Intra-arrest therapeutic hypothermia

Reviewed and revised 1 December 2014


  • Sudden cardiac arrest is defined as the abrupt loss of mechanical cardiac activity and concomitant global loss of blood flow
  • Therapeutic hypothermia (T33°C) after return of spontaneous circulation (ROSC) was not found to confer benefit compared to normothermia (T36°C) in the TTM trial
  • It has been hypothesised the intra-arrest therapeutic hypothermia (IATH) may still be beneficial, as the irreversible injury may occur soon after arrest and prior to ROSC
  • IATH is generally performed by administering IV boluses of cold normal saline (T4°C) in combination with external cooling


  • Therapeutic hypothermia may have these effects:
    • decreased cerebral metabolic rate
    • decreased oxygen demand
    • decreased reperfusion injury, global inflammation and endothelial dysfunction
  • hypoxic-ischemic injury is in part due to reperfusion injury resulting in ‘post-cardiac arrest syndrome’, which is characterised by a cascade of pathophysiological mechanisms that damage various organs including the brain
  • early administration of therapeutic hypothermia, during the arrest, may limit or prevent end-organ injury


  • rapid maximal protective effects on brain and other tissues
  • may help limit or reduce myocardial infarction size (if the cause of the arrest)
  • concomitant volume resuscitation may be beneficial


  • optimal target temperature is unknown
  • optimal time of initiation (if any) is unknown
  • optimal rate and mode of cooling are unknown
  • animal studies suggest decreased cardiac and cerebral blood flow with fluid loading during cardiac arrest (due to increased right atrial pressures and intra-cerebral pressures)
  • cold fluid may alter coronary perfusion pressure
  • potential for over-cooling
  • excessive fluid may lead to pulmonary edema, respiratory compromise and harmful effects due to hypoxia and/or hypercapnia
  • excessive chloride load from IV normal saline


  • numerous animal models have suggested that intra-arrest therapeutic hypothermia (IATH) may be beneficial
  • Debaty et al 2014
    • non-blinded MCRCT in France, n=245
    • therapeutic hypothermia induced with IV cold saline (up to 2L) and external cooling performed intra-arrest (IATH) versus post-ROSC
    • no difference in primary endpoint of neuron specific enolase levels at 24h, or secondary endpoints such as IL-6, IL-8, and IL-10 concentrations, and clinical outcome
    • IATH decreased time to reach temperature ≤34 °C by 75 min (95 % CI: 4; 269), yet survival to hospital or at 1 month, or cerebral function at 1 month, were no different
    • clinical benefit may not have been seen asthe patients may have been “too damaged” for IATH to be beneficial
      • approx 65% had asystole as an initial rhythm
      • there was a median of 17min from call to ALS
      • overall only 16% survival in patients with ROSC


  • total liquid ventilation with temperature controlled perfluorocarbons (animal studies)
  • transnasal evaporative cooling – allows rapid cooling of the brain (animal studies, MCRCT currently in progress)


  • at present intra-arrest cooling should only be performed as part of a clinical trial or study
  • intra-arrest cooling is currently part of the protocol for ECPR at The Alfred in Melbourne, as part of the CHEER trial

References and Links

Journal articles

  • Cariou A, Sunde K. Cold fluids during cardiac arrest: faster cooling but not better outcome! Intensive Care Med. 2014 Dec;40(12):1963-5. PMID: 25392035.
  • Debaty G, Maignan M, Savary D, Koch FX, Ruckly S, Durand M, Picard J, Escallier C, Chouquer R, Santre C, Minet C, Guergour D, Hammer L, Bouvaist H, Belle L, Adrie C, Payen JF, Carpentier F, Gueugniaud PY, Danel V, Timsit JF. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med. 2014 Dec;40(12):1832-42. PMID: 25348858.
  • Dell’anna AM, Scolletta S, Donadello K, Taccone FS. Early neuroprotection after cardiac arrest. Curr Opin Crit Care. 2014 Jun;20(3):250-8. PMID: 24717694.
  • Scolletta S, Taccone FS, Nordberg P, Donadello K, Vincent JL, Castren M. Intra-arrest hypothermia during cardiac arrest: a systematic review. Crit Care. 2012 Dec 12;16(2):R41. PMC3681365.

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Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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