Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass

Abstract

Background: The calcium sensitizer levosimendan has been used in cardiac surgery for the treatment of postoperative low cardiac output syndrome (LCOS) and difficult weaning from cardiopulmonary bypass (CPB).

Objectives: To evaluate the effects of preoperative treatment with levosimendan on 30-day mortality, the risk of developing LCOS and the requirement for inotropes, vasopressors and intra-aortic balloon pumps in patients with severe left ventricular dysfunction.

Methods: Patient with severe left ventricular dysfunction and an ejection fraction <25% undergoing coronary artery bypass grafting with CPB were admitted 24 h before surgery and were randomly assigned to receive levosimendan (loading dose 10 μg/kg followed by a 23 h continuous infusion of 0.1μg/kg/min) or a placebo.

Results: From December 1, 2002 to June 1, 2008, a total of 252 patients were enrolled (127 in the levosimendan group and 125 in the control group). Individuals treated with levosimendan exhibited a lower incidence of complicated weaning from CPB (2.4% versus 9.6%; P<0.05), decreased mortality (3.9% versus 12.8%; P<0.05) and a lower incidence of LCOS (7.1% versus 20.8%; P<0.05) compared with the control group. The levosimendan group also had a lower requirement for inotropes (7.9% versus 58.4%; P<0.05), vasopressors (14.2% versus 45.6%; P<0.05) and intra-aortic balloon pumps (6.3% versus 30.4%; P<0.05).

Conclusion: Patients with severe left ventricle dysfunction (ejection fraction <25%) undergoing coronary artery bypass grafting with CPB who were pretreated with levosimendan exhibited lower mortality, a decreased risk for developing LCOS and a reduced requirement for inotropes, vasopressors and intra-aortic balloon pumps. Studies with a larger number of patients are required to confirm whether these findings represent a new strategy to reduce the operative risk in this high-risk patient population.

Keywords: Cardiac surgery; Hemodynamic optimization; Inotropic agents; Levosimendan; Postoperative low cardiac output.

Figures

Figure 1)

An improvement in the cardiac index was observed immediately following administration of the levosimendan loading dose and was sustained for 48 h postoperatively. T0 Time 0, defined as the initial hemodynamic measurement; T1 Time 1, recorded immediately after the levosimendan loading dose; T2 Time 2, before anesthesia induction in the operating room; T3 Time 3, on arrival back in the cardiovascular intensive care unit following surgery; T4 to T7 Time 4 to Time 7, representing 6 h, 12 h, 24 h and 48 h after arrival back in the cardiovascular intensive care unit, respectively

Figure 2)

A rapid improvement in the mixed venous pressure was observed in the levosimendan group following administration of the loading dose and was sustained for 48 h postoperatively. T0 Time 0, defined as the initial hemodynamic measurement; T1 Time 1, recorded immediately after the levosimendan loading dose; T2 Time 2, before anesthesia induction in the operating room; T3 Time 3, on arrival back in the cardiovascular intensive care unit following surgery; T4 to T7 Time 4 to Time 7, representing 6 h, 12 h, 24 h and 48 h after arrival back in the cardiovascular intensive care unit, respectively

Figure 3)

An improvement in the pulmonary artery occlusion pressure was observed immediately following administration of the levosimendan loading dose and was sustained for 48 h postoperatively. T0 Time 0, defined as the initial hemodynamic measurement; T1 Time 1, recorded immediately after the levosimendan loading dose; T2 Time 2, before anesthesia induction in the operating room; T3 Time 3, on arrival back in the cardiovascular intensive care unit following surgery; T4 to T7, Time 4 to Time 7, representing 6, 12, 24 and 48 h after arrival back in the cardiovascular intensive care unit, respectively

Figure 4)

Levosimendan’s unique properties are attributed to its multiple and complementary mechanisms of action