Effects of Inotropes on the Mortality in Patients With Septic Shock

Abstract

Background: Although surviving sepsis campaign guidelines recommend the use of inotropes in the presence of myocardial dysfunction, the effects of inotropes, including epinephrine, dobutamine, and milrinone, on in-hospital mortality in patients with septic shock remains unclear. Materials and Methods: We conducted an international,2-center, retrospective cohort study. The Cox proportional hazards regression model with time-varying covariates was used to investigate whether epinephrine, milrinone, or dobutamine reduces in-hospital mortality in patients with septic shock. Sensitivity analysis was performed using propensity score matching. The primary outcome was in-hospital mortality. The secondary outcome included atrial fibrillation (Afib) with a rapid ventricular response (RVR) in the intensive care unit (ICU) and ICU-free days. Results: A total of 417 patients with septic shock were included, 72 (17.3%) of whom received inotropes. The use of epinephrine and dobutamine was associated with significantly higher in-hospital mortality (epinephrine, hazard ratio [HR]: 4.79, 95% confidence interval [CI]: 2.12-10.82, P = .001; dobutamine, HR: 2.53, 95% CI: 1.30-4.95, P = .046). The effects of epinephrine and dobutamine were time- and dose-dependent. The use of milrinone was not associated with increased mortality (HR: 1.07, 95% CI: 0.42-2.68, P = .345). The use of epinephrine, dobutamine, and milrinone was associated with significantly increased odds of Afib with RVR (epinephrine, odds ratio [OR]: 3.88, 95% CI: 1.11-13.61, P = .034; dobutamine, OR: 3.95, 95% CI: 1.14-13.76; and milrinone, OR: 3.77, 95% CI: 1.05-13.59). On the other hand, the use of epinephrine, dobutamine, and milrinone was not associated with less ICU-free days (epinephrine, adjusted OR: 0.30, 95% CI: 0.09-1.01, P = .053; dobutamine, adjusted OR: 0.91, 95% CI: 0.29-2.84; and milrinone, adjusted OR: 0.60, 95% CI: 0.19-1.87). Conclusion: The present study showed that the use of epinephrine and dobutamine was associated with significantly increased in-hospital mortality in patients with septic shock. These effects were both time- and dose-dependent. On the other hand, the use of milrinone was not associated with increased in-hospital mortality.

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“…Therefore, a vicious cycle is established in viral sepsis leading to high mortality despite the current therapies. Epinephrine and dobutamine use in sepsis is reported to be associated with increased mortality and atrial fibrillation [3].…”

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“…154 Interestingly, Sato et al reported milrinone was not associated with increased mortality in septic shock (HR: 0.885; 95% CI: 0.44-1.79; P = .734), unlike epinephrine and dobutamine. 131 However, milrinone was associated with increased incidence of AF similar to both epinephrine and dobutamine. 131 Milrinone showed no detrimental effects and possibly enhanced cardiac function when used in combination with β-blockers (BBs) in sepsis to combat concerns for catecholamine-induced myocardial depression by avoiding dobutamine.…”

“…131 However, milrinone was associated with increased incidence of AF similar to both epinephrine and dobutamine. 131 Milrinone showed no detrimental effects and possibly enhanced cardiac function when used in combination with β-blockers (BBs) in sepsis to combat concerns for catecholamine-induced myocardial depression by avoiding dobutamine. 155,156 Unlike dobutamine, phosphodiesterase inhibitor efficacy is not altered by concomitant BBs, 157 but the specific application of milrinone use preferentially to dobutamine in patients on chronic BB therapy is not established.…”

“…Arguing against dobutamine use, Sato et al associated dobutamine with higher mortality and incidence of AF in septic shock. 131 Hernandez et al found dobutamine failed to improve perfusion parameters in septic shock, despite an increase in HR, CO, and EF. 145 Hayes et al 146 found no clinical improvement in cardiac index or oxygenation status from dobutamine among critically ill patients (72% sepsis/septic shock) and associated dobutamine with increased hospital mortality (54% vs 34%; P = .04).…”

“…In a retrospective cohort, Sato et al suggested increased arrhythmias and mortality with the use of epinephrine in septic shock (mortality HR: 4.79; 95% CI: 2.12-10.82; P < .001). 131 In a clinical trial of ICU patients requiring NE or epinephrine, no difference in time to goal mean arterial pressure (MAP) or mortality was found in patients with severe sepsis and circulatory failure. 132 However, epinephrine produced more metabolic side effects and tachycardia.…”