Anesthetic Effects in Mitochondrial Disease

This study has been terminated.
(Among the three interventions, dexamethasone alone reduced inflammation. However, no intervention reduced the risk of major morbidity or 1 yr mortality)
Sponsor:
Information provided by (Responsible Party):
d sessler, Cleveland Clinic Foundation
ClinicalTrials.gov Identifier:
NCT01001585
First received: October 21, 2009
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Mitochondrial Disease
Drug: sevoflurane

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Anesthetic Effects in Mitochondrial Disease

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Measure cardiovascular stability and electrical brain activity during slow induction with sevoflurane. [ Time Frame: during induction ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Use cardiovascular and electrical brain measurements to limit amount of sevoflurane and predict individual sensitivity. [ Time Frame: during induction ] [ Designated as safety issue: No ]
    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.


Enrollment: 55
Study Start Date: September 2006
Study Completion Date: October 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   12 Months to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01001585

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
d sessler
Investigators
Study Chair: Danield I Sessler, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: d sessler, Medical Doctor, Cleveland Clinic Foundation
ClinicalTrials.gov Identifier: NCT01001585     History of Changes
Other Study ID Numbers: 06-644
Study First Received: October 21, 2009
Last Updated: May 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:
mitochondrial disease
sevoflurane
mitochondrial disease and sevoflurane sensitivity

Additional relevant MeSH terms:
Mitochondrial Diseases
Metabolic Diseases
Anesthetics
Sevoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Hematologic Agents
Anesthetics, Inhalation
Anesthetics, General

ClinicalTrials.gov processed this record on October 01, 2014