Elsevier

Resuscitation

Volume 117, August 2017, Pages 50-57
Resuscitation

Clinical paper
Protocol-driven neurological prognostication and withdrawal of life-sustaining therapy after cardiac arrest and targeted temperature management

https://doi.org/10.1016/j.resuscitation.2017.05.014Get rights and content

Abstract

Background

Brain injury is reportedly the main cause of death for patients resuscitated after out-of-hospital cardiac arrest (OHCA). However, the majority may actually die following withdrawal of life-sustaining therapy (WLST) with a presumption of poor neurological recovery. We investigated how the protocol for neurological prognostication was used and how related treatment recommendations might have affected WLST decision-making and outcome after OHCA in the targeted temperature management (TTM) trial.

Methods

Analyses of prospectively recorded data: details of neurological prognostication; recommended level-of-care; WLST decisions; presumed cause of death; and cerebral performance category (CPC) 6 months following randomization.

Results

Of 939 patients, 452 (48%) woke and 139 (15%) died, mostly for non-neurological reasons, before a scheduled time point for neurological prognostication (72 h after the end of TTM). Three hundred and thirteen (33%) unconscious patients underwent prognostication at a median 117 (IQR 93–137) hours after arrest. Thirty-three (3%) unconscious patients were not neurologically prognosticated and for 2 patients (1%) data were missing. Related care recommendations were: continue in 117 (37%); not escalate in 55 (18%); and withdraw in 141 (45%). WLST eventually occurred in 196 (63%) at median day 6 (IQR 5–8). At 6 months, only 2 patients with WLST were alive and 248 (79%) of prognosticated patients had died. There were significant differences in time to WLST and death after the different recommendations (log rank <0.001).

Conclusion

Delayed prognostication was relevant for a minority of patients and related to subsequent decisions on level-of-care with effects on ICU length-of-stay, survival time and outcome.

Introduction

Out-of-hospital cardiac arrest (OHCA) is a common cause of death worldwide with reported survival less than 11% [1], [2]. Up to 50% of patients admitted to an intensive care unit (ICU) after successful resuscitation survive [3], [4], often with few sequelae or only mild cognitive disability [5]. For those who die during hospitalization, the most frequent presumed cause of death is brain injury but the majority of these patients actually die following withdrawal of life-sustaining therapy (WLST) [6], [7], [8], [9], [10], [11], [12]. Decisions about care, including WLST, often involve testing a patient's potential for a ‘meaningful’ neurological recovery [13]. For neurological prognostication, the reliability and optimal timing of clinical, radiological and electrophysiological tests is debatable, especially if patients are treated with targeted temperature management (TTM) [14]. Current guidelines recommend a multimodal approach starting 72 h after cardiac arrest [15], [16]. Recent reports have raised concerns about ‘early’ WLST [7], [9], [17], [18] but the decision-making processes leading to WLST are not well described or explained. The aim of the present study is to describe the practice of protocol-driven neurological prognostication in the TTM trial, related treatment recommendations, and outcomes for patients.

Section snippets

Methods

Post hoc analysis of data from the TTM trial approved by the steering group before the analyses commenced [4]. The study protocol, design and primary outcome are published [19], [20], [21]. Between November 2010 and January 2013, 939 adult comatose survivors of OHCA of primary cardiac origin were randomized to two target temperatures (33 °C or 36 °C) after return of spontaneous circulation (ROSC). To reduce risks of consecutive bias and ‘self-fulfilling prophecies’, a standardized protocol for

Results

Of the 939 patients included in the TTM study, 452 (48%) woke and 139 died (15%) before neurological prognostication. Three hundred and thirteen patients (33%) underwent neurological prognostication. Prognostication was not performed in 33 (3%) patients. Data were missing for 2 (1%) patients (Fig. 1). Characteristics of these groups are presented in Table 1.

Discussion

Outcome studies of OHCA survivors may be prone to bias because pessimistic and premature determinations of neurological outcome might increase WLST and mortality. To address this issue, the TTM trial protocol incorporated commonly used neurological prognostication tests for unconscious patients after OHCA and linked criteria for WLST [21], [22]. These elements of the trial design might represent a standard of clinical practice that could reduce the risk of unfounded WLST.

However, we observed

Author's contribution

I.D. and T.C. designed the study and wrote the first draft of the manuscript. M.P.W., H.F., and N.N. contributed to the present study concept and design. H.F. was senior investigator in the TTM trial. M.P.W. and T.P were national investigators. J.C., N.A.S., G.G., A.W. were principal investigators. N.N. was the chief-investigator of the TTM trial. R.R. was study statistician. All authors of the manuscript were involved in the analysis and interpretation of the data and reviewed and edited the

Funding

The TTM-trial and the present study was funded by independent research grants from the non-profit or governmental agencies: Swedish Heart-Lung Foundation (grant no. 20090275); Arbetsmarknadens försäkringsaktiebolag AFA-Insurance Foundation (grant no. 100001); The Swedish Research Council (grant nos. 134281, 296161, 286321); Regional research support, Region Skåne; Governmental funding of clinical research within the Swedish NHS (National Health Services) (grant nos. M2010/1837, M2010/1641,

Conflict of interest statement

I. Dragancea receives academic support from the County Council of Skåne.

M.P. Wise was funded 40% WTE during the study by a National Institute for Social Care and Health Research (NISCHR) Academic Health Science Collaboration (AHSC) Clinical Research Fellowship; received travel costs from the British Thoracic Society, Intensive Care Society, Scottish Intensive Care Society, Orion Ltd.; Royalties from Willey Publishing; Honorarium for lecturing at educational meeting Fisher & Paykel, and Merck;

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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.2017.05.014.

    1

    A complete list of investigators participating in the TTM trial is available in the Supplemental Data file.

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