1、威胁人类生命的急症 癫癎持续状态,癫癎持续状态（Status epilepticus, SE）是神经科的急症，其死亡率为10%-12%。有资料统计显示：美国每年约有15万人口遭受着SE的威胁。SE如果持续时间过长，可能会造成严重的全身性和神经元损伤，增加以后癎性发作的危险性。研究表明：SE有年龄依赖性。比如，同样遭受SE侵袭，儿童(70 years old)更有希望存活下来。然而，在此情况下，儿童更容易发展成慢性癫癎。,SE的概念：连续多次癫癎发作且发作间期意识不清或一次癫癎发作持续30分钟以上者。,SE的病因及促发因素,多为继发性，包括颅脑外伤、颅内感染、脑血管病、颅内肿瘤、代谢性脑病、药物
2、中毒、变性与脱髓鞘疾病等。而颅内肿瘤（尤其额叶肿瘤）是继发性SE的常见原因。促发因素中最常见者为突然停药、换药、减药或漏服AEDS。其次为发热、感染、饮酒、劳累、熬夜、妊娠及分娩等。,SE的分类1 全身性惊厥性癫癎持续状态：最常见2 全身性非惊厥性癫癎持续状态(失神性癫癎持续 状态)：EEG呈广泛的3Hz棘慢波综合发放。 3 简单部分性发作持续状态4 复杂部分性发作持续状态：EEG改变主要在颞叶 或颞额叶局限性癎样放电。5 肌阵挛性癫癎持续状态6 偏侧性癫癎持续状态7 新生儿癫癎持续状态,SE的急性生理学改变 (并发症)全身系统性改变： 酸中毒、肺水肿、血压改变、心率紊乱、白细胞增多、高热、肾
3、脏损伤(肌球蛋白尿所致)CNS的改变： 颅内压升高、BBB损伤、脑对氧和葡萄糖的利用增加、脑水肿,SE的后遗症 智力障碍 持久的神经系统损害 反复的癫癎发作,SE 的 治 疗,治疗原则 1 迅速终止癫癎发作：通常惊厥状态在1.5h内得到控制，可以获得完全恢复；惊厥持续10h才获得控制，则常引起脑损伤。 2 维持通气、呼吸和循环功能的稳定， 防治并发症。 3 病因治疗 4 预防再发,一般处理,就地松开衣领，把头转向一侧，使其唾液与呕吐物流出口腔，以防止窒息和吸入性肺炎的发生。以纱布或手帕叠成条状塞入上下臼齿间，以减少舌尖咬破。加强护理，以防精神异常者发生意外。定期记录并观察生命体征，纠正异常。注
4、意吸痰吸氧，必要时行气管切开，呼吸机辅助呼吸。最好选用大静脉建立静脉通道，并用生理盐水维持，不要用葡萄糖。怀疑SE的病因可能是低血糖或发现有明显的低血糖时，应静脉补充50%葡萄糖50ml（儿童25葡萄糖2ml/kg），之前先静推100mg维生素B1。待通气、呼吸和循环功能稳定后，取静脉血测生化、血糖、血细胞分析、毒理检测，并定期做动脉血气分析。,药物治疗1 静脉注射安定是迅速控制癫癎的首选方法。 成人以每分钟2mg（年高者酌减）的速度匀速注射，直 至发作停止或总量达20-30mg； 儿童以每分钟1mg的速度匀速注射， 用量0.3-0.5mg/kg.最大剂量婴儿不超过2-5mg，儿童不超过5-1
5、0mg。 若病人复发，可在20min后在注射一次，成人24小时剂 量不超过120mg，儿童日剂量不超过0.25-1.0mg/kg。 若频繁静推安定达不到控制效果，应静滴氯硝安定，成人首次剂量为3mg。2 发作停止后，应注意使用长效抗癫癎药苯巴比妥维持。 苯巴比妥 0.1 肌注，q 6h。,3 防治脑水肿。 20甘露醇 125ml 静推 q 8h 合并甘油果糖 250ml 静注 q12h。4 防治感染。 青霉素400万U入5葡萄糖250ml，静注，Bid 合并头孢噻肟钠2.0入5葡萄糖30ml，静推，q12h。5 高热者宜物理降温。6 纠正水电解质紊乱和酸中毒。,From: Daniel H L
6、owenstein.Treatment options for status epilepticus. Current Opinion in Pharmacology 2005, 5: 334339Initial therapyLZP(劳拉西泮)比DZP（安定）好；在小孩、老人及不方便静脉给药情况下主张用fosphenytoin ；院外处理主张用LZP。New drug options静脉注射VPA（丙戊酸钠）； 用量1215 mg/kg ，血药浓度 75 mg/l 用量25 mg/kg，血药浓度 100150 mg/l 儿童用量3040 mg/kg 神经保护剂的应用 NMDAR拮抗剂：克他命
7、（ Ketamine ）和MK-801,Treatment of refractory status epilepticus （RSE）二十世纪90年代初，美国主张用戊巴比妥（pentobarbital ），而欧洲主张用硫喷妥钠（thiopentone ）；近年来，许多人主张用propofol or midazolam；有人将pentobarbital 、propofol 、 midazolam三药对比后发现，后两种药物的治疗效果相似，而pentobarbital 的治疗失败率较midazolam相对要少 ，但需要治疗的低血压却比propofol or midazolam要多。三药在各组间总的
8、死亡率相同。(三药疗效等分析对比见下页Table 2),A 50-year-old patient (70 kg) presents to the emergency room with a 30min history of continuous generalized tonicclonic seizures. Upon admission, the patient is comatose, shows twitching of the right face and arm, has a blood glucose of 80 mg/dl, and has stable vital sign
9、s. He has no history of seizures. Further history of the present illness and past medical history are not available.(1) First-line therapy. What benzodiazepine would you give and at what dose?(2) Second-line therapy. The patient is still seizing 10 min after receiving the benzodiazepine. He has now
10、been intubated, and vital signs are stable. What would be your next anticonvulsant medication and what would be the dose?,(3) Third-line therapy. Twenty minutes after receiving the first-line anticonvulsant medication, the patient is still seizing. Vital signs are stable. He is now in your ICU. What
11、 would be your next anticonvulsant medication and what would be the dose?(4) Fourth-line therapy. After receiving maximum doses of the above medications, the patient remains in convulsive status epilepticus. What would be your next anticonvulsant medication and what would be the dose?,(5) Electrogra
12、phic SE. The convulsions are terminated. However, the patient remains stuporous and EEG reveals electrographic status epilepticus (nonconvulsive status epilepticus,NCSE). What would be your medication of choice in this setting and what would be the dose?(6) Periodic lateralized epileptiform discharg
13、es (PLEDs). The NCSE is stopped. The patient is lethargic with a right hemiplegia. The following day, an EEG reveals left-sided PLEDs. What would be your treatment of PLEDs and what would be the dose?,Fig. Treatment preferences of neurologists for generalized convulsive status epilepticus. Data are
14、presented as n (%). All medications are given as single or repeated IV doses, unless otherwise noted. *Midazolam (three), diazepam PR (three), clonazepam PO (one). *Lorazepam (two), phenobarbital (one), diazepam PR (one), midazolam (one). ycIV propofol (eight), cIV pentobarbital (six), cIV midazolam
15、 (six). zMidazolam (five), lorazepam (two), phenytoin (one), fosphenytoin (one), phenobarbital PO (one). bLorazepam (two), midazolam (two), cIV thiopental (one), cIV lorazepam (one), cIV phenobarbital (one). cIV = continuous infusion; AED= antiepileptic drug.Derived from: Jan Claassen, Lawrence J. H
16、irsch, Stephan A. Mayer. Treatment of status epilepticus: a survey of neurologists. Journal of the Neurological Sciences 211 (2003) 3741,Survey respondents did not agree on the question as to whether or not to treat NCSE patients refractory to four AEDs: about half (42%) would add a new cIV-AED and
17、the other half (41%) would not. Prior surveys have not specifically addressed this question. After failure of three AEDs, cIV pentobarbital and cIV midazolam were the most popular treatment choices for partial SE in the expert consensus method. Of note, these authors did not allow for the selection
18、of no additional AEDs. The clinical significance of PLEDs is controversial; some consider them to be part of an ictalinterictal continuum. However, most respondents (85%) would not add additional AEDs to treat patients with this EEG finding in the aftermath of SE.,Taken together, status epilepticus
19、that is refractory to treatment remains a major problem that will require the development of new, more potent drugs, and large scale clinical trials with which to test their safety and efficacy. Moreover,treatment of refractory GCSE and NCSE needs to be studied in a large, prospective, randomized, multicenter trial so that physicians may be able to implement evidence-based treatment strategies for the treatment of refractory SE.,谢谢,
