Testing the Transportability of Sepsis Subtypes to Patients With ARDS for Postdischarge Outcomes

Survivors of ARDS experience significant morbidity and mortality after hospital discharge. A latent class analysis (LCA) proposed 5 sepsis survivor subtypes that may be of use for ARDS patients as well, but did not include an operationalization algorithm for assigning patients to subtypes.

Can the Taylor sepsis survivor subtypes be operationalized in an ARDS population, and does such operationalizations distinguish patients at varying risk of post-discharge mortality and readmission?

We conducted a secondary analysis of adults with acute respiratory distress syndromes requiring mechanical ventilation enrolled in the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial. We compared two methods of operationalizing subtype to develop an assignment rule: transported subtypes based on an algorithm developed using five variables from the previously published derivation cohort, and de novo subtypes derived from a new latent class analysis (LCA). Random-effect logit models were used to estimate the association between subtype and the primary outcome of mortality at 12 months.

580 participants were assigned to five subtypes using the transported approach. In age-adjusted regression, transported subtype was significantly associated with mortality at 12 months (p=0.027) and readmission at 3 months (p=0.043). A de novo LCA identified 5 distinct subtypes as the optimal solution; subtypes were associated with mortality at 3, 6, and 12 months (p<0.001) and readmission at 3 months (p=0.008). Agreement between the two assignment methods was 48% (kappa 0.361), and concentrated in the lowest (134/145, 92.4%) and highest risk (44/44, 100%) groups.

Sepsis survivor subtypes can be transported and operationalized in ARDS patients. Different approaches to operationalization yield similar but not identical subgroups classifications. Both approaches assign individuals to groups that are significantly associated with patient-important outcomes among ARDS survivors. Optimal strategies to transport externally derived subtypes, versus internal rederivation, may depend on the specific use case.