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Pharmacologic Management of Acute Pain in Children: A Systematic Review and Network Meta-Analysis
Laura Olejnik1,2, João Pedro Lima3, Behnam Sadeghirad3,4
1Department of Emergency Medicine, London Health Sciences, London, Ontario, Canada.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs), ketamine, and opioids effectively reduce acute pediatric pain compared to placebo. NSAIDs offer the most benefits with the fewest harms, making them a recommended first-line treatment for children
Area of Science:
- Pediatric pharmacology
- Pain management
- Evidence-based medicine
Background:
- Acute pediatric pain management has multiple pharmacologic options.
- Comparative effectiveness of these treatments is not well-established.
Purpose of the Study:
- To conduct a network meta-analysis of randomized clinical trials.
- To assess the comparative benefits and harms of pharmacotherapy for acute pediatric pain.
Main Methods:
- Searched multiple databases (Cochrane, Medline, Embase, etc.) up to October 2023.
- Included randomized trials of children (<18 years) with acute pain.
- Used frequentist random-effects models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for certainty of evidence.
Main Results:
- 41 trials with 4935 children were analyzed.
- NSAIDs, ketamine, and mid-high potency opioids significantly reduced pain compared to placebo.
- NSAIDs were most effective in reducing pain and need for rescue medication, with no increased risk of gastrointestinal adverse events.
Conclusions:
- NSAIDs, ketamine, and mid-high potency opioids are effective for acute pediatric pain.
- NSAIDs demonstrate the best balance of efficacy and safety.
- NSAIDs should be considered first-line therapy for acute painful conditions in children.
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.
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