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Yapa Wijeratne

Malignant hyperthermia

Malignant hyperthermia is a life-threatening elevation in body temperature usually

resulting from a hypermetabolic response to concurrent use of a depolarizing muscle

relaxant and a potent, volatile inhalational general anesthetic.

Manifestations can include muscle rigidity, hyperthermia, tachycardia, tachypnea,

rhabdomyolysis, and respiratory and metabolic acidosis.

Diagnosis is clinical; patients at risk can be tested for their susceptibility. The highest

priority treatments are rapid cooling and aggressive supportive measures.

The muscle relaxant involved is usually succinylcholine; the inhalational anesthetic is

most often halothane, but other anesthetics (eg, isoflurane, sevoflurane, desflurane)

may also be involved. This drug combination causes a similar reaction in some

patients with muscular dystrophy and myotonia.

Pathophysiology

Malignant hyperthermia affects about 1/20,000 people.

Susceptibility is inherited, with autosomal dominant inheritance and variable

penetrance. Most often, the causative mutation affects the ryanodine receptor of

skeletal muscle; however, > 22 other causative mutations have been identified.

In susceptible patients.

↓

Anesthetic-induced potentiation of ca exit from the sarcoplasmic reticulum of skeletal

muscle

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Ca-induced biochemical reactions are accelerated

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Causing severe muscle contractions & elevation of the metabolic rate.

Complications 1. K↑

2. Respiratory and metabolic acidosis,

3. Ca↓

4. Rhabdomyolysis with CK elevation and myoglobinemia may occur,

5. Coagulation abnormalities (particularly DIC). In older patients and patients

with comorbidities, DIC may increase the risk of death.

Symptoms and Signs

Malignant hyperthermia may develop during anesthesia or the early postoperative

period. Clinical presentation varies, depending on the drugs used and the patient's

susceptibility.

1. Muscular rigidity, especially in the jaw, is often the first sign, followed by

2. tachycardia,

3. other arrhythmias,

4. tachypnea,

5. acidosis,

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6. shock, and

7. hyperthermia. Temperature is usually ≥ 40° C and may be extremely high (ie,

> 43° C).

8. Urine may appear brown or bloody if rhabdomyolysis and myoglobinuria have

occurred.

Diagnosis

o Clinical evaluation

o Testing for complications

o Susceptibility testing for people at risk

The diagnosis is suspected by the appearance of typical symptoms and signs within 10

min to, occasionally, several hours after inhalational anesthesia is begun. Early

diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea,

tachycardia, and increased end-tidal CO2.

There are no immediately confirmatory tests, but patients should have testing for

complications, including ECG, blood tests (CBC with platelets, electrolytes, BUN,

creatinine, CK, Ca, PT, PTT, fibrinogen, d-dimer), and urine testing for

myoglobinuria.

Other diagnoses must be excluded. Perioperative sepsis may cause hyperthermia but

rarely as soon after induction. Inadequate anesthesia can cause increased muscle tone

and tachycardia but not elevated temperature. Thyroid storm and pheochromocytoma

rarely manifest immediately after anesthetic induction.

Susceptibility testing

Recommended for people at risk based on a

o Family history of the disorder

o Personal history of a severe or incompletely characterized previous adverse

reaction to general anesthesia.

The caffeine halothane contracture test (CHCT) is the most accurate. It measures the

response of a muscle tissue sample to caffeine and halothane. This test can be done

only at certain referral centers and requires excision of about 2 g of muscle tissue.

Genetic testing has limited sensitivity (about 30%) but is quite specific; patients in

whom a mutation is identified do not require the CHCT.

Treatment

1. Rapid cooling and supportive measures

It is critical to cool patients as quickly and effectively as possible to prevent

damage to the CNS and also to give patients supportive treatment to correct

metabolic abnormalities. Outcome is best when treatment begins before

muscular rigidity becomes generalized and before development of

rhabdomyolysis, severe hyperthermia, and DIC.

2. Dantrolene; (a muscle relaxant) (2.5 mg/kg IV q 5 min as needed, up to a total

dose of 10 mg/kg) should be given in addition to the usual physical cooling

measures. In some patients, tracheal intubation, paralysis, and induced coma

are required to control symptoms and provide support.

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3. Benzodiazepines given IV, often in high doses, can be used to control

agitation.

4. Malignant hyperthermia has a high mortality and may not respond to even

early and aggressive therapy.

Prevention 1. Local or regional anesthesia is preferred to general anesthesia when possible.

2. Potent inhalational anesthetics and depolarizing muscular relaxants should be

avoided in patients who are susceptible.

3. Nondepolarizing muscular blockers are the preferred preanesthetic drugs.

Preferred anesthetics include barbiturates (eg, thiopental), etomidate, and

propofol.

4. Dantrolene should be available at the bedside.