Abstract

BackgroundVolatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation.MethodsA prospective, randomized, double-blind trial in living donor kidney transplant recipients was conducted at a single center, tertiary-care, academic university hospital in Thailand during August 2015 – June 2017. Sixty-six patients were assessed for eligibility and 40 patients who fulfilled the study requirement were equally randomized and allocated to desflurane versus sevoflurane anesthesia during transplant surgery. The primary outcome included absolute changes of peripheral blood CD4+CD25+FoxP3+Tregs which measured by flow cytometry and expressed as the percentage of the total population of CD4+ T lymphocytes at pre-exposure (0-h) and post-exposure (2-h and 24-h) to anesthetic gas. P-value < 0.05 denoted statistical significance.ResultsDemographic data were comparable between groups. No statistical difference of peripheral blood Tregs between desflurane and sevoflurane groups observed at the baseline pre-exposure (3.6 ± 0.4% vs. 3.1 ± 0.4%; p = 0.371) and 2-h post-exposure (3.0 ± 0.3% vs. 3.5 ± 0.4%; p = 0.319). At 24-h post-exposure, peripheral blood Tregs was significantly higher in desflurane group (5.8 ± 0.5% vs. 4.1 ± 0.3%; p = 0.008). Within group analysis showed patients receiving desflurane, but not sevoflurane, had 2.7% increase in peripheral blood Treg over 24-h period (p < 0.001).ConclusionThis study provides the clinical trial-based evidence that desflurane induced peripheral blood Tregs increment after 24-h exposure, which could be beneficial in the context of kidney transplantation. Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future.Trial registrationClinicalTrials.gov, NCT02559297. Registered 22 September 2015 - retrospectively registered

Highlights

  • Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes

  • This study provides the clinical trial-based evidence that desflurane induced peripheral blood Regulatory T cells (Tregs) increment after 24-h exposure, which could be beneficial in the context of kidney transplantation

  • Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future

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Summary

Introduction

Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation. Evidence indicates CD4+CD25+FoxP3+ cells, commonly known as regulatory T cells (Tregs), play a critical role in preventing graft rejection by suppression of recipient alloimmune response [5,6,7,8]. High peripheral blood Tregs were associated with stable graft function. Low peripheral blood Tregs was associated with allograft rejection [12,13,14,15,16,17]

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