Effects of adjunctive milrinone versus placebo on hemodynamics in patients with septic shock: a randomized controlled trial

Background: Refractory septic shock can lead to multiorgan failure and death due to myocardial dysfunction-induced inadequate tissue perfusion. Current guidelines advocate inotropic adjuncts to norepinephrine, but the efficacy of milrinone remains understudied in this context. This study aimed to evaluate the hemodynamic changes in septic shock patients treated with adjunctive milrinone compared to those treated with a placebo. Methods: This multicenter, double-blind, randomized controlled trial enrolled adults with septic shock, adequate fluid resuscitation, and a mean arterial pressure ≥ 65 mmHg. Eligible patients exhibited poor tissue perfusion or impaired left ventricular systolic function. Participants were randomized 1:1 to milrinone or placebo. Echocardiographic hemodynamic assessments were performed pre- and postintervention. The primary outcome was the change in cardiac output from baseline to 6 h after drug administration. The study was prospectively registered at www.clinicaltrials.gov (NCT 05122884). Results: Among 271 screened patients, 64 were randomized. The baseline characteristics were comparable between the groups. The milrinone group demonstrated a significantly greater change in cardiac output at 6 h (median [IQR] 0.62 L/min [-0.51 to 1.47]) than did the placebo group (0.13 L/min [-0.59 to 0.46]; p = 0.043). The percentage change in the cardiac index was also significantly greater with milrinone (median [IQR] 22.5% [-10.4% to 45.3%]) than with placebo (4.4% [-10.9% to 11.4%]; p = 0.041). There were no significant differences in complication rates between the groups. The 28-day mortality rates of the groups were also statistically nonsignificant and equivalent (16/32 [50.0%] for both; p = 1.000). Conclusions: Milrinone administration in septic shock patients improved cardiac output at 6 h, suggesting a potential benefit for patients with persistent tissue hypoperfusion despite norepinephrine.