Use of Ketamine and Esketamine in the Pediatric Population: Current Evidence and Clinical Applications

Ketamine is a well-established anesthetic agent that is gaining increasing recognition for its diverse therapeutic applications, including the management of chronic pain, refractory status epilepticus, major depressive disorder, and suicidality. Although it has been used clinically since the 1960s, multiple clinical trials with ketamine and esketamine in adults and pediatric populations are ongoing. There has been recent growing interest in ketamine and esketamine for psychiatric conditions in children and adolescents. The clinical use of ketamine is complex, in part because of the numerous available formulations and administration routes. Ketamine has different bioavailability depending on the route of administration: intravenous (100%), intramuscular (64%-93% in adults, 41% in pediatric populations), intranasal (43%-48% in adults, 50% in pediatric populations), sublingual (29%-32%), rectal (25%-30%), epidural (77%), and oral (17%-18%), which is due to extensive first-pass hepatic metabolism. Differences in dosing also produce distinct clinical effects. The challenges associated with ketamine use are further magnified in pediatric populations, for which developmental stage, pharmacokinetics, and neurodevelopmental factors play critical roles in guiding safe and effective treatment. In this review, the authors summarize the pharmacodynamics, pharmacokinetics, adverse effects and contraindications, and clinical applications of ketamine and esketamine among adult and pediatric populations.