To evaluate the relative importance of increased lactate production as opposed to decreased utilization in hyperlactatemic patients, as well as their relation to glucose metabolism.
Prospective observational study.
Surgical intensive care unit of a university hospital.
Seven patients with severe sepsis or septic shock, seven patients with cardiogenic shock, and seven healthy volunteers.
C-labeled sodium lactate was infused at 10 micromol/kg/min and then at 20 micromol/kg/min over 120 mins each. H-labeled glucose was infused throughout.
Baseline arterial lactate was higher in septic (3.2 +/- 2.6) and cardiogenic shock patients (2.8 +/- 0.4) than in healthy volunteers (0.9 +/- 0.20 mmol/L, p < .05). Lactate clearance, computed using pharmacokinetic calculations, was similar in septic, cardiogenic shock, and controls, respectively: 10.8 +/- 5.4, 9.6 +/- 2.1, and 12.0 +/- 2.6 mL/kg/min. Endogenous lactate production was determined as the initial lactate concentration multiplied by lactate clearance. It was markedly enhanced in the patients (septic 26.2 +/- 10.5; cardiogenic shock 26.6 +/- 5.1) compared with controls (11.2 +/- 2.7 micromol/kg/min, p < .01). C-lactate oxidation (septic 54 +/- 25; cardiogenic shock 43 +/- 16; controls 65 +/- 15% of a lactate load of 10 micromol/kg/min) and transformation of C-lactate into C-glucose were not different (respectively, 15 +/- 15, 9 +/- 18, and 10 +/- 7%). Endogenous glucose production was markedly increased in the patients (septic 14.8 +/- 1.8; cardiogenic shock 15.0 +/- 1.5) compared with controls (7.2 +/- 1.1 micromol/kg/min, p < .01) and was not influenced by lactate infusion.
In patients suffering from septic or cardiogenic shock, hyperlactatemia was mainly related to increased production, whereas lactate clearance was similar to healthy subjects. Increased lactate production was concomitant to hyperglycemia and increased glucose turnover, suggesting that the latter substantially influences lactate metabolism during critical illness.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
"Other factors, particularly abnormal lactate clearance, may also contribute to hyperlactatemia in the presence of adequate perfusion, although the evidence is not uniform. Whereas Levraut et al.  demonstrated that impaired clearance was a significant cause of mild hyperlactatemia in stable septic patients, Revelly et al.  demonstrated, with stable isotopes, that lactate clearance was not the main cause of hyperlactatemia. More recently, Tapia et al.  showed an almost negligible exogenous lactate clearance in early experimental septic shock despite preserved liver perfusion and a concomitant normal clearance of the alcohol sugar sorbitol. "
"In addition, hepatic lactate metabolism might even be a saturable process  influenced by pH192021, substrate availability [13,22], and sepsis [1,11]. Part of these conflicting results could be explained by the extreme variability in the design of both experimental and clinical studies678910111213141516. Nevertheless, common opinion suggests a significant role for hepatic dysfunction in delayed lactate clearance. "
[Show abstract][Hide abstract]ABSTRACT: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and considered relevant only in patients with liver ischemia or cirrhosis. Our objectives were to establish if endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock.
After anesthesia twelve sheep were subjected to a hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to LPS (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a 3 h study period. After 60 min of shock, animals were fluid resuscitated to normalize MAP. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. In both cases the procedure included an IV bolus followed by serial blood sampling to draw a curve using the least squares method.
A significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 [3.1-6.7] vs. 1.8 [1.5-3.7] mmol/L) increasing to 10.2 [7.8-12.3] mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. However, no difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (915 [773-1046] vs. 655 [593-1175] ml/min at point D), mitochondrial respiration, liver enzymes or sorbitol clearance within groups was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 [30-180] vs. 1212 [743-2116] ml/min, p < 0.01; point D: 113 [65-322] vs. 944 [363-1235] ml/min, p < 0.01).
Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.
"During shock the heart undergoes a major shift in substrate utilization such that it oxidizes lactate for the majority of its energy needs . Revelly and coworkers demonstrated that an infusion of sodium lactate increased cardiac performance in patients with both cardiogenic and septic shock . Similarly, during increased demand on brain metabolism, lactate is increasingly utilized as an energy substrate –. "
[Show abstract][Hide abstract]ABSTRACT: Current teaching and guidelines suggest that aggressive fluid resuscitation is the best initial approach to the patient with hemodynamic instability. The source of this wisdom is difficult to discern, however, Early Goal Directed therapy (EGDT) as championed by Rivers et al. and the Surviving Sepsis Campaign Guidelines appears to have established this as the irrefutable truth. However, over the last decade it has become clear that aggressive fluid resuscitation leading to fluid overload is associated with increased morbidity and mortality across a diverse group of patients, including patients with severe sepsis as well as elective surgical and trauma patients and those with pancreatitis. Excessive fluid administration results in increased interstitial fluid in vital organs leading to impaired renal, hepatic and cardiac function. Increased extra-vascular lung water (EVLW) is particularly lethal, leading to iatrogenic salt water drowning. EGDT and the Surviving Sepsis Campaign Guidelines recommend targeting a central venous pressure (CVP) > 8 mmHg. A CVP > 8 mmHg has been demonstrated to decrease microcirculatory flow, as well as renal blood flow and is associated with an increased risk of renal failure and death. Normal saline (0.9% salt solution) as compared to balanced electrolyte solutions is associated with a greater risk of acute kidney injury and death. This paper reviews the adverse effects of large volume resuscitation, a high CVP and the excessive use of normal saline.
Full-text · Article · Jun 2014 · Annals of Intensive Care