Malignant hyperthermia is one of the few crises on the NCE where the exam cares about order as much as content. You can know every fact about the ryanodine receptor and still miss the question if you give dantrolene before you turn off the vaporizer. Learn it as a sequence.
What is actually going wrong
MH is a pharmacogenetic disorder of skeletal muscle. In susceptible patients, usually through a variant in the RYR1 gene (less often CACNA1S), a triggering agent opens the calcium release channel in the sarcoplasmic reticulum and it does not close. Calcium floods the cell, the muscle contracts and burns ATP trying to pump it back, and the result is a hypermetabolic state.
- Triggers: all volatile anesthetics and succinylcholine.
- Safe: propofol, opioids, benzodiazepines, ketamine, etomidate, nitrous oxide, nondepolarizing relaxants, and local anesthetics.
Nitrous oxide is not a trigger. That shows up as a distractor more than you would expect.
How it presents, in the order you will see it
The earliest and most sensitive sign is an unexplained rise in end tidal CO2 that does not come down when you increase minute ventilation. The muscle is producing CO2 faster than you can blow it off.
- Rising EtCO2 despite increased ventilation
- Tachycardia, often with arrhythmias
- Masseter rigidity after succinylcholine, or generalized rigidity
- Mixed respiratory and metabolic acidosis
- Hyperkalemia, from muscle breakdown
- Hyperthermia, which is a late sign
- Rhabdomyolysis, myoglobinuria, rising CK, and in the worst cases DIC
If an answer choice offers “temperature above 40 C” as the earliest sign, it is wrong.
The treatment sequence
Say it out loud until it is automatic. The NCE loves to ask what you do first.
- Stop all triggers. Turn off the volatile, do not give more succinylcholine.
- Call for help and the MH cart. You need hands to mix dantrolene.
- Hyperventilate with 100 percent oxygen at high fresh gas flows, at least 10 L/min. Insert activated charcoal filters on the inspiratory and expiratory limbs if available. Do not waste time changing the machine.
- Give dantrolene 2.5 mg/kg IV, and repeat until the signs reverse. Doses above 10 mg/kg are sometimes needed.
- Treat the complications: hyperkalemia, acidosis, arrhythmias, temperature.
- Monitor in an ICU for at least 24 hours.
Dantrolene, the numbers
Dantrolene works by blocking calcium release at the ryanodine receptor. Know two formulations.
| Formulation | Vial | Mix with |
|---|---|---|
| Dantrium or Revonto | 20 mg | 60 mL sterile water (not saline, not D5W) |
| Ryanodex | 250 mg | 5 mL sterile water |
A typical test calculation: an 80 kg patient needs 2.5 mg/kg, which is 200 mg. With 20 mg vials that is 10 vials, each mixed with 60 mL. That volume is the reason you call for help early.
After the crisis, dantrolene is continued at about 1 mg/kg every 4 to 6 hours (or as an infusion) for at least 24 hours, because recrudescence happens in a meaningful share of patients.
Treating the complications
- Hyperkalemia: calcium chloride or gluconate, insulin with glucose, bicarbonate, hyperventilation.
- Acidosis: hyperventilation, and bicarbonate guided by the blood gas.
- Arrhythmias: standard ACLS drugs, but avoid calcium channel blockers. Combined with dantrolene they can cause hyperkalemia and cardiovascular collapse.
- Temperature: active cooling with cold IV saline, cold packs and lavage of body cavities, but stop cooling at about 38 C to avoid overshooting into hypothermia.
- Kidneys: keep urine output above 1 to 2 mL/kg/hr with fluids and diuretics to protect against myoglobin.
Masseter spasm, the gray zone
Jaw rigidity after succinylcholine can be a normal variant or the first sign of MH. If the jaw cannot be opened at all, many clinicians switch to a nontriggering technique, follow EtCO2, CK and urine closely, and consider the patient potentially susceptible until proven otherwise.
Testing for susceptibility
The gold standard is the caffeine halothane contracture test on a fresh muscle biopsy. Genetic testing for RYR1 variants can confirm susceptibility, but a negative genetic test does not rule it out.
Quick hits for test day
- First sign: rising EtCO2. Last sign: fever.
- First action: stop the trigger.
- Dantrolene: 2.5 mg/kg, 20 mg vials in 60 mL sterile water.
- No calcium channel blockers with dantrolene.
- Stop cooling at 38 C.
- MHAUS runs a 24 hour hotline for clinicians in a crisis: 1-800-644-9737.
The CRNA Dojo lesson on malignant hyperthermia is one of the five free lessons, so you can work through the whole crisis with a free account. If you want a fast check on where you stand, take the free sample exam.
Sources
- Malignant Hyperthermia Association of the United States (MHAUS), emergency treatment guidance
- Nagelhout, Nurse Anesthesia
- Barash, Clinical Anesthesia
