Effective short-term diazepam prophylaxis in febrile convulsions

doi:10.1016/S0022-3476(85)80688-0

The Journal of Pediatrics

Volume 106, Issue 3, March 1985, Pages 487-490

https://doi.org/10.1016/S0022-3476(85)80688-0 Get rights and content

The efficacy of short-term diazepam prophylaxis in febrile convulsions was evaluated in a prospective, controlled study. A total of 289 consecutive children admitted with their first febrile seizure were randomized into two groups. One group received short-term prophylaxis for 18 months with rectally administered diazepam in solution whenever the temperature was ≥38.5°C. The control group received no prophylaxis, but diazepam rectally in the event of new seizures. The short-term prophylaxis, a mean of five doses of diazepam per child per year, afforded effective seizure control; the 18-month recurrence rate was reduced from 39% to 12% (P<0.001), the total number of recurrences from 77 to 23 (P<0.001), the long-lasting recurrences from 5.0% to 0.7% (P<0.05). The risk of subsequent epilepsy within the first 2 years was the same, regardless of receiving prophylaxis (3%) or not (3%); it was low after simple febrile convulsions (no cases of epilepsy in 230 children) but considerable after complex febrile seizures (20%) or seizures associated with severe interictal EEG abnormalities (50%).

References (17)

DulacO et al.
Blood levels of diazepam after single rectal administration in infants and children
J Pediatr
(1978)
DianeseG
Treatment of febrile seizures
J Pediatr
(1980)
KnudsenFU
Plasma-diazepam in infants after rectal administration in solution and by suppository
Acta Paediatr Scand
(1977)
GreenblattDJ et al.
Benzodiazepines in clinical practice
KnudsenFU
Rectal administration of diazepam in solution in the acute treatment of convulsions in infants and children
Arch Dis Child
(1979)
KnudsenFU et al.
Prophylactic diazepam or phenobarbitone in febrile convulsions: A propective, controlled study
Arch Dis Child
(1978)
ThornI
Prevention of recurrent febrile seizures: Intermittent prophylaxis with diazepam compared with continuous treatment with phenobarbitol
KnudsenFU
Successful intermittent diazepam prophylaxis in febrile convulsions: Preliminary results of a prospective, controlled study

There are more references available in the full text version of this article.

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Febrile seizures (FSs) are common. Based on the child’s presentation and examination, the evaluation may range from parental reassurance to the need for additional testing such as cerebrospinal (CSF) studies, imaging, and electroencephalography (EEG) to locate the source of the fever and to exclude other seizure etiologies. Although it is appreciated that a prolonged complex FS (i.e., febrile status epilepticus, fSE) requires emergent treatment and may result in neurological injury, the vast majority of FSs are benign and do not require daily treatment or prophylactic treatment at the time of illness. It is imperative to understand that seizures, whether febrile or unprovoked, can be stressful to families and require supportive care. To reduce this stress, education and support are paramount and should include discussion of FS recurrence, immunizations, risk of subsequent epilepsy, as well as providing the family with a seizure action plan and consideration of a rescue medication.
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Epidemiological studies have made substantial contributions to our understanding of the frequency, natural history, and prognosis of febrile seizures. Using a wide variety of methods for case ascertainment, epidemiological studies have consistently estimated that febrile seizures occur in 2%–5% of children under 5 years of age, though there are geographical, seasonal, and sex-related differences in incidence and prevalence. In certain populations (e.g., Japan, Guam), febrile seizures may be even more common (8%–14%). Reasons for these discrepancies remain unexplained, but the susceptibility to febrile seizures likely depends on genetic predisposition, environmental factors, or both. This chapter critically reviews the studies that have led to the widely accepted febrile seizure occurrence rates (incidence, prevalence) and examines the assumptions, methods, and confounding factors underlying those studies.
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Citation Excerpt :
The author concluded carbamazepine makes the recurrence worse. The efficacy of Diazepam administration during febrile illnesses in prevention of recurrent seizure was also evaluated (class IV).47 One group received short-term prophylaxis for 18 months with rectally administered diazepam whenever the temperature was greater than or equal to 38.5°C.
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The prophylactic use of diazepam is one of the most important topics in the guidelines. The effectiveness of oral or suppository diazepam during febrile illness for prophylaxis of FS is reported in the literature [36–38]. On the other hand, two thirds of children with first FS do not have recurrence of the FS, and these patients do not need diazepam prophylaxis [32,39].
In 2015, the Japanese Society of Child Neurology released new guidelines for the management of febrile seizures, the first update of such guidelines since 1996. In 1988, the Conference on Febrile Convulsions in Japan published “Guidelines for the Treatment of Febrile Seizures.” The Task Committee of the Conference proposed a revised version of the guidelines in 1996; that version released in 1996 was used for the next 19 years in Japan for the clinical management of children with febrile seizures. Although the guidelines were very helpful for many clinicians, new guidelines were needed to reflect changes in public health and the dissemination of new medical evidence. The Japanese Society of Child Neurology formed a working group in 2012, and published the new guidelines in March 2015. The guidelines include emergency care, application of electroencephalography, neuroimaging, prophylactic diazepam, antipyretics, drugs needing special attention, and vaccines. While the new guidelines contain updated clinical recommendations, many unsolved questions remain. These questions should be clarified by future clinical research.
Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy
2011, Pediatrics and Neonatology
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If given later in the course of the seizure, it was effective in only 57% of patients. When given prophylactically at the time of fever, rectal diazepam was as effective as daily phenobarbital in preventing febrile seizures.22,23 Caregivers can be taught to use rectal diazepam at home.24–27
Acute seizures are readily recognizable episodes requiring urgent treatment. This study was conducted to compare the efficacy and safety of suppository use of rectal diazepam solution [Stesolid rectal tube (SRT), Alpharma, Inc., Lierskogen, Norway] with those of intravenous diazepam (IVD), Li Ta Pharma Co, Ltd., Taichung, Taiwan for control of acute seizures in children with intractable epilepsy.
Subjects were patients, aged 1–18 years, with intractable epilepsy under at least three kinds of antiepileptic treatments. Caregivers were trained to rectally administer SRT or IVD (dosage varying from 0.2 to 0.5 mg per kilogram of body weight) and to monitor respiration condition, seizure severity, and adverse drug effects.
Among the 24 subjects, 9 males and 15 females, treated for a period of 3 months, the ages ranged from 2 to 18 years, with a mean of 9.1 years. Seizure types were generalized tonic and/or clonic. Seizure frequency varied from once per week to 20 times per day. Twenty-one (87.5%) of them had mental retardation and/or developmental delay, and 103 of the 127 (81.1%) IVD administrations and 90 of the 103 (87.3%) SRT administrations resulted in rapid cessation of seizures within 10 minutes. Each first dose failed to control seizures in 24 and 13 episodes, respectively. A second dose of IVD achieved cessation of seizure in 21 of the 24 episodes and a second dose of SRT in 12 of the 13 episodes within another 10 minutes. Four episodes (3 with rectal IVD and 1 with SRT) of prolonged seizure beyond 20 minutes needed IVD injection at our emergency room. Sedation occurred in 17% of patients, which was attributed to IVD in 8% and SRT in 9% of patients. No respiratory depression was attributable to IVD or SRT. There was no significant statistical difference in efficacy and safety between these two forms of diazepam.
Rectal diazepam solution, administered by capable caregivers, is as effective and safe as rectal administration of IVD for children with intractable epilepsy.
Treatment of febrile seizures: Historical perspective, current opinions, and potential future directions
2010, Brain and Development
Although most febrile seizures do no harm and two-thirds of initial cases have no witnessed recurrence, the seizures cause much family anxiety, and are sometimes prolonged. In rare cases they are the first evidence of important epilepsy syndromes or are implicated in the development of epilepsy with mesial temporal sclerosis in later life. There have been trials of prophylactic treatment with antiepileptic drugs including carbamazepine, diazepam, phenobarbital, phenytoin, and sodium valproate. Several strategies have been employed with these drugs, including continuous secondary prophylaxis, intermittent secondary prophylaxis in response to later episodes of fever, and rescue medication early in the course of further seizures. Another treatment strategy has been using one or more antipyretic agents in early response to fever using agents such as acetaminophen and ibuprofen. Over the years, researchers have identified a variety of clinical, genetic, and environmental risk factors for more severe or prolonged febrile seizures and higher risk of recurrence. This review evaluates the rationale for secondary prophylaxis of febrile seizures, the potential effectiveness of such treatment, and whether it can be recommended as a general approach to treating febrile seizures or as an approach to be used in groups identified to be at increased risk.

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^†: Supported by Grants 12-2922 and 12-3674 from the Danish Medical Research Council.

^††: Presented in part at the 15th Epilepsy International Symposium, Washington, D.C., September, 30, 1983.

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Effective short-term diazepam prophylaxis in febrile convulsions†,††

J Pediatr

J Pediatr

Plasma-diazepam in infants after rectal administration in solution and by suppository

Acta Paediatr Scand

Benzodiazepines in clinical practice

Rectal administration of diazepam in solution in the acute treatment of convulsions in infants and children

Arch Dis Child

Prophylactic diazepam or phenobarbitone in febrile convulsions: A propective, controlled study

Arch Dis Child

Prevention of recurrent febrile seizures: Intermittent prophylaxis with diazepam compared with continuous treatment with phenobarbitol

Successful intermittent diazepam prophylaxis in febrile convulsions: Preliminary results of a prospective, controlled study