Document Detail

Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: a pharmacokinetic and pharmacodynamic analysis.
MedLine Citation:
PMID:  15329589     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol. METHODS: After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 microg x kg(-1) x min(-1)) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. RESULTS: The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale. CONCLUSIONS: Hemorrhagic shock followed by resuscitation with lactated Ringer's solution did not alter the pharmacokinetics but did increase the potency of propofol. These results demonstrate that alterations in propofol pharmacokinetics observed in moderate to severe blood loss can be reversed with resuscitation. These results suggest that a modest reduction in propofol is prudent to achieve a desired drug effect after resuscitation from severe hemorrhagic shock.
Ken B Johnson; Talmage D Egan; Steven E Kern; Scott W McJames; Mark L Cluff; Nathan L Pace
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  101     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-26     Completed Date:  2004-09-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  647-59     Citation Subset:  AIM; IM    
Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah 84132-2304, USA.
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MeSH Terms
Anesthetics, Intravenous / pharmacokinetics*,  pharmacology*
Cardiac Output / drug effects,  physiology
Cardiopulmonary Resuscitation*
Computer Simulation
Electroencephalography / drug effects
Hemodynamics / drug effects,  physiology
Nonlinear Dynamics
Propofol / pharmacokinetics*,  pharmacology*
Respiration, Artificial
Shock, Hemorrhagic / metabolism*
Grant Support
Reg. No./Substance:
0/Anesthetics, Intravenous; 2078-54-8/Propofol
Comment In:
Anesthesiology. 2005 May;102(5):1068-9; author reply 1069-70   [PMID:  15851900 ]
Anesthesiology. 2004 Sep;101(3):567-8   [PMID:  15329579 ]
Anesthesiology. 2005 May;102(5):1068; author reply 1069-70   [PMID:  15851901 ]

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