Mitochondrial Myopathy

This is not malignant hyperthermia - Mitochondrial disease is not at increased risk for MH and should not be managed with an MH protocol. Worth saying out loud in the pre-op huddle, because the word myopathy pulls the room toward the wrong plan.

Succinylcholine is contraindicated - Upregulated skeletal muscle nicotinic acetylcholine receptors make lethal hyperkalemia a genuine possibility, and succinylcholine can also trigger a myotonic crisis that leaves you unable to intubate or ventilate.

Nondepolarizers work, but unpredictably - Increased sensitivity, prolonged duration of action, and inconsistent responses are the rule. Use strict train-of-four monitoring and dose to the twitch. Where the case allows it, skip the relaxant entirely.

Reversal - Neostigmine is not ideal here: muscarinic effects (bradycardia, QT prolongation, nausea) plus the potential to trigger myotonic rigidity. Sugammadex offers more complete reversal in a patient who starts out weak, and case reports in myopathy support its use, though dosing evidence specific to this population is still thin. The 2023 ASA guideline dosing is 2 mg/kg from moderate block (TOF count 2 or more), 4 mg/kg from deep block (post-tetanic count 1 to 2), and 16 mg/kg for rescue, with neostigmine reserved for high levels of spontaneous recovery. Either way, confirm a quantitative TOF ratio of 0.9 or greater at the adductor pollicis before extubation.

Volatiles: more sensitive, not forbidden - These patients are hypersensitive to volatile anesthetics. Titrate incrementally against clinical depth or processed EEG rather than against a MAC number.

Limit propofol - Propofol interferes with mitochondrial function through several pathways, including inhibition at complex I and uncoupling of oxidative phosphorylation, and subclinical mitochondrial disease is a recognized risk factor for propofol infusion syndrome. An induction dose is a different question from a long infusion; it is the prolonged infusion to avoid.

No lactated Ringer's - Lactate metabolism is impaired, so normal saline is the fluid of choice. If pH needs help, bicarbonated Ringer's has been reported to hold pH better than acetated Ringer's, since bicarbonate does not have to be metabolized to alkalinize.

Minimize the fast - Prolonged fasting is exactly the catabolic stress these patients tolerate worst. Book them early in the day and follow your institution's clear-liquid policy rather than defaulting to overnight NPO.

Keep them warm - Hypothermia depresses mitochondrial function and then costs more energy to reverse. Forced air from the start, warm fluids, warm room.

Opioids - Opioid-sparing technique is what is recommended. Remifentanil has been used successfully, and a modified-Delphi consensus panel supports fentanyl as a safe choice in mitochondrial disease.

Local anesthetic choice - Regional anesthesia is appropriate and local anesthetics are generally well tolerated for peripheral blockade and infiltration. Bupivacaine is best avoided: like propofol it interferes with carnitine palmitoyl transferase, inhibiting fatty acid beta-oxidation and reducing oxidative phosphorylation. Ropivacaine and lidocaine inhibit those processes less and are preferred. Use the minimum effective concentration.

If the case is a diagnostic muscle biopsy - Hold the local anesthetic until the specimen is harvested. Its mitochondrial depressant effect can degrade the diagnostic value of the biopsy.

Cardiac and neurologic baseline - Conduction disease travels with some phenotypes, including complete heart block in Kearns-Sayre, so a baseline ECG earns its place. Ask about seizures, which are part of the MERRF and MELAS picture, and about stroke-like episodes.

No single technique is safer - The literature has not shown one anesthetic plan to be safer than another here. Build the plan around avoiding catabolic stress and titrating everything you give.

Mitochondrial myopathy sits inside a heterogeneous group of genetic disorders that disrupt mitochondrial respiration at the electron transport chain and oxidative phosphorylation, so the cell cannot make enough ATP. Mitochondrial disease affects roughly 1 in 4,000 people, and the organ systems with the highest metabolic demand declare themselves first: central nervous system, cardiac, ocular, musculoskeletal, and gastrointestinal.

The named phenotypes overlap. MELAS brings lactic acidosis and stroke-like episodes, MERRF myoclonic epilepsy with ragged red fibers on biopsy, Kearns-Sayre external ophthalmoplegia with cardiac conduction defects. What unites them at the board is a narrow energy margin: every general anesthetic interferes with mitochondrial bioenergetic pathways, and catabolic stress — fasting, cold, pain — is paid for out of a reserve these patients do not have.