Endotracheal bretylium tosylate in a canine model

This study was conducted to determine whether bretylium tosylate (BT) is effectively and safely absorbed through the endotracheal route in the canine model. Eleven adult mongrel dogs were anesthetized with pentobarbital, were orally intubated, and had continuous blood pressure and electrocardiographic monitoring. Four dogs received 5 mg/kg BT, three dogs received 10 mg/kg BT, two dogs received 20 mg/kg BT, and two control dogs were given volumes of normal saline equal to those given the 5- and 10-mg/kg groups. Each dog received the same dose of BT both endotracheally and intravenously, but in a random order and on different dates. Following each drug administration arterial blood was drawn at various intervals over two hours and sent for immediate gas analysis; serum samples were frozen for future determination of BT levels. Regardless of the amounts delivered, the peak levels of BT in the arterial blood following administration by the endotracheal route were consistently low (4.13 micrograms/mL to 14.00 micrograms/mL) when compared to those levels following intravenously administered BT (120 micrograms/mL to 268 micrograms/mL) (all P less than .002 for the 5- and 10-mg/kg groups). No depot effect was observed during a two-hour period. The arterial blood gases did not change significantly following the administration of BT by the endotracheal route in the 5- and 10-mg/kg groups, and sections of these autopsied dog lungs showed no apparent pathologic changes.