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Three Part Question

In [children who have experienced a febrile seizure] does [prescribing antipyretics] [reduce recurrences of febrile seizures]?

Clinical Scenario

A one year old child is admitted following their first febrile seizure (FS). We wish to prevent recurrences during further febrile episodes. The nursing staff ask you to prescribe an antipyretic. Later you come to advise the parents on methods of preventing further febrile seizures.

Search Strategy

Secondary Sources: Cochrane Library and DARE
Prodigy Evidence Based Clinical guidance
Primary resources: Pubmed clinical queries (1966-Jan 2003)
Cochrane Library and DARE – "Febrile convulsions/ seizures and antipyretics", "febrile convulsions/seizures and paracetamol", "febrile convulsions/seizures and ibuprofen"
Prodigy Evidence Based Clinical guidance - "febrile convulsions"
Pubmed - "Antipyretics and febrile convulsions"

Search Outcome

Cochrane Library and DARE - One systematic review found (Paracetamol for treating fever in children); two protocols
Prodigy Evidence Based Clinical guidance - Nil relevant found.
PubMed - 80 references. Of these three were randomised controlled trials but one was irrelevant (investigating antipyretic effects rather than subsequent seizure reduction)

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Uhari et al, 1995,	180 children after first febrile seizure randomised to 4 groups: (a) placebo+ placebo (b) placebo+ paracetamol (c) diazepam+paracetamol (d) diazepam + placebo	Randomised double blind placebo controlled trial (Level 1b)	Number of recurrence of FS	(a)14 (25.4%) (b) 9 (16.4%) (c)14 (25.5%) (d)18 (32.7%) (no statistical difference)	Duration of follow-up: two years
Schnaiderman D et al, 1993,	104 children after first febrile seizure randomised to two groups (a) paracetamol 4-hourly versus (b) paracetamol as required	Randomised controlled trial (Level 1b)	Early recurrence of FS	(a) Regular paracetamol = 4 (7.5%) (b) PRN paracetamol = 5 (9.8%) (p= not significant)	In hospital only (no follow-up)
Van Stuijvenberg M et al, 1998,	230 children after first febrile seizure randomised to (a) Ibuprofen (n=111)versus (b) placebo (n=119)	Randomised double blind placebo controlled trial (Level 1b)	Number of recurrence of FS	(a) 31 (35.7%) (b) 36 (33%) (p= not significant)	Mean duration of follow-up 1.04y
Von Esch et al, 2000,	Treatment group with (a) ibuprofen or paracetamol (n=109) versus (b) no antipyretics (n=103)	Non-randomised controlled trial (Level 2a)	Number of recurrence of FS	Recurrence risk per fever: (a) 6.3% ( treatment group) (b) 12.2% (control group) ARR = 5.9%; (95% Confidence interval: -0.2% to 12%)
Meremikwu M & Oyo-Ita A, 2002,	RCTs with Paracetamol compared to Placebo	Systematic review (Level 1a)	Number of recurrence of FS	Conclusion: no evidence that paracetamolis effective in preventing FS

Comment(s)

As the essential precursor of a febrile seizure is a fever, physicians and paediatric nurses have concluded that antipyretic measures should prevent febrile seizures. Antipyretics continue to be among the most commonly prescribed medications, especially for children at risk of such seizures. Parents are usually advised that the administration of antipyretics to at risk children may reduce the risk of further convulsions. When asked the majority of medical trainees and paediatric nurses in our unit replied that the reason for giving paracetamol to children who were at risk of febrile seizure recurrence was to prevent further convulsions. However, the evidence suggests that antipyretics have no effect on preventing further febrile seizures. At this hospital, 13% of children admitted with their first FS subsequently developed repeated FS soon after admission despite the routine administration of paracetamol to control fever prior to the seizure (1). Children with high risk of recurrences of FS (complex features of FS, family history of FS, age less one year, low grade fever at the onset of FS) develop recurrences in at least 80% while those without these risk factors rarely develop recurrences. Antipyretics are used for both groups of children, suggesting that it is these risk factors, and not antipyretics, which are the crucial determinants of the risk of recurrence. Controlled studies of antipyretic medications, given during the original acute illness following a febrile seizure or during subsequent febrile episodes have failed to demonstrate a preventive effect in children at risk of FS (Table). A randomised, placebo-controlled trial on children at risk of FS found no evidence that paracetamol, with or without diazepam, was effective in preventing FS during subsequent febrile episodes (2). A second randomised trial compared the antipyretic effectiveness of paracetamol administered at regular intervals (Group 1) versus paracetamol administered at the time of fever (Group 2) in children presenting with a FS. Early recurrences of FS (within the first 24 hours) were similar in both groups (4). Ibuprofen was also evaluated in a randomised, double-blind, placebo-controlled trial in children at risk of FS. The recurrence rate was similar in both groups (5). These four studies concluded that the antipyretics paracetamol and ibuprofen had no preventive effect on the recurrence of FS. A recent review (6) of trials assessing the effects of paracetamol on the clearance time of fever and on FS identified 12 randomised or quasi-randomised controlled trials. It concluded that the trials failed to demonstrate any convincing evidence that paracetamol is effective in reducing fever or preventing FS. While antipyretics may have a role in improving comfort and general wellbeing we should surely not be advocating medication for purposes that have been shown not to work.

Clinical Bottom Line

There is no evidence that antipyretics reduce the risk of subsequent febrile convulsions in at risk children Prescription of paracetamol following febrile seizures may provide comfort and symptomatic relief, but should not be recommended to prevent further febrile convulsions

References

1. Uhari M, Rantala H, Vainionpaa L, et al. Effects of acetaminophen and of low intermittent doses and diazepam on prevention of recurrences of febrile seizures. J Pediatr 1995;126:991-995.
2. Schnaiderman D, Lahat E, Sheefer T, et al. Antipyretic effectiveness of acetaminophen in febrile seizures: ongoing prophylaxis versus sporadic usage. Europ J Pediatr 1993;152:747-749.
3. Van Stuijvenberg M, Derksen-Lubsen G, Steyerberg EW, et al. Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile recurrences. Pediatrics 1998;102:1-7.
4. Van Esch A, Steyerberg EW, Moll HA et al. A study of the efficacy of antipyretic drugs in the prevention of febrile seizure recurrence. Ambulatory Child Health 2000;6:19-26.
5. Meremikwu M, Oyo-Ita A. Paracetamol for treating fever in children. The Cochrane Database of Systematic Reviews 2002;4.
6. El-Radhi AS. Lower degree of fever is associated with increased risk of subsequent convulsions. Eur J Paediatr Neurol 1998;2:91-6.