Effects of lidocaine administration on hemodynamics and cytokine responses to endotoxemia in rabbits

Abstract

Objective: To investigate the effects of lidocaine administration on hemodynamics and cytokine concentrations in Escherichia coli endotoxemia in rabbits.

Design: Randomized, prospective laboratory study.

Setting: University laboratory.

Subjects: Thirty-two Japanese rabbits anesthetized with urethane and ventilated mechanically.

Interventions: Animals were randomly assigned to one of four groups: endotoxemic controls (n = 8), receiving intravenous E. coli endotoxin (0.5 mg/kg bolus) via the mesenteric vein; laparotomy controls (n = 8), treated identically to the endotoxemic controls except for the substitution of 0.9% saline for endotoxin; lidocaine controls (n = 8), treated identically to the laparotomy controls with the addition of intravenous lidocaine (3 mg/kg bolus followed by infusion at 2 mg/kg/hr) administered immediately after the injection of 0.9% saline; and lidocaine-treated rabbits (n = 8), treated identically to the endotoxemic controls with the addition of intravenous lidocaine (3 mg/kg bolus followed by infusion at 2 mg/kg/hr) administered immediately after the injection of endotoxin.

Measurements and main results: We compared the cardiac output, systemic vascular resistance, blood gases, and plasma cytokine concentrations (tumor necrosis factor, interleukin [IL]-6, and IL-8) for each group. After endotoxin injection, the mean arterial pressure, cardiac output, and systemic vascular resistance decreased progressively in the endotoxemic controls. At 4 hrs after injection, all of the variables except the heart rate and central venous pressure were lower in the endotoxemic controls than in the other groups. At 4 hrs after endotoxin injection, both IL-6 and IL-8 concentrations increased in all groups. However, the mean concentrations of IL-6 and IL-8 in the endotoxemic controls significantly exceeded those in the other groups. No significant differences existed between the laparotomy controls and lidocaine-treated rabbits.

Conclusions: Lidocaine had a profound inhibitory effect on the hemodynamic and cytokine responses to endotoxemia when it was administered immediately after exposure to endotoxin. Our results demonstrate the potential usefulness of lidocaine as an anti-inflammatory agent in endotoxemia.