Impaired Hepatic Extraction and Increased Splanchnic Production Contribute to Lactic Acidosis in Canine Sepsis

Abstract

In septic shock, the extent to which lactic acidosis (LA) is a consequence of splanchnic lactate overproduction (SLP) or impaired hepatic lactate extraction (HLE) is not clear. We examined SLP and HLE in E. coli sepsis in dogs. We further determined the effects of vasopressor treatments, which included phenylephrine, dopamine, norepinephrine, and a combination of dobutamine and norepinephrine treatment, on SLP and HLE in respective groups. The animals were studied while anesthetized and ventilated. During sepsis, SLP increased as compared with presepsis (-0.017 versus 0.07 mmol/min, p < 0.05), but this increase could not be explained by reduced splanchnic oxygen delivery (SOD). During sepsis, HLE increased as compared with baseline (0.8 versus 8%, p < 0.05), but was significantly lower than that found during lactic acid loading in nonseptic dogs. None of the vasopressor treatments had a detrimental effect on SLP. These results indicate that LA in sepsis occurs secondary to an increase in splanchnic lactate production that is not related to reduced splanchnic oxygen delivery, as well as to a decrease in hepatic lactate extraction. Effects of different vasoactive agents did not alter either splanchnic lactate production or hepatic lactate extraction in this sepsis model.

Treatment of severe lactic acidosis during the pre-anhepatic stage of liver transplant surgery with intraoperative hemodialysis

“…It was used throughout the case for renal protection as a part of the existing protocol, and was unlikely to have contributed to the lactic acidosis. Dopamine infusion in sepsis models had no effect on either splanchnic lactate production or hepatic lactate utilization [23]. At doses of 10 μg/kg/min, dopamine significantly improved hepatic oxygenation [24] and increased portal and total HBF during hypoxia, while having no effect on HBF at any dose [25].…”

“…At doses of 10 μg/kg/min, dopamine significantly improved hepatic oxygenation [24] and increased portal and total HBF during hypoxia, while having no effect on HBF at any dose [25]. Phenylephrine, which was also used throughout the case to compensate for the low SVR and to maintain MAP around 75 to 80 mmHg, has no effect on lactate production and hepatic lactate utilization [23], and it has been associated with a substantial decrease in blood lactate concentrations [26]. At least one animal study supports the lack of effect of dopamine and phenylephrine on lactic acidosis during liver transplant surgery [27].…”

Effects of AM281, a cannabinoid antagonist, on circulatory deterioration and cytokine production in an endotoxin shock model: comparison with norepinephrine

“…Numerous reports have noted that administration of NE could improve systemic hemodynamics, but whether administration of NE can improve intestinal perfusion during septic shock remains controversial [21][22][23][24][25][26][27]. Agents such as phenylephrine and NE that display α-adrenergic effects have been considered to cause intestinal ischemia by decreasing intestinal perfusion during septic shock [21].…”

Role of Sodium Bicarbonate to Treat Neonatal Metabolic Acidosis: Beneficial or Not

“…14 It appears that circulating inflammatory mediators which extract lactate from any organ produces excess lactate due to impaired hepatic clearance. 3,15,16 Reduced oxygen availability leads to acidosis in all body compartments and liberate lactic acid by anaerobic metabolism. Lactate accompanies metabolic acidosis, in turn, consumes blood buffer bases, 7,11 mostly HCO 3 in extracellular fluid.…”