Mechanical Ventilation with Room Air is Feasible in a Moderate Acute Respiratory Distress Syndrome Pig Model - Implications for Disaster Situations and Low-Income Nations.

INTRODUCTION: Patients with respiratory failure are usually mechanically ventilated, mostly with fraction of inspired oxygen (FiO2) > 0.21. Minimizing FiO2 is increasingly an accepted standard. In underserved nations and disasters, salvageable patients requiring mechanical ventilation may outstrip oxygen supplies. STUDY OBJECTIVE: The hypothesis of the present study was that mechanical ventilation with FiO2 = 0.21 is feasible. This assumption was tested in an Acute Respiratory Distress Syndrome (ARDS) model in pigs. METHODS: Seventeen pigs were anesthetized, intubated, and mechanically ventilated with FiO2 = 0.4 and Positive End Expiratory Pressure (PEEP) of 5cmH2O. Acute Respiratory Distress Syndrome was induced by intravenous (IV) oleic acid (OA) infusion, and FiO2 was reduced to 0.21 after 45 minutes of stable moderate ARDS. If peripheral capillary oxygen saturation (SpO2) decreased below 80%, PEEP was increased gradually until maximum 20cmH2O, then inspiratory time elevated from one second to 1.4 seconds. RESULTS: Animals developed moderate ARDS (mean partial pressure of oxygen [PaO2]/FiO2 = 162.8, peak and mean inspiratory pressures doubled, and lung compliance decreased). The SpO2 decreased to <80% rapidly after FiO2 was decreased to 0.21. In 14/17 animals, increasing PEEP sufficed to maintain SpO2 > 80%. Only in 3/17 animals, elevation of FiO2 to 0.25 after PEEP reached 20cmH2O was needed to maintain SpO2 > 80%. Animals remained hemodynamically stable until euthanasia one hour later. CONCLUSIONS: In a pig model of moderate ARDS, mechanical ventilation with room air was feasible in 14/17 animals by elevating PEEP. These results in animal model support the potential feasibility of lowering FiO2 to 0.21 in some ARDS patients. The present study was conceived to address the ethical and practical paradigm of mechanical ventilation in disasters and underserved areas, which assumes that oxygen is mandatory in respiratory failure and is therefore a rate-limiting factor in care capacity allocation. Further studies are needed before paradigm changes are considered.

The Effect of Anesthetic Regimens on Intestinal Absorption of Passively Absorbed Drugs in Rats.

PURPOSE: Different anesthetic regimens are used during single pass intestinal perfusion (SPIP) experiments for the study of intestinal drug absorption in rats. We examined the ketamine/xylazine anesthetic combination to evaluate its influence on drug absorption compared to older regimens. Additionally, we examined whether supplementary analgesia has any effect on drug absorption and the effect of the different anesthetic regimens on induction time and stress response. METHODS: Rats were anesthetized using four different anesthetic regimens; ketamine/midazolam, pentobarbital, ketamine/xylazine and ketamine/xylazine/butorphanol. Three model drugs were administered to rat intestines and Peff was calculated. Stress response was evaluated by quantifying blood corticosterone levels and induction time was recorded. RESULTS: We found absorption under pentobarbital to be higher or similar to absorption under ketamine/midazolam. These results partly correlate with past literature data. Ketamine/xylazine was found to give similar or higher Peff compared to pentobarbital and ketamine/midazolam. Addition of butorphanol did not affect absorption and reduced induction time and stress. CONCLUSIONS: In studies of intestinal drug absorption, the ketamine/xylazine combination is superior to other anesthetic regimens as it is more convenient and seems to affect absorption to a lesser extent. Addition of butorphanol is highly recommended as it did not affect absorption but led to a more effective and less stress inducing experiment.