Question 21

Critically evaluate the role of therapeutic hypothermia following out of hospital cardiac arrest.

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College answer

Not available.



  • Therapeutic hypothermia has been advanced as a means of improving survival and good neurological outcome following cardiac arrest.
  • Therapeutic hypothermia modulates the activity of body proteins and electrolytes.
  • This modulation is thought to have some beneficial effects in scenarios where inflammatory damage is anticipated.
  • This also involves the down-modulation of the overall metabolic rate, which decreases the metabolic demands of the organism in poor cardiac output states
  • Decrease in oxygen consumption matches decreased demand with decreased supply in "penumbra" areas, at the watersheds, where hypoxic injury has caused oedema


  • Decreased granulocyte migration into the brain tissue.
  • Decreased cerebral oedema
  • Intrinsic anticonvulsant effects of hypothermia


  • Decreased rate of drug metabolism
  • Impaired immunity
  • Decreased cardiac output and bradycardia
  • Prolongation of QT
  • Risk of arrhythmias
  • Increased haematocrit and blood viscosity
  • Hyperglycaemia
  • Counterproductive energy expenditure via shivering


  • Pseudorandomised unblinded trial in 1996 showed promising results
  • Bernard et al (2002), in a small study (n=77) demonstrated a marked difference in survival (26% vs 49%) in out of hospital VF arrest survivors using 33°C.
  • HACA trial (2002) in a small study (n=134) demonstrated good neurological outcomes in 55% of cooled patients, vs. 39% of non-cooled patients.
  • TTM trial (2013) in a larger and more methodologically robust study (n=950) had demonstrated non-inferiority of a more conservative hypothermia (36°C), in terms of mortality.
  • HYPERION trial (2019), specifically among patients with nonshockable rhythm (n=584) , found a benefit to good neurological outcome (10.2% vs 5.7%) using 33°C.
  • TTM2 trial (2021), the largest so far (n=1861) had further demonstrated that merely maintaining normothermia (under 37.8°C) was also non-inferior to using  33°C (54% vs 54% mortality).

Society recommendations

Own practice:

  • Any reasonable response, so long as it incorporates the avoidance of fever, eg. "In my practice, I cool patients to keep their temperature in the normal range, under 37.8° C"


Bernard, Stephen A., et al. "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia." New England Journal of Medicine346.8 (2002): 557-563. The famous study from Melbourne.

"Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest." N Engl J Med
2002; 346: 549–56

Bernard, Stephen A., and Michael Buist. "Induced hypothermia in critical care medicine: a review." Critical care medicine 31.7 (2003): 2041-2051.

Nielsen, Niklas, et al. "Targeted temperature management at 33 C versus 36 C after cardiac arrest." New England Journal of Medicine 369.23 (2013): 2197-2206.

Hypothermia after Cardiac Arrest Study Group. "Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest." New England Journal of Medicine 346.8 (2002): 549-556.

Lascarrou, J. B., et al. "Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm" N Engl J Med 381.24 (2019): 2327-2337.

Dankiewicz, Josef, et al. "Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest." New England Journal of Medicine 384.24 (2021): 2283-2294.