Mean arterial pressure to mean pulmonary arterial pressure ratio (mAP/mPAP) has been identified as a strong predictor of perioperative complications in cardiac surgery. We therefore investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationship of inhaled milrinone in these patients using this ratio (R) as a PD marker. Following approval by the ethics and research committee and informed consent, we performed the following experiment. Before initiation of cardiopulmonary bypass in 28 pulmonary hypertensive patients scheduled for cardiac surgery, milrinone (5 mg) was nebulized, plasma concentrations measured (up to 10 h) and compartmental PK analysis carried out. Baseline (R₀) and peak (R_max) ratios as well as magnitude of peak response (∆_Rmax-R0) were measured. During inhalation, individual area under effect-time (AUEC) and plasma concentration–time (AUC) curves were correlated. Potential relationships between PD markers and difficult separation from bypass (DSB) were explored. In this study, we observed that milrinone peak concentrations (41–189 ng ml⁻¹) and Δ_Rmax-R0 (− 0.12–1.5) were obtained at the end of inhalation (10–30 min). Mean PK parameters agreed with intravenous milrinone published data after correction for the estimated inhaled dose. Paired comparisons yielded a statistically significant increase between R₀ and R_max (mean difference, 0.58: 95% CI 0.43–0.73; P < 0.001). Individual AUEC correlated with AUC (r = 0.3890, r² = 0.1513; P = 0.045); significance increased after exclusion of non-responders (r = 4787, r² = 0.2292; P = 0.024). Individual AUEC correlated with ∆R_max-R0 (r = 5973, r² = 0.3568; P = 0.001). Both ∆R_max-R0 (P = 0.009) and CPB duration (P < 0.001) were identified as predictors of DSB. In conclusion, both magnitude of peak response of the mAP/mPAP ratio and CPB duration were associated with DSB.

平均动脉压与平均肺动脉压之比 (mAP/mPAP) 已被确定为心脏手术围手术期并发症的有力预测指标。因此，我们使用该比率 (R) 作为 PD 标志物研究了这些患者吸入米力农的药代动力学/药效学 (PK/PD) 关系。在获得伦理和研究委员会的批准和知情同意后，我们进行了以下实验。在计划进行心脏手术的 28 名肺动脉高压患者开始体外循环之前，雾化米力农 (5 mg)，测量血浆浓度（长达 10 小时）并进行房室 PK 分析。基线 (R ₀ ) 和峰值 (R _max ) 比率以及峰值响应的幅度 (∆ _Rmax-R0) 进行了测量。在吸入过程中，个体面积-时间 (AUEC) 和血浆浓度-时间 (AUC) 曲线相关。探讨了 PD 标记与旁路分离困难 (DSB) 之间的潜在关系。在这项研究中，我们观察到米力农的峰值浓度 (41–189 ng ml ^-1 ) 和 Δ _Rmax-R0 (− 0.12–1.5) 是在吸入结束时（10–30 分钟）获得的。校正估计吸入剂量后，平均 PK 参数与静脉注射米力农公布的数据一致。_{配对比较在 R 0}和 R _max之间产生了统计学上显着的增加（平均差异，0.58：95% CI 0.43–0.73；P  < 0.001）。个体 AUEC 与 AUC 相关 (r = 0.3890, r ² = 0.1513；P  = 0.045); 排除无反应者后显着性增加（r = 4787，r ²  = 0.2292；P  = 0.024）。_{个体 AUEC 与 ∆R max-R0}相关（r = 5973，r ²  = 0.3568；P  = 0.001）。ΔR _max-R0 ( P  = 0.009) 和 CPB 持续时间 ( P  < 0.001) 都被确定为 DSB 的预测因子。总之，mAP/mPAP 比率的峰值响应幅度和 CPB 持续时间都与 DSB 相关。