Which Analgesic is Best for Acute Pediatric Pain?

For acute pain in kids, nonsteroidal anti-inflammatory drugs (NSAIDs) appeared to work as well as ketamine and mid- to high-potency opioids, but carried less risk, a meta-analysis affirmed.

All three categories of drugs were better than placebo with at least moderate certainty across 41 randomized clinical trials, reported Laura Olejnik, MD, of London Health Sciences in Ontario, Canada, and colleagues.

But the reduction in pain severity was “modest” across the board and reached only around the minimally important difference (MID) of 1 cm on a 10-cm visual analog scale on which 10 represents the worst possible pain, the group wrote in JAMA Pediatrics.

Only NSAIDs reduced the need for rescue medication, with a relative risk of 0.31 (95% CI 0.14-0.68) versus placebo and the numerically largest modeled risk difference of 16% for meeting the minimally important difference in pain score.

And NSAIDs didn’t increase the risk of short-term gastrointestinal adverse events (RR 0.69, 95% CI 0.31-1.55), unlike the other painkillers aside from acetaminophen (RR 0.63, 95% CI 0.21-1.87).

The findings largely match conclusions published alongside the recent American Academy of Pediatrics’ clinical practice guidelines for prescribing opioids to children and adolescents with acute pain in outpatient settings. A technical report accompanying the guidelines noted that studies comparing opioids versus no opioids “support the use of NSAIDs as first-line therapy for postoperative pain on the basis of similar pain control and fewer side effects.”

Acute pain is reported in nearly 60% of pediatric emergency department (ED) visits, Olejnik and colleagues noted, and “clinical management of acute pain remains variable,” with opioids often given “despite minimal and sometimes contradictory evidence regarding their efficacy.”

For a “comprehensive comparison of the safety and efficacy of the available analgesics to inform clinical guidelines and practice,” the group examined 41 trials with a total of 4,935 participants under age 18 years (median 9.7) presenting with pain of less than 4 weeks’ duration. The trials compared a pharmacologic analgesic versus an alternative analgesic or placebo.

Twenty-five trials enrolled participants with musculoskeletal pain, six with otorhinolaryngologic pain, five with abdominal pain, and five with mixed types of painful conditions.

Thirty-five of the trials were conducted in the ED. Twenty-nine of the trials had healthcare professionals administer the medication, and 34 had outcomes measured in the hospital. Of the trials, 19 were deemed to be at high risk of bias.

Interventions were grouped as placebo, acetaminophen, NSAIDs, tramadol, codeine, mid- to high-potency opioids, ketamine, or a combinations of interventions.

The weighted mean difference in visual analog scale pain score compared with placebo was:

• NSAIDs: −1.29 (95% CI −1.89 to −0.70)
• Ketamine: −1.12 (95% CI −2.09 to −0.14)
• Mid-to high-potency opioids: −1.19 (95% CI −1.83 to −0.55)

Other comparisons showed moderate-certainty evidence of little to no difference from placebo, or were supported by low- or very low-certainty evidence, Olejnik and colleagues noted.

Limitations of the analysis included low- or very low-certainty evidence for several interventions and lack of data on short-term harms such that the research team was unable to assess subgroup effects on adverse drug events (ADEs) across differing analgesic routes.

Additionally, the research team was not able to assess long-term harms, such as opioid misuse, or severe ADEs, such as gastrointestinal bleeding, because there were no trials that reported these outcomes, they added. And generalizability was potentially limited by the predominance of ED-based trials.

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