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痙攣重積(小児科)

著者: 内野俊平 東京大学医学部附属病院小児科

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2022/11/09
参考ガイドライン:
  1. 日本小児神経学会:小児けいれん重積治療ガイドライン2017
患者向け説明資料

概要・推奨   

  1. 痙攣発作が30分以上持続するもの、または痙攣発作を反復し、発作間欠期にも意識が回復しない状態が30分以上続くものを痙攣重積という。
  1. 30分以上の痙攣重積は脳に不可逆な変化を起こすため、それより早く痙攣をコントロールすることを目指すべきである(推奨度1)
  1. 痙攣が5分以上続く場合は、痙攣重積の治療を開始する(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
内野俊平 : 未申告[2022年]
監修:五十嵐隆 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 小児けいれん重積治療ガイドライン2017に基づき改訂を行った。
  1. ミダゾラム口腔用液の情報を追加した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 痙攣発作が30分以上持続するもの、または痙攣発作を反復し、発作間欠期にも意識が回復しない状態が30分以上続くものを痙攣重積という。
  1. 痙攣の原因はさまざまであるが、痙攣重積の原因としては、中枢神経において興奮性に働くグルタミン酸作動性の神経系の異常、抑制性に働くGABA作動性の神経系の異常、イオンチャネルの異常の関与が想定されている。
  1. 日本では15歳未満の痙攣重積の発症頻度は、年間10万人当たり37.6人という報告がある[1][2]
  1. 痙攣重積による死亡率は年々減少しているが、現在は約3%とされている[3][4][5]
  1. 神経学的後遺症としては、麻痺、てんかん、発達の遅れ、高次機能障害などがある。
  1. 後遺症を残す確率は痙攣の原因により異なるが、一般的に痙攣重積の持続時間が長いほど後遺症を残しやすい。
  1. 痙攣発作が30分以上持続することで神経細胞に不可逆な障害が生じるといわれており[6][7]、可能な限り早期に重積を終了させる介入が重要である。
  1. 迅速な対応のために、施設ごとに一定のプロトコールを作成し、日頃より薬剤の使用方法などに習熟しておくことが必要である。
問診・診察のポイント  
  1. まず痙攣の有無を確認する。痙攣が重積している場合は痙攣の対応を優先する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

R J DeLorenzo, W A Hauser, A R Towne, J G Boggs, J M Pellock, L Penberthy, L Garnett, C A Fortner, D Ko
A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia.
Neurology. 1996 Apr;46(4):1029-35.
Abstract/Text This report presents the initial analysis of a prospective, population-based study of status epilepticus (SE) in the city of Richmond, Virginia. The incidence of SE was 41 patients per year per 100,000 population. The frequency of total SE episodes was 50 per year per 100,000 population. The mortality rate for the population was 22%, 3% for children and 26% for adults. Evaluation of the seizure types for adult and pediatric patients demonstrated that both partial and generalized SE occur with a high frequency in these populations. Based on the incidence of SE actually determined in Richmond, Virginia, we project 126,000 to 195,000 SE events with 22,200 to 42,000 deaths per year in the United States. The majority of SE patients had no history of epilepsy. These results indicate that SE is a common neurologic emergency.

PMID 8780085
B S Meldrum, R W Horton
Physiology of status epilepticus in primates.
Arch Neurol. 1973 Jan;28(1):1-9.
Abstract/Text
PMID 4629380
B S Meldrum, R A Vigouroux, J B Brierley
Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons.
Arch Neurol. 1973 Aug;29(2):82-7.
Abstract/Text
PMID 4197956
B K Alldredge, A M Gelb, S M Isaacs, M D Corry, F Allen, S Ulrich, M D Gottwald, N O'Neil, J M Neuhaus, M R Segal, D H Lowenstein
A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
N Engl J Med. 2001 Aug 30;345(9):631-7. doi: 10.1056/NEJMoa002141.
Abstract/Text BACKGROUND: It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus.
METHODS: We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed.
RESULTS: Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08).
CONCLUSIONS: Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.

PMID 11547716
I E Leppik, A T Derivan, R W Homan, J Walker, R E Ramsay, B Patrick
Double-blind study of lorazepam and diazepam in status epilepticus.
JAMA. 1983 Mar 18;249(11):1452-4.
Abstract/Text Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted.

PMID 6131148
Jason McMullan, Comilla Sasson, Arthur Pancioli, Robert Silbergleit
Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis.
Acad Emerg Med. 2010 Jun;17(6):575-82. doi: 10.1111/j.1553-2712.2010.00751.x.
Abstract/Text BACKGROUND: Rapid treatment of status epilepticus (SE) is associated with better outcomes. Diazepam and midazolam are commonly used, but the optimal agent and administration route is unclear.
OBJECTIVES: The objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam, by any route, in terminating SE seizures in children and adults. Time to seizure cessation and respiratory complications was examined.
METHODS: We performed a search of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, American College of Physicians Journal Club, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and International Pharmaceutical Abstracts for studies published January 1, 1950, through July 4, 2009. English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE, and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures, were eligible. Two reviewers independently screened studies for inclusion and extracted outcomes data. Administration routes were stratified as non-IV (buccal, intranasal, intramuscular, rectal) or IV. Fixed-effects models generated pooled statistics.
RESULTS: Six studies with 774 subjects were included. For seizure cessation, midazolam, by any route, was superior to diazepam, by any route (relative risk [RR] = 1.52; 95% confidence interval [CI] = 1.27 to 1.82). Non-IV midazolam is as effective as IV diazepam (RR = 0.79; 95% CI = 0.19 to 3.36), and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 1.54; 95% CI = 1.29 to 1.85). Midazolam was administered faster than diazepam (mean difference = 2.46 minutes; 95% CI = 1.52 to 3.39 minutes) and had similar times between drug administration and seizure cessation. Respiratory complications requiring intervention were similar, regardless of administration route (RR = 1.49; 95% CI = 0.25 to 8.72).
CONCLUSIONS: Non-IV midazolam, compared to non-IV or IV diazepam, is safe and effective in treating SE. Comparison to lorazepam, evaluation in adults, and prospective confirmation of safety and efficacy is needed.

(c) 2010 by the Society for Academic Emergency Medicine.
PMID 20624136
Abstract/Text All children who presented in a convulsion, including convulsive status epilepticus, to the accident and emergency department over a 12-month period and who required treatment, were reviewed retrospectively to identify the effectiveness and safety of a specific treatment protocol. This protocol recommends the initial use of one, or if necessary, two doses of rectal or intravenous diazepam (0.4 mg/kg) followed by the simultaneous administration of phenytoin (18 mg/kg) and rectal paraldehyde (0.4 mL/kg), with instructions for maximum doses and timings of administration. Eighty-one evaluable children (52 male) were audited. The mean age of the study population was 4.1 (range 0.1 to 14.9) years. Overall, the presenting convulsion was successfully terminated in 76 children (94%) within the accident and emergency department. In 69 children (85% of the entire study population) this was after a single dose of diazepam (rectal in 41 and intravenous in 28). In only an additional two children did the presenting convulsion stop after a second dose of diazepam. In five of the 10 children (50%) who received paraldehyde and phenytoin as a combination, the convulsion stopped. Nine patients (11%) required admission to the intensive-care unit, five because of persisting convulsive activity, and four because of respiratory depression. The results of this retrospective audit suggest that the current treatment protocol appears to be effective and relatively safe in treating acute convulsions, including convulsive status epilepticus. The audit is to be repeated prospectively to either confirm or refute these findings before recommending any changes to the protocol.

PMID 10068049
Jan Claassen, Lawrence J Hirsch, Ronald G Emerson, Stephan A Mayer
Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review.
Epilepsia. 2002 Feb;43(2):146-53.
Abstract/Text BACKGROUND: New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients.
METHODS: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to "seizure suppression" versus "EEG background suppression").
RESULTS: Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001).
CONCLUSIONS: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.

PMID 11903460
Sunit Singhi, Aruna Murthy, Pratibha Singhi, M Jayashree
Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus.
J Child Neurol. 2002 Feb;17(2):106-10.
Abstract/Text The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean +/- SD = 4.9 +/- 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P < .05). The maximum dose (mean +/- SD) of midazolam and diazepam required was 5.3 +/- 2.6 microg/kg/min and 0.04 +/- 0.02 mg/kg/min, respectively. About half of the patients needed mechanical ventilation and 40% had hypotension in both groups, but the mortality was higher in the midazolam group (38%) as compared to the diazepam group (10.5%, P < .1 > .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections.

PMID 11952069
C Remy, N Jourdil, D Villemain, P Favel, P Genton
Intrarectal diazepam in epileptic adults.
Epilepsia. 1992 Mar-Apr;33(2):353-8.
Abstract/Text Intrarectally (i.r.) administered diazepam (DZP) solution at doses of 20 and 30 mg in the treatment of serial seizures was studied in 39 adult patients with refractory partial epilepsy. Patients were randomly distributed into two groups (20 mg, n = 21; 30 mg, n = 18). Plasma levels of DZP were assessed over 24 h following i.r. injection. The efficacy of i.r. DZP in the treatment of serial seizures in adults was confirmed; onset of effect was noted approximately 10 min after the injection, and the effective dose was 0.50 mg/kg. Tolerance and acceptability were good. Intrarectal injection of DZP can be performed even by unskilled personnel and may be recommended in patients with serial seizures in the hope of preventing development of status epilepticus.

PMID 1547766
R A Dieckmann
Rectal diazepam for prehospital pediatric status epilepticus.
Ann Emerg Med. 1994 Feb;23(2):216-24.
Abstract/Text STUDY OBJECTIVES: To compare the feasibility, effectiveness, and safety of rectal diazepam and intravenous diazepam in the treatment of pediatric prehospital status epilepticus.
DESIGN AND SETTING: Retrospective analysis of a 30-month consecutive sample of ambulance-transported children in a large urban emergency medical service region.
TYPE OF PARTICIPANTS: Study group included 324 patients with seizure who were less than 18 years of age; 36 had status epilepticus, of whom 16 received rectal diazepam and 15 received IV diazepam.
INTERVENTIONS: For children with status epilepticus, paramedics administered the 5-mg/mL IV solution of diazepam by one of two routes: rectally either through a 5F feeding tube with an attached syringe or by lubricated tuberculin syringe inserted 4 to 5 cm into the rectum at a one-time dose of 0.2 to 0.5 mg/kg or intravenously using a one-time dose of 0.1 to 0.3 mg/kg. Cardiopulmonary status was carefully monitored in the field and emergency department.
MEASUREMENTS AND MAIN RESULTS: Thirteen of 16 children (81%) who received rectal diazepam stopped seizing after a single dose ranging from 0.16 to 0.57 mg/kg. Convulsions recurred before arrival at the ED in four of the 13 (30.8%). All of three patients who did not respond to rectal diazepam initially were 3 to 5 years old and had serious underlying comorbidity; two required endotracheal intubation in the ED and multiple anticonvulsants to terminate the seizure. No child treated with rectal diazepam required prehospital endotracheal intubation. All children who received IV diazepam stopped seizing after one dose ranging from 0.04 to 0.33 mg/kg. Convulsions recurred before arrival at the ED in nine of 15 children (60%); two required prehospital endotracheal intubation for profound respiratory depression.
CONCLUSION: Rectal diazepam is a simple, effective, and safe method of prehospital management of pediatric status epilepticus. Compared with IV diazepam, rectal diazepam is easier to administer, especially in infants and toddlers; is equally efficacious; and is less likely to produce respiratory depression. Although respiratory depression is rare with rectal diazepam, prehospital personnel must be prepared to provide definitive respiratory support. Short duration of action is an important limitation of both treatments.

PMID 8304602
R C Scott, F M Besag, B G Neville
Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.
Lancet. 1999 Feb 20;353(9153):623-6. doi: 10.1016/S0140-6736(98)06425-3.
Abstract/Text BACKGROUND: Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures.
METHODS: At a residential school with on-site medical facilities 42 young people with severe epilepsy were enrolled. Continuous seizures of more than 5 min duration were randomly treated with buccal midazolam or rectal diazepam. If the seizure did not stop within 10 min additional medication chosen by the attending physician was administered. We monitored oxygen saturation and blood pressure for 30 min after treatment. The main outcome measures were efficacy, time from arrival of the nurse to drug administration, time from drug administration to end of seizure, and incidence of adverse cardiorespiratory events.
FINDINGS: Buccal midazolam was used to treat 40 seizures in 14 students, and rectal diazepam 39 seizures in 14 students. Midazolam stopped 30 (75%) of 40 seizures and diazepam 23 (59%) of 39 (p=0.16). The median time from arrival of the nurse to administration of medication was 2 min. Time from administration to end of seizure did not differ significantly between the two treatments. No clinically important adverse cardiorespiratory events were identified in the two groups. Buccal midazolam was universally acceptable to the nursing and care staff.
INTERPRETATION: Buccal midazolam is at least as effective as rectal diazepam in the acute treatment of seizures. Administration via the mouth is more socially acceptable and convenient and may become the preferred treatment for long seizures that occur outside hospital.

PMID 10030327
Tunç Fişgin, Yavuz Gurer, Tahsin Teziç, Nesrin Senbil, Pelin Zorlu, Cetin Okuyaz, Deniz Akgün
Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study.
J Child Neurol. 2002 Feb;17(2):123-6.
Abstract/Text In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol. In the diazepam group, the seizures of 13 (60%) patients terminated in 10 minutes; however, 9 (40%) patients did not respond. In the midazolam group, 20 (87%) patients responded in 10 minutes, but 3 (13%) patients did not respond. Regarding the anticonvulsant effect, midazolam was found to be more effective than diazepam, and the difference was statistically significant (P < .05). The necessity of a second drug for the seizures that did not stop with the first drug was higher in the diazepam group than the midazolam group, and the difference was statistically significant (P < .05). We conclude that as an antiepileptic agent, intranasal midazolam is more effective than rectal diazepam. After administration, we did not observe any serious complications. Further investigations are necessary; however, intranasal administration is easy, so if the nasal drop and spray forms used in some European countries and the United States are available worldwide, it will be very useful for physicians in the emergency room.

PMID 11952072
J M Chamberlain, M A Altieri, C Futterman, G M Young, D W Ochsenschlager, Y Waisman
A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children.
Pediatr Emerg Care. 1997 Apr;13(2):92-4.
Abstract/Text OBJECTIVE: To compare treatment of ongoing seizures using intramuscular (IM) midazolam versus intravenous (IV) diazepam.
DESIGN: Controlled clinical trial.
PATIENTS: Children with motor seizures of at least 10 minutes' duration.
MAIN OUTCOME MEASURES: Time to cessation of seizures.
RESULTS: Twenty-four patients were enrolled (13 midazolam, 11 diazepam). Initial treatment with either midazolam or diazepam was successful in 22 of the 24 patients. One patient in each group failed therapy and eventually required endotracheal intubation and general anesthesia for convulsive status epilepticus lasting more than one hour. Patients in the midazolam group received medication sooner (3.3 +/- 2.0 vs 7.8 +/- 3.2 minutes, P = 0.001) and had more rapid cessation of their seizures (7.8 +/- 4.1 vs 11.2 +/- 3.6, P = 0.047) than patients randomized to receive diazepam.
CONCLUSIONS: IM midazolam is an effective anticonvulsant for children with motor seizures. Compared to IV diazepam, IM midazolam results in more rapid cessation of seizures because of more rapid administration. The IM route of administration may be particularly useful in physicians' offices, in the prehospital setting, and for children with difficult IV access.

PMID 9127414
K Minagawa, H Miura, S Mizuno, H Shirai
Pharmacokinetics of rectal diazepam in the prevention of recurrent febrile convulsions.
Brain Dev. 1986;8(1):53-9.
Abstract/Text To determine the optimum dosage schedule for intermittent rectal diazepam in suppository form for the prevention of recurrent febrile convulsions, we studied the pharmacokinetics of diazepam administered in repeated rectal doses. The plasma concentration-time data for diazepam on twice repeated rectal dosing with 0.5 mg/kg at 8-hour intervals in six infants showed that therapeutic plasma levels could be attained within 30 minutes and maintained for the first 24 hours. Most of the observed plasma diazepam levels were found to be within +/- one standard deviation of the values calculated from the pharmacokinetic parameters in six other infants with single rectal dosing. Computer-simulated plasma level profile suggested that plasma diazepam levels may reach the toxic range after administration of five or more doses. Twice repeated rectal dosing with 0.5 mg/kg of diazepam in suppository form at 8-hour intervals during the febrile period may be a rational approach for the prevention of recurrent febrile convulsions.

PMID 3706661
D M Treiman, P D Meyers, N Y Walton, J F Collins, C Colling, A J Rowan, A Handforth, E Faught, V P Calabrese, B M Uthman, R E Ramsay, M B Mamdani
A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.
N Engl J Med. 1998 Sep 17;339(12):792-8. doi: 10.1056/NEJM199809173391202.
Abstract/Text BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled.
RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days.
CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

PMID 9738086
Abstract/Text In a randomized, nonblinded clinical trial, 36 consecutive patients with generalized convulsive status epilepticus were treated with either combination diazepam and phenytoin (DZ/DPH) or phenobarbital (PB). Phenytoin was added to the PB regimen if seizures persisted for 10 minutes after beginning therapy. The cumulative convulsion time (total time spent in active convulsive movements) was shorter for the PB group than for the DZ/DPH group (median, 5 versus 9 minutes, p less than 0.06); the response latency (elapsed time from initiation of therapy to the end of the last convulsion) was also shorter for the PB group (median, 5.5 versus 15 minutes, p less than 0.10). The median cumulative convulsion time is between 0 and 14 minutes shorter for the PB regimen than for the DZ/DPH regimen (95% confidence interval). Similarly, the median response latency for the PB regimen is between 1 minute longer and 20 minutes shorter than that for the DZ/DPH regimen (95% confidence interval). The frequencies of intubation, hypotension, and arrhythmias were similar in the two groups. Eleven of 18 patients in the PB group responded to phenobarbital monotherapy. We conclude that the PB regimen is rapidly effective, comparable in safety, and enjoys certain practical advantages in comparison with the DZ/DPH regimen.

PMID 3277082
R J DeLorenzo, E J Waterhouse, A R Towne, J G Boggs, D Ko, G A DeLorenzo, A Brown, L Garnett
Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus.
Epilepsia. 1998 Aug;39(8):833-40.
Abstract/Text PURPOSE: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures.
METHODS: One hundred sixty-four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected.
RESULTS: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after-SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported.
CONCLUSIONS: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.

PMID 9701373
H Meierkord, B Will, D Fish, S Shorvon
The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry.
Neurology. 1991 Oct;41(10):1643-6.
Abstract/Text A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.

PMID 1922808
Martin Holtkamp, Jalal Othman, Katharina Buchheim, Hartmut Meierkord
Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting.
Neurology. 2006 Jun 13;66(11):1727-9. doi: 10.1212/01.wnl.0000218299.15988.9d.
Abstract/Text Episodes of psychogenic nonepileptic status epilepticus (PNESE) characterized by pronounced generalized motor features were compared with those of refractory generalized convulsive status epilepticus. Patients with PNESE were younger, had port systems implanted more frequently, received higher doses of benzodiazepines until seizure termination or respiratory failure, and had lower serum creatine kinase levels.

PMID 16769948
Takashi Ichiyama, Hironori Matsufuji, Naoko Suenaga, Miki Nishikawa, Takashi Hayashi, Susumu Furukawa
[Low-dose therapy with carbamazepine for convulsions associated with mild gastroenteritis].
No To Hattatsu. 2005 Nov;37(6):493-7.
Abstract/Text We investigated the effect of carbamazepine on convulsions associated with mild gastroenteritis. Sixteen infants and young children (aged 9 months to 3 years) who experienced repetitive convulsions associated with mild gastroenteritis were admitted to our hospital. We treated the sixteen affected patients with 5 mg/kg of carbamazepine once per day until the diarrhea had stopped. Thirteen of the sixteen patients were subjected to intravenous and/or suppository administration of diazepam (0.3-0.5 mg/kg/time), and one patient suppository administration of 0.5 mg/kg diazepam and 5.7 mg/kg phenobarbital before the administration of carbamazepine. In all patients who were given diazepam and/or phenobarbital, the convulsions recurred after the administration of these medicines. The convulsions occurred 2 to 8 times (mean, 4.1 times) before the administration of carbamazepine. Fifteen of the sixteen patients had no seizures after the administration of carbamazepine. One patient had one convulsion 15 min after the administration of carbamazepine. All patients were treated with 5 mg/kg of carbamazepine once per day until the diarrhea had stopped, i.e. for 2 to 9 days (mean, 6.4 days). Low dose therapy with carbamazepine once per day is thus effective for convulsions associated with mild gastroenteritis.

PMID 16296353

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