CEREBRAL PROTECTION
Anthony Delaney MBBS MSc FACEM FCICM
Staff Specialist in Intensive Care, Royal North Shore Hospital
Se...
Cerebral Protection
Cerebral protection
 Surgical:
 Decompressive craniectomy
 Medical:
 Hypothermia
Decompressive craniectomyin diffuse traumatic
brain injury
 Population:
 Aged 15-59
 Severe non penetrating brain injur...
Decompressive craniectomyin diffuse traumatic
brain injury
 Intervention:
 Standardised large bifrontotemperoparietal
cr...
Decompressive craniectomyin diffuse traumatic
brain injury
 Comparison:
 Second tier therapy for refractory raised
intra...
Decompressive craniectomyin diffuse traumatic
brain injury
 Allocation concealment:
 Yes, automated telephone system
 B...
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
 Results
 December 2002-April 2010
 15 ICUs in Australasia-i...
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
Decompressive craniectomyin diffuse traumatic
brain injury
 However the adjusted analysis
 Age, last GCS before intubati...
Decompressive craniectomyin diffuse traumatic
brain injury
 So…….
 RESCUE ICP
 ICP>25 for 1-12 hours
 Abnormal CT
 Pr...
Hypothermia for cerebral protection
 Pathophysiology:
 Reduction of CMRO2 of 6-7% per 1o drop in temp
 Reduction in ICP...
Hypothermia for cerebral protection
Hypothermia for neuroprotection in adults after
cardiopulmonary resuscitation
 Question:
 To assess the effectiveness of...
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
mil...
 Higher risk of bias in existing trials ->
overestimation of treatment effect
 Low inclusion rate (8%) -> poor
generalis...
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
 L...
Contradicted research
 Original clinical research cited more than
1000 times 1990-2003
 Compared to subsequent studies b...
So, wherefore hypothermia
 Dilemma
 Hypothermia has a good physiological
rationale
 Supported by at least
reasonable tr...
QUESTIONS ??
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
Delaney on Cerebral protection
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Delaney on Cerebral protection

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Research guru and PI for the ARISE study, college examiner and semi-professional forrest-based carpenter, Anthony always gives a fascinating talk. This time he gives an intelligent and considered breakdown on the nebulous topic of cerebral protection.

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Delaney on Cerebral protection

  1. 1. CEREBRAL PROTECTION Anthony Delaney MBBS MSc FACEM FCICM Staff Specialist in Intensive Care, Royal North Shore Hospital Senior Lecturer, Sydney Medical School, University of Sydney
  2. 2. Cerebral Protection
  3. 3. Cerebral protection  Surgical:  Decompressive craniectomy  Medical:  Hypothermia
  4. 4. Decompressive craniectomyin 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
  5. 5. Decompressive craniectomyin diffuse traumatic brain injury  Intervention:  Standardised large bifrontotemperoparietal craniectomy with opening of the dura
  6. 6. Decompressive craniectomyin 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
  7. 7. Decompressive craniectomyin 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
  8. 8. Decompressive craniectomyin diffuse traumatic brain injury
  9. 9. Decompressive craniectomyin diffuse traumatic brain injury
  10. 10. Decompressive craniectomyin diffuse traumatic brain injury
  11. 11. Decompressive craniectomyin diffuse traumatic brain injury  Results  December 2002-April 2010  15 ICUs in Australasia-ish (inc Saudi Arabia)  Revised primary outcome
  12. 12. Decompressive craniectomyin diffuse traumatic brain injury
  13. 13. Decompressive craniectomyin diffuse traumatic brain injury
  14. 14. Decompressive craniectomyin diffuse traumatic brain injury
  15. 15. Decompressive craniectomyin diffuse traumatic brain injury
  16. 16. Decompressive craniectomyin diffuse traumatic brain injury
  17. 17. Decompressive craniectomyin 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)
  18. 18. Decompressive craniectomyin 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
  19. 19. 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
  20. 20. Hypothermia for cerebral protection
  21. 21. 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
  22. 22. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation  5 Studies
  23. 23. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation  3 studies thought suitable for pooling
  24. 24. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation  3 studies thought suitable for pooling
  25. 25. 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
  26. 26.  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
  27. 27. Adverse effects of hypothermia  Prospective observational study  22 centres
  28. 28. Most published research findings are false  Really?
  29. 29. 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
  30. 30. 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
  31. 31. So, wherefore hypothermia  Dilemma  Hypothermia has a good physiological rationale  Supported by at least reasonable trials
  32. 32. QUESTIONS ??

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