Abstract

Malignant hyperthermia （MH） can be fatal if the crisis is not appropriately treated．

It is an inherited disease usually triggered by the administration of volatile inhalational anesthetics and／or succinylcholine， a muscle relaxant． In a patient with suspected MH， the mechanism of calcium release from storage in the sarcoplasmic reticulum in the skeletal muscle is abnormally accelerated．

Unexplained hypercarbia representing ＞55 mmHg of end－tidal carbon dioxide， tachycardia， and muscle rigidity （including masseter muscle rigidity） are early signs of the initiation of MH， because the metabolism is accelerated． The body temperature can rise by ＞0．5 °C／15 min and may reach ≥40 °C． Respiratory and metabolic acidosis， arrhythmia， cola－colored urine， increased levels of serum potassium， and tented T－waves on electrocardiogram are common and can lead to cardiac arrest．

MH should be treated by discontinuation of the triggering agents， administration of intravenous dantrolene （initially 1 mg／kg）， and reduction of the body temperature．

Early diagnosis and sufficient dantrolene with body temperature reduction are essential to relieve the patient’s MH crisis．

This guideline in Japanese translation has been posted on the website： http：／／www．anesth．or．jp／guide／pdf／guideline＿akuseikounetsu．pdf．

Keywords Malignant hyperthermia · Dantrolene · Malignant hyperpyrexia · Hypercarbia · Hypercapnia

Abbreviations

MH Malignant hyperthermia

PMH Postoperative malignant hyperthermia

1．停用挥发性麻醉剂和琥珀胆碱。

2． 请外科医生立即停止手术，并呼吁帮助，因为这个紧急危机需要一个团队 合作。＊b

3．如果手术必须继续进行，请使用静脉麻醉剂和非去极化肌肉松弛剂维持麻醉。

4． 在流量为10L／min的情况下，100％氧气过度通气冲洗挥发性麻醉剂（通过加倍分通量）和较低的ETCO2。

5． 准备丹曲林≥1．0毫克／公斤，因为这是必要的，以解决持续的肌肉僵硬和复发。

6． 用60毫升蒸馏水摇动溶解20毫克丹曲林。通过大口径IV给予丹曲林1．0毫克／公斤（2．0毫克／公斤更优）超过15分钟。重复，直到病人有ETCO2的下降，肌肉僵硬和／或心率降低。丹曲林的最大剂量为7．0mg／kg。

7． 建立动脉管路进行血气分析，以确定代谢性酸中毒的程度。

8． 给予冷却的生理盐水，至少50－60毫升／公斤静脉注射。＊c

9．如果核心温度＞为39°C，则通过强制冷气冷却病人的体表。当温度下降到＜38°C时停止冷却。

10． 用标准药物治疗心律失常治疗，但不要使用Ca通道阻滞剂，因为这些将导致使用单曲林的患者发生心脏骤停。

11． 每小时保持尿量≥1．0ml／kg。如有必要，给予速尿0．5－1mg／kg（最大剂量20mg）。每小时给碳酸氢钠1．0mEq／kg，如果BE＜−8．0mEq／L（最大50mEq／L）。考虑每小时使用碳酸氢钠1．0mEq／kg来治疗CK、钾和肌红蛋白尿水平的升高。

12．如果可能的话，拆卸麻醉剂并更换麻醉电路，但这是不必要的。

13． 如果存在高钾血症（K＞5．9mEq／L），用50％的葡萄糖加常规胰岛素（10U IV），每小时检查血糖水平，或氯化钙10mg／kg（最大剂量2000mg），或葡萄糖酸钙30mg／kg（最大剂量3000mg）。

14． 实验室检查：主要是血气分析、血糖、电解质、乳酸、CK、尿液和血肌红蛋白以及凝血。在MH的开始，最好在30分钟和4、1 2、24和48小时后进行反复评估。

15． 当病人病情稳定时，转移到重症监护病房至少24小时。关键指标呼气末二氧化碳稳定性下降到正常范围，心动过速正常化，无心律失常，体温恢复，全身肌肉强直得到解决。＊d，＊e

Q＆A

Q  高钾水平和乳酸水平是否足以决定给予丹曲林？

A  不足以，因为他们不是MH的特异性表现。 高热，代谢酸中毒，全身肌肉僵直，尽管人工过度通气ETCO2还是持续性升高，这些是考虑给予丹曲林的基本条件。

Q 我们是否应该尽快要求终止手术？当病人对治疗有反应时，我们能继续手术吗？

A 面对MH的发现，建议尽快停止手术并推迟。如果体温＞40°C，强烈建议立即停止手术，因为死亡率在这些条件下是相当高的。如果体温＜37°C且稳定，ETCO2保持下降，手术也许可以重新开始。

Q 生理盐水是MH危机所必需的唯一液体吗？ 还有其他输液吗？

A  欧洲和北美推荐生理盐水输注，尽管当给予大量生理盐水时可能产生稀释性酸中毒。乳酸林格溶液不推荐，因为它可能加重代谢性酸中毒下的乳酸酸中毒。 碳酸林格液似乎比乳酸林格溶液更可取；然而，在MH危机中没有明确的证据推荐输液的解决方案。

Q 当治疗成功病情得到改善时，是否有任何明显的标准来判断拔管时机或解除麻醉危机事件？

A 判断应当交给那些正在治疗患者的人，因为他们更好地了解病人的个人情况。仔细观察是必要的，即使拔管后至少48小时，因为如果镇痛和镇静不足，MH可能会复发．

Q 对接受丹曲林的病人，气管插管和人工通气是必不可少的吗？

A 它们不一定需要。判断应交给当场的麻醉医生。没有特殊的限制；然而，大量的丹曲林可能导致肌肉无力和呼吸功能障碍，包括误吸。

Perioperative management

Preoperative evaluation

1． Preoperative evaluation of a patient with suspected MH History taking of intraoperative and postoperative episodes of hyperthermia， muscle rigidity， cola－colored urine， and muscle pain is important． If a history of this kind of episode is apparent， take care to treat the patient as potentially susceptible to MH．Even if there is no apparent history of previous anesthesia experience， it is not appropriate to rule out MH because MH is not necessarily provoked even if triggering agents are used ［16］．

2． Past history of heat stroke， exercise－induced rhabdomyolysis， and familial history

3． How to assess an increased serum CK level

4． Congenital myopathy related to MH

Caution in planning safe anesthesia

5． Consider what kind of anesthesia is safe for those who are MH susceptible．

6． An agonist of the L－type Ca channel has been reported to increase intracellular Ca levels ［28， 29］． It is recommended that Ca blockers such as verapamil should not be used along with dantrolene， since hyperkalemia and profound hypotension may occur with this drug combination ［16］．

7． Adequate sedation is necessary to prevent excessive anxiety and tension throughout the perioperative period ［16］．

8． Preparation of the anesthesia machines， use of nontriggering anesthetics， adequate monitoring， availability of sufficient quantities of dantrolene and appropriate postoperative care are essential for performing safe anesthesia ［30］．

9． Prepare sufficient quantities of dantrolene according to the body weight of the patient． Prepare 1 mg／kg of dantrolene to keep close at hand， because the recommended initial dose of dantrolene is 1 mg／kg in Japan；however， it is 2 mg／kg in Europe and North America． Disolve 20 mg／vial in 60 ml of distilled water．

10． Prepare anesthesia machines by detaching the vaporizer and washing out the remaining volatile inhalational anesthetic agents to reduce the risk of exposure． Modern anesthesia workstations are more complex and contain more gas－absorbing materials inside． It is recommended that protocols are prepared for the new generation anesthesia machines ［31］． The washout times with 10 L／min of fresh gas flow for the Avance™ and Aisys™ require flushing of these workstations for 10 to ＞90 min ［32］． It is not necessary to flush machines equipped with non－rebreathing circuits． CO2 absorbent and rebreathing circuits including a reservoir bag must be replaced with new ones．

11． Maintaining anesthesia and postoperative care．

5． 考虑哪种麻醉对MH易感者是安全的。

6． L型Ca通道的激动剂已被报道可提高细胞内Ca水平［28，29］。这是推荐的钙通道阻滞剂，如维拉帕米，不应与丹曲林一起使用，因为高钾血症和严重的低血压可能发生在这种药物组合时［16］。

7． 在整个围手术期充分镇静是必要的［16］，防止过度焦虑和紧张。

8． 麻醉机的准备，非触发麻醉剂的使用，足够的监测，可用足够数量的丹曲林和适当的术后护理是执行安全麻醉［30］所必需的。

9． 根据体重准备足够数量的丹曲林病。准备1mg／kg的丹曲林保持在手边，因为在日本建议的初始剂量丹曲林是1mg／kg；然而，在欧洲和北美，它的推荐剂量是2mg／kg。将20mg／kg溶于60毫升蒸馏水中。

10． 准备麻醉机，分离汽化器，清洗剩余的挥发性吸入麻醉剂，以减少暴露的风险。现代麻醉工作站更复杂，内部含有更多的气体吸收材料。建议为新一代麻醉机［31］准备方案。新鲜气体流量为10L／min的冲洗时间至少＞90分钟［32］。没有必要冲洗装有非回呼吸电路的机器。二氧化碳吸收和再呼吸电路，包括储油袋，必须更换为新的。

11． 保持麻醉和术后护理。

Explaining the disease to a patient and family members after MH has been diagnosed 这部分和家属的解释很重要

Include the following items that are immediately relevant：

1． MH is not caused by a drug allergy but is a hereditary disease．

2． It is a pharmacogenetic disorder of skeletal muscle presenting as a hypermetabolic response to inhalational anesthetics and depolarizing muscle relaxant ［34］．

3． Patients are free from any signs of MH in their everyday activities， with the exception of hard physical labor．

4． The standard for diagnosis of MH is currently a muscle contraction test． Other biochemical， hematological， and physical tests lack significant sensitivity and specificity to be used diagnostically ［35］．

5． If MH or MH susceptibility has been determined in blood relatives， treat the patient as MH susceptible and notify the relatives of the possibility of MH．

6． Stressing with exercise and heat stroke are potential triggers for MH ［36–40］． Death due to non－anesthetic MH occurs in a small percentage of patients who develop heat stroke； nonetheless， MH susceptibility should be considered as these patients may demonstrate an exaggerated response to stress

1．MH不是由药物过敏引起的，而是一种遗传性疾病。

2． 它是骨骼肌的一种药物遗传疾病，表现为对吸入麻醉药和去机化肌松药的高代谢反应［34］。

3． 患者在日常活动中没有任何MH的迹象，除了经常做一些艰苦的体力劳动。

4． 目前MH的诊断标准是肌肉收缩试验。其他生化，血液学，还有物理测试缺乏明显的敏感性和特异性可用于诊断［35］。

5． 如果在直系亲属中已确定MH或MH易感，则将患者视为MH易感并通知亲属MH的可能性。

6． 强调运动和中暑是MH［36－40］的潜在触发因素。非麻醉性MH死亡的比例很小，发生在中暑的患者；尽管如此，MH易感性应该被考虑，因为这些患者可能表现出对压力的夸大反应。

Include the following items concerning future anesthesia：

1． Prescribing oral dantrolene before anesthesia is not recommended because it produces severe muscle weakness ［41–43］．

2． Local anesthetics and regional anesthesia including subarachnoidal and epidural anesthesia are safe ［34， 43， 44］． It is preferable to prescribe sedatives intravenously to lessen anxiety and stress ［34， 43–45］．

3． Avoid inhalational anesthetics when receiving medical treatment needing general anesthesia． Intravenous anesthetics are assumed to be safe for performing the anesthesia．

4． It is recommended that these patients receive medical treatment in the facilities of qualified members of the JSA because adequate treatment is available there ［46］．

5． Even when the results of the muscle biopsy test and genetic test are negative， this is not sufficient to rule out MH ［47–49］．

包括以下有关未来的麻醉计划：

1． 不推荐在麻醉前给口服丹曲林，因为它会产生严重的肌肉无力［41－43］。

2． 局麻药和区域麻醉包括蛛网膜下腔麻醉和硬膜外麻醉是安全的［34，43，44］。最好静脉注射镇静剂，以减轻焦虑和压力。

3． 在接受需要全麻治疗时避免吸入麻醉药。静脉麻醉被认为是安全的。

4． 建议这些患者在JSA合格成员的设施内接受医疗，因为那里有足够的治疗设备。

5． 即使肌肉活检试验和遗传试验结果为阴性，这也不足以排除MH［47–49］。

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