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The maintenance of adequate tissue oxygenation during acute anemia depends on an increase in both cardiac output and tissue oxygen extraction. This study tested the hypothesis that anesthesia blunts the cardiac output response associated with acute normovolemic hemodilution.Forty patients undergoing major abdominal surgery were prospectively randomized to undergo acute normovolemic hemodilution (ANH) either awake (awake group, n = 20) or with fentanyl–nitrous oxide–isoflurane anesthesia (anesthetized group, n = 20). Radial and pulmonary artery catheters were placed in all patients. After hemodynamic measurements were taken, patients in the two groups underwent hemodilution to decrease their hemoglobin concentration from 13 to 8 g/dl. A total of 1,875 ± 222 ml (mean ± SD) of blood was collected and simultaneously replaced by the same volume of medium molecular weight hydroxyethylstarch in both groups.In the awake group, ANH resulted in a significant increase in cardiac index (from 3.1 ± 0.5 to 4.8 ± 1.0 l · min−1 · m−2) related to both an increase in heart rate and stroke index. Oxygen delivery remained unchanged, but oxygen consumption increased significantly, resulting in an increase in oxygen extraction ratio. In the anesthetized group, ANH resulted in a significantly smaller increase in cardiac index (from 2.3 ± 0.5 to 3.1 ± 0.7 l · min−1 · m−2) related solely to an increase in stroke index. Oxygen delivery decreased but oxygen consumption was maintained as oxygen extraction increased.Anesthesia significantly reduces the cardiac output response associated with ANH. This could be related to the effects of the anesthetic drugs on the autonomic and the cardiovascular systems.