Targeted Temperature Management

Many organs, especially the brain, are sensitive to the ischemia that occurs during cardiac arrest. Even after restoration of circulation, reperfusion and reoxygenation can cause further damage to the brain. Fewer than half of all patients who survive cardiac arrest have good neurologic recovery.

Targeted temperature management (TTM), which involves lowering a patient’s body temperature to 32°C-34°C, is also known as therapeutic hypothermia, or cooling. This intervention is intended to limit neurologic injury after cardiac arrest. Initial studies indicated that treatment with hypothermia was associated with improved neurologic outcomes in patients with ventricular fibrillation (VF) and ventricular tachycardia (VT). Based on these studies, therapeutic hypothermia has been used widely in centers with the capability to do so, including in patients with pulseless electrical activity (PEA) and asystolic arrest, who were not included in the initial studies. Hypothermia is postulated to suppress oxidative stress, apoptosis, and inflammation, as well as early hyperemia and delayed hypoperfusion. Cooling may have beneficial effects on other systems, but it is focused mainly on limiting neurologic injury.

Indications: The American Heart Association (AHA) and the European Resuscitation Council (ERC) recommend that comatose adult patients who experience return of spontaneous circulation (ROSC) after cardiac arrest should be treated with TTM and maintained at a constant temperature between 32°C and 36°C for at least 24 hours. However, the quality of evidence to support these recommendations is low, and as a result, recommendations may change as new evidence emerges.

Contraindications: There are few recognized contraindications to TTM. The ERC suggests that a higher temperature could be targeted in patients with severe cardiovascular impairment at 33°C.

[Image] — **Cooling Methods Used in Clinical Practice**

For more on TTM, see Cardiopulmonary Emergencies in the IM Emergency Medicine rotation guide. Also see Neuroprognostication of Hypoxic-Ischaemic Coma in the Therapeutic Hypothermia Era for “A Suggested Approach to the Comatose Post-Cardiac Patient, with and without Therapeutic Hypothermia” (figure 3) and “Reliability of Predictors of Neurological Outcomes after Cardiac Arrest” (table 1).

Research

Landmark clinical trials and other important studies

Research

Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial

Wolfrum S et al. Circulation 2022.

In a randomized, controlled trial of patients with in-hospital cardiac arrest, mortality and functional outcome at 6 months were not improved with active cooling compared with normothermia.

Read the NEJM Journal Watch Summary

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

Dankiewicz J et al. N Engl J Med 2021.

Survival, Neurological and Safety Outcomes After Out of Hospital Cardiac Arrests Treated by Using Prehospital Therapeutic Hypothermia: A Systematic Review and Meta-Analysis

Szarpak L et al. Am J Emerg Med 2021.

Although prehospital therapeutic hypothermia may improve patient outcomes after out-of-hospital cardiac arrest, data on efficacy and safety are lacking. In this analysis, therapeutic hypothermia did not improve survival at discharge or neurological outcome in patients with out-of-hospital cardiac arrest.

Prediction of Poor Neurological Outcome in Comatose Survivors of Cardiac Arrest: A Systematic Review

Sandroni C et al. Intensive Care Med 2020.

This systematic review examined predictors of poor neurologic outcome after cardiac arrest in comatose resuscitated patients.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

Lascarrou JB et al. N Engl J Med 2019.

Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia.

Read the NEJM Journal Watch Summary

Therapeutic Hypothermia After Cardiac Arrest: A Systematic Review/Meta-Analysis Exploring the Impact of Expanded Criteria and Targeted Temperature

Schenone AL et al. Resuscitation 2016.

In this meta-analysis, the use of therapeutic hypothermia after out-of-hospital cardiac arrest was associated with a survival and neuroprotective benefit. No evidence supported one specific temperature over another during hypothermia.