Effects of Sevoflurane and Desflurane on Treg

Transplant; Failure, Kidney Clinical Trial

Official title:

Effects of Sevoflurane and Desflurane Anesthesia on Regulatory T Cells in Patients Undergoing Living Donor Kidney Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02559297
• Other study ID #: 04-58-23
• Status: Completed
• Phase: Phase 2
• First received: September 22, 2015
• Last updated: June 14, 2017
• Start date: August 10, 2015
• Est. completion date: June 3, 2017

Study information

• Verified date: June 2017
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective interventional study aims to compare sevoflurane and desflurane anesthetic agents on regulatory T cell (Treg) numbers and its cytokine production in patients undergoing Living Donor Kidney Transplant (LDKT).

Description:

All patients with end stage renal disease (ESRD) need renal replacement therapy, either dialysis or kidney transplantation. Dialysis, despite its effectiveness in prolonging ESRD patients' lives, is a burden. Successfulness in kidney transplantation will restore good quality of life in ESRD patients. However, one of the most important complications that lead to transplant failure is graft rejection. It is already known that the pathophysiology of the rejection is immune response. Recent evidence showed that regulatory T cell (Treg) plays a central role in preventing graft rejection by inhibiting recipient alloimmune response (1-3). Characterization of Treg numbers and/or functional changes under various conditions may lead to a new preventive measure and/or a novel therapeutic strategy for graft rejection.

Kidney transplantation is conducted under general anesthesia. Interestingly, several agents used in general anesthesia have also modulated immune functions (4-12). Although the effect of inhalation anesthetic agents on leukocyte count has been shown, the effect on Treg function has totally been unknown. Knowing the effects of inhalation agents on Treg numbers and functions will be beneficial to intraoperative management during transplant surgery, aiming toward reducing the risk of graft rejection in the future.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 3, 2017
• Est. primary completion date: June 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients receiving 1st living donor kidney transplantation

Exclusion Criteria:

• Hyperacute graft rejection

• Pre-existing autoimmune or immunodeficiency diseases in recipients

• Receiving blood product during 24-h perioperative period

• Patient refuse to participate this study at any time point

Related Conditions & MeSH terms

• Renal Insufficiency
• Transplant; Failure, Kidney

Intervention

Drug:
• Sevoflurane
After induction of anesthesia and successful intubation, 2 L/min N2O, 2 L/min O2 , and 2% to 2.5% sevoflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 minimal alveolar concentration (MAC) of sevoflurane in 50% O2 and 50% N2O. Ventilation will be adjusted to keep end-tidal carbon dioxide 30-35 mmHg (Tidal volume 7-10 mL/kg).
• Desflurane
After induction of anesthesia and successful intubation, 2 L/min N2O, 2 L/min O2 , and 6% to 8% desflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 minimal alveolar concentration (MAC) of desflurane in 50% O2 and 50% N2O. Ventilation will be adjusted to keep end-tidal carbon dioxide 30-35 mmHg (Tidal volume 7-10 mL/kg).

Locations

Country	Name	City	State
Thailand	Ramathibodi Hospital	Ratchathewi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (12)

Edozie FC, Nova-Lamperti EA, Povoleri GA, Scottà C, John S, Lombardi G, Afzali B. Regulatory T-cell therapy in the induction of transplant tolerance: the issue of subpopulations. Transplantation. 2014 Aug 27;98(4):370-9. doi: 10.1097/TP.0000000000000243. Review. — View Citation

Hisano T, Namba T, Hashiguchi-Ikeda M, Ito T, Hirota K, Fukuda K. Inhibition of E-selectin-mediated leukocyte adhesion by volatile anesthetics in a static condition. J Anesth. 2005;19(1):1-6. — View Citation

Ji FH, Wang YL, Yang JP. Effects of propofol anesthesia and sevoflurane anesthesia on the differentiation of human T-helper cells during surgery. Chin Med J (Engl). 2011 Feb;124(4):525-9. — View Citation

Kim WH, Jin HS, Ko JS, Hahm TS, Lee SM, Cho HS, Kim MH. The effect of anesthetic techniques on neutrophil-to-lymphocyte ratio after laparoscopy-assisted vaginal hysterectomy. Acta Anaesthesiol Taiwan. 2011 Sep;49(3):83-7. doi: 10.1016/j.aat.2011.08.004. Epub 2011 Sep 22. — View Citation

Koksoy S, Sahin Z, Karsli B. Comparison of the effects of desflurane and bupivacaine on Th1 and Th2 responses. Clin Lab. 2013;59(11-12):1215-20. — View Citation

Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, Hoetzel A, Schmidt R, Borner C, Pahl HL, Geiger KK, Pannen BH. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005 Jun;102(6):1147-57. — View Citation

López-Hoyos M, Segundo DS, Fernández-Fresnedo G, Marín MJ, González-Martín V, Arias M. Regulatory T cells in renal transplantation and modulation by immunosuppression. Transplantation. 2009 Aug 15;88(3 Suppl):S31-9. doi: 10.1097/TP.0b013e3181af7b99. Review. — View Citation

Pirbudak Cocelli L, Ugur MG, Karadasli H. Comparison of effects of low-flow sevoflurane and desflurane anesthesia on neutrophil and T-cell populations. Curr Ther Res Clin Exp. 2012 Feb;73(1-2):41-51. doi: 10.1016/j.curtheres.2012.02.005. — View Citation

San Segundo D, Millán O, Muñoz-Cacho P, Boix F, Paz-Artal E, Talayero P, Morales JM, Muro M, De Cos MÁ, Guirado L, Llorente S, Pascual J, Arias M, Brunet M, López-Hoyos M. High proportion of pretransplantation activated regulatory T cells (CD4+CD25highCD62L+CD45RO+) predicts acute rejection in kidney transplantation: results of a multicenter study. Transplantation. 2014 Dec 15;98(11):1213-8. doi: 10.1097/TP.0000000000000202. — View Citation

Schneemilch CE, Hachenberg T, Ansorge S, Ittenson A, Bank U. Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. — View Citation

Zhang T, Fan Y, Liu K, Wang Y. Effects of different general anaesthetic techniques on immune responses in patients undergoing surgery for tongue cancer. Anaesth Intensive Care. 2014 Mar;42(2):220-7. — View Citation

Zhou D, Gu FM, Gao Q, Li QL, Zhou J, Miao CH. Effects of anesthetic methods on preserving anti-tumor T-helper polarization following hepatectomy. World J Gastroenterol. 2012 Jun 28;18(24):3089-98. doi: 10.3748/wjg.v18.i24.3089. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of regulatory T cells	Assessing change of Treg numbers by flow cytometry from baseline (before exposure to sevoflurane or desflurane) to after exposure to sevoflurane or desflurane for 2-h and 24-h	Within 24-h peri-operative period
Secondary	T lymphocyte cytokine production	Assessing change of T lymphocyte cytokine production using Multiplex immunoassay of interleukin (IL)-10, Tumor Necrosis Factor (TGF)-beta, IL-2, Interferon (IFN)-gamma, IL-4, IL-5, IL-13, from baseline (before exposure to sevoflurane or desflurane) to after exposure to sevoflurane or desflurane for 2-h and 24-h	Within 24-h peri-operative period