View Abstract

A6859 - Propofol Infusion Syndrome and HMG Co-A Lyase Deficiency: A Case Report
Author Block: S. Sangli1, A. Nei2, D. Kelm3, B. Lanpher4, R. A. Oeckler1; 1Mayo Clinic, Rochester, MN, United States, 2Pharmacy, Mayo Clinic, Rochester, MN, United States, 3Pulmonary Critical Care Medicine, Mayo Clinic, Rochester, MN, United States, 4Medical Genetics, Mayo Clinic, Rochester, MN, United States.
Introduction: HMG-CoA lyase (HMGCAL) deficiency is an uncommon inherited metabolic disorder of leucine catabolism and ketone production that may result in episodic crises of hypoglycemic hypoketotic state and acidosis. HMGCAL is primarily expressed in liver, pancreas and to a lesser extent, brain. There is minimal expression in skeletal muscle. Here we present a case of mitochondrial HMGCAL deficiency associated with development of severe rhabdomyolysis and renal failure following propofol infusion. Case Presentation: A 29 year-old male with HMGCAL deficiency diagnosed in early childhood presented to an outside hospital with hypoglycemia-induced seizure and encephalopathy requiring intubation for airway protection. Sedation was achieved with infusions of propofol and fentanyl. His diagnosis of HMGCAL was made at age 7 after hypoglycemia. He was not on a monitored diet and had been lost to metabolic follow up prior to the current presentation. It is unclear what triggered the current episode of hypoglycemic seizure, as there were no signs of infection, recent psychosocial stressors, and no history of fasting. At our institution, acylcarnitine profile was consistent with HMGCAL deficiency with massive elevation of C5 hydroxy-acylcarnitine and C6-DC acylcarnitine. After consultation with genetics and nutrition therapy, he was started on a low-fat, high-carbohydrate feeding regimen with low-protein diet and leucine restriction. Prior to transfer to our institution he developed severe rhabdomyolysis, worsening renal failure requiring continuous renal replacement therapy, liver injury, and multiple metabolic derangements. EEG did not identify seizure activity. Total exposure to propofol was estimated at 100 hours (averaging 3.5 mg/kg/hr). Due to persistently increasing creatinine phosphokinase levels (CPK), he was transitioned to midazolam and fentanyl. His CPK levels peaked at >197,500 IU/L . Rhabdomyolysis resolved within in one week of propofol discontinuation. Due to persistent renal failure presumed due to pigment related nephropathy, he ultimately required prolonged renal replacement therapy. Conclusion: There is little evidence in the literature to suggest propofol-associated mitochondrial toxicity. This case highlights the increased susceptibility of patients with mitochondrial HMGCAL deficiency to the development of sedation-related propofol infusion syndrome (PRIS). Careful review of risk factors for PRIS including young age, low carbohydrate intake and high lipid intake, a pre-existing mitochondrial disorder, >48 hour exposure at dosage >4mg/kg/hour is essential to guide sedative choice in critically ill patients requiring sedation.