# Effects of Endotoxemia and Blood Pressure on Microcirculation and Noradrenaline Needs With or Without Dexmedetomidine in Beagle Dogs—A Blinded Cross-Over Study

## TL;DR

This study in Beagle dogs found that endotoxemia and blood pressure changes did not affect microcirculation, and dexmedetomidine did not reduce noradrenaline needs or improve microcirculation.

## Contribution

The study is one of the few to investigate microcirculation and vasopressor requirements in endotoxemic dogs using a cross-over design.

## Key findings

- Endotoxemia did not cause significant changes in microcirculation in Beagle dogs.
- Dexmedetomidine did not reduce noradrenaline requirements or improve microcirculatory parameters.
- Endotoxemia decreased cardiac output but did not alter microcirculation significantly.

## Abstract

Endotoxemia often leads to a drop of systemic blood pressure and subsequently deranged microcirculation. This needs to be aggressively addressed with the use of fluids and, if needed, supported by cardiovascular supportive drugs with vasoconstrictive properties, e.g., noradrenaline. As dexmedetomidine also induces vasoconstriction, its use could potentially reduce the dose of noradrenaline. Additionally, some animal studies suggest that dexmedetomidine may improve microcirculatory derangements induced by endotoxemia. However, little data is available on microcirculation in endotoxemic dogs. In this study we investigated the effects of endotoxemia and blood pressure on microcirculation and noradrenaline requirements with or without dexmedetomidine in six sevoflurane anaesthetised Beagle dogs. Using side stream dark field microscopy, we assessed microcirculatory parameters on buccal mucosa and markers of sepsis. After intravenous injection of endotoxin and consequent cardiovascular collapse, dogs were hemodynamically stabilised with fluids and noradrenaline with or without dexmedetomidine (cross-over). Endotoxemia resulted in no changes in microcirculation. Dexmedetomidine did not improve microcirculation or reduce noradrenaline requirements. Markers of sepsis showed alterations. Early and aggressive treatment of endotoxemia might prevent microcirculatory derangements.

Endotoxemia often leads to microcirculatory derangement. In six sevoflurane anaesthetized Beagle dogs, we investigated the effects of 1 mg/kg of Escherichia coli lipopolysaccharide endotoxin intravenous and blood pressure (mean arterial pressure of 65 mmHg versus 85 mmHg) on microcirculation assessed on buccal mucosa using side stream dark field microscopy. Dogs were afterwards resuscitated with fluids and noradrenaline. We investigated dose requirements of noradrenaline with or without dexmedetomidine. Microcirculatory parameters, and markers of sepsis (cardiac output, mixed venous oxygen saturation, carbon dioxide gap, and lactate) were analysed before endotoxemia, after endotoxemia, after a 30 mL/kg of Ringer’s acetate fluid bolus, and during noradrenaline +/− dexmedetomidine infusion, after a second fluid bolus, and a second time after vasopressor treatment in a cross-over fashion. Endotoxemia and mean arterial pressure had no statistically significant effect on microcirculation; however, endotoxemia resulted in a decrease in cardiac output. Dexmedetomidine neither improved microcirculation nor reduced noradrenaline requirements.