Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials

Anesthesiology. 2005 Dec;103(6):1296-304. doi: 10.1097/00000542-200512000-00025.


The authors analyzed data from 52 randomized placebo-controlled trials (4,893 adults) testing acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors given in conjunction with morphine after surgery. The median of the average 24-h morphine consumption in controls was 49 mg (range, 15-117 mg); it was significantly decreased with all regimens by 15-55%. There was evidence of a reduction in pain intensity at 24 h (1 cm on the 0- to 10-cm visual analog scale) only with nonsteroidal antiinflammatory drugs. Nonsteroidal antiinflammatory drugs also significantly reduced the incidence of nausea/vomiting from 28.8% to 22.0% (number needed to treat, 15) and of sedation from 15.4% to 12.7% (number needed to treat, 37) but increased the risk of severe bleeding from 0% to 1.7% (number needed to harm, 59). Selective cyclooxygenase-2 inhibitors increased the risk of renal failure in cardiac patients from 0% to 1.4% (number needed to harm, 73). A decrease in morphine consumption is not a good indicator of the usefulness of a supplemental analgesic. There is evidence that the combination of nonsteroidal antiinflammatory drugs with patient-controlled analgesia morphine offers some advantages over morphine alone.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects
  • Acetaminophen / therapeutic use*
  • Analgesia*
  • Analgesia, Patient-Controlled / methods*
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Humans
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Pain Measurement / drug effects
  • Randomized Controlled Trials as Topic


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Acetaminophen
  • Morphine