McCormick A S M, Thomas V L, Berry D, Thomas P W
Shackleton Department of Anaesthetics, Southampton University Hospital NHS Trust, Tremona Road, Southampton SO16 6YD, UK.
Br J Anaesth. 2008 May;100(5):631-6. doi: 10.1093/bja/aen072. Epub 2008 Apr 2.
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.
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'.
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).
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.
咪达唑仑是一种用于镇静和麻醉前用药的药物，一种有效、可靠且非侵入性的给药途径具有明显优势。本研究比较了两种通过鼻腔和雾化途径给予咪达唑仑的潜在方法。
在一项随机、双盲交叉研究中，对10名健康志愿者分别通过雾化器和经鼻腔滴注给予咪达唑仑（0.2 mg·kg⁻¹）。在60分钟内测量咪达唑仑的血浆浓度、拉姆齐镇静评分、视觉模拟评分、临界闪烁融合频率以及心血管和呼吸功能参数，并使用“曲线下面积”进行总结。
鼻腔滴注比雾化给药引起的镇静作用更强。这通过更高的拉姆齐镇静评分（P = 0.005）、更低的视觉模拟评分（P < 0.001）和更低的临界闪烁融合频率（P < 0.02）得以证明。鼻腔滴注与更高的咪达唑仑血浆浓度相关（P < 0.001）。6名鼻腔给药组志愿者和1名雾化给药组志愿者记录了不适症状（P = 0.06）。
有一些证据表明，与经鼻给药相比，雾化给予咪达唑仑时引起的不适更少。通过60分钟血浆浓度曲线下面积的比值（雾化：鼻腔）估计，咪达唑仑的相对生物利用度为1:2.9。当通过雾化器给予咪达唑仑进行充分的麻醉前用药时，可能需要给予更高的剂量。
