Recovery from Disturbed Cerebral Ion Homeostasis Following Severe Incomplete Ischemia and Modification by the Metabolic Depressant Drug Etomidate

Abstract

Therapeutic management with metabolic depressant drugs (e.g. barbiturates, althesin, etomidate) in patients suffering from major disturbances in cerebral blood flow (GBF) and metabolism has become increasingly accepted. Results from animal studies with different approaches to cerebral ischemic lesion (11, 23, 24) as well as from patients with severe head injuries (9,27) have indicated that pharmacologically induced “low flow and low metabolism” do benefit to the brain by preventing a mismatch between oxygen demand and delivery under critical flow conditions with subsequent lactacidosis and membrane failure; such conditions are regarded as the most important precursors of irreversible cell damage (2,21). Despite numerous promising results under regional and incomplete global cerebral ischemia (1,13), it must be admitted that the majority of the results subsequent to global interruption of cerebral circulation are unfavorable. Consequently, metabolic depression may only represent one part of the ideal therapeutic regimen and may be ineffective in those cases in which functional activity is already abolished (10). It has been suggested by several authors that the beneficial effects of these drugs under the above mentioned conditions are not only due to depression of oxidative metabolism, but also to other peculiar effects which are characteristic of each drug. This hypothesis has been supported by the work of Carlsson and Rehncrona (3) who demonstrated that chlormethiazole does not exert protective effects on cerebral postischemic recovery, but reduces CBF and metabolism to the same degree as barbiturates