兒科癲癇重積狀態之常規處置 Management of convulsive status epilepticus in children

場景 小兒科急診室

焦急的家長: 醫師，我女兒兩歲大，已經高燒好幾天了，前幾天精神活力都還好，也去過診所，吃過退燒藥。今天開始叫她都叫不太醒，早上還吐過一次，趕快幫我看看她是怎麼了。

檢傷護理站check vital signs:

體溫:39.1'C 呼吸:40cpm 心跳:140bpm 血壓:102/67(78)mmHg 血氧:100% at room air

醫師開始問診及評估病人，此時看起來嗜睡的妹妹突然往後一倒，失去意識，手腳開始不由自主的抽動，牙關緊閉，眼神上吊，此時你是急診室醫師，該如何處置?

醫師初步判斷為全身性抽筋發作，合併意識喪失，合併發燒。
病人及家屬過去無熱痙孿病史，且已經燒三天以上，吐，嗜睡有可能是
中樞神經感染合併腦壓上升的表現，不像典型的熱痙孿，此時病人還在抽筋。

0~5~10 分鐘 - Vital signs,  BZD

1. 先穩定生命五徵 (體溫，呼吸，心跳，血壓，血氧)

 Oxygen, IV, Monitor

 One touch 測血糖: 若低血糖 給予 D10W 2.5 mL/kg

 若持續低血氧: 準備插管(RSI)

 Antipyretics : 退燒塞劑 Voren 1mg/kg/dose 一歲內不建議使用

 BZD: 病人在抽筋，點滴還沒打上可以給:

●IM midazolam(Dormicum) 0.2 mg/kg, maximum 10 mg

●Rectal diazepam(Stesolid) 0.5 mg/kg, maximum 20 mg

 打上IV後第一線BZD : 本院有的

 lorazepam(Anxicam) : 0.1 mg/kg IV 
 diazepam(Dupin) : 0.2 mg/kg IV

若五分鐘後抽筋持續可以再給予首劑的半量

統計學上兩者(lorazepam, diazepam)對於控制兒童癲癇重積狀態無顯著差異 

若高度懷疑敗血症 腦膜炎 考慮給予抗生素
穩定病人狀況後，再去做影像學檢查

Uptodate告訴我們
Neuroimaging is generally deferred until the patient is stabilized. 
However, if LP is considered, computed tomography (CT) is generally recommended beforehand 
to exclude a mass lesion, especially in a patient with focal neurologic signs. 
Later, a magnetic resonance imaging study (MRI) is recommended if the etiology of SE is unknown.


醫師要做的事














2. 根據病史，接觸史，用藥史，家族史，發展史，進行相關檢查

所有病人:
Serum electrolytes

Serum calcium, phosphate, and magnesium

Brain imaging (CT or MRI)

EEG

有用抗癲癇藥病人: 測藥物濃度!

發燒病人:

CBC with differential

Blood culture

Urinalysis, urine culture

CSF culture

筆者補充: 要根據TOCC與身體檢查 做所有可能的bacterial and viral study
腸病毒PCR 流感快篩 EBV, HSV, CMV, VZV, Adeno 等病毒的血清學or抗原抗體檢查 mycoplasma IgM, Rota virus Ag, Stool culture for Shigella, Campylobactor 等

疑似中毒病人:

Urine screen for cocaine, amphetamines, and PCP

Aspirin level

Venous or arterial pH and pCO2

EKG once seizures stop

小於六個月大嬰幼兒:

Blood gas

Plasma ammonia

Plasma amino acids

PT, PTT

Serum AST, ALT, LDH, Alkaline phosphatase

Blood lactate and pyruvate

Urinalysis

Urine for reducing substances

Urine organic acids

Urine amino acids

Check newborn urine screening results

持續發作超過10分鐘 - 2nd line AED Phenobarbital 

若你已經努力了10分鐘，給了兩次BZD，病人還在抽，此時建議就要一定要放置氣管內管來維持呼吸道了，本院有 phenobarbital可以開始loading，起始劑量 20mg/kg ，滴速勿超過1mg/kg/min 以免產生呼吸抑制，假設病人15公斤，則滴至少 20 mins。

2nd line AED首選為 fosphenytoin 國內無，本院有phenytoin，但本院兒科少用。

補充Uptodate

Phenobarbital slowly infused IV (maximum infusion rate 2 mg/kg per minute with a ceiling of 50 mg/min) in an initial dose of 20 mg/kg, and followed by repeated increments of approximately 8 to 10 mg/kg every 30 minutes, can achieve high levels and seizure control, usually without significant hypotension or respiratory depression.

持續發作超過15分鐘 - 3rd line AED Keppra

15分鐘過去，病人還在抽，壓力超大。加油，你還能給予第三線的抗癲癇藥。

本院常用的第三線AED為Keppra，Depakin因擔心影響肝功能比較少用，

Keppra loading劑量為20~30，最多60mg/kg/dose，滴速不超過5mg/kg/min。

若病人體重20kg，起始劑量20mg/kg/dose，至少要滴 4 mins以上。

也可補充針劑的維他命B群，但本院目前廠缺。

補充Uptodate

In patients with ongoing seizure activity despite two initial doses of benzodiazepine and a second-line antiseizure drug, preparation for a continuous infusion of midazolam, propofol, or pentobarbital should occur simultaneously with administration of a third-line antiseizure drug.

此時除了可以給予第三線AED，也要做好continue infusion for heavy sedation的準備

因為若沒有把一開始的放電壓下來，會越來越難控制，病人的預後也越差。

Heavy sedation的同時最好有bed side continue EEG監測，把大腦放電波打到平。

30分鐘後，抽筋終於停止了，還要做麼?

Uptodate

POSTICTAL RECOVERY — Most children begin to recover responsiveness within 20 to 30 minutes after generalized convulsions, although there is a broad range of duration. Close monitoring during this period is critical. The two most common reasons for delayed postictal recovery are sedation from medications and ongoing nonconvulsive seizures, and these two causes can be impossible to distinguish clinically. All children who do not return to a normal level of consciousness within a few hours after initial treatment of status epilepticus should therefore be monitored with electroencephalogram (EEG)

要靠EEG區分是真的停了，還是病人被你用一大堆的藥打暈了。如果病人對你的刺激還是沒有適當的反應，意識仍然不清楚，可能還是有放電，只是沒有明顯的抽筋動作，你看不出來。


二次評估 - NE, CT, LP

Uptodate

Secondary assessment — During the postictal recovery period it is also important to repeat a full neurological examination, looking for asymmetric or focal findings that may suggest clues to the underlying etiology. A neuroimaging study should be obtained when status epilepticus is the first presentation of epilepsy as well as in children whose recovery from SE does not follow the expected course. A lumbar puncture should be obtained if there is evidence of systemic or central nervous system infection, provided that the child’s level of consciousness is appropriate and there are no other contraindications to immediate lumbar puncture.

檢查小朋友的神經學症狀，是否有不對稱，若病人第一次發生癲癇重積症，或病人意識未完全恢復，
需執行影像學檢查(CT or MRI)，若病人沒有LP的禁忌症，需做LP(腰椎穿刺)，排除感染。

30分鐘後還在抽->頑固型抽筋 Refractory seizures
continue Midazolam, Phenobarbital, Propofol

抽筋持續越久，臨床上抽筋動作越不明顯，所以必須有連續的EEG監測

Uptodate

REFRACTORY SEIZURES — If convulsive status epilepticus (SE) persists for 30 minutes after initial measures are instituted, further pharmacologic therapy is required, usually in the form of continuous infusional therapy. The longer convulsive SE continues, the less convulsive it appears clinically, and continuous electroencephalogram (EEG) monitoring should be instituted.

需給予 Dormicum, Phenobarbital, Propofol continue IV pump infusion 與 continue EEG 監測

Dormicum

Midazolam is given as an initial bolus infusion of 0.2 mg/kg intravenous (IV) followed by a continuous infusion of 0.05 to 2 mg/kg/hour; for breakthrough seizures, additional 0.1 to 0.2 mg/kg boluses can be given and the continuous infusion rate increased by 0.05 to 0.1 mg/kg/hr every 3 to 4 hours.

Phenobarbital

Phenobarbital is given as an initial bolus infusion of 5 to 15 mg/kg IV followed by a continuous infusion of 0.5 to 5.0 mg/kg/hour. Loading 1~2hour, 最大滴速 2mg/kg/min。

Propofol 

臨床很少用超過三天以上 因為會造成 TG上升與肺水腫 
短期使用可能造成低血壓 apnea/bradycardia 也有可能造成致命的酸中毒與橫紋肌溶解

(Others have found that propofol may be used without severe adverse effects if the dose is not titrated above 5 mg/kg per hour and with continuous monitoring and stopping the infusion if side effects appea)

Propofol 滴注 1~3mg/kg/dose in 5 mins，接著 2~10mg/kg/hour 維持劑量，最大滴速 25~75ug/kg/min 

補充:
Mannitol用在IICP病人身上，需要監測尿量，腎功能與Na。
Dose: 本院常用劑量為 0.25gm/kg/dose IV Q6H
Mannitol 20% (0.2g/ml)
Usual range: 0.25 to 1 g/kg/dose infused over 20 to 30 minutes; 
repeat as needed to maintain serum osmolality <300 to 320 mOsm/kg

Reference:
Uptodate: Management of convulsive status epilepticus in children(last updated: Jun 07, 2018)