1、恶性高热专业知识讲座恶性高热专业知识讲座概述 恶性高热（Malignant Hyperthermia，MH）是一个基因性临床病理综合征，患者平时无异常表现，在全麻过程中接触挥发性吸入麻醉药和去极化肌松药（琥珀酰胆碱）后出现骨骼肌强直性收缩，产生大量能量，导致体温持续快速增高，在没有特异性治疗药物的情况下，一般的临床降温措施难以控制体温的增高，最终可导致患者死亡。在一般人群中，预计MH发作的发生率为每100,000次麻醉剂给予1例Exposure of an individual who has a genetic susceptibility(ryanodine receptor RYR1 o
2、r dihydropyridine receptor DHP mutation)to an anesthetic triggering agent(ie,volatile inhalational anesthetic agent,succinylcholine,or both)may result in malignant hyperthermia.This reaction is caused by an altered calcium balance between the lumen of the sarcoplasmic reticulum(SR)and the sarcoplasm
3、.Normally,muscle cell depolarization is sensed by the DHP receptor,which is thought to signal RYR1 opening by a direct physical connection.In malignant hyperthermia,accumulation of abnormally high levels of calcium in the sarcoplasm causes uncontrolled anaerobic and aerobic metabolism and sustained
4、muscle cell contraction.This results in the clinical manifestations of respiratory acidosis,metabolic acidosis,muscle rigidity,and hyperthermia.If the process continues unabated,adenosine triphosphate(ATP)depletion eventually causes widespread muscle fiber hypoxia(cell death,rhabdomyolysis),which ma
5、nifests clinically as hyperkalemia and myoglobinuria and an increase in creatine kinase.Dantrolene sodium binds to RYR1,causing it to favor the closed state,thereby reversing the uninhibited flow of calcium into the sarcoplasm.Larach MG,Gronert GA,Allen GC,et al.Clinical presentation,treatment,and c
6、omplications of malignant hyperthermia in North America from 1987 to 2006.Anesth Analg 2010;110:498.发病机制骨骼肌细胞膜发育缺陷诱发药物肌细胞浆内钙离子浓度迅速增高，使肌肉挛缩产热急剧增加，体温迅速升高酸中毒高血钾低血氧心律失常死亡（MOF，DIC）诱发药物 吸入麻醉药：乙醚、氟烷、安氟烷、异氟烷、地氟烷和七氟烷。去极化肌松药：琥珀胆碱 其它有过报道的药物：氯胺酮、利多卡因和氟哌啶醇。Typical order of appearance of Typical order of appearan
7、ce of clinical signs of malignant clinical signs of malignant hyperthermiahyperthermiaMasseter spasm(in some cases)HypercarbiaSinus tachycardiaGeneralized muscular rigidityTachypneaCyanosisRapidly increasing temperatureElevated temperatureSweatingVentricular tachycardiaCola-colored urineVentricular
8、fibrillationExcessive bleedingLarach MG,Gronert GA,Allen GC,et al.Clinical presentation,treatment,and complications of malignant hyperthermia in North America from 1987 to 2006.Anesth Analg 2010;110:498.高热 高钾血症相关的心电图改变 心室异位起搏/二联率 室性心动过速/心室颤动 肌红蛋白尿 出血过多 高碳酸血症 窦性心动过速 咬肌强直(MMR)全身肌肉强直体征Clinical signClin
9、ical signPercentage with signPercentage with signHypercarbia92.2Sinus tachycardia72.9Rapidly increasing temperature64.7Elevated temperature52.2Generalized muscular rigidity40.8Tachypnea27.1Masseter spasm26.7Sweating17.6Cola-colored urine13.7Cyanosis9.4Ventricular tachycardia3.5Excessive bleeding2.7V
10、entricular fibrillation2.4 Larach MG,Gronert GA,Allen GC,et al.Clinical presentation,treatment,and complications of malignant hyperthermia in North America from 1987 to 2006.Anesth Analg 2010;110:498.实验室检查Laboratory studyLaboratory studyTypical value in MHTypical value in MHPatient conditionsPatient
11、 conditionsCreatine kinase20,000 international unitsWith succinylcholine10,000 international unitsWithout succinylcholineUrine myoglobin60 mcg/LSerum myoglobin170 mcg/LSerum K6 mEq/LWithout renal failurePaCO260 mmHgDuring controlled ventilation65 mmHgDuring spontaneous ventilationArterial pH10L/min）
12、进行过度通气（分钟通气量达正常值的23倍）病情汇报，寻求帮助 换用非诱发药物维持麻醉（全凭静脉麻醉TIVA）告知外科医生，终止或推迟手术处理 丹曲林：丹曲林：尽快获取足够丹曲林（3650瓶）静脉注射丹曲林首剂量2.5mg/kg，随后再静脉内单次快速给予1mg/kg，并重复该剂量直到急性MH的体征消退。（每瓶丹曲林20mg以60ml灭菌注射用水溶解。注意：禁用生理盐水或葡萄糖溶液溶解丹曲林禁用生理盐水或葡萄糖溶液溶解丹曲林）根据病情发展，每4-6小时静注或静滴追加丹曲林1mg/kg 用药时间至少不短于24小时，直至体温退烧或血CK下降，心血管系统功能稳定。最后被观察到的急性MH体征出现后持续使用
13、24-48小时。支持治疗 监测和治疗高钾血症(即钙、碳酸氢盐、胰岛素-葡萄糖)监测和治疗酸中毒；考虑碳酸氢盐。持续监测核心温度(如，食管、鼓室、直肠体温计探头)（38.5以下）留置导尿管，监测尿液颜色和尿量（CK值通常会在MH发病大约14小时后达到峰值）监测各肌肉筋膜室以预防急性筋膜室综合征 采取措施来防止肌红蛋白尿引起的肾衰竭(即补液、利尿剂、碳酸氢盐)监控DIC死亡率死亡率 常规使用ETCO2监测和能获取丹曲林治疗，死亡率1%-17%。未接受体温监测的患者死亡的可能性至少是接受了核心体温监测的患者的2倍。所有的死亡均发生于体温的峰值为38.9或更高的患者中。增加MH患者发生心搏骤停和死亡的风险的其他因素包括高龄、共存疾病、肌肉发达体型(如年轻男性)和发生了DIC
