Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets

Shannon M Fernando^{1

2}, Pietro Di Santo^{3

4}, Behnam Sadeghirad^{5

6}, Jean-Baptiste Lascarrou⁷, Bram Rochwerg^{6

8}, Rebecca Mathew^{9

3}, Mypinder S Sekhon¹⁰, Laveena Munshi^{11

12

13}, Eddy Fan^{11

12

13

14}, Daniel Brodie^{15

16}, Kathryn M Rowan¹⁷, Catherine L Hough¹⁸, Shelley L McLeod^{6

19

20}, Christian Vaillancourt^{21

4

22}, Sheldon Cheskes^{20

23}, Niall D Ferguson^{11

12

13

14}, Damon C Scales^{11

12

23

24}, Claudio Sandroni^{25

26}, Jerry P Nolan^#^{27

28}, Benjamin Hibbert^#^{3

4}

Affiliations

¹ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada. sfernando@qmed.ca.
² Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada. sfernando@qmed.ca.
³ CAPITAL Research Group, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
⁴ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
⁵ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Service de Médecine Intensive Reanimation, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes Cedex, France.
⁸ Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.
⁹ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Division of Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
¹¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹² Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹³ Department of Medicine, Sinai Health System and University Health Network, Toronto, ON, Canada.
¹⁴ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
¹⁵ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
¹⁶ Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA.
¹⁷ Intensive Care National Audit and Research Centre, Napier House, London, UK.
¹⁸ Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA.
¹⁹ Schwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, ON, Canada.
²⁰ Division of Emergency Medicine, Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
²¹ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
²² Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²³ Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
²⁴ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁵ Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
²⁶ Department of Intensive Care, Emergency Medicine and Anesthesiology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
²⁷ Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK.
²⁸ Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.

^# Contributed equally.

PMID: 34389870
DOI: 10.1007/s00134-021-06505-z

Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets

Shannon M Fernando et al. Intensive Care Med. 2021 Oct.

. 2021 Oct;47(10):1078-1088.

doi: 10.1007/s00134-021-06505-z. Epub 2021 Aug 13.

Authors

Affiliations

¹ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada. sfernando@qmed.ca.
² Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada. sfernando@qmed.ca.
³ CAPITAL Research Group, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
⁴ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
⁵ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Service de Médecine Intensive Reanimation, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes Cedex, France.
⁸ Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.
⁹ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Division of Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
¹¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹² Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹³ Department of Medicine, Sinai Health System and University Health Network, Toronto, ON, Canada.
¹⁴ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
¹⁵ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
¹⁶ Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA.
¹⁷ Intensive Care National Audit and Research Centre, Napier House, London, UK.
¹⁸ Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA.
¹⁹ Schwartz/Reisman Emergency Medicine Institute, Sinai Health, Toronto, ON, Canada.
²⁰ Division of Emergency Medicine, Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
²¹ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
²² Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²³ Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
²⁴ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁵ Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
²⁶ Department of Intensive Care, Emergency Medicine and Anesthesiology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
²⁷ Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK.
²⁸ Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.

^# Contributed equally.

PMID: 34389870
DOI: 10.1007/s00134-021-06505-z

Abstract

Purpose: Targeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31-32 °C), moderate hypothermia (33-34 °C), mild hypothermia (35-36 °C), and normothermia (37-37.8 °C) during TTM.

Methods: We searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates.

Results: We included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73-2.30), moderate hypothermia (OR 1.34, 95% CI 0.92-1.94) and mild hypothermia (OR 1.44, 95% CI 0.74-2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61-1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86-1.77) and deep hypothermia (OR 1.27, 95% CI 0.70-2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08-1.94) and deep hypothermia (OR 3.58, 95% CI 1.77-7.26), compared to normothermia (both high certainty).

Conclusions: Mild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit.

Keywords: Critical care medicine; Emergency medicine; Hypoxic; Ischemic brain injury; Out-of-hospital cardiac arrest; Targeted temperature management.

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Comment in

Sweeping TTM conclusion may deprive many post-arrest patients of effective therapy.
Rivera-Lara L, Cho SM, Geocadin RG. Rivera-Lara L, et al. Intensive Care Med. 2021 Dec;47(12):1509-1510. doi: 10.1007/s00134-021-06529-5. Epub 2021 Sep 14. Intensive Care Med. 2021. PMID: 34519844 No abstract available.
Sweeping TTM conclusion may deprive many post-arrest patients of effective therapy. Author's reply.
Fernando SM, Lascarrou JB, Sandroni C, Nolan JP, Hibbert B. Fernando SM, et al. Intensive Care Med. 2021 Dec;47(12):1511-1512. doi: 10.1007/s00134-021-06533-9. Epub 2021 Sep 16. Intensive Care Med. 2021. PMID: 34529117 No abstract available.
Targeted temperature management after out-of-hospital cardiac arrest, no de-implementation required based on network meta analysis.
Gravesteijn BY, Sewalt CA. Gravesteijn BY, et al. Intensive Care Med. 2021 Dec;47(12):1505-1506. doi: 10.1007/s00134-021-06520-0. Epub 2021 Sep 18. Intensive Care Med. 2021. PMID: 34536089 Free PMC article. No abstract available.
Targeted temperature management after out-of-hospital cardiac arrest, no de-implementation required based on network meta analysis. Author's reply.
Fernando SM, Lascarrou JB, Sandroni C, Nolan JP, Hibbert B. Fernando SM, et al. Intensive Care Med. 2021 Dec;47(12):1507-1508. doi: 10.1007/s00134-021-06516-w. Epub 2021 Sep 20. Intensive Care Med. 2021. PMID: 34545439 No abstract available.

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Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets

Affiliations

Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets

Authors

Affiliations

Abstract

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References

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Medical