Malignant Hyperthermia

Question 1

What is malignant hyperthermia?

Answer 1

It is a rare, life-threatening, hypermetabolic skeletal muscle disorder.

Question 2

How does malignant hyperthermia occur?

Answer 2

Triggering agents induce significantly increased calcium concentrations in the skeletal muscle cells. Sustained muscle contraction occurs. Energy-dependent calcium channels try to
remove the excess calcium which increases the metabolism of the skeletal muscles. The increased metabolism depletes ATP stores and causes lactic acidosis. The acidosis and increased temperature destroys the sarcolemma which releases creatine
kinase, myoglobin, and potassium.

Question 3

What is the mortality rate of malignant hyperthermia?

Answer 3

1-5%

Question 4

What is the earliest sign of malignant hyperthermia?

Answer 4

A rise in the ETCO2 level is the earliest sign. In the absence of capnography, an elevated heart rate would most likely be the first symptom.

Question 5

How long after induction of general anesthesia does

malignant hyperthermia usually occur?

Answer 5

Most episodes occur within 1 hour of exposure.

Question 6

What intravenous anesthetics trigger malignant

hyperthermia?

Answer 6

No intravenous anesthetics are known to trigger malignant hyperthermia.

Question 7

Is masseter spasm after administration of
succinylcholine diagnostic of malignant
hyperthermia?

Answer 7

No, but it may be the first indication that a patient has malignant hyperthermia. Many clinicians advocate observing closely for any signs of hypermetabolism after a patient exhibits masseter
spasm on administration of succinylcholine. Some studies indicate that up to 50% of children who exhibit masseter spasm with succinylcholine have malignant hyperthermia.

Question 8

What are the triggering agents for malignant

hyperthermia?

Answer 8

The volatile agents (halothane, sevoflurane, isoflurane, and desflurane) as well as succinylcholine trigger malignant
hyperthermia in susceptible individuals.

Question 9

How early an indicator of malignant hyperthermia is

an increase in temperature?

Answer 9

An increase in temperature is typically a late sign, but the temperature may increase as much as 0.5 degrees Celsius every 15 minutes up to temperatures of 46 degrees Celsius.

Question 10

How is malignant hyperthermia transmitted

genetically?

Answer 10

It is an autosomal dominant genetic disorder.

Question 11

How does delayed onset malignant hyperthermia

occur?

Answer 11

Delayed onset malignant hyperthermia has been reported to occur with desflurane and sevoflurane. Episodes have been noted to occur as much as 6 hours after exposure.

Question 12

How does cardiac irritability result from malignant

hyperthermia?

Answer 12

The presence of hyperkalemia, acidosis, and increased body temperature results in an increased susceptibility to potentially
lethal cardiac arrhythmias.

Question 13

Can regional anesthesia be used in patients with

malignant hyperthermia?

Answer 13

Yes. Both amide and ester local anesthetics may be used for regional anesthesia in patients with malignant hyperthermia.

Question 14

Should patients with malignant hyperthermia receive a prophylactic dose of dantrolene prior to receiving an anesthetic?

Answer 14

Dantrolene prophylaxis is not necessary as long as the patient receives a non-triggering anesthetic.

Question 15

What are the laboratory signs of malignant

hyperthermia?

Answer 15

Increased PaCO2, metabolic and respiratory acidosis, hyperkalemia, elevated creatine kinase, myoglobinemia, and myoglobinuria.

Question 16

What is the treatment for malignant hyperthermia?

Answer 16

1) Discontinue any volatile agents and hyperventilate the patient with 100% oxygen
2) Dantrolene should be administered
3) Active cooling using stomach lavage with cold
water, surface cooling, and infusion of cold saline in the bladdermay be performed
4) Sodium bicarbonate may be administered
to treat hyperkalemia and acidosis
5) Saline should be administered to maintain a urine output of at least 2 mL/kg/hour
and
6) Osmotic or tubular diuretics should be administered

Question 17

How is dantrolene packaged?

Answer 17

It is packaged as a lyophilized (freeze dried) powder that must be mixed with 60 cc of sterile water prior to injection.

Question 18

How does dantrolene work to treat malignant

hyperthermia?

Answer 18

Dantrolene works directly on the ryanodine type 1 receptor to inhibit the efflux of calcium from the sarcoplasmic reticulum.

Question 19

What is the dose of dantrolene in the treatment of

malignant hyperthermia?

Answer 19

Treatment of acute episodes is 2.5 mg/kg IV every 5-10 minutes to a maximum dose of 10 mg/kg. Even if the episode is under control, dantrolene may have to be repeated at a dose of 1-2
mg/kg every 6 hours for a 24 hour period to prevent recurrence.

Question 20

What are the side effects of large doses of

dantrolene?

Answer 20

Nausea, vomiting, skeletal muscle weakness, and blurred vision.

Question 21

What receptor has been linked to malignant

hyperthermia and where is this receptor found?

Answer 21

The ryanodine receptor, which is a major calcium release trigger located in the sarcoplasmic reticulum

Question 22

What are some of the hypermetabolic conditions that can mimic malignant hyperthermia under general anesthesia?

Answer 22

Sepsis, thyrotoxicosis, pheochromocytoma, CNS injury, light anesthesia, and release of a lower extremity tourniquet or aortic cross-clamp

Question 23

What is neuroleptic malignant syndrome and how

does it compare to malignant hyperthermia?

Answer 23

NMS is similar to malignant hyperthermia in that it is associated with fever, rhabdomyolysis, hypertension, tachycardia, muscle rigidity, and acidosis. It differs from MH in that it is related to the administration of haloperidol and the atypical antipsychotic medications. Dantrolene, benzodiazepines, and bromocriptine have proved useful in the treatment of NMS. Also, MH occurs
acutely with exposure while NMS occurs after long-term therapy with its triggering agents. Sudden discontinuation of drugs used
to treat Parkinson’s disease can cause NMS.

Question 24

When does myoglobin appear in the plasma after the onset of malignant hyperthermia?

Answer 24

Myoglobin appears in the plasma within minutes.

Question 25

When do creatine kinase levels peak after the onset of malignant hyperthermia?

Answer 25

CK levels peak 12 to 24 hours after the onset of MH.

Question 26

How does the anesthesia-induced rhabdomyolysis
associated with Duchenne’s muscular dystrophy
compare to malignant hyperthermia?

Answer 26

Duchenne’s muscular dystrophy was once thought to be associated with MH, but is now accepted that it is a completely separate condition. The anesthesia-induced rhabdomyolysis associated with Duchenne’s is triggered by the same agents
and clinically exhibits most of the same symptoms. The difference is that dantrolene does not treat anesthesia-induced rhabdomyolysis and may produce marked skeletal muscle weakness which is of particular concern for these patients.

Question 27

Is there a test to diagnose malignant hyperthermia?

Answer 27

Yes. In North America, the caffeine-halothane contracture test can diagnose MH.

Question 28

How does the caffeine-halothane contracture test

work?

Answer 28

A muscle biopsy is obtained. High-doses of caffeine release calcium from the sarcolemma. This effect is enhanced by halothane. The muscle tissue in patients with malignant hyperthermia contracts abnormally when exposed to these two
patients, confirming a diagnosis of MH.

Question 29

Are there any other tests for malignant hyperthermia other than the halothane contracture test?

Answer 29

Yes, there is a molecular genetic test that examines the gene coding for the RYR1 (ryanodine receptor) that has a low sensitivity, but is much less invasive than the contracture test.

Question 30

Does nitrous oxide trigger malignant hyperthermia?

Answer 30

No