Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies

Abstract

Background Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. Methods Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. Results MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. Conclusions In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Association Between Lactate and 28-Day Mortality in Elderly Patients with Sepsis: Results from MIMIC-IV Database

“…Elevated level of lactate caused by sepsis could be explained with several mechanisms. Sepsis usually leads to adrenergic stimulation, which results in activation of some enzymes and acceleration of glycolysis tissues, resulting in excess production of lactate [ 27 ]. Moreover, mitochondrial function, which normally converts lactate into energy, is impaired by sepsis, potentially causes lactate accumulation and hyperlactatemia [ 28 ].…”

50 Years of Sepsis Investigation/Enlightenment Among Adults—The Long and Winding Road

“…Possible mechanisms include overproduction, decreased clearance/ utilization, an inflammatory response to adrenergic therapy, as well as anaerobic and aerobic glycolysis (122)(123)(124)(125). Mitochondrial dysfunction as well as endogenous and exogenous catecholamines may also contribute to lactate elevation (126,127). Despite sufficient amounts of oxygen and nutrients for aerobic glycolysis, some cancer cells use a less efficient pathway for energy production, preferentially metabolizing glucose through lactate fermentation, yielding high lactate levels.…”

The Lactate Gradient, an unrecognized biomarker of potential significance

“…This catecholamine is one of several secreted in response to sympathetic nervous system activity in the adrenal glands. Sympathetic stimulation was found to increase serum lactate concentrations in patients with sepsis (Jagan, et al 2021). Wang et al (2021) found that norepinephrine enhances mRNA expression of several key glycolytic enzymes in tumor cells.…”