PREMEDICATION WITH MIDAZOLAM IN CHILDREN - EFFECT OF INTRANASAL, RECTAL AND ORAL ROUTES ON PLASMA MIDAZOLAM CONCENTRATIONS

We report a study performed to compare the time and plasma drug concen trations necessary to achieve a similar state of sedation after midazo lam premedication given by various routes in children of 2-5 years old . Children were randomly allocated to one of three groups to receive m idazolam 0.2 mg.kg(-1) given intranasally, 0.5 mg.kg(-1) given orally at. 0.3 mg.kg(-1) given rectally. Sedation was measured regularly unti l venepuncture was possible in a cooperative child. Ar this time, a fi rst blood sample was taken to measure plasma concentration, followed b y another 10 min later. Anaesthesia consisted of intravenous propofol supplemented with regional analgesia. At recovery from anaesthesia, a third blood sample was taken. Adequate sedation occurred sooner (7.7, SD 2.4 min) with intranasal than oral (12.5, SD 4.9 min) at rectal (16 .3, SD 4.2 min) midazolam. The initial blood levels were lower when th e drug was given by the alimentary routes despite higher doses (146, S D 51 ng.ml(-1) in 11.5, SD 3.9 min; 104, SD 34 ng.ml(-1) in 21+/-min; and 93, SD 63 ng.ml(-1) in 23.1, SD 3.5 min for the intra nasal, recta l and oral routes respectively). Duration of surgical procedures, and of propofol infusion, and recovery from anaesthesia was similar for th e three groups. The only problem arose in a 30-month-old boy in the in tranasal group who developed respiratory depression with a plasma mida zolam concentration of 169 ng.ml(-1). Intranasal midazolam is an excel lent alternative for rapid premedication provided that respiratory mon itoring is used.