Levosimendan and systemic vascular resistance in cardiac surgery patients: a systematic review and meta-analysis

Abstract

Levosimendan is a potent non-adrenergic inodilator agent. The net effect of hemodynamic changes may result in a hyperdynamic state with low systemic vascular resistance. We conducted a systematic review and meta-analysis assessing hemodynamics in cardiac surgery patients treated with levosimendan. English-language literature was searched systematically from 2006 until October 2018, including randomized controlled trials and case-matched or retrospective studies providing at least two sequentially measured hemodynamic variables in adult patients who underwent cardiac surgery with cardiopulmonary bypass and were treated with levosimendan in comparison to alternative drugs or devices. Cardiac index significantly increased in the levosimendan group by 0.74 (0.24 to 1.23) [standardized mean difference (95% CI); p = 0.003] from baseline to postoperative day (POD) 1, and by 0.75 (0.25 to 1.25; p = 0.003) from baseline to POD 7, when corrected for the standardized mean difference at baseline by a multivariate mixed effects meta-analysis model. With this correction for baseline differences, other hemodynamic variables including systemic vascular resistance did not significantly differ until POD 1 [−0.17 (−0.64 to 0.30), p = 0.48] and POD 7 [−0.13 (−0.61 to 0.34), p = 0.58] between the levosimendan and the comparator group. Levosimendan increases cardiac index in patients undergoing cardiac surgery. Although levosimendan has inodilator properties, this meta-analysis finds no clinical evidence that levosimendan produces vasopressor-resistant vasoplegic syndrome.

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

“…Separately, Terbeck and colleagues, arguing from the premise that patients with heart failure may be especially susceptible to the vasodilatory effects of drugs, explored whether the use of levosimendan increases the risk of vasoplegic syndrome (i.e., severe refractory hypotension and low systemic vascular resistance in the absence of a low cardiac output [CO] state) in patients undergoing cardiac surgery with attendant cardiopulmonary bypass (CPB) [ 7 ]. All but one of the 16 included studies (14 RCTs plus two other published studies) examined the use of preoperatively administered levosimendan.…”

“…d) Focus on eight therapeutic settings of intensive care unit (ICU) and emergency medicine (EM), excluding hospitalization for AHF or advanced heart failure (because described in a separate update [3]). The selected areas are (1) postoperative settings, (2) septic shock, (3) weaning from ventilator, (4) weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO), ( 5) cardiogenic shock, (6) Takotsubo syndrome (TTS), (7) acute cardiac care complicated by renal dysfunction/failure, and (8) pulmonary hypertension (PH) and right ventricular dysfunction.…”

Overview of the current use of levosimendan in France: a prospective observational cohort study

“…A recent meta-analysis including 16 studies found no evidence that levosimendan produces vasopressor-resistant vasoplegic syndrome [ 26 ]. Our results are consistent with this finding, since only 25.7% of all patients required addition of norepinephrine for a median period of 12 h. The prevalence of hypotension in our cohort was 36.2% (very common), a figure that is less than the 50% observed in the REVIVE II trial [ 27 ] despite the fact that we included all hypotensive episode occurring up to 6 days after levosimendan initiation.…”

The role of levosimendan as inotropic agents in patients with LV dysfunction admitted to ICU post cardiac surgery

“…Despite an improvement in ventricular function, levosimendan does not increase myocardial oxygen uptake significantly. An increase in coronary blood flow and a reduction in coronary vascular resistance have been observed (5). Common adverse effects reported are hypotension, headache, and dizziness secondary to the vasodilating properties.…”