Twenty-nine RCTs (n=1,271) were included in the review. Ten RCTs were crossover studies performed in healthy participants (n=262).
None of the included studies reported sample size estimations and power analysis.
Opioid adjunct: 10 studies (n=412) were identified. Three studies found no intra-operative analgesic benefit following fentanyl adjunct alone, while the combination of fentanyl with pancuronium was associated with an intra-operative analgesic benefit. Morphine was associated with an intra-operative analgesic benefit in one study, but no benefit in another. Meperidine was associated with an intra-operative analgesic benefit in one study and a post-operative analgesic benefit in a further study. Sufentanil was not associated with a post-operative analgesic benefit (1 study). The incidence of nausea, dizziness and light-headedness was significantly higher in 2 studies evaluating fentanyl adjunct (P<0.05). Meperidine was also associated with a higher incidence of nausea, light-headedness, sedation and dizziness in 2 studies (P<0.05).
Tramadol adjunct (1 study, n=60): tramadol combined with lidocaine was associated with an intra-operative analgesic benefit. However, compared with the control, skin rash was significantly higher in those receiving tramadol plus lidocaine (P<0.05).
Non-steroidal anti-inflammatory adjunct: 6 studies (n=370) were identified. A post-operative analgesic benefit was associated with the use of ketorolac in 2 studies, while both intra- and post-operative analgesic benefits were observed in another. No statistically-significant side-effects were found. Two studies evaluating tenoxicam and one study evaluating aspirin found a post-operative analgesic benefit. No statistically-significant side-effects were found.
Clonidine adjunct: 5 studies (n=246) were identified. An intra-operative analgesic benefit was observed in 2 studies, while a post-operative analgesic benefit was observed in another. One study observed both intra- and post-operative analgesic benefits. One study found no significant benefit. Two studies evaluating higher doses of clonidine reported a significantly higher incidence of sedation (P<0.05) and hypertension (P<0.05), respectively. No side-effects were reported for lower doses.
Alkalinisation agents: 3 studies (n=131) were identified. An intra-operative analgesic benefit was observed with sodium bicarbonate in 2 studies, while another study found no significant benefit. No statistically-significant side-effects were observed.
Muscle relaxants: 5 studies (n=186) were identified. Atracurium was associated with an intra-operative analgesic benefit in 2 studies and a post-operative analgesic benefit in another. The combination of fentanyl with pancuronium was also associated with a intra-operative analgesic benefit in 2 studies. No statistically-significant side-effects were found in 4 studies. In the fifth study, which found no statistically-significant benefit associated with the use of mivacurium, LA toxicity was observed in all patients.
Temperature control: 2 studies (n=50) were identified. Warming the LA solution prior to administration was associated with an intra-operative analgesic benefit in one study. The other study found no analgesic benefit associated with increasing the temperature of the limb prior to administration of the LA solution.
Potassium (1 study, n=12): no analgesic benefit was observed for the potassium adjunct.