• Zeev N Kain, Jill MacLaren, Brenda C McClain, Haleh Saadat, Shu-Ming Wang, Linda C Mayes, and George M Anderson.
• Center for the Advancement of Perioperative Health, Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA. kain@biomed.med.yale.edu
• Anesthesiology. 2007 Oct 1; 107 (4): 545-52.

BackgroundMultiple studies document the beneficial effect of midazolam on preoperative anxiety in children. Many clinicians report, however, that some children may in fact not benefit from the administration of this drug.MethodsAfter screening for relevant exclusion criteria, children undergoing surgery were enrolled in the study (n = 262) and received 0.5 mg/kg oral midazolam at 20-40 min before induction of anesthesia. Personality instruments were administered to all children, and anxiety levels were evaluated before and after administration of midazolam as well as during induction of anesthesia. Blood was drawn during the induction process and later analyzed for midazolam levels. A priori definitions of responders and nonresponders to midazolam were established using a multidisciplinary task force, videotapes of induction, and a validated and reliable anxiety scale, the modified Yale Preoperative Anxiety Scale.ResultsWhile 57% of all children scored at the minimum of the modified Yale Preoperative anxiety scale, 14.1% of children fell in the a priori defined group of midazolam nonresponders. Midazolam blood levels (94 +/- 41 vs. 109 +/- 40 ng/ml) and timing between administration of midazolam and induction (28 +/- 9 vs. 29 +/- 8 min) did not differ between midazolam responders and nonresponders. In contrast, midazolam nonresponders were younger (4.2 +/- 2.3 vs. 5.9 +/- 2.0 yr), more anxious preoperatively (49.7 +/- 22.9 vs. 38.3 +/- 19.1), and higher in emotionality (13.6 +/- 3.6 vs. 11.3 +/- 3.8) as compared with responders (P < 0.05).ConclusionsAlthough midazolam is an effective anxiolytic for most children, 14.1% of children still exhibit extreme distress. This subgroup is younger, more emotional, and more anxious at baseline. Future studies are needed to determine the best strategy to treat these children.

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