LORAZEPAM TOXICITY IN A PREMATURE-INFANT

OBJECTIVE: To report a case of lorazepam toxicity in a premature infan t and discuss the importance of altered pharmacodynamics and pharmacok inetics in the neonatal population. CASE SUMMARY: A 2025-g, 33-weeks' gestation infant was born with respiratory distress syndrome that requ ired mechanical ventilation. Lorazepam was used to establish sedation and prevent asynchronous breathing while the infant was on the ventila tor. Shortly after the first dose of lorazepam, the infant experienced a seizure and was subsequently given a loading dose of phenobarbital. Lorazepam therapy was continued for sedation. The patient was transfe rred to our tertiary care center on day 2 of life for evaluation of po ssible cardiac disease. Upon arrival, the infant was extremely hypoton ic and unresponsive; therefore, all sedative medications were disconti nued. Two days after admission, the infant continued to exhibit very l ittle spontaneous activity and a lorazepam serum concentration was obt ained (63 h after the last dose). Analysis revealed a toxic lorazepam serum concentration of 4453 nmol/L. The patient eventually was weaned to room air and was transported back to die referring hospital. DISCUS SION: Lorazepam is commonly prescribed in the pediatric population for sedative, anticonvulsant, anxiolytic, antiemetic, and amnestic activi ty. Few data exist regarding the safety of long-term lorazepam therapy in the neonatal subpopulation. There have been some reports of neurol ogic toxicity secondary to lorazepam in preterm infants. Its metabolis m depends on glucuronidation, an enzymatic process that is very depres sed in the premature infant. Accumulation of the drug in the neonate a ccompanied by clinical toxicity is highly likely. CONCLUSIONS: The ina bility to establish a clear pharmacokinetic-pharmacodynamic relationsh ip, along with the increased incidence of reported adverse events of l orazepam in neonates, is concerning. Clinicians should be aware of the altered metabolism and elimination of lorazepam in the premature infa nt.