title: Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Karolinska Institute at Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Stockholm, Sweden. ake.norberg@karolinska.se
authors.forename: Ake
authors.initials: A
authors.lastname: Norberg
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hahn
authors.forename: Husong
authors.initials: H
authors.lastname: Li
authors.forename: Joel
authors.initials: J
authors.lastname: Olsson
authors.forename: Donald S
authors.initials: DS
authors.lastname: Prough
authors.forename: Elisabet
authors.initials: E
authors.lastname: Børsheim
authors.forename: Scott
authors.initials: S
authors.lastname: Wolf
authors.forename: Regina K
authors.initials: RK
authors.lastname: Minton
authors.forename: Christer H
authors.initials: CH
authors.lastname: Svensén
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D004396:Coloring Agents; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007208:Indocyanine Green; D007530:Isoflurane; D008297:Male; D008954:Models, Biological; D011153:Population; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012727:Sex Characteristics; D012965:Sodium Chloride / Q000493:pharmacokinetics*
chemical_list: D018685:Anesthetics, Inhalation; D004396:Coloring Agents; D006454:Hemoglobins; D006728:Hormones; D012965:Sodium Chloride; D007530:Isoflurane; D007208:Indocyanine Green