BACKGROUND: The bispectral index for measurement of anesthetic depth may be modified by extreme hypotension during hemorrhagic shock. In this study, the influence of progressive hemorrhage and subsequent cardiopulmonary resuscitation on the bispectral index was investigated under controlled anesthetic depth. METHODS: Fifteen swine were anesthetized through inhalation of isoflurane under bispectral index monitoring. Hemorrhagic shock was induced using a stepwise hemorrhage model in which 20%, 10%, and 10% of estimated blood volume were removed over three 30-minute periods and then 5% was removed every 30 minutes until the mean arterial pressure was less than 10 mm Hg. After reaching this criterion, chest compression with 0.2-mg/kg epinephrine and hydroxyethyl starch infusion was performed for 20 minutes or until the mean arterial pressure exceeded 50 mm Hg. The pharmacodynamics of the isoflurane effect was examined before hemorrhage, after 40% bleeding, and after resuscitation. RESULTS: A mean (SD) volume of 836 (78) mL of blood was drained before resuscitation. The bispectral index suddenly decreased at a mean ( SD) arterial pressure of 22 (3) mm Hg and showed isoelectric activity in most animals before resuscitation. Eight pigs were resuscitated, and the bispectral index recovered during a range of periods after recovery of the mean arterial pressure. The pharmacodynamic effect of isoflurane did not change after 40% bleeding but increased after resuscitation, with the alteration correlated with the time for resuscitation. CONCLUSION: In hemorrhagic shock, the bispectral index merely reflects the anesthetic depth until development of lethal hypotension at which brain electrical activity cannot be sustained. After recovery from depression, the potency of isoflurane can increase depending on the cerebral hypoperfusion time. The increased bispectral index for anesthetics after resuscitation might reflect the degree of cerebral damage due to hypoperfusion. (J Trauma Acute Care Surg. 2012;72: 1614-1619. Copyright (C) 2012 by Lippincott Williams & Wilkins)