Does Sevoflurane Cause Genomic Damage

Study Overview
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Brief Summary
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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.

Detailed Description
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STUDY GOALS AND OBJECTIVES To find out if sevoflurane induces genomic instability in children undergoing cleft lip and palate repair. To assess the magnitude of genomic damage caused by the sevoflurane anaesthesia. 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

Official Title
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Does Sevoflurane Induce Genomic Instability in Patients Undergoing General Anaesthesia?

Conditions
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Anesthesia; Adverse Effect

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All children will be randomly allocated into two groups - group S and P. Children in group S will be anaesthetised with sevoflurane, whereas children in group P will be anaesthetised with propofol. 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. These blood samples will be evaluated for genomic instability using Alkaline Comet Assay and micronucleus test by the Genetics Lab of our hospital.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group S<br>These patients will be induced and maintained with sevoflurane during anaesthesia. | Drug: Sevoflurane<br>* The patients in the group S will be exposed to routine concentrations of sevoflurane during anaesthesia.<br>* Other names: sevorane;|
| Sham Comparator: Group P<br>These patients will be induced and maintained with propofol during anaesthesia. | Drug: Propofol<br>* These patients will be induced with propofol 1.5 mg / kg and maintained with propofol infusion.<br>* Other names: fresofol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomic instability | Genomic instability will be assessed using comet assay | It will be assessed at 2 hours after anaesthesia. | 
| Genomic instability | Genomic instability will be assessed using comet assay. | It will be assessed 48 hours after anaesthesia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reversibility of the genomic instability | Assessed using comet assay | It will be assessed on fifth day after anaesthesia. | 
| Reversibility of genomic instability | It will be assessed using comet assay. | It will be assessed on the 14th day after anaesthesia. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genomic instability, Sevoflurane, General anaesthesia