Intra-arrest therapeutic hypothermia

Reviewed and revised 1 December 2014

OVERVIEW

• 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

RATIONALE

• 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

PROS

• 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

CONS

• 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

EVIDENCE

• 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

OTHER EXPERIMETAL APPROACHES TO IATH

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

AN APPROACH

• 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.