The effect of milrinone on mortality in adult patients: A systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Abstract

OBJECTIVE: Milrinone is commonly used for patients performed coronary artery bypass graft surgery (CABG) because of its effectiveness in decreasing cardiac index and mitral regurgitation. This study was to perform a systematic meta-analysis of existing studies in the past 20 years to evaluate the impact of milrinone on mortality in patients undergoing CABG surgery. EASUREMENTS AND MAIN RESULTS: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significantly difference in mortality between the milrinone group and the placebo/standard care group [11/352 (3.13%) vs. 9/346 (2.60%), risk ratio = 1.18 (0.53–2.62), p for effect = 0.69, I 2 = 0 %] when patients underwent CABG surgery. Besides that, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmias in the milrinone group were decreased in comparsion with the placebo/standard care group, respectively. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction was [5/219 (2.28 %) vs. 25/212 (17.79 %), odds ratio(OR) = 0.19 (0.08–0.49), p value = 0.0005, I 2 = 5%], the occurrence of myocardial ischemia was [12/106 (11.32 %) vs. 41/106 (36.68 %), OR = 0.20 (0.10–0.42), p value <0.0001, I 2 = 0 %], and the occurrence of arrhythmias was [16/234 (6.84 %) vs. 31/236 (13.14 %), OR= 0.46 (0.24–0.88), p value = 0.02, I 2 =0 %]. However, the occurrence of stroke and renal failure, duration of inotropic support (h), need for intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences. CONCLUSION: Based on the current results, milrinone might be unable to decrease the mortality in adult CABG surgical patients, but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmias compared with placebo-treated patients. These results provide evidence for further clinical application of milrinone and therapy strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient randomized clinical trials need to be collected, and the potential benefit and adverse effects should be analyzed and reevaluated.