Abel Wakai, Carol Blackburn, Aileen McCabe, Emilia Reece, Ger O'Connor, John Glasheen, Paul Staunton, John Cronin, Christopher Sampson, Siobhan C McCoy, Ronan O'Sullivan, Fergal Cummins

There is increasing evidence that propofol is efficacious and safe for procedural sedation (PS) in the emergency department (ED) setting. However, propofol has a narrow therapeutic window and lacks of a reversal agent. The aim of this review was to cohere the evidence base regarding the efficacy and safety profile of propofol when used in the ED setting for PS. To identify and evaluate all randomized controlled trials (RCTs) comparing propofol with alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1950 to September week 2 2013) and EMBASE (1980 to week 2 2013). We searched the Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (September 2013). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. We re-ran the search in February 2015. We will deal with the one study awaiting classification when we update the review. RCTs comparing propofol to alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS in participants of all ages. Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using The Cochrane Collaboration tool for assessing risk of bias. Ten studies (813 participants) met the inclusion criteria. Two studies only included participants 18 years and younger; six studies only included participants 18 years and older; one study included participants between 16 and 65 years of age and one study included only adults but did not specify the age range. Eight of the included studies had a high risk of bias. The included studies were clinically heterogeneous. We undertook no meta-analysis.The primary outcome measures of this review were: adverse effects (as defined by the study authors) and participant satisfaction (as defined by the study authors). In one study comparing propofol/fentanyl with ketamine/midazolam, delayed adverse reactions (nightmares and behavioural change) were noted in 10% of the ketamine/midazolam group and none in the propofol/fentanyl group. Seven individual studies reported no evidence of a difference in adverse effects between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions. Three individual studies reported no evidence of a difference in pain at the injection site between intravenous propofol and alternative interventions. Four individual studies reported no evidence of a difference in participant satisfaction between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions (ketamine, etomidate, midazolam). All the studies employed propofol without the use of an adjunctive analgesic and all, except one, were small (fewer than 100 participants) studies. The quality of evidence for the adverse effects and participant satisfaction outcomes was very low.Nine included studies (eight comparisons) reported all the secondary outcome measures of the review except mortality. It was not possible to pool the results of the included studies for any of the secondary outcome measures because the comparator interventions were different and the measures were reported in different ways. Seven individual studies reported no evidence of difference in incidence of hypoxia between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions. No firm conclusions can be drawn concerning the comparative effects of administering intravenous propofol, with or without an adjunctive analgesic agent, with alternative interventions in participants undergoing PS in the ED setting on adverse effects (including pain at the injection site) and participant satisfaction. The review was limited because no two included studies employed the same comparator interventions, and because the number of participants in eight of the included studies were small (fewer than 100 participants).