Elsevier

Resuscitation

Volume 84, Issue 8, August 2013, Pages 1056-1061
Resuscitation

Clinical paper
Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest

https://doi.org/10.1016/j.resuscitation.2012.11.003Get rights and content

Abstract

Objective

Therapeutic hypothermia, also known as targeted temperature management (TTM), improves clinical outcomes in patients resuscitated from cardiac arrest. Hyperthermia after discontinuation of active temperature management (“rebound pyrexia”) has been observed, but its incidence and association with clinical outcomes is poorly described. We hypothesized that rebound pyrexia is common after rewarming in post-arrest patients and is associated with poor neurologic outcomes.

Methods

Retrospective multicenter US clinical registry study of post-cardiac arrest patients treated with TTM at 11 hospitals between 5/2005 and 10/2011. We assessed the incidence of rebound pyrexia (defined as temperature >38 °C) in post-arrest patients treated with TTM and subsequent clinical outcomes of survival to discharge and “good” neurologic outcome at discharge, defined as cerebral performance category (CPC) 1–2.

Results

In this cohort of 236 post-arrest patients treated with TTM, mean age was 58.1 ± 15.7 y and 106/236 (45%) were female. Of patients who survived at least 24 h after TTM discontinuation (n = 167), post-rewarming pyrexia occurred in 69/167 (41%), with a median maximum temperature of 38.7 (IQR 38.3–38.9). There were no significant differences between patients experiencing any pyrexia and those without pyrexia regarding either survival to discharge (37/69 (54%) v 51/98 (52%), p = 0.88) or good neurologic outcomes (26/37 (70%) v 42/51 (82%), p = 0.21). We compared patients with marked pyrexia (greater than the median pyrexia of 38.7 °C) versus those who experienced no pyrexia or milder pyrexia (below the median) and found that survival to discharge was not statistically significant (40% v 56% p = 0.16). However, marked pyrexia was associated with a significantly lower proportion of CPC 1–2 survivors (58% v 80% p = 0.04).

Conclusions

Rebound pyrexia occurred in 41% of TTM-treated post-arrest patients, and was not associated with lower survival to discharge or worsened neurologic outcomes. However, among patients with pyrexia, higher maximum temperature (>38.7 °C) was associated with worse neurologic outcomes among survivors to hospital discharge.

Introduction

Therapeutic hypothermia improves both survival and neurologic outcome when initiated after resuscitation from cardiac arrest.1, 2, 3, 4 Contemporary protocols for therapeutic hypothermia, known more broadly as therapeutic temperature management (TTM), consist of a cooling phase, a maintenance phase in which temperature is held at 32–34 °C, and a rewarming phase in which normothermia is restored and active temperature control is removed. Subsequent to rewarming, “rebound pyrexia” has been observed, with temperature elevations >38 °C within 24 h of the cessation of active temperature control. Pyrexia has been associated with worsened neurologic outcomes in other disease states such as subarachnoid hemorrhage and traumatic brain injury.5, 6 While investigations have evaluated temperature dynamics during induction and maintenance of post-arrest TTM,7, 8, 9 rebound pyrexia immediately following post-arrest TTM remains poorly characterized with regard to frequency as well as its association with clinical outcomes.

We sought to measure the incidence of rebound pyrexia in patients who received post-arrest TTM. We hypothesized that post-rewarming pyrexia was common and would be associated with worsened clinical outcomes at hospital discharge following cardiac arrest.

Section snippets

Methods

A retrospective analysis was performed using data from the Penn Alliance for Therapeutic Hypothermia (PATH) registry. PATH was established in 2010 as a multicenter U.S.-based registry hosted by the University of Pennsylvania Health System, to serve as a clinical data repository for cardiac arrest and post-arrest care. All PATH member institutions received Institutional Review Board approval or waiver to participate in studies of the pooled registry data. The current investigation received

Results

A total of 2023 adult cardiac arrests from 11 institutions were evaluated for inclusion in the current analysis, occurring between 5/2005 and 10/2011. Of those, 981/2023 (49%) cases exhibited return of spontaneous circulation (ROSC) and 236/981 (24%) were treated with TTM following resuscitation. The 236 TTM-treated patients served as the primary cohort for this investigation.

Demographic and event data from the TTM-treated cohort are shown in Table 2. The mean age was 58.1 ± 15.7 y; 106/236 (45%)

Discussion

In this multicenter analysis of resuscitated cardiac arrest patients treated with TTM, pyrexia within 24 h after rewarming was frequent (occurring in 41% of patients) and pronounced (pyrexic patients had a median temperature maximum of 38.7 °C). Patients with any magnitude of pyrexia had similar survival to discharge and neurologic status at discharge to patients without temperature elevations. However, pyrexia with temperature greater than the median temperature of 38.7 °C was associated with

Conclusions

Pyrexia, defined as a temperature ≥38 °C within 24 h following rewarming from post-arrest TTM, occurred in 41% of patients in our multicenter cohort. The subset of patients with maximum temperatures above the median pyrexia temperature had worse neurologic status at discharge than patients with milder or no pyrexia. The addition of a period of “therapeutic normothermia” subsequent to TTM rewarming should be evaluated as a component of post-arrest critical care; the duration of this period of time

Conflict of interest statement

Ms. Leary has received consulting fees from Stryker Medical; Dr. Abella has received honoraria from Medivance Corporation, Stryker Medical and Philips Healthcare and research support from Philips Healthcare; Dr. Gaieski has received honoraria and research support from Stryker Medical.

Acknowledgements

We would like to thank the participating PATH hospitals for their continued efforts to improve cardiac arrest care for their patients. We would also like to thank Anna Tommasini and Marisa Cinousis for their help with data processing.

References (25)

  • R.M. Merchant et al.

    Therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets

    Crit Care Med

    (2006)
  • www.med.upenn.edu/resuscitation/hypothermia/PennAllianceforTherapeuticHypothermiaPATH.shtml [last accessed...
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    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.11.003.

    1

    On behalf of the PATH investigators (see Appendix A).

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