The epidemic of toxicity related to prescription opioid use among U.S. adults is thought to be related to drug abuse. Thus, the public health response has focused on programs to reduce non-medical uses. However, little attention has been given to the possibility of a parallel epidemic among children, particularly vulnerable to opioid toxicit. Preliminary Tennessee Medicaid data suggest this epidemic now possibly affects children: the proportion of children 2-17 years old prescribed opioid analgesics increased from 5% in 1996 to 11% in 2007, with a comparable trend in medical care possibly consistent with opioid toxicity. What is the appropriate public health response to this potential threat to the safety of children? Because children's prescriptions must be filled by a parent or guardian, non-medical use is less plausible, particularly for young children. For this reason, pediatric opioid toxicity is most likey to be an unintended consequence of therapeutic use, which would need to be considered as part of prescription risk-benefit evaluation. Thus, there is an urgent need to quantify the incidence of opioid toxicity in children to inform pediatric practitioners' decision-making. Furthermore, opioid prescribing practices associated with elevated risk need to be identified so these can be avoided when possible. Potentially hazardous practices include higher doses, high-potency opioids such as oxycodone, and concurrent central nervous system depressants. To address this unmet public health need, we will conduct a large retrospective cohort study in an estimated 500,000 Tennessee Medicaid children 2-17 years of age with 1,000,000 filled opioid prescriptions and 1400 confirmed cases of opioid toxicity. There are two specific aims:
Aim 1. Quantify the incidence of toxicity related to prescription opioid use according to a) the child's age, b) toxicity severity, and c) whether or not the toxicity was related to therapeutic use.
Aim 2 Test the hypothesis that opioid toxicity risk increases with: a) increased opioid dose, b) high-potency opioids, and c) concurrent use of other CNS-depressant drugs. These data on the risks of opioid medications increasingly used by children will provide a sound basis for altering pediatric practice to address a novel threat to the safety of this vulnerable population.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Behavioral Genetics and Epidemiology Study Section (BGES)
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Zajicek, Anne
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Vanderbilt University Medical Center
Independent Hospitals
United States
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Chung, Cecilia P; Callahan, S Todd; Cooper, William O et al. (2018) Outpatient Opioid Prescriptions for Children and Opioid-Related Adverse Events. Pediatrics 142:
Ray, Wayne A; Liu, Qi; Shepherd, Bryan E (2015) Performance of time-dependent propensity scores: a pharmacoepidemiology case study. Pharmacoepidemiol Drug Saf 24:98-106
Chung, Cecilia P; Callahan, S Todd; Cooper, William O et al. (2015) Development of an algorithm to identify serious opioid toxicity in children. BMC Res Notes 8:293
Ray, Wayne A; Murray, Katherine T; Kawai, Vivian et al. (2013) Propoxyphene and the risk of out-of-hospital death. Pharmacoepidemiol Drug Saf 22:403-12