A Systematic Review of the Peripheral Analgesic Effects of Intraarticular Morphine

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Abstract
The analgesic effects of intraarticular morphine are controversial. To systematically evaluate the effects, we performed a review of the literature and a metaanalysis of the peripheral effects of morphine injected intraarticularly. Research databases were searched to identify articles in which peripheral analgesic effects of morphine were studied in patients undergoing arthroscopic knee procedures under local, regional, or general anesthesia. The review was performed on three issues: does morphine injected intraarticularly produce analgesia, is it a dose-dependent effect, and, if so, is the effect systemic or mediated via peripheral opioid receptors? Visual analog score (VAS) and analgesic consumption were studied during the early phase (0–2 h), intermediate phase (2–6 h), and late phase (6–24 h) postoperatively after injection of morphine intraarticularly. Metaanalysis of these effect variables was performed by the weighted-analysis technique, and the essential homogeneity assumption was tested by the χ2 test. Forty-five articles could be identified in which the effects of morphine were studied in a prospective, randomized manner, and 32 of these studies included a placebo control. Pooled analyses of data from 19 studies suitable for metaanalysis showed an improvement in analgesia after morphine compared with placebo in the order of 12–17 mm on the VAS during all three phases of treatment. Studies with high quality scores showed somewhat smaller improvements. Total analgesic consumption could not be analyzed statistically, but the number of studies showing decreased analgesic consumption or no differences between groups was identical (six and six). No clear dose-response effect was seen when VAS was used as a measure of pain, but it was seen when area under the curve was used as a measure of pain. A systemic effect of peripherally-injected morphine was not possible to exclude because of the very limited data available. We conclude from this metaanalysis that intraarticularly administered morphine has a definite but mild analgesic effect. It may be dose dependent, and a systemic effect cannot be completely excluded.