title: Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials.
abstract: OBJECTIVE
  To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery.
  
  
  METHODS
  We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults.
  
  
  RESULTS
  Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them.
  
  
  CONCLUSIONS
  Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.
authors.affiliation: Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI), Western University, London, ON, Canada.|Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.|Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesia and Pain Medicine, and Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.|Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Bradley
authors.initials: B
authors.lastname: Johnston
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Alka
authors.initials: A
authors.lastname: Kaushal
authors.affiliation: Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI), Western University, London, ON, Canada.|Department of Anesthesia & Perioperative Medicine, Western University, London, ON, Canada.
authors.forename: Davy
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI), Western University, London, ON, Canada.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI), Western University, London, ON, Canada. jmarti83@uwo.ca.|Department of Anesthesia & Perioperative Medicine, Western University, London, ON, Canada. jmarti83@uwo.ca.|Department of Epidemiology & Biostatistics, Western University, London, ON, Canada. jmarti83@uwo.ca.|Centre for Medical Evidence, Decision Integrity and Clinical Impact (MEDICI), and Department of Anesthesia & Perioperative Medicine, Schulich School of Medicine & Dentistry, Western University, Room B3-412, 339 Windermere Road, London, ON, N6A 5A5, Canada. jmarti83@uwo.ca.
authors.forename: Janet
authors.initials: J
authors.lastname: Martin
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000328:Adult; D016058:Analgesia, Patient-Controlled / Q000379:methods*; D004338:Drug Combinations; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D017063:Outcome Assessment, Health Care; D010149:Postoperative Pain / Q000188:drug therapy*; D017060:Patient Satisfaction; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic
chemical_list: D004338:Drug Combinations; D007649:Ketamine; D009020:Morphine; D004091:Hydromorphone