Abstract: We included 85 studies, 82 of which (10,350 participants) were eligible for quantitative analysis in the review. All participants, aged 13 years to 89 years, were American Society of Anesthesiologists (ASA) I-III patients undergoing elective surgery. Each study was conducted in a single centre in high- , middle- and low-income countries worldwide. According to the risk of bias assessment, all except five studies were identified as being of satisfactory methodological quality, allowing 82 studies to be combined in the meta-analysis. Five of the 82 studies were assessed as high risk of bias: one for participant and personnel blinding, one for incomplete outcome data, and three for other potential sources of bias. The overall incidence of pain and high-intensity pain following propofol injection in the control group were 63.7% (95% CI 60% to 67.9%) and 37.9% (95% CI 33.4% to 43.1%), respectively while those in the lidocaine group were 30.2% (95% CI 26.7% to 33.7%) and 11.8% (95% CI 9.7% to 13.8%). Both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection (lidocaine admixture OR 0.19, 95% CI 0.15 to 0.25, 31 studies, 4927 participants, high-quality evidence; lidocaine pretreatment OR 0.13, 95% CI 0.10 to 0.18, 41 RCTs, 3918 participants, high-quality evidence). Similarly, lidocaine administration could considerably decrease the incidence of pain when premixed with the propofol (OR 0.19, 95% CI 0.15 to 0.24, 36 studies, 5628 participants, high-quality evidence) or pretreated prior to propofol injection (OR 0.14, 95% CI 0.11 to 0.18, 50 studies, 4722 participants, high-quality evidence). Adverse effects of lidocaine administration were rare. Thrombophlebitis was reported in only two studies (OR not estimated, low-quality evidence). No studies reported patient satisfaction. Overall, the quality of the evidence was high. Currently available data from RCTs are sufficient to confirm that both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection. Furthermore, there were no significant differences of effect between the two techniques.

Plain-language summary: We searched the databases until October 2014. We included 85 studies, 82 of which (10,350 participants) were eligible for quantitative analysis. The study participants were randomly selected to receive either intravenous lidocaine injection or normal saline (placebo) at the same time as the propofol injection. We reran the search in November 2015. We found 11 potential studies of interest, those studies were added to the list of ‘Studies awaiting classification' and will be fully incorporated into the formal review findings when we update the review. Three out of the 85 studies were funded by either a pharmaceutical manufacturer with a commercial interest in the results of the studies or the company which supplied the propofol. Eight studies were supported by government hospital or university funds and one study was funded by a charitable grant. We found that the injection of lidocaine into a vein, either mixing lidocaine with propofol or injecting lidocaine before propofol, could effectively reduce the incidence and the high levels of pain associated with the injection of propofol. Adverse effects such as inflammation (redness, swelling) of the vein at the injection site were rare and in two studies were not more frequent with the use of lidocaine. No study reported on patient satisfaction. Based on these results we would expect that out of 1000 patients receiving intravenous propofol, about 384 who did not also receive intravenous lidocaine, would experience moderate to severe pain, compared to only 89 patients who also received intravenous lidocaine. The overall quality of evidence was high with a very large beneficial effect obtained by the administration of lidocaine to reduce painful propofol injections.