Elsevier

Resuscitation

Volume 182, January 2023, 109650
Resuscitation

Clinical paper
Time in therapeutic range for targeted temperature management and outcomes following out-of-hospital cardiac arrest

https://doi.org/10.1016/j.resuscitation.2022.11.016Get rights and content

Abstract

Objective

For comatose survivors of out-of-hospital cardiac arrest (OHCA), current guidelines recommend targeted temperature management (TTM) with a goal temperature of 32 °C–36 °C for at least 24 h. We examined adherence to temperature targets, quantified as time-in-therapeutic range (TTR), and association of TTR with survival and neurologic outcomes.

Methods

We conducted a retrospective cohort study of the Resuscitation Outcomes Consortium-Continuous Chest Compressions trial, including adults with OHCA who underwent TTM for >12 h. We imputed continuous temperatures between consecutive temperature measurements using the linear interpolation method and calculated TTR for multiple target temperatures. The association of TTR with survival to hospital discharge and favorable neurological outcome was evaluated using hierarchical regression models.

Main results

Among 2,637 patients (mean age 62.3 years, 29.9 % female), the median duration of TTR for TTM between 32 °C–36 °C was 23 (IQR: 21–24) hours with a median time outside therapeutic range of 0.9 (IQR: 0.0–4.2) hours. In risk-adjusted analyses, there was no association of TTR of 32 °C–36 °C with overall survival (OR 1.00 [95 % CI, 0.90–1.10]) or favorable neurologic outcome (1.02 [95 % CI, 0.90–1.14]). However, in assessments of TTR 33 °C–36 °C, there was a significant association with favorable neurologic survival (OR 1.12 [1.01–1.25]) but not overall survival (OR 1.04 [0.94–1.15]).

Conclusions

Among patients with OHCA who underwent TTM, we found variability in adherence to guideline-recommended treatment targets. Higher TTR was not associated with overall survival, but for certain temperature thresholds, TTR was associated with favorable neurologic outcome.

Section snippets

Background

Only 1 in 10 patients with an out-of-hospital cardiac arrest (OHCA) survives to hospital discharge, and 1 in 5 of those have a poor neurological outcome.1 Targeted temperature management (TTM) is recommended by international guidelines to reduce hypoxic-ischemic brain injury in patients who remain unable to follow commands post-arrest.2, 3 This recommendation is based on initial randomized clinical trials which found that maintaining a target temperature of 33 °C was associated with higher

Data source

The ROC-CCC was a large, randomized controlled trial that included 8 regional sites and 114 emergency medical services (EMS) agencies across North America which enrolled patients with a non-traumatic OHCA from 2011-2015.9 The sites and EMS services were divided into 49 clusters for randomization, representing a set of EMS agencies serving the same set of hospitals in a regional site. Detailed methods regarding these data are described elsewhere.9, 10 Briefly, exclusion criteria included

Results

There were 3,457 patients in ROC-CCC who underwent TTM and had at least one recorded temperature. Of these, 2,637 patients underwent TTM at least 12 h and had at least four temperature measurements (eFig. 2 in the Online Supplement). The mean age of patients was 62.3 (SD ± 15.2) years, 784 (29.7 %) were women, 1,468 (55.7 %) had VF/VT as the first recorded pulseless rhythm, and the other 1,158 (43.9 %) had PEA, asystole, or an undefined non-shockable rhythm (n = 11 had no documented rhythm).

Discussion

In a post-hoc secondary analysis of a large clinical trial that enrolled patients with OHCA at multiple sites across North America, we found adherence to current TTM guideline recommendations was generally high. However, over a third of participants spent more than 10 % of the time outside the therapeutic range for the recommended temperature target of 32 °C–36 °C, with only modest difference if the target temperature ranges were defined at different thresholds (>32 °C, >33 °C, 33 °C–36 °C, or

Conclusion

Among patients with OHCA who underwent TTM, we found variability in adherence to guideline-recommended treatment targets. Higher TTR was not associated with overall survival, but for certain temperature thresholds, TTR was associated with favorable neurologic outcome.

Funding

This study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under the award K23HL153775. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflict of Interest

Dr Khera receives support from the Doris Duke Charitable Foundation (under award, 2022060). He also receives research support, through Yale, from Bristol-Myers Squibb. He is a coinventor of U.S. Provisional Patent Applications 63/177,117 and 63/346,610, unrelated to current work. He is also a founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. The other authors have no relevant disclosures.

CRediT authorship contribution statement

Kevin M Wheelock: Methodology, Software, Formal analysis, Writing – original draft, Writing – review & editing, Visualization. Paul S Chan: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. Lian Chen: Methodology, Software, Formal analysis, Visualization. James A de Lemos: Conceptualization, Methodology, Writing – review & editing. P Elliott Miller: Methodology, Writing – review & editing. Brahmajee K Nallamothu: Conceptualization, Methodology, Writing –

Acknowledgements

None

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