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Dexmedetomidine ameliorates gut lactate production and impairment of exogenous lactate clearance in an endotoxic sheep model
Intensive Care Medicine Experimental volume 3, Article number: A414 (2015)
The mechanisms of persistent hyperlactemia during endotoxic shock are probably multifactorial. Both hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation have been implicated. More recently an early and severe impairment in exogenous lactate clearance has also been described . Theoretically, an excessive adrenergic response could influence all these mechanisms and thus aggravate the problem.
To assess the effects of dexmedetomidine (DEX) on lactate production and exogenous lactate clearance in an endotoxic shock model.
Twelve anesthetized sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, sublingual microcirculation, and muscle microdialysis. After the monitoring phase, all received a 5 mcg/kg LPS bolus (E coli O127:B8®) and then 4 mcg·kg1·hr1 for the rest of the experiment. After 1hr they were volume resuscitated, and then randomized to placebo or DEX. Sampling and exogenous lactate clearances  were performed at 4 points (figure 1).
DEX was not associated with any adverse hemodynamic effect in terms of cardiac output, heart rate, mixed venous oxygen saturation, central venous-arterial pCO2 gradient and NE requirements as compared to placebo. DEX animals presented significant lower epinephrine levels (4.6 ± 1.3 vs 7.1 ± 1.4 ng/ml), arterial lactate levels (6.4 ± 3.1 vs 9.2 ± 1.8 mmol/l), portal vein lactate levels (6.2 ± 2.2 vs 8.1 ± 2.0 mmol/l); and higher portal vein O2 saturations (78 ± 16 vs 68 ± 11 %), and exogenous lactate clearance (7.2 ± 5.4 vs 2.9 ± 1.5 ml/kg/min) as compared to placebo at point D. No differences in muscle lactate production or sublingual microcirculatory parameters could be observed.
Dexmedetomidine ameliorates the increase in gut lactate production and impairment of exogenous lactate clearance in experimental endotoxic shock. This effect is associated with a significant reduction in systemic epinephrine levels.
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Tapia P, Soto D, Bruhn A, Regueira T, Jarufe N, Alegria L, et al: 0101. Early and severe impairment of lactate clearance in endotoxic shock is not related to liver hypoperfusion: preliminary report. Intensive Care Medicine Experimental. 2014, 2 (Suppl 1): P12
Levraut J, Ciebiera JP, Chave S, Rabary O, Jambou P, Carles M, Grimaud D: Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J Respir Crit Care Med. 1998, 157: 1021-1026.
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Hernandez, G., Tapia, P., Ospina-Tascón, G. et al. Dexmedetomidine ameliorates gut lactate production and impairment of exogenous lactate clearance in an endotoxic sheep model. ICMx 3, A414 (2015). https://doi.org/10.1186/2197-425X-3-S1-A414
- Endotoxic Shock
- Epinephrine Level
- Sublingual Microcirculation
- Arterial Lactate Level