Citrate Toxicity-Induced Tetany During High-Volume Therapeutic Plasma Exchange in Acute Liver Failure: Recognition and Prevention

Introduction: Acute liver failure (ALF) is associated with significant morbidity and mortality. High-volume therapeutic plasma exchange (HV-TPE) has been shown to improve transplant-free survival in patients with ALF and is now recommended by multiple guidelines in the management of ALF. The use of high volumes of fresh frozen plasma in patients with ALF increases risk for citrate toxicity; however, severe adverse events were not described in initial studies. This case of citrate toxicity during HV-TPE for ALF highlights the need to revisit the unique risks associated with this procedure and for nephrologists to develop protocols to prevent severe adverse events. Case Description: Here we report the case of a 31-year-old female with alcohol use disorder who presented with acute liver injury that quickly progressed to acute liver failure. She was treated with high-volume therapeutic plasma exchange but developed tetany resulting in broken teeth and vasopressor-dependent shock. She was found to have severe hypocalcemia due to citrate toxicity. The next HV-TPE treatment was split into two sessions, interjected by renal replacement therapy (table 1). Severe hypocalcemia was avoided and hemodynamic stability maintained. Discussion: HV-TPE is increasingly used as a part of guideline-directed therapy for ALF. Severe hypocalcemia from citrate toxicity is an under-recognized severe adverse event that can occur during HV-TPE in ALF. Minimizing the risk of this is essential to safely performing this procedure and could involve dividing HV-TPE into multiple sessions and increasing calcium replacement beyond standard protocols. Table 1 - HV-TPE 1 HV-TPE 2A HV-TPE 2B Treatment 15% IBW exchange- 7.5 L FFP 4mL 10% CaCl2 per liter replacement fluid Plasma Removed (L): 7.614 Replacement Fluid (L): 7.500 8% IBW exchange- 4 L FFP 10mL 10% CaCl2 per liter replacement fluid Plasma Removed (L): 4.124 Replacement Fluid (L): 3.980 7% IBW exchange-3.5 L FFP 10mL 10% CaCl2 per liter replacement fluid Plasma Removed (L): 3.620 Replacement Fluid (L): 3.500 Post-treatment BP: 98/63, T: 36.4, RR: 34, HR: 128 BP: 99/59, T: 37.1, RR: 13, HR:104 BP: 141/60, T: 36.9, RR: 15, HR:113 Total Calcium (mg/dL) 7.8, 10.4, 10.4 8.9, 11.4, 12.9 11.4, 13.2, 12.4 Ionized Calcium (mmol/L) 1.07, 1.32, 0.42 1.21, 1.01, 1.26 1.27, 1.09, 1.28