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

Abstract

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.

Premedication with midazolam in young children: a comparison of four routes of administration

“…Many body orifices and other ways serve as tentative routes for administration: the most popular routes in descending order being oral (2,10,11,13,14) followed by rectal (3,4,6,12,15). Other possibilities include intranasal administration (16,17), sublingual (5,6), intramuscular (18) and jet injection (19). Intramuscular injection is not practicable today (2).…”

Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

“…administration to children. [2][3][4][5][6] Mean bioavailability was estimated at 55% when plasma concentrations after i.n. or i.v.…”

Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit

“…New routes of midazolam administration have already been reported recently: rectal route (11), intranasal route (12)(13)(14), 'Jet injection' route (15,16) and submucosal injection (17). These studies took stress as the starting point.…”