New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation/cutaneous flame burn injury

Abstract
To develop a predictable, dose-dependent, clinically relevant model of severe respiratory failure associated with a 40% total body surface area, full-thickness (third-degree) cutaneous flame burn and smoke inhalation injury in adult sheep. Model development. Research laboratory. Adult female sheep (n = 22). Animals were divided into three groups, determined by the number of smoke breaths administered (24, 36, 48) for a graded inhalation injury. The smoke was insufflated into a tracheostomy with a modified bee smoker at airway temperatures 60 mm Hg and PaCO2 <40 mm Hg. Arterial blood gases and ventilator settings were monitored every 6 hrs postinjury for up to 7 days. All animals survived the induction of injury. In the 24 smoke breath/40% total body surface area burn (24/40) group, PaO2/FIO2 never decreased below 300, and peak inspiratory pressure was consistently <14 cm H2O with normal arterial blood gases throughout the observation period. With 36 smoke breaths/40% total body surface area burn (36/40) (n = 7), all animals had PaO2/FIO2 of <200 and peak inspiratory pressure of 26 cm H2O within 40-48 hrs, as 30% died during the study period. With 48 smoke breaths/40% total body surface area burn (48/40) (n = 12), all animals developed respiratory distress syndrome (RDS) in 24-30 hrs, but none survived the experimental period. Development of RDS by smoke and cutaneous flame burn injury depends on smoke inhalation dose. A combination of 36 breaths of smoke and a 40% total body surface area (third-degree) cutaneous flame burn injury can induce severe RDS (PaO2/FIO2 <200) within 40-48 hrs to allow evaluation of various treatment modalities of RDS.