Pratical Guidelines for Physicians in the Management of Febrile Seizures

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    ELSEVIER Brain & Development 1996; 18 : 479-484

    Consensus StatementPractical guidelines for physicians in the managem ent of febrileseizures

    Yukio Fukuyama aY*,Tohru Seki b , Chikaya Ohtsuka , Hisao M iura d, Michiko Hara eaChild Neurology Inst it ut e, c/o Sanbancho TY Plaz a 5F, 24 Sanbancho, Chiyod a-ku. Toky o 102, Japan

    b Deparhnent of Pediat rics, School of Medicine, Keio University, Tohyo. Japan Juntendo University School of Medicine, Urayasu Hospital, Uravasu, Chiba, Japan

    d Department of Pediatrics, Kitasat o University School of Medicine, Sagamihara. Kanagawa, Japane Department of Special Education for the Handicapped, Fault?, of Education. Gunma University. M aebashi. Japan

    Received 5 May 1996; accepted 5 June 1996

    Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It hasalso been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions ariseas to whether or not FS should b e prevented, particularly in light of the risks of side effects from drugs. W hich kindsof FS can be prevented, if necessary ? The guidelines presented here are aimed primarily at helping generalpractitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should beindividualized, while referring to a few specific warning factors. The guidelines follow a laissez-faire principle forthe majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with eitherphenobarbital or valproate ar e indicated in other limited cases meeting respective definite criteria.

    Keyw ords; Febrile seizure: Diazepam suppository; Intermittent therapy; Physicians guideline; Prophylaxis; Risk factor: Warning factor

    1. INTRODUCTIONIn 1988, the Conference on Febrile Convulsions (Chairman:

    Yukio Fukuyama) published Guidelines for the treatment offebrile seizures in Japanese (Shonika Rinsho (Japanese Journalof Pediatrics) 1988 ; 41: 16-35). The Task Committee of theConference here proposes a newly revised version of theseguidelines based on the results of subseq uent investigations con-ducted in Japan and overseas.

    These measures for dealing with febrile seizures (FS) areroughly divided into primary care, understanding the nature ofFS, prevention of recurrences, propriety of vaccinations, and soon. The Committee proposes the following guidelines in the hopethat they will be of service to physicians as a reference in

    * Corresponding author. Fax: +81 3 3238-1502.

    providing the most appropriate treatment for FS patients and howto best counsel their families.

    2. DEFINITION AND INCIDENCEFS is a seizure disorder (most commonly convulsive, butoccasionally non-convulsive) occurring in infants and young

    children, in association with a fever of 38.O C or higher butwithout evidence of any definite causative disease (abnorm ality),such as a central nervous system (C NS) infection, metabolicabnormality, intoxication, etc.

    The prevalence of this disorder in Japan has been reported,almost unanimously, to be 7-8% based on data obtained inseveral stud ies [l]. Mos t of these investigations were, however,carried ou t retrospectively on the occasions of obligatory childhealth examinations at public health centers or primary schools.The only exception is an epidemiological study carried o ut byOhtahara et al. [2] in Tamano city, Okayama prefecture, whichshowed a much lower figure of about 3.4% for children under the

    0387-7604/96/$15.00 Copyright 0 1996 Elsevier Science B.V. All rights reservedPII SO387-7604(96)00066-6

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    480 Y. Fukqama et al. /Brain & Deuelopment 1996; 18: 479-484

    age of 5 years. In the USA and European countries, the incidenceof FS is 2-5% [3] for the entire ped iatric population.

    3. PRIMARY CARE3.1. Home first-aid when a seizure has occurred1. Do not panic, remain calm.2. Loosen the subjects clothing, particularly around the neck.3. If unconsc ious, place the subject in the supine po sition, keep-

    ing the head lower than the body, and turn the head so as toface side ways while tilted upward. Wipe off any vomit ordischarge in the perioral region or nasal cavity with gauze.Although the teeth may be clenched, do not attempt to insertanything into the mouth.

    4. Take the subjects temperature, and observe and record theduration (length) and features of the seizure (any differencesbetween the right and left sides, eye deviation, etc.).

    5. Do not give any drugs or fluid orally.6. Stay near the patient until the seizure has subsided.3.2. Circumstances under which the patient should beimmediately taken to a physician (any one of the fol-lowing is applicable)1. Cases with a seizure duration of 10 min or longer.2. Cases with frequently repeating short-term seizures with con-

    tinued disturbance of consciousness in between.3. Cases in which seizure either occurs locally (involving only

    one part of the body) or is focused in one part of the bodyalthough the entire body appears to be involved (indicated aspartial seizures).

    4. Cases of first seizure at any age, particularly those of infantsunder the age of 6 months.5. Cases in which neurological symptoms (prolonged disturbance

    of consciousnes s, postictal paralysis, and so on), in addition tofever and seizure, are present.

    3.3. Emergency treatment in cases of prolonged seizure1. Maintenance of respiratory/circulatory competence.2. Inhibition o f convulsion : implemen t immed iate p otential anti-

    convulsive treatment. The procedure for this is shown inSupplement 1.

    3. Treatment for high fever.4. Investigation of cause.Measures for dealing with the cause of fever: the mostcommon causes of fever are viral upper respiratory tract infec-tions, and occasionally, urinary tract infections. Other bacterialinfections may also contribute at times.

    However, CNS infections (encephalitis/meningitis) and/orencephalopathy can induce clinical features similar to those ofFS, and it is therefore importan t to differentiate FS from thesediseases. Close attention should be paid, in particu lar, to caseswith the first seizure o ccurring before the age of 6 months, caseswith seizures occurring 24 h or more after the onset of fever, andthose with atypical seizures as defined below (Section 5.1.21,always keeping in mind the presence or absence of any prolongeddisturbance of consciousness or meningeal signs (such as

    headache, vomiting, stiff neck) around the seizure period. Incases in whom a CNS infection is suspected, confirmation shouldbe obtained by performing a lumbar puncture. However, cautionmust be exercised regard ing the possible presence of space-oc-cupying lesions in the crania l cavity.

    4. PROGNOSIS1. More than half of all FS patients never have a repeat

    seizure after the first episode, remainin g seizure free for the restof their lives.

    2. The recurrence rate for FS in patients who have experi-enced one FS is 25-50% (average, approximately 3Os% ) [4].Cases in whom seizures recur three times or more account for 9%of the total FS population [4]. Recurrences are most commonwithin 1 year following the first seizure, being seen in about 7 0%of cases, and 90% of recurrences are within 2 years [5].

    3. The incidence of epilepsy in FS patients is 2-3% [4,6]before 5-7 years of age, 4.5% [6] before the 10 years of age, and7% [6] before the 25 years of age.

    4. The estimated recurrence rate for FS, or the likelihood ofdeveloping non-febrile seizures (epilepsy), in individua l casesmay differ according to the presence or absence of certainwarning factors as described in Section 5 below.

    5. In cases in whom no neurological abnormality or develop-mental disturbance is immed iately evident, the likelihood ofmajor neurological abnormalities emerging later is very low. Theclaim raised by some investigators that the incidence of cogni-tive/behavioral and learning disorders in children with FS, or ahistory of FS, is higher than for controls , has not been gen erallysupported by the majority [7,8], although room remains forfurther investigation.

    6. The incidence of FS among the siblings of FS patients bothof whose parents have a history of this disorder is variable ,ranging from 40 to SO%, according to different sources. Theoccurrence risk in siblings is reportedly 20-30% for those withone FS positive parent, and about 20% for those whose parentsare both FS negative [l].

    5. WARNING FACTORSNumerous studies have focused on factors related to recurrent

    FS, and factors c orrelated with the subseq uent onset of epilepsy.Although views differ in detail, it is impor tant to empha size thateach case should be carefully observed and evaluated bearingthese factors in mind when establishing manag emen t principlesand estimating the prognosis for individu al patients. It meritsemphas is that, in these guidelines, the use of the term riskfactors has been avoided, and the term warning factors usedinstead (for an explanation, refer to Supplement 21.

    5.1. Warning factors related to the onset of epilepsy(EP factors)1. Apparent m anifestations of neurological abnormalities or de-

    velopmental retardation before the onset of FS.2. Atypical seizures (i. partial seizures; ii. long-lasting seizures

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    Y. Fukuy ama et al./Brain & DeLaelopment1996; 18: 479-484 481

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    of more than 15-20 min duration; iii. clustering (two or more) either continuous or intermittent, and simply monitor the naturalseizures within 24 h). course of the seizure without treatment.Fam ily history of epilepsy in parents/siblings.The probability of manifesting epilepsy before 7 years of age

    1% in cases in whom the above factors are absent (60% of the 6.4. Cases for whom rectal or oral administration ofdiazepam as an emergency measure when feverish, thatis, intermittent therapy, is recom men dedotal FS population), 2% in cases with only one positive factor(34% of the total FS population), and 10 % in cases with 2-3

    positive factors (6% of the total FS population) [4] (see Supple-ment 3).5.2. Warning factors related to the recurrence of FS(FS factors)1. FS onset un der the age of 6 months.2. Family history of FS in one or both parents.

    In cases in whom either on e of the above factors obtains, therecurrence rate may reach approximately 50% [3] (see Supple-ment 4).

    6. PROPHYLAXIS FOR RECURRENT FEBRILESEIZURES6.1. Health care guidance

    To reduce the frequenc y of febrile episodes, patients and theirparents/guardians should be encouraged to pay appropriate atten-tion to physical hygiene and, whenever necessary, remove an ychronic focus of infection, and to avoid contact with infectivesources.

    Furthermore, appropriate treatment should be administeredproph ylactically in cases in which the subject is suffering from acold, and so on.6.2. Preven tion by anticonvulsant medication

    Several investigations have demonstrated that the continuousadministration of an anticonvulsant, such as phenobarbital, primi-done or valproa te, is effective in preventing recurre nt FS, so longas the serum concentration is kept within a therapeutic range.There are, however, a number of drawbacks to this method, suchas non-compliance, economic as well as psychological burdens,and particularly, potential side effects which ma y far outweighthe benefits of seizure prevention.

    Intermittent therapy with diazepa m is also effective in pre-venting recurre nt FS, provided that it is given at the onset offebrile episodes. Howe ver, mild side effects are inevitable here,also.Thus, the decision to implement anticonvulsant therapy shouldbe made only after due consideration of both the merits anddemerits of such treatment, and with full regard to the opinion ofthe patients guardians.

    On such occasions, the following guidelines are recommendedfor the physician.6.3. Cases in which the laissez-faire or wait and seeprinciple is prefera ble

    In cases without warning factors (either E P or FS factors), andin whom the total number of FS episodes remains at two or less.it is advisable to refrain from active anticonvulsant medication.

    For patients with any one of the following three indications, itis advisable to administer diazepam early in the event of febrileepisodes.

    6.4.1. Indications(a) Cases in whom there is a history of long-lasting seizures,

    exceeding 15-20 min in duration.(bl Cases in whom two or more warning factors are present

    nnd who have a history of two or more FS.(cl Cases with frequent seizures occurring over a short period

    of time (e.g., twice in half-a-day ; three or more times in 6months; four or more times in a year).

    6.4.2. ProceduresSee Supplement 5.

    6.4.3. Effectiveness and side effectsIt has been reported that the emergency preventive use of

    diazepam during acute febrile episodes decreases the FS recur-rence rate by l/3. Over a study period of 2 years, the recurrencerate was 12- 14% for the intermittent therapy group in contrast to38-45% for the control group with no treatment [9].

    Furthermore, recurrent FS in the intermittent therapy grouptook place mostly in patients to whom diazepam had not beenappropriately administered for various reasons. The actual pre-vention failure rate was found to be 7.5% for the total number ofFS recurrences, when only recurrences in cases to whom di-azepam had been appropriately administered were taken intoconsideration [101.

    Althoug h it is rare to observe serious side effects under theabove r egimen, it is still importa nt to give parents adequ ateinformation on any potential side effects, even if usua lly mild andtransient, which tend to occur rather often (see Supplement 5).

    6.4.4. UtilityUsage and portability of the preparation are uncomplicated,

    and there is also an advantage in that it can be immediatelyadministered by the guardian. whether at home, or elsewhere.The parents/guardian may feel more at ease and obtain a senseof satisfaction from being able to contribute to the prevention ofseizure recurrence by themselves, and from having appropriatemeans of coping with the emergency at hand. On the other hand,rigorous cautions to the user are mandatory. As this individual ismost likely to be a layperson , a full explana tion of the potentialrisks of diazepam overdosage, precipitated by panic, is essential.

    6.5. Case s in which daily continuous anticonvulsanttherapy is preferable

    It is advisable to recommend daily oral administration of ananticonv ulsant, in cases correspond ing to any of the followingthree indications.

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    482 Y. Fukuyama et al. /Brain & Development 1996; 18: 479-484

    6.51. Indications 8. VACCINATIONS(a) Cases with a previous history of two or more seizure

    episodes occurring in conjunction with a low fever (< 38.O C).(b) Cases with a previous history of prolonged FS lasting

    more than 15-20 min, and, in addition, in whom there is thepossibility that the diazepa m may not be given in time, asprevious experience has shown that parents may fail to notice theonset of fever prior to a seizure.

    (c) Cases with a previous history of prolonged FS lastingmore than 15-20 min, and, in addition, a history of failedprevention in which prolonged FS have occurred despite thetimely administration of diazepam.

    6.5.2. ProcedureSe e Supplement 6.

    6.5.3. Effectiveness and side effectsDaily continuous anticonvulsant therapy is as effective for the

    prevention of recurrent FS as is emergency therapy with di-azepam during febrile episodes. However, such therapy wouldnot be effective for the prevention of evolving afebrile seizures(meaning epileptic seizures). which can subsequently occur.However, the use of a single appropriate drug at the optimumdosage would decrease side effects to a minimum, making signif-icant adverse reactions rather more rare. Therefore, it is stronglyrecommended that the physician be circumspect and appliescaution in reaching a decision.

    None of the current standard vaccinations are contraindicated.However, all vaccinations should be given individually under thepersona l supervision of the patients family doc tor who is respon-sible for providing the necessary information regard ing theirutility and potential side effects. The doctor should also obtainthe parents/guardians consent beforehand and give guidance onmeasures for coping w ith fever/convulsion.

    Particularly, when giving a measles vaccination to a FSpatient who has a family history of convulsions, including FS, orhas complications such as neurological abnormalities or mentalor developmental retardation, it is recommended that either of thefollowing measures be applied; that is, (1) Oral phenobarbital isprophylactically administered daily for 22 days extending from10 days prior to vaccination to 12 days after [12], with the aim ofachieving and maintaining serum phenobarbital at a therapeuticlevel during the highest risk period for fever developm ent afterthe vaccination, or (2) while keeping the patient under closeobserv ation with no active intervention after the vaccina tion,parents/physician stand ready to immediately administer a sup-pository or oral dosage of diazepam in the event of a feverdeveloping, especially during aforementioned high risk period.

    9. ESSENTIAL POINTS OF GUIDANCE FOR PAR-ENTS / GUARDIAN

    6.5.4. UtilityThe utility of this therapy depends significantly on mutual

    trust between physician and parents. Comp liance, along witheconomic and practical burdens for the patient and his/herfamily, should not be overlooked.

    (il. Explan ation of the charac teristics of FS (incidence, agedependen cy, recurren ce rate, incidence in siblings, differencebetween epilepsy and this disorder, prognosis for onset ofepilepsy, prognosis for mental/behavioral development).

    (ii). Measures for coping with fever as well as seizure episodes.(iii). Explanation of why over-reliance on drug therapy should

    6.6. Cases in which recommended therapy remainsunspecified and it is advisable that therapy be decidedon an individual basis

    be avoided and of the side effects of drugs.In giving guidance, it is advisable to provide an explanatory

    booklet or leaflet along with a verbal explanation.

    If a case does not come under any of the aforementionedindications (6.3., 6.4., and 6.5.1, the selection of treatment shouldbe based on decisions made jointly by the patients guardian(s)and the attending physician.

    7. USAGE O F ANTIPYRETIC DRUGSThe effectiveness of administering antipyretic drugs during

    febrile e pisodes for the prevention of recurre nt FS has not beendemonstrated. Although antipyretic drugs may be necessary forthe relief of discomfort associated with high tempera tures, over-use should be avoided and only minimum requisite doses admin-istered.

    In cases in which a diazepam suppository is to be givenconcur rently with an antipyretic drug, it is advisable that theantipyretic drug be given either orally o r as a suppository 30 minor more after the administration of a diazepam suppository. Theconcomitant rectal administration of an antipyretic suppositorymay interfere with early absorption of the diazepam, if the aboveprocedure is not followed [l 11.

    ACKNOWLEDGEMENTS The authors are deeply grateful to everymember of the Conference on Febrile Convulsion for their active partici-pation in consensus development and for their expert review and critiqueof the manuscript. Special thanks are addressed to the following col-leagues who made enormous contribution to this work and kindly agreedto publicize their names as collaborators:Dr A Abe (Teikyo University, Tokyo), Dr Y Awaya (Seibo Hospital,Tokyo), Dr H Horita (Jikei University 3rd Hospital, Komae). Dr TIshikawa (Nagoya City University, Nagoya), Dr H Koide (Saitama Medi-cal School, Higashimoro). Dr K Komiya (Tokyo Metropolitan Neurologi-cal Hospital, Fuchu), Dr T Konishi (Toyama Medical & PharmaceuticalUniversity, Toyama), Dr K Maekawa (Jikei University, Tokyo). Dr TMatsumoto (Matsumoto Clinic for Children, Fukuoka), Dr S Miyake(Yokohama Ryoikuen, Yokohama), Dr T Nagai (Osaka University, Os-aka), Dr M Osawa (Tokyo Womens Medical College, Tokyo), Dr KSumi (Osaka Kohsei Nenkin Hospital. Osaka), Dr H Wada (KenwakaiHospital, Iida).

    Appendix APapers presented at the 17 consecutive Conferences on Febrile

    Convulsions, held annually in Tokyo since 1978 , were published

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    Y. Fukuyama et al./Brain & Development 1996; 18: 479-484 48 3Table 1 Publications from the Conference on Febrile Conuulsions,Tokyo, 1978- I995Annual English proceedings Selected originalconference (abstracts) published papers published in Japanese

    in Brain & Development in special issues of ShonikaRinsho (Jpn J Pediatr) (Tokyo)

    1st (1978) -2nd (1979) -3rd (1980) 1981; 3: 103-94th (1981) 1982; 4: 305-I 15th (1982) 1983; 5: 338-436th (1983) 1984; 6: 66-737th (1984) 1985; 7: 253-60

    8th ( 1985) 1986: 8: 557-669th (1986) 1988; 10: 197-205

    10th (1987) 1988: 10: 333-41

    llth(1988) 1989: 11: 266-76

    12th (1989) 1990; 12: 538-4613th (1990) 1991; 13: 203-1114th (1991) 1992; 14: 188-9615th (1992) 1993; 15: 390-716th (1993) 1994; 16: 339-4617th (1994) 1995: 17: 383-918th (1995) 1996; 18: 471-8

    1979; 32: 577-87,599-681_

    1984; 37: 2223-3281985; 38: 2225-821987; 40: 53-81987; 40: 7-451988; 41: 16-681988; 41: 1983-20101989; 42: 1013-81989; 42: 2368-4421990: 43: 863-71991; 44: 7-521992; 45: 6-441993; 46: 214-711994; 47: 231-741995; 48: 7-281996; 49: 197-2801996; 50:

    either as English abstracts or original articles in Japanese or both,as shown in Table 1.

    Supplement 1. Emergency drug therapy for convulsions(status epilepticus)

    (a) First-step procedure: Intravenous diazepam (products:CercineR (T akeda Pharmaceut Co, Osaka), HorizonR(Yamano uchi Pharmaceut Co, Tokyo)) 0.3 mg/kg (or 1 mg Xyears of age + 1 mgl shou ld be administered slowly over 2-3min while closely mo nitoring respiratory conditions. If this proto-col is effective, the seizure should subside during the course ofthe injection. If the seizure is refractory, the same dosage may berepeated , either consecutively or after a lo-mm interval o f obser-vation, again with full attention being paid to respiration/pu lse.

    (b) Second-step procedure: Patient should be hospitalized fortreatment and given an intravenous administration of phenytoin(product: AleviatinR, Dainippon Pharmaceut Co, Osaka) when:(1) the aforem entioned first-step treatment is ineffective in con-trolling seizures; and (2) seizure relapse occurs one to severalhours after the administration of diazepam, owing to its character-istically rapid but short duration of action. Therefore, in cases ofserious status epilepticus, long-acting phenytoin should be givenintraveno usly subsequ ent to the aforeme ntioned first-step treat-ment. 15 -20 mg/kg of phenytoin should be given slowly byintravenous drip infusion over 20-30 min while monitoringclosely for arrhythmia or any decrease in blood pressure.

    cc) Other procedures: In cases of status epilepticus, treatmen tis best given by securing a venous line and vital signs andintracranial pressure should be carefully monitored. When seizuresare intractable despite the above measures (diazepam, phenytoin).more potent drugs such as general anesthetics can be used.

    Care-givers should be ready to apply cardiopulmonary resuscita-tion measures whenever indicated.

    Supplemen t 2. Risk factors and warning factorsCurrently, the term risk factors is widely used in the medical

    literature to designate factors per taining to the prognosis ofrecurrent FS or the onset of epilepsy. The expression risk maybe scientifically proper, but it carries a connotation which engen-ders an unnecessary sense of crisis in laypersons and is deemedunsu itable for use in consultation with families. In this docum ent,therefore, the term w arning factors has been adopted to desig-nate useful parameters for selecting those patients who should becarefully monitored.

    Supplement 3. Significance of EP factorsThe implications of the three EP factors differ accordin g to

    the type of evolving epileptic seizure. Partial s eizure is stronglyrelated to atypical seizures (EP factor 2). In cases in which all ofthe subitems (i-iii) of EP factor 2 concerning atypical seizuresare applicable, the incidence of partial epilepsy is anticipated toreach 50% before adulthood (in this circumstance, the duration ofsubitem ii would be 30 minutes or more) [6]. However, suchcases account for only 1% of the total FS population. On theother hand, generalized seizures are strongly related to EP factor3, that is, a family history of epilepsy, and recurrent FS number-ing 3 or more episodes [6]. However, the presence of a singlefactor, such as frequently recurring FS, onset under the age of 6months, or gender, bears little relation to the onset of epilepsy.Paroxysmal discharges seen on an electroencephalogram (EEG)are generally considered to be a significant EP factor in Japan,althoug h it is also stressed that it is necessary to take intoconsideration the characteristic features of paroxysmal discharges(e.g.. benign Rolandic discharges are disregarded in most cases>[13]. In the USA and European countries, however, many holdthe view that EEG findings are not useful in predicting eitherrecurrent FS or the onset of epilepsy, although data contradictingthis view have been reported.

    Supplemen t 4. Significance of FS factorsThe effect of a positive FS history in siblings on the likeli-

    hood of FS recurring is controversial [3]. Although none of theabove described EP factors has a significant effect on the recur-rence of FS, one view holds that the recurrence rate increases incases with a combination of FS factors p ertaining to items 1 and2 [Sl.

    Supplement 5. Procedure for the emergency administra-tion of diazepam during febr ile episodes(1) Drug: the drug of first choice should be a diazepam

    solution for rectal use, which has a property of quick and reliableabsorption. In Japan, however, it is not available, and as analternative, a rectal diazepam suppository (products: 4 mg, 6 mg,10 mg of DiappR suppository, Wakod o Co, Tokyo), or an oraldosage of diazepam (products: powder, tablets, syrup of CercineRor HorizonR1 is used.

    (2) Dosage: a 0.4-0.5 mg/kg/dose should be given bysuppository or orally.

    (3) Usage: (i) The patients physician should determine theappropriate dosage, and provide an appropriately adjusted di-azepam preparation for the parent/guardian. (ii) In cases in

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    484 Y. Fukuyam a et al/Brain & Develop ment 1996; 18: 479-484

    which there has been a febrile episode at a temperature exceeding375C the parent/guardian should promptly administer either arectal suppository or an oral product. If the fever continues for upto 8 h after the first dose, the same dosage of diazepam may berepeated. Usua lly, the admin istration of diazepam is limited totwo doses [lo]. A third dose may be given if the situationdemands, but only if 24 h have elapsed since the first dose [14].

    (4) Side effects: Mild ataxia, agitation or lethargy often occurtransiently, but serious side effects, s uch as respiratory depres-sion, bradycardia or hypotension, are rare.

    (5) Treatment period: Usually, a period of 2 years or until theage of 4-5 years, is the landmark for this therapy.

    (6) In cases in whom it is difficult to use diazepam (myastheniagravis, glaucoma, diazepam allergy, etc.), a chloral hydrate sup-pository m ay be used alternatively (products: EscreR suppository,SS Pharmaceut Co, Tokyo; 2 50 mg/dose, under 3 years of age;500 mg/dose, 3 years of age or over).

    Supplement 6. Procedure for daily continuous anticonvul-sant therapy

    (1) Drugs, dosage, usage: Phenobarbital (products: PhenobalR(Fujinaga Pharmaceut Co, Tokyo) or PhenobarbitalR in bulkpow-der, powder or elixir form) 3-5 mg/kg once or twice a day, orsodium valproate (products: Dep akeneR (Kyowa Hakk o KogyoCo, Tokyo), HyserenineR (Kanebo Co, Tokyo) o r ValerinR(Dainippon Pharmaceut Co, Osaka) in fine granule or syrupform) lo-15 mg/kg bid, should be administered orally on adaily basis. However, over the first two weeks, this dosageshould be half of that stated above, and from the third weekonward, the dosage is increased so as to reach the amountdescribed above.

    (2) Blood concentration: This should be monitored every 3-6months, and kept within therapeutic ranges (phenobarbital 15-30p,g/ml, valproic acid 50-10 0 kg/ml).

    (3) Side effects: Phenobarbital may cause lethargy, shortattention span, and hyperkinesis. Valproate may cause thrombo-cytopenia, and particularly in young infants, liver dysfunction,hyperammonemia, or Reye-like syndrome.

    (4) Duration of treatment: For the prevention of recurrent FS,the duration of therapy should be limited to l-2 years.

    Supplemen t 7. Books on febrile seizures pub lished after1980

    1. Nelson KB, Ellenberg JH, eds. Febrile seizures. NewYork: Raven Press, 1981.

    2. Wallace SJ. The child w ith febrile seizures. London: Wright,1988.

    3. Fukuyama Y, ed. Febrile seizures: recent aduances (inJapanese). Tokyo: Nihon Shoni Iji Pub1 Co, 1991 .

    4. Nihei K, ed. Febrile seizures (in Japanese), New mook ofpediatrics series No 2. Tokyo: Kanehara Pub1 Co, 1992.

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