Modifications of Blood Volume Alter the Disposition of Markers of Blood Volume, Extracellular Fluid, and Total Body Water1
- Tom C. Krejcie,
- Thomas K. Henthorn,
- W. Brooks Gentry,
- Claus U. Niemann,
- Cheri Enders-Klein,
- Colin A. Shanks and
- Michael J. Avram
Abstract
Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither antipyrine-defined total body water volume nor antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO.
Footnotes
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Send reprint requests to: Michael J. Avram, Ph.D., Department of Anesthesiology, Northwestern University Medical School, 303 E. Chicago Ave., CH-W139, Chicago, IL 60611-3008. E-mail:mja190{at}nwu.edu
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↵1 This study was supported in part by National Institutes of Health Grants GM43776 and GM47502. Portions were presented in part at the 1994 and 1997 annual meetings of the American Society of Anesthesiologists [Krejcie TC, Henthorn TK, Gentry WB, Shanks CA, Enders C, Van Drie J and Avram MJ (1994) The effect of altered blood volume on intravascular mixing. Anesthesiology81:A410; and Krejcie TC, Henthorn TK, Niemann CU, Klein C, Shanks CA and Avram MJ (1997) The effect of blood volume on drug disposition from the moment of injection. Anesthesiology87:A351].
- Abbreviations:
- CO
- cardiac output
- AUC
- area under the blood concentration-versus-time relationship
- Hct
- hematocrit
- ICG
- indocyanine green
- PA
- pulmonary artery
- MAP
- mean arterial pressure
- MTT
- mean transit time
- VC
- central volume
- VT-P
- pulmonary tissue volume
- VND-F
- fast nondistributive peripheral pathway volume
- ClND-F
- clearance to the fast nondistributive peripheral pathway
- VND-S
- slow nondistributive peripheral pathway volume
- ClND-S
- clearance to the slow nondistributive peripheral pathway
- VT-F
- rapidly (fast) equilibrating tissue volume
- ClT-F
- clearance to the rapidly (fast) equilibrating peripheral tissue compartment
- VT-S
- slowly equilibrating tissue volume
- ClT-S
- clearance to the slowly equilibrating peripheral tissue compartment
- ClE
- elimination clearance
- VSS
- total (steady-state) volume of distribution
- ΣCl
- total (sum of) all (peripheral and elimination) clearances
- LSD
- least significant difference
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- Received June 4, 1999.
- Accepted August 31, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
