Background/Purpose:  There is a well-described epidemic of deaths and hospitalizations related to opioid prescriptions in adults. However, little is known about opioid toxicity in children. We investigated the incidence of opioid toxicity and compared the safety of the most frequently prescribed opioid, codeine, to that of other opioids used by children and adolescents without serious diseases.

Methods:  We studied a Tennessee Medicaid cohort of 424,382 children aged 2–17 years, who filled 1,133,089 opioid prescriptions for non-cancer pain. We excluded children with prior encounters indicating serious diseases (cancer, sickle cell anemia, congenital anomalies, hospitalization for a total of more than 30 days in the preceding year, or history of organ transplant), institutional residence, and history of drug abuse. The primary study endpoint was opioid toxicity, defined as an emergency department visit, hospitalization, or death attributed to opioid analgesic use. Medical records were reviewed to adjudicate the outcomes.

Results:  The median length of opioid prescription was three days. Most prescriptions were for acute, self-limited conditions including dental procedures (31%), outpatient procedure/surgery (24%), trauma (18%), and minor infections (17%). There were 365 confirmed cases of opioid toxicity with a median follow-up time of opioid exposure of 17 days. At 17 days, the cumulative incidence of opioid toxicity was 33.2/100,000 prescriptions. Children taking any opioid at doses in the highest tertile had higher risk of toxicity than those in the lowest tertile (IRR=1.85, 95% CI=1.36-2.51). The use of tramadol [incident rate ratio (IRR)=3.03, 95% confidence interval (CI)=2.0-4.60] and oxycodone (IRR=1.87, 95% CI=1.19-2.95) was associated with increased risk of opioid toxicity compared to codeine. An analysis restricted to events leading to deaths, hospitalizations or escalation of care showed increased risk with meperidine (IRR=3.43, 95% CI 1.05-11.24) and tramadol (IRR=4.73, 95% CI 2.07-10.82).

Conclusion:  We studied a cohort of children without serious underlying conditions who received opioid analgesics for mostly minor and self-limited outpatient disorders. The cumulative incidence of opioid toxicity was 33.2/100,000 prescriptions at 17 days of follow-up. The use of tramadol, oxycodone, and meperidine, and higher doses of opioids in general increased the risk of toxicity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/opioid-prescriptions-and-adverse-reactions-in-children-and-adolescents-without-serious-diseases/