Abstract
BACKGROUND: The current guidelines recommend redosing of prophylactic intraoperative antimicrobials based on their half-life or in case of bleeding greater than 1,500 mL. However, data to support this practice is scarce. Orthotopic liver transplantation is often accompanied by massive bleeding. Therefore, we aimed to characterize the intraoperative pharmacokinetics of the prophylactic antimicrobial to analyze the pharmacokinetic parameters in recipients of living-donor liver transplantation (LDLT). METHODS: The recipients of LDLT who were 20 years or older without allergy to any beta-lactams were included. All participants received intravenous ampicillin-sulbactam (ABPC-SBT) 2-1 gram one hour before and every three hours during surgery over 30 minutes. The amount of blood loss and relevant parameters were recorded. Blood samples were collected every hour during surgery. The total plasma concentrations of ABPC and SBT were determined using a liquid chromatography-tandem mass spectrometry. Noncompartmental analysis was applied to calculate the clearances of ampicillin and sulbactam. The probability of target attainment (PTA) was determined based on the breakpoints proposed by The Clinical Laboratory Standards Institute assuming that the protein binding rate of ABPC and SBT were 28% and 38%, respectively. RESULTS: Twenty recipients were included (Table). The median age, weight, and amount of blood loss of the recipients were 52 years, 62.1 kg, and 11,158 mL, respectively. A median of calculated creatinine clearance were 99.6 mL/min. The total concentrations of ABPC and SBT in plasma and the amount of blood loss are shown (Figure 1, 2). Twelve participants (60%) achieved the PTA of 100% in both ABPC and SBT during surgery. The model-independent clearances of ABPC and SBT were 80.3 and 77.2 mL/min, respectively. Although bleeding greater than 20,000mL tended to increases the clearances of ABPC and SBT, the overall time above minimum inhibitory concentration of common pathogens was at acceptable level during surgery. [Table: see text] The pharmacokinetics of ampicillin in the recipients in the living donor liver transplantation. [Figure: see text] The pharmacokinetics of sulbactam in the recipients in the living donor liver transplantation. [Figure: see text] CONCLUSION: Intraoperative redosing of ABPC-SBT every three hours achieved the PTA of 100% in 60% of the LDLT recipients despite intraoperative massive bleeding. DISCLOSURES: All Authors: No reported disclosures