Pharmacologic Management of Acute Pain in Children: A Systematic Review and Network Meta-Analysis

Abstract

Importance: Several pharmacologic options exist for the management of acute pediatric pain; however, their comparative effectiveness remains uncertain.

Objective: To assess the relative benefits and harms of pharmacotherapy for acute pediatric pain through a network meta-analysis of randomized clinical trials.

Data sources: Cochrane Database of Systematic Reviews, Medline, Embase, CINAHL, Web of Science, and Scopus to October 2023.

Study selection: Trials that enrolled children (aged <18 years) with acute pain and randomized them to receive a pharmacologic analgesic vs an alternate analgesic or placebo were included.

Data extraction and synthesis: Pairs of reviewers independently reviewed abstracts, extracted data, and assessed risk of bias of eligible trials. A frequentist random-effects model was used for all meta-analyses, and the certainty of evidence was assessed for treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Main outcomes: The primary outcomes were pain severity (range, 0-10 cm using a visual analog scale; minimally important difference [MID], 1 cm), need for rescue medication, symptom relief, and adverse drug events.

Results: A total of 41 trials involving 4935 children were included. High- to moderate-certainty evidence found that compared with placebo, nonsteroidal anti-inflammatory drugs (NSAIDs) (weighted mean difference [WMD], -1.29; 95% CI, -1.89 to -0.70; modeled risk difference [RD] for achieving the MID, 16%), ketamine (WMD, -1.12; 95% CI, -2.09 to -0.14; modeled RD for achieving the MID, 14%), and mid-high potency opioids (WMD, -1.19; 95% CI, -1.83 to -0.55; modeled RD for achieving the MID, 15%) reduced pain. Only NSAIDs reduced the need for rescue medication (relative risk [RR], 0.31; 95% CI, 0.14 to 0.68; modeled RD, 16% fewer patients). Neither NSAIDs (RR, 0.69; 95% CI, 0.31 to 1.55) nor acetaminophen (RR, 0.63; 95% CI, 0.21 to 1.87) increased the risk of short-term gastrointestinal adverse events. All other comparisons showed moderate-certainty evidence of little to no difference from placebo or were supported by low/very low-certainty evidence.

Conclusions and relevance: Compared with placebo, NSAIDs, ketamine, and mid- to high-potency opioids are effective in reducing acute pediatric pain. NSAIDs provide the greatest benefits and least harm, suggesting that they should be the first-line therapy for acute painful conditions in children.