(1758) Use of N-Acetylcysteine in Acute Liver Injury Secondary to Propofol-Related Infusion Syndrome

Introduction: Propofol-related infusion syndrome (PRIS) is a rare but well-documented phenomenon that can cause irreversible mitochondrial toxicity, leading to cardiovascular collapse and multi-organ failure. Amongst the manifestations of PRIS is hepatotoxicity and liver failure, in which use of N-acetylcysteine (NAC) has been documented only in one animal model in 2016. In this study, propofol administered with NAC led to lower biomarkers of liver injury, decreased periportal inflammation, and cellular necrosis compared to propofol alone in rats. NAC increases activation of guanylate cyclase and glutathione levels to decrease inflammation and improves mitochondrial function. This is the first description of using NAC in PRIS-induced hepatotoxicity in a previously healthy adolescent female.

Description: A previously healthy fourteen-year-old female was struck by a truck going 60mph while riding a bike; she suffered a severe traumatic brain injury among other complicating injuries. She was started on sedation for management of refractory increased intracranial pressure (ICP), including propofol. Sedation was maximized due to refractory ICP spikes. She received less than 72 hours of propofol at at varying doses but up to 150 mcg/kg/min, precipitating propofol-related infusion syndrome with fulminant hemodynamic instability, metabolic acidosis, hypertriglyceridemia, acute kidney injury necessitating hemodialysis, and acute liver injury. The patient’s transaminitis peaked on hospital day 12 with AST 1071 and ALT 698 with preservation of synthetic function. Given the rate of rise of transaminases, three doses of N-Acetylcysteine were administered, leading to rapid resolution of her transaminitis with normalized values and no sequala of liver injury.

Discussion: N-Acetylcysteine is frequently used in hepatic injury induced by acetaminophen- and non-drug-induced hepatic injury. Propofol theoretically induces hepatotoxicity through mitochondrial dysfunction and oxidative stress, therefore through its mechanism, NAC may have potential to attenuate liver injury in PRIS. This is the only documented case of using NAC in PRIS-induced hepatotoxicity in humans with known resolution of liver injury.