Malignant Hyperthermia

Question 1

What is malignant hyperthermia?

Answer 1

It is a rare, life-threatening, hypermetabolic skeletal muscle
disorder.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 829.

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.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 830.

Question 3

What is the mortality rate of malignant hyperthermia?

Answer 3

1-5%
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1491.

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.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1497.

Question 5

How long after induction of general anesthesia does

malignant hyperthermia usually occur?

Answer 5

Most episodes occur within 1 hour of exposure.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1497.

Question 6

What intravenous anesthetics trigger malignant

hyperthermia?

Answer 6

No intravenous anesthetics are known to trigger malignant
hyperthermia.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1497

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 637.

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.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1491.

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 636.

Question 10

How is malignant hyperthermia transmitted

genetically?

Answer 10

It is an autosomal dominant genetic disorder.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1491

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.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 830.

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.
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 830.

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 639

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 639.

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.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1491.

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 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
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 638.

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.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 1188.

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.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 1188.

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 639

Question 20

What are the side effects of large doses of

dantrolene?

Answer 20

Nausea, vomiting, skeletal muscle weakness, and blurred vision.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 639.

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
Nagelhout JJ, Plaus KL. Nurse Anesthesia. 5th ed. St. Louis,
MO: Elsevier Saunders Company; 2014: 830.

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
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1497.

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.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 1190.

Question 24

When does myoglobin appear in the plasma after the

onset of malignant hyperthermia?

Answer 24

Myoglobin appears in the plasma within minutes.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 636.

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.
Nagelhout JJ, Zaglaniczny KL. Nurse Anesthesia. 4th ed.
Philadelphia, PA: WB Saunders Company; 2010: 792.

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.
Hines RL, Marschall KE. Anesthesia & Co-Existing Diseases.
6th ed. Philadelphia, PA: Elsevier-Saunders; 2012: 637.

Question 27

Is there a test to diagnose malignant hyperthermia?

Answer 27

Yes. In North America, the caffeine-halothane contracture test
can diagnose MH.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1502.

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.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1491.

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.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 1186.

Question 30

Does nitrous oxide trigger malignant hyperthermia?

Answer 30

No.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1497.