Unexpected versus all-cause mortality as the endpoint for investigating the effects of a Rapid Response System in hospitalized patients

Brunsveld-Reinders et al. Critical Care (2016) 20:168 DOI 10.1186/s13054-016-1339-9 RESEARCH Open Access Unexpected versus all-cause mortality as the endpoint for investigating the effects of a Rapid Response System in hospitalized patients Anja H. Brunsveld-Reinders1*, Jeroen Ludikhuize3, Marcel G. W. Dijkgraaf4, M. Sesmu Arbous1,2, Evert de Jonge1 and for the COMET study group Abstract Background: The purpose of this study was to assess the effect of replacing all-cause mortality by death without limitation of medical treatments (LOMT) as the endpoint in a study of rapid response teams (RRTs) in hospitalized patients. We also described the time course of LOMT orders in patients dying on a general ward and the influence of RRTs on such orders. Methods: This study is a secondary analysis of the COMET trial, a pragmatic prospective Dutch multicenter before-after study. We repeated the original analysis of the influence of RRTs on death before hospital discharge by replacing all-cause mortality by death without an LOMT order. In a subgroup of all patients dying before hospital discharge, we documented patient demographics, admission characteristics and LOMT orders of each patient. Patients age 18 years or above were included. Results: In total, 166,569 patients were included in the study. The unadjusted ORs were 0.865 (95 % CI 0.77-0.98) in the original analysis using all-cause mortality and 0.557 (95 % CI 0.40-0.78) when choosing death without LOMT as the endpoint. In total, 3408 patients died before discharge. At time of death, 2910 (85 %) had an LOMT order. Median time from last change in LOMT status and death was 2 days (IQR 1–5) in the before-phase and median time after introduction of the RRT was 1 day (IQR 1–4) (p value not significant). Conclusions: The improvement in survival of hospitalized patients after introduction of a rapid response team in the COMET study was more pronounced when choosing death without limitation of medical treatment, rather than all deaths as the endpoint. Most patients who died during hospitalization had limitation of medical treatments ordered, often shortly before death. Rapid response teams did not influence the institution of limitation of medical treatments. Keywords: Limitations of medical treatment, Patient safety, Unexpected death, Rapid response team, Medical record Background Patients who are admitted to general wards in hospitals may deteriorate, which may result in unplanned ICU admission, cardiac arrest, or even death [1]. Rapid response systems have been developed for timely identification and treatment of patients on general wards, who are at risk of clinical deterioration [2]. These systems have different * Correspondence: 1 Department of Intensive Care, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, Netherlands Full list of author information is available at the end of the article names in the literature, including rapid response team, outreach team, or medical emergency team. In this paper we will use the term rapid response team (RRT) for both the actual outreach team and the rapid response system as a whole. Three large controlled studies investigated the effects of the introduction of an RRT on clinical outcomes [3–5]. The endpoints of these studies were mortality, unplanned ICU admission and cardiac arrest rates. While studies in the UK and the Netherlands reported improved survival [4, 5] and decreased cardiac arrest rates [4], in an © 2016 Brunsveld-Reinders et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Brunsveld-Reinders et al. Critical Care (2016) 20:168 Page 2 of 7 Australian study there was no improvement in a composite endpoint including mortality, unplanned ICU admission, and cardiac arrests [3]. Crude mortality may not be the optimal endpoint for studying the effects of an RRT on survival. Patients with untreatable diseases may be admitted to a hospital for palliative end-of-life care. Clearly, RRTs are not set up to prevent death in those patients. For this reason, unexpected death has been proposed as a more suitable endpoint for studying the effects of RRTs on survival [3]. Death was considered as expected if a patient was subject to a limitation of medical treatment (LOMT) order at the time of death. This, however, may not be the correct definition of expected death. First, some patients may prefer not to undergo life-sustaining treatments in the event of cardiac arrest, but this does not mean that death is imminent or that these patients do not want optimal treatment. Furthermore, treatment limitation orders are sometimes instituted shortly before death when the clinical condition has deteriorated progressively to a point that survival is no longer considered possible. Clearly, RRTs could have been beneficial in these patients if called in an earlier phase when the clinical condition was not yet hopeless. The aim of our study was to explore the association between treatment-limitation orders and hospital death in a multicenter study of RRTs in the Netherlands. First, what is the effect of an RRT on mortality if all-cause hospital mortality is replaced by the endpoint of death without an LOMT order? Second, what proportion of patients dying on a general hospital ward are given an LOMT order, how do these LOMT orders change over time during hospitalization, and are LOMT policies influenced by the introduction of an RRT. Methods Design, setting, and participants This study is a part of the Cost and Outcomes analysis of Medical Emergency Teams (COMET) multi-center study. The COMET study was designed as a prospective pragmatic before-after trial enabling the analysis of clinical outcomes after sequential introduction of the rapid response system components. Twelve Dutch hospitals participated in this study. Four study wards, comprising two surgical and two medical wards were included in each hospital, the so-called COMET wards. Patients included were 18 years of age or above. The full design of this study has been described previously [4, 6] and is shown in Fig. 1. The study consisted of a before-period followed by two study phases. The before-period comprised 5 months during which baseline characteristics were collected. After that a two-step implementation of the RRT was performed. The first phase lasted 7 months during which the modified early warning score (MEWS) and the situation background assessment recommendation (SBAR) communicat (...truncated)