BACKGROUND: The routine use of sedation and analgesia during post-cardiac arrest care and its association with clinical outcomes remain unclear. This study aimed to describe the use of sedatives and analgesics in post-cardiac arrest care, and evaluate associations with good functional outcome, survival, clinical seizures, and late awakening. METHODS: This was a post hoc analysis of the TTM2-trial, which randomized 1900 out-of-hospital cardiac arrest patients to either normothermia or hypothermia. In both groups, deep sedation (Richmond Agitation and Sedation Scale ≤ -4) was mandatory during the 40-h intervention. Cumulative doses of sedatives and analgesic drugs were recorded within the first 72 h from randomization. Outcomes were functional outcome (modified Rankin Scale) and survival status at 6 months, occurrence of clinical seizures during the intensive care stay, and late awakening (Full outline of unresponsiveness motor score of four 96 h after randomization). Cumulative propofol doses were divided into quartiles (Q1-Q4). Logistic regression models were used to assess associations between sedative doses and functional outcome and survival, clinical seizures, and late awakening, adjusting for the severity of illness and other clinical factors influencing sedation. RESULTS: A total of 1861 patients were analyzed. In a multivariable logistic regression model, higher propofol doses (Q3, 100.7-153.6 mg/kg) were associated with good functional outcome (OR 1.62, 95%CI 1.12-2.34) and (Q2 and Q3, 43.9-153.6 mg/kg) with survival (OR 1.49, 95%CI 1.05-2.12 and OR 1.84, 95%CI 1.27-2.65, respectively). Receiving fentanyl and remifentanil were associated with good functional outcome (OR 1.69, 95%CI 1.27-2.26 and OR 1.50, 95%CI 1.11-2.02) and survival (OR 1.80, 95%CI 1.35-2.40 and OR 1.56, 95%CI 1.16-2.10). Receiving fentanyl (OR 0.64, 95%CI 0.48-0.86) and higher propofol doses (Q2-4 (43.9-669.4 mg/kg) were associated with the occurrence of clinical seizures. The highest quartile of propofol dose (153.7-669.4 mg/kg, OR 3.19, 95%CI 1.91-5.42) was associated with late awakening. CONCLUSIONS: In this study, higher doses of propofol and the use of remifentanil and fentanyl were associated with good functional outcome and survival, occurrence of clinical seizures, and late awakening.

Adult Critical Care University Hospital of Wales Cardiff UK

Anaesthesiology and Intensive Care Department of Surgical Sciences Uppsala University and Uppsala University Hospital Uppsala Sweden

Anesthesia and Intensive Care Department of Clinical Sciences Lund University Skane University Hospital Carl Bertil Laurels Gata 9 214 28 Malmö Sweden

Anglia Ruskin School of Medicine Essex Cardiothoracic Centre MSE NHS Trust Essex UK MTRC Chelmsford Essex UK

Cardiology Department Lund University Skåne University Hospital Lund Lund Sweden

Copenhagen Trial Unit Centre for Clinical Intervention Research Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Medicine Aarhus University Aarhus N Denmark

Department of Clinical Sciences Anaesthesia and Intensive Care Lund University Helsingborg Hospital Helsingborg Sweden

Department of Clinical Sciences Anaesthesia and Intensive Care Lund University Skåne University Hospital Malmö Sweden

Department of Clinical Sciences Anaesthesia and Intensive Care Skåne University Hospital Lund University Lund Sweden

Department of Clinical Sciences Lund Neurology and Rehabilitation Lund University Lund Sweden

Department of Critical Care Maine Medical Center Portland ME USA

Department of Intensive Care Hôpital Universitaire de Bruxelles Université Libre de Bruxelles Brussels Belgium

Department of Intensive Care Medicine Aarhus University Hospital Aarhus N Denmark

Department of Intensive Care Medicine University Hospital Bern University of Bern Bern Switzerland

Department of Intensive Care University Hospitals Bristol and Weston Bristol UK

Division of Critical Care and Trauma George Institute for Global Health and Bankstown Lidcombe Hospital South Western Sydney Local Health District Sydney Australia

Institute of Heart Diseases Wroclaw Medical University Wroclaw Poland

Institute of Intensive Care Medicine University Hospital Zurich Rämistrasse 100 8091 Zurich Switzerland

Intensive Care Department Kantonsspital St Gallen St Gallen Switzerland

Intensive Care Unit Wellington Hospital Wellington New Zealand and Medical Research Institute of New Zealand Wellington New Zealand

IRCCS Policlinico San Martino; Genoa Italy and Dipartimento Di Scienze Chirurgiche Diagnostiche E Integrate University of Genoa Genoa Italy

Medical ICU Cochin University Hospital AP HP Centre Université Paris Cité Paris France

Nd Department of Internal Mediciny Cardiovascular Medicine General University Hospital and 1St Medical School Prague Prague Czech Republic

Neurology Department of Clinical Sciences Lund Lund University Skåne University Hospital Lund Sweden

Neurology Department of Clinical Sciences Lund University Lund Sweden

Skåne University Hospital Lund Lund University and Clinical Studies Sweden Forum South Skåne University Hospital Lund Sweden

The Australian and New Zealand Intensive Care Research Centre Monash University Melbourne Australia

The Faculty of Health Sciences Department of Regional Health Research University of Southern Denmark Odense M Denmark

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