What is malignant hyperthermia?
Malignant hyperthermia (MH) is not just a high fever; it is a rare, inherited disorder of skeletal muscle that triggers a hypermetabolic crisis in susceptible individuals. This occurs primarily when a person is exposed to certain inhaled anesthetics or the muscle relaxant succinylcholine during general anesthesia. It is important to distinguish MH from other causes of fever or hyperthermia that may occur during or after surgery, such as infection or dehydration.
The root cause of MH lies in a genetic mutation, most commonly affecting the RYR1 gene, which controls calcium release in muscle cells. In affected individuals, exposure to a triggering anesthetic causes an uncontrolled release of calcium within the muscle cells. This leads to a cascade of events, including sustained muscle contractions, a dramatically increased metabolism, and excessive heat production. Without immediate intervention, this can lead to severe complications and be fatal.
Symptoms and signs of malignant hyperthermia
Recognizing the early signs of MH is critical for a favorable outcome. While the most well-known symptom is a dangerously high body temperature, this is often a late sign. The initial indicators can be more subtle but require immediate attention from the anesthesia team.
- Increased End-Tidal Carbon Dioxide ($ETCO_2$): This is often the earliest and most sensitive sign of an MH event. As the body's metabolism speeds up, it produces more carbon dioxide, which is exhaled and measured by the anesthetic machine.
- Tachycardia: An unexplained increase in heart rate is another common and early indicator.
- Muscle Rigidity: Severe, widespread muscle stiffness or spasms can occur, particularly in the jaw after the administration of succinylcholine.
- Metabolic Acidosis and Hyperkalemia: The hypermetabolic state leads to an increase in blood acid levels and dangerously high potassium levels, which can cause cardiac arrhythmias.
- Skin Mottling: The skin may appear blotchy or mottled due to poor blood circulation.
- Myoglobinuria: The breakdown of muscle fibers (rhabdomyolysis) releases myoglobin, which can cause the urine to turn dark brown or reddish.
Triggers and risk factors
Not all anesthetic agents pose a risk for MH. The key triggers are the volatile halogenated inhalational anesthetics and the muscle relaxant succinylcholine. Common volatile anesthetics to avoid in susceptible patients include isoflurane, sevoflurane, and desflurane. Safe alternatives are widely used and include intravenous anesthetics like propofol, opioids, and nitrous oxide.
Genetic susceptibility is the primary risk factor. Patients with a family history of MH or a history of unexplained, severe reactions during anesthesia are at higher risk. Certain inherited muscle diseases, such as central core disease, are also associated with a higher likelihood of MH susceptibility.
Management and treatment
When MH is suspected, a standardized protocol is activated immediately. The cornerstone of treatment is a specific medication, the muscle relaxant dantrolene.
- Stop Triggering Agents: All triggering anesthetic agents and succinylcholine are discontinued immediately.
- Hyperventilate with 100% Oxygen: The patient is hyperventilated to eliminate excess carbon dioxide.
- Administer Dantrolene: The antidote, dantrolene, is given intravenously to halt the release of calcium from the muscle cells. A newer, more rapidly dissolving formulation is also available.
- Cool the Patient: Active cooling measures are initiated, such as applying ice packs to the patient's groin and armpits, using a cooling blanket, and infusing cold intravenous fluids.
- Address Complications: Supportive care is provided to manage complications like hyperkalemia, metabolic acidosis, and arrhythmias.
Post-crisis care involves continued monitoring in an intensive care unit (ICU) for at least 24 to 48 hours, as MH can reoccur. A referral to the Malignant Hyperthermia Association of the United States (MHAUS) is recommended for genetic testing and family counseling.
Prevention and safety measures
Prevention is the most effective strategy for managing MH risk. Anesthesiologists take a comprehensive approach to identify susceptible patients and use non-triggering anesthetic techniques. During a preoperative evaluation, an anesthesiologist will ask about any personal or family history of issues with anesthesia.
For patients with confirmed or suspected MH susceptibility, a specific plan is put in place:
- Use Safe Anesthetics: Non-triggering drugs like propofol, opioids, and regional anesthesia are used instead.
- Prepare Equipment: The anesthesia machine and circuit are thoroughly prepared to eliminate any residual triggering agents. Activated charcoal filters are sometimes used to speed this process.
- Continuous Monitoring: Close monitoring of vital signs, including temperature and $CO_2$ levels, is maintained throughout and after the procedure.
Comparison of Malignant Hyperthermia vs. Other Hyperthermias
| Feature | Malignant Hyperthermia | Other Perioperative Hyperthermias | Heat Stroke |
|---|---|---|---|
| Cause | Genetic predisposition triggered by specific anesthetic agents (inhalants, succinylcholine). | Infection (sepsis), hypothalamic injury, dehydration, excessive warming. | Environmental heat exposure and/or intense physical exertion. |
| Mechanism | Uncontrolled release of calcium from muscle cells causing hypermetabolism. | Failed thermoregulation or systemic inflammatory response. | Overwhelmed thermoregulation from external factors. |
| Symptoms | Rapidly rising $CO_2$, tachycardia, muscle rigidity, late fever, acidosis. | Fever, tachycardia, but typically without severe, rigid muscle contractions. | High body temperature, altered mental status, cessation of sweating. |
| Treatment | Specific antidote (dantrolene), cessation of triggers, cooling measures. | Treatment of underlying cause (e.g., antibiotics for infection), cooling. | Aggressive cooling, fluid resuscitation. |
| Emergency Status | Medical emergency requiring immediate, specific treatment. | May be an emergency depending on the underlying cause and severity. | Medical emergency. |
Genetic testing and diagnosis
Diagnosis of MH susceptibility can be confirmed through genetic testing or a muscle biopsy procedure known as the caffeine-halothane contracture test. Genetic testing looks for specific mutations in genes like RYR1, but can have limited sensitivity. The contracture test, while more definitive, is invasive and only performed at specialized centers. For families with a known history of MH, genetic counseling is often recommended.
Conclusion
While the prospect of a rare but life-threatening reaction to anesthesia may sound alarming, the key takeaway is that MH is manageable and preventable with proper care. Medical awareness has dramatically reduced the mortality rate from what it was in the past. Patients should be proactive by discussing any family history of anesthesia complications with their healthcare providers. For those with known or suspected susceptibility, anesthesiologists are highly trained to use safe, non-triggering agents and follow strict protocols to ensure a safe surgical experience. This preparation and vigilance are what transform MH from a potentially fatal event into a manageable complication.
