Early Immunoparalysis Was Associated with Poor Prognosis in Elderly Patients with Sepsis: Secondary Analysis of the ETASS Study

Abstract

Purpose

Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality.

Patients and Methods

A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome.

Results

Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis 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 and immunotherapy did not affect the outcomes.

Conclusion

The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

Keywords:

• early immune status
• elderly
• mHLA-DR
• immunosuppression
• immunoparalysis
• sepsis

Acknowledgments

We would like to thank all of the doctors, nurses, technicians, and patients involved at the six participating centres for their dedication to the ETASS study.

Abbreviations

APACHE II, Acute Physiology and Chronic Health Evaluation II; CIs, confidence intervals; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; ETASS, Efficacy of Thymosin Alpha 1 for Severe Sepsis; ICU, intensive care unit; IQR, interquartile range; MAP, mean arterial pressure; mHLA-DR, monocyte human leukocyte antigen-DR; MV, mechanical ventilation; ORs, odds ratios; RRT, renal replacement therapy; SBP, systolic blood pressure; SD, standard deviation; SOFA, sequential organ failure assessment; SSC, surviving sepsis campaign; Tα 1, thymosin alpha 1.

Data Sharing Statement

The datasets in this study are available from the corresponding author on reasonable request.

Ethics Approval

The original study was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University, the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, the Ethics Committee of Sixth Affiliated Hospital, Sun Yat-sen University, the Ethics Committee of Sun Yat-sen University Cancer Center, Sun Yat-sen University, the Ethics Committee of Foshan First Municipal People’s Hospital and the Ethics Committee of Guangzhou First Municipal People’s Hospital. Written informed consents were obtained from patients or next of kin for patients unable to consent. The clinical trial registry number is NCT0711620. We make sure to conduct this trial in accordance with the Declaration of Helsinki.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare that they have no competing interests.