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Inotropic Support During Experimental Endotoxemic Shock: Part II. A Comparison of Levosimendan with Dobutamine

Cunha Goncalves, Doris LU ; Perez de Sá, Valéria LU ; Larsson, Anders; Thorne, Johan and Blomquist, Sten LU (2009) In Anesthesia and Analgesia 109(5). p.1576-1583
Abstract
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 (VO2) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 mu g . kg(-1) . h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid... (More)
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 (VO2) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 mu g . kg(-1) . 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 mu g . kg(-1) . h(-1)), dobutamine (10-20 mu g . kg(-1) . min(-1)), and control. In the first two groups, norepinephrine (0.5-2 mu g . kg(-1) . min(-1)) was added when mean arterial blood pressure (MAP) <= 65 mm Hg. Crystalloids were given to maintain filling pressures >= 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 VO2 (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. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO2. However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations. (Anesth Analg 2009;109:1576-83) (Less)
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Contribution to journal
publication status
published
subject
in
Anesthesia and Analgesia
volume
109
issue
5
pages
1576 - 1583
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000271032500037
  • scopus:70350710318
ISSN
1526-7598
DOI
10.1213/ane.0b013e3181af40e0
language
English
LU publication?
yes
id
ce6c1289-d2e8-4651-b508-fcefbb882f78 (old id 1505876)
date added to LUP
2009-11-23 16:45:51
date last changed
2017-01-01 05:37:21
@article{ce6c1289-d2e8-4651-b508-fcefbb882f78,
  abstract     = {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 (VO2) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 mu g . kg(-1) . 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 mu g . kg(-1) . h(-1)), dobutamine (10-20 mu g . kg(-1) . min(-1)), and control. In the first two groups, norepinephrine (0.5-2 mu g . kg(-1) . min(-1)) was added when mean arterial blood pressure (MAP) &lt;= 65 mm Hg. Crystalloids were given to maintain filling pressures &gt;= 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 &lt; 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P &lt; 0.001), systemic vascular resistance was 30% lower (P &lt; 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 &lt; 0.001), and 20% (P &lt; 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P &lt; 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO2 (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P &lt; 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 &lt; 0.001) and control groups (70% and 45%, respectively, P &lt; 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P &lt; 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 &lt; 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. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO2. However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations. (Anesth Analg 2009;109:1576-83)},
  author       = {Cunha Goncalves, Doris and Perez de Sá, Valéria and Larsson, Anders and Thorne, Johan and Blomquist, Sten},
  issn         = {1526-7598},
  language     = {eng},
  number       = {5},
  pages        = {1576--1583},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Anesthesia and Analgesia},
  title        = {Inotropic Support During Experimental Endotoxemic Shock: Part II. A Comparison of Levosimendan with Dobutamine},
  url          = {http://dx.doi.org/10.1213/ane.0b013e3181af40e0},
  volume       = {109},
  year         = {2009},
}