Lidocaine therapy in awake endotoxemic Yucatan minipigs. II. Hepatosplanchnic metabolism

Abstract

Reductions in hepatosplanchnic blood flow and oxygen delivery contribute to the hepatic metabolic dysfunction observed in endotoxemia. Through its membrane-stabilizing activity, systemic lidocaine therapy may modify visceral hemodynamics and preserve hepatocellular metabolic function in endotoxic shock. Twelve 50-kg pigs were surgically fitted with jugular, portal, hepatic venous and carotid arterial catheters, and hepatic arterial and portal venous flow cuffs to quantitate portosystemic and transhepatic kinetics. Seventy-two hours later they were placed in slings, and following a 3-h control period were infused with Escherichia coli endotoxin (Difco 055:B5) at 15 micrograms/kg/h 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. Hepatosplanchnic blood flow was relatively unaffected by lidocaine infusion. In both untreated and treated pigs, hepatic arterial flow decreased by 25-30%, portal venous flow fell by approximately 60%, and hepatic venous flow was reduced by 50%. Following 2 h of endotoxin infusion, net splanchnic glucose uptake was increased significantly in lidocaine-treated pigs, but not in untreated endotoxemic animals. Transhepatic lactate kinetics were unaffected by treatment, but net hepatic pyruvate uptake in the lidocaine-treated group increased as compared to the untreated group by 140 min postendotoxin, being significantly greater at 220, 280, and 320 min. Hepatic oxygen input was significantly reduced by 25-30% in both groups within 1 h of the onset of endotoxemia, but hepatic oxygen extraction efficiency increased two-to-three-fold, thereby maintaining net hepatic oxygen uptake. Despite the maintenance of hepatic oxygen uptake and improved hepatic pyruvate extraction in lidocaine treated endotoxemic pigs, no significant improvements in glucose homeostasis were incurred, leading to the conclusion that lidocaine therapy offered few significant advantages in the treatment of overall metabolic derangements during acute endotoxemia.