Sixty-four RCTs (5,018 participants) were included in the review.
Six trials of NSAIDs and two of COX-2 inhibitors showed significant effects on pain and/or opioid needs compared with placebo. Study quality was moderate or poor in all but one trial. One poor-quality trial showed no difference between NSAIDs and acetaminophen (paracetamol). Pre-operative intravenous ketoprofen significantly reduced pain and opioid needs in comparison with post-operative administration (1 good-quality trial).
Six out of 8 trials of incisional local anaesthetics showed a significant effect on pain compared with placebo, while treatment had a significant opioid-sparing effect in 4 trials. The quality of these trials was moderate or poor.
The effect of intraperitoneal local anaesthetics on pain and opioid needs was inconsistent across 24 trials. Fifteen trials (1 good quality) showed a significant difference in at least one outcome in favour of treatment compared with placebo, whereas 9 trials (1 good quality) found no difference. The trial protocols varied considerably.
Two good-quality trials of incisional and intraperitoneal local anaesthesia together showed a significant effect on incisional pain, but not on shoulder or visceral pain. In one of the trials overall pain and opioid need was reduced in the first 2 or 3 hours after surgery. The trials varied in the dose, site and timing of the intervention.
Opioids were compared with placebo in 3 trials. One poor-quality trial showed a significant reduction in the need for additional opioids but no effect on pain, whereas 2 moderate-quality trials found no difference in either outcome. Opioids were compared with alternative opioid regimens in 4 trials. One good-quality trial showed better post-operative pain control when treatment was given at the beginning rather than at the end of surgery. One good-quality trial showed a significant effect on both outcomes with intraperitoneal versus intramuscular pethidine. Two moderate-quality trials found no difference in effect between alternative regimens.
One good-quality placebo-controlled trial of dexamethasone showed a significant reduction in overall, incisional and visceral pain, but not shoulder pain, and a significant reduction in opioid needs.
Pain was significantly reduced by epidural analgesia compared with unspecified controls in 2 poor-quality trials. Pain and opioid needs were significantly reduced by intrathecal local anaesthesia/morphine in one moderate-quality placebo-controlled trial.
Pre-operative gabapentin significantly reduced pain and opioid consumption compared with placebo or tramadol in one moderate-quality trial.
Clonidine was compared with placebo in 2 poor-quality trials. One showed that treatment significantly reduced post-operative pain. Both trials showed a significant difference in opioid needs.
NMDA receptor antagonists.
Significant beneficial effects on pain and opioid needs were shown in 3 trials of dextromethorphan compared with placebo and/or intravenous lidocaine or tramadol. The trials were of moderate or poor quality. Two trials, one poor and one moderate quality, found no difference between ketamine and placebo or tramadol.
Multimodal analgesia comprising pre-operative intramuscular opioids, ketorolac, and incisional-intraperitoneal local anaesthetic blockade significantly reduced pain and opioid needs compared with placebo in one moderate-quality trial.
Interventions to reduce incisional, visceral and shoulder pain.
Few trials investigated the different components of post-operative pain following laparoscopic cholecystectomy. On the basis of the aforementioned studies included in the review, incisional local anaesthetics and dexamethasone reduced incisional pain, while intraperitoneal local anaesthetics and dexamethasone reduced visceral pain. Evidence for the treatment of shoulder pain was lacking.