Decoupling lactate from DO2 VO2 rethinking the physiology of stress hyperlactatemia during cardiac failure

Abstract Introduction Lactate has traditionally been interpreted as a biomarker of tissue hypoxia and anaerobic metabolism. However, growing evidence shows that hyperlactatemia in critical illness may develop under fully aerobic conditions through β₂-adrenergic–driven glycolysis. In septic shock, elevated lactate often occurs despite adequate oxygen delivery, reflecting a stress-induced metabolic adaptation rather than an oxygen debt. While this concept is well established in sepsis, it remains largely unexplored in cardiogenic shock (CS), where lactate is still frequently viewed as a marker of oxygen delivery-to-consumption (DO₂/VO₂) imbalance and cellular hypoxia. Purpose This study tested whether lactate reliably reflects anaerobic metabolism by examining its relationship with the DO₂/VO₂ ratio in PAC-monitored cardiac ICU patients. Methods Simultaneous biochemical hemodynamic measurements of systemic oxygen delivery (DO₂=CO×1.34×Hb×SaO₂×10) and oxygen consumption (VO₂=13.4×CO×Hb×(SaO₂−SvO₂)) were paired with corresponding arterial lactate values. Correlation analyses and receiver operating characteristic (ROC) curves were performed to evaluate the association and discriminative ability of the DO₂/VO₂ ratio for predicting elevated lactate (≥4 mmol/L). Results We retrospectively analyzed 1,533 critically ill cardiac patients (86% post-surgical, 14% medical) admitted to a quaternary cardiac intensive care unit, all monitored with a PAC. Patients were predominantly male (67%) with a mean age of 59.6 ± 16.3 years; 63% had no prior cardiac history. Overall ICU mortality was 31.4% and mean vaso-inotropic score (VIS) was 19,8 (±13,6), indicating a very sick cardiac patient population under severe support. 3135 DO₂/VO₂ data points were matched with arterial lactate values. Across the cohort, DO₂/VO₂ values ranged from 0.98 to 9.95, while lactate concentrations varied between 0.3 and 20 mmol/L. There was no significant correlation between DO₂/VO₂ and lactate (r = 0.11, p 0.0001; Fig. panel A). ROC analysis (lactate ≥ 4 mmol/L), demonstrated poor discriminative capacity of DO₂/VO₂ for hyperlactatemia (AUC = 0.603, optimal DO₂/VO₂ cutoff = 2.85, sensitivity = 49%, specificity = 70%; Fig. panel B). These findings indicate that systemic oxygen delivery and consumption balance does not predict lactate elevation in a large cohort of cardiac critically ill patients. Conclusions In this large, invasively monitored cardiac ICU cohort, lactate concentration did not correlate with the DO₂/VO₂ ratio. These data suggest that elevated lactate is certainly not always a reliable indicator of anaerobic metabolism or oxygen debt. Instead, hyperlactatemia likely reflects stress-induced aerobic glycolysis mediated by catecholamine activity. The dissociation between lactate and DO₂/VO₂ in our cohort, underscores the need to interpret lactate elevation rather as part of an adaptive metabolic response, rather than as a direct measure of tissue hypoxia.