Phase I trial of olprinone for low central venous pressure management aimed at hemorrhage control during open and laparoscopic hepatectomy

Low central venous pressure (CVP) management reduces blood loss during hepatectomy but may cause hemodynamic instability. This study evaluated the safety and efficacy of olprinone, a phosphodiesterase III inhibitor, for intraoperative CVP control. This phase I dose-escalation trial used a 3 + 3 design to assess olprinone administered at cardiovascular doses (0.10–0.30 µg/kg/min). The primary objective was to evaluate safety and identify dose-limiting toxicities (DLTs) during dose escalation. The secondary objective was to evaluate hemodynamic effects and feasibility of low-CVP management. Thirty-three patients (15 open, 18 laparoscopic) were enrolled. Dose escalation proceeded to the protocol-defined maximum approved maintenance dose of 0.30 µg/kg/min, at which no DLTs were observed. One postoperative DLT (renal dysfunction) occurred in the laparoscopic cohort at 0.25 µg/kg/min, and it was considered to be related to pre-existing comorbidities. Olprinone administration significantly reduced the CVP during liver transection (mean CVP reduced from 6.7 to 4.1 cmH₂O, p < 0.0001) while maintaining overall hemodynamic stability. In the laparoscopic cohort, higher olprinone doses showed a trend toward reduced intraoperative blood loss. Olprinone was safely administered up to 0.30 µg/kg/min and reduced CVP while maintaining overall hemodynamic stability. The exploratory trend toward reduced blood loss warrants validation in future controlled trials.