Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials

Abstract

In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient-controlled analgesia (PCA) for postoperative pain in order to clarify this controversy. Our primary aim was to compare the effectiveness and safety of postoperative administered ketamine in addition to opioid for i.v. PCA compared with i.v. PCA with opioid alone. Studies were identified from the Cochrane Library 2003, MEDLINE (1966-2009), and EMBASE (1980-2009) and by hand-searching reference lists from review articles and trials. Eleven studies were identified with a total of 887 patients. Quality and validity assessment was performed on all trials included using the Oxford Quality Scale with an average quality score of 4.5. Pain was assessed using visual analogue scales or verbal rating scales. Six studies showed significant improved postoperative analgesia with the addition of ketamine to opioids. Five studies showed no significant clinical improvement. For thoracic surgery, the addition of ketamine to opioid for i.v. PCA was superior to i.v. PCA opioid alone. The combination allows a significant reduction in pain score, cumulative morphine consumption, and postoperative desaturation. The benefit of adding ketamine to morphine in i.v. PCA for orthopaedic or abdominal surgery remains unclear. Owing to huge heterogeneity of studies and small sample sizes, larger double-blinded randomized studies showing greater degree of homogeneity are required to confirm these findings.