Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401]

BACKGROUND: The antipyretic effectiveness of rectal versus oral acetaminophen is not well established. This study is designed to compare the antipyretic effectiveness of two rectal acetaminophen doses (15 mg/kg) and (35 mg/kg), to the standard oral dose of 15 mg/kg. METHODS: This is a randomized, double-dummy, double-blind study of 51 febrile children, receiving one of three regimens of a single acetaminophen dose: 15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally. Rectal temperature was monitored at baseline and hourly for a total of six hours. The primary outcome of the study, time to maximum antipyresis, and the secondary outcome of time to temperature reduction by at least 1°C were analyzed by one-way ANOVA. Two-way ANOVA with repeated measures over time was used to compare the secondary outcome: change in temperature from baseline at times1, 2, 3, 4, 5, and 6 hours among the three groups. Intent-to-treat analysis was planned. RESULTS: No significant differences were found among the three groups in the time to maximum antipyresis (overall mean = 3.6 hours; 95% CI: 3.2–4.0), time to fever reduction by 1°C or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature < 36.5°C) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group. CONCLUSION: Standard (15 mg/kg) oral, (15 mg/kg) rectal, and high-dose (35 mg/kg) rectal acetaminophen have similar antipyretic effectiveness

Pilocarpine Seizures Cause Age-Dependent Impairment in Auditory Location Discrimination

Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this question using an animal model of status epilepticus. Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures. Mature rats were trained with sound-source location and sound-silence discriminations. Control (saline P20) rats acquired both discriminations immediately. In status epilepticus (P20) rats, acquisition of the sound-source location discrimination was moderately impaired. Status epilepticus (P45) rats failed to acquire either sound-source location or sound-silence discriminations. Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans