Malignant Hyperthermia

1.    What is Malignant hyperthermia

Malignant hyperthermia (MH) is a potentially fatal complication of general anesthesia following a depolarizing muscle relaxant and/or volatile anesthetics, and disordered Ca2+ regulation by the sarcoplasmic reticulum (SR) of skeletal muscle is thought to contribute to the development of MH. In Japan, the incidence of MH in Japan may be 1/50000-150000 of general anesthesia. However, the study of MH associated gene reported the incidence of predisposition to MH may be 1/2000. After total vinous anesthesia is popular, incidence of MH has decreased, but the mortality rate has been approximately 10-15%. The mortality rate is high in young male and individuals with muscular build.

MH has been associated with a mutation in the ryanodine receptor type 1 (RYR1), encoding the skeletal muscle calcium release channel of the sarcoplasmic reticulum (SR), and CACNA1S, encoding the α1 subunit of the dihydropyridine receptor.

 

2.    Clinical sign

The major signs of MH are tachycardia, arrhythmia, cola-colored urine, muscle rigidity, jaw tightness.

According to recent statistics, elevation of ETCO2 has been increasing for the initial signs of MH.

 

3.    Diagnosis

1) Clinical diagnosis

We have developed the criteria for the diagnosis of MH, originally presented and established by Emeritus professor Morio M. in 1988. These criteria are presented the following. In North America and Europe, Clinical grading scale (CGS) is used for clinical diagnosis.

Clinical criteria in Japan

Fliminant MH (f-MH) : A and B

Abortive MH (a-MH) : not A but B

A.   Temperature increase

①   Maximum body temperature ≧ 40°C

②   40°C>maximum body temperature ≧ 38°C

And increasing rate of body temperature ≧ 0.5°C/15 min.

B.   Clinical presentations of MH except for temperature

①    Unexpected tachycardia, arrhythmia, unstable circulation

②    Respiratory and/or metabolic acidosis (hyperventilation)

③    Muscle rigidity (masseter muscle spasm)

④    Cola colored urine (myoglobin urine)

⑤    Dark colored blood, decrease of PaO2

⑥    Increase of serum K+，CK，AST，ALT，LDH

⑦    Abnormal sweat

⑧    Abnormal bleeding tendency

2) Muscle biopsy

①    CICR rate test

Susceptibility to MH is traditionally made by the Ca2+-induced Ca2+ release (CICR) rate test in Japan. We believe that muscle biopsy is effective to investigate the cause of MH. In our institute, Ca-induced Ca release rate has been measured with chemically skinned muscle fibers. We have reported that the incidense of accelerated CICR rate in f-MH pstients is approximately 78.7%. This method relatively has fewer time limits.

②    IVCT

In Europe and North America, in vitro contracture tests (IVCT; North American MH Group protocol) and caffeine-halothane contracture tests (European MH Group protocol) are used. In Japan, they are not clinically used. They are sensitive to the abnormality of muscle contraction. However, there is some limitation to perform this test; time-limitation after biopsy, and amount of muscle volume.

3) Genetic analysis

MH has been considered hereditary disease. The main locus of genetic abnormality is focused on RYR1 in chromosome 19q13.1. Over 200 point mutations are reported in RYR1 gene. In North America and Europe, genetic screening is performed. However, in Japan, genetic analysis for MH is not clinically performed. If you would like to try a genetic analysis, you can contact following MH association.

4.    Treatment and prognosis

Important treatment is disconnection of trigger agents, hyperventilation by pure oxygen, administration of dantrolene, and coping care. Whole body cooling is important.

MH-related complications are ventricular arrhythmia, renal dysfunction, disseminated intravenous coagulation, brain edema, and so on. Complications decide the prognosis.

 

5.    Anesthesia for patient with predisposition to MH

A depolarizing muscle relaxant and volatile anesthetics are MH trigger agents. Intravenous anesthetics, narcotic analgesics, non-depolarizing muscle relaxant are not trigger agents. Total intravenous anesthesia (TIVA) is safe for individuals with predisposition to MH. Epidural anesthesia and spinal anesthesia are also safe.

Prior a surgery, you have to say to an anesthesiologist that you have a predisposition to MH. The anesthesiologist selects safety anesthesia for you.

 

6.    The CICR rate test at Hiroshima University Hospital

The CICR rate test is performed only at Hiroshima University Hospital and Saitama Medical University.

At Hiroshima University Hospital, the CICR rate test (containing muscle biopsy) is designated as developed medicine and costs about eighty thousand yen. However, if muscle biopsy is performed at other hospital and muscle sample is sent to Hiroshima University Hospital, cost of muscle biopsy is covered by medical insurance and the CICR rate test is free. .

Skeletal muscle sample is obtained by biopsy of the quadriceps or biceps brachii muscle. Sample size is necessary about 15mm length. Muscle biopsy is performed under local anesthesia in case of adult and under general anesthesia with venous anesthetics in case of child.

 

7.     Japan Malignant Hyperthermia Association

4th Nishi Tenma Park Bldg, 3-13-9 Nishi Tenma, Kita-ku, Osaka-shi, 530-0047, Japan
C/O COML(Consumer Organization for Medicine & Law)
Japan Malignant hyperthermia Association membership and inquiry counter
Telephone &Fax: 06-6361-3446 (Direct)

E-mail: JMHA2829@hotmail.com

 

References

1.    Hopkins PM. Malignant hyperthermia: advances in clinical management and diagnosis. Br J Anaesth 2000; 85: 118-28

2.    Sambuughin N, Holley H, Muldoon S, Brandom BW, de Bentel AM, et al. Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the North American population. Anesthesiology 2005; 102: 515–21

3.    Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology 1994; 80: 771-9

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2011.1.23