Early craniectomy in neurotrauma– pros and cons (RESCUEicp)

PJ HutchinsonProfessor of NeurosurgeryUniversity of Cambridge

UK

Decompressive craniectomy (DC) in Traumatic Brain Injury

• Secondary DC– Removing a large bone flap to control raised

intracranial pressure

• Primary DC– Leaving the bone flap out following initial surgery for

a mass lesion• acute subdural haematoma

Secondary DC for raised ICP

Primary DC for mass lesion

RESCUE-ASDH• 990 patients• On-going • ASDH that needs to

evacuated with a large bone flap

• Randomisation intra-operatively

DECRA• 155 patients• Published in 2011• 15-60 years• Severe diffuse TBI within 72 hours post-injury

• ICP > 20 mmHg,15 mins

RESCUEicp• 400 patients• Published 2016•10-65 years• Raised ICP refractory to protocol-based medical management

• ICP > 25 mmHg, 60 mins

Decompressive craniectomy for TBI

Kolias AG, Kirkpatrick PJ, Hutchinson PJ.

Nature Reviews Neurology 2013

DECRA

DECRA – EndpointsDC- similar mortality; increased rate of unfavourable

September 7th 2016 21:00 GMTDisclosures and article at www.nejm.org

www.RESCUEicp.com

Hypothesis

Decompressive craniectomy can improve outcomes

as a last-tier therapy for refractory post-traumatic

intracranial hypertension

Study DesignProspective randomised study

Target study group:Ventilated TBI patients with refractory ICP

Advanced medical management (inc barbiturates)V

Surgical management (decompressive craniectomy)

Study EndpointsEndpoints

Primary 6 months GOS-ESecondary 12 months GOS-E

24 months GOS-E(analysis pending)GCS at discharge from ICUControl of ICPLength of stay in ICUQuality of life (analysis pending)Health economic analysis (analysis pending)

Extended Glasgow Outcome Scale (GOS-E)

GOS-E category Abbreviation ExplanationDeath Death DeadVegetative state VS Unable to obey commandsLower severe disability LSD Dependent on others for careUpper severe disability USD Independent at home

Lower moderate disability LMDIndependent at home and outside the home but with some physical or mental disability

Upper moderate disability UMD

Independent at home and outside the home but with some physical or mental disability, with less disruption than LMD

Lower good recovery LGR Able to resume normal activities with some injury-related problems

Upper good recovery UGR No injury-related problems

Sample size400 patients to be randomised

15% difference in outcome at upper severe disability (independent at home) or better

Power 80%, p<0.05

Allowance for loss to follow-up (10%)

52 centres20 countries

Baseline characteristics

There were no significant between-group differences in the baseline characteristicsexcept for history of drug or alcohol abuse (P = 0.02).

Treatments and Interventions

Bifrontal DCfor diffuse brain injury/swelling

Dura opened, division of falx, frontal sinus cranialisation

p=0.12

p=0.01

Outcome of “extra survivors” with craniectomy

6 monthsFor every 100 patients treated with surgical versus medical intent:• 22 more survivors

– 6 (27%) VS– 8 (36%) LSD– 8 (36%) USD or better

12 monthsFor every 100 patients treated with craniectomy versus medical intent:• 22 more survivors

– 5 (23%) VS– 4 (18%) LSD– 13 (59%) USD or better

Outcome of “extra survivors” with craniectomy

Sub group analysis

• Benefits may be greater in young patients (<40 years)

• supplementary appendix

ICP data

Complications and adverse events

DECRA RESCUEicp

Recruitment<72hrspost-TBI 100% 56%

ICPthresholdlevel >20mmHg >25mmHg

ICPthresholdduration 15mininanyhour 1-12hours

PriorICPtherapies Tier1 Tiers1&2

Expectedmortality

Pooledmortality 18.7% 37.5%

Mortalityintwostudyarms 19%vs18% 26.9%vs48.9%

DichotomizationonGOSE LowerMD/UpperSD UpperSD/LowerSD

Documentedfollowup 6months 6and12months

RESCUEicp- interpretation• Data informative for clinicians and families

• Class I evidence for using last-tier DC as a life-saving intervention for refractory raised ICP following TBI

• Patients with extremely severe TBI pathophysiology as a consequence of initial injury severity and/or host response

• Consequently, dichotomization at upper severe disability (= independent at home) was a reasonable outcome threshold (pre-specified analysis).

• At 6 months DC reduced mortality from TBI from 48.9% to 26.9%, but more DC patients were likely to be dependent (30.3% compared to 16.5%).

• At 12 months DC subjects continued improving and 45.4% were at least independent at home, versus 32.4% in the medical group

• For every 100 patients treated with - 22 extra survivors- 59% were at least independent at home

RESCUEicp – interpretation• Caveats

• 37.2% crossover from the medical to DC arm – not sure of impact on results

• Data do not specifically cover the risks and complications of cranioplasty

• 12 months may be still too early for maturation of outcomes in DC

• Take home messages• The choice to provide rescue DC has to be individualized• We need to identify patients most likely to benefit. • We need to find ways to make the procedure better• We need to better understand physiology post-DC and modify Rx• We need to refine the cranioplasty timing and technique

Conventional CT is the first line gold standard for imaging in TBI

Brainstem lesions

But CT may miss important pathology that defines prognosiswhich is not improved with DC

Mannion RJ, Cross J, Bradley P, Coles JP, Chatfield D, Carpenter A, Pickard JD, Menon DK, Hutchinson PJ. A mechanism-based MRI classification of traumatic brainstem injury

and its relationship to outcome. J Neurotrauma 2007;24: 128-135.

Diffuse axonal injury

But CT may misses important pathology that defines prognosiswhich is not improved with DC

DC is not a panacea!

RESCUEicp - talking to families• DECRA & RESCUEicp provide information that aids discussions with

families

• We urge against using loaded terms such as “favourable” or “unfavourable”

• More desirable to simply state that the best evidence we have suggests that:– DC before other Rx options does not improve mortality or outcome– DC as a rescue when most interventions have failed reduces mortality– About 40% of the survivors are dependent– About 60% of the survivors are independent at home or better– It takes a long time (over a year) for the full benefit of DC to declare itself

• We should offer to provide details of outcome categories & clarify issues

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Quality of Life in TBI SF-36 data

Spectrum of Outcomes Following Traumatic Brain Injury- Relationship Between Functional Impairment and Health-Related Quality of Life.

Anastasia Tsyben, Mathew Guilfoyle, Ivan Timofeev, Fahim Anwar, Judith Allanson, Joanne Outtrim, David Menon, Peter Hutchinson, Adel Helmy

Acta Neurochir in press

• Decisions to recommend decompressivecraniectomy must always be made not only in the context of its clinical indications but also after consideration of an individual patient's preferences and quality of life expectations.

• Martin Smith • Anesth Analg 2017

Secondary Rescue Decompressive Craniectomy for TBI

Pros• Decreased mortality • 59% of survivors at least

independent at home• Improved ICP control• Reduction in intensive

medical treatment -barbiturates

Cons• Survival with disability

– 18% VS, 23% LSD• Increased complications• Requirement for cranioplasty• Requirement for rehabilitation• Translation to LMICs• Does not address primary

decompression for mass lesions (hence RESCUE-ASDH)

Primary DCAcute subdural haematomas

Acute Subdural Haematomas (ASDH)• Present in up to 1/3 of patients with severe TBI

• Often associated with underlying cerebral parenchymal injury

• Historically associated with a high mortality rate (between • 40-60%) and functional recovery which ranges from 19 to 45%

• Approximately 2/3 of patients with TBI undergoing emergency • cranial surgery have an ASDH evacuated

• 37% of patients undergoing craniotomy for ASDH have uncontrollable ICP

1. Bullock et al. Surgical management of acute subdural hematomas. Neurosurgery, 20062. Compagnone et al. The management of patients with intradural post-traumatic mass lesions: a multicentersurvey of current approaches to surgical management in 729 patients coordinated by the European Brain InjuryConsortium. Neurosurgery, 20053. Miller JD et al, J Neurosurg, 1981 Further experience in the management of severe head injury.

RESCUE-ASDH trial§ Research question

§ Does decompressive craniectomy lead to better functional outcomes compared to craniotomy for adult head-injured patients undergoing evacuation of an acute subdural haematoma?

§ Randomised study of head-injured patients with acute subdural haematoma§ Patients randomised to craniotomy i.e. replacing bone flap

versus hemi-craniectomy i.e. leaving bone flap out

§ Sample size – 990 patients to detect 8% absolute difference in the rate of favourable outcome at 1 year

RESCUEASDH.org

RESCUE Acknowledgements • We thank the patients who participated in this

trial and their families• We also thank:

– All the collaborating clinicians and research staff (see appendix at NEJM.org for details)

– Members of the trial steering committee (independent chair Prof AB Bell) – Members of the data monitoring and ethics committee (independent chair Mr DM

Shaw)

RESCUE-ASDH we welcome more centres!

rescueasdh.org

pjah2@cam.ac.uk

@rescueicp@rescueasdh@ag_kolias