Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study.

OBJECTIVE

To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock.

DESIGN

Prospective, controlled experimental study.

SETTING

University-based research laboratory.

SUBJECTS

Nineteen anesthetized, mechanically ventilated sheep.

INTERVENTIONS

Endotoxin-treated sheep were randomly assigned to three groups: control (n=7), dobutamine (10 microg/kg/min, n=6) and levosimendan (100 microg/kg over 10 min followed by 100 microg/kg/h, n=6) and treated for 120 min.

MEASUREMENTS AND MAIN RESULTS

After endotoxin administration, systemic and intestinal DO(2) decreased (24.6+/-5.2 vs 15.3+/-3.4 ml/kg/min and 105.0+/-28.1 vs 55.8+/-25.9 ml/kg/min, respectively; p<0.05 for both). Arterial lactate and the intramucosal-arterial PCO(2) difference (DeltaPCO(2)) increased (1.4+/-0.3 vs 3.1+/-1.5 mmHg and 9+/-6 vs 23+/-6 mmHg mmol/l, respectively; p<0.05). Systemic DO(2) was preserved in the dobutamine-treated group (22.3+/-4.7 vs 26.8+/-7.0 ml/min/kg, p=NS) but intestinal DO(2) decreased (98.9+/-0.2 vs 68.0+/-22.9 ml/min/kg, p<0.05) and DeltaPCO(2) increased (12+/-5 vs 25+/-11 mmHg, p<0.05). The administration of levosimendan prevented declines in systemic and intestinal DO(2) (25.1+/-3.0 vs 24.0+/-6.3 ml/min/kg and 111.1+/-18.0 vs 98.2+/-23.1 ml/min/kg, p=NS for both) or increases in DeltaPCO(2) (7+/-7 vs 10+/-8, p=NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6+/-0.3 vs 2.5+/-0.7 and 1.4+/-0.4 vs. 2.9+/-1.1 mmol/l, p=NS between groups).

CONCLUSIONS

Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.