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Cited by 24Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyTrauma, Hemostasis, Coagulopathy, Resuscitation

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

Cunha-Goncalves, Doris, Perez-de-Sa, Valeria, Larsson, Anders, Thörne, Johan, Blomquist, Sten·2009·Anesthesia & Analgesia
DOI 10.1213/ane.0b013e3181af40e0
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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 (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= 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. CONCLUSION: 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.

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  • Dobutamine increases cardiac output and oxygen transport, increases splanchnic perfusion and tissue oxygenation, and improves intramucosal acidosis and hyperlactatemia.

    “Physiologic studies demonstrate that dobutamine increases CO and oxygen transport, increases splanchnic perfusion and tissue oxygenation, improves intramucosal acidosis and hyperlactatemia [369].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [369]

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Authors
Cunha-Goncalves, D., Perez-de-Sa, V., Larsson, A., Thörne, J., & Blomquist, S.
Affiliations
  • Uppsala University Hospital (SE)
  • Helsingborgs lasarett (SE)
  • Skåne University Hospital (SE)
Corresponding author
Blomquist, Sten
ORCID
Larsson, Anders
Venue
Anesthesia & Analgesia
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-11
Volume
109
Issue
5
Pages
1576-1583
ISSN
0003-2999 (ISSN-L)
DOI
10.1213/ane.0b013e3181af40e0
OpenAlex
W2024647297
Cited by
24
References
42
Citations by year
2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
1.57
Type
journal article
Language
en
Open access
closed
Locations
  • Anesthesia & Analgesia (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
Keywords
levosimendan, dobutamine, inotropic support, norepinephrine, systemic perfusion, cardiac output, systemic vascular resistance, oxygen delivery, lipopolysaccharide, fluid resuscitation, vasopressor comparison, regional blood flow, systemic hypotension
MeSH terms
Simendan, Animals, Blood Pressure, Blood Volume, Cardiac Output, Cardiotonic Agents, Combined Modality Therapy, Disease Models, Animal, Dobutamine, Drug Therapy, Combination, Fluid Therapy, Heart Rate, Hemodynamics, Hydrazones, Hypotension, Lipopolysaccharides, Liver Circulation, Norepinephrine, Oxygen, Pyridazines, Regional Blood Flow, Shock, Septic, Splanchnic Circulation, Swine, Time Factors, Vascular Resistance, Lactic Acid

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