Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials

Background. Acetaminophen is commonly used for the management of perioperative pain. However, there is a marked discrepancy between the extent to which acetaminophen is used and the available evidence for an analgesic effect after major surgery. The aim of this systematic review is to determine the morphine-sparing effect of acetaminophen combined with patient-controlled analgesia (PCA) with morphine and to evaluate its effects on opioid-related adverse effects. Methods. MEDLINE and the Cochrane Library were searched to select randomized controlled trials which compared PCA morphine alone with PCA morphine plus acetaminophen administered orally or intravenously. Studies were evaluated for their quality based on the Oxford Quality Scale. Outcome measures were morphine consumption over the first 24 h after surgery, patient satisfaction and the incidence of morphine side-effects, including nausea and vomiting, sedation, urinary retention, pruritus and/or respiratory depression. Results. Seven prospective randomized controlled trials, including 265 patients in the group with PCA morphine plus acetaminophen and 226 patients in the group with PCA morphine alone, were selected. Acetaminophen administration was not associated with a decrease in the incidence of morphine-related adverse effects or an increase in patient satisfaction. Adding acetaminophen to PCA was associated with a morphine-sparing effect of 20% (mean, -9 mg; CI -15 to -3 mg; P=0.003) over the first postoperative 24 h. Conclusion. Acetaminophen combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period.