Title: Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension
P.J. Hutchinson, A.G. Kolias, I.S. Timofeev, E.A. Corteen, M. Czosnyka,J. Timothy, I. Anderson, D.O. Bulters, A. Belli, C.A. Eynon, J. Wadley,A.D. Mendelow, P.M. Mitchell, M.H. Wilson, G. Critchley, J. Sahuquillo,A. Unterberg, F. Servadei, G.M. Teasdale, J.D. Pickard, D.K. Menon, G.D. Murray, and P.J. Kirkpatrick, for the RESCUEicp Trial Collaborators*
Back ground & Clinical Question:
Decompressive craniectomy (DC) as a rescue measure for refractory raised ICP had been tested against possible medical therapy by DECRA trial.(1) The results of this trial did not favor decompressive craniectomy and was associated with more unfavorable outcome. In spite of a decrease in ICP achieved by decompressive craniectomy, it was not reflected as a better Extended Glasgow Outcome scale (GOS-E). The current study aimed to evaluate this uncertainty in clinical out come after decompressive craniectomy with a higher ICP value (>25mm Hg for 1 to 12 hours) as enrollment criteria for decompression.
Multicenter, parallel-group, superiority, randomized trial.
Setting (Population, Timeframe & Enrolment):
January 2004 to March 2014
10 to 65 years of age
TBI with abnormal Computed tomography (CT) of brain
ICP monitor already placed
With ICP >25 mm Hg for 1 to 12 hours despite tier 1 & 2 therapy.
All patients received type 1 & 2 therapy.
Tier 1- sedation, analgesia, head elevation, neuromuscular paralysis (optional), Cerebral Perfusion Pressure (CPP) >60 mm Hg, normothermia, normoglycemia, mild hypocapnia (PaCO2 34-38 mm Hg and SPO2>97%.
Tier-2- Ventriculostomy (External ventricular drain EVD placement if not placed earlier), blood pressure augmentation by pharmacologic agents, osmotherapy, Modrate hypocapnia (PaCO2 30-34 mm hg), hypothermia (<34 degree C)
If ICP still remained >25 for 1 to 12 hours then tier-3 approach was followed
Tier-3- Patients randomly assigned to either undergo decompressive craniectomy with continuation of all previous medical therapy or only maximal medical therapy with or without barbiturate coma.
Any patient with immediate evacuation of hematoma but no craniectomy could be included.
Patients with bilateral fixed & dilated pupils, bleeding diathesis and any injury not compatible with life were excluded.
Large unilateral fronto-temporo-parietal craniectomy for unilateral hemispheric brain swelling.
Bifrontal craniectomy for diffuse brain swelling.
Surgeries were recommended to be performed no later than 4 to 6 hours after randomization. Crossover from medical to decompressive surgeries was allowed depending on discretion of treating physician.
There was a definite survival advantage with decompressive craniectomy compared to medical management, which is seen both dependent and independent living at 6 and 12 months. Moderate and good recovery were similar in the two groups. GOS-E results did not show a significantly higher percentage of patients with a favorable outcome in the surgical group at 12 months of follow up. At the same time there were higher rates of vegetative state, lower severe disability, and upper severe disability in the surgical group.
The improved mortality in craniectomy group might have been due to the better control of ICP with surgical decompression. About 9% of patients in the surgical group did not have their intracranial pressure controlled and required barbiturate infusion.
Other secondary outcome measures-
Assessment of ICP control- Median reduction in ICP and the duration of ICP control was significantly better in the decompressive surgery group.
Median cerebral hypoperfusion index 60 (the number of end-hourly measures of cerebral perfusion pressure of <60 mm Hg divided by the total number of measurements, multiplied by 100)– Significantly less in decompressive surgery group.
Though decompressive craniectomy can result in better survival rate and control of ICP, it did not reflect a better out come in terms of independent neurological recovery.
Large multicenter trial with a follow up period of more than two years.
More generalized enrollment of head injury patients compared to DECRA trial which excluded head injury patients with intracranial mass/hemorrhage
More acceptable definition of refractory ICP compared to DECRA trial.
The nature of trial is so obvious that effective blinding is impossible.
This study did not incorporate any direct measures of cerebral oxygenation or cerebral blood flow, though the hypothesis was based on the fact that improved ICP control leads to better oxygen delivery to brain.
Patients with fixed dilated pupils were excluded. This sign can be very non-specific and can not specify an irreversible brain damage.
Bifrontotemporoparietal decompressive craniectomy was mentioned as the surgical decompression procedure in diffuse brain injury in the study protocol, instead bifronatal craniectomy was done. The impact of this change in type of procedure can have difference in impact and cannot be used for comparison with other historical study. There was also no mention why the study deviated from the original protocol.
There was a significant cross over (37% of medically treated patients) from medical to rescue decompressive surgery. There was no mention of type of surgery done in these cases. Moreover, there was no comparison of outcomes between the two surgical procedure.
Primary decompressive craniectomy has not been addressed in this study.
Relevance to current practice:
Secondary decompressive craniectomy as a tier three therapy for control of refractory high ICP should be considered keeping in mind the poor functional outcome associated with it.
Literature before this study and basis of the current trial:
Difference between DECRA and RESCUEicp
In DECRA the enrollment criteria were ICP of 20 mm Hg or more for any 15 mins continuously or intermittently in 1 hour. Patients with evacuation of space occupying lesions not included. Decompression was considered after failed first tier therapy which can be considered as suboptimal medical therapy. Bifrontoparietotemporal craniectomy was employed as only decompressive surgery
In RESCUEicp the enrollment ICP was >25mm Hg between 1to 12 hrs. Patients with previous evacuation of intracranial blood post TBI were included but primary decompressive craniectomies were excluded by both DECRA and RESCUEicp trials. DC was considered only after failure of tier 2 therapy. Bifrontal or unilateral frontoparietotemporal craniectomy was the planned surgeries depending on patients presentation.
Secondary decompressive surgery
There are two indications to a decompressive craniectomy that can be performed
As a secondary decompressive surgery for control of ICP .
As decompressive surgery for malignant hemispheric stroke.
The prior evidence for all the above three discussed below
Secondary decompressive surgery for control of ICP in TBI
DECRA trial (1) (Decompressive Craniectomy)- A multicenter, randomized, controlled trial compared bifrontotemporoparietal craniectomy with standard medical therapy in patients under age of 60 years with traumatic brain injury. Conducted in 15 ICUs in Australia-New Zealand and Saudi Arabia.
Enrollment criteria was spontaneous increase in ICP>20 for ongoing 15 mins (continuously or intermittently) in one hour period with maximal 1st tier therapy (see above for tier of terapy). Significant exclusion was patients with any intracranial surgery for a space occupying mass (blood) due to traumatic brain injury.
The study concluded that, decompressive craniectomy decreased the mean intracranial pressure significantly. It also reduced the duration of the ICU stay and ventilator support. But at 6 months it was associated with significantly high mortality as measured by the score on the Extended Glasgow Outcome Scale.
The criticism for this study were
A softer trigger for enrollment into the refractory ICP classification when continued medical therapy would have been beneficial.
It did not incorporate any measure of cerebral blood flow or oxygenation.
A significant proportion of TBI patients were left out who had an evacuation of hematoma post TBI and in whom ICP management is essential.
The poor outcome measures were thought to be due to sudden increase in transcapillary hydrostatic pressure on decompression due to an impaired blood brain barrio lead to secondary brain injury and reflected as poor function recovery.
2. Decompressive surgery for malignant hemispheric stroke.
There has been 7 distinct trial for addressing the outcome of decompressive surgery after malignant hemispheric stroke. DECIMAL2007, DESTINY2007, HAMLET2009, DEMITUR Trial, HEADDFIRST, DESTINY 2, HeMMI 2004.
An initial pooled analysis of three trials in 93 patients (DECIMAL2007, DESTINY2007, HAMLET2009) showed that decompressive surgery (within 48 h) of stroke reduced mortality and increases the number of patients with a favorable functional outcome. (Lancet 2007).(2) A Cochrane review in 2012 including the same 3 studies (all completed) extended the findings that surgical decompression reduces mortality, and severe disability (Modified Ratkin’s score mRS > 4) in patients 60 years of age or younger but showed no beneﬁt for disability or death deﬁned as mRS > 3.(3) This review concluded that the intervention improves survival at the expense of an increased proportion of survivors with severe disability.
A more recent extensive meta-analysis including all previous RCTs (8 RCTS, 341 patients) concluded that DC (within 48 h after stroke onset) decreased mortality and poor functional outcome (modified Rankin scale (mRS)>3) at one year of follow-up in patients with malignant MCA infarction who are <60 years of age. The same benefit was also observed in patients aged>60 years but old age was an important predictor for poor outcome.(4)
Reference & further reading:
Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011; 364:1493-502.
Vahedi K, Hofmeijer J, Juettler E, Vicaut E. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomized controlled trials. Lancet Neurology 2007;6:215–22.
Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD003435. DOI: 10.1002/14651858.CD003435.pub2.
XiaoCheng Lu, BaoSheng Huang, JinYu Zheng, Yi Tao, Wan Yu, LinJun Tang, RongLan Zhu, Shuai Li, LiXin Li. Decompressive craniectomy for the treatment of malignant infarction of the middle cerebral artery. Sci Rep. 2014; 4: 7070.
MD, FNB, FCCP,EDIC