Purpose In this study, we sought to investigate the relationship between lactate clearance rate per hour (LCRperhour) and 28-day mortality, aiming to determine the inflection point where changes in LCRperhour correspond to significant shifts in mortality risk. Methods We conducted a retrospective analysis using the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU databases (eICU Collaborative Research Database), including patients with sepsis with a peak lactate level (Lacpeak) ≥ 2 mmol·L−1 within 24 hr of intensive care unit (ICU) admission. Using the key lactate metrics Lacpeak, lactate decline (Lacdecline), and decline duration (Timedecline), we calculated the LCRperhour as: (Lacpeak – Lacdecline) ÷ (Lacpeak × Timedecline). Peak lactate level was the highest lactate measured within the first 24 hrs of ICU admission, and Lacdecline was the first lactate measurement captured after the peak value. We assessed its association with 28-day mortality via odds ratios (ORs) using multivariable logistic regression. We examined the linearity of the relationship using an adjusted restricted cubic spline (RCS) model. We stratified patients into high- and low-lactate-clearance groups on the basis of the RCS inflection point. We conducted a subgroup mortality analysis for patients with a Lacpeak below or above 4 mmol·L−1. Results We retrospectively analyzed data from 53,150 patients from the MIMIC-IV database and 55,887 patients from the eICU database; of these, 13,586 patients with sepsis met the inclusion criteria. Among these, 3,313 (24.4%) patients died within 28 days. Multivariable logistic regression showed that a higher LCRperhour was significantly associated with reduced 28-day mortality (OR, 0.03; 95% confidence interval, 0.01 to 0.09; P < 0.001). The adjusted RCS model revealed a reverse J-shaped relationship between LCRperhour and 28-day mortality (overall P < 0.001; P for nonlinearity < 0.001), with an inflection point on the OR curve at an LCRperhour value of 0.11. Among patients with high lactate levels (> 4 mmol·L−1) and those with low lactate levels (2–4 mmol·L−1), the mortality was significantly lower in those with a LCRperhour ≥ 0.11 than in those with a LCRperhour < 0.11 (both P < 0.05). Conclusions In patients with sepsis, the relationship between lactate clearance during resuscitation and 28-day mortality was nonlinear. The mortality rate declined steeply with increasing lactate clearance until a point was reached, after which the survival benefit plateaued. These findings provide new insights for clinicians in defining individualized endpoints for fluid resuscitation in sepsis management.

Association between lactate clearance rate and 28-day mortality in patients with sepsis: a retrospective cohort study and exploration of an optimal lactate clearance as an endpoint of resuscitation

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发表日期：

2026年6月22日

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Taotao Liu,
Mei Wang

摘要

Purpose

In this study, we sought to investigate the relationship between lactate clearance rate per hour (LCR_perhour) and 28-day mortality, aiming to determine the inflection point where changes in LCR_perhour correspond to significant shifts in mortality risk.

Methods

We conducted a retrospective analysis using the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU databases (eICU Collaborative Research Database), including patients with sepsis with a peak lactate level (Lac_peak) ≥ 2 mmol·L⁻¹ within 24 hr of intensive care unit (ICU) admission. Using the key lactate metrics Lac_peak, lactate decline (Lac_decline), and decline duration (Time_decline), we calculated the LCR_perhour as: (Lac_peak – Lac_decline) ÷ (Lac_peak × Time_decline). Peak lactate level was the highest lactate measured within the first 24 hrs of ICU admission, and Lac_decline was the first lactate measurement captured after the peak value. We assessed its association with 28-day mortality via odds ratios (ORs) using multivariable logistic regression. We examined the linearity of the relationship using an adjusted restricted cubic spline (RCS) model. We stratified patients into high- and low-lactate-clearance groups on the basis of the RCS inflection point. We conducted a subgroup mortality analysis for patients with a Lac_peak below or above 4 mmol·L⁻¹.

Results

We retrospectively analyzed data from 53,150 patients from the MIMIC-IV database and 55,887 patients from the eICU database; of these, 13,586 patients with sepsis met the inclusion criteria. Among these, 3,313 (24.4%) patients died within 28 days. Multivariable logistic regression showed that a higher LCR_perhour was significantly associated with reduced 28-day mortality (OR, 0.03; 95% confidence interval, 0.01 to 0.09; P < 0.001). The adjusted RCS model revealed a reverse J-shaped relationship between LCR_perhour and 28-day mortality (overall P < 0.001; P for nonlinearity < 0.001), with an inflection point on the OR curve at an LCR_perhour value of 0.11. Among patients with high lactate levels (> 4 mmol·L⁻¹) and those with low lactate levels (2–4 mmol·L⁻¹), the mortality was significantly lower in those with a LCR_perhour ≥ 0.11 than in those with a LCR_perhour < 0.11 (both P < 0.05).

Conclusions

In patients with sepsis, the relationship between lactate clearance during resuscitation and 28-day mortality was nonlinear. The mortality rate declined steeply with increasing lactate clearance until a point was reached, after which the survival benefit plateaued. These findings provide new insights for clinicians in defining individualized endpoints for fluid resuscitation in sepsis management.