Early immunosuppression was associated with poor prognosis in elderly patients with sepsis: secondary analysis of the ETASS study

Background: Although immunosuppression has been investigated in adult septic patients, early immune status remains unclear. In this study, we aimed to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Methods: From post hoc analysis of a multicenter, randomized controlled trial, 273 patients whose levels of monocyte human leukocyte antigen-DR (mHLA-DR) were obtained within 48 hours after onset of sepsis were enrolled. All patients were divided into elderly (≥60yrs) group and non-elderly (<60yrs) group. Early immune status was evaluated by the percentage of mHLA-DR in total monocytes within 48 hours after onset of sepsis and it was classified as immunosuppression (mHLA-DR≤30%) or non-immunosuppression (>30%). Changes in immune status were assessed by the value change in mHLA-DR on day 3 compared with the first measurement. Three logistic regression models were conducted to test the associations between early immunosuppression and hospital mortality. We also did a sensitivity analysis to find out if the definition of early immune status (24 vs. 48 hours after onset of sepsis) affects the outcomes. Results: Of the 181 elderly and 92 non-elderly septic patients, 71 (39.2%) elderly and 25 (27.2%) non-elderly died in hospital. The percentage of early immunosuppression in the elderly was twice of that of the non-elderly patients (32% vs. 16%, p=0.006). Immunosuppressed elderly had higher hospital mortality than the non-immunosuppressed elderly (53.4% vs. 32.5%, p=0.009), but there was no significant difference in mortality between immunosuppresed non-elderly patients and non-immunosuppressed non-elderly patients (33.5% vs. 26.0%, p=0.541). In all of the three logistic regression models, we found that early immunosuppression was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status did not affect the outcomes. In addition, immune status improvement on day 3 was associated with reduced hospital mortality in both elderly and non-elderly patients. Conclusion: In adult patients with sepsis, the elderly were more susceptible to early immunosuppression after onset of sepsis. Early immunosuppression was independently associated with poor prognosis in elderly patients. Trial registration: ClinicalTrials.gov NCT00711620 , 9 July 2008, https://clinicaltrials.gov/ct2/show/NCT00711620