Abstract
BACKGROUND: Sepsis is a highly heterogeneous organ dysfunction syndrome. There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels. We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients. METHODS: The Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU databases were used to conduct a retrospective cohort study. Adult sepsis patients were included. Lactate was measured via blood gas, and the same assay type was used across both databases. Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission. The first measurement window (T1) comprised the initial 24 h post-admission, whereas the second window (T2) covered 24-48 h post-admission. The lactate difference was defined as the numerical change between the highest lactate level at T2 and the highest level at T1. The time interval between these two measurements was fixed, with T2 commencing immediately after T1, together encompassing the first 48 h post-ICU admission. A normal lactate level was defined as ≤2 mmol/L, and an elevated level was defined as >2 mmol/L. Sepsis patients were stratified into four trajectory phenotypes: (1) normal‒normal (N‒N); (2) normal-elevated (N‒E); (3) elevated-normal (E‒N); and (4) elevated-elevated (E‒E). The primary outcome was in-hospital mortality. RESULTS: This study enrolled 6,926 sepsis patients. The clinical phenotypes of the sepsis patients were as follows: N‒N (24.4%), N‒E (3.8%), E‒N (36.4%), and E‒E (35.3%). The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows (N‒N: 18.9% vs. 17.6%, P=0.66; N‒E: 35.3% vs. 29.2%, P=0.45; E‒N: 16.6% vs. 14.2%, P=0.14; E‒E: 43.6% vs. 37.8%, P=0.01). After adjusting for age, sex, Sequential Organ Failure Assessment (SOFA) score, vasopressor therapy, and infection sites, the N‒E phenotype was associated with a higher risk of in-hospital mortality (odds ratio [OR] 1.44; 95% confidence intervals [95% CI] 1.11-1.86; P=0.006; adjusted OR 1.61; 95% CI 1.23-2.11; P<0.001). The E‒N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis (adjusted OR 0.41; 95% CI 0.36-0.46; P<0.001). The E‒E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort (adjusted OR 3.00; 95% CI2.67-3.37; P<0.001). CONCLUSION: In sepsis patients with normal initial lactate levels, serial lactate measurements could be valuable for prognostic assessment.