Volume kinetic development and application

Background: Fluid therapy is a cornerstone in shock resuscitation in a such as treatment of anesthesia induce down regulation of the circulation and also restores many different types of dehydrated states. Current guidelines for fluid therapy are, however, based on experience, rules of thumb and effect-related end points, such as restoration of physiological parameters, which do not directly represent the volume effect of the fluid. Many efforts have been made to measure the actual volume effect of different fluids. The methods used are mainly based on isotope labeling of substances. Such a method has two inherent limitations. One is that labeling of substances results in volume estimations from the dispersal of the substance in the body, often leading to the conclusion that the volume effect of the fluid acts in the same space. The second limitation is the stationary result for each labeled substance infused. Such a method is not suited for dynamic analysis of fluid volume dispersal and elimination, whereas volume kinetics provides a time resolution. Methods: This thesis is based on the analysis of serial measurements of blood hemoglobin concentration in conjunction with intravenous fluid infusion, analyzed by a lest sqare regression curve rifting procedure. In paper I, the dilution-time profile was used to calculate the relative intravascular percentage of the infused amount of volume. In papers II-V, the analysis was based on volume kinetics using four different models. Results: Paper I showed that hypotension might modulate the preference of fluid to remain in the intravascular compartment. Papers II-V showed similar volume kinetic parameter results when no bleeding was induced and that the obtained volumes were significantly smaller than the expected extracellular spaces. Paper IV showed that hemorrhage resulted in a clearly reduced rate of elimination and that the V1 reduced by about the hemorrhaged volume. The use of urine volume as an input measurement in the two-volume model was justified when there was a high degree of intercorrelation between the elimination rate parameter and the parameter for the peripheral fluid space (paper III). Paper V compared the efficiency of five different infusion fluids and showed that volume kinetics could be used to analyze of the mechanism behind altered fluid handling. Conclusion: Time dilution profiles can be used to analyze the functional mechanisms controlling fluid distribution and elimination. The obtained parameters were the about same in experiments using different infusion volumes and rates. When strong parameter intercorrelation occurs, it is justified to use the urine volume in the calculation to reduce the estimated parameters so as to enhance the precision in the remaining ones. Additionally, serial analyze of blood dilution and volume kinetic interpretations were useful for creating a dynamic dosage scheme for hemorrhage in volunteers and also in the comparison between different fluids pinpointing the specific functional mechanisms causing differences in fluid handling. Thus, volume kinetics provides a new tool for the analysis of fluid dynamics. Volume kinetics is also a tool for the analysis of the mechanisms of pathological fluid handling, such as in septicemia, anesthesia, or heart failure (comparative studies)