In a recent big-data, real-world study, researchers demonstrated that hospital mortality is not significantly different between septic patients treated with the inotropic agents dobutamine or milrinone. However, milrinone was found to be associated with more renal replacement therapy and longer intensive care unit and hospital stays.
Inotropic agents against sepsis
Sepsis is a potentially life-threatening, extreme response to infection that inadvertently causes damage to healthy tissues. It may progress to septic shock if blood pressure drops dramatically, leading to organ damage and higher risk of mortality. Of note, many deaths from COVID-19 infection are due to sepsis.
Some septic patients exhibit low cardiac output, known as myocardial depression. Myocardial depression in septic patients was observed to be associated with higher mortality and morbidity compared to those without. As such, dobutamine is recommended for septic patients with myocardial depression. Dobutamine is an inotropic agent that increases myocardial oxygen consumption and cardiac output. However, some studies have suggested that the drug is cardiotoxic.
Milrinone, another inotropic agent, has recently been put forward as an alternative to dobutamine. Animal and small sample studies have shown that it was beneficial for septic patients. Thus far, there have been no randomised controlled trials to assess whether there are differences between the two treatments on clinical outcomes in septic patients.
Patient population to assess the effects of inotropic agents on sepsis
The present study, now available online in the International Journal of Clinical Practice, aimed to assess whether dobutamine or milrinone is a better treatment for patients with sepsis. To achieve this, researchers from Jinan University in Guangzhou, China, performed a big-data, real-world analysis with MIMIC-III data. MIMIC-III (Medical Information Mart for Intensive Care) is a comprehensive public database consisting of anonymised information associated with 38,605 patients admitted to intensive care units (ICUs) at the Beth Israel Deaconess Medical Centre in Boston, Massachusetts between 2001 and 2012.
Following database screening, the researchers included 235 septic patients and categorised them into two groups according to treatment use. In total, 183 patients were in the dobutamine group and 52 were in the milrinone group.
Study design
The researchers investigated how dobutamine use affects patient outcomes compared to milrinone. For each outcome of interest, the researchers calculated the odds ratio between the two patient groups. The odds ratio represents the likelihood of an outcome occurring when a given exposure is present compared to the likelihood of the outcome occurring in the absence of that exposure.
As the MIMIC-III database was retrospective, it inevitably exhibited selection bias. To adjust for confounding variables, the researchers employed propensity score matching to compare dobutamine-treated patients with milrinone-patients of similar characteristics. The matching variables included demographic characteristics, admission type, cardiometabolic health measures and comorbidities. Each milrinone patient was matched to 3 dobutamine patients with the closest propensity score when analysing hospital mortality.
Outcomes
The analysis revealed no significant difference in hospital mortality between the two patient groups. The result remained consistent even after propensity score matching.
However, more patients in the milrinone group received renal replacement therapy (RRT) compared to those in the dobutamine group (46.2% vs 22.4%). Milrinone patients also had a significantly longer length of ICU (20.97±22.84 vs. 11.10±11.54 days) and hospital stay (26.14±25.13 vs. 14.51±13.11 days) than those in the dobutamine group. Meanwhile, 56.2% of milrinone patients experienced cardiac arrhythmias compared to 42.1% of dobutamine patients.
However, several haemodynamic variables were not included due to data insufficiency. This study may therefore not capture all the possible effects of milrinone. Future large-scale, randomised controlled studies are necessary to validate these findings.
Summary
This analysis showed that milrinone use in septic patients did not significantly decrease hospital mortality compared to dobutamine use. Moreover, patients treated with milrinone received more RRT and stayed longer in the ICU and hospital. These findings suggested that the benefits of milrinone may have been exaggerated. Ultimately, this study demonstrated that the use of large-scale, real-world data is highly informative when evaluating patient outcomes in response to different treatments.
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