Increased muscle-to-serum lactate gradient predicts progression towards septic shock in septic patients

During septic shock, muscle produces lactate and pyruvate by way of an exaggerated Na⁺, K⁺-ATPase-stimulated aerobic glycolysis associated with epinephrine stimulation. We hypothesized that patients with sepsis without shock and increased epinephrine levels or an increased muscle-to-serum lactate gradient are likely to evolve towards septic shock. Thus, in sepsis patients, we investigated (1) whether muscle produces lactate and pyruvate, and (2) whether muscle lactate production is linked to epinephrine levels and the severity of the patient's condition.

We studied 40 ventilated patients with sepsis without shock or hyperlactatemia and a control group of 10 ICU patients without infection. A microdialysis probe was inserted into the quadriceps muscle. Plasma lactate and pyruvate concentrations were measured in both the dialysate fluid and arterial blood samples every 6 h.

There was no gradient between muscle and arterial levels for lactate and pyruvate in the control group. In the sepsis group, muscle lactate and pyruvate concentrations were consistently higher than the arterial levels (P < 0.01). Plasma epinephrine concentrations were also elevated (P < 0.05). A total of 15/40 patients further developed septic shock, and on admission these patients had significantly higher musculo-arterial gradients of lactate (2.9 ± 0.3 vs. 0.7 ± 0.2 mmol/l) (P < 0.05) and pyruvate (740 ± 60 vs. 200 ± 20 μmol/l) (P < 0.05), and higher levels of epinephrine concentrations (6.2 ± 0.7 vs. 2.5 ± 0.24 nmol/l) (P < 0.05). Both the lactate gradient and epinephrine concentrations measured on admission were good predictors of the evolution towards septic shock.

Muscle produces lactate and pyruvate during sepsis, and this production is highly correlated with plasma epinephrine secretion and severity of illness.