 1978;2(3):195–200. 

4.         Cooper PR, Hagler H, Clark WK, Barnett P. Enhancement of experimental cerebral edema after decompressive craniectomy: implications for the management of severe head injuries. Neurosurgery. 1979 Apr;4(4):296–300. 

5.         Gaab MR, Rittierodt M, Lorenz M, Heissler HE. Traumatic brain swelling and operative decompression: a prospective investigation. Acta Neurochir Suppl (Wien). 1990;51:326–8. 

6.         Servadei F. Clinical Value of Decompressive Craniectomy. N Engl J Med. 2011 Apr 21;364(16):1558–9. 

7.         Taylor A, Butt W, Rosenfeld J, Shann F, Ditchfield M, Lewis E, et al. A randomized trial of very early decompressive craniectomy in children with traumatic brain injury and sustained intracranial hypertension. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg. 2001 Feb;17(3):154–62. 

8.         Cooper DJ, Rosenfeld JV, Murray L, Arabi YM, Davies AR, D’Urso P, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011 Apr 21;364(16):1493–502. 

9.         Gooch MR, Gin GE, Kenning TJ, German JW. Complications of cranioplasty following decompressive craniectomy: analysis of 62 cases. Neurosurg Focus. 2009 Jun;26(6):E9. 

10.       Polin RS, Shaffrey ME, Bogaev CA, Tisdale N, Germanson T, Bocchicchio B, et al. Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral edema. Neurosurgery. 1997 Jul;41(1):84–92; discussion 92-94. 

11.       Hutchinson PJ, Kolias AG, Timofeev IS, Corteen EA, Czosnyka M, Timothy J, et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension. N Engl J Med. 2016 Sep 22;375(12):1119–30. 

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