Abstracts

Rationale: Propofol is increasingly being used for treatment of refractory status epilepticus. Its short half-life offers rapid onset and short recovery times allowing efficient assessments. Although unrecognized by many, there are increasing reports in the literature of Propofol Infusion Syndrome, (PRIS), a deadly adverse reaction due to prolonged and high dose use of the drug characterized by severe metabolic acidosis, rhabdomyolysis, hyperkalemia, lipemia, renal failure, hepatomegaly, and cardiovascular collapse. Methods: Three cases of PRIS are presented: two cases of refractory status epilepticus and one case of increased ICP due to head trauma. Propofol was used for obtaining burst-suppression on continuous EEG or for lowering ICP. Data were obtained by retrospective chart review. Results: Case 1: 24 year old male with neuronal ceroid lipofuscinosis and intractable seizures. He had onset of continuous focal motor seizures on high dose zonisamide and leviteracetam. Seizures continued despite use of Diastat, lorazepam and fosphenytoin. Due to a previous reaction to phenobarbital, Propofol was used. High doses were required to obtain burst suppression, (295 mcg/kg/min). At 17 hours of infusion, methemoglobinemia (4.3) appeared. At 29 hours his pH dropped from 7.34 to 7.17. Propofol was turned off. Rhabdomyolysis (CK 73,172), renal failure (Creat. 1.8), hyperkalemia (K 7.2) and cardiac arrest ensued. ACLS failed. Case 2: 10 year old male with intractable partial onset seizures due to a cortical dysplasia. Prolonged simple partial status occurred while on lamotrigine and oxcarbazepine. Fosphenytoin and midazolam failed to stop the seizures. The EEG was unhelpful. Patient’s own report of seizures was used to gauge therapy. Propofol was used to facilitate rapid awakening and assessment. High doses were required to obtain burst suppression (300 mcg/kg/min). At 23 hours of infusion, his pH dropped from 7.38 to 6.81. Propofol was turned off. Rhabdomyolysis (CK 364,890), methemoglobinemia (3.0), renal failure (Creat. 2.5), hyperkalemia (13.9), and hepatotoxicity (AST 6374, ALT 1233) ensued. Heroic measures failed. Case 3: 35 year old male after trauma with increased ICP. Pentobarbital failed to control ICP’s. Propofol at high doses was used (100mcg/kg/min). At 47 hours of infusion, methemoglobinemia (3.4) and metabolic acidosis appeared. Propofol was turned off. Rhabdomyolysis (CK 2320), renal failure (Creat. 1.5) and hepatotoxicity (AST 515, ALT 268) ensued. All parameters returned to baseline within 6 days. Patient lived. Conclusions: Published reports have recommended avoiding high dose Propofol greater than 67 mcg/kg/min or 4 mg/kg/hr for longer than 48 hours. However, these cases demonstrate that at high doses, shorter durations of infusion can result in PRIS. Use caution when using Propofol infusions longer than 24 hours at doses higher than 4 mg/kg/hr. Stop Propofol if metabolic acidosis, methemoglobinemia, increased CK, K+, AST/ALT or creatinine occur.