NASAL MIDAZOLAM IN CHILDREN, PLASMA-CONCENTRATIONS AND THE EFFECT ON RESPIRATION

Twenty ASA 1 children, one to six years old, weighing 10-20 kg, schedu led for a combination of general and caudal anaesthesia received at ra ndom midazolam 0.2, 0.4, or 0.6 mg . kg(-1) or NaCl 0.9% (control grou p) intranasally. Drug or NaCl 0.9% were administered in one nostril, a fter inhalation induction of anaesthesia, intubation without relaxant and caudal anaesthesia. Spontaneous respiration was via a circle syste m and fresh gas flow of 61 . min(-1) (N2O/O-2 = 2:1), PEEP 5 cm H2O, e ndtidal halothane 0.4%. Immediately before and 2, 5, 8, 12, 16, 20, 30 , 60 and 120 min after application of the drug 2.5 ml blood was sample d for plasma levels of midazolam. Endtidal CO2, respiratory rate, and oxygen saturation were recorded as long as the children were intubated . Endtidal CO2 and respiratory rate showed no statistical difference b etween the groups at any time, however, in the group receiving 0.6 mg . kg(-1), endtidal CO2 increased significantly from 5.3 kPa (41 mm Hg) at the start to 5.9 kPa (45.5 mm Hg) after 30 min. Plasma levels of m idazolam were detected 2 min after application in 10 of 15 patients. M edian peak levels were found between 12 and 16 min. Medians of peak pl asma levels showed no statistical difference between the three groups (0.2 mg . kg(-1):111 ng . ml(-1), 0.4 mg . kg(-1):136 ng . ml(-1) 0.6 mg . kg(-1):277 ng . ml(-1)). After 30, 60 and 120 min medians of mida zolam plasma concentration were significantly higher in the group 0.6 mg . kg(-1).