Targeted temperature management after cardiac arrest: hypothermia "not better than" normothermia

doi:10.3877/cma.j.issn.2096-1537.2026.02.012

Abstract

Abstract:

Targeted temperature management (TTM) refers to the controlled reduction of core body temperature to a predefined target in order to attenuate tissue injury caused by inadequate tissue perfusion and ischemia-reperfusion damage. TTM has long been regarded as a cornerstone of post-cardiac arrest care and remains the only guideline-recommended neuroprotective strategy for comatose patients after return of spontaneous circulation (ROSC). However, an increasing number of recently published trials showed that lower-temperature TTM does not confer additional benefits in neurological outcomes or survival compared with targeted normothermia. These findings have prompted ongoing debate regarding the optimal temperature target, patient selection, and implementation strategies for post-resuscitation temperature management. This article reviews and discusses current evidence and emerging perspectives related to TTM after cardiac arrest.

Key words: Targeted temperature management, Cardiac arrest, Return of spontaneous circulation, Neuroprotection, Post-resuscitation care

Zhibao Guo, Lina Zhang. Targeted temperature management after cardiac arrest: hypothermia "not better than" normothermia[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2026, 12(02): 161-165.

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References 30

1	Nunnally ME, Jaeschke R, Bellingan GJ, et al. Targeted temperature management in ctical care: a report and recommendations from five professional societies [J]. Crit Care Med, 2011, 39(5): 1113-1125.
2	Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxicischemic encephalopathy [J]. N Engl J Med, 2005, 353(15): 1574-1584.
3	Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 ℃ versus 36 ℃ after cardiac arrest [J]. N Engl J Med, 2013, 369(23): 2197-2206.
4	Kirkegaard H, Søreide E, de Haas I, et al. Targeted temperature management for 48 vs 24 hours and neurologic outcome after out-of-hospital cardiac arrest: a randomized clinical trial [J]. JAMA, 2017, 318(4): 341-350.
5	Le May M, Osborne C, Russo J, et al. Effect of moderate vs mild therapeutic hypothermia on mortality and neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest: the CAPITAL CHILL randomized clinical trial [J]. JAMA. 2021, 326(15): 1494-1503.
6	Dankiewicz J, Cronberg T, Lilja G, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest [J]. N Engl J Med. 2021, 384(24): 2283-2294.
7	Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm [J]. N Engl J Med, 2019, 381(24): 2327-2337.
8	Lopez-de-Sa E, Juarez M, Armada E, et al. A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial [J]. Intensive Care Med, 2018, 44(11): 1807-1815.
9	Moler FW, Silverstein FS, Holubkov R, et al. Therapeutic hypothermia after in-hospital cardiac arrest in children [J]. N Engl J Med, 2017, 376(4): 318-329.
10	Moler FW, Silverstein FS, Holubkov R, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children [J]. N Engl J Med, 2015, 372(20): 1898-1908.
11	Sandroni C, Cronberg T, Sekhon M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis [J]. Intensive Care Med, 2021, 47(12): 1393-1414.
12	Tsai MS, Barbut D, Tang W, et al. Rapid head cooling initiated coincident with cardiopulmonary resuscitation improves success of defibrillation and post-resuscitation myocardial function in a porcine model of prolonged cardiac arrest [J]. J Am Coll Cardiol, 2008, 51(20): 1988-1990.
13	Abella BS, Zhao D, Alvarado J, et al. Intra-arrest cooling improves outcomes in a murine cardiac arrest model [J]. Circulation, 2004, 109(22): 2786-2789.
14	Lu J, Shen Y, Qian HY, et al. Effects of mild hypothermia on the ROS and expression of caspase-3 mRNA and LC3 of hippocampus nerve cells in rats after cardiopulmonary resuscitation [J]. World J Emerg Med, 2014, 5(4): 298-305.
15	Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system [J]. J Cereb Blood Flow Metab, 2003, 23(5): 513-530.
16	Nakashima K, Todd MM. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization [J]. Stroke, 1996, 27(5): 913-918.
17	Gong P, Li CS, Hua R, et al. Mild hypothermia attenuates mitochondrial oxidative stress by protecting respiratory enzymes and upregulating MnSOD in a pig model of cardiac arrest [J]. PLoS One, 2012, 7(4): e35313.
18	Chatauret N, Rose C, Therrien G, et al. Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure [J]. Metab Brain Dis, 2001, 16(1/2): 95-102.
19	Ohmura A, Nakajima W, Ishida A, et al. Prolonged hypothermia protects neonatal rat brain against hypoxic-ischemia by reducing both apoptosis and necrosis [J]. Brain Dev, 2005, 27(7): 517-526.
20	Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest [J]. N Engl J Med, 2002, 346(8): 549-556.
21	Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia [J]. N Engl J Med, 2002, 346(8): 557-563.
22	Arrich J, Herkner H, Mullner D, Behringer W. Targeted temperature management after cardiac arrest. A systematic review and meta-analysis of animal studies [J]. Resuscitation, 2021, 162: 47-55.
23	Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia [J]. Crit Care Med, 2009, 37(7 Suppl): S186-S202.
24	Nielsen N, Friberg H, Gluud C, et al. Hypothermia after cardiac arrest should be further evaluated--a systematic review of randomised trials with Meta-analysis and trial sequential analysis [J]. Int J Cardiol, 2011, 151(3): 333-341.
25	Zhang XW, Xie JF, Chen JX, et al. The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomised controlled trials [J]. Crit Care, 2015, 19: 417.
26	Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome [J]. Arch Intern Med, 2001, 161(16): 2007-2012.
27	Nishikimi M, Ogura T, Nishida K, et al. Outcome related to level of targeted temperature management in postcardiac arrest syndrome of low, moderate, and high severities: a nationwide multicenter prospective registry [J]. Crit Care Med, 2021, 49(8): e741-e750.
28	Callaway CW, Coppler PJ, Faro J, et al. Association of initial illness severity and outcomes after cardiac arrest with targeted temperature management at 36 ℃ or 33 ℃ [J]. JAMA Netw Open, 2020, 3(7): e208215.
29	Duan J, Zhai Q, Shi Y, et al. Optimal time of collapse to return of spontaneous circulation to apply targeted temperature management for cardiac arrest: a bayesian network meta-analysis. Frontiers in cardiovascualr medicine [J]. Front Cardiovasc Med, 2022, 8: 784917.
30	Perman SM, Bartos JA, Del Rios M, et al. Temperature management for comatose adult survivors of cardiac arrest: a science advisory from the American Heart Association [J]. Circulation, 2023, 148(12): 982-988.

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