Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis
7 Project III: Transmucosal nasal delivery of low-dose
midazolam – evaluation of two preparations for
procedural anxiolysis
7.1 Introduction
During MRI (magnet resonance imaging) examinations up to 30% of patients experience moderate
to severe anxiety and 10% of al MRI examinations cannot successfully be completed because of
claustrophobia [Münte Sinikka 2002].
For radiological investigations anxiolysis usually is provided by oral or intravenous application of
benzodiazepines (e.g., lorazepam or midazolam). Claustrophobic patients who are afraid or even
panic before or during MRI examination profit from conscious sedation, which helps them to cope
with the situation in the narrow MRI tunnel. Conscious sedation refers to anxiolysis and only slight
sedation, not impairing patient’s ability to maintain his airways and to respond appropriately to
physical stimulation and verbal commands [Merrick and Ramsby 1994]. This is required for
procedural anxiolysis during MRI examinations because some examinations require the
cooperation of the patients (e.g., in- and exhaling on command). Nasal application of low-dose
midazolam has been reported to be effective in procedural anxiolysis (conscious sedation),
furthermore the rapid onset is considered beneficial for MRI workflow [Moss, et al. 1993; Münte
2002]. Compared to oral application of 7.5 mg midazolam, the benefit of nasal delivered low-dose
midazolam (1-2 mg) was faster onset of anxiolysis and the absence of deep sedation. Therefore,
patients were able to follow the instructions during MRI examinations [Tschirch, et al. 2006]. For
nasal application of low-dose midazolam, no preparation is commercially available. Usually,
midazolam formulations for i.v. application are administered nasally or local Hospital Pharmacy
provides nasal midazolam preparations according to the monograph of NRF [NRF 2002].
The aim of this multicenter trial was to compare the benefit of two different preparations for nasal
delivery of low-dose midazolam to provide procedural anxiolysis during MRI examinations.
7.2 Methods
The ethics committees of Zurich and Basel and the national authorities (Swissmedic) approved the
clinical protocol of this multicenter trial, that was carried out at Center A (Institute of Diagnostic
Radiology, University Hospital Zurich), Center B (Institute of Radiology, Kantonsspital Winterthur),
Center C (Imamed Radiologie Nordwest, Basel), and Center D (Department of Radiology,
Orthopedic University Hospital Balgrist, Zurich). Coordination and monitoring was performed in
collaboration with Akroswiss AG, Zurich.
Katja Suter-Zimmermann Page 83 of 188 University of Basel, 2008