Am. J. Respir. Crit. Care Med., Vol 150, No. 3, 09 1994, 790-794.
Proximate delivery of a large experimental dose from salbutamol MDI induces epithelial airway lesions in intubated rabbits
IA Spahr-Schopfer, J Lerman, E Cutz, MT Newhouse and M Dolovich
Department of Anaesthesia, Hospital for Sick Children, University of Toronto, Ontario, Canada.
The delivery of aerosolized drugs by metered dose inhaler (MDI) to
intubated patients can be substantially improved by actuating the MDI
through a narrow catheter placed inside the tracheal tube. However, the
deposition of increased quantities of drug, surfactant, in particular oleic
acid, and chlorofluorocarbon propellants on the lung surface could result
in adverse effects not observed after oral MDI administration. To
investigate this hypothesis, 42 adult intubated rabbits (six groups, n = 6
to 9/group) received Ventolin MDI, Ventolin placebo, a placebo MDI
containing lecithin as surfactant, instilled salbutamol sulfate, instilled
oleic acid solution, or no treatment (control). Heart rate, invasive blood
pressure, and hemoglobin oxygen saturation, recorded continuously for the
3-h experiment, were unchanged from baseline (awake) values. Sections of
trachea and lungs were reviewed blindly and graded using a four-point,
nine-variable Ophoven scale. Blood was obtained after either 1 puff or 20
puffs MDI salbutamol to determine the pharmacokinetic profile of
salbutamol. Multiple doses of both Ventolin and Ventolin placebo aerosols
produced significant lesions to the epithelium of the trachea and main
bronchi (p < 0.05). The histologic injury after lecithin placebo or
salbutamol solution did not differ significantly from control, and all were
significantly less than that observed after Ventolin MDI administration.
Instilled oleic acid caused gross airway lesions. Maximum serum
concentrations of salbutamol were 4.4 +/- 1.8 ng/ml after 1 puff and 419
+/- 168 ng/ml after 20 puffs. After 20 puffs, the total body clearance of
salbutamol was 108 +/- 27 ml/min/kg, volume of distribution was 3.6 +/- 1.8
L/kg, and the elimination half-life was 22 +/- 7 min.(ABSTRACT TRUNCATED AT
250 WORDS)
