Outcomes for Milrinone vs Dobutamine in Cardiogenic Shock

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Which inotropic agent should clinicians use in patients with cardiogenic shock, milirone or dobutamine?

No difference was found between inotropic agents milrinone and dobutamine in regard to the risk of in-hospital death or adverse cardiovascular and neurological outcomes in patients with cardiogenic shock, according to study findings published in the New England Journal of Medicine.

The study enrolled 192 adult patients with cardiogenic shock from a quaternary cardiac intensive care unit. Investigators randomly assigned patients to treatment with either milrinone (n=96; mean age, 68.9±13.8 years) or dobutamine (n=96; mean age, 72.0±11.3 years). Enrolled patients were primarily in Society for Cardiovascular Angiography and Intervention cardiogenic shock class C (80% for milrinone and 81% for dobutamine).

Inotropes were administered at doses determined using a standardized dosing scale ranging from stage 1 to 5, corresponding with doses of 2.5 μg, 5.0 μg, 7.5 μg, 10.0 μg, and more than10.0 μg per kilogram of body weight per minute in the dobutamine arm and 0.125 μg, 0.250 μg, 0.375 μg, 0.500 μg, and more than 0.500 μg per kilogram per minute in the milrinone group.

The primary outcome included a composite of in-hospital death and several cardiovascular and neurological events, including resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or neurologist-diagnosed stroke, or renal replacement therapy initiation. The secondary outcomes were each of the individual components of the composite outcome. Outcomes were limited to the index hospitalization.

There was no significant difference between the milrinone and dobutamine treatment arms in the proportion of patients who met criteria for the composite primary outcome (49% vs 54%, respectively; relative risk [RR], 0.90; 95% CI, 0.69-1.19; P =.47).

Additionally, the researchers found no significant differences between the milrinone and dobutamine groups in regard to the individual outcomes of in-hospital death (37% vs 43%, respectively; RR, 0.85; 95% CI, 0.60-1.21), resuscitated cardiac arrest (7% vs 9%; hazard ratio [HR], 0.78; 95% CI, 0.29-2.07), receipt of mechanical circulatory support (12% vs 15%; HR, 0.78; 95% CI, 0.36-1.71), or renal replacement therapy initiation (22% vs 17%; HR, 1.39; 95% CI, 0.73-2.67).

A limitation of this randomized study was the assessment of only in-hospital outcomes, suggesting further outcomes could have occurred following the index hospitalization. The study also included patients from a single center, potentially limiting the generalizability of the findings across external centers.

The researchers wrote that while “inotropes form a foundation of therapy in patients with cardiogenic shock, our trial addresses an important knowledge gap in the management of this condition.”


Mathew R, Di Santo P, Jung RG, et al. Milrinone as compared with dobutamine in the treatment of cardiogenic shock. N Engl J Med. 2021;385(6):516-525. doi:10.1056/NEJMoa2026845