Abstract 2048: Levosimendan Improves Myocardial and Pulmonary Function in Ovine Septic Shock
Introduction: Septic cardiomyopathy and pulmonary hypertension are frequent complications in septic shock. Levosimendan, a calcium sensitizer, improves myocardial contractility at low energy costs and has vasodilating properties by simultaneously stimulating adenosine triphosphate-sensitive potassium channels. Hypothesis: We assessed the hypothesis that combined levosimendan and arginine-vasopressin (AVP) improve myocardial and pulmonary dysfunction in septic shock. Therefore, the present study was conducted as a prospective, randomized, laboratory experiment in ovine septic shock.
Methods: Twenty-one ewes were anesthetized and instrumented for chronic hemodynamic monitoring using an established protocol. A median laparotomy was performed to take faeces from the caecum under sterile conditions. After baseline measurements had been performed, the faeces were injected into the peritoneal cavity. Following the onset of septic shock (defined as mean arterial pressure (MAP) < 60 mmHg), animals were randomly assigned to receive either AVP (0.5 mU/kg/min) or AVP and levosimendan (0.2 μg/kg/min; each n = 7) during the 24h study period. The control group (n = 7) received only the vehicle. If necessary, norepinephrine (NE) was titrated to maintain MAP at 70 ± 5 mmHg in all groups.
Results: Baseline characteristics, NE requirements and troponin I levels did not differ between groups. Following 8 h of septic shock, left ventricular stroke work index was significantly higher in animals receiving the combination therapy (61± 3 g·m·m−2) as compared to AVP treatment alone (48 ± 5 g·m·m−2) and the control group (43 ± 5 g·m·m−2). In addition, combined levosimendan and AVP reduced pulmonary vascular resistance index within 8 h (88 ± 7 dyne·s·cm−5·m2 vs. AVP: 145 ± 28 dyne·s· −5·m2 vs. Control: 123 ± 28 dyne·s· −5·m2). No acute respiratory distress syndrome (ARDS; defined as PaO2/FiO2 ratio < 200) occurred in levosimendan-treated animals. In contrast, 5 animals of the control and 4 animals of the AVP group suffered from ARDS after 8 and 12 h of septic shock, respectively.
Conclusions: Early institution of combined levosimendan and AVP may be a useful option to attenuate sepsis-associated cardiopulmonary dysfunction.