Comparison of intravenous and endotracheal administration of midazolam and the effect on pulmonary function and histology in the lamb model

To determine the effect of endotracheal administration of midazolam on pulmonary function and histology in lambs. Prospective, randomized, controlled study. Laboratory of the UpJohn Pharmaceutical Company. Twenty male and female lambs weighing 10 to 20 kg. The animals were anesthetized and placed on controlled ventilation. The animals were divided into four groups. The first two groups received endotracheal midazolam 0.1 and 0.2 mg/kg. The other two groups received IV midazolam 0.1 and 0.2 mg/kg. The endotracheal group had a catheter placed through the endotracheal tube, and midazolam was rapidly injected through the catheter followed by a 2-mL normal saline flush. Two rapid insufflations were administered, and the animals were then returned to the ventilator. Serum midazolam levels were drawn at one, two, five, ten, 15, and 20 minutes after both IV and endotracheal administration. Heart rate, respirations, SaO 2 by oximetry, peak and mean airway pressure, compliance, airway resistance, and end-tidal CO 2 were measured throughout the experiment. Lung sections were taken from control and treated animals receiving 0.1 and 0.2 mg/kg endotracheal midazolam, respectively. Sample lung sections were taken at 24, 48, and 120 hours after endotracheal midazolam administration. There were no statistical or clinically significant differences for pulmonary function between endotracheally and IV-administered midazolam. Histologic examination of the lungs at 24, 48, and 120 hours after endotracheal midazolam showed no pathologic changes in the control and study animals. Acceptable serum midazolam levels were achieved endotracheally with no clinically deleterious effects. Endotracheal midazolam showed no significant deleterious effect on pulmonary function or histology in the lamb model.