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Published on: February 10, 2013
Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study
Arnaldo Dubin1, Gastón Murias, Juan Pablo Sottile
1Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 42 No 577, 1900, La Plata, Argentina. arnaldodubin@speedy.com.ar
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.