Effects of endotoxin on lactate metabolism in humans

Abstract

IntroductionHyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge.MethodsFourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose.ResultsIn both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged.ConclusionsLPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production.Trial registrationClinicalTrials.gov NCT01647997

Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients

“…Both taurine and GSx are potent anti-inflammatory molecules that are generated in response to pro-inflammatory states (Tabas & Glass, 2013). In turn, lactate, a normal end point of the anaerobic breakdown of glucose, has been shown to increase in blood following bacterial LPS administration (Michaeli et al, 2012); inflammation triggers CMV reactivation (Cook et al, 2006), thus it could be hypothesized that the risk of CMV DNAemia in the Allo-SCT setting might be directly related to the net state of systemic inflammation after transplant. In this context, plasma levels of the aforementioned metabolites may be reflective of the magnitude of either systemic inflammation (methylamines), ongoing compensatory antiinflammatory responses (taurine and total GSx) or both.…”

Temporal Metabolic Profiling of Plasma During Endotoxemia in Humans

“…Although these techniques ensure that subsets of metabolites with coherent temporal profiles are captured; at the same time, they might have masked some subtle changes which might be significant but not necessarily correspond to the observed dominant patterns. Metabolites which have a quickly resolving perturbation early in the time course, such as lactate (36), can be an example to this limitation. Furthermore, there is limited number of time points in the study and that the last two time points are considerably far from each other.…”

On the origins of lactate during sepsis

“…It is also worth noting that this phenomenon may not be confined to sepsis but might also apply to other forms of shock, including low-output forms [5,6]. This mechanism may not occur during mild endotoxemia, however, and, as suggested by the authors [1], lactate is produced elsewhere.…”

“…In the previous issue of Critical Care , Michaeli and colleagues tried to answer these questions [1]. They used a well-established model of endotoxemia in 14 fasting healthy volunteers to assess the effect of lipopolysaccharide (LPS) administration on lactate production and lactate clearance.…”

“…In hemodynamically stable septic shock patients, Levraut and colleagues observed that this clearance was decreased to 473 ml/kg/hour [8], while it remained unaltered at 858 ml/kg/hour in Michaeli and colleagues' study [1]. The severity of the insult may thus probably influence lactate clearance.…”