Malignant Hyperthermia Status in China

An international phone conference on malignant hyperthermia (MH) status in China was inspired by a recent case in which a young healthy patient in the northeast region died of fulminant MH before IV dantrolene was mobilized from a hospital several hours flying distance away in Beijing.a This resulted in a joint discussion among 4 major societies: MHAUS, Malignant Hyperthermia Association of the US; CSA, Chinese Society of Anesthesiology; CASA, Chinese American Society of Anesthesiology; ICAA, International Chinese Academy of Anesthesiology The societies met to review the current MH status in China and offer recommendations to strengthen the education, diagnosis, and care of patients with MH in China. CURRENT STATUS OF MH IN CHINA It is estimated that approximately 35 million surgeries are conducted in China every year.1 However, an epidemiologic study addressing MH incidence and outcome is lacking. It is not clear whether the incidence of MH is lower in the Asian population than in the Caucasian population. A recent report suggested that the MH incidence in Japan may be similar to that in the United States.2 It is also speculated that there may be a difference between the varied ethnic groups of China and the majority Han people (>90%) with respect to MH susceptibility (presentation, Francis S. Stellaccio).3 To our knowledge, 24 MH cases occurred in mainland China between 1998 and 2002 (presentation, Xiangyang Guo). Another estimate indicates the occurrence of 34 cases between 1978 and 2004 with a mortality rate as high as 73.5%,4,5 and 21 cases between 2004 and 2008.5,6 The actual incidence could be much higher considering the incidence of fulminant MH is generally 1 in 200,000 anesthetics (presentation, Henry Rosenberg),7,8 and, thus, mortality may be higher as well. While applauding the hard work of Chinese experts to improve management of MH,9–11 more effort is needed to strengthen early diagnosis and effective treatment of MH cases. For example, an MH Web site and a hotline were established in 2006. Unfortunately, it was discontinued in 2009 (presentation, Xiangyang Guo). In Sichuan province, the West China Hospital in Chengdu has expanded from 2500 beds in the year 2000 to approximately 6000 beds and provided approximately 1 million anesthetics in the past 15 years. Of these, 90% to 95% were general anesthetics. Six (6) ethnic Chinese were diagnosed with MH crises, 4 were successfully treated, and 2 (33.3%) died (presentation, Jin Liu). It should be noted that West China Hospital is one of the largest and most respected academic medical centers in China.b West China Hospital is also one of the few hospitals in China that stores IV dantrolene.Table 1: Six Malignant Hyperthermia Cases from Chongqing City and Chengdu, Sichuan Province During the Past 5 YearsInformation about the occurrence of MH is also available from Chongqing City and Chengdu, Sichuan province. During the past 5 years, there were 6 identified cases of MH, including 1 child. Efforts were made to obtain IV dantrolene from West China Hospital (Table 1). Because IV dantrolene for MH is still not on the list of government-approved drugs in China, these MH cases demonstrate that efforts should be made to hasten dantrolene’s approval and improve its distribution. WORLDWIDE EXPERIENCE OF MHAUS MHAUS was founded in 1981, at about the same time dantrolene became commercially available in the United States. Because information about MH was lacking, even among anesthesiologists, MHAUS established educational programs for anesthesiologists and patients. Current information about MH can be found on the MHAUS website.c The situation in China is very similar to that of the United States in 1976 (presentation, Henry Rosenberg).d,12 Scientists attempted to get oral dantrolene into solution and found that it was not only difficult but it was also hard to predict the plasma concentration.12 Although this method may be better than nothing, it is inefficient and should be unnecessary because IV dantrolene is commercially available. In the United States, dantrolene was approved and became commercially successful by making the medical community aware that patients would die of MH without immediate IV dantrolene. The result was that hospitals necessarily maintained stocks of dantrolene. Interestingly, the current status of MH awareness in China is not unlike the initial stages of MH awareness in other countries (presentations, Henry Rosenberg and Kumar Belani).13–15 While MH was initially thought to have a lower insignificant incidence in these countries when compared with the United States,5,14,16,17 this belief is changing because of the increased recognition and publication of MH cases in these countries. Obviously, there is an urgent need to set up diagnostic and skilled sites for genetic and muscle biopsy diagnosis of patients and families with MH both in India and in China. SUGGESTIONS FOR IMPROVEMENT OF MH DIAGNOSIS AND TREATMENT IN CHINA The education concerning MH incidence, clinical presentation, pathophysiology, diagnosis, and treatment should be strengthened in the Chinese medical community,18 especially among anesthesiologists working in remote regions. A collaborative committee between anesthesiologists in China and those in other countries may facilitate this process. Presentations centering on MH should be scheduled during major meetings such as the annual meeting of the Chinese Society of Anesthesiology (CSA) and/or the Chinese Association of Anesthesiologists (CAA). Potential collaboration between CSA and CAA with MHAUS or with societies of anesthesiologists from other countries (e.g., The Indian College of Anaesthesiologists) is encouraged. In addition, efforts should be made to translate and circulate the information available on the MHAUS website to both the Chinese medical community and the Chinese people as a whole. An MH educational website could be initiated by a governmental or nongovernmental body. It could also be incorporated into an existing educational website such as Xinqingnianmazuiluntan (Young Anesthesiologists Forum)e or Jichengmazuiwang (Regional Anesthesia Web)f and Zhongguomazuiluntan (China Anesthesiology Forum).g It is recommended that a 24-hour hotline and a registry similar to that of MHAUS should be set up in China. Social media, such as WeChat groups (Chinese version of online Facebook chatting groups), are also encouraged. Diagnosis Currently, monitoring end-tidal CO2 (ETCO2) and core temperature is not mandatory in China. Many small hospitals lack ETCO2 and temperature monitoring capability. We advocate increasing investment of appropriate medical monitoring equipment at healthcare facilities in China. This would include creating regulations and standards requiring ETCO2 monitoring and core temperature monitoring19 for all general anesthetics longer than 30 minutes. Genetic laboratories similar to those in the United States and other countries should be set up to improve the diagnosis of MH, especially for patients with an MH family history.20 Biopsy centers would be useful but are less efficient and convenient than direct genetic studies (presentation, Henry Rosenberg).21,22 In West China Hospital, direct genetic study has been recently conducted in a research laboratory, including identifications of mutations in the ryanodine receptor, RYR1, in 2 clinically diagnosed MH patients (presentation, Jin Liu). Overall, raising awareness of MH and early diagnosis22–24 are fundamental to successful treatment of MH. Treatment The lack of IV dantrolene25,26 in most hospitals in China is the major limitation in MH treatment. Hospitals in China are not required to stock IV dantrolene, as is required in the United States, because of the low perceived incidence of MH, high cost, and insufficient recognition. To address this problem, policy makers in China should be educated to the importance of IV dantrolene in patient safety and encourage the approval of IV dantrolene by the Chinese Food and Drug Administration (CFDA) as soon as possible. New guidelines should recommend that IV dantrolene be stocked in hospitals where general anesthesia is performed or within a reasonable distance. It has been planned that IV dantrolene will be manufactured and available for clinical use in approximately 3 years by a Chinese pharmaceutical company (presentation, Xiangyang Guo). Currently, based on website information, oral dantrolene is produced by some Chinese pharmaceutical companies for the treatment of some neurologic disorders. Although oral dantrolene is not the ideal method to treat MH because of its unpredictable absorption and blood concentration, it is better than nothing27,28 based on previous case reports.29,30 Both India and China need to take the steps adopted in the United States and Europe (and encouraged by MHAUS) to improve the care of patients during an MH episode. The consensus of the reporting members is as follows: It is important and critical to have IV dantrolene available and approved in China for the treatment of MH. Chinese anesthesiologists should increase the awareness and the education process concerning MH in China. This would include conferences, websites, and collaboration with international colleagues. ETCO2 monitoring should be instituted in all patients during general anesthesia, and core temperature monitoring should be available for all cases lasting longer than 30 minutes. China should establish a 24-hour hotline for MH consultation similar to the one of MHAUS. China should establish a registry to summarize the reported cases periodically. Kumar G. Belani, MBBS, MS Department of Anesthesiology University of Minnesota Minneapolis, Minnesota Cathy Cao, MD Department of Anesthesiology MedStar Washington Hospital Center Washington, DC Dianne Daugherty Malignant Hyperthermia Association of the United States Sherburne, New York Xiangyang Guo, MD, PhD Department of Anesthesiology Peking University Third Hospital Beijing, China Lingqun Hu, MD Department of Anesthesiology Northwestern University Feinberg School of Medicine Chicago, Illinois Jiapeng Huang MD, PhD, FASE Department of Anesthesiology and Perioperative Medicine Jewish Hospital, University of Louisville Louisville, Kentucky Henry Liu, MD Department of Anesthesiology Drexel University College of Medicine Philadelphia, Pennsylvania Jin Liu, MD, PhD Department of Anesthesiology West China Hospital, Sichuan University Chengdu, Sichuan, China Ronald S. Litman, DO Department of Anesthesiology and Critical Care Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Henry Rosenberg, MD, CPE Malignant Hyperthermia Association of the United States Livingston, New Jersey Department of Anesthesiology Rutgers New Jersey Medical School Newark, New Jersey Francis S. Stellaccio, MD Department of Anesthesiology Stony Brook University School of Medicine State University of New York at Stony Brook Health Science Center Stony Brook, New York Huafeng Wei, MD, PhD Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, Pennsylvania [email protected] Shuchun Yu, MD, PhD Department of Anesthesiology The Second Affiliated Hospital to Nanchang University Nanchang, Jiangxi, P.R. China [email protected] Xiaoyan Zhang, MD South Bay Anesthesia Medical Group Patient Safety and QA Committee, CASA Rancho Palos Verdes, California Yunxia Zuo, MD, PhD Department of Anesthesiology West China Hospital Sichuan University Chengdu, Sichuan, China