A systematic review and meta-analysis of interventions to prevent pain from injection of propofol has been published early online in the British medical Journal (BMJ).
The authors note that propofol is the drug of choice for induction of anaesthesia; however despite its many attributes, around three out of every five patients who receive it will experience pain on injection, and in one of these it will be described as severe or excruciating. As a result, a number of interventions to reduce the pain associated with administration of propofol have been investigated. The purpose of this systematic review was to determine the most effective approach.
The authors searched PubMed, Embase the Cochrane Library and www.clinicaltrials.gov for randomised controlled trials (RCTs) comparing one intervention to either another intervention or placebo in the alleviation of pain associated with injection of propofol in adults. They additionally carried out a hand search of the reference lists of located papers, to identify any further relevant RCTs.
A total of 177 RCTs (total n=25,260) were included in the review; the average trial size was 142 patients (range 24 to 388) and 27 interventions (including 19 drug-interventions) were assessed. Meta-analyses were carried out using direct comparisons of intervention versus control (pairwise) and also using indirect comparisons between the interventions shown to be significant individually. The primary outcome was the number of patients reporting any pain (response rate of pain); meta-analysis of pain scores was not carried out as they were reported rarely and inconsistently.
The main findings reported were as follows (taken from the abstract):
• 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% CI 0.07 to 0.30).
• Pre-treatment with lidocaine 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); pre-treatment 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.
The authors note the limitations of their research, and comment that further research is needed to verify the efficacy of a number of other techniques that were found to be effective in only a small number of studies, some of which lack biological plausibility (e.g. antiemetics, cholinesterase inhibitors, antihistamines, stimulants).
On the basis of their findings they recommend the routine use of a small dose of opioids prior to propofol injection, and the use of an antecubital vein rather than a hand vein for propofol administration. If a hand vein is chosen then they recommend pre-treatment with lidocaine in conjunction with venous occlusion. Another practical alternative would be pre-treatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides.