Ivabradine use in critical care: a systematic review and metanalysis of cardiogenic and septic shock patients.

Abstract

Introduction: In patients with acute illness, compensatory tachycardia initially serves to maintain adequate cardiac output, oxygen delivery and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation or may be secondary to inotropic therapy. Sustained tachycardia is a predictor of adverse outcomes in critical illness. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (I_f or "funny" current), mitigates tachycardia by modulating diastolic depolarization slope without affecting contractility.

Aim: To report the existing evidence on the use of ivabradine in critically ill patients and assess its effect on rate control.

Methods: A systematic literature search was performed up to May 2024 in the MEDLINE/PubMed®, Cochrane Controlled Clinical Trial register, EMBASE® and Scopus® databases. The search included: P- only original studies conducted in humans admitted to the Intensive Care Unit (ICU); I - when ivabradine administration was tested; C - in presence or absence of a control group; O - for any outcome; S - including case reports, randomized and observational trials, published in English in peer-reviewed journals.

Results: After the first screening, 39 studies were assessed for eligibility on a total of 682 records identified. Among those, 29 were excluded; 10 studies (4 randomized controlled trial, 5 case report/series, 1 prospective observational), including a total of 243 patients, were included in the qualitative analysis, 6 studies were included in the quantitative analysis. The use of ivabradine resulted in a pooled mean heart rate reduction of 18.70 [12.70-24.80] bpm (p < 0.01) without a significant decrease in cardiac index (p = 0.59). A significant reduction of noradrenaline dose was reported in one study (-0.134 mcg/kg/min; 95% CI -0.172 to -0.012; p = 0.027). In addition, the combination of dobutamine with ivabradine has been reported to optimize dobutamine inotropic action, while mitigating its positive chronotropic effects, resulting in a more efficient cardiac cycle and improved hemodynamics.

Conclusions: Ivabradine may be a useful alternative to beta-blocker in the management of inappropriate sinus tachycardia. Yet, evidence is limited and inconsistent. Larger randomized trials are needed to investigate the potential benefits or hazards of ivabradine use on hemodynamics and long-term outcomes.