The use of carbogen for interruption of febrile seizures - the randomized controlled CARDIF trial

Febrile seizures are the most common seizure disorders in children. Fever-induced hyperventilation and subsequent hypocapnia may precipitate febrile seizures. In preclinical studies and in individual children, increasing CO2 partial pressure has shown potential to terminate febrile seizures. We hypothesized that the use of carbogen (5% CO2 plus 95% O2) in the home environment would be an effective and safe treatment for recurrent febrile seizures. The CARDIF (CARbon DIoxide against Febrile seizures) trial is a randomized, monocentric, prospective, double-blind, placebo-controlled, crossover study to determine whether short-term inhalation of carbogen in the home environment can stop febrile seizures. 100% oxygen was used as a placebo control. We included children aged 0.5 to 5.0 years who presented after a first febrile seizure in the absence of severe organ or neurological disease, pathological EEG changes, or a history afebrile seizures. We noted parent-reported seizure duration, benzodiazepine use, and any serious adverse events. We enrolled n = 92 patients. In n = 20 children, at least one recurrent febrile seizure was treated with either carbogen or oxygen. Six of these children received both carbogen and oxygen in a planned crossover design. The febrile seizure was terminated in 5/15 episodes on carbogen and in 8/11 episodes on oxygen (Fischer's exact test; p = 0.11). Children with ≥2 recurrent febrile seizures completed the crossover arm. In these children, febrile seizures stopped during carbogen administration in 3/6 cases and during oxygen administration in 5/6 cases. In conclusion, carbogen did not interrupt acute febrile seizures more often than placebo. Home caregivers had difficulty determining when a seizure had stopped. Trial registration ClinicalTrials.gov NCT01370044.