Epinephrine Nebulization Delays Need for Life-Saving Intervention After Smoke Inhalation in Ovine Model

Smoke inhalation injury, alone or combined with burns and other traumas, remains a serious threat for military members as well as the civilian population. It causes acute respiratory distress syndrome requiring life-saving interventions (LSI), including various respiratory support, for example, oxygen supplementation, intubation, and noninvasive or invasive mechanical ventilation. While potentially scarce in austere environments and/or during mass casualties, LSI require trained personnel, equipment, and resources. In this study, we tested the hypothesis that nebulized epinephrine can delay the need for LSI using the clinically relevant ovine model of smoke inhalation.

Adult Merino female sheep were surgically instrumented with multiple catheters 5-7 days before the study. After recovery from surgery, sheep were subjected to smoke inhalation (48 breaths of cooled cotton smoke inhalation below 40°C) under anesthesia and analgesia. Then, sheep were randomly allocated to two groups. Sheep in the control group were injured and treated with saline nebulization (n = 6). Sheep in the treatment group were injured and treated with epinephrine nebulization (n = 6). Nebulization was started immediately after injury and repeated every 4 hours. After the smoke inhalation injury, sheep were allowed to spontaneously breathe room air via a mechanical ventilator set with positive end-expiratory pressure (PEEP) = 0 and pressure support = 0, which is equal to no mechanical support. An arterial blood gas analysis was determined every hour to adjust respiratory support, if needed. The changes in FiO 2 , PaO 2 /FiO 2 ratio, PEEP, and pressure support were recorded every hour from the onset of smoke injury. The primary outcomes were variables comparing oxygen demand, PaO2/FiO2 ratio, PEEP, and PS as representatives of the LSI. The secondary outcomes were comparison of systemic hemodynamics, bloodless lung wet-to-dry weight ratio, and histological analysis. Statistical significance was set at P < 0.05.

The time from the onset of smoke injury until the FiO 2 increased over 25% in the treatment group was significantly longer than in the control group ( P = 0.0406). The time until the FiO 2 increased over 30% in the treatment group was significantly longer ( P = 0.0474). The time until the PaO 2 /FiO 2 ratio decreased below 300 in the treatment group was significantly longer than in the control group ( P = 0.0195). The time for the increase in PEEP over 5 cmH 2 O in the treatment group was significantly delayed compared with the control group ( P = 0.0050). One animal in the control group required positive-pressure mechanical ventilation versus zero in the treatment group.

The present data indicate that nebulized epinephrine delays the need for LSI after smoke inhalation injury in the ovine model. If it is also effective in humans, nebulized epinephrine may be immediately used at the injury site as an effective resuscitation tool for smoke inhalation victims until they are admitted to the hospital for more progressive care.