Cardiovascular compensation for mild (85 to 90% Sao₂), moderate (75 to 85% Sao₂), severe (50 to 75% Sao₂), and profound (<50% Sao₂) hypoxemia. Increased cardiac output, mainly mediated by increased heart rate, is the main cardiovascular response to hypoxemia, but is limited by age and cardiovascular disease. Mild to moderate hypoxemia causes increased cellular glycolysis, which generates 2,3 diphosphoglycerate and increases the P₅₀ of hemoglobin. Decreased tolerance of physical exertion or even normal activity is a sensitive indicator of the adequacy of early cardiovascular response to hypoxemia. Loss of consciousness becomes likely at saturations less than 50%. Failure of cardiovascular adaptation ultimately involves bradycardia, asystole, or pulseless electrical activity, with rapidly ensuing tissue injury and death. CO, cardiac output; HR, heart rate; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance.