[學(xué)習(xí)]威脅人類生命的急癥

1、威脅人類生命的急癥 －癲癎持續(xù)狀態(tài),,癲癎持續(xù)狀態(tài)（Status epilepticus, SE）是神經(jīng)科的急癥，其死亡率為10%-12%。有資料統(tǒng)計顯示：美國每年約有15萬人口遭受著SE的威脅。SE如果持續(xù)時間過長，可能會造成嚴(yán)重的全身性和神經(jīng)元損傷，增加以后癎性發(fā)作的危險性。研究表明：SE有年齡依賴性。比如，同樣遭受SE侵襲，兒童(70 years old)更有希望存活下來。然而，在此情況下，兒童更容易發(fā)展成慢性癲癎。,

2、SE的概念：連續(xù)多次癲癎發(fā)作且發(fā)作間期意識不清或一次癲癎發(fā)作持續(xù)30分鐘以上者。,SE的病因及促發(fā)因素,多為繼發(fā)性，包括顱腦外傷、顱內(nèi)感染、腦血管病、顱內(nèi)腫瘤、代謝性腦病、藥物中毒、變性與脫髓鞘疾病等。而顱內(nèi)腫瘤（尤其額葉腫瘤）是繼發(fā)性SE的常見原因。促發(fā)因素中最常見者為突然停藥、換藥、減藥或漏服AEDS。其次為發(fā)熱、感染、飲酒、勞累、熬夜、妊娠及分娩等。,SE的分類1 全身性驚厥性癲癎持續(xù)狀態(tài)：最常見2 全身性非驚厥性癲癎持

3、續(xù)狀態(tài)(失神性癲癎持續(xù) 狀態(tài))：EEG呈廣泛的3Hz棘慢波綜合發(fā)放。 3 簡單部分性發(fā)作持續(xù)狀態(tài)4 復(fù)雜部分性發(fā)作持續(xù)狀態(tài)：EEG改變主要在顳葉 或顳額葉局限性癎樣放電。5 肌陣攣性癲癎持續(xù)狀態(tài)6 偏側(cè)性癲癎持續(xù)狀態(tài)7 新生兒癲癎持續(xù)狀態(tài),SE的急性生理學(xué)改變 (并發(fā)癥)全身系統(tǒng)性改變： 酸中毒、肺水腫、血壓改變、心率紊亂、白細(xì)胞增多、高熱、腎臟損傷(肌

4、球蛋白尿所致)CNS的改變： 顱內(nèi)壓升高、BBB損傷、腦對氧和葡萄糖的利用增加、腦水腫,SE的后遺癥 智力障礙 持久的神經(jīng)系統(tǒng)損害 反復(fù)的癲癎發(fā)作,SE 的 治 療,治療原則 1 迅速終止癲癎發(fā)作：通常驚厥狀態(tài)在1.5h內(nèi)得到控制，可以獲得完全恢復(fù)；驚厥持續(xù)10h才獲得控制，則常引起腦損傷。 2 維持通氣、呼吸和循環(huán)功能的穩(wěn)定， 防治并發(fā)癥。 3 病因治療 4 預(yù)防再

5、發(fā),一般處理,就地松開衣領(lǐng)，把頭轉(zhuǎn)向一側(cè)，使其唾液與嘔吐物流出口腔，以防止窒息和吸入性肺炎的發(fā)生。以紗布或手帕疊成條狀塞入上下臼齒間，以減少舌尖咬破。加強(qiáng)護(hù)理，以防精神異常者發(fā)生意外。定期記錄并觀察生命體征，糾正異常。注意吸痰吸氧，必要時行氣管切開，呼吸機(jī)輔助呼吸。最好選用大靜脈建立靜脈通道，并用生理鹽水維持，不要用葡萄糖。懷疑SE的病因可能是低血糖或發(fā)現(xiàn)有明顯的低血糖時，應(yīng)靜脈補(bǔ)充50%葡萄糖50ml（兒童25％葡萄糖2m

6、l/kg），之前先靜推100mg維生素B1。待通氣、呼吸和循環(huán)功能穩(wěn)定后，取靜脈血測生化、血糖、血細(xì)胞分析、毒理檢測，并定期做動脈血?dú)夥治觥?藥物治療1 靜脈注射安定是迅速控制癲癎的首選方法。 成人以每分鐘2mg（年高者酌減）的速度勻速注射，直 至發(fā)作停止或總量達(dá)20-30mg； 兒童以每分鐘1mg的速度勻速注射， 用量0.3-0.5mg/kg.最大劑量嬰兒不超過2-5mg，兒童不超過5-10mg。 若病人復(fù)發(fā)，

7、可在20min后在注射一次，成人24小時劑 量不超過120mg，兒童日劑量不超過0.25-1.0mg/kg。 若頻繁靜推安定達(dá)不到控制效果，應(yīng)靜滴氯硝安定，成人首次劑量為3mg。2 發(fā)作停止后，應(yīng)注意使用長效抗癲癎藥苯巴比妥維持。 苯巴比妥 0.1 肌注，q 6h。,3 防治腦水腫。 20％甘露醇 125ml 靜推 q 8h 合并甘油果糖 250ml 靜注 q12h。4 防治感染。 青霉素400萬U入5

8、％葡萄糖250ml，靜注，Bid 合并頭孢噻肟鈉2.0入5％葡萄糖30ml，靜推，q12h。5 高熱者宜物理降溫。6 糾正水電解質(zhì)紊亂和酸中毒。,,,From: Daniel H Lowenstein.Treatment options for status epilepticus. Current Opinion in Pharmacology 2005, 5: 334–339Initial therapyLZP(

9、勞拉西泮)比DZP（安定）好；在小孩、老人及不方便靜脈給藥情況下主張用fosphenytoin ；院外處理主張用LZP。New drug options靜脈注射VPA（丙戊酸鈉）； 用量12–15 mg/kg ，血藥濃度 75 mg/l 用量25 mg/kg，血藥濃度 100–150 mg/l 兒童用量30–40 mg/kg 神經(jīng)保護(hù)劑的應(yīng)用 NMDAR拮抗劑：克他命（ Ketami

10、ne ）和MK-801,Treatment of refractory status epilepticus （RSE）二十世紀(jì)90年代初，美國主張用戊巴比妥（pentobarbital ），而歐洲主張用硫噴妥鈉（thiopentone ）；近年來，許多人主張用propofol or midazolam；有人將pentobarbital 、propofol 、 midazolam三藥對比后發(fā)現(xiàn)，后兩種藥物的治療效果相似，而pen

11、tobarbital 的治療失敗率較midazolam相對要少 ，但需要治療的低血壓卻比propofol or midazolam要多。三藥在各組間總的死亡率相同。(三藥療效等分析對比見下頁Table 2),,,A 50-year-old patient (70 kg) presents to the emergency room with a 30min history of continuous generalized tonic–

12、clonic 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 signs. He has no history of seizures. Further history of the pres

13、ent 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 benzod

14、iazepine. He has now 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 anticon

15、vulsant medication, the patient is still seizing. Vital signs are stable. He is now in your ICU. What would be your next anticonvulsant medication and what would be the dose?(4) Fourth-line therapy. After receiving maxi

16、mum 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) Electrographic SE. The convulsions are terminate

17、d. However, the patient remains stuporous and EEG reveals electrographic status epilepticus (non－convulsive status epilepticus,NCSE). What would be your medication of choice in this setting and what would be the dose?(6

18、) Periodic lateralized epileptiform discharges (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

19、 what would be the dose?,,Fig. Treatment preferences of neurologists for generalized convulsive status epilepticus. Data are presented as n (%). All medications are given as single or repeated IV doses, unless otherwise

20、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 (six). zMidaz

21、olam (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;

22、 AED= antiepileptic drug.Derived from: Jan Claassen, Lawrence J. Hirsch, Stephan A. Mayer. Treatment of status epilepticus: a survey of neurologists. Journal of the Neurological Sciences 211 (2003) 37–41,Survey respond

23、ents 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 the other half (41%) would not. Prior surveys have not specifically add

24、ressed 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 s

25、election of ‘no additional AEDs.’ The clinical significance of PLEDs is controversial; some consider them to be part of an ictal–interictal continuum. However, most respondents (85%) would not add additional AEDs to trea

26、t patients with this EEG finding in the aftermath of SE.,Taken together, status epilepticus that is refractory to treatment remains a major problem that will require the development of new, more potent drugs, and large s

27、cale 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