Ivabradine in Septic Shock: A Narrative Review

Abstract

In patients with septic shock, compensatory tachycardia initially serves to maintain adequate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventricular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (I_f or "funny" current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock.

Keywords: MODS; cardiac dysfunction; ivabradine; multiple organ disfunction syndrome; sepsis; septic cardiomyopathy; septic shock; ventriculo-arterial coupling; β-blockers.

Figure 1

Ivabradine action on HCN-4 channels responsible for I_f current, prolonging the diastolic slow depolarization phase of SAN myocytes. HCN = hyperpolarization-activated cyclic-nucleotide; Na = sodium; K = potassium; HR = heart rate.

Figure 2

Beneficial effects of heart rate reduction by ivabradine. The ventriculo-arterial coupling graph represents the putative change between tachycardic cardiac dysfunction (blue lines and area) and the ivrabradine effect (red lines and area) on the cardiac cycle and on the coupling between the left ventricle and the arterial elastances. HRV: heart rate variability; MVO₂: myocardial oxygen consumption; LAP: left atrial pressure; RAP: right atrial pressure; LVEDV: left ventricle end-diastolic volume; RVEDV: right ventricle end-diastolic volume; CI: cardiac index; LV-CPI: left ventricle cardiac power index; RV-CPI: right ventricle cardiac power index; GEDVI: global end-diastolic volume index.