Anesthetic Effects in Mitochondrial Disease

Summary. At the present, the investigators do not have the perfect anesthetic for mitochondrial patients. When possible, consideration should be given to the use of local anesthetics in small amounts. When a general anesthetic is necessary, they each carry significant risks and have been associated with poor outcomes. At present it is not possible to eliminate one group as less safe than others. What is clear is that these patients must be monitored more closely than other patients. The advent of the bispectral index (BIS) monitor may allow us to monitor their depth of anesthesia more closely and thus expose these patients only to the minimum amount of drug necessary to carry out the surgical procedure.

Purpose. The investigators hypothesize that specific mitochondrial diseases, in particular those that decrease complex I function, make certain children hypersensitive to volatile anesthetics. These same patients may be at increased risk for adverse outcomes following general anesthesia. The specific aims of this application are:

1. Determine which molecular defects in mitochondrial function lead to alter sensitivity to the VA sevoflurane.
2. Establish the relative safety of sevoflurane in treatment of patients with mitochondrial disease.

The investigators plan to monitor patients with mitochondrial disease using expanded measures of cardiovascular stability and measurements of brain electrical activity while slowly inducing general anesthesia. The investigators will use those measurements to limit the amount of anesthetic these patients receive in an attempt to minimize their risk. In addition, the investigators will correlate their sensitivity to the type of mitochondrial defect so that the investigators may be able to predict which patients are likely to have an increased sensitivity.

Study Overview

• Status: Terminated
• Conditions: Mitochondrial Disease
• Intervention / Treatment: Drug: sevoflurane

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting to the operating room for muscle biopsy as part of their diagnostic workup for possible mitochondrial disease.

Exclusion Criteria:

• Patients more than 16 years of age.
• Patients with concurrent acute infectious disease.
• Patients not tolerating a slow induction for emotional reasons.
• Initial BIS measurement of less than 95.
• Documented pulmonary disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: slow induction with sevoflurane; Only children with a BIS greater than 95 prior to inhalation of sevoflurane will be included in the study. Inductions will be done using a tight fitting mask with continuous monitoring of end tidal gas concentrations. During induction, concentration of inspired sevoflurane will begin at .5%, and slowly increased by 0.5% every two minutes, until a Bispectral Index (BIS) of 60 or less is reached. Inspired sevoflurane will be increased only after end tidal concentration of sevoflurane is constant for at least one minute. Each induction (except for the patients requiring very low doses of sevoflurane) will take approximately 10 minutes.

Drug: sevoflurane; During induction, concentration of inspired sevoflurane will begin at .5%, and slowly increased by 0.5% every two minutes, until a Bispectral Index (BIS) of 60 or less is reached, which will take approximately 10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure cardiovascular stability and electrical brain activity during slow induction with sevoflurane.	The investigators plan to monitor patients with mitochondrial disease using expanded measures of cardiovascular stability and measurements of brain electrical activity while slowly inducing general anesthesia. The investigators will use those measurements to limit the amount of anesthetic these patients receive in an attempt to minimize their risk.	during induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use cardiovascular and electrical brain measurements to limit amount of sevoflurane and predict individual sensitivity.	In addition, the investigators will correlate their sensitivity to the type of mitochondrial defect so that it may be possible to predict which patients are likely to have an increased sensitivity.	during induction

Collaborators and Investigators

• Sponsor: d sessler
• Investigators: Study Chair: Danield I Sessler, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: October 21, 2009
• First Submitted That Met QC Criteria: October 23, 2009
• First Posted (Estimate): October 26, 2009

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: sevoflurane; mitochondrial disease; mitochondrial disease and sevoflurane sensitivity
• Additional Relevant MeSH Terms: Metabolic Diseases; Mitochondrial Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane
• Other Study ID Numbers: 06-644