Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers

Åke Norberg, Robert G. Hahn, Husong Li, Joel Olsson, Donald Prough, Elisabet Børsheim, Scott Wolf, Regina K. Minton, Christer H. Svensén

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

Original languageEnglish (US)
Pages (from-to)24-32
Number of pages9
JournalAnesthesiology
Volume107
Issue number1
DOIs
StatePublished - Jul 2007

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Isoflurane
Volunteers
Population
Anesthesia
Aldosterone
Renin
Albumins
Body Fluid Compartments
Arterial Pressure
Hemoglobins
High Cardiac Output
Fluid Shifts
Vasopressins
Sheep
Healthy Volunteers
Software
Pharmacokinetics
Hemodynamics
Hormones

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers. / Norberg, Åke; Hahn, Robert G.; Li, Husong; Olsson, Joel; Prough, Donald; Børsheim, Elisabet; Wolf, Scott; Minton, Regina K.; Svensén, Christer H.

In: Anesthesiology, Vol. 107, No. 1, 07.2007, p. 24-32.

Research output: Contribution to journalArticle

Norberg, Åke ; Hahn, Robert G. ; Li, Husong ; Olsson, Joel ; Prough, Donald ; Børsheim, Elisabet ; Wolf, Scott ; Minton, Regina K. ; Svensén, Christer H. / Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers. In: Anesthesiology. 2007 ; Vol. 107, No. 1. pp. 24-32.
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abstract = "BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9{\%}, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50{\%} of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9{\%} saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9{\%} saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.",
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T1 - Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers

AU - Norberg, Åke

AU - Hahn, Robert G.

AU - Li, Husong

AU - Olsson, Joel

AU - Prough, Donald

AU - Børsheim, Elisabet

AU - Wolf, Scott

AU - Minton, Regina K.

AU - Svensén, Christer H.

PY - 2007/7

Y1 - 2007/7

N2 - BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

AB - BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

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