• Christine H Meyer-Frießem, Erik Lipke, Stephanie Weibel, Peter Kranke, Sylvia Reichl, Esther M Pogatzki-Zahn, Peter K Zahn, and Alexander Schnabel.
• Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, BG-Universitätsklinikum Bergmannsheil gGmbH, Medical Faculty of Ruhr University Bochum, Bürkle-de-la-Camp-Platz 1, Bochum, Germany. Electronic address: christine.meyer-friessem@rub.de.
• J Clin Anesth. 2022 Jun 1; 78: 110652.

Study ObjectivePostoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients.Study DesignA systematic review of randomised controlled trials (RCT) with meta-analysis and assessment of the quality of evidence by GRADE was performed.SettingPerioperative pain treatment.PatientsAdult opioid users undergoing surgery.InterventionsPerioperative administration of ketamine.MeasurementsPrimary outcomes were postoperative acute pain at rest/during movement after 24 h and number of patients with ketamine-related adverse events.Main ResultsNine RCTs (802 patients with at least two weeks opioid-intake) were included. There is low-quality evidence that ketamine may slightly reduce postoperative pain during movement after 24 h (mean difference: -0.79; 95% confidence interval (CI): -1.22 to -0.36). Based on a very low-quality of evidence, we are uncertain on any effect of ketamine on pain at rest after 24 h and incidences of adverse events like hallucinations and confusion within 48 h. However, perioperative ketamine reduced cumulative mean opioid consumption by 97.3 mg (95%CI: -164.8 to -29.7) after 24 h and 186.4 mg (95%CI: -347.6 to -25.2) after 48 h. The relative risks (RR) for opioid-related adverse events were significantly different for sedation within 24 h (RR: 0.54; 95%CI 0.37 to 0.78).ConclusionsThere is currently limited evidence for a reduced postoperative pain intensity using perioperative ketamine in preoperative opioid-consuming patients. However, a clinically relevant opioid-sparing effect was evident associated with a reduced risk for postoperative sedation and without increased harm. Therefore, ketamine might be a useful anti-hyperalgesic adjuvant in these patients. Nevertheless, with clinical heterogeneity being considerable, it's too premature to suggest any specific ketamine protocol. Furthermore, many questions (like ideal dosing, treatment duration and more favourable patient-related outcome measures including long-term effects) remain open and need to be addressed in future studies.Protocol RegistrationProspero CRD42020185497.Copyright © 2022 Elsevier Inc. All rights reserved.

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