Case Study: Mitochondrial myopathy

An 11-month-old female is scheduled for a diagnostic muscle biopsy and open gastrostomy tube insertion. She has a history of hypotonia, developmental delay, and failure to thrive secondary to poor feeding effort. Chromosomal analysis is normal, and her neurologist suspects she may have a mitochondrial myopathy.

What is a mitochondrial myopathy? Is it associated with unique considerations for administration of general anesthesia?

A mitochondrial myopathy is a type of genetic disease that is encompassed within a broad category of entities whose origin is a defect in mitochondrial function, and thus interfere with normal adenosine triphosphate (ATP) production. Although mitochondrial defects can affect almost every organ system, those organs with high metabolic rates – such as the heart, brain, and skeletal muscle – are particularly vulnerable. ATP depletion results in accumulation of lactate, a byproduct of anaerobic metabolism. Clinical manifestations include abnormalities of the heart (e.g., cardiomyopathy, conduction defects), skeletal muscle (e.g., atrophy, weakness), and central nervous system (e.g., seizures, encephalopathy, peripheral neuropathies, ophthalmologic manifestations), among many others. Examples of mitochondrial diseases include chronic progressive external ophthalmoplegia, Kearns–Sayre syndrome, Leigh’s disease, Leber’s hereditary optic neuropathy (LHON), mitochondrial myopathy, and myoclonic epilepsy with lactic acidosis and stroke-like episodes (MELAS syndrome). Treatment options are limited, and primarily supportive. Carnitine may lessen muscle weakness and fatigue in some children, and does not interact with anesthetic agents.

Preanesthetic assessment of a child with a suspected or confirmed mitochondrial disease includes evaluation of comorbidities – in particular, cardiac, respiratory, hepatic, and renal function. Premedication should be tailored to the individual patient; respiratory depressants should be avoided in children with weak ventilatory drive. The overall goal of anesthetic management is avoidance of metabolic stressors, such as hypoxemia and hypoglycemia, which may potentially exacerbate lactic acidosis. Clear glucose-containing liquids should be administered 2 hours prior to the anticipated induction of anesthesia. All anesthetic agents have been used safely in patients with mitochondrial diseases, although prolonged use of propofol should be avoided because of its association with lactic acidosis in the critical care setting. Preliminary and unpublished evidence suggests that children with mitochondrial myopathies may be more sensitive to inhalational anesthetics, and thus, require less concentrations than usual. Neuromuscular blockers should be carefully titrated to maintain one or two twitches on train-of-four monitoring, as patients with myopathies may demonstrate a unique sensitivity to these drugs. Steroidal neuromuscular blockers, which depend on adequate liver function for metabolism and termination of action, should be avoided if the patient has known liver dysfunction.

Should this patient be considered malignant hyperthermia (MH)-susceptible?

There is no genetic link between mitochondrial disease and MH susceptibility. In the presence of muscle atrophy, elective use of succinylcholine is contraindicated, as it may cause life-threatening hyperkalemia. Inhalational agents have been used safely in patients with mitochondrial diseases.

How would you induce and maintain general anesthesia? Is a muscle relaxant necessary?

Induction and maintenance of general anesthesia will be routine: inhaled sevoflurane and N2O for induction of anesthesia, or an IV induction agent if the child has IV access. Since this child has preexisting hypotonia, I don’t expect that he will be able to adequately ventilate and oxygenate using a spontaneous ventilation technique. Therefore, I will likely use controlled ventilation, using either a laryngeal mask or an endotracheal tube. Depending on the severity of the child’s hypotonia, I may choose to omit neuromuscular blockade from the induction regimen, since there are no surgical requirements for paralysis.

What are appropriate extubation criteria for this patient?

Extubation criteria for patients with hypotonia or developmental delay are ill-defined. The three criteria that are used in healthy children are: (1) sufficient muscle strength to maintain upper airway patency; (2) a regular respiratory pattern; and (3) wakefulness (e.g., spontaneous eye opening, following commands). The child in this case may demonstrate abnormalities for one or more of these criteria. Tracheal extubation will therefore become incumbent on the child attaining their preoperative or baseline parameters.

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