Dynamic Lactate Trajectories are Associated with Mortality in Severe Pneumonia: A Retrospective Cohort Study with External Validation
- 1Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, People’s Republic of China
- 2Department of Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, 201600, People’s Republic of China
Abstract
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.
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BibTeX
@article{wang2026dynamic,
title = {{Dynamic Lactate Trajectories are Associated with Mortality in Severe Pneumonia: A Retrospective Cohort Study with External Validation}},
author = {Rui Wang and Ao Zhang and Daonan Chen and Cheng Chen and Ruilan Wang},
journal = {Journal of Inflammation Research},
year = {2026},
month = oct,
doi = {10.2147/jir.s632447},
url = {https://doi.org/10.2147/jir.s632447},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Dynamic Lactate Trajectories are Associated with Mortality in Severe Pneumonia: A Retrospective Cohort Study with External Validation
AU - Rui Wang
AU - Ao Zhang
AU - Daonan Chen
AU - Cheng Chen
AU - Ruilan Wang
PY - 2026
DA - 2026/10/27
JO - Journal of Inflammation Research
DO - 10.2147/jir.s632447
UR - https://doi.org/10.2147/jir.s632447
AB - 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.
SN - 1178-7031
ER -