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Objective To systematically determine the most efficacious approach for preventing pain on injection of propofol. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Cochrane Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers. Study selection Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults. Results Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions. Conclusions The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.

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