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Association between Milrinone Use and Mortality Risk in Sepsis: Insights from the MIMIC-IV Database
Jiali Wu1, Cong Liu1, Xiaojing Ji2
1Department of Emergency, General Hospital of Ningxia Medical University, Yinchuan, China.
Background:
Milrinone is established in the management of heart failure. However, its therapeutic role in patients with sepsis remains uncertain and warrants further investigation. Objective: To examine the association between milrinone administration and mortality in patients diagnosed with sepsis.
Methods:
This retrospective cohort study utilized data from the MIMIC-IV database. The primary exposure of interest was milrinone use. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to balance baseline characteristics. The association between milrinone use and 7-，14-，and 28-day mortality in sepsis patients was assessed using multivariate Cox proportional hazards models, restricted cubic spline (RCS) curves, and longitudinal targeted maximum likelihood estimation (TMLE).
Results:
Among 27,070 sepsis patients, 523 received milrinone at a median interval of 5.24 hours after ICU admission. In the unadjusted Cox model, milrinone use was associated with significantly lower mortality at 7 days (HR = 0.53, 95% CI: 0.33-0.85), 14 days (HR = 0.54, 95% CI: 0.38-0.78), and 28 days (HR = 0.60, 95% CI: 0.45-0.82). This association remained consistent after adjusting for multiple confounders. In the IPTW-adjusted cohort, Cox regression showed no significant association between milrinone use and mortality at day 7 or day 14; however, a statistically significant association was observed at day 28. Longitudinal TMLE analyses further indicated a protective effect for both 14-day (RR = 0.65, 95% CI: 0.48-0.88; P = 0.01) and 28-day mortality (RR = 0.58, 95% CI: 0.45-0.74; P < 0.001). RCS analysis demonstrated a linear inverse relationship between cumulative milrinone dosage and 7-day mortality risk, while a non-linear association was observed with 14-day and 28-day mortality. Subgroup analysis revealed a significant interaction between milrinone use and heart failure status, with reduced mortality associated with milrinone use only in patients with heart failure.
Conclusion:
Milrinone use appeared to be associated with reduced mortality risk at 7, 14, and 28 days in sepsis patients. This association was linear for 7‑day mortality, but nonlinear and potentially indicative of a threshold effect for 14‑and 28‑day mortality.
Insights
Milrinone administration may reduce mortality in sepsis patients, particularly those with heart failure. Further research is needed to understand the optimal dosage and its effects on sepsis outcomes.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Epidemiology
Background:
- Milrinone is a known treatment for heart failure.
- Its effectiveness in sepsis patients is not well-established.
- This study investigates milrinone's impact on sepsis mortality.
Purpose of the Study:
- To analyze the association between milrinone use and mortality in sepsis patients.
- To evaluate the dose-response relationship and identify potential threshold effects.
- To explore the interaction between milrinone and pre-existing heart failure in sepsis.
Main Methods:
- Retrospective cohort study using MIMIC-IV database.
- Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) for confounder adjustment.
- Multivariate Cox models, restricted cubic splines (RCS), and targeted maximum likelihood estimation (TMLE) for mortality analysis.
Main Results:
- Milrinone use was linked to lower 7-, 14-, and 28-day mortality in unadjusted and adjusted analyses.
- IPTW-adjusted Cox regression showed significant association only for 28-day mortality.
- TMLE indicated protective effects for 14- and 28-day mortality (RR 0.65 and 0.58, respectively).
- RCS revealed a linear association with 7-day mortality and non-linear associations with 14- and 28-day mortality.
- Reduced mortality with milrinone was significant only in patients with heart failure.
Conclusions:
- Milrinone use is associated with reduced mortality in sepsis patients.
- The association appears linear for 7-day mortality and non-linear for 14- and 28-day mortality, suggesting a potential threshold effect.
- Milrinone's benefit in sepsis may be more pronounced in patients with co-existing heart failure.