RESCUEicp
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Clinical Question
What is the role of decompressive craniectomy compared to barbiturate coma for patients with a traumatic brain injury (TBI) and intracranial hypertension refractory to typical medical management?
Bottom Line
Decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of severe disability at 6 months compared to medical care.
Major Points
The role of decompressive craniectomy in patients with post-traumatic intracranial hypertension that is refractory to medical management alone remains unclear. The 2011 DECRA study[1] suggested that no benefit was gained from decompressive bifrontal craniectomy, however the trial was limited by its restrictive eligibility criteria. RESCUEicp was an international randomized trial of surgical decompression among a broader range of patients more typical of those encountered in routine practice.
The Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) randomized 408 patients with TBI and refractory intracranial hypertension, age 10-65 years, to either surgical decompression or continued medical groups. Patients in the surgical group received decompressive craniectomy plus continued medical care, while patients in the medical group received medical care alone including barbiturate coma. The primary outcome was based on measurement of the Extended Glasgow Outcome Scale (GOS-E) score, which takes into account death, vegetative state, grades of physical and mental disability, and recovery. At 6 months, death was less common in the surgical group (26.9% vs. 48.9%), whereas the surgical group had more patients in vegetative state (8.5% vs. 2.1%) and dependence on others for care (21.9% vs. 14.4%); rates of moderate disability and good recovery with surgical were similar between groups.
Limitations of the study included the understandably non-blinded nature of the design, which was managed with outcome adjudication, as well as the fact that a large proportion of patients in the medical group ultimately underwent salvage decompression. Also, this trial studied surgical decompression among patients with medically refractory intracranial hypertension and thus its results should not be extrapolated to patients undergoing primary surgical decompression.
Guidelines
As of July 2018, no guidelines have been published that reflect the results of this trial.
Design
- International, multicenter, parallel-group, superiority, randomized trial
- N=398 with refractory intracranial hypertension following TBI
- Surgery (n=202)
- Control (n=196)
- Setting: 52 centers in 20 countries
- Enrollment: 2004-2014
- Primary outcome: The primary-outcome measure was assessed with the use of the Extended Glasgow Outcome Scale (GOS-E) at 6 months after randomization
- Scondary outcomes: GOS-E results at 12 and 24 months after randomization; mortality at 6, 12, and 24 months after randomization; quality of life at 6, 12, and 24 months after randomization; Glasgow Coma Scale (GCS) score at discharge from the neurosciences hospital; assessment of intracranial-pressure control; time in the ICU; time to discharge from the neurosciences hospital; and economic evaluation.
Population
Inclusion Criteria
- Age between 10 and 65 years
- TBI with an abnormal brain CT
- Intracranial pressure monitor already in place
- Raised intracranial pressure (>25 mm Hg for 1 to 12 hours) despite intensive medical management.
- Patients who had undergone an immediate operation for evacuation of an intracranial hematoma could be included as long as the operation was not a craniectomy.
- Trial sites were hospitals that provide acute neurosciences care for patients with severe TBI and that have 24-hour neurosurgical services.
Exclusion Criteria
- Bilateral fixed and dilated pupils
- Bleeding diathesis
- Injury that was deemed to be unsurvivable
Baseline Characteristics
Comparisons are surgery vs. control
- Age, yr (SD): 32.3 (13.2) vs. 34.8 (13.7)
- Male sex, no./total no. (%): 165/202 (81.7) vs. 156/195 (80.0)
- GCS motor score at first hospital, no./total no. (%):
- 1-2: 96/181 (53.0) vs. 85/170 (50.0)
- 3-6: 85/181 (47.0) vs. 85/170 (50.0)
- Pupillary abnormality, no. (%): 59 (29.2) vs. 57 (29.1)
- Hypotension, no. (%): 40 (19.8) vs. 42 (21.4)
- Hypoxemia, no. (%): 49 (24.3) vs. 52 (26.5)
- History of drug or alcohol abuse, no. (%): 50 (24.8) vs. 69 (35.2)
- Extracranial injury, no. (%): 75 (37.1) vs. 83 (42.3)
- Injury classification on basis of CT imaging, no./total no. (%):
- Diffuse injury: 161/198 (81.3) vs. 141/186 (75.8)
- Mass lesion: 37/198 (18.7) vs. 45/186 (24.2)
Interventions
All patients were treated in ICUs with a target intracranial pressure of 25 mm Hg or less achieved with head elevation, ventilation, sedation, analgesia, normothermia, normoglycemia, cerebral perfusion pressure >60 mm Hg, mild hypocapnia (PaCO2 34 to 38 mmHg), oxygen saturation >97%, and paralysis (optional). If the intracranial pressure was not controlled despite these measures, subsequent options included ventriculostomy (if an external ventricular drain had not already been inserted for intracranial-pressure monitoring), inotropes (blood-pressure augmentation), osmotherapy (mannitol, hypertonic saline, loop diuretics), moderate hypocapnia (PaCO2 30 to 34 mm Hg), and hypothermia.
If the intracranial pressure remained above 25 mm Hg for 1 to 12 hours despite the above measures, then patients were randomly assigned to undergo surgical or continued medical management.
- Surgical treatment:
- Large unilateral frontotemporoparietal craniectomy (hemi-craniectomy) was recommended for patients with unilateral hemispheric swelling
- Bifrontal craniectomy was recommended for patients with diffuse brain swelling affecting both hemispheres on imaging studies.
- The exact type of craniectomy was left to the discretion of the surgeons.
- 92.6% of the patients underwent decompressive craniectomy
- The median time from randomization to craniectomy was 2.2 hours.
- Medical treatment:
- 87.2% of the patients received a barbiturate infusion
- The median time from randomization to barbiturate infusion was 1.5 hours.
- The median duration of barbiturate therapy was 53 hours.
- Decompressive craniectomy was performed in 37.2% of the patients in the medical group after further clinical deterioration.
Outcomes
Comparisons are surgery vs. control groups.
Primary Outcomes
GOS-E distributions at 6 months:
- Death
- 26.9% versus 48.9%
- Vegetative state
- 8.5% versus 2.1%
- Lower severe disability (dependent on others for care)
- 21.9% versus 14.4%
- Upper severe disability (independent at home)
- 15.4% versus 8.0%
- Moderate disability
- 23.4% versus 19.7%
- Good recovery
- 4.0% versus 6.9%
- Favorable outcomes (upper severe disability or better on the GOS-E) at 6 months
- 42.8% versus 34.6% (P = 0.12)
Secondary Outcomes
GOS-E distributions at 12 months
- Death
- 30.4% versus 52.0%
- Vegetative state
- 6.2% versus 1.7%
- Lower severe disability
- 18.0% versus 14.0%
- Upper severe disability
- 13.4% versus 3.9%
- Moderate disability
- 22.2% versus 20.1%
- Good recovery
- 9.8% versus 8.4%
- Favorable outcomes (upper severe disability or better) at 12 months
- 45.4% versus 32.4% of those in the medical group (P=0.01)
- Median time to discharge among survivors
- 15.0 days vs. 20.8 days (P=0.01)
- Control of ICP
- Better in surgical group than in the medical group.
Subgroup Analysis
Results were explored for six a priori subgroups:
- Diffuse injury versus non‐diffuse
- Initial GCS total score 3‐8 versus 9‐15
- Age ≤40 versus age >40 years
- Craniotomy for evacuation of mass lesions before randomization; yes versus no
- Time from injury to randomization ≤ 72 versus >72 hours
- Patients randomized in the UK versus rest of the world.
Adverse Events
- Any adverse event
- 16.3% vs. 9.2% (P=0.03)
- Most commonly pneumonia, surgical site infection, postoperative hematoma.
Criticisms
- Recruitment was slow, taking over 10 years. Half of centers recruited 3 or fewer patients.
- Therapeutic hypothermia (optional treatment in this study) may have a deleterious effect on neurological outcome after TBI based on Eurotherm3235[2]. The study was commenced before Eurotherm3235 was published.
- Clinical teams who cared for the patients were aware of trial group assignments, although this was mitigated by outcome adjudication.
- A large proportion of patients in the medical group underwent decompressive craniectomy (37%); this situation may have diluted the observed treatment effect
Funding
Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 [3]