1239

Abstract

Introduction: Pentobarbital (PB) is a barbiturate used as a treatment for status epilepticus and alternate agent for sedation. PB contains 40% propylene glycol (PG) and could result in lactic acidosis (LA). A previous report in an adult suggested probable PG-induced LA following PB continuous infusion (CI); however this has not been reported in children. A 3 year-old male was admitted for new-onset seizures. He was initially treated with IV lorazepam and midazolam and loaded with levetiracetam and fosphenytoin, which continued on as maintenance therapy. He was later intubated for respiratory depression and transferred to the PICU. Despite repeat loading doses and increased maintenance doses of his antiepileptics, he continued to have clinical and electrographic subclinical seizures. A midazolam CI was initiated but failed to control his seizures. On hospital day (HD) 3, he was started on PB due to continual subclinical seizures. He was initiated with a 10 mg/kg loading dose followed by a 5 mg/kg/dose IV q 12 hr. The seizures continued, and he was initiated on a PB CI on HD 5 to achieve burst suppression. His CI was titrated to a peak dose of 10 mg/kg/hour. He also received maintenance antiepileptics including phenobarbital, fosphenytoin, levetiracetam, lacosamide, topiramate, and valproic acid. On HD 15, he developed hypotension with a mean arterial pressure (MAP) in the 40s and had a venous LA of 3.01 (nl 0.4-2.0 mmol/L). He received epinephrine and his PB was decreased to 8 mg/kg/hour. His PB serum concentration was 68 mcg/mL (20-40 mcg/ml). The cumulative PG dose from all medications was calculated on HD 15 and was 1398 mg/kg. Over the next few weeks, he continued to have subclinical seizures and required an increase in PB back to 10 mg/kg/hour. On HD 37, he developed hypotension and LA of 6.28, with an osmolar gap of 20.4 mOsm/kg. He received a Lactated Ringer's bolus, sodium bicarbonate IV, dopamine CI, and PB decreased to 5 mg/kg/hr. His pentobarbital concentration was 79 mcg/mL and cumulative PG dose on HD 37 was 4045.8 mg/kg. After discussion with his parents, his PB was tapered off, and the decision was made to treat clinical seizures only. He was discharged home on levetiracetam, valproic acid, and diazepam. The World Health Organization recommends a maximum of 25 mg/kg of PG. On HD 15 and 37, our patient received more than this threshold. The Naranjo probability scale supports a high-probable drug-related adverse event in our patient. Practitioners should be aware of this potential adverse effect with medications containing large amounts of PG. Routine monitoring of osmolar gap should be performed for patients with prolonged use or higher PB doses.