CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

Journal of Translational Medicine

Markus Schuelke³  Dietmar Schmitz²  Steffen Weber-Carstens⁴  Peter Martus⁵  Claudia Weiß³  Tobias Wollersheim⁴  Stephanie Ohlraun¹ 

[1] NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany;Bernstein Center for Computational Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany;Department of Neuropediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany;Department of Anesthesiology and Operative Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany;Institute for Clinical Epidemiology and Applied Biostatistics, Eberhard-Karls-University, Tübingen, Germany

关键词: Translation;    Intervention;    Clinical Trial;    Carbon Dioxide;    Carbogen;    Alkalosis;    Febrile Seizure;   

Others  :  827328
DOI  :  10.1186/1479-5876-11-157

 received in 2013-01-09, accepted in 2013-06-14,  发布年份 2013

【 摘 要 】

Background

2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO₂-elevation via re-breathing or inhalation of 5% CO₂ instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO₂ is effective and safe to suppress febrile seizures in children.

Methods

The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO₂ plus 95% O₂) or placebo (100% O₂). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents.

Prospect

The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy.

Trial registration

ClinicalTrials.gov identifier: NCT01370044

【 授权许可】

   
2013 Ohlraun et al.; licensee BioMed Central Ltd.

【 图 表 】

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