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.

◊ Reviewed by F. Bonnet, MD
Professor, Dept. of Anesthesiology, Tenon University Hospital, Paris, France

Intrathecal (IT) morphine has been used for more than 25 years to achieve postoperative analgesia. IT morphine is an alternative to intravenous (IV) PCA morphine and to spinal or epidural local anesthetic administration. Several studies have reported the efficacy of IT morphine but there are several drawbacks such as the occurrence of side effects including nausea, vomiting, urinary retention and prolongation of postoperative ileus. Martin Tramer and his colleagues have therefore conducted a systematic review on the use of spinal morphine for postoperative analgesia after major surgery.

The authors retrieved 70 trials and subsequently excluded 43. The remaining 27 trials tested IT morphine versus placebo, using IV PCA morphine as rescue analgesic. Studies included cardio-thoracic (N=6) and non-cardiothoracic surgical procedures. A large range of IT morphine doses was administered from 100 to 4000 mcg. Median dose of IT morphine varied according to the surgical procedure from 500 mcg for cardiothoracic surgery to 300 mcg for abdominal surgery.

IT morphine obviously decreased 24 hours IV morphine consumption (weighted mean difference: ‑16.9 mg [‑23.7; ‑10.1]). Pain intensity at rest and on movement also decreased. The effect of IT morphine was mainly documented during the first 24 hours after surgery. No dose-range effect was observed. Although there was a trend to reduce pulmonary complications, the difference was not significant despite more than 150 patients in each arm. Eventually, IT morphine dramatically increased the risk of respiratory depression (OR: 7.86 [1.54-40.3]). Surprisingly, the incidence of nausea and vomiting was not affected.

This meta-analysis clearly demonstrates that IT morphine provides effective analgesia after major surgical procedures. Nonetheless, there are several limitations related to the heterogeneity of results. In addition, the design of studies (IT morphine versus placebo, IV morphine as a rescue) was adapted to the demonstration of an analgesic effect of IT morphine through an IV morphine sparing effect, but was far from clinical practice. Indeed, in clinical practice, the combination of IT and IV morphine is not recommended due to the risk of respiratory depression. The use of IV morphine as a rescue also blunted the difference in VAS scores between patients who received IT morphine and placebo. Considering the risk of side effects, the limited duration of the analgesic effect, and the opportunity to use alternatives such as epidural local anesthetics, IT morphine should no longer be considered as gold standard for postoperative pain treatment.