Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials

Br J Anaesth. 2009 Feb;102(2):156-67. doi: 10.1093/bja/aen368.


Intrathecal morphine without local anaesthetic is often added to a general anaesthetic to prevent pain after major surgery. Quantification of benefit and harm and assessment of dose-response are needed. We performed a meta-analysis of randomized trials testing intrathecal morphine alone (without local anaesthetic) in adults undergoing major surgery under general anaesthesia. Twenty-seven studies (15 cardiac-thoracic, nine abdominal, and three spine surgery) were included; 645 patients received intrathecal morphine (dose-range, 100-4000 microg). Pain intensity at rest was decreased by 2 cm on the 10 cm visual analogue scale up to 4 h after operation and by about 1 cm at 12 and 24 h. Pain intensity on movement was decreased by 2 cm at 12 and 24 h. Opioid requirement was decreased intraoperatively, and up to 48 h after operation. Morphine-sparing at 24 h was significantly greater after abdominal surgery {weighted mean difference, -24.2 mg [95% confidence interval (CI) -29.5 to -19.0]}, compared with cardiac-thoracic surgery [-9.7 mg (95% CI -17.6 to -1.80)]. The incidence of respiratory depression was increased with intrathecal morphine [odds ratio (OR) 7.86 (95% CI 1.54-40.3)], as was the incidence of pruritus [OR 3.85 (95% CI 2.40-6.15)]. There was no evidence of linear dose-responsiveness for any of the beneficial or harmful outcomes. In conclusion, intrathecal morphine decreases pain intensity at rest and on movement up to 24 h after major surgery. Morphine-sparing is more pronounced after abdominal than after cardiac-thoracic surgery. Respiratory depression remains a major safety concern.

Publication types

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

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Anesthesia, General
  • Anesthetics, Local
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Injections, Spinal
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Pain Measurement / methods
  • Pain, Postoperative / prevention & control*
  • Randomized Controlled Trials as Topic
  • Respiratory Insufficiency / chemically induced


  • Analgesics, Opioid
  • Anesthetics, Local
  • Morphine