The Role of Hypothermia in Head Injury by yaofenjin


									The Role of Hypothermia in
       Head Injury
       The Evidence

          Paul Ferris
• Introduction
• The science
• The evidence
• Long been recognised that hypothermia
  conferred neuroprotection
  – Ancient Egypt, Greece & Rome
  – Hippocrates
• Clinical interest began in 30’s & 40’s
  – Successful resuscitation of hypothermic near-
    drowning victims
  – Trials in 60’s unsuccessful (Deep
• Animal studies in 80’s
  – Benefits with mild (32-35oC)
  – Fewer & less severe side effects
• Improvements in ICU meant larger trials
  now feasible
              The Science
• Cerebral metabolism reduced by 5-7% for
  each oC reduction
  – Decreased glucose & O2 consumption
• Ischaemic cells either:
  – Necrose
  – Recover
  – Enter an apoptosis pathway
               The Science
• Hypothermia prevents cell injury leading to
  – Inhibition of caspase activation
  – Prevents mitochondrial dysfunction
  – Decreased excitatory neurotransmitters
  – Modification of intracellular ion concentration
  – Modification of intracellular acidosis
             The Science
• Hypothermia suppresses inflammatory
• Decreases free radical production
• Reduces vascular permeability
  – Reduced brain oedema
• Helps maintain cell membrane integrity
• Prevents hyperthermia
            The Science
• In short hypothermia influences many
  key destructive mechanisms following
  brain injury
               The Evidence
• Strongest evidence supports use following
  – 23% improvement in good neurological
    outcome (Bernard et al. NEJM 2002;346:557-663)
  – Most damage occurs with reperfusion
  – Hypothermia able to attenuate destructive
• Good evidence for intraoperative use
  – Deep hypothermic arrest
             The Evidence
• Traumatic brain injury is a different
• Focus on preventing ‘secondary injury’
  – Mainly caused by accumulation of vasogenic
    fluid leading to cerebral oedema and raised
  – Local hyperthermic regions of brain
               The Evidence
• In theory hypothermia should help!
• TBI 1st condition for which hypothermia
  was studied
  – Several studies in 1950’s, with varying
    protocols, failed to demonstrate benefit
  – Animal studies showed clear benefits in
    experimental brain injury
     • Protective effects enhanced by Mg!
              The Evidence
• 13 studies involving 1321 patients in last
  15 years
  – All but one in patients with high ICP (>20/25)
  – All reported a reduction in ICP with
  – Most observed improved neurological
    outcome especially in patients with low GCS
    (4-7) on admission
  – Results however not significant
               The Evidence
• Clifton et al in 2001 (NEJM;344:556-563)
   – 392 patients in 11 centres
   – Decreased ICP
   – No benefits in survival or neurological
   – More ‘days with complications’ in hypothermia
   – Only subgroup to benefit were those who
     were hypothermic at admission
              The Evidence
• Therefore hypothermia for TBI ‘a good
  idea proved ineffective’

• However some criticism
  – Hypothermia stopped at 48 hours
  – Lot of complications
• 2 recent ‘positive’ trials
               The Evidence
• Polderman et al (ICM 2002;28:1563-1567)
   – 136 patients
   – Hypothermia as ‘last resort’
   – Patients with GCS 5-6 at admission
      • 21% more with better neurological outcome
      • 24% lower mortality
   – Rigid protocol to maintain BP, CPP,
     electrolytes etc., & cooling maintained until
     ICP controlled > 24 hrs
   – Slow rewarming
               The Evidence
• Zhi et al in China 2003 (Surg Neurol;59:381-385)
   – 396 patients
   – Good neurological outcome 38.8 vs 19.7%
   – Moderate disability 22.7 vs 18.2%
   – Death 25.7 vs 36.4%
   – Brain temperature measured
   – Other factors well controlled
   – Cooling maintained until ICP controlled
   – Slightly faster rewarming but still > 12 hours
             The Evidence
• Treatment of TBI is complex
• Differences between units
• Side effects of cooling may negate any
  – Hypotensive episodes and bradycardia more
    common in hypothermia group in Clifton study
  – Low magnesium
  – Insulin resistance
               The Evidence
• Routine use can’t be recommended at
• However:
   – Fever should be prevented in 1st 48 hours
   – TBI patients with mild hypothermia on
     admission should be allowed to remain so if
     haemodynamically stable
   – Possible role in the future if rigid protocols
(Polderman KH. Int Care Med 2004;30:556-575)
Any Questions

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