Efficacy of milrinone and dobutamine in low cardiac output states: Systematic review and meta-analysis

Patients in cardiac intensive care units (ICU) are admitted with increasingly higher disease acuity and a larger burden of non-cardiac critical illness. Accordingly, positive inotropes are being used with increased frequency and little comparative data to support drug selection. We compared the effectiveness and safety of dobutamine and milrinone in low cardiac output states (LCOS) and/or cardiogenic shock (CS). We performed a systematic review comparing dobutamine to milrinone on all-cause mortality, length of stay in the ICU (LOS-ICU), length of stay in hospital (LOS-H) and significant arrhythmias in hospitalized patients with LCOS and/or CS. We identified 11 studies that meet eligibility requirements and which were published between 2001 and 2016 and included 23,056 patients. Only one randomized clinical trial was identified, with the remaining studies comprising observational cohort studies. The primary outcome, all-cause mortality, trended towards a benefit with milrinone but did not meet pre-specified significance (OR 1.13, 95% CI 1.00-1.29, p=0.06). While LOS-ICU (mean difference -0.72, 95% CI -1.10- -0.34, p=0.0002) was shorter with dobutamine, there was no difference in LOS-H (mean difference -1.22, 95% CI -4.68 - 2.24, p=0.49). Significant arrhythmias, specifically symptomatic and/or requiring antiarrhythmic therapy, were no different between the groups (OR 1.78, 95% CI 0.85-3.76, p=0.13). Currently available data comparing milrinone to dobutamine in patients requiring inotropic support is limited. Dobutamine may be associated with a shorter LOS in the ICU, with a worrisome signal of increased risk of allcause mortality. Randomized data are needed to guide inotrope selection in patients with LCOS and/or CS.