Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs

Lothar A. Schwarte, Olaf Picker, Stefan R. Bornstein, Artur Fournell, Thomas W.L. Scheeren

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Objective: The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (μHbO2) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (ḊO2) and/or oxygen consumption (V̇O2). We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine. Design: Laboratory experiment. Setting: University animal research laboratory of experimental anesthesiology. Subjects: Chronically instrumented dogs with flow probes for cardiac output measurement. Interventions: Anesthetized, mechanically ventilated dogs (each group n = 6) on different days randomly received levosimendan (10 μg·kg-1, followed by four infusion steps: 0.125-1.0 μg·kg-1·min-1), milrinone (5.0 μg·kg-1, followed by 1.25-10 μg·kg -1·min-1), or dobutamine (2.5-10.0 μg·kg-1·min-1). Since these drugs may modify regional or systemic responses to fluid load, an additional predefined volume challenge was subsequently performed with hydroxyethyl starch 6% (10 mL·kg-1). Measurements and Main Results: We measured μHbO2 (reflectance spectrophotometry), ḊO2, V̇O2, and systemic hemodynamics. Levosimendan significantly increased μHbO2 from baseline (∼55% for all groups) to 64 ± 4% and further to 69 ± 2% with volume challenge (mean ± SEM). At the systemic level, levosimendan alone only slightly increased ḊO2 at a stable V̇O2. Milrinone elicited similar systemic effects (ḊO2, V̇O2, hemodynamics) but failed to increase μHbO2. Dobutamine, conversely, increased μHbO2 to a similar extent as levosimendan; however, this was accompanied by marked increases in ḊO2 and V̇O2. The gastric mucosa selectivity of these interventions, expressed as slope of the μHbO2/ḊO2 relation, was highest for levosimendan (+1.89 and +1.14, without and with volume challenge), compared with milrinone (+0.45 and + 0.47) and dobutamine (+0.48 and + 0.33). Conclusions: Levosimendan is superior to milrinone (no significant regional effects) and dobutamine (marked systemic effects) in increasing gastric mucosal oxygenation selectiveiy (i.e., at only moderately increased ḊO2 and stable V̇O 2). If our experimental data apply to the clinical setting, levosimendan may serve as an option to selectively increase gastrointestinal mucosa oxygenation in patients at risk to develop splanchnic ischemia.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalCritical Care Medicine
Issue number1
Publication statusPublished - Jan 2005

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