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. 2024 Feb 1;81(2):126-133.
doi: 10.1001/jamaneurol.2023.4820.

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis

Fabio Silvio Taccone  1   2 , Josef Dankiewicz  3 , Alain Cariou  2   4 , Gisela Lilja  5   6 , Pierre Asfar  7 , Jan Belohlavek  8 , Thierry Boulain  9 , Gwenhael Colin  10 , Tobias Cronberg  5   6 , Jean-Pierre Frat  11 , Hans Friberg  12   13 , Anders M Grejs  14   15 , Guillaume Grillet  16 , Patrick Girardie  17 , Matthias Haenggi  18 , Jan Hovdenes  19 , Janus Christian Jakobsen  20   21 , Helena Levin  22 , Hamid Merdji  23   24 , Hassane Njimi  1 , Paolo Pelosi  25 , Christian Rylander  26 , Manoj Saxena  27   28 , Matt Thomas  29 , Paul J Young  30   31   32   33 , Matt P Wise  34 , Niklas Nielsen  11 , Jean-Baptiste Lascarrou  2   35   36
Affiliations

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis

Fabio Silvio Taccone et al. JAMA Neurol. .

Abstract

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable.

Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm.

Data sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis.

Study selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score.

Data extraction and synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation.

Main outcomes and measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5.

Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups.

Conclusions and relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Taccone reported received lecture fees from Becton Dickinson and Zoll, outside the preparation of this article. Dr Cariou reported personal fees from Beckton Dickinson for lectures during the conduct of the study. Dr Frat reported grants and personal fees from Fisher and Paykel Healthcare for lecture at medical meetings, nonfinancial support from Fisher and Paykel Healthcare for payment of travel and accommodation for medical meetings, personal fees from SOS Oxygène as member of a scientific board, and nonfinancial support from SOS Oxygène payment of travel and accommodation for medical meetings outside the submitted work. Dr Friberg reported grants from Lund University during the conduct of the study and outside the submitted work. Dr Grejs reported grants from Central Denmark Region, Research Funding; fees from Beckton Dickinson for transport and fees paid outside the submitted work. Dr Haenggi reported that The Department of Intensive Care Medicine of the University Hospital Bern, Switzerland, received reimbursement of travel expenses for a presentation related to therapeutic hypothermia at the Symposium Intensivmedizin + Intensivpflege 2023 in Bremen/Germany from Becton Dickinson, no personal fees were paid to the author. Dr Saxena reported unrestricted grants from Bard MD (manufacturer of a physical cooling device) for lectures and consultancy to support the 7th International Hypothermia and Temperature Management Symposium. Dr Nielsen reported grants from the Swedish Research Council during the conduct of the study. Dr Lascarrou reported personal fees from Beckton Dickinson during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Body Temperature Curves in the Hypothermia and Normothermia Groups for Patients in Whom a Core Temperature Was Recorded
Temperature curves show the median and 95% CIs of the observations are within the error bars.
Figure 2.
Figure 2.. Subgroup Analysis of Death From Any Cause at 90 Days and of Unfavorable Functional Outcome Last Day of Follow-Up
Relative risks are derived from a multilevel mixed-effects generalized linear models with trial site as a random intercept. The forest plot shows the relative risks for prespecified subgroups. The horizontal bars represent 95% CIs. CAHP indicates cardiac arrest hospital prognosis; PEA, pulseless electrical activity; ROSC, return on spontaneous circulation; TTM, Targeted Normothermia After Out-of-Hospital Cardiac Arrest.
Figure 3.
Figure 3.. Kaplan-Meier Estimates of the Probability of Survival Until 90 Days After Randomization Among Patients Assigned to Undergo Hypothermia or Normothermia
Data are for the 912 patients included in the final analysis. Data were censored according to the last day of follow-up.
See this image and copyright information in PMC

Comment in

References

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