Background and Aims Widespread adoption of intrathecal morphine into clinical practice is hampered by concerns of its potential side-effects. We undertook a systematic review, meta-analysis and trial sequential analysis with the primary objective of determining the efficacy and safety of intrathecal morphine. Our secondary objective was to determine the dose associated with greatest efficacy and safety.

Methods We systematically searched the literature for any trials comparing intrathecal morphine with a control group in patients undergoing hip, knee arthroplasty under spinal anaesthesia. Our primary efficacy outcome was rest pain score (0–10) at 8–12h; our primary safety outcome was the rate of PONV within 24h.

Results Twenty-nine trials including 1814 patients were identified. Rest pain score at 8–12h was significantly reduced in the intrathecal morphine group with a mean difference (95%CI) of -1.7(-2.0,-1.3),I²=71%,p<0.0001, without subgroup difference between doses (p=0.35). Intrathecal morphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.4(1.2,1.6),I²=4%,p<0.0001. However, a subgroup analysis according to doses revealed that rates of PONV within 24h was similar between groups with doses of 100µg, while the risk significantly increased with doses above (p value for subgroup difference=0.03). The quality of evidence for our two primary outcomes was high and moderate-to-high for the secondary outcomes.

Conclusions There is high level evidence that intrathecal morphine provides effective analgesia after lower limb arthroplasty but at the expense of an increased profile of side-effects. However, a dose of 100µg represents a ceiling dose for analgesia and a threshold dose for increased rate of PONV.