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Type: Journal article
Title: The effect of rate of administration on brain concentrations of propofol in sheep
Author: Ludbrook, G.
Upton, R.
Grant, C.
Martinez, A.
Citation: Anesthesia and Analgesia, 1998; 86(6):1301-1306
Publisher: International Anesthesia Research Society
Issue Date: 1998
ISSN: 0003-2999
Statement of
Guy L. Ludbrook, Richard N. Upton, Cliff Grant, and Alison Martinez
Abstract: <h4>Unlabelled</h4>A marked reduction in the dose of propofol required to achieve the onset of anesthesia with slower administration rates has previously been reported, but the mechanism of this phenomenon is unclear. We used a chronically instrumented sheep preparation to examine the effects of different administration rates of propofol on its distribution in the brain using mass balance principles to calculate brain concentrations. The administration of 100 mg of propofol i.v. at rates of 200, 50, and 20 mg/min had minimal effect on both the peak brain concentrations of propofol and the total amount of drug entering the brain. The more rapid administration rates increased the rate of uptake into the brain but resulted in large increases in peak arterial blood propofol concentrations. These faster administration rates have previously been associated with high arterial propofol concentrations and an increased risk of hypotension. Simulation of titration to an end point revealed that the dose sparing previously reported at induction with slow administration rates relates only to improved titration to effect, and does not result in more anesthesia for a given dose. Therefore, we conclude that the administration of propofol over 2 min provides a reasonable rate of induction and improved titration to effect, yet avoids excessively high arterial concentrations.<h4>Implications</h4>Alterations in the rate of administration of propofol in sheep have been shown to have little effect on the quantity of propofol delivered to the brain. At induction of anesthesia, administration rates of approximately 50 mg/min seem likely to provide improved titration to effect without excessively prolonging induction.
Keywords: Brain
Anesthetics, Intravenous
Anesthesia, Intravenous
Infusions, Intravenous
Injections, Intravenous
Drug Administration Schedule
Area Under Curve
Risk Factors
Cerebrovascular Circulation
Dose-Response Relationship, Drug
Description: Copyright © 1998 by International Anesthesia Research Society
DOI: 10.1097/00000539-199806000-00032
Published version:
Appears in Collections:Anaesthesia and Intensive Care publications
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