Research article summary (published 25 Aug 2009):

Inotropic support during experimental endotoxemic shock: part II. A comparison of levosimendan with dobutamine.

Full 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.

Author information

Author/s: Cunha-Goncalves, Doris (D); Perez-de-Sa, Valeria (V); Larsson, Anders (A); Thörne, Johan (J); Blomquist, Sten (S);

Affiliation: Heart and Lung Division, Department of Cardiothoracic Surgery, Anesthesia and Intensive Care, Lund University Hospital, SE-221 85 Lund, Sweden. doris.cunha_goncalves(-atsign-)med.lu.s

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Anesthesia and analgesia (Anesth Analg), published in United States. (Language: eng)

Reference: 2009-Nov; vol 109 (issue 5) : pp 1576-83

Dates: Created 2009/10/21; Completed 2009/11/05;

PMID: 19713252, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Anesth Analg. 2009 Nov;109(5):1367-9. (PMID: 19843771)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Blood Pressure - drug effects Blood Volume Cardiac Output - drug effects Cardiotonic Agents - pharmacology Combined Modality Therapy Disease Models, Animal Dobutamine - pharmacology Drug Therapy, Combination Fluid Therapy Heart Rate - drug effects Hemodynamics - drug effects Hydrazones - pharmacology

Hypotension - drug therapy; physiopathology Lactic Acid - blood Lipopolysaccharides Liver Circulation - drug effects Norepinephrine - pharmacology Oxygen - blood Pyridazines - pharmacology Regional Blood Flow - drug effects Shock, Septic - chemically induced; drug therapy; physiopathology Splanchnic Circulation - drug effects Swine Time Factors Vascular Resistance - drug effects

Associated Chemicals: Cardiotonic Agents (0) ; Hydrazones (0) ; Lipopolysaccharides (0) ; Pyridazines (0) ; lipopolysaccharide, Escherichia coli 0111 B4 (0) ; simendan (131741-08-7) ; Dobutamine (34368-04-2) ; Lactic Acid (50-21-5) ; Norepinephrine (51-41-2) ; Oxygen (7782-44-7)

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