Effects of etomidate and hypothermia on cerebral metabolism and blood flow in a canine model of hypoperfusion

Etomidate is a nonbarbiturate hypnotic agent which, like the barbiturates, decreases the cerebral metabolic rate of oxygen consumption (CMRO₂) 35-50%. The present studies assessed whether etomidate decreased CMRO₂ through temperature-dependent mechanisms and whether the combination of etomidate and moderate hypothermia (28°C) decreased CMRO₂ more than hypothermia alone. Nineteen anesthetized dogs were treated with saline, etomidate (burst- suppressive doses), etomidate with hypothermia, or hypothermia alone. Etomidate did not affect (p > 0.05) the mean arterial pressure (MAP, mm Hg) but modestly lowered the heart rate [HR; 124 ± 6 to 105 ± 14, (mean ± SEM); p < 0.05] whereas hypothermia (without or with etomidate) lowered (p < 0.05) both MAP (141 ± 4 to 116 ± 5 and 135 ± 6 to 81 ± 7) and HR (135 ± 14 to 84 ± 3 and 135 ± 10 to 69 ± 5, respectively). Etomidate administration did not result in a change (p > 0.05) in the esophageal, brain parenchymal, or subdural temperature. CMRO₂ (ml/100 g/min) decreased (p < 0.05) during etomidate administration (3.2 ± 0.4 to 1.7 ± 0.2) and hypothermia (3.5 ± 0.2 to 1.1 ± 0.2), but the addition of etomidate to hypothermia did not further reduce CMRO₂ in the animals (3.1 ± 0.5 to 1.3 ± 0.2) despite decreasing their brain hemispheric electrical activity from 9 ± 1 Hz to a burst-suppressive state. During hypotension (MAP 30 ± 2) induced by sodium nitroprusside and trimethaphan administration, the cerebral arteriovenous difference in O₂ (AVDO₂) increased (p < 0.05) in the saline group (5.4 ± 0.9 to 10.7 ± 1.0 ml/dl) but not in the other groups. Thus, etomidate does not have adverse cardiovascular effects associated with moderate hypothermia, and decreases CMRO₂ independently of brain temperature changes. Etomidate, however, in this model does not further reduce CMRO₂ in moderately hypothermic animals despite decreasing their brain hemispheric electrical activity. Etomidate, hypothermia, and the combination of etomidate and hypothermia all blunt the hypotension-induced increase in cerebral AVDO₂.