However, no intervention reduced the risk of major morbidity or 1 yr mortality

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.

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.