Limited protective effects of etomidate during brainstem ischemia in dogs

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✓ To evaluate etomidate as a neuroprotective agent in the brain stem, 33 dogs were divided into seven groups and were exposed to isolated, reversible brainstem ischemia in the presence or absence of etomidate using a newly developed canine model of brainstem ischemia. Brainstem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured during ischemia and for 5 hours after reperfusion. This model provides a potential physiological environment in which to test the efficacy of putative brainstem ischemic protective strategies.

During ischemia, BAEP were abolished in all animals. Without etomidate 10 minutes of ischemia was of short enough duration to allow complete recovery of BAEP. Ischemia of 20 or 30 minutes' duration resulted in minimal recovery. The dose of etomidate administered did not suppress BAEP or brainstem cardiovascular response to ischemia. In animals receiving etomidate and rendered ischemic for 20 minutes, a significant but only temporary recovery in BAEP was seen. Etomidate failed to have a significant effect in animals rendered ischemic for 30 minutes.

The minimal effect of etomidate on the current measures of brainstem function is in contrast to etomidate's known suppressive effect on cortical electroencephalogram and predicts that etomidate does little to alter brainstem metabolism. Etomidate's failure to provide for permanent recovery of BAEP suggests that the drug does not give sufficient protection from ischemia to the brainstem neurons in the auditory pathway. If these auditory neurons reflect brainstem function as a whole, etomidate may not be the protective agent of choice during temporary arterial occlusion of posterior circulation.

Article Information

Address reprint requests to: H. Hunt Batjer, M.D., Department of Neurological Surgery, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235–8855.

© AANS, except where prohibited by US copyright law.

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Figures

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    Ventral view showing dog's brain stem. The illustration shows the site of glue embolization and the site of catheter insertion. Post. Com. A. = posterior communicating artery; PCA = posterior cerebral artery; SCA = superior cerebellar artery; BA = basilar artery; III–XII = cranial nerves; VA = vertebral artery; VSA = ventral spinal artery.

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    Graph showing typical brainstem auditory evoked potential for a Group II (20 minutes of ischemia) animal. The amplitude quantified is the mean amplitude at Point II with respect to Points I and III. During the ischemic period the amplitude at Point II falls to zero. After 30 minutes of reperfusion the amplitude returns to 80% of the baseline. During later reperfusion the wave form further deteriorates and the Peak II amplitude drops. µV = microvolts.

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    Upper: Chart showing amplitude of brainstem auditory evoked potential (BAEP) for the four groups of animals not receiving etomidate. Lines I through IV represent 0, 10, 20, and 30 minutes of ischemia, respectively. The BAEP in animals experiencing 10 minutes of ischemia recovers to baseline while the animals experiencing 20 or 30 minutes of ischemia show only partial or no recovery. Lines I and II are significantly different from Lines III and IV (p < 0.0001). Lower: Chart showing amplitude of BAEP for the three groups that did receive etomidate. Group I controls show no significant change in BAEP on etomidate infusion. During ischemia, Groups II and III show total loss of BAEP. On reperfusion, Group II (20 minutes of ischemia) shows partial return of the BAEP amplitude. This return is maximum at 30 minutes of reperfusion and then decays to approximately 30% of baseline during later reperfusion. Group III (30 minutes of ischemia) shows no significant recovery of BAEP.

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    Bar chart comparing various ischemic groups with and without etomidate (five animals in each group). At 30 and 60 minutes of reperfusion, animals rendered ischemic for 20 minutes and treated with etomidate had different results than animals not treated with etomidate (p < 0.015).

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