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This randomized, prospective clinical study investigated the effects of supplemental inspired oxygen on arterial hemoglobin desaturation and myocardial ischemia in premedicated patients who have critical coronary artery stenosis, identified predictors for these adverse events, and examined the temporal relationship between hemoglobin desaturation and myocardial ischemia. Before elective coronary artery bypass surgery, 104 patients were monitored continuously by using a real-time electrocardiogram (V4 and V5 leads) recorder and a digital pulse oximeter. After a 2-h baseline monitoring period (Interval A), patients were given sub-lingual lorazepam 0.03 mg/kg, and were randomized to receive continuous supplemental inspired oxygen by nasal catheters [4 L/min (Oxygen Group, n = 52)] or to receive no supplemental inspired oxygen (Control Group, n = 52) (Interval B). One hour later, all patients received intramuscular morphine 0.15 mg/kg with perphenazine 0.05 mg/kg (Interval C). Interval C lasted 1 h, and the study was terminated. In the Oxygen Group, the incidence of desaturation was 25% before premedication and 11.5% after premedication (NS). In the Control Group after premedication, the incidence of desaturation increased from 25% to 56.9% (P < 0.001). There was no significant difference in the incidence of myocardial ischemia before or after premedication within or between the two groups. Arterial hemoglobin desaturation was not associated temporally with myocardial ischemia at any time. Predictors of desaturation after premedication included absence of supplemental O2, increased weight, age, and occurrence of desaturation before premedication. There were no identifiable predictors for myocardial ischemia after premedication. During Intervals A and C, episodes of hemoglobin desaturation were associated with small but statistically significant increases in mean heart rate. There was no increase in heart rate associated with development of myocardial ischemia. Premedication without supplemental O2 is associated with an increased incidence of hemoglobin desaturation, but has no significant impact on the incidence of myocardial ischemia. Supplemental O2 reduces the incidence, but not the degree or duration of desaturation. Supplemental O2 does not affect the incidence of myocardial ischemia in patients with critical coronary artery stenosis after premedication.