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Factors Associated With Rebound Hyperthermia After Targeted Temperature Management in Out-of-Hospital Cardiac Arrest Patients: An Explorative Substudy of the Time-Differentiated Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Survivors Trial

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  • Aki Holm, University of Helsinki
  • ,
  • Hans Kirkegaard
  • Fabio Silvio Taccone, Erasme Hospital
  • ,
  • Eldar Søreide, Stavanger University Hospital
  • ,
  • Anders M Grejs
  • Valdo Toome, Department of Intensive Cardiac Care, North Estonia Medical Centre, Tallinn, Estonia.
  • ,
  • Christian Hassager, University of Copenhagen
  • ,
  • Bodil S Rasmussen, Aalborg University
  • ,
  • Timo Laitio, University of Turku
  • ,
  • Christian Storm, Charité – Universitätsmedizin Berlin
  • ,
  • Johanna Hästbacka, University of Helsinki
  • ,
  • Markus B Skrifvars, University of Helsinki

To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome.

DESIGN: Post hoc analysis.

SETTING: Ten European ICUs.

PATIENTS: Patients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months.


MEASUREMENTS AND MAIN RESULTS: Of 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95-0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13-0.91; p = 0.03) were associated with less rebound hyperthermia, whereas male gender (odds ratio, 3.94; 95% CI, 1.34-11.57; p = 0.01), highest C-reactive protein value (odds ratio, 1.04; 95% CI, 1.01-1.07; p = 0.02), and use of mechanical chest compression during cardiopulmonary resuscitation (odds ratio, 2.00; 95% CI, 1.10-3.67; p = 0.02) were associated with more rebound hyperthermia. Patients with favorable functional outcome spent less time after rewarming over 38.5°C (2.5% vs 6.3%; p = 0.03), 39°C (0.14% vs 2.7%; p < 0.01), and 39.5°C (0.03% vs 0.71%; p < 0.01) when compared with others. Median time to rebound hyperthermia was longer in the unfavorable functional outcome group (33.2 hr; interquartile range, 14.3-53.0 hr vs 6.5 hr; interquartile range, 2.2-34.1; p < 0.01). In a predefined multivariate binary logistic regression model, rebound hyperthermia was associated with decreased odds of favorable functional outcome (odds ratio, 0.42; 95% CI, 0.22-0.79).

CONCLUSIONS: One-third of targeted temperature management patients experience rebound hyperthermia, and it is more common in younger male patients with an aggravated inflammatory response and those treated with a mechanical chest compression device. Later onset of rebound hyperthermia and temperatures exceeding 38.5°C associate with unfavorable outcome.

Original languageEnglish
Article numbere0458
JournalCritical care explorations
Publication statusPublished - Jul 2021

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