Evolution of lactate/pyruvate and arterial ketone body ratios in the early course of catecholamine-treated septic shock

Objectives: To measure arterial lactate/pyruvate (UP) and arterial ketone body ratios as reflection of cytoplasmic and mitochondrial redox state at different stages of catecholamine-treated septic shock and compare them with normal and pathologic values obtained in patients in shock who have decreased oxygen transport (cardiogenic shock), and to assess the relationship between the time course of lactate, VP ratio, and mortality in septic shock. Design: Prospective, observational human study. Setting: A university intensive care unit. Patients: Sixty consecutive adult patients who developed septic shock and lactic acidosis requiring the administration of vasopressors. Twenty patients in the intensive care unit without shack, sepsis, and hypoxia and with normal lactate values and 10 patients with cardiogenic shock were also studied. Measurements: Hemodynamic measurements, arterial and mixed venous blood gases, arterial lactate and pyruvate concentrations, and arterial ketone body ratio were measured within 4 hrs after the introduction of catecholamine and 24 hrs later. Main Results.. Fifteen patients (25%) died within the first 24 hrs of septic shock, and these early fatalities had a higher blood lactate (12.2 +/- 3 versus 4.6 +/- 1.3 mmol/L; p < .01) concentration and a higher VP ratio (37 +/- 4 versus 20 +/- 1; p < .01) than those who died later. No difference was found for arterial ketone body ratio (0.41 +/- 0.1 verses 0.50 +/- 0.06). Forty-five patients survived >24 hrs including 25 survivors and 20 nonsurvivors. Although there was no difference between survivors and nonsurvivors in initial lactate concentration (4.1 +/- 0.4 and 4.6 +/- 0.3, respectively), VP ratio (19 +/- 1 and 20 +/- 1, respectively), and arterial ketone body ratio (0.5 +/- 0.06 and 0.52 +/- 0.07, respectively), blood lactate and UP ratio significantly decreased during the first 24 hrs in the survivors (2.8 +/- 0.4 and 14 +/- 1, respectively; p < .05). and were stable in the nonsurvivors (4 +/- 0.3 and 22 +/- 1, respectively) Although returning to normal values after 24 hrs in survivors and nonsurvivors, arterial ketone body ratio was higher in survivors (1.72 +/- 0.17 versus 1.09 +/- 0.15; p < .05). Lactate and UP ratio were closely correlated (r(2) = .8, p < .0001). In the cardiogenic shock group, lactate concentration was 4 +/- 1 mmol/L, UP ratio was 40 +/- 6, and arterial ketone body ratio was 0.2 +/- 0.05. The mortality rate was 60%. Conclusions: The main result of the present study is that hemodynamically unstable patients with sepsis needing catecholamine therapy had a lactic acidosis with an elevated UP ratio and a decreased arterial ketone body ratio, suggesting a decrease in cytoplasmic and mitochondrial redox state. The duration of lactic acidosis is associated with the development of multiple organ failure and death.