RESEARCH ARTICLE


Repeated Intranasal Flumazenil Administration in Adult Subjects During Prolonged Benzodiazepine-induced Sedation



Trevor J. Szymanski1, Michael D. Curley2, Mirjana M. Lovrincevic3, Beverly K. Philip1, Juli Wyle-gala4, Massimo Ferrigno1, *
1 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
2 Center for Research and Education in Special Environments (CRESE) and Department of Physiology and Biophysics, University at Buffalo, Buffalo, NY, USA
3 Department of Anesthesiology, Roswell Park Cancer Institute, Buffalo, NY, USA
4 Rehabilitation Science, University at Buffalo, Buffalo, NY, USA


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Creative Commons License
© 2013 Szymanski et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Anesthesiol-ogy, Perioperative and Pain Medicine, Brigham & Woman’s Hospital, 75 Francis Street, Boston, MA 02115, USA; Tel: 617-732-8749; Fax: 617-277-2192; E-mail: maxmd@aol.com


Abstract

As part of a study exploring the use of oral diazepam to reduce carbon dioxide production and extend survival in a disabled submarine, intranasal flumazenil was used repeatedly over 48 hours to intermittently reverse benzodiazepine-induced sedation in six adult male subjects. Previous reports of intranasal flumazenil have been limited to pediatric pa-tients. Here we report the time course of administration of intranasal flumazenil and its effects on adult subjects, in whom flumazenil was given during sedation/reversal/re-sedation cycles. Sedation scores increased with flumazenil administra-tion in 24 of the 30 cycles, and in 100% of cases when subjects were at deeper levels of sedation.

Keywords: Diazepam, large doses, benzodiazepines, benzodiazepine antagonist, sedation/reversal/re-sedation cycles, alternative route.