CEREBRAL PROTECTION

Anthony Delaney MBBS MSc FACEM FCICM

Staff Specialist in Intensive Care, Royal North Shore HospitalSenior Lecturer, Sydney Medical School, University of Sydney

Cerebral Protection

Cerebral protection

Surgical: Decompressive craniectomy

Medical: Hypothermia

Decompressive craniectomy in diffuse traumatic brain injury

Population: Aged 15-59 Severe non penetrating brain injury (GCS 3-8),

Class III Marshall score Exclusion: mass lesion on CT, dilated unreactive

pupils, spinal cord injury, cardiac arrest ICP > 20 for 15 minutes within an hour after;

Sedation, Normal CO2, osmotic therapy, NM blockade and CSF drainage

Within 72 hours of injury

Decompressive craniectomy in diffuse traumatic brain injury

Intervention: Standardised large bifrontotemperoparietal

craniectomy with opening of the dura

Decompressive craniectomy in diffuse traumatic brain injury

Comparison: Second tier therapy for refractory raised

intracranial hypertension Hypothermia Barbiturate coma Decompression after 72 hours

Outcome: Extended Glasgow Outcome Score

Initially dichotomised Ordinal scale

Decompressive craniectomy in diffuse traumatic brain injury

Allocation concealment: Yes, automated telephone system

Blinding: Outcome assessment by telephone by blinded assessors

Complete follow-up: Yes

Intention-to-treat analysis: Yes

Baseline balance: More patients in DC group had bilateral unreactive pupils

Concommittant interventions: Different between the 2 groups

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Results December 2002-April 2010 15 ICUs in Australasia-ish (inc Saudi Arabia) Revised primary outcome

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

Decompressive craniectomy in diffuse traumatic brain injury

However the adjusted analysis Age, last GCS before intubation, GCS post

resuscitation, Marshall score; GOSe 1.66 (95% CI 0.94 to 2.94, p=0.08) Good v Evil OR 2.31 (95% CI 1.10 to 4.83, p=0.03)

And non reactive pupils GOSe 1.53 (95% CI 0.86 to 2.73, p=0.15) Good v Evil OR 1.9 (95% CI 0.95 to 3.79, p=0.07)

Decompressive craniectomy in diffuse traumatic brain injury

So……. RESCUE ICP

ICP>25 for 1-12 hours Abnormal CT Primary decompression excluded but prior

surgery not an exclusion Recruitment commenced 2005 334/400 recruited as of 18/9/12

Hypothermia for cerebral protection Pathophysiology:

Reduction of CMRO2 of 6-7% per 1o drop in temp Reduction in ICP Decreases excitatory amino acids and lactate in

ischaemia/reperfusion injury Reduces intracellular Ca++ sequestration Reduces neutrophil adhesion Reduces apoptosis Reduces free radical production

• Induced hypothermia in critical care medicine: A review. Bernard et al CCM 2003;31:2041-2051

• Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: indications and evidence. Polderman. ICM 2004;30:556-575

Hypothermia for cerebral protection

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

Question: To assess the effectiveness of therapeutic hypothermia in patients after

cardiac arrest

Studies: Randomised and quasi-randomised studies

Population: Adult patients who suffered cardiac arrest (in or out of hospital)

Intervention: Temperature target <35oC

Control: Standard treatment

Outcome: Neurological recovery

Cerebral performance category

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

5 Studies

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

3 studies thought suitable for pooling

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

3 studies thought suitable for pooling

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurological outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines

Higher risk of bias in existing trials -> overestimation of treatment effect

Low inclusion rate (8%) -> poor generalisability Or better signal to noise ratio Target population

Early stopping and no power calculation More of a type II error problem

Non-standard change to palliative treatment Dude ?!?

Adverse effects of hypothermia

Adverse effects of hypothermia Prospective observational study 22 centres

Most published research findings are false

Really?

Most published research findings are false

Complicated statistical argument Prior probability Power of the study Level of significance Bias

Flexibiilty in design Definition Outcomes Analysis

Contradicted research

Original clinical research cited more than 1000 times 1990-2003

Compared to subsequent studies bigger and/or better

49 studies 45 claimed a treatment effect 16% contradicted 16% lesser treatment effect 44% replicated 24% not challenged

So, wherefore hypothermia

Dilemma Hypothermia has a good physiological

rationale Supported by at least

reasonable trials

QUESTIONS ??