BJA Advance Access originally published online on April 2, 2008
British Journal of Anaesthesia 2008 100(5):631-636; doi:10.1093/bja/aen072
Plasma concentrations and sedation scores after nebulized and intranasal midazolam in healthy volunteers
1 Shackleton Department of Anaesthetics, Southampton University Hospital NHS Trust, Tremona Road, Southampton SO16 6YD, UK
2 Medical Toxicology Unit, Avonley Road, London SE14 5ER, UK
3 Dorset Research and Development Support Unit, Poole Hospital NHS Trust, Longfleet Road, Poole, Dorset BH15 2JB, UK
4 Institute of Health and Community Studies, Bournemouth University, Bournemouth, UK
* Corresponding author: Department of Anaesthetics, Poole Hospital NHS Trust, Longfleet Road, Poole, Dorset BH15 2JB, UK. E-mail: law_mckenna{at}hotmail.com
Background: An efficacious, reliable, and non-invasive route of administration for midazolam, a drug used for sedation and pre-anaesthetic medication, would have obvious advantages. This study compares two potential methods of administering midazolam by the nasal and nebulized routes.
Methods: Midazolam (0.2 mg kg–1) was given by both nebulizer and nasally by liquid instillation to 10 healthy volunteers in a randomized, double-blind crossover study. Plasma concentrations of midazolam, Ramsay sedation scores, visual analogue scores, critical flicker fusion frequency, and parameters of cardiovascular and respiratory function were measured over 60 min and summarized using ‘area under the curve’.
Results: Nasal instillation caused more sedation than nebulized administration. This was demonstrated by higher Ramsay sedation scores (P=0.005), lower visual analogue scores (P<0.001), and lower critical flicker fusion frequency (P<0.02). Nasal instillation was associated with higher plasma concentrations of midazolam (P<0.001). Unpleasant symptoms were recorded by six volunteers in the intranasal and one in the nebulized group (P=0.06).
Conclusions: There was some evidence that midazolam caused less discomfort when given by nebulizer compared with intranasally. Comparative bioavailability of midazolam, estimated by the ratio (nebulized:nasal) of area under the 60 min plasma concentration curve, was 1:2.9. A higher dose may need to be administered for adequate pre-anaesthetic medication when midazolam is given by nebulizer.
Keywords: sedation; pharmacokinetics, midazolam; premedication, midazolam