J Anesth Perioper Med. 2018;5(3):125-135. https://doi.org/10.24015/ebcmed.JAPM.2017.0017

Thymosin α1-Based Immunomodulatory Therapy for Sepsis: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

Wan-Jie Gu, Xiao-Ping Gu, and Zheng-Liang Ma

From Department of Anesthesiology, Nanjing Drum Tower Hospital, Medical College of Nanjing University, Nanjing, China.

Correspondence to Dr. Zheng-Liang Ma at mazhengliang1964@nju.edu.cn.

EBCMED ID: ebcmed.JAPM.2017.0017 DOI: 10.24015/ebcmed.JAPM.2017.0017


Abstract

Background
Preclinical studies suggest that thymosin α1 has immunoregulatory and anti-inflammatory properties in various septic models. However, whether these effects will transform into improved outcomes in humans with sepsis remains unclear. We performed a meta-analysis to define the role of thymosin α1-based immunomodulatory therapy in sepsis.

Methods
We searched Medline and Embase to identify randomized controlled trials that assessed the effect of thymosin α1-based immunomodulatory therapy compared with standard care for adults with sepsis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. The primary outcome was 28-day mortality.

Results
Nine articles with 10 trials involving 1425 patients were included. Compared with standard care, thymosin α1-based immunomodulatory therapy was associated with a significant 31% relative risk reduction of 28-day mortality (RR 0.69, 95% CI 0.60-0.80, P<0.001), with no statistical heterogeneity (I2=0%). The benefit was confirmed by trial sequential analysis and was consistent across all subgroup analyses. For secondary outcomes, thymosin α1-based immunomodulatory therapy was associated with shorter length of intensive care unit (ICU) stay and duration of mechanical ventilation, increased T lymphocyte subsets (CD3+, CD4+, and CD4+/CD8+), and decreased inflammatory mediators (tumor necrosis factor- α, interleukin-1β, and interleukin-6).

Conclusions
Thymosin α1-based immunomodulatory therapy decreases 28-day mortality in patients with sepsis. The benefit might be attributed to its immunomodulatory and anti-inflammatory effects. However, caution should be used to translate these findings to clinical practice, because current evidence is potentially subject to bias. Hence, high-quality and adequately powered trials are still warranted. (PROSPERO registration number, CRD42016048421.)

Article Type
Systematic Review and Meta-Analysis

Declaration of Interests
The authors declare that they have no competing interests.

Acknowledgements
Authors’ Contributions: WJG conceived the study, participated in the design, collected the data, performed statistical analyses, and drafted the manuscript. XPG conceived the study, participated in the design, collected the data, and revised the manuscript critically for important intellectual content. ZLM conceived the study, participated in the design, collected the data, and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.