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The following is a summary of “Derivation and validation of generalized sepsis-induced acute respiratory failure phenotypes among critically ill patients: a retrospective study,” published in the October 2024 issue of Critical Care by Choudhary et al. 

Patients with sepsis suffering from acute respiratory failure requiring (ARF) mechanical ventilation exhibit a heterogeneous clinical course, and identifying distinct phenotypes may reveal insights into the broader heterogeneity of sepsis.  

Researchers conducted a retrospective study to examine novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes.  

They evaluated patients in the ICU with sepsis who required mechanical ventilation for at least 24 hours. Data from 2 high-volume academic hospital centers were used, where all phenotypes were derived in the medical ICU (MICU) of Hospital-I (N=3225). The derived phenotypes were validated in the MICU of Hospital-II (N=848), surgical ICU (SICU) of Hospital-I (N=1112), and SICU of Hospital-II (N=465). Clinical data from the 24 hours preceding intubation were employed to derive distinct phenotypes by a machine learning-based clustering model interpreted by clinical professionals.  

The results showed 4 distinct ARF phenotypes: severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure, severe hypoxemic respiratory failure with a median P/F ratio of 123, mild hypoxia with a median P/F ratio of 240, and severe MOD with hepatic injury, coagulopathy, and lactic acidosis. Patients in each phenotype differed in clinical course and mortality rates with similar demographics and admission co-morbidities. The phenotypes were produced in an external validation using the MICU of Hospital-II and SICUs from Hospital-I and -II. A significant difference in 28-day mortality was analyzed by Kaplan-Meier across the phenotypes (P< 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated different treatment effects associated with a high positive end-expiratory pressure (PEEP) strategy.  

They concluded that the phenotypes showed special characteristics of organ injury and differences in clinical outcomes, which might help inform future research and clinical trial design for tailored management strategies. 

Source: ccforum.biomedcentral.com/articles/10.1186/s13054-024-05061-4