Background: Patients on extracorporeal membrane oxygenation (ECMO) are vulnerable to infections, coagulopathy, and metabolic derangements. Acalculous cholecystitis is a rare but potentially occult source of sepsis in critically ill ECMO patients. We report a case highlighting the interplay of occult infection, refractory hyperammonaemia, and ECMO-associated coagulopathy. Case Description: A 40-year-old male with Influenza B–related acute respiratory distress syndrome (ARDS) required veno-venous ECMO. Concurrent acute kidney injury necessitated renal replacement therapy (RRT). During the first week, blood cultures grew vancomycin-resistant Enterococcus faecium, treated with linezolid. Despite therapy, the patient’s neurological status remained impaired, suggestive of septic encephalopathy. ECMO was decannulated on day 14, but within 48 hours, pneumomediastinum and respiratory failure prompted re-initiation of VV-ECMO. The patient developed thrombocytopenia and coagulopathy, attributed to sepsis-induced coagulopathy (SIC) and ECMO-related coagulopathy. Inflammatory markers remained elevated (CRP >150 mg/L; procalcitonin 8 ng/mL), but repeated cultures and imaging failed to localize infection. Refractory hyperammonaemia (peak 250 µmol/L) persisted despite RRT. Serial abdominal ultrasounds noted gallbladder distension without classic features of acalculous cholecystitis. Percutaneous cholecystostomy on day 25 yielded purulent fluid, which cultured vancomycin-resistant E. faecium. Despite targeted therapy, the patient died on day 28. Conclusion: This case underscores three critical lessons for ECMO management: 1) acalculous cholecystitis can be an occult source of sepsis, 2) refractory hyperammonaemia may reflect underlying infection and metabolic dysregulation, and 3) coagulopathy during ECMO should prompt aggressive infection screening rather than assuming circuit-related etiology. Vigilance, serial imaging, and early intervention are essential to improve outcomes in ECMO patients with unexplained deterioration.
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