Decompressive Craniectomy in Diffuse Traumatic Brain Injury - ICU

Original ArticleDecompressive Craniectomy in Diffuse TraumaticBrain InjuryD. 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., ThomasKossmann, M.D., Jennie Ponsford, Ph.D., Ian Seppelt, M.B., B.S., Peter Reilly, M.D.,Rory Wolfe, Ph.D., for the DECRA Trial Investigators and the Australian and NewZealand Intensive Care Society Clinical Trials Group•Multicenter 15 centre: Australia, New Zealand, Saudi Arabia•2002-2010•155 adults (3478 assesed) 15-59 years with severe non-penetratingtraumatic brain injury ( GCS 3-8 or Marshall class III)•88% are patients from Australia or New ZealandN Engl J MedVolume 364(16):1493-1502April 21, 20111

Study OverviewPatients with severe traumatic brain injury andrefractory intracranial hypertension were randomlyassigned either to receive standard care or toundergo standard care plus bifrontotemporoparietaldecompression craniectomy.Hypothesis: decompressive craniectomy decreasesintracranial pressure hereby improves functionaloutcomes, and decrease the proportion ofsurvivors with severe disability.2

Design Inclusion Between 15-59 years Severe non penetrating brain trauma (GCS 3-8 ofMarshall III) Exclusion No full active treatment ( Staff decision) Dilated unreactive pupils Mass lesions (unless to small for surgery) Spinal Cord injury or cardiac arrest3

Groups Randomization stratified, according to centre and ICPmeasurement technique in blocks of 2 to 4 patients. Group A: Standard care alone (Lifesaving decompressivecraniectomy after 72 hours since admissionpermitted) Group B: Standard care plus large bifrontotemporoparietalmaximize thecraniectomy with bilateral dural opening toreduction in intracranial pressure. The sagittal sinus andfalx cerebri were not divided.Bone replacement after 2-3 months5

Second line TreatmentFor refractory ICP > 20 after randomizationFor Both Groups: Mild Hypothermia (T° 35 C) Optimized use of barbiturates6

Outcome Measuresevaluated by telephone by three trained blinded assessorsoriginal primary outcome was the proportion of patients with an unfavorableoutcome: a composite of death, a vegetative state, or severe disability (a score of 1 to 4 on theExtended Glasgow Outcome Scale), as assessed with the use of a structured, validatedtelephone questionnaire at 6 months after injury.After the interim analysis in January 2007, the primary outcome was revised tobe the functional outcome at 6 months after injury on the basis of proportional oddsanalysis of the Extended Glasgow Outcome Scale.Secondary outcomes:intracranial pressure measured hourlythe intracranial hypertension index (defined as the number of end-hourly measures ofintracranial pressure of more than 20 mm Hg divided by the total num- ber ofmeasurements, multiplied by 100)the proportion of survivors with a score of 2 to 4 on the Extended Glasgow Outcome Scale(defined as severe disability and requiring assistance in daily living activities)the numbers of days in the ICU and in the hospital7

StatisticsProportion of favorable outcomes (defined as a score of 5 to 8 on theExtended Glasgow Outcome Scale) from 30% among patients receivingstandard care to 50% among patients undergoing craniectomy, with a twosidedtype I error of 0.05 and a power of 80% with a sample size of 210patients.At the interim analysis (with the study-group assignments concealed), itwas determined that if the score on the 8-grade Extended Glasgow OutcomeScore were analyzed by ordinal logistic regression, 150 patientswould be required to detect a between-group difference of 1.5 in the medianscore with a power of 80% and a two-sided type I error of 0.05.8

StatisticsOrdinal logistic regression for univariate between-group comparisons ofscores on the Extended Glasgow Outcome ScaleLogistic regression for comparisons of unfavorable outcomes.Followed by adjusted comparisons with inclusion in the regression modelsof the prespecified covariates:age,the last Glasgow Coma Scale score before intubationGlasgow Coma Scale motor score after resuscitationThe Marshall class.A post hoc adjusted comparison included one variable (pupil reactivity) thatdiffered significantly between groups at baseline.9

Intracranial Pressure before and after Randomization.Cooper DJ et al. N Engl J Med 2011;364:1493-150210

Cumulative Proportions of Results on the Extended Glasgow Outcome Scale.Cooper DJ et al. N Engl J Med 2011;364:1493-150211

Baseline Characteristics of the Patients.Cooper DJ et al. N Engl J Med2011;364:1493-150212

Primary and Secondary Outcomes at 6 monthsCooper DJ et al. N Engl J Med 2011;364:1493-150213

Medical and Surgical Complications.Cooper DJ et al. N Engl J Med 2011;364:1493-150214

Results Primary outcome was worse in the craniectomy group odds ratio 1.84; 95%[CI], 1.05 to 3.24; P=0.03Unfavorable outcomes occurred in 51 patients (70%) in the craniectomygroup and in 42 patients (51%) in the standard care group (odds ratio, 2.21;95% CI, 1.14 to 4.26;P = 0.02After adjustment for pre- specified covariates, the results were similar forthe score on the Extended Glasgow Outcome Scale (adjusted odds ratiofor a lower score in the craniectomy group, 1.66; 95% CI, 0.94 to 2.94; P =0.08) and for the risk of an unfavorable outcome (adjusted odds ratio, 2.31;95% CI, 1.10 to 4.83;P = 0.03).After posthoc adjustment for pupil reactivity at baseline (Table 1), thebetween group differences were no longer significant for the score on theExtended Glasgow Outcome Scale (adjusted odds ratio, 1.53; 95% CI, 0.86to 2.73;P = 0.15) and for the risk of an unfavorable outcome (adjusted oddsratio, 1.90; 95% CI, 0.95 to3.79;P = 0.07).15

Conclusions In adults with severe diffuse traumaticbrain injury and refractory intracranialhypertension, earlybifrontotemporoparietal decompressivecraniectomy decreased intracranialpressure and the length of stay in the ICUbut was associated with moreunfavorable outcomes.16

Craniectomy--> ICP lower-->no improvement in clinical outcome and no decreasein proportion of survivors with severe disability.Why?:Craniectomy increases rate of survival of the severly injured --> same rate of deathsbetween groups despite increased number of vegetative patients AND patients becomemore dependent by craniectomie (worse outcome score)Axonale stretchSurgical procedure:unilat bilat craniectomy (more complications)Sagittal Sinus and falx cerebri division yes or noComplications due to surgery (craniectomy and bone replacement)17

LimitationsOnly assesors were blinded>30% patients are from 1 centreImbalances in baseline characteristics (pupil reactivity)Primary outcome revisionBifrontal craniectomydecompressive craniectomy for ICP around 20 mm Hg for such a short time inpatients with diffuse injury without mass lesions Clinical practiceOnly 155 of 3478 patients after 7 years enrollment -->study applies to a restrictedsubpopulation of patients with traumatic brain injury18