Lidocaine therapy in awake endotoxemic Yucatan minipigs. I. Metabolic parameters and glucose biokinetics.
Cellular membrane destabilization induced by endotoxin and endogenous inflammatory mediators contributes significantly to the progression of metabolic and hemodynamic dysfunction in endotoxemia. Owing to its membrane-stabilizing properties, lidocaine may prove beneficial in the treatment of endotoxic shock. Twelve 50-kg pigs were surgically fitted with jugular venous and carotid arterial catheters. Seventy-two hours later they were placed in restraint slings, and following a 3-h control period, were infused with Escherichia coli endotoxin (Difco 055:B5) at 15 micrograms/kg for 6 h. Eight were controls and four received a primed (2 mg/kg) continuous infusion (2 mg/kg/h) of lidocaine 1 h following the initiation of endotoxin infusion. In the lidocaine-treated group, arterial hypotension (113 mmHg) developed by 60 min, continued to fall to 104 mmHg by 200 min and rose terminally to 118 mmHg. These values were higher than the control group, but were below those of the control period of the lidocaine group. Six -3H-glucose-derived Rd values were increased above their own control period at 60 min, but were approximately 55% lower than in the untreated group. Ra values were not significantly changed in the lidocaine-treated group resulting in a net glucose deficit which was more profound than in untreated pigs, whose Ra values did increase. The degree of hypoglycemia was more profound in lidocaine-treated pigs from 100-260 min, stabilizing at 29-37 mg/dl. Blood lactate (70 mg/dl) was above those of the control pigs (44 mg/dl) from 160 to 220 min. U-14C-glucose-derived glucose recycling was increased above the lidocaine group's preendotoxin control period and reached values twice those of the untreated pigs' endotoxin infusion period. Compared to their own control period and the untreated group's endotoxin infusion period, percentage lactate/glucose was decreased from 40 min on. Lidocaine treatment elicited modest improvements in systemic arterial blood pressure and reduced relative glucose utilization and gluconeogenesis, but in itself, was not a sufficient therapy for endotoxic shock in this model.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D004731:Endotoxins / Q000097:blood*; D004734:Energy Metabolism / Q000187:drug effects*; D004926:Escherichia coli; D005260:Female; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008012:Lidocaine / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid; D013552:Swine; D013556:Swine, Miniature
D001786:Blood Glucose; D004573:Electrolytes; D004731:Endotoxins; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D008012:Lidocaine; D010100:Oxygen