Twenty-eight studies (n=1,314 patients) were included in the review. In the assessment of methodological quality, 25 trials (89%) recorded a score of 3 or higher, with six trials recording the highest quality score of 5 points. A total of 790 patients received intrathecal morphine and 524 patients received a placebo.
There were statistically significant increases in the following outcomes observed with the use of intrathecal morphine: nausea (RR 1.3, 95% CI 1.1 to 1.5; 24 RCTs), vomiting (RR 1.6, 95% CI 1.1 to 2.2; 19 RCTs) and pruritus (RR 2.0, 95% CI 1.6 to 2.4; 25 RCTs). There were no statistically significant changes in urinary retention or respiratory depression after treatment with intrathecal morphine.
Lower doses of less than 0.3mg of intrathecal morphine were associated with increased incidences of vomiting (RR<0.3mg 3.1, 95% CI 1.5 to 6.4) compared with trials in which 0.3mg or more of morphine were used (RR≥0.3mg 1.3, 95% CI 0.9 to 1.9). Conversely, higher doses of 0.3mg or more intrathecal morphine were found to increase the incidence of pruritus (RR≥0.3mg 5.0, 95% CI 2.9 to 8.6) compared with doses lower than 0.3mg (RR<0.3mg 1.8, 95% CI 1.4 to 2.2). There were no differences observed between the dosing groups for the outcomes of nausea and urinary retention. The incidence of respiratory depression in patients treated with less than 0.3mg of intrathecal morphine was two out of 247 (1%) patients, compared with seven out of 80 (9%) patients when given a dose of 0.3mg or more.
Increased relative risks of nausea (RR 3.4, 95% CI 1.7 to 6.6) and vomiting (RR 2.5, 95% CI 0.9 to 6.6) were found in the trials with a quality assessment method quality score of 4 points, but not in trials with a method quality score of 5 point. The relative risk of pruritus increased as the method scores increased, although the highest relative risk was calculated in the two trials with a method quality score of 2 points (RR 11.5, 95% CI 1.6 to 83.1). No association was found between the incidence of urinary retention or the risk of respiratory depression and the method quality scores of the trials.
There was no statistically significant heterogeneity reported in any of the analyses of the pooled results for the outcomes examined.