Table 4.

Previous Randomized Controlled Studies of Prevention of Febrile Seizure Recurrences, Including Antipyretic Treatment

Camfield, 1980Schnaiderman, 1993Uhari, 1995
Treatment groups (number of children)Single daily dose of phenobarbital per os 5 mg/kg plus antipyretic instruction of the parents (n = 39) versus antipyretic instruction including oral antipyretics only (n = 40)Prophylaxis of acetaminophen orally 15–20 mg/kg per 4-hourly dose (n = 53) versus sporadic usage of acetaminophen of a similar oral dose contingent at fever >37.9°C (n = 51)Diazepam 0.2 mg/kg 8-hourly during fever >38.5°C (n = 81), of which the first dose to be given rectally and additional doses per os, versus placebo (n = 80); additional: cross-over per fever episode with acetaminophen 10 mg/kg 6-hourly during fever >40.0°C (route of administration not reported) versus placebo
Temperature measurementsOral and rectal measurements by the parents at homeRectal measurements by nurses or parents during hospitalizationMeasurements by the parents at home (oral or rectal)
Outcome measureFirst febrile seizure recurrence in the same or following fever episodesFirst febrile seizure recurrence in the same fever episode (multiple type)Number of febrile seizure recurrences in any of the following fever episodes
Body temperatureBody temperature
Maximum study duration12 moOne fever episode2 y
Patient inclusionSimple initial febrile seizureSimple initial febrile seizureSimple or complex initial febrile seizure
Major difficulties in the evaluation of the resultsNo standardization of the antipyretic treatment4-a No placebo control group of antipyretic treatmentNo standardization of the antipyretic treatment4-b
No placebo control group of antipyretic treatmentNoncomparable outcome measure
Results2 of the 39 patients using phenobarbital plus antipyretic instruction and 10 of the 40 patients with only instruction had a recurrent febrile seizure4-c 4 of the 53 children using ongoing prophylaxis vs 5 of the 51 children in the sporadic-use group had a recurrent seizure in the same fever episode9 of the 173 fever episodes were associated with a recurrence in the acetaminophen group vs 14 of the 170 fever episodes in the placebo group4-d
Efficacy of antipyretic preventive treatment as concludedNot effectiveNot effectiveNot effective
  • F4-a All parents received instructions about fever control; no standardized dose per kilogram of bodyweight was administered.

  • F4-b All parents were allowed to administer extra antipyretics whenever they believed they should.

  • F4-c Survival analysis was performed to compare seizure recurrence in the phenobarbital-plus-instruction group and the instruction-only group (P < .02, log-rank).

  • F4-d Survival analysis was performed to compare seizure recurrence in the diazepam group and the placebo group (P = .41, log-rank).