Dynamic Lactate Trajectories are Associated with Mortality in Severe Pneumonia: A Retrospective Cohort Study with External Validation
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Rui Wang1, Ao Zhang2, Daonan Chen1
1Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, People's Republic of China.
Background:
Severe pneumonia represents a major threat to survival. Lactate, routinely measured in the intensive care unit (ICU), provides valuable clinical insights. Exploring its dynamic trajectories and their association with outcomes may help guide risk-stratified interventions and optimize management.
Methods:
This retrospective cohort study included patients with severe pneumonia from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (2008-2022, derivation cohort) and Shanghai General Hospital (2016-2024, external validation cohort). Latent growth mixture modeling (LGMM) was applied to five serial lactate measurements (0, 12, 24, 36, and 48 hours) to identify trajectory subgroups. The outcome was all-cause mortality at 28-, 60-, and 90-days. Associations between trajectories and mortality were assessed using Kaplan-Meier analysis and multivariable Cox regression, with sensitivity analyses including landmark analysis and restricted mean survival time estimation. Discriminative performance was assessed using Harrell's C-index.
Results:
In the derivation cohort (n = 870), four trajectories were identified: stable-normal (T1, 40.1%), fluctuating-worsening (T2, 7.8%), rapid-resolving (T3, 32.3%), and persistent-abnormal (T4, 19.8%). T2 was associated with the highest adjusted mortality risk at 28 days (HR 2.82, 95% CI 1.93-4.11), 60 days (HR 2.75, 95% CI 1.92-3.93), and 90 days (HR 2.63, 95% CI 1.85-3.73). T4 had the longest mechanical ventilation and ICU stay (p < 0.05). The same four trajectories were reproduced in the external validation cohort (n = 289), and T2 was again independently associated with 90-day mortality (HR 3.02, 95% CI 1.19-7.67, p = 0.02), although the four-group Log rank tests did not reach statistical significance in this smaller cohort.
Conclusion:
Dynamic lactate trajectories are associated with prognosis in severe pneumonia. The fluctuating-worsening trajectory (T2), in which lactate rose again after an initial decline to values around 7.5 mmol/L, was associated with the highest mortality in this cohort, whereas the persistent-abnormal trajectory (T4) was associated with prolonged mechanical ventilation and ICU stay without a significant increase in adjusted mortality.