Inhaled milrinone significantly increased the mean arterial pressure to mean pulmonary arterial pressure ratio from baseline to peak by a mean difference of 0.58 in cardiac surgical patients with pulmonary hypertension.
Observational (n=28)
No
Inhaled milrinone administered before cardiopulmonary bypass significantly improves the mAP/mPAP ratio, and the magnitude of this response is associated with the ease of separation from bypass.
Effect estimate: MD 0.58 (95% CI 0.43-0.73)
p-value: p=<0.001
Abstract 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 (R 0 ) 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 R 0 and R max (mean difference, 0.58: 95% CI 0.43–0.73; P < 0.001). Individual AUEC correlated with AUC (r = 0.3890, r 2 = 0.1513; P = 0.045); significance increased after exclusion of non-responders (r = 4787, r 2 = 0.2292; P = 0.024). Individual AUEC correlated with ∆R max-R0 (r = 5973, r 2 = 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.
Nguyen et al. (Thu,) conducted a observational in Pulmonary hypertension in cardiac surgery (n=28). Inhaled milrinone vs. None (baseline comparison) was evaluated on Change in mean arterial pressure to mean pulmonary arterial pressure ratio (mAP/mPAP) from baseline to peak (MD 0.58, 95% CI 0.43-0.73, p=<0.001). Inhaled milrinone significantly increased the mean arterial pressure to mean pulmonary arterial pressure ratio from baseline to peak by a mean difference of 0.58 in cardiac surgical patients with pulmonary hypertension.