Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials

Preventive analgesia using non-opioid analgesic strategies is recognized as a pathway to improve postoperative pain control while minimizing opioid-related side effects. Ketorolac is a nonsteroidal antiinflammatory drug frequently used to treat postoperative pain. However, the optimal dose and route of administration for systemic single dose ketorolac to prevent postoperative pain is not well defined. We performed a quantitative systematic review to evaluate the efficacy of a single dose of perioperative ketorolac on postoperative analgesia.

We followed the PRISMA statement guidelines. A wide search was performed to identify randomized controlled trials that evaluated the effects of a single dose of systemic ketorolac on postoperative pain and opioid consumption. Meta-analysis was performed using a random-effects model. Effects of ketorolac dose were evaluated by pooling studies into 30- and 60-mg dosage groups. Asymmetry of funnel plots was examined using Egger regression. The presence of heterogeneity was assessed by subgroup analysis according to the route of systemic administration (IV versus IM) and the time of drug administration (preincision versus postincision).

Thirteen randomized clinical trials with 782 subjects were included. The weighted mean difference (95% confidence interval [CI]) of combined effects showed a difference for ketorolac over placebo for early pain at rest of -0.64 (-1.11 to -0.18) but not at late pain at rest, -0.29 (-0.88 to 0.29) summary point (0-10 scale). Opioid consumption was decreased by the 60-mg dose, with a mean (95% CI) IV morphine equivalent consumption of -1.64 mg (-2.90 to -0.37 mg). The opioid-sparing effects of ketorolac compared with placebo were greater when the drug was administered IM compared with when the drug was administered IV, with a mean difference (95% CI) IV morphine equivalent consumption of -2.13 mg (-4.1 to -0.21 mg). Postoperative nausea and vomiting were reduced by the 60-mg dose, with an odds ratio (95% CI) of 0.49 (0.29-0.81).

Single dose systemic ketorolac is an effective adjunct in multimodal regimens to reduce postoperative pain. Improved postoperative analgesia achieved with ketorolac was also accompanied by a reduction in postoperative nausea and vomiting. The 60-mg dose offers significant benefits but there is a lack of current evidence that the 30-mg dose offers significant benefits on postoperative pain outcomes.