Concise Critical Appraisal: Temperature Management After Cardiac Arrest

Critical care practitioners frequently seek innovative treatments to improve mortality and functional outcomes in patients after cardiac arrest. The only neuroprotective effort previously shown to provide benefit has been targeting patient temperatures to hypothermic levels.¹ This has raised several concerns, leading to repeated guideline recommendation updates by the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM). Recently published guidelines have again been revised based on updated literature surrounding hypothermia and temperature control.² This Concise Critical Appraisal examines the previously reported recommendations and evidence, reviews the ERC-ESICM updated recommendations, and highlights areas that still lack investigation and clarity.

In 2003, the International Liaison Committee on Resuscitation (ILCOR) recommended targeting a core body temperature of 32 °C to 36 °C in patients with out-of-hospital cardiac arrest (OHCA) when the initial rhythm was ventricular fibrillation. This recommendation was based on two trials from 2002 that showed that maintaining a temperature of 32 °C to 34 °C for 12 to 24 hours in patients with OHCA was associated with improved survival to hospital discharge and functional outcome at 6 months. It is important to note that these trials studied a specific population of patients with OHCA who had a shockable rhythm.^3,4

Practices changed in 2013, when the Targeted Temperature Management (TTM) trial showed no difference in all-cause mortality or neurologic function at 6 months when comparing patients cooled to 33 °C versus 36 °C.⁴ This led some clinicians to target 36 °C while others still targeted 33 °C. In 2019, two studies found differing outcomes. The HYPERION trial showed better functional outcomes at 90 days in patients with nonshockable cardiac arrest cooled to 33 °C compared to maintaining normothermia, regardless of where the cardiac arrest occurred.⁵ The TTM-2 trial showed no difference in 6-month mortality or functional outcome in patients cooled to 33 °C versus intervening only if the patient developed a fever over 37.7 °C.⁶ These variable study findings have led to variable cooling practices after cardiac arrest, and it has become apparent that guidelines need clarification.

The ERC and ESICM conducted a systematic review and meta-analysis in an effort to clarify recommendations surrounding temperature control and thermoregulatory methods in patients following in-hospital cardiac arrest and OHCA with any underlying heart rhythm. In March 2022, the panel provided six updated recommendations for patients who remain comatose after return of spontaneous circulation (ROSC)⁷:

1. Continuous, rather than intermittent, monitoring of core temperature is recommended to maintain normothermia, defined as 35.3 °C to 37.3 °C.
2. Fever (> 37.7 °C) prevention for 72 hours is imperative. Because the recommended treatment goal is no longer to achieve hypothermia, the term “targeted hypothermia” has been replaced with “targeted temperature management.”
3. Temperature control can be achieved by patient exposure, antipyretics, or an external cooling device with a target temperature of 37.5 °C. Trials have shown no difference in survival or neurologic outcome when comparing endovascular versus surface cooling.
4. There is insufficient evidence for or against temperature control at 32 °C to 36 °C in subpopulations of patients with cardiac arrest or those for whom early cooling was used.
5. Active rewarming to achieve normothermia should be avoided in comatose patients who passively become mildly hypothermic after ROSC.
6. Prehospital cooling via rapid infusion of cold fluids should be avoided. Prehospital IV fluid cooling was associated with pulmonary edema and rearrest.

There are still areas that need clarity and further investigation regarding temperature control in comatose patients after cardiac arrest. Data comparing normothermia to no temperature control are still lacking. The optimal duration of temperature control and the therapeutic window within which hypothermia is effective is still unknown. There is still no clarity on the degree of brain injury that benefits most from temperature management and the optimal sedation strategy in comatose patients after cardiac arrest.

In summary, the updated recommendations have been revised and focus mainly on avoiding: 1) fever, 2) rewarming passively hypothermic patients, and 3) prehospital cooling with rapid infusions of cold IV fluids. The recommendations may be updated again after the multicenter randomized controlled investigations comparing hypothermia to normothermia in hospitalized patients with cardiac arrest are published.


References:

1. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-556. https://pubmed.ncbi.nlm.nih.gov/11856793/

2. Sandroni C, Nolan JP, Andersen LW, et al. ERC-ESICM guidelines on temperature control after cardiac arrest in adults. Intensive Care Med. 2022 Mar;48(3):261-269. https://pubmed.ncbi.nlm.nih.gov/35089409/

3. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2022 Feb 21;346(8):557-563. https://pubmed.ncbi.nlm.nih.gov/11856794/

4. Nielsen N, Wetterselv J, Cronberg T, et al; TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-2206. https://pubmed.ncbi.nlm.nih.gov/24237006/

5. Lascarrou JB, Merdji H, Le Gouge A, et al; CRICS-TRIGGERSEP Group. Targeted temperature management for cardiac arrest with nonshackable rhythm. N Engl J Med. 2019 Dec 12;381(24):2327-2337. https://pubmed.ncbi.nlm.nih.gov/31577396/

6. Dankiewicz J, Cronberg T, Lija G, et al; TTM2 Trial Investigators. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021 Jun 17; 384(24):2283-2294. https://pubmed.ncbi.nlm.nih.gov/34133859/

7. Nordberg P, Taccone FS, Truhlar A, et al. Effect of trans-nasal evaporative intra-arrest cooling on functional neurologic outcome in out-of-hospital cardiac arrest: the PRINCESS randomized clinical trial. JAMA. 2019 May 7;321(17):1677–1685. https://pubmed.ncbi.nlm.nih.gov/31063573/