Efficacy of levosimendan in shock

Levosimendan is used intravenously for the management of heart failure. At the therapeutic dose, levosimendan acts predominantly as a calcium sensitizer and ATP-sensitive K⁺-channel (KATP-channel) opener. It binds directly to the calcium-dependent site on troponin C, stabilizing the calcium-induced conformational change and enhances the calcium sensitivity of the cardiac myofilaments. The advantages of a calcium sensitizer over dobutamine is the lack of intracellular calcium overload and that it acts without increasing the energy demand for handling intracellular calcium.

Method

Fifteen patients with cardiogenic, septic or mixed cardiogenic/septic shock were administered a loading dose of 12 μg/kg/min levosimendan, followed by a continuous infusion of 0.1 μg/kg/min for 24 hours. Five patients were diagnosed with septic shock, six with cardiogenic shock and four with mixed septic and cardiogenic shock. The mean APACHE II score was 21.3 ± 6.4 The arterial blood pressures of the patients were monitored closely via arterial catheters. Intravenous noradrenaline was administered, where necessary, to maintain mean arterial pressure > 65 mmHg. Echocardiographic left ventricular ejection fraction (LVEF) (Simpson's method) and plasma B-type natriuretic peptide (Biosite Triage method) were measured before and after (within 1 hour) levosimendan infusion.

Results

The LVEF showed a significantly but relatively small improvement in response to levosimendan infusion (pre, 25.7 ± 11.0% vs post, 29.8 ± 8.6%), representing an absolute change of 4.1 ± 8.4% (P = 0.039). The plasma B-type natriuretic peptide concentrations demonstrated a significant decrease, from 993 ± 389 to 644 ± 408 pg/ml, before and after levosimendan infusion (P = 0.001).

Conclusion

The use of levosimendan in shock patients proved to be feasible, and holds promise as a potential alternative to catecholamine inotropes.