title: The effect of rate of administration on brain concentrations of propofol in sheep.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia and Intensive Care, University of Adelaide and Royal Adelaide Hospital, North Tce, Australia. gludbroo@medicine.adelaide.edu.au
authors.forename: G L
authors.initials: GL
authors.lastname: Ludbrook
authors.forename: R N
authors.initials: RN
authors.lastname: Upton
authors.forename: C
authors.initials: C
authors.lastname: Grant
authors.forename: A
authors.initials: A
authors.lastname: Martinez
mesh_terms: D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D012307:Risk Factors; D012756:Sheep; D017186:Titrimetry
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol