Nasal midazolam in children, plasma concentrations and the effect on respiration

Twenty ASA 1 children, one to six years old, weighing 10-20 kg, scheduled for a combination of general and caudal anaesthesia received at random midazolam 0.2, 0.4, or 0.6 mg.kg-1 or NaCl 0.9% (control group) intranasally. Drug or NaCl 0.9% were administered in one nostril, after inhalation induction of anaesthesia, intubation without relaxant and caudal anaesthesia. Spontaneous respiration was via a circle system and fresh gas flow of 6 l.min-1 (N2O/O2 = 2:1), PEEP 5 cm H2O, endtidal 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 sampled 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 between 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 midazolam were detected 2 min after application in 10 of 15 patients. Median peak levels were found between 12 and 16 min. Medians of peak plasma 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 midazolam plasma concentration were significantly higher in the group 0.6 mg.kg-1.