Abstract Introduction Acute liver failure is a rare, life-threatening syndrome characterized by hepatic injury, coagulopathy (INR 1.5), and hepatic encephalopathy within days to weeks in patients without pre-existing liver disease. In North America and other Western countries, the most common cause is acetaminophen toxicity, though other etiologies include viral hepatitis, ischemic injury, autoimmune disease, vascular disorders (e.g., Budd-Chiari), and idiosyncratic drug reactions. Mortality exceeds 40% overall and can surpass 70% in non-acetaminophen cases without transplantation. We report a case of trimethoprim-sulfamethoxazole-associated fulminant hepatic failure complicated by refractory vasoplegic shock. Case Presentation A 51-year-old woman with multiple sclerosis (MS) and new-onset atrial fibrillation was recently discharged to subacute rehabilitation after an MS exacerbation. She was started on a prednisone taper and trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii prophylaxis. Two days later, she presented with altered mental status. On arrival, she was tachycardic in atrial fibrillation with rapid ventricular response (RVR), hypertensive (140s/110s mmHg), encephalopathic, and hypoglycemic, without improvement after IV dextrose. Labs revealed AST 7000 U/L, ALT 4000 U/L, INR 16, lactate 19 mmol/L, bicarbonate 4 mEq/L, and arterial pH 7.0. One week earlier, liver enzymes were only mildly elevated (AST/ALT ∼ 100 U/L). Brain and abdominal imaging were unremarkable, and autoimmune and viral hepatitis panels was negative. Acetaminophen level was undetectable. She remained in atrial fibrillation with RVR and developed profound hypotension (SBP 60-80 mmHg) unresponsive to fluids and cardioversion. Despite high-dose norepinephrine (1.5 µg/kg/min), vasopressin (0.04 U/min), phenylephrine (9 µg/kg/min), hydrocortisone 100 mg IV, N-acetylcysteine infusion, and sodium bicarbonate, she remained hypotensive and acidotic. Transfer to a tertiary hepatology center was initiated but declined due to hemodynamic instability. Given refractory vasoplegia, methylene blue (2 mg/kg bolus then 0.5 mg/kg/hr infusion) was administered without effect. Angiotensin II was considered, but after family discussion, goals of care were transitioned to comfort measures, and she passed shortly thereafter. Discussion TMP-SMX is a rare but recognized cause of idiosyncratic fulminant hepatic failure, likely mediated by hypersensitivity-induced hepatocellular necrosis. Severe hepatic injury can trigger refractory vasoplegia through inflammatory and nitric oxide-mediated vasodilation. Management is primarily supportive, however early NAC, hemodynamic optimization, and timely transfer for transplant evaluation are critical. Rescue agents such as angiotensin II may be considered for catecholamine-resistant shock. This case highlights a catastrophic complication of a widely prescribed antibiotic and underscores the need for early suspicion of drug-induced liver injury and the potential for severe vasoplegia in acute hepatic failure. This abstract is funded by: None
Leitch-Casey et al. (Fri,) studied this question.