MH

1 in 100,000 surgical procedures in adults. 1 in 30,000 surgeries in children. Basically, more common in children.
Key risk factors include:
- Family history of MH
- Young boys (Children under 15 years comprise 52% of all reactions)
- Geographic location impacts risk: Wisconsin, Nebraska, West Virginia, Michigan

Inherited, autosomal dominant disorder affecting skeletal muscle characterized by impaired regulation and maintenance of calcium levels.
- **non-depolarizers are not the best choice for tx as you are not treating the main cause.
Associated with 34 genetic mutations primarily linked to the RYR1 (ryanodine) gene.
- The RYR1 gene encodes the ryanodine receptor, the major calcium release channel. Defective ryanodine receptors lead to excessive calcium release from the sarcoplasmic reticulum (sarcolemma) into the cell.
- The SERCA2 pump's attempt to return excess calcium to the sarcoplasmic reticulum.
- Breakdown of the sarcolemma allows potassium and myoglobin (toxic to kidneys) to enter systemic circulation (Aka, rhabdomyolysis occurs).
- Summary: Massive outflow Ca —> sustained muscle contraction —> hypermetabolism (as the body tries to pump it back into the cell) —> sarcolemma de-stability (cell membrane failure) —> myoglobin/potassium leakage —> Cardiac arrest
Summary: Consequences of excessive intracellular calcium:
- Increased muscle rigidity due to sustained contractions.
- Increased oxygen consumption
- Increased metabolic rate (hypermetabolism) and rapid ATP depletion.
- Increased CO₂ and heat production.
- Overall: respiratory + lactic acidosis
**can occur even hours after surgery. You can differentiate from other neuroleptic disorders bc NMBDs will not resolve s/s.

**Unexplained, sudden rise in end tidal CO₂ >55 mm Hg (which cannot be treated by increasing RR)
Unexplained tachycardia or arrythmias (cardiac arrest likely d/t hyperkalemia)
Masseter muscle or generalized muscle rigidity.
Rising patient temperature (late sign)
Cola-colored urine (myoglobinuria).
Mottled, cyanotic skin.
Decreased oxygen saturation (Sao2).
Tachypnea.
Labile blood pressure

Conduct a thorough preoperative evaluation to identify risks:
- Family history of unexpected complications, high fever, or death.
- hx of muscle rigidity under anesthesia.
- Dark-colored urine after exercise or surgery.
- Hx of central core disease, King Denborough syndrome, or multi mini core disease.
Consider alternatives to general anesthesia: Regional and TIVA anesthetics.
Remove any trace has from the machine (even if not using!):
- Change CO₂ absorbent.
- Remove or tape off vaporizers.
- Flush the machine with a new circuit and fresh gas flows exceeding 10 L/min for 20-90 minutes
- Apply charcoal filters.

Immediate actions:
- #1: Discontinue the triggering agent. Use an ambu bag until the entire circuit is changed out.
  - Remember that MH is a self-sustaining chemical reaction, so it must be reversed!
- Call for help and utilize the MH crisis hotline.
Medication protocol:
- Administer Dantrolene at a dose of 2.5 mg/kg, repeating every 5-10 minutes until symptoms cease.
- Continuation of Dantrolene in ICU for a minimum of 24 hours at 1 mg/kg every 4 hours as a bolus or 0.25 mg/kg/hr for continuous infusion.
Hyperventilation with 100% oxygen at flows >10L/min to improve oxygenation and decrease CO₂ levels.
Laboratory tests required: Coagulation profile, ABGs, electrolytes, CK, and myoglobin and liver enzymes.
Cooling of the patient: Administer IV fluids and apply ice packs to the groin, axilla, and neck. However, stop cooling at 38 C to prevent hypothermia
Tx arrhythmias: Avoid calcium channel blockers. You can use amio if needed.
- CCBs such as verapamil can further cause hyperkalemia if given to a patient who also received dantrolene!
Treatment for hyperkalemia: hyperventilation, bicarbonate (1-2 mEq/kg), intravenous insulin/glucose, calcium chloride (10 mg/kg), albuterol, diuresis
Maintain hydration with a urine output goal of >1 ml/kg/hour (d/t rhabdo effects)

MOA: Acts directly on skeletal muscle by Binding to ryanodine receptors to inhibit calcium efflux from the sarcoplasmic reticulum
- Tip: treat as quickly as possible because it is a rapid biochemical crisis where seconds = muscle cells dying
MHAUS recommends either drug version to be immediately available at all times:
- Dantrolene (Dantrium/Revonto): 20 mg vials, stocked to a minimum of 36 vials. Each bottle contains 3 g of mannitol and must be diluted with 60 ml of sterile WATER, shaken vigorously until clear due to poor solubility (very hard to mix together).
  - **mannitol is added for 1) diuresis effects since pt will have rhabdomyolsis and 2) increase solubility of the dantrolene powder to try and help make it more mixable with liquid
- Ryanodex is 250 mg vial, stocked to minimum of x3 vials (MUCH more expensive). Each bottles contains 0.125 g mannitol and must be diluted with 5 mL of sterile WATER. A little easier to mix than dantrolene, but still hard.
Adverse effects of dantrolene:
- Muscle weakness.
- Hepatotoxicity.
- CNS depression.
- Myocardial depression.

The most accurate and accepted test is the Caffeine Halothane Contracture Test (CHCT).
- Availability: Only at 5 medical centers in North America.
- Costs: $6,000 or more, and insurance may not cover it.
- Patients must travel to testing centers as the muscle biopsy needs to be fresh.
Genetic testing for RYR1, CACNA1S, or STAC3 gene mutations is a less expensive alternative but has lower accuracy.