What do you need to know about pediatric toxicology?

Children exposed to poisonous agents present unique concerns in the medical field. In the home, they may encounter illicit substances, cosmetics, pesticides, vitamins, or similar products. Alternatively, they may ingest toxic medications such as opioids, antiarrhythmics, or hypoglycemics. Accidental ingestion is the most common cause of pediatric poisoning, but environmental exposure is also possible. Intentional poisonings are rare, but 10-fold calculation errors account for 6% of exposures in young children and 12% of poisonings that result in death (Calello and Henretig, 2014). In addition, drug positivity is common in child abuse and neglect cases. Due to stark differences between children and adults, minor ingestions lead to profound effects in the pediatric population.

While not a comprehensive list, here we explore differences that highlight why pediatric poisonings present with challenges that require unique therapeutic approaches. Neonates have greater surface to body mass and underdeveloped skin, leading to higher absorption rates than adults. Blood volume is 0.3L and total body water is 85-90% at birth but 3.5L and 55%, respectively, in adults, which affects volume of distribution particularly for hydrophilic drugs (Magnani et al., 2020). Neonatal livers are immature and CYP enzyme activity and elimination half-lives vary by age. For example, the half-life of morphine is 7-13 hours in neonates, but 2-4 hours in adults. Neonates also have lower protein binding and potentially higher concentrations of free drug for highly protein bound substances, such as phenytoin (Magnani et al., 2020). Due to their higher metabolic rate and decreased reserve, young children are more sensitive to hypoxia, respiratory failure, and are unable to fully compensate for acid-base disturbances. This results in more severe academia at initial presentation with certain poisons, such as salicylism or alcohol (Calello and Henretig, 2014). Respiratory differences result in higher accumulation of airborne toxins and children <6 months old have higher concentrations of fetal hemoglobin (HbF), which binds carbon monoxide (CO) more avidly. As a result, neonates undergoing the same exposure as adults develop higher CO concentrations and exhibit symptoms earlier (Magnani et al., 2020). Combined, these differences may lead to worse outcomes and require additional monitoring time after certain poisonings in children.

Two specific trends in pediatric poisonings have arisen over the last several years. First, pediatric exposure to edible marijuana products has steadily increased as states continue to legalize recreational use (Wang, 2017). Second, analgesics are now the third most frequently involved in pediatric (≤5 years old) exposures, but the most frequently involved in deaths (Gummin et al., 2022; Magnani et al., 2020). This is in part due to the rise in opioid use during the overdose epidemic. In children, the onset of opioid toxicity is delayed and the clinical symptoms are prolonged (Hui et al., 2021). Treatment requires a lower starting dose of I.V. naloxone compared to adults. Another analgesic, acetaminophen has become one of the most commonly used analgesics used in pediatric suicides, presumably due to the ease of over-the-counter access (Ross 2022).

Pediatric toxicology is an under studied field with major consequences. Toxic exposures in children may affect neurological development and lead to cognitive control deficits and risk-taking behaviors, including drug abuse and suicidality, later in life (Magnani et al., 2020). Unintentional poisonings of the curious child can be minimized by keeping drugs in their original, child-proof containers, overdoses can be prevented using single dose packaging, and some deaths can be avoided by having intranasal naloxone on hand if any opioids are present in the house. After an exposure, interdisciplinary involvement of pediatric experts, social workers, toxicologists and emergency physicians will ensure the best outcome for a poisoned child.

REFERENCES

1. Calello, D.P., Henretig, F.M., 2014. Pediatric toxicology: specialized approach to the poisoned child. Emerg Med Clin North Am 32, 29–52. https://doi.org/10.1016/j.emc.2013.09.008
2. Gummin, D.D., Mowry, J.B., Beuhler, M.C., Spyker, D.A., Rivers, L.J., Feldman, R., Brown, K., Nathaniel, P.T.P., Bronstein, A.C., Weber, J.A., 2022. 2021 Annual Report of the National Poison Data System© (NPDS) from America’s Poison Centers: 39th Annual Report. Clin Toxicol (Phila) 60, 1381–1643. https://doi.org/10.1080/15563650.2022.2132768
3. Hui, W.F., Hon, K.L., Leung, A.K.C., 2021. An Overview of the Pediatric Toxidromes and Poisoning Management. Curr Rev Clin Exp Pharmacol 16, 318–329. https://doi.org/10.2174/1574884715666201201090210
4. Magnani, B., Kwong, T., McMillin, G.A., Wu, A., 2020. Clinical Toxicology Testing: A Guide For Laboratory Professionals, 2nd edition-PUB227, 2nd ed. CAP.
5. Wang, G.S., 2017. Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization. J Med Toxicol 13, 99–105. https://doi.org/10.1007/s13181-016-0552-x