Showing papers by "Elisabet Børsheim published in 2007"

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. 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. INTRAVENOUS administration of fluid is important during anesthesia and surgery. However, inability to correctly predict fluid shifts between tissues impedes precise matching of the rate of infusion with ongoing losses and volume demands. Volume kinetics has previously been applied to data from awake 1 and anesthetized 2 humans to study fluid shifts between different body fluid compartments. The current view is that fluid retention and postoperative tissue edema after surgery are promoted by trauma-induced stress 3,4 and by mechanical ventilation 5 rather than by the administration of an anesthetic per se. However, a study in sheep 6 demonstrated that the combination of isoflurane anesthesia and mechanical ventilation significantly alters the disposition of crystalloid fluid in comparison with conscious, spontaneously ventilating sheep. In a follow-up study in sheep, isoflurane was singled out as the cause for reduced urinary excretion and peripheral fluid accumulation. 7 The first aim of the current study was to investigate the hypothesis that isoflurane anesthesia promotes peripheral fluid retention and reduces urinary excretion in humans. To further develop kinetic modeling, a second aim was to apply population kinetic analysis to the plasma dilution data. With the development of a population kinetic model, it could be possible to attribute differences in fluid distribution to such parameters as body weight, age, and sex.