Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Abstract

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 10 9 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/or norepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes.Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m 2 ; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

The Protective Effect of Dexmedetomidine on the Liver Injury in Sepsis Through Inhibition of Necroptosis

“…This is also consistent with our findings that medium and high doses of DEX reduced mortality in sepsis rats. Meanwhile, liver is one of the organs most prone to sepsis injury, and the recovery of liver function is considered to be the key factor affecting the survival of patients (26). Thus, we explored the effect of DEX on hepatic injury in sepsis.…”

“…Microcirculation abnormality is one of the characteristics of septic liver (26). The key elements in the pathophysiology of sepsis often involve endothelial dysfunction, which often leads to hypotension.…”

“…The key elements in the pathophysiology of sepsis often involve endothelial dysfunction, which often leads to hypotension. Persistent tissue hypoxia caused by microcirculation dysfunction can develop into ischemia-reperfusion injury and multiple organ failure (26,28). Studies have shown that hypoxic liver injury has been found in sepsis (29).…”

Comparison of sublingual microcirculatory parameters measured by sidestream darkfield videomicroscopy in anesthetized pigs and adult humans

“…Pigs are already commonly used to model sepsis with multiple recent studies examining sublingual microcirculatory function in this context. 17,18 The validation data presented here is supplementary to the existing body of work involving use of pigs to model critical illness and informs researchers adopting a porcine model to study microcirculatory changes in disease of some differences between pig and human but the similarity in sublingual PPV.…”

Effect of Perioperative Dexmedetomidine on Cardiac Surgery Outcome

“…Different studies have shown that dexmedetomidine positively impacts the lungs, kidneys, brain, and heart (Duncan et al, 2018;Kartal et al, 2020). Additionally, dexmedetomidine is reported to attenuate plasma cytokine levels, has `anti-inflammatory properties, and decreases mortality (Carnicelli et al, 2022). Therefore, in this study, more definitive outcomes like death or MI effect of dexmedetomidine on acute renal failure, infection, delirium, stroke, arrhythmia, and congestive heart failure after cardiac surgery are evaluated.…”