Malignant Hyperthermia

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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 3

Is there a test to diagnose malignant hyperthermia?

Answer 3

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

Question 4

How does the caffeine-halothane contracture test work?

Answer 4

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 5

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

Answer 5

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 6

Does nitrous oxide trigger malignant hyperthermia?

Answer 6

No.

Question 7

What is malignant hyperthermia?

Answer 7

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

Question 8

How does malignant hyperthermia occur?

Answer 8

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 9

What is the mortality rate of malignant hyperthermia?

Answer 9

1-5%

Question 10

What is the earliest sign of malignant hyperthermia?

Answer 10

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 11

How long after induction of general anesthesia does malignant hyperthermia usually occur?

Answer 11

Most episodes occur within 1 hour of exposure.

Question 12

What intravenous anesthetics trigger malignant hyperthermia?

Answer 12

No intravenous anesthetics are known to trigger malignant hyperthermia.

Question 13

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

Answer 13

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 14

What are the triggering agents for malignant hyperthermia?

Answer 14

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

Question 15

How early an indicator of malignant hyperthermia is an increase in temperature?

Answer 15

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 16

How is malignant hyperthermia transmitted genetically?

Answer 16

It is an autosomal dominant genetic disorder.

Question 17

How does delayed onset malignant hyperthermia occur?

Answer 17

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 18

How does cardiac irritability result from malignant hyperthermia?

Answer 18

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

Question 19

Can regional anesthesia be used in patients with malignant hyperthermia?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

What are the laboratory signs of malignant hyperthermia?

Answer 21

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

Question 22

What is the treatment for malignant hyperthermia?

Answer 22

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 bladder may 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 23

How is dantrolene packaged?

Answer 23

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

Question 24

How does dantrolene work to treat malignant hyperthermia?

Answer 24

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

Question 25

What is the dose of dantrolene in the treatment of malignant hyperthermia?

Answer 25

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 26

What are the side effects of large doses of dantrolene?

Answer 26

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

Question 27

What receptor has been linked to malignant hyperthermia and where is this receptor found?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

What is neuroleptic malignant syndrome and how does it compare to malignant hyperthermia?

Answer 29

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 30

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

Answer 30

Myoglobin appears in the plasma within minutes.