Hypoproteinemia does not alter plasma volume expansion in response to a 0.9% saline bolus in awake sheep.

OBJECTIVE: To test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. DESIGN: Prospective and observational. SETTING: Laboratory. SUBJECTS: Five female merino sheep (n = 5) weighing 37 ± 3 kg were anesthetized. INTERVENTIONS: Each animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 L of 0.9% saline were performed in increments. MEASUREMENTS AND MAIN RESULTS: Fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. There was a significant reduction in total plasma protein concentration after plasmapheresis (p < .05). Colloid osmotic pressures were also significantly lowered (p < .05). A crystalloid infusion of 0.9% saline did not alter any of these values compared with baseline. The hemodynamic measurements did not show significant differences between the experiments. The plasma volume expansion reached approximately 20% at the end of infusion and stayed at 10-15% during the experiments. No difference was found in plasma volume expansion produced by a bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the euproteinemic state (p = .61). No difference in cumulative urinary output was found between the two states. CONCLUSIONS: In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.

Sepsis produced by Pseudomonas bacteremia does not alter plasma volume expansion after 0.9% saline infusion in sheep.

Clinicians generally consider sepsis to be a state in which fluid is poorly retained within the vasculature and accumulates within the interstitium. We hypothesized that infusion of 0.9% saline in conscious, chronically instrumented sheep with hyperdynamic bacteremic sepsis would be associated with less plasma volume expansion (PVE) and greater interstitial fluid volume expansion than in conscious, nonseptic sheep. Six conscious adult sheep received an IV infusion of 25 mL/kg of 0.9% saline over 20 min (1.25 mL.kg(-1).min(-1)) in a control nonseptic state and during early and late sepsis (4 and 24 h, respectively, after initiation of a standard infusion of live Pseudomonas aeruginosa). The distribution and elimination of infused fluid were studied by mass balance (after measurement of plasma volume using Evans blue dye) and volume kinetic analysis. Mass balance demonstrated no significant differences in the time-course of PVE between control, early sepsis, and late sepsis. At the end of the infusions, which averaged 1050 +/- 125 mL in sheep weighing an average of 42 +/- 5 kg, calculated PVE was 312 +/- 50 mL, 386 +/- 34 mL, and 400 +/- 51, respectively. Volume kinetic analysis was similar in all three protocols. In both nonseptic and septic sheep, infusion of 0.9% saline resulted in similar peak PVE and resolution of PVE over a 3-h interval and similar kinetic parameters. Contrary to clinical impressions and to our hypothesis, the distribution of 0.9% saline in this animal model was not changed by bacteremia produced by infusion of Pseudomonas aeruginosa.

Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and the combination of hemorrhage and fluid infusion in sheep.

BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts. METHODS: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion. RESULTS: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments. CONCLUSION: Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.

Volume kinetic analysis of the distribution of 0.9% saline in conscious versus isoflurane-anesthetized sheep.

BACKGROUND: The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. METHODS: Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes. RESULTS: The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma. CONCLUSIONS: In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.