Abstract
BackgroundPersistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock.MethodsEighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments.ResultsDexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups.ConclusionsDexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.
Highlights
Persistent hyperlactatemia during septic shock is multifactorial
Our model addressed three of the major determinants of persistent hyperlactatemia: muscle lactate generation as potentially representing adrenergic-driven aerobic glycolysis through microdialysis and serum epinephrine levels; gut lactate production as potentially representing anaerobic generation through portal oxygen venous saturation and lactate levels; and clearance using the exogenous lactate clearance technique proposed by Levraut et al [12]
LPS induced a progressive hyperlactatemia in the three groups, serum lactate levels at point C were lower with DEX and ESM as compared to controls
Summary
Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. Some current guidelines recommend targeting resuscitation at normalizing lactate levels [4]. Serum lactate levels during septic shock resuscitation represent a balance between aerobic or anaerobic generation, and clearance by different tissues. In a recent experimental study, we found an early and severe impairment of exogenous lactate clearance to 10 % of sham values 1 hour after endotoxic [lipopolysaccharide (LPS)] shock induction [13]. This finding was not explained by liver hypoperfusion as tested with different techniques [13], the pathogenic mechanisms were not explored. The term “lactate clearance” has somehow been erroneously used in medical literature because a decrease in serum lactate levels could be caused either by a decreased production or increased clearance, and the inverse is true [13, 14]
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