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Dopexamine hydrochloride in septic shock: effects on oxygen delivery and oxygenation of gut, liver, and muscle
N Lund1, R J de Asla, F Cladis
1Department of Anesthesiology, University of Rochester Medical Center, NY 14642, USA.
Abstract:
It has been suggested that septic shock is a disorder of microvascular autoregulation. Tissue blood flow is modulated by the state of activation of upstream endothelial receptors controlling the vascular smooth muscle tone. Because vascular receptor populations vary between organs, it should be expected that vasoactive drugs affect tissue oxygenation differently in different organs. We studied the effects of dopexamine HCl (a novel inotrope) and septic shock on oxygen delivery as well as tissue Po2 in gut, liver, and skeletal muscle in anesthetized rabbits. Employing the thermodilution technique, cardiac output was measured across the pulmonary bed and used to calculate oxygen delivery. Three eight-channel Mehrdraht Dortmund Oberfläche oxygen electrodes were placed on gut serosa, liver, and skeletal muscle surfaces, respectively, and sufficient readings were obtained to calculate tissue Po2 distributions. During septic shock mean arterial pressure, cardiac output, oxygen delivery, and mean tissue Po2 decreased in all organs. Our results suggest that the observed changes in tissue oxygenation during septic shock were caused by defective regulation of microvascular blood flow. In conclusion, during baseline conditions dopexamine HCl caused no statistically significant changes in tissue oxygenation in any organ, except in skeletal muscle at 10 micrograms/kg/min when tissue Po2 increased. During septic shock, however, dopexamine HCl improved oxygenation in all three organs in a dose-dependent manner.
Insights
Septic shock impairs tissue oxygenation due to microvascular dysfunction. Dopexamine HCl improved oxygen delivery and tissue oxygen levels in the gut, liver, and skeletal muscle during septic shock.
Area of Science:
- Physiology
- Pharmacology
- Critical Care Medicine
Background:
- Septic shock is hypothesized to involve microvascular autoregulation disorders.
- Endothelial receptor activation influences vascular smooth muscle tone and tissue blood flow.
- Organ-specific variations in vascular receptors may lead to differential drug responses.
Purpose of the Study:
- To investigate the effects of dopexamine HCl and septic shock on oxygen delivery and tissue partial pressure of oxygen (Po2) in the gut, liver, and skeletal muscle.
- To assess the role of microvascular regulation in septic shock-induced tissue hypoperfusion.
Main Methods:
- Anesthetized rabbits were used to study the effects of dopexamine HCl and induced septic shock.
- Cardiac output was measured using thermodilution to calculate oxygen delivery.
- Tissue Po2 distributions were measured using multi-channel oxygen electrodes placed on gut serosa, liver, and skeletal muscle surfaces.
Main Results:
- Septic shock led to decreased mean arterial pressure, cardiac output, oxygen delivery, and mean tissue Po2 in all studied organs.
- Dopexamine HCl did not significantly alter tissue oxygenation at baseline, except for an increase in skeletal muscle Po2 at a specific dose.
- During septic shock, dopexamine HCl demonstrated a dose-dependent improvement in tissue oxygenation across the gut, liver, and skeletal muscle.
Conclusions:
- The observed alterations in tissue oxygenation during septic shock are likely due to impaired microvascular blood flow regulation.
- Dopexamine HCl can ameliorate tissue hypoperfusion and improve oxygenation in multiple organs during septic shock, suggesting a therapeutic potential.