8 CQ 8 1 status epilepticus SE ILAE ILAE ILAE t1 t t1 5 2,3 SE t2 2 1 Proposal for revised clinical and electr

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1 8 CQ 8 1 status epilepticus SE ILAE ILAE ILAE t1 t t1 5 2,3 SE t2 2 1 Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on classi fication and Terminology of the International League Against Epilepsy. Epilepsia Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out of hospital status epilepticus. N Engl J Med PubMed Status Epilepticus AND define* OR definition* 136 PubMed "Status Epilepticus/classification" Majr OR "Status Epilepticus/etiology" Majr

2 1 5 early status epilepticus 30 established status epilepticus refractory status epilepticus 1 stage super refractory status epilepticus 1 1 Shorvon S, Ferlisi M. The treatment of super refractory status epilepticus a critical review of available therapies and a clinical treatment protocol. Brain Pt Brophy GM, Bell R, Claassen J, et al. Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guide lines for the evaluation and management of status epilepticus. Neurocrit Care Mazurkiewicz Be dzi ska M, Szmuda M, Zawadzka M, et al. Current treatment of convulsive status epilepticus a thera peutic protocol and review. Anaesthesiol Intensive Ther Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol PubMed Status Epilepticus/drug therapy" AND first line OR first choice 49 PubMed Anticonvulsants/therapeutic use Majr AND Status Epilepticus/drug therapy Majr OR Status Epilepticus/drug therapy MajrAND first line OR first choice CQ 8 2 8CQ 8 2

3 78 第8章てんかん重積状態血液検査薬物血中濃度注 4 抗てんかん薬などジアゼパム注射液注腸注 1 ミダゾラム注 2 鼻腔口腔内筋注投与静脈確保が困難な場合ジアゼパム CT/MRI 注 5 脳波難治てんかん重積状態 refractory status epilepticus 持続持続 mg/kg mg/kg/時で mg/kg mg/kg/時で髄液検査注 6 持続 mg/kg mg/kg/時で mg/kg/時で持続小児 mg/kg/時またはプロポフォール 1 2 有効であれば 2 5 小児では禁忌またはチオペンタール 3 5 有効であれば 2 5 またはチアミラール 3 5 有効であれば 2 5 ミダゾラム注 2 第 3 段階気管内挿管人工呼吸脳波モニタリング 60 分 120 分以上ホスフェニトイン 22.5 mg/kg 150 mg/分以下またはフェノバルビタール mg/kg 100 mg/分以下または注 2 ミダゾラム mg/kg 1 mg/分その後 mg/kg/時で持続小児 mg/kg/時またはレベチラセタム注 3 1,000 3,000 mg 2 5 mg/kg/分で小児 mg/kg 最大 3,000 mg 第 2 段階持続確定したてんかん重積状態 established status epilepticus 気道確保酸素投与循環モニタリング 30 分 5 10 mg 5 mg/分小児 mg/kg ロラゼパム 4 mg 2 mg/分小児 0.1 mg/kg 最大 4 mg 小児ではミダゾラム注 mg/kg 持続早期てんかん重積状態 early status epilepticus 血糖 60 mg/dl 以下の場合塩酸チアミン 100 mg ブドウ糖 50% 50 ml 第 1 段階静脈確保バイタルサイン 5分図 1 てんかん重積状態の治療フローチャート文献 1-5 より作成保険適用外注 1 ジアゼパム注射液注腸の用量は mg 小児では mg/kg 注 2 ミダゾラムを鼻腔口腔内筋注投与する場合は 0.5% 注射液を 10 mg 小児では 0.3 mg/kg 使用する保険適用外持続する場合は 0.1% 注射製剤が保険適用であるミダゾラム 0.1% 注射製剤の添付文書での投与量は静脈投与 0.15 mg/kg 持続投与 mg/kg/時となっている全身麻酔療法では適宜増減する注 3 てんかん重積状態には保険適用外である注 4 てんかん治療中であれば服用中の抗てんかん薬血中濃度を確認するまたけいれん誘発性薬物テオフィリンなどの過量が疑われる場合は可能であれば血中濃度を確認する注 5 必要に応じて頭部 MRI または CT を行い原因を検索する必要があれば急性症候性発作に準じて治療を開始する心因性発作の鑑別や治療効果の判定のために持続脳波モニタリングができれば理想的であるが困難であっても治療後にてんかん重積状態が終息しているか脳波で確認することが望ましい注 6 髄膜炎脳炎などが疑われる症例は髄液検査を行う髄液一般培養顕鏡などのほかに後に抗神経抗体などの検索ができるように一部を冷凍保存することが望ましいロラゼパム製剤は 2017 年 12 月現在わが国では未発売である検査薬剤投与処置モニタリング Stage

4 , mg 0.3 mg/kg 0.5% 0.1% % 63.4% Remy C, Jourdil N, Villemain D, et al. Intrarectal diazepam in epileptic adults. Epilepsia Dieckmann RA. Rectal diazepam for prehospital pediatric status epilepticus. Ann Emerg Med Minagawa K, Miura H, Mizuno S, et al. Pharmacokinetics of rectal diazepam in the prevention of recurrent febrile convul sions. Brain Dev McMullan J, Sasson C, Pancioli A, et al. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta analysis. Acad Emerg Med Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med Appleton R, Macleod S, Martland T. Drug management for acute tonic clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev CD PubMed Status Epilepticus/drug therapy" AND first line OR first choice 49 CQ CQ 8 2 1

5 PubMed Anticonvulsants/therapeutic use Majr AND Status Epilepticus/drug therapy Majr OR Status Epilepticus/drug therapy MajrAND first line OR first choice

6 mg 76% %CI % Leppik IE, Derivan AT, Homan RW, et al. Double blind study of lorazepam and diazepam in status epilepticus. JAMA Prasad K, Krishnan PR, Al Room K, et al. Anticonvulsant therapy for status epilepticus. Br J Clin Pharmacol Chamberlain JM, Okada P, Holsti M, et al. Lorazepam vs diazepam for pediatric status epilepticus a randomized clinical trial. JAMA Prasad M, Krishnan PR, Sequeira R, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev CD PubMed Status Epilepticus/drug therapy" AND first line OR first choice 49 PubMed Anticonvulsants/therapeutic use Majr AND Status Epilepticus/drug therapy Majr OR Status Epilepticus/drug therapy MajrAND first line OR first choice CQ 8 2 8CQ 8 2 2

7 CQ % % 95%CI % 3 4, % 1 1 Thomson A. Fosphenytoin for the treatment of status epilepticus an evidence based assessment of its clinical and economic outcomes. Core Evid Shorvon S, Walker M. Status epilepticus in idiopathic generalized epilepsy. Epilepsia Suppl Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine resistant convul sive status epilepticus a meta analysis of published studies. Seizure Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status Epilepticus. N Engl J Med Lowenstein DH. The management of refractory status epilepticus an update. Epilepsia Suppl

8 PubMed Status Epilepticus AND "Diazepam" OR "Phenytoin" OR "Midazolam" OR "Propofol" 357 PubMed "Status Epilepticus" MeshAND "Phenytoin/therapeutic use" Mesh CQ 8 2 8

9 CQ % 95%CI % Shaner DM, McCurdy SA, Herring MO, et al. Treatment of status epilepticus a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology Treiman DM, Meyers PD, Walton NY et al. A comparison of four treatments for generalized convulsive status Epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine resistant convul sive status epilepticus a meta analysis of published studies. Seizure Scottish intercollegiate guidelines network. Diagnosis and management of epilepsy in adults. A national clinical guideline. April Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America s Working Group on Status Epilepticus. JAMA PubMed Status Epilepticus AND "Diazepam" OR "Phenytoin" OR "Midazolam" OR "Propofol" 357 PubMed "Status Epilepticus" MeshAND "Phenobarbital/therapeutic use" Mesh

10 , Singhi S, Murthy A, Singhi P, et al. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol Claassen J, Hirsch LJ, Emerson RG, et al. Treatment of refractory Status epilepticus with pentobarbital, propofol, or midazolam a systematic review. Epilepsia McMullan J, Sasson C, Pancioli A, et al. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta analysis. Acad Emerg Med Prasad M, Krishnan PR, Sequeira R, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev CD Claassen J, Hirsch LJ, Emerson RG, et al. Continuous EEG monitoring and midazolam infusion for refractory nonconvul sive status epilepticus. Neurology PubMed Status Epilepticus AND "Diazepam" OR "Phenytoin" OR "Midazolam" OR "Propofol" 357 PubMed "Status Epilepticus" MeshAND "Midazolam/therapeutic use" Mesh CQ 8 2 8CQ 8 2 5

11 CQ % % % 3 1 Deshpande LS, Delorenzo RJ. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy. Front Neurol Zelano J, Kumlien E. Levetiracetam as alternative stage two antiepileptic drug in status epilepticus a systematic review. Seizure Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine resistant convul sive status epilepticus a meta analysis of published studies. Seizure Alvarez V, Januel JM, Burnand B, et al. Second line status epilepticus treatment comparison of phenytoin, valproate, and levetiracetam. Epilepsia Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus a randomized, open labeled pilot study. J Neurol PubMed "Status Epilepticus" MeshAND "levetiracetam/therapeutic use" Mesh

12 % CQ8 2 5 mg/kg/ Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus effect of treatment aggressiveness on prognosis. Arch Neurol Rossetti AO. Which anesthetic should be used in the treatment of refractory status epilepticus? Epilepsia Suppl CQ CQ 8 3

13 3 van Gestel JP, Blussé van Oud Alblas HJ, Malingre M, et al. Propofol and thiopental for refractory status epilepticus in children. Neurology Parviainen I, Kälviäinen R, Ruokonen E. Propofol and barbiturates for the anesthesia of refractory convulsive status epilep ticus pros and cons. Neurol Res Prabhakar H, Kalaivani M. Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database Syst Rev CD PubMed Status Epilepticus AND general anesthesia 48 PubMed "Status Epilepticus" MeshAND "Anesthesia, General" MeshOR "general anesthesia" TIAB

14 1 psychogenic nonepileptic seizure PNES 2 3 nonconvulsive status epilep ticus NCSE 4 5 PNES 1,2 PNES % subtle convulsion electrical status 3 flat EEG 3,4 burst suppression 5 NCSE 6,7 6 NCSE 82% Meierkord H, Will B, Fish D, et al. The clinical features and prognosis of pseudoseizures diagnosed using video EEG telemetry. Neurology Holtkamp M, Othman J, Buchheim K, et al. Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting. Neurology DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia Krishnamurthy KB, Drislane FW. Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refrac tory status epilepticus. Epilepsia Shorvon S, Baulac M, Cross H, et al. The drug treatment of status epilepticus in Europe consensus document from a workshop at the first London Colloquium on Status Epilepticus. Epilepsia Claassen J, Taccone FS, Horn P, et al. Recommendations on the use of EEG monitoring in critically ill patients consensus statement from the neurointensive care section of the ESICM. Intensive Care Med Sutter R, Kaplan PW. Electroencephalographic criteria for nonconvulsive status epilepticus synopsis and comprehensive survey. Epilepsia Suppl Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG monitoring in criti cally ill patients. Neurology CQ CQ 8 4

15 9 Alvarez V, Drislane FW, Westover MB, et al. Characteristics and role in outcome prediction of continuous EEG after status epilepticus A prospective observational cohort. Epilepsia PubMed Status Epilepticus AND "Electroencephalography" 178 PubMed Status Epilepticus majr AND "Electroencephalography" Mesh AND "Monitoring, Physiologic" Mesh OR monitor*

第 8 章てんかん重積状態 73 CQ 8-2 てんかん重積状態に使う薬剤はなにか推奨図 1 にてんかん ( けいれん ) 重積状態での治療フローチャートを示す 1) ( グレード C). 1) Recommendations of the Epilepsy Foundation of Amer

第 8 章てんかん重積状態 73 CQ 8-2 てんかん重積状態に使う薬剤はなにか推奨図 1 にてんかん ( けいれん ) 重積状態での治療フローチャートを示す 1) ( グレード C). 1) Recommendations of the Epilepsy Foundation of Amer 72 第 8 章てんかん重積状態 CQ 8-1 てんかん重積状態の定義はなにか推奨国際抗てんかん連盟 (ILAE, 1981) によれば, てんかん重積状態 (status epilepticus; SE) とは, 発作がある程度の長さ以上に続くか, または, 短い発作でも反復し, その間の意識の回復がないものと定義されている 1). これまで持続時間については,30 分とすることが多かった 2).