Abstract
Rationale Despite increasing recognition of mixed cardiogenic shock-particularly in patients with concomitant sepsis, there remains limited guidance on optimal inotropic selection, and the comparative effectiveness of different inotropes in this population is unclear. Objective To examine the association between inotrope selection and in-hospital outcomes, including all-cause mortality, among patients with cardiogenic shock and sepsis. Methods Using the PINC AI enhanced-claims Database (2016-2022), we identified patients with cardiogenic shock and sepsis using International Classification of Diseases, 10th revision codes (ICD-10) that were present on hospital admission and a pharmacy charge code for dobutamine or milrinone within 2 days of hospitalization. The primary outcome was all-cause hospital mortality. Secondary outcomes included inotrope duration, in-hospital length of stay, atrial arrhythmia, initiation of renal replacement therapy (RRT), use of mechanical circulatory support devices (MCS), and heart transplantation. We used generalized full matching on the propensity score (dobutamine vs. milrinone) followed by g-computation to estimate effects of inotrope selection on outcomes. We examined heterogeneity of treatment effect in patients with renal disease, congestive heart failure, pulmonary circulatory diseases, and on epinephrine prior to inotrope initiation. Results Out of 10,447 included patients, 74.4% received dobutamine and 25.6% received milrinone. Post-matching characteristics between the milrinone and dobutamine groups were similar (all Standard Mean Differences< 0.1). The primary outcome all-cause mortality was similar between post-matched milrinone and dobutamine groups (41.6% vs. 42.7%, risk difference -1.4 (95% confidence interval [CI}: -3.7, 1.5] %, p= 0.40). Patients initiated on milrinone (vs. dobutamine) had longer inotrope durations (5.1 days vs. 3.5 days, mean difference 1.7 [95% CI: 1.4, 1.9] days, p< 0.001), longer in-hospital length of stay (10.0 days vs. 9.1 days, mean difference 0.9 [95% CI: 0.4, 1.3] days, p<0.001), and more usage of antiarrhythmic agents (56.0% vs. 44.5%, mean difference 11.5 [95% CI: 8.9, 14.1] %, p<0.001). We did not observe any heterogeneity of treatment effect for all-cause mortality based on the pre-existing conditions of interest. Conclusions Using a large multicenter cohort, we identified no differences in all-cause mortality between dobutamine and milrinone among patients with concurrent cardiogenic shock and sepsis overall. However, secondary outcomes favored dobutamine.