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      Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database

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          Abstract

          Background

          While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects ( sedatives).

          Methods

          A retrospective analysis of adult inpatient discharges from 2008–2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives.

          Results

          Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40–3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569.

          Conclusions

          Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study.

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          Most cited references25

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          Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation.

          The National Registry of Cardiopulmonary Resuscitation (NRCPR) is an American Heart Association (AHA)-sponsored, prospective, multisite, observational study of in-hospital resuscitation. The NRCPR is currently the largest registry of its kind. The purpose of this article is to describe the NRCPR and to provide the first comprehensive, Utstein-based, standardized characterization of in-hospital resuscitation in the United States. All adult (>/=18 years of age) and pediatric (<18 years of age) patients, visitors, employees, and staff within a facility (including ambulatory care areas) who experience a resuscitation event are eligible for inclusion in the NRCPR database. Between January 1, 2000, and June 30, 2002, 14720 cardiac arrests that met inclusion criteria occurred in adults at the 207 participating hospitals. An organized emergency team is available 24 h a day, 7 days a week in 86% of participating institutions. The three most common reasons for cardiac arrest in adults were (1) cardiac arrhythmia, (2) acute respiratory insufficiency, and (3) hypotension. Overall, 44% of adult in-hospital cardiac arrest victims had a return of spontaneous circulation (ROSC); 17% survived to hospital discharge. Despite the fact that a primary arrhythmia was one of the precipitating events in nearly one half of adult cardiac arrests, ventricular fibrillation (VF) was the initial pulseless rhythm in only 16% of in-hospital cardiac arrest victims. ROSC occurred in 58% of VF cases, yielding a survival-to-hospital discharge rate of 34% in this subset of patients. An automated external defibrillator was used to provide initial defibrillation in only 1.4% of patients whose initial cardiac arrest rhythm was VF. Neurological outcome in discharged survivors was generally good. Eighty-six percent of patients with Cerebral Performance Category-1 (CPC-1) at the time of hospital admission had a postarrest CPC-1 at the time of hospital discharge.
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            Rapid Response Teams: A Systematic Review and Meta-analysis.

            Although rapid response teams (RRTs) increasingly have been adopted by hospitals, their effectiveness in reducing hospital mortality remains uncertain. We conducted a meta-analysis to assess the effect of RRTs on reducing cardiopulmonary arrest and hospital mortality rates. We conducted a systematic review of studies published from January 1, 1950, through November 31, 2008, using PubMed, EMBASE, Web of Knowledge, CINAHL, and all Evidence-Based Medicine Reviews. Randomized clinical trials and prospective studies of RRTs that reported data on changes in the primary outcome of hospital mortality or the secondary outcome of cardiopulmonary arrest cases were included. Eighteen studies from 17 publications (with 1 treated as 2 separate studies) were identified, involving nearly 1.3 million hospital admissions. Implementation of an RRT in adults was associated with a 33.8% reduction in rates of cardiopulmonary arrest outside the intensive care unit (ICU) (relative risk [RR], 0.66; 95% confidence interval [CI], 0.54-0.80) but was not associated with lower hospital mortality rates (RR, 0.96; 95% CI, 0.84-1.09). In children, implementation of an RRT was associated with a 37.7% reduction in rates of cardiopulmonary arrest outside the ICU (RR, 0.62; 95% CI, 0.46-0.84) and a 21.4% reduction in hospital mortality rates (RR, 0.79; 95% CI, 0.63-0.98). The pooled mortality estimate in children, however, was not robust to sensitivity analyses. Moreover, studies frequently found evidence that deaths were prevented out of proportion to reductions in cases of cardiopulmonary arrest, raising questions about mechanisms of improvement. Although RRTs have broad appeal, robust evidence to support their effectiveness in reducing hospital mortality is lacking.
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              Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression.

              Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor kinetics) of the opioid that needs reversal. Short elimination of naloxone and biophase equilibration half-lives and rapid receptor kinetics complicates reversal of high-affinity opioids. An opioid with high receptor affinity will require greater naloxone concentrations and/or a continuous infusion before reversal sets in compared with an opioid with lower receptor affinity. The clinical approach to severe opioid-induced respiratory depression is to titrate naloxone to effect and continue treatment by continuous infusion until chances for renarcotization have diminished. New approaches to prevent opioid respiratory depression without affecting analgesia have led to the experimental application of serotinine agonists, ampakines, and the antibiotic minocycline.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 February 2016
                2016
                : 11
                : 2
                : e0150214
                Affiliations
                [1 ]Department of Anesthesiology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, United States of America
                [2 ]North American Partners in Anesthesia, Melville, NY, United States of America
                [3 ]Department of Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, United States of America
                [4 ]Covidien Healthcare Economics and Outcomes Research, Mansfield, MA, United States of America
                [5 ]Covidien Respiratory and Monitoring Solutions, Boulder, CO, United States of America
                [6 ]Harrier Consultancy, Lancaster, United Kingdom
                [7 ]Boulder Medical Writing, Boulder, CO, United States of America
                [8 ]Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands
                [9 ]Department of Anesthesiology, Stony Brook University (SUNY), Stony Brook, NY, United States of America
                Azienda Ospedaliero-Universitaria Careggi, ITALY
                Author notes

                Competing Interests: This analysis was supported by Covidien Healthcare Economics and Outcomes Research. JQ, HLC, and ME are Covidien employees. FJO and JM are employed by North American Partners in Anesthesia. NM is employed by Harrier Consultancy. BH is employed by Boulder Medical Writing. FJO and TJG report grant support and honorarium from Covidien, unrelated to the submitted work. NM and BH report personal fees from Covidien during the conduct of the study. AD reports grants and personal fees from Mundipharma Int. Cambridge, UK; grants from Galleon Pharmaceuticals Corp. PA, USA; grants and personal fees from Revive Therapeutics, Ontario, Canada; grants and personal fees from Gruenenthal GmbH, Aachen, Germany; grants from Royal Dutch Shell, The Hague, Netherlands; grants and personal fees from MSD Netherlands, outside the submitted work. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: FJO OD JM JJQ HLC ME NM BH AD TJG. Performed the experiments: JQ HLC. Analyzed the data: FJO OD JM JQ HLC ME NM BH AD TJG. Wrote the paper: FJO OD JM JJQ HLC ME NM BH AD TJG.

                Article
                PONE-D-15-42141
                10.1371/journal.pone.0150214
                4767404
                26913753
                4799da30-d6cf-4b32-91e1-5f28d3bfc2f9
                © 2016 Overdyk et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 September 2015
                : 10 February 2016
                Page count
                Figures: 2, Tables: 3, Pages: 13
                Funding
                This analysis was supported by Covidien Healthcare Economics and Outcome Research. JQ, HLC, and ME are Covidien employees. The funder, Covidien, provided support in the form of salaries for authors JQ, HLC, and ME, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. FJO and JM are employed by North American Partners in Anesthesia. NM is employed by Harrier Consultancy. BH is employed by Boulder Medical Writing. North American Partners in Anesthesia, Harrier Consultancy, and Boulder Medical Writing provided support in the form of salaries for authors FJO, JM, NM, and BH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pain Management
                Analgesics
                Opioids
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Opioids
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Sedatives
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Intensive Care Units
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Resuscitation
                Medicine and Health Sciences
                Cardiology
                Cardiac Arrest
                Medicine and Health Sciences
                Health Care
                Patients
                Inpatients
                Medicine and Health Sciences
                Diagnostic Medicine
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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