Zhe Li, Wan Chen, Chenglong Li, Lei Shi, Guozheng Qiu, Wenlong Duan, Mingyu Pei, Yao Zhou, Bo Wang, Xiaotong Hou, Liwen Lyu
In this multicenter retrospective study (Chinese Society of Extracorporeal Life Support [CSECLS] registry), we evaluated early lactate trajectories in 1,465 adults with cardiogenic shock surviving greater than 24 hours on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Unsupervised k-means clustering of serial lactates (baseline, 4 hours, 24 hours) defined four metabolic phenotypes. The "Persistent High" phenotype (5.7%) exhibited refractory hyperlactatemia (median 24 hour lactate 17.0 mmol/L) and the highest in-hospital mortality (85.7% vs. 27.9% in the "Low Stable" group; p < 0.001). Notably, this persistent hyperlactatemia occurred despite comparable ECMO flow indices (2.8 vs. 2.6 L/min/m2) and preserved venous oxygen saturation (72.2% ≥ 50%). The "Persistent High" trajectory independently predicted mortality (adjusted hazard ratio [HR]: 6.36, 95% confidence interval [CI]: 4.83-8.36) and severe organ failure, with findings reproduced in an external validation cohort (MIMIC-IV, n = 136). In conclusion, persistent hyperlactatemia during VA-ECMO may reflect impaired systemic oxygen utilization rather than insufficient macrocirculatory flow. Early trajectory-based phenotyping helps identify a refractory state of flow-metabolism decoupling, signaling a high-risk subgroup where conventional flow escalation alone may be insufficient.