Effect of milrinone on cardiac functions in patients undergoing coronary artery bypass graft: a meta-analysis of randomized clinical trials

Abstract

Background and aim: Inotropes are commonly used to treat myocardial dysfunction, which is the major complication after coronary artery bypass graft (CABG). Milrinone, a phosphodiesterase 3 inhibitor, is one of these inotropes. Recently, a number of clinical studies have been carried out to evaluate the effects of milrinone on cardiac function in patients with low ventricular ejection fraction undergoing CABG. However, it has been inconclusive because of the inconsistent results. In addition, some studies found that milrinone increased the incidence of postoperative atrial arrhythmias and did not show any long-term beneficial effects on survival. Therefore, it is very important to perform a meta-analysis to summarize the results so as to determine the clinical efficacy and safety of milrinone.

Method: Several databases and websites for clinical trials were searched until October 2015 for prospective clinical studies comparing milrinone versus placebo on cardiac functions in patients undergoing CAGB.

Results: Four articles were identified by our search strategy. 1) Milrinone decreased incidence of myocardial ischemia and myocardial infarction (15.6% versus 44.4%; 4.7% versus 18% in milrinone and control group, respectively). 2) Milrinone decreased duration of inotropic support (95% confidence interval [CI]: -6.52 to -1.68; P=0.0009) and mechanical ventilation (h) support (95% CI -5.00 to -0.69; P=0.010), but did not decrease the requirement for intra-aortic balloon pump or inotropic support (P>0.05). 3) Milrinone did not decrease the overall mortality or morbidity, intensive care unit stay (P>0.05).

Conclusion: Perioperative continuous infusion of milrinone is effective to lower incidence of myocardial ischemia and myocardial infarction in patients post-CABG, but it was unable to improve the overall morbidity and mortality or decreased duration of intensive care unit stay. The available sample size is small; therefore, future studies should be directed toward a better understanding of the benefit of milrinone to CABG patients.

Keywords: cardiac function; clinical trial; inotropic support; intra-aortic balloon pump; meta-analysis.

Figure 1

Funnel plot comparing the requirement of intra-aortic balloon pump (%) between milrinone group and control/nesiritide group. Abbreviations: OR, odds ratio; SE, standard error.

Figure 2

Flow diagram of study selection.

Figure 3

Forest plots comparing between milrinone group and placebo/nesiritide group the (A) requirement of intra-aortic balloon pump (%); (B) inotropic support requirement; (C) duration of inotropic support; (D) duration of mechanical ventilation support. Abbreviation: CI, confidence interval.

Figure 4

Forest plots comparing incidence of post-CABG complications between milrinone group and placebo/nesiritide group in (A) myocardial ischemia; (B) myocardial infarction. Abbreviations: CABG, coronary artery bypass graft; CI, confidence interval.

Figure 5

Forest plot comparing ICU stay between milrinone group and placebo/nesiritide group. Abbreviations: CI, confidence interval; IV, independent variable; ICU, intensive care unit.

Figure 6

Forest plots comparing overall survival between milrinone group and placebo/nesiritide group in (A) mortality; (B) morbidity. Abbreviations: CI, confidence interval; IV, independent variable.