Inotropic support during experimental endotoxemic shock: part II. A comparison of levosimendan with dobutamine.
BACKGROUND
We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock.


METHODS
Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO(2)) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 microg x kg(-1) x h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 microg x kg(-1) x h(-1)), dobutamine (10-20 microg x kg(-1) x min(-1)), and control. In the first two groups, norepinephrine (0.5-2 microg x kg(-1) x min(-1)) was added when mean arterial blood pressure (MAP) <or= 65 mm Hg. Crystalloids were given to maintain filling pressures >or= baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant.


RESULTS
At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO(2) (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan.


CONCLUSIONS
In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO(2). However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations.
Cunha-Goncalves
Doris
D
Heart and Lung Division, Department of Cardiothoracic Surgery, Anesthesia and Intensive Care, Lund University Hospital, SE-221 85 Lund, Sweden. doris.cunha_goncalves@med.lu.s
Perez-de-Sa
Valeria
V
Larsson
Anders
A
Thörne
Johan
J
Blomquist
Sten
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005440:Fluid Therapy; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D008102:Liver Circulation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D011724:Pyridazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000077464:Simendan; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D006835:Hydrazones; D008070:Lipopolysaccharides; D011724:Pyridazines; C440499:lipopolysaccharide, Escherichia coli O111 B4; D019344:Lactic Acid; D000077464:Simendan; D004280:Dobutamine; D010100:Oxygen; D009638:Norepinephrine