Anesth Analg 2006;103:983-985
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000237289.66136.cd
GENERAL ARTICLES
Malignant Hyperthermia in China
Zhong-huang Xu, MD*,
Ai-lun Luo, MD*,
Xiang-yang Guo, MD*,
Hong-zhi Ren, MD*,
Ying-lin Wang, MD*,
Xue Zhang, PhD ,
Yu-guang Huang, MD*, and
Tie-hu Ye, MD*
From the *Department of Anesthesiology, Peking Union Medical College Hospital; and Department of Genetics, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Address correspondence and reprint requests to Ai-lun Luo, MD, Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. Address e-mail to luoailun{at}pumch.ac.cn.
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Abstract
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Malignant hyperthermia has rarely been reported in China. We report the first case of malignant hyperthermia, verified by caffeine–halothane contracture test and genetic testing, in a Chinese patient.
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CASE REPORT
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A 62-year-old, 76-kg Chinese man presented for resection of gastric cancer under general anesthesia. Neither the patient nor his family had any history of muscular or anesthetic problems. His preoperative vital signs were normal (temperature 36.8°C, heart rate 76 bpm, and arterial blood pressure 160/95 mm Hg). Anesthesia was induced with 1 mg haloperidol, 50 µg fentanyl, 140 mg propofol, 140 mg succinylcholine followed by 7 mg vecuronium. Anesthesia was maintained with isoflurane 1%–2% in 50% nitrous oxide/50% oxygen. Minute ventilation was 6500 mL. His vital signs remained stable.
Six hours after the induction, the patient’s electrocardiogram developed ST changes, and arterial oxygen saturation decreased to 88%. Severe hypercarbia ensued, with an increase in end-tidal CO2 to 120 mm Hg. The patient began profusely sweating, his axillary temperature reached 39.6°C, his urine color changed to dark brown, and rigidity of extremities was noticed. We concluded that the patient had malignant hyperthermia (MH).
Dantrolene is not generally available in China, because MH is virtually unheard of in Chinese patients. Although we could not give dantrolene, we instituted the following measures: 1) discontinued the triggering anesthetic (isoflurane, nitrous oxide) and operation; 2) initiated a nontriggering anesthetic (propofol infusion at 40–50 mg/h); 3) provided 100% oxygen; 4) exchanged the entire anesthetic circuit; 5) increased the fresh gas flow rate to 15 L/min to prevent rebreathing; 6) measured the pharyngeal temperature; 7) began aggressive cooling (ice packs, rinsing the abdominal cavity with ice water, and cooling blankets); 8) administered furosemide; and 9) administered 5% sodium bicarbonate as indicated by blood gas analysis.
Sixty minutes after the life-saving interventions, the patient’s pharyngeal temperature decreased to 36.5°C. Two hours and 50 min later, he was transferred to the intensive care unit for further management. His hemodynamic status was stable throughout the procedure, and his renal function and coagulation function remained within normal range. The time course of his temperature and markers of rhabdomyolysis are shown in Figures 1 and 2, respectively. The postoperative period was uneventful. Thirty-one days after the operation, the patient was discharged from the hospital, with no postoperative complications.
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Figure 1. The temperature of the patient did not exceed 40°C during the procedure, reflecting very aggressive cooling intraoperatively.
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Figure 2. Serum creatine kinase level reached a maximum value of 6751 IU/L (normal: 18–198 IU/L). Serum myoglobin reached a maximum value of 8615 ng/mL (normal: 15–61 ng/mL). Urinary myoglobin reached a maximum of 11,037 ng/mL. These data suggest rhabdomyolysis.
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At the onset of MH, a sample of rectus abdominis was obtained for caffeine–halothane contracture test, which verified MH (Fig. 3). This was further confirmed by genetic analysis (Fig. 4) in the patient and his two relatives (Figs. 4 and 5).
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Figure 3. Caffeine–halothane contracture test: according to North American Malignant Hyperthermia Group protocol (1), caffeine–halothane contracture test was taken as follows: after removal of connective tissue, rectus abdominis strip measuring 2–3 cm in length was placed in a muscle bath with physiological solution, bubbled with oxygen and 5% carbon dioxide. The strip was attached to an electrical stimulator that produced twitches every 10 s. The strength of the contraction was measured electronically and recorded on a piece of paper. The muscle length was adjusted to produce a maximal force of contraction. The muscle was then allowed to stabilize, and when the baseline was stable, halothane was added to the gases that bubbled through the solution; the caffeine test was performed in a similar manner though there was no change in the gas bubbled through the solution. Instead, when the baseline was stable, caffeine was added to the bath to produce progressively larger concentrations of caffeine in the bath. The upper graph shows the halothane contracture test with negative result. The caffeine contracture test with positive result is shown in the lower graph.
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Figure 4. Genetic testing: polymerase chain reaction was used to amplify the ryanodine receptor (RyR1) gene mutation hot spots (exons 2–18, 39–46, and 90–104). DNA sequencing reaction was performed to identify the nucleotide mutation shown in the upper figure. The C6724T mutation was detected with encoding amino acid substitution Thr2206Met. Gel electrophoresis verified the mutation in two family members as well as the proband (lower figure).
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DISCUSSION
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We believe that this is the first diagnosis of MH in China on the basis of the caffeine–halothane contracture test using the North American MH Group protocol (1). MH occurs in persons who have a genetic susceptibility from mutations in calcium channel proteins that mediate excitation–contraction coupling, with the ryanodine receptor calcium release channel representing the major locus. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13.1) responsible for conferring MH susceptibility. RyR1 mutations are found in at least 25% of known MH-susceptible individuals in North America (2). The nucleotide mutation detected in this case has been reported in the United States and Europe (3), but never before in China.
Dantrolene is considered essential for the management of MH. As Chinese patients are rarely considered to be at risk of MH, dantrolene is not widely available in China. Aggressive management of the patient’s temperature, attention to acidosis, and prompt termination of MH-triggering drugs resulted in a good outcome in this patient. However, our experience suggests that dantrolene should be made available for MH emergencies in China.
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Footnotes
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Accepted for publication June 15, 2006.
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REFERENCES
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- Larach MG. Standardization of the caffeine halothane muscle contracture test. North Am Malignant Hyperthermia Group. Anesth Analg 1989;69:511–15.[Free Full Text]
- Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA 2005;293:2918–24.[Abstract/Free Full Text]
- Sambuughin N, Muldoon S, Barbara BW. 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.[Web of Science][Medline]
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Abstract
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