Twenty-six RCTs (published in 25 reports) were included. Of the 952 patients, 485 received an opioid.
The average size was 15 patients per group (range: 10 to 32). The median quality score was 2 out of a possible 5 (range: 1 to 4). There was a relationship between the quality scores of the reports and the original authors' conclusions on the efficacy of peripheral opioids. The quality scores of the 10 trials which reported positive estimates of efficacy were 2 or below. Seven of the 16 remaining trials (2 experimental and 14 clinical) that had negative conclusions had a quality score of 3 or 4.
The results of the experimental pain trials were not taken into account when estimating the overall efficacy of peripheral opioids.
Bier's block (4 trials).
Fentanyl was used in 2 trials, one of which did not show any significant difference between fentanyl plus local anaesthetic and local anaesthetic alone. The other trial reported significantly improved quality of the sensory block after 15 minutes with 200 microg fentanyl, compared with either saline or 100 microg fentanyl, but concluded that this was not clinically relevant. Morphine was used in 2 trials; in one there was no significant difference between morphine and saline, while in the other both onset of, and recovery from anaesthesia and analgesia were significantly better compared with local anaesthetic alone. However, the review's authors concluded these differences were not clinically relevant.
Other peripheral sites (5 trials).
All 5 trials used morphine. Four did not show any difference between morphine and control during the post-operative period when applied into a tooth socket, a surgical wound, or by intraperitoneal or intrapleural block. The fifth trial reported a statistically-significant improvement in verbal pain rating scores, which were lower for 20 hours, with 20 mg morphine given intrapleurally compared with the same drug and dose given intravenously. The review's authors considered the outcome to be of little clinical relevance due to the atypically high dose used.
Perineural (3 trials).
No trials reported any significant difference between the opioid and the control.
Brachial plexus (10 trials).
In 3 trials, morphine was combined with a local anaesthetic and applied by an axillary or interscalene route. The comparators were systemic morphine or axillary saline. No improvement was demonstrated in 2 of the 3 trials. The third trial (axillary route) reported similar pain scores in the groups, but ignificantly lower post-operative analgesic consumption with the opioid. However, the review's authors did not consider this difference clinically important in this acute setting.
Four trials combined fentanyl with a local anaesthetic and compared it with a local anaesthetic alone or with another route of injection. Two reported a significant improvement with fentanyl, one of which was considered by the trial's authors to be clinically relevant since the speed of onset of sensory block with fentanyl was 5 minutes faster.
Alfentanil added to a local anaesthetic led to a significant improvement in the duration of sensory and motor block after surgery, compared with local anaesthetic plus placebo.
Butorphanol perfusion into the plexus sheath led to significantly lower visual analogue scale scores for pain intensity up to 24 hours, compared with the same drug given intravenously.
Buprenorphine 3 microg/kg was compared with morphine 50 microg/kg; both were added to local anaesthetic before supraclavicular injection. The duration and quality of post-operative analgesia were significantly better with buprenorphine.
No adverse effects attributable to the route of administration were reported.