The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane, and thiopental. 1977

E H Stullken, and J H Milde, and J D Michenfelder, and J H Tinker

The relationship between cerebral oxygen consumption (CMRO2) and anesthetic concentration has been assumed (based upon isolated measurements) to be approximately linear at concentrations less than 1 MAC. The shapes of the anesthetic dose-response curves for both CMRO2 and cerebral blood flow (CBF) were examined by multiple measurements made at small, progressive concentration increments from 0 to 2 MAC halothane (six dogs), enflurane (six dogs), and isoflurane (six dogs), and during a constant 23 mg/kg/hr infusion of thiopental (six dogs). The EEG was continuously recorded and changes in EEG patterns from "awake" to "anesthetic" were correlated with changes in anesthetic concentration, CBF, and CMRO2. The significance of changes in the slopes of regression lines for CMRO2 before, during and after changes in EEG patterns from "awake" to "anesthetic" were then determined. Contrary to previous inferences, CMRO2 dose-response curves were found to be nonlinear at anesthetic concentrations less than 1 MAC for all anesthetics studied. CMRO2 decreased precipitously until a stable "anesthetic" pattern was observed on the EEG; thereafter, CMRO2 decreased at a markedly reduced rate. The onset of this change occurred at concentrations well below MAC for the inhalational anesthetics. With the thiopental infusion, CMRO2 decreased most rapidly during the first 25 minutes. With halothane and enflurane, CBF was maximal during the period of transition in the EEG from an "awake" to an "anesthetic" pattern. CBF was elevated at all concentrations of isoflurane studied. CBF decreased rapidly during thiopental infusion until the EEG pattern changed from "awake" to "anesthetic" and then more slowly. The results demonstrate that the change in the EEG to an "anesthetic" pattern, which occurs at concentrations well below MAC, is accompanied by an abrupt metabolic depression. It is speculated that these events coincide with the onset of functional depression.

UI MeSH Term Description Entries
D007530 Isoflurane A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
D008738 Methyl Ethers A group of compounds that contain the general formula R-OCH3. Ethers, Methyl
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002560 Cerebrovascular Circulation The circulation of blood through the BLOOD VESSELS of the BRAIN. Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004737 Enflurane An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate. Alyrane,Enfran,Enlirane,Ethrane,Etran
D006221 Halothane A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178) 1,1,1-Trifluoro-2-Chloro-2-Bromoethane,Fluothane,Ftorotan,Narcotan

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