Does Sevoflurane Cause Genomic Damage

Anesthesia; Adverse Effect Clinical Trial

Official title:

Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03109119
• Other study ID #: 08/16/IEC / JMMC&RI
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2018
• Est. completion date: December 2019

Study information

• Verified date: January 2019
• Source: Jubilee Mission Medical College and Research Institute
• Contact: Vigil Peter, MD
• Phone: 918593821000
• Email: drpeteralapatt[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to find out if sevoflurane causes any cell damage to patients undergoing general anaesthesia. In case of any damage, the reversibility of the damage is also assessed. This is a prospective, comparative study carried out in all children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery under Smile Train organisation ìn our hospital,who satisfy the inclusion and exclusion criteria.

Description:

STUDY GOALS AND OBJECTIVES

1. To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair.

2. To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia.

3. To evaluate the reversibility of the induced genomic instability when exposure is discontinued.

STUDY DESIGN Type of study : Prospective Comparative Study Research population : All children scheduled for surgical repair of cleft lip or palate admitted in the Department of Plastic Surgery of our hospital, who satisfy the inclusion and exclusion criteria.

Sample Size : A total of 30 children will be enrolled for the study. METHODOLOGY Children scheduled to undergo surgical repair of cleft lip or palate were enrolled for the study, after addressing the inclusion and exclusion criteria.

A peripheral blood sample of 1.5 ml (S-1) will be taken before the induction of anaesthesia .All children will be randomly allocated into two groups - group S and P.All children will be premedicated with Inj.Glycopyrolate 0.01 mg/kg . Children in group S will be induced with sevoflurane, whereas children in group P will be induced with propofol.All children will be intubated using I / V Vecuronium 0.1 mg / kg .Analgesia will be provided using I / V Fentanyl 1.5 mcg / kg. Depth of anaesthesia will be maintained with sevoflurane in group S and with propofol infusion in group P. The vitals will be monitored as usual intraop and the children will be extubated at the end of the surgery.

Peripheral blood samples of 1.5 ml each will be taken immediately after extubation (S-2) , after 48 hours (S-3)and after 120 hours (S-4).A fifth blood sample (S-5) will be taken on the 14th postoperative day All the blood samples will be evaluated for genomic instability using Alkaline Comet Assay by the Genetics Lab of our hospital.

STATISTICAL ANALYSIS

The findings of this study will be analysed using Chi-square test, Student's t-test, Mann-Whitney U test, mean and standard deviation to yield the final results. The study will be considered statistically significant with a p value of less than 0.05

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Months

Eligibility

Inclusion Criteria

• Children must have isolated cleft lip or palate.

• The surgery must be a primary repair of cleft lip or palate.

• The minimum duration of the surgery must be 90 minutes.

Exclusion Criteria

• Children who have undergone previous surgery.

• Children who have syndromic cleft lip or palate.

• Children with bleeding disorders.

• Children with known allergy to any of the concerned drugs.

Related Conditions & MeSH terms

• Anesthesia; Adverse Effect

Intervention

Drug:
• Sevoflurane
The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.
• Propofol
These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.

Locations

Country	Name	City	State
India	Jubilee Mission Medical College and Research Institute	Thrissur	Kerala

Sponsors (1)

Lead Sponsor	Collaborator
Jubilee Mission Medical College and Research Institute

Country where clinical trial is conducted

India, 

References & Publications (8)

Alcaraz M, Quesada S, Armero D, Martin-Gíl R, Olivares A, Achel GD. Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation. Colomb Med (Cali). 2014 Sep 30;45(3):104-9. eCollection 2014 Jul-Sep. — View Citation

Braz MG, Braz LG, Barbosa BS, Giacobino J, Orosz JE, Salvadori DM, Braz JR. DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia. Mutat Res. 2011 Dec 24;726(2):251-4. doi: 10.1016/j.mrgentox.2011.09.00 — View Citation

Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 1999 Jul 16;428(1-2):271-83. Review. — View Citation

Musak L, Smerhovsky Z, Halasova E, Osina O, Letkova L, Vodickova L, Polakova V, Buchancova J, Hemminki K, Vodicka P. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Wor — View Citation

Rozgaj R, Kasuba V, Brozovic G, Jazbec A. Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health. 2009 Jan;212(1):11-7. Epub 2007 Nov 26. — View Citation

Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jaloszynski P. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet. 2004;45(3):369-74. — View Citation

Tania K.de Araujo, Roseane L, Flora M.B.B, Nilson C.R, Cristina W.P, Ricardo Manoel da Cruz et al-Genotoxic effects of anaesthetics in OT personnel evaluated by micronuclei tests Journal of Anaesthesia and Clinical Science ISSN 2049-9752,10.7243/2049-9752

Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008 Aug;63(8):861-4. doi: 10.1111/j.1365-2044.2008.05498 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genomic instability	Genomic instability will be assessed using comet assay	It will be assessed at 2 hours after anaesthesia.
Primary	Genomic instability	Genomic instability will be assessed using comet assay.	It will be assessed 48 hours after anaesthesia.
Secondary	Reversibility of the genomic instability	Assessed using comet assay	It will be assessed on fifth day after anaesthesia.
Secondary	Reversibility of genomic instability	It will be assessed using comet assay.	It will be assessed on the 14th day after anaesthesia.