Acute Pain Management in Children: NSAIDs Offer Best Balance of Benefits and Harms

What is the best medication for relieving moderate to severe acute pain in children?

In the network meta-analysis of multiple small but decent-quality studies of children with moderate to severe pain, nonsteroidal anti-inflammatory drugs (NSAIDs), mid- and high-potency opioids, and ketamine were the most effective at relieving pain. When considering adverse effects, NSAIDs are the most effective and safest of the available analgesics. Acetaminophen did not fare well, which is probably a reflection of the baseline severity of pain. (Level of Evidence = 1a−)

The authors systematically searched several databases and registries and the reference lists of relevant studies to identify randomized trials that evaluated medications for treating acute pain (less than 4 weeks' duration) in children. The included trials compared active medications with placebo or other analgesics. The authors excluded inpatient trials and those managing procedure-related pain, dental pain, sickle crisis, and migraine. To account for different pain assessment tools, they converted them into a 10-cm visual analog scale and set the minimum important difference at 1 cm. The authors conducted a network meta-analysis to estimate the relative effectiveness of each medication. They included 41 trials with 4,935 children. The median baseline pain score in the trials was 6.9 cm, and 25 (61%) of the trials evaluated musculoskeletal pain. Most (85%) took place in emergency departments. The authors grouped the medications into eight clusters: placebo, acetaminophen, NSAIDs, tramadol, codeine, mid- to high-potency opioids, ketamine, or combinations of medications. Overall, the studies were of decent methodologic quality; 21 were at low risk of bias and 19 had at least one high risk of bias domain.

The authors do not present the data in a manner that is conducive to estimating the numbers needed to treat for benefit or harm. Among the best-quality studies, the most effective group of medications in achieving meaningful pain reductions were NSAIDs, followed by opioids and ketamine (all with large effect sizes ranging from 1.3 to 1.1 on the visual analog scale). NSAIDs were also the most effective at eliminating the need for rescue therapy (relative risk = 0.31). NSAIDs (and acetaminophen) were also no more likely to cause gastrointestinal upset than placebo. Based on a single study, topical NSAIDs appeared to be more effective than other routes of administration.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Foundation

Setting: Various (meta-analysis)

Reference: Olejnik L, Lima JP, Sadeghirad B, et al. Pharmacologic management of acute pain in children: a systematic review and network meta-analysis. JAMA Pediatr. 2025;179(4):407-417.