Malignant hyperthermia is a hypermetabolic crisis that is fatal if left untreated. It occurs in individuals with a specific genetic condition when they are exposed to certain anesthetic gasses or the medication succinylcholine.

Malignant hyperthermia pathophysiology

When susceptible patients are exposed to triggering agents, calcium accumulates in the myoplasm of skeletal muscle cells. The accumulation of calcium causes sustained muscle contractions and the cells must utilize both aerobic and anaerobic metabolism in order to maintain the contraction. The result is ATP depletion, oxygen depletion, carbon dioxide production, and the development of acidosis. This pathological process is responsible for the early signs of malignant hyperthermia, which are tachycardia, hypercapnia and muscle rigidity. 

Once energy stores are depleted, the muscle cells breakdown (rhabdomyolysis), and release potassium and myoglobin into the bloodstream, resulting in hyperkalemia and myoglobinuria. Hyperkalemia can lead to dangerous cardiac arrhythmias, and myoglobinuria damages the kidneys, leading to acute renal failure.

While in this hypermetabolic state, the body generates more heat than it is able to dissipate. This leads to hyperthermia which can occur early or later as the condition progresses. Studies show that in some cases, body temperature can increase by as much as 1 to 2 degrees Celsius every five minutes. Organ dysfunction sets in once the temperature reaches dangerously high levels above 41.5-degree Celsius (106.7-degrees Fahrenheit). 

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Hyperthermia leads to DIC, which causes widespread coagulopathy and, ultimately, hemorrhage. If the patient gets to this point, the outcome is dire and the patient will not survive.

Let’s review the key components of the pathophysiology: 

  • Influx of calcium causes sustained muscle contraction
  • Muscle cells must use anaerobic metabolism to maintain the contraction, which leads to acidosis
  • Muscle cells deplete ATP (their energy source) and die, releasing potassium and myoglobin into the bloodstream
  • The increased oxygen demand of the muscles and increased buildup of CO2 causes tachycardia
  • Hyperkalemia leads to cardiac arrhythmias
  • Myoglobin damages the kidneys leading to acute renal failure
  • The hypermetabolic state causes body temperature to increase which leads to widespread organ dysfunction and DIC

Malignant hyperthermia has a mortality rate of 4 to 10% even with treatment. Without treatment, mortality rates have been reported to be around 70%.

Who is most at risk for being MH susceptible? 

Individuals with the genetic mutation that allows too much calcium to flow into skeletal muscle cells experience malignant hyperthermia when exposed to a triggering agent. This is an autosomal dominant disorder, meaning it can be passed on to children if only one parent has the genetic mutation. Each child of a parent with MH susceptibility has a 50% chance of inheriting the disorder. Anyone with a blood relative who is MH susceptible should be considered at high risk.

Other individuals at risk of experiencing malignant hyperthermia include those with a history of unexplained rhabdomyolysis, muscular dystrophy, myotonia (impaired muscle relaxation) and rare muscular diseases including Central Core disease and King Denborough Syndrome. 

Now that you have some background information on MH, let’s dive into the specifics using the Straight A Nursing LATTE method

L: How does the patient LOOK? What are the signs and symptoms of malignant hyperthermia?

While under the effects of anesthesia, either during surgery or in the immediate post-op period, the patient is not going to be able to communicate that something is wrong. It is up to you and the other members of the healthcare team (surgeon and anesthesiologist) to notice when something unexpected is happening with the patient. The earliest signs include tachycardia, increased ETCO2 and muscle rigidity. 

While tachycardia and increased ETCO2 will be immediately displayed on monitoring equipment, muscle rigidity may be difficult to notice while a patient is under the effects of anesthesia. One clue could be the surgeon asking the anesthesiologist for additional muscle relaxants, which could be an indicator that rigidity has set in. Another clue is an inability to open the jaw due to rigidity of the masseter muscle, which can occur within 60 to 90 seconds after administering a triggering agent, especially succinylcholine.

As the condition progresses, other key things to notice are:

  • Tall, peaked T-waves, widened QRS and cardiac arrhythmias due to hyperkalemia
  • Elevated body temperature, though this can vary 
  • Flushed skin, sweat, mottling (mottling is more common in children than in adults)
  • Tachypnea, hypoxemia, hypercapnia
  • Tea or cola-colored urine due to myoglobinuria and rhabdomyolysis

A: How do you ASSESS the patient?

Symptom onset in malignant hyperthermia can vary from patient to patient. Symptoms may manifest as early as a few minutes up to several hours after exposure to the triggering agent. 

Important things to assess include:

  • HR and rhythm – tachycardia and arrhythmias can occur
  • Core body temperature
  • Muscle tone – rigidity can set in quickly, especially at the masseter muscle
  • End tidal CO2 – an abrupt increase in ETCO2 is a sign of MH
  • Urine output and characteristics – with myoglobinuria and rhabdomyolysis the urine will be dark in color and as the kidneys suffer injury, output will decrease
  • Prior to surgery, patients should be screened for history of anesthesia complications in themselves and blood relatives

T: What TESTS will be conducted for a patient with malignant hyperthermia?

In patients with suspected MH, no specific tests are utilized. Treatment is initiated based on a presumptive diagnosis and display of symptoms – unexplained rise in ETCO2, tachycardia, muscle rigidity, hyperthermia, hyperkalemia, and acidosis. 

Lab tests utilized in the evaluation of MH are: 

  • Serum and urine myoglobin to evaluate presence of rhabdomyolysis.
  • Electrolytes – specifically potassium, which will be elevated as the muscle cells release their cellular contents. Additionally, calcium levels may be low since calcium is being utilized in the skeletal muscles.
  • Creatine kinase – will be elevated in rhabdomyolysis.
  • CBC and coagulation tests to evaluate for DIC.
  • Arterial blood gas will show respiratory and metabolic acidosis.

Tests are also utilized to identify individuals with the genetic predisposition for MH. These include genetic testing and muscle biopsy. Genetic testing is conducted via a blood draw while a muscle biopsy test must be conducted at specialized testing centers. This test, called the caffeine-halothane contracture test, exposes freshly biopsied muscle tissue to caffeine and halothane to see how strongly the muscle contracts. 

T: What TREATMENTS are provided to treat malignant hyperthermia?

When malignant hyperthermia is suspected, it’s important to get help immediately as many interventions will need to be implemented. A key component of this is calling the Malignant Hyperthermia Association of the US hotline which was created to assist health care workers in appropriate management of patients in crisis. 

The only antidote for malignant hyperthermia is the medication dantrolene, which is a skeletal muscle relaxant that stops the sustained contraction and prevents the hypermetabolic processes associated with the condition. It works by binding to a specific receptor to inhibit the release of calcium from the sarcoplasmic reticulum. Note that dantrolene must be reconstituted in a very specific way and this will depend on which formulation you are using. 

The formulation Dantrium comes in a 20 mg vial which is reconstituted with 60 ml sterile water, while the formulation Ryanodex is a nanosuspension that comes in a 250 mg vial which is reconstituted with 5 ml sterile water. Many hospitals use Ryanodex because the full dose reconstitutes much faster than Dantrium (less than one minute as opposed to up to 20 minutes) and requires only one vial versus multiple vials. For example, a patient weighing 80 kg would require only one vial of Ryanodex but would require 10 vials of Dantrium.

The standard dose for all formulations of dantrolene is 2.5 mg/kg and both formulations are reconstituted with sterile water. Shaking the vial vigorously can help the medication reconstitute more quickly and the medication is given via IV push. Note that lower or higher doses may be used and can vary. Dantrolene is administered until the patient displays a reduction in symptoms. Some patients with severe rigidity may require doses greater than 10 mg/kg.

Other key interventions for malignant hyperthermia include:

  • Immediate cessation of the triggering agent as applicable. In some cases, MH may be recognized during surgery and in other cases, it becomes apparent in the postoperative period. If a patient goes into MH during surgery, the anesthesiologist and surgeon will decide if surgery must continue. If it must, then the anesthesiologist will switch to non-triggering agents for the remainder of the procedure. This could include propofol with an opioid, local anesthetics, barbiturates and some muscle relaxants.
  • Cool the patient with chilled IV fluids, ice packs (at the groin, axilla and neck), cold saline lavage (if body cavities are open during surgery), and cooling blankets. Cooling is important because increased temperatures cause more cellular calcium to be released which can exacerbate the condition and lead to more rigidity and poor perfusion. Without adequate perfusion, delivery of dantrolene to the tissues will be compromised. Patients are actively cooled when core temperature is above 39-degrees Celsius, and cooling measures are discontinued when body temperature reaches 38-degrees Celsius.
  • Oxygenation and ventilation support involves hyperventilating the patient with100% FiO2 to flush out any volatile anesthetics and reduce end tidal CO2. Using activated charcoal filters in the ventilatory circuit helps absorb inhaled anesthetics. Note these become saturated quickly and are typically changed out every hour.
  • Treat hyperkalemia as needed. Hyperkalemia is typically treated with insulin plus glucose (insulin opens the cell and glucose enters, bringing potassium along with it), sodium bicarbonate and calcium chloride. Note that calcium is still used in MH since it reduces cardiac excitability and helps reduce the risk for dangerous arrhythmias in the presence of hyperkalemia. Some patients will also need high-doses of albuterol, which also shifts potassium into the cell.
  • Treat metabolic acidosis as needed. Some patients may benefit from sodium bicarbonate administration and hyperventilation as a way to increase pH.
  • Treat cardiac arrhythmias as needed, though the evidence shows that correction of acidosis, hyperkalemia and hyperthermia reduces arrhythmias. If necessary, follow ACLS guidelines for the treatment of arrhythmias. Note that the evidence shows verapamil and diltiazem, which are calcium channel blockers, should be avoided since they can exacerbate hyperkalemia, hypotension, and myocardial depression when administered concurrently with dantrolene. 
  • Treat rhabdomyolysis, myoglobinuria, and oliguria as needed. This involves increasing urine output to a goal of 1 to 2 ml/kg/hr. Note that the formulation Dantrium contains 3 grams of mannitol, which acts as an osmotic diuretic to help offset the large amount of fluid patients receive with this medication. Other strategies for increasing urine output and preventing acute kidney injury in rhabdomyolysis include IV fluids and alkalinization of urine with sodium bicarbonate infusion. Patients who do suffer from acute renal failure may require dialysis. Learn more about rhabdomyolysis here.
  • Treat compartment syndrome as needed. Patients who develop rhabdomyolysis can also develop compartment syndrome, especially in the presence of DIC. The treatment for compartment syndrome is a fasciotomy. Learn more about compartment syndrome here.
  • Treat DIC as needed. Patients who develop DIC will require prompt treatment with platelets, FFP, and/or cryoprecipitate.

Again, it is vital that once the signs of malignant hyperthermia are recognized that additional resources be utilized and prompt intervention initiated. The studies show that for every thirty minutes that pass, there is a 1.6x increase for the development of a serious complication. 

In order to make it possible for health care workers to provide prompt treatment for malignant hyperthermia, many hospitals stock an “MH Cart” in operative areas. These carts contain vital items such as: 

  • Dantrolene
  • Sterile water and syringes for reconstitution
  • Chilled 0.9% sodium chloride
  • Sodium bicarbonate
  • Dextrose and regular insulin
  • Calcium chloride
  • Possibly ACLS medications, though these are often housed in their own cart
  • Charcoal filters
  • Various nursing supplies including IV catheters in various sizes, pressure bag for the rapid administration of fluids, disposable cold packs, Foley catheter (preferably with temperature probe), plastic bags and bucket for ice, test strips for urine hemoglobin, ABG kits, and lab specimen vials.

E: How do you EVALUATE and EDUCATE?

Evaluating a patient with malignant hyperthermia involves monitoring for a reduction in symptoms and normalization of body systems. Some goals of care include normothermia, absence of muscle rigidity, regular heart rate and rhythm, absence of hyperkalemia, normalized pH, adequate urine output, absence of myoglobin in the urine, and no signs of bleeding (or any other complication).

The most important education component for a patient with malignant hyperthermia susceptibility is that they must always share this information with any surgeon and anesthesiologist so that the proper anesthetic agents can be chosen. They should also wear a medic alert ID so their condition is known in the case of an emergency. It’s also important they know to share their susceptibility with their family since other relatives may be at risk. These individuals, in turn, should let their healthcare team know of their family history for MH as they will likely require testing prior to any surgical procedures.

Take this topic on the go by tuning in to episode 302 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.


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