癫痫持续状态的临床及治疗

null癫痫持续状态的诊断及其治疗癫痫持续状态的诊断及其治疗复旦大学华山医院神经内科 朱国行癫痫持续状态的概念癫痫持续状态的概念又称癫痫状态（Status epilepticus, SE），为持久发作所形成的固定状态 According to the International Classification of Seizures, it is ''a condition characterized by an epileptic seizure that is so frequent or so prolonged as to create a fixed and lasting condition" 癫痫持续状态的概念癫痫持续状态的概念Recurrent epileptic seizures without full recovery of consciousness before next seizure begins 癫痫连续多次发作，发作间期意识不清 癫痫持续状态的概念癫痫持续状态的概念more or less continuous clinical and/or electrical seizure activity lasting >30 minutes, whether or not consciousness is impaired 一次发作持续达30min以上癫痫持续状态的概念癫痫持续状态的概念5 minutes of continuous convulsive seizures 3 discrete convulsions within an hour 癫痫持续状态的分类癫痫持续状态的分类●按病因：原发性、继发性 ●按发作部位分：全身性、部分性 ●按有无惊厥分：惊厥性、非惊厥性癫痫持续状态的病因癫痫持续状态的病因原发性 继发性 肿瘤、外伤、颅内感染、CVD、代谢性脑病、变性、脱髓鞘疾病、中毒等促发因素促发因素突然停药、换药、减药、漏药 发热、感染 酗酒、过劳、妊娠、分娩 停用其他镇静药 服用异菸肼、三环或四环抗抑郁药等Etiology of Status EpilepticusEtiology of Status EpilepticusMedication change 33 (39%) Infection 10 (12%) Structural 8 (9%) Metabolic 6 (7%) Ethanol/drug-related 5 (6%) Not status epilepticus 3 (4%) Other 20 (24%)全身性癫痫持续状态全身性癫痫持续状态●全身性惊厥性癫痫持续状态（GCSE） △全身强直-阵挛性癫痫（大发作）持续状态 △强直性癫痫持续状态 △阵挛性癫痫持续状态 △肌阵挛性癫痫持续状态 ●全身性非惊厥性癫痫持续状态（GNCSE） △失神发作（小发 作）持续状态部分性癫痫持续状态部分性癫痫持续状态●简单部分性运动性癫痫持续状态（Kojewnikow癫痫） ●简单部分性感觉性癫痫持续状态 ●复杂部分性癫痫持续状态 ●偏侧性癫痫持续状态 ●新生儿期癫痫持续状态全身强直-阵挛性癫痫状态 generalized tonic-clonic status epilepticus全身强直-阵挛性癫痫状态 generalized tonic-clonic status epilepticus●全身强直-阵挛反复发作 ●有70%～80%起始为部分性 ●不同程度意识障碍 ●EEG改变 ●首次癫痫发作即呈GTCSE要考虑为脑肿瘤全身强直-阵挛性癫痫状态的后果全身强直-阵挛性癫痫状态的后果GTCSE常可导致严重合并症 △呼吸障碍、窒息、吸入性肺炎——脑缺氧 △长时间抽搐——高热、电解质紊乱、酸中 毒、失水，心力、循环衰竭全身强直-阵挛性癫痫状态的原因全身强直-阵挛性癫痫状态的原因感染 外伤 突然停药 断药 失神状态 absence status失神状态 absence status●又称棘慢波木僵 spike-wave stupor ●多见于成人 ●持续性不同程度意识障碍（Roger） △轻度模糊—思维缓慢、情呆板（19%） △显著模糊—少动、缄默、智能损害（64%） △嗜睡—不动，不言，自己不能进食，失禁， 强刺激能唤醒（7%） △昏睡—木僵状态（8%）失神状态的EEG失神状态的EEG●双侧同步对称1-4Hz S&W ●对生理刺激无或轻反应 ●额区明显多棘慢或棘慢 ●分割爆发式，棘慢节律，爆发间可正常 ●δ、θ背景上出现散在或爆发棘-慢波 ●可有亚临床脑电失神状态失神状态的诊断与鉴别诊断失神状态的诊断与鉴别诊断●临床表现 ●EEG特征 ●需要与精神分裂症等木僵相鉴别 ●需与CPS状态相鉴别（EEG）失神状态与CPS状态鉴别失神状态与CPS状态鉴别项 目 失神状态 CPS状态 先兆 — + 自动症 主要面、手部 复杂行为自动症 发作后精神错乱 — + 脑电图 3Hz S&W 颞、额叶棘波 简单部分性发作状态 Simple partial status epilepticus (SPSE) 简单部分性发作状态 Simple partial status epilepticus (SPSE)●身体某部持续不停抽搐，连续数时，数日甚至数周（Kojewnikow癫痫）；还可有感觉障碍发作 ●发作后可有Todd麻痹 ●意识清楚 ●多由局灶病变引起 ●EEG呈局灶性改变复杂部分性癫痫状态 Complex partial status epilepticus(CPSE)复杂部分性癫痫状态 Complex partial status epilepticus(CPSE)●旧称精神运动性癫痫持续状态 Psychomotor status epilepticus ●临床表现形式多样 △持续性精神异常或意识障碍 △反复CPS，发作间精神错乱和意识障 碍 ●持续数时数日甚至数月CPSE脑电图改变CPSE脑电图改变●颞区或额区局限性异常 ●继发性普遍性癫痫样放电 ●局限或弥漫性棘波、尖波、棘（尖）慢波综合 ●爆发性θ活动CPSE诊断依据CPSE诊断依据●持续性复杂症状 ●反复发作复杂症状，间歇期仍有意识障碍或精神错乱 ●连续的局灶性（常于颞、额叶）或泛化为普遍性痫样放电 ●应与癔病、抑郁症、精神分裂症、肝性及肾性脑病等相鉴别其他形式的癫痫状态其他形式的癫痫状态●偏侧性SE ●肌阵挛性SE ●新生儿期SE偏侧性SE偏侧性SE △多见于婴幼儿，半侧阵挛性抽搐 △半身惊厥-偏瘫-癫痫（HHE）综合征偏侧性SE偏侧性SE本型多见于小儿，其中婴幼儿发生率占72％，多为一侧性阵挛状态，少数为一侧性强直状态，持续发作时间平均在l小时左右偏侧性SE偏侧性SE有的一开始呈杰克森氏发作，开始即有双眼同向偏视，然后一侧眼险、面肌抽搐，继之同侧上肢或下肢呈阵挛性抽搐，有时发作可左右交替，意识障碍程度不等偏侧性SE偏侧性SE在发作间歇期，常有神经系统异常体征,如抽搐侧偏瘫及病理征，偏瘫程度不等，多为一过性,在数小时或数日后自然恢复 肌阵挛性SE肌阵挛性SE△持续数时～数日肌阵挛 △多无意识障碍新生儿期SE新生儿期SE△ 症状不典型，形式不固定 △ 呼吸暂停，意识不清 △ 脑电图：1～4Hz慢波；2～6Hz节律性 S&W等SE的危险性与并发症SE的危险性与并发症●致死率在12%～50%，但GTCSE仍高 ●致残主要GTCSE，1.5h控制可完全恢复，10h控制多致脑损害 ●强直-阵挛 △乳酸堆积——酸中毒 △呼吸停止、氧耗增加 △去甲肾上腺素，肾上腺素水平升高可达80倍 △肺内压升高，吸入性肺炎 △肌蛋白尿 △高热、脱水、低血糖Annual Hospital Visits for Acute SeizureAnnual Hospital Visits for Acute Seizure368,000 patient visits to emergency rooms* 50,000 breakthrough seizures treated annually Status epilepticus 50,000~60,000 annually First seizure in 12% of patients* Scott Levin AuditAdverse effect of prolonged seizureAdverse effect of prolonged seizure When seizure lasts more than 30 to 60 minutes, CNS damage may result Vasodilatation, break down in blood brain barrier Increased intracranial pressure MRI may show focal edema Neuronal loss, especially in hippocampus Age Distribution of Status Epilepticus (SE)Age Distribution of Status Epilepticus (SE)Cases in Richmond, Virginia, from 1982 to 1989. 1982 to 1989 retrospective data base (n=546).Number of Patients 0204060801001201401601800~2~5~10~920~940~960~980+Age GroupDeLorenzo RJ, et al. Epilepsia. 1992;33(suppl 4):515-525.Mortality in Status Epilepticus by Age GroupMortality in Status Epilepticus by Age GroupAmong 546 patients with status epilepticus in Richmond, Virginia, from 1982 to 1989.% Mortalitiy01020304050600~2~5~10~920~940~960~980+Age GroupDeLorenzo RJ, et al. Epilepsia. 1992;33(suppl 4):515-525.Mortality in Status EpilepticusMortality in Status EpilepticusSE lasting longer than 60 minutes carried a mortality of 32% Mortality is about 2.7% for a shorter duration. SE caused by anoxia was associated with 70% mortality in adults Survival in Status Epilepticus by Duration of SeizureSurvival in Status Epilepticus by Duration of SeizureLength of Seizure >1 h <1 hSurvival curves for prolonged (solid line) and nonprolonged (dashed line) seizure duration. The data are presented as percent survival based on a 30-day follow-up period.DaysDeLorenzo RJ, et al. Epilepsia. 1992;33(suppl 4):515-525.% Survival60708090100051015202530Management of Status Epilepticus: General PrinciplesManagement of Status Epilepticus: General PrinciplesMedical emergency Prolonged electrical seizure activity causes neuronal damage EEG monitoring essential Systemic factors exacerbate SE-induced neuronal damage The longer the duration, the later the EEG stage, and the more subtle the motor manifestations, the harder SE is to stop A predetermined Rx protocol more effective 癫痫持续状态的治疗原则癫痫持续状态的治疗原则诊断要准、要快 迅速控制发作: 用药及时、强力、足量 维持生命机能、维持呼吸、循环、水电解质平衡，处理高热、感染、脑水肿 积极寻找病因，对因治疗 发作控制后，密切监护，维持抗痫治疗控制癫痫持续状态的常用药物控制癫痫持续状态的常用药物作用特点 苯二氮 卓类 巴比妥类 苯妥英类 丙戊酸类 其他 快速作用 安定 异戊巴比妥 副醛 氯硝安定 硫喷妥钠 利多卡因 氯羟安定 乙醚 慢速作用 苯巴比妥 苯妥英钠 德巴金 水合氯醛 苯妥英磷 (丙戊酸钠) 常用抗SE药物剂量及用法常用抗SE药物剂量及用法安定（地西泮，diazepam） 静注 成人10～20mg/次，<2mg/min 儿童0.25～0.5mg/kg/次，<1mg/min 每岁1～2mg 总量<10mg （婴儿<2～5mg，儿童<5～10mg） 静滴成人60～100mg+5%Glu 500ml 　　　　　　　40～１２０ml/h 抑制呼吸、降血压及使呼吸道分泌增加 null氯硝安定（氯硝西泮 clonazepam） 成人：1～4mg/次，IV， 0.1mg/min 儿童：0.1mg/kg 灌肠 氯羟安定（lorazepam, 劳拉西泮） 成人：0.1mg/kg，首次<5mg 注射速度1～2mg/min 儿童：0.05～0.1mg/kg，速度>2minnull异戊巴比妥（amobarbitalum, amytal） 成人0.2～0.5g，IV， <50mg/min 儿童1～4岁，0.1g静脉缓注 5岁以上，0.2g静脉缓注 苯巴比妥（phenobarbital） 肌注：成人0.1～0.2/次，儿童4～7mg/kg，　 　　　　每4～6h一次 静注：5mg/kg+生理盐水，30mg/min 静滴：5～10mg/kg·d+生理盐水，维持数日后逐渐停药 头4h总量达15mg/kg 24h总剂量<35mg/kgnull苯妥英钠（Phenytoin） 起效慢（30～60min后），半衰期长（10～15h） 不抑制呼吸、不影响意识，影响心律 成人15～18mg/kg，儿童18mg/kg 生理盐水稀释成5%溶液静滴(0.5+NS 10ml)，成人<50mg/min，小儿<1mg/kg/minIncidence and Clinical Consequences of Purple Glove Syndrome in Patients Receiving IV Phenytoin: A Mayo Clinic Study*Incidence and Clinical Consequences of Purple Glove Syndrome in Patients Receiving IV Phenytoin: A Mayo Clinic Study*Rationale: To study incidence and consequences of purple glove syndrome in patients receiving IV phenytoin Methods: Retrospective analysis of pharmacy records (3 mos) in Neurology Department Results: Eight (5.7%) of 140 patients who received phenytoin developed PGS Possibly dose-related: Median initial dose (total IV dose) 700 mg (900 mg) in affected vs 362.5 mg (500 mg) in unaffected (P>0.05; P<0.01, respectively) Possibly age-related: Median age 70 yrs in affected vs 49 yrs in unaffected (P=0.059) Conservative treatment of PGS sufficient in most patients Hospitalization prolonged in affected: Median stay 16.5 d for affected vs 10 d for unaffected (P<0.05) Conclusions: Possible prevention by using fosphenytoin *O払rien TJ, Cascino GD, So EL, Hanna DR. Epilepsia. 1997:38(suppl 8):Abstract 3.009.Purple Glove SyndromePurple Glove SyndromeStage I: 90 min after phenytoin extravasationHanna DR. J Neurosci Nurs. 1992;24:340-345.Purple Glove SyndromePurple Glove SyndromeStage II: 19 hr after phenytoin extravasationHanna DR. J Neurosci Nurs. 1992;24:340-345.Purple Glove SyndromePurple Glove SyndromeStage II: 40 hr after phenytoin extravasationHanna DR. J Neurosci Nurs. 1992;24:340-345.Necrosis of Hand After Phenytoin ExtravasationNecrosis of Hand After Phenytoin ExtravasationHayes & Chesney. J Am Acad Dermatol. 1990;28-360-363.Fosphenytoin Benefits: SummaryFosphenytoin Benefits: SummaryFosphenytoin Benefits: TolerabilityFosphenytoin Benefits: TolerabilitySignificantly better tolerated than IV phenytoin at injection site in IV administration Extremely well-tolerated option of IM injection Parallels AEs expected with phenytoin Fewer site changes due to irritation Dosing adjustments may be required with IV loading in patients with renal or hepatic impairment, the elderly, or those with hypoalbuminemia Fosphenytoin Benefits: Rapid AdministrationFosphenytoin Benefits: Rapid AdministrationCompletely and rapidly converted to phenytoin following IV infusion and IM injection When infused at the maximum rate of 150 mg PE/min, bioequivalent to equimolar dose of phenytoin at 50 mg/min Therapeutic levels reached within 30 minnull德巴金（丙戊酸钠 Depakine） 静注成人首次400～800mg/3～5min(<15mg/kg) 静滴1mg/kg·h 总剂量<2500mg/d 注意：每支400mg+4ml溶剂 可与葡萄糖液、生理盐水、碳酸氢钠及THAM配伍Depakine德巴金Depakine德巴金注：DPK 400mg +溶剂 4ml+Glu或生理盐水静滴null副醛（Paraldehyde） 肌注：成人8～12ml，儿童0.1～0.3ml/kg 静注：成人5～8ml，稀释0.2%，<1ml/min 灌肠：儿童5～15ml，用温开水稀释至30～50ml 利多卡因（lidocainum） 静滴成人100mg+5%Glu 200ml <2mg/min，<1200mg/6h 儿童5～10mg/kg·hnull水合氯醛 10%水合氯醛20~30ml (儿童0.5ml/Kg)保留灌肠 控制SE药物使用技巧控制SE药物使用技巧迅速控制发作 预防再发 长期维持治疗 越快越好 安定、苯巴比妥或 选择药物 首次足量 苯妥英钠缓慢静滴 长期口服 首选快速作用 12-24小时以上， 查找原因 的安定、异戊 重视一般治疗 对因治疗 巴比妥钠， 静脉给药 控制SE药物使用技巧控制SE药物使用技巧 首选安定 　 用12～24H 24H不发 继用苯巴比妥 肌注 48～72H不发　　停用苯巴比妥 口服 鼻伺 控制SE药物使用技巧控制SE药物使用技巧主意呼吸抑制 异戊巴比妥 副醛 安定 一般治疗一般治疗保持呼吸道通畅，气管切开及或人工呼吸 高热降温 纠正水电解质平衡 防治感染 减轻脑水肿，防治脑疝治疗举例 （American's working Group on SE, 1993）治疗方案举例 （American's working Group on SE, 1993）时间（min） 处 理 0～5 依据发作做出诊断 给氧或插管 观察生命体征、ECG监护、 纠正异常，建立静脉通道 测血糖，血生化、常规 6～9 血糖低或不明，成人先用Vit B1 100mg 成人50% Glu 50ml，儿童25% Glu 2ml/kg, IVnull10～20 NZP 0.1mg/kg 2mg/min IV DZP 0.2mg/kg 5mg/min IV, 5min 后可重复 21～60 PHT10～20mg/kg+生理盐水IV （500mg+NS 20ml), 限速成人 <50mg/min(2ml)，儿童<1mg/kg/min >60 PHT给后仍抽可再给药，最大<30mg/kg，或 PB20mg/kg，IV，限速100mg/min，仍抽给 于硫喷妥钠麻醉等 nullTreat complications of SE Treatment of cerebral edema secondary to SE has not been well studied. SE and cerebral edema may be caused by the same underlying condition. Hyperventilation and mannitol Edema due to SE is vasogenic in origin, so steroids may be useful. nullTreat complications of SE Hyperthermia: Usually remits rapidly after termination of SE. External cooling usually suffices if the core temperature remains elevated. High dose pentobarbital generally produces poikilothermia. Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)GENERAL CARE OF PATIENT Protect the Patient from injury Maintain the Airway Cardiac and Blood Pressure Intravenous Line Electrolytes and Ca, Mg, Glucose AED levels ABGTreatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)GENERAL CARE OF PATIENT Diagnostic Procedures toxic screen LP (when clinically indicated) EEG (when clinically indicated) CT (when clinically indicated)Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)ALL AEDs USUALLY GIVEN BY IV ROUTE Conventional AEDs Lorazepam Phenytoin/Fosphenytoin Phenobarbital (Paraldehyde) Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Status: Lorazepam Benzodiazepine shown to be effective in SE half life 13-15 hours (longer acting then diazepam) some respiratory depression 0.05-0.1 mg/kg given with repeated doses q 20 min. (up to 2-3 time) Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Status: Phenytoin very effective, first line drug 15-20 mg/kg up to 1 gm at 1mg/kg/min may cause cardiac arrhythmias and arrest produces minimal depression of consciousness Maximal brain concentration in 10-30 minutes Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Status: Fosphenytoin Prodrug of phenytoin Can be given iv or im IV rate up to 3 mg/kg/min Less cardiotoxic SE and vein irritation Converted quickly to phenytoin Load with 15-20 mg/kg (PE) ivTreatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Status: Phenobarbital 10-20 mg/kg up to 1 gm using 10mg/kg bolus initially, then repeating in 30 minutes maximum brain concentration in 1 hour respiratory depressant, especially with benzodiazepine Treatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Status: WHAT NOW? Following control of seizure, patient should be placed on maintenance does of anticonvulsant. Phenytoin particularly helpful because of lack of CNS depressing action (except at very high levels). Mental status may be depressed for one or two days due to status itself or medicationsTreatment of Status EP (STANFORD)Treatment of Status EP (STANFORD)Treatment of Refractory Status Epilepticus Pentobabital Coma Benzodiazepine Coma General AnesthesiaAfter control of SEAfter control of SEOther Tests as indicated CT/MRI: bleed, infection, AV malformations, neoplasm Lumbar puncture: if CNS infection suspected Blood cultures: Sepsis 癫痫持续状态的对策癫痫持续状态的对策迅速控制发作 首选安定 、异戊巴比妥钠静注 防止再发 选用安定、苯巴比妥、苯妥因钠、德巴金缓慢静滴 治疗并发症 病因治疗 ADEs长期应用 null