UMEM Educational Pearls

Background: A cornerstone of therapy for cardiogenic shock is inotropic support with medications including dobutamine, epinephrine and milrinone.  Few studies have examined these head-to-head and between dobutamine and milrinone (including only one RCT of 36 patients)

The investigators conducted a RCT of milrinone versus dobutamine for cardiogenic shock in a single quaternary care center cardiac ICU.

Inclusion: Patients over 18 with cardiogenic shock (largely clinical determination)

Exclusion: Out-of-hospital cardiac arrest, pregnancy, prior initiation of dobutamine or milrinone, or physician discretion.

Methods: 1:1 randomization stratified by affected ventricle (LV vs RV). Primary outcome was a composite of in-hospital death, resuscitated cardiac arrest, cardiac transplant, mechanical circulator support, nonfatal MI, TIA, stroke, or renal replacement therapy. Powered to detect a 20% improvement in this measure in the milrinone group (192 pts).

Results:  192 patients enrolled (96 in each arm). Average age was 70, 36% female, 90% LV dysfunction, 67% ischemic disease, 33% non-ischemic, average LVEF 25%, 68% on vasopressors. ICU admission to randomization was 23+/-92.6h for dobutamine and 17.6+/-50.6h for milrinone arms. 80% were SCAI class C shock.

Primary outcome for milrinone 49% versus dobutamine 54%, HR 0.9(0.69-1.19), p=0.47, death was the primary driver of the composite (37% vs 43%).  Arrythmia requiring intervention was not different between groups (50% vs 46%). No difference in a host of other endpoints including AKI (92% vs 90%), RRT (22% vs 17%), HR, lactate, MAP, UOP, and creatinine.

Discussion: No significant differences observed in outcomes for patients with cardiogenic shock randomized to milrinone versus dobutamine.  The trial addressed an important clinical question for management of cardiogenic shock and relied largely on clinical diagnosis for inclusion and likely reflected a somewhat broad range of patients. The trial was too small given observed treatment effects and few patients with RV failure. Notably, similar rates of adverse events observed in each group.  

Many limitations for practice including a single specialized ICU setting, limited information on events leading to ICU admission including invasive or medical interventions during the index visit and no long term follow-up.  Time to randomization, exclusion of cardiac arrest, and lack of reporting pre-ICU setting (ED, floor, cath lab) also significantly limits utility in an emergency setting.

Bottom Line: 192 patient single-center cardiac ICU-based trial shows no difference in composite or secondary endpoints between milrinone and dobutamine for cardiogenic shock, adds to a body of very limited RCTs comparing inotropes in cardiogenic shock but provides no practice changing evidence.

 

References

Mathew R, et al. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021 Aug 5. 

DOI: 10.1056/NEJMoa2026845