A Dynamic Concept of the Distribution of Thiopental in the Human Body

Price, Henry L.

doi:10.1097/00000542-196001000-00008

Cited by 130 publications

(41 citation statements)

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“…They point out that central nervous system depression by short acting barbiturates is terminated by redistribution to peripheral tissues and metabolic breakdown of drug and that redistribution is the major process determining the duration of anaesthesia after a single bolus of thiopentone. Several studies indicate [28, [31][32][33][34][35] that the process of redistribution leading to subanaesthetic thiopentone plasma concentrations after thiopentone bolus injection takes only a few minutes. This is in accordance with the results of our study.…”

Section: Discussionmentioning

confidence: 99%

Midlatency auditory evoked potentials and purposeful movements after thiopentone bolus injection

Schwender¹,

Klasing²,

Madler³

et al. 1994

Anaesthesia

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Section: Discussionmentioning

confidence: 99%

Midlatency auditory evoked potentials and purposeful movements after thiopentone bolus injection

Schwender¹,

Klasing²,

Madler³

et al. 1994

Anaesthesia

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“…When simulating drug disposition in the presence of altered physiology, physiological modelers adjust regional blood flows to unadjusted tissue volumes in direct proportion to changes in cardiac output (Davis and Mapleson, 1993), arbitrarily and independently (Price, 1960), or on the basis of radioactive microsphere regional blood flow measurements (Benowitz et al, 1977). In performing the present simulations, the areas under the curves observed during the first 3 min after antipyrine administration to ␤-blocked volunteers were compared with those predicted by the simulations making the common assumption of physiologic models (Davis and Mapleson, 1993).…”

Section: Figmentioning

confidence: 99%

“…Price (1960) recognized the importance of cardiac output on early drug concentrations after rapid intravenous administration reasoning, for example, that the hypnotic dose requirement of patients in hemorrhagic shock is less because the fraction of the dose received by their brain is high and its rate of removal is low due to decreased blood flow to indifferent tissues. However, a study of the patient-specific variables age, sex, weight, lean body mass, and cardiac output that were associated with differences in thiopental induction dose requirements revealed that cardiac output alone could not account for inter-individual differences in dose requirements (Avram et al, 1993).…”

mentioning

confidence: 99%

β-Adrenergic Blockade Affects Initial Drug Distribution Due to Decreased Cardiac Output and Altered Blood Flow Distribution

Avram

Krejcie²,

Henthorn

et al. 2004

J Pharmacol Exp Ther

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␤-Adrenergic receptor blockers decrease intravenous anesthetic dose requirements. The present study determined the effect of propranolol on indocyanine green and antipyrine disposition from the moment of rapid intravenous injection. Antipyrine is a physiological marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a pharmacokinetic surrogate for many lipophilic drugs, including intravenous anesthetics. Antipyrine and indocyanine green disposition were determined twice in five healthy adult males in this Institutional Review Board-approved study, once during propranolol infusion. After rapid indocyanine green and antipyrine injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma indocyanine green and antipyrine concentrations were measured by high-performance liquid chromatography. Indocyanine green and antipyrine disposition were characterized, using SAAM II, by a recirculatory pharmacokinetic model that describes drug disposition from the moment of injection. Parameters were compared using the paired t test. The disposition of indocyanine green demonstrated that propranolol decreased cardiac output at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. The area under the antipyrine concentration versus time relationship was doubled for at least the first 3 min after injection due to both decreased cardiac output and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. The increase in antipyrine area under the curve due to propranolol-induced alteration of initial antipyrine disposition could explain decreased intravenous anesthetic dose requirements in the presence of ␤-adrenergic receptor blockade.␤-Adrenergic receptor blockade has been reported to decrease intravenous anesthetic dose requirements. Chronically administered propranolol decreased the sufentanil dose required to produce unconsciousness (Stanley et al., 1982). The acute administration of esmolol decreased potent volatile anesthetic requirements to prevent movement in response to skin incision by interacting with small doses of alfentanil (Johansen et al., 1998). In addition, although ␤-blockade produced by a bolus and infusion of esmolol did not affect the hypnotic concentration of propofol, it decreased the propofol dose requirement significantly, as reflected in the increased bias and inaccuracy of a target-controlled infusion (Orme et al., 2002). Although the mechanism by which ␤-blockers decrease intravenous anesthetic dose requirements is unclear, the latter observation suggests that the interaction is pharmacokinetic (Orme et al., 2002). Pharmacokinetic interactions with ␤-blockers are not unexpected because they decrease cardiac output and hepatic blood flow, so they would be expected to decrease the elimination clearance of high clearance drugs (Conrad et al., 1983). How...

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“…The 1960s saw increasing attention to the dose-related effects of anesthesia on the vital processes of the body. Investigators interested in anesthesia developed tools for defining anesthetic kinetics (what the body does to anesthetics) 1 and comparative pharmacodynamic effects (the relative effects of what anesthetics do to the body). In 1968, the Canadian Journal of Anaesthesia published an article by Tsutomu Oyama (1923Oyama ( -2008) et al entitled ''Effects of halothane anaesthesia and surgery on adrenocortical function in man'', 2 which is an exemplar presaging the expansion of pharmacodynamic studies.…”

Section: Introductionmentioning

confidence: 99%

From the Journal archives: A harbinger of modern anesthesia

Eger

2013

Can J Anesth/J Can Anesth

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A Dynamic Concept of the Distribution of Thiopental in the Human Body

Cited by 130 publications

References 0 publications

Midlatency auditory evoked potentials and purposeful movements after thiopentone bolus injection

Midlatency auditory evoked potentials and purposeful movements after thiopentone bolus injection

β-Adrenergic Blockade Affects Initial Drug Distribution Due to Decreased Cardiac Output and Altered Blood Flow Distribution

From the Journal archives: A harbinger of modern anesthesia

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