Metabolic changes detected by microdialysis during endotoxin shock and after endotoxin preconditioning

Objective: Preconditioning with low doses of endotoxin has been shown to induce endotoxin hyporesponsiveness. The present study was designed to assess the metabolic response of various tissues during endotoxemia and after pretreatment with endotoxin. Design: Controlled experimental animal study. Setting. Research laboratory of a university hospital. Measurements and results: Ten pigs were randomly assigned to a control (n = 5) or a treatment group (n = 5), the latter receiving incremental doses of endotoxin 5-2 days prior the experiments. Apart from hemodynamics and oxygen transport variables, lactate, glucose, and glycerol were measured in muscle, subcutaneous fat, and hepatic tissue using microdialysis. Endotoxin was infused (1 μg·kg·h) until the animals died. A significant increase in tissue lactate (eightfold) and glycerol (fivefold) was observed in the control animals. This effect was almost completely abolished in the endotoxin pretreated group. Endotoxin pretreatment had no significant effects on mean arterial pressure [56 (range 34-89) mmHg vs 70 (47-88) mmHg, n.s.] or cardiac output [4.8 (3.0-5.9) 1/min vs 3.2 (2.1-4.2) 1/min, n.s.], but significantly improved arterial pO₂ and pH (P<0.05). Increase of oxygen extraction was higher in control animals [from 34% (range 24-47%) to 72% (range 61-79%)] compared to the pretreatment group [from 30% (range 22-42%) to 44% (range 34-50%), P<0.05]. Endotoxin pretreatment increased survival time from 5.3 h (5.0-5.8) to 8.0 h (7.0-8.5) (P<0.05), respectively. Conclusions: Microdialysis monitoring revealed that endotoxin preconditioning ameliorates the increase in tissue metabolism during endotoxemia, accompanied by decreased systemic oxygen demand despite unchanged global hemodynamics.