Clinical paperProtocol-driven neurological prognostication and withdrawal of life-sustaining therapy after cardiac arrest and targeted temperature management☆
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.
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A complete list of investigators participating in the TTM trial is available in the Supplemental Data file.