Anesthesia in Patients With Mitochondrial Disease

Study Overview
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Brief Summary
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This pilot study is a prospective, randomized clinical trial to evaluate the effect of anesthesia in the mitochondrial dysfunction patient.

Detailed Description
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Study subjects undergoing a routine medical care non-emergent procedure will be randomized into three different groups to receive one of the following anesthetic agents; Sevoflurane, Propofol or Dexmedetomidine. The primary outcome of this pilot study is to evaluate and compare the incidence of adverse events in mitochondrial patients undergoing a diagnostic or therapeutic procedure up to 48 hours post anesthesia. The secondary outcome is to compare the metabolic derangements between three study groups by comparing changes in blood sugar, serum pH, serum bicarbonate, serum lactate and serum pyruvate levels before, during and after anesthesia in the groups.

Official Title
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Anesthesia in Patients With Mitochondrial Disease

Conditions
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Mitochondrial Diseases

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Dexmedetomidine
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must fulfill the following inclusion criteria: Subject is informed and given ample opportunity to consider his/her participation and has given his/her written consent. Subject is willing and able to comply with all study requirements. Subject is between 0 - 17 years of age. Subject has been diagnosed with mitochondrial dysfunction based on modified Walker criteria. Subject is scheduled to have a non-emergent diagnostic or therapeutic procedure for routine medical care requiring general anesthesia estimated to last at least one hour. Subject is classified ASA I - IV Exclusion Criteria: Subjects are not permitted to enroll in the study if any of the following criteria are met: Subject is older than 17 years Subject is pregnant Subject is a nursing female and Subject has participated in the same study within 48 hours Subject is allergic or has had any adverse effect to any of the study agents in the past Anesthesia time is less than one hour Subject is classified ASA V

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 17 Years

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sevoflurane<br>In the Operating Room (OR) after applying routine monitors, anesthesia will be induced with a mask using Sevoflurane up to 8%. Sevoflurane will be used for maintenance for the rest of the procedure with dosage between 1.5% and 4%. Vitals will be monitored. Fentanyl will be used as needed. Rocuronium will be used as needed for muscle relaxation. At the end of the procedure twitches will be evaluated and muscle relaxation will be reversed. Sevoflurane will be turned off at the end of procedure. | Drug: Sevoflurane<br>* Sevoflurane up to 8% will be administered to study subjects<br>* Other names: Ultane;|
| Active Comparator: Dexmedetomidine (Precedex®)<br>These subjects will receive Dexmedetomidine intravenously. In the OR routine monitors will be placed. Vitals will be monitored. A loading dose of Precedex 1mcg/ kg will be given over 10 minutes. Infusion will be started using Precedex 1mcg/ kg/ hr and can be increased or decreased as needed. Fentanyl will be used as needed. Rocuronium will be used as needed for muscle relaxation. At the end of the procedure twitches will be evaluated and muscle relaxation will be reversed. Precedex infusion will be stopped at the end of the procedure. | Drug: Dexmedetomidine<br>* Dexmedetomidine (Precedex) infusion starting at 1mcg/ kg/ hr will be administered to study subjects.<br>* Other names: Precedex;|
| Active Comparator: Propofol<br>These subjects will receive propofol for anesthesia maintenance. In the OR routine monitors will be placed. Vitals will be monitored. A loading dose of Propofol 2mg/ kg will be given over 2 minutes. Infusion will be started using Propofol 50 mcg/ kg/min and can be increased or decreased as needed (range 50-300mcg/kg/min). Fentanyl will be used as needed. Rocuronium will be used as needed for muscle relaxation. At the end of the procedure twitches will be evaluated and muscle relaxation will be reversed. Propofol infusion will be stopped at the end of the procedure. | Drug: Propofol<br>* Propofol up to 50 mcg/ kg/min will be administered to study subjects.<br>* Other names: Diprivan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure of this study is to evaluate and compare the incidence of adverse events in mitochondrial patients undergoing a diagnostic or therapeutic procedure between the three drug groups. | An adverse event (AE) is any untoward medical occurrence in a subject, compared with pre-existing condition that occurs during any phase of the research study. An AE is defined as being independent of assumption of any causality. The following laboratory values and physical findings are to be considered AEs: Laboratory value(s) of blood glucose, serum lactate, serum pyruvate, serum bicarbonate and pH that change from a subject's baseline by greater than 10% and is outside the normal range. Any of the following parameters; feeding difficulties, temperature >100 F, vomiting, nausea, lethargy, change in admission plan and any other change in baseline that are clinically relevant. | Up to 48 hours post anesthesia. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitochondrial Diseases, Sevoflurane, Dexmedetomidine (Precedex®), Propofol