ObjectiveTo assess the effects of lidocaine on the hemodynamic and inflammatory responses to Escherichia coli endotoxemia in rabbits.DesignProspective, randomized, controlled experimental study.SettingUniversity laboratory.SubjectsTwenty-seven female Japanese rabbits, anesthetized with urethane and ventilated mechanically.InterventionsAnimals were randomly assigned to one of three groups: a) endotoxemic control group (n equals 9), receiving intravenous Escherichia coli endotoxin (0.5 mg/kg bolus) via the mesenteric vein; b) laparotomy control group (n equals 9), treated identically to the endotoxemic control group, except for substitution of 0.9% saline for endotoxin; and c) lidocaine-treated group (n equals 9), treated identically to the endotoxemic controls and additionally, intravenous lidocaine (3 mg/kg bolus, followed by infusion at 2 mg/kg/hr) was administered immediately after endotoxin.Measurements and Main ResultsWe compared hemodynamics, blood gases, and microscopic findings of lung tissue obtained at necropsy in each group. Laparotomy alone had a minimal effect on the parameters and findings. Endotoxin injection decreased mean systolic arterial pressure from 135 plus minus 6 (SD) to 95 plus minus 25 mm Hg (p less than .05) and increased the mean base deficit from minus 1.2 plus minus 1.8 to minus 14.4 plus minus 4.2 mmol/L (p less than .05), and caused the infiltration of neutrophils into the lungs. Lidocaine administration abolished the hypotension and attenuated the increase of base deficit to minus 9.5 plus minus 2.1 mmol/L (p less than .05) and the cellular infiltration in comparison with endotoxemic controls.ConclusionsLidocaine attenuated the hemodynamic and inflammatory responses to endotoxemia in rabbits. Findings suggest that lidocaine administration may prevent the development of hypotension and metabolic acidosis during endotoxemia.(Crit Care Med 1996; 24:642-646)