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Patients in hemorrhagic shock often require emergent airway management. Clinical experience suggests that oxygen desaturation occurs rapidly in these patients; however, data are scant. The hypothesis of this study was that increasing levels of hemorrhagic shock, varying levels of fraction of inspired oxygen (Fio2) for preoxygenation, and fluid resuscitation significantly affect the duration until critical desaturation occurs.Fifteen pigs were studied in a hemorrhagic shock model with controlled hemorrhage (15, 30, and 45 ml/kg blood loss) and randomized to standard fluid resuscitation or no fluids. At each shock level, three apnea experiments (in randomized order) were performed after 5 min of preoxygenation at 21, 50, or 100% Fio2. After preoxygenation, ventilation was discontinued and the time to peripheral oxygen saturation of 70% or less was measured.During normovolemia, peripheral oxygen desaturation to less than 70% occurred after 33 ± 7 s (Fio2 = 0.21, mean ± SD), 89 ± 12 s (Fio2 = 0.5), and 165 ± 22 s (Fio2 = 1.0; P < 0.001). During increasing blood loss, peripheral oxygen desaturation to Spo2 less than 70% occurred significantly (P < 0.001) faster compared with normovolemia, but no effect of fluid resuscitation was observed. With 45 ml/kg blood loss, peripheral oxygen desaturation to less than 70% occurred after approximately 15 (Fio2 = 0.21) to 65 (Fio2 = 0.5) to 140 s (Fio2 = 1.0).Findings from this swine hemorrhagic shock model confirm that Fio2 and the level of hemorrhagic shock, but not fluid resuscitation, influence the rate of apneic desaturation. A five-fold increase in time until critical oxygen desaturation occurs can be achieved when preoxygenating with 100% oxygen compared with room air, underscoring the importance of adequate preoxygenation before emergent airway management.