Christer H. Svensén

We studied whether central hemodynamics measured by a pulmonary artery catheter can serve as a pharmacodynamic expression of fluid therapy in 10 patients undergoing open abdominal surgery. We examined how closely hemodynamic variables follow plasma dilution, which is an index of plasma volume expansion, during and after an IV infusion of 25 mL/kg of lactated Ringer's solution over 45 min. Pulmonary artery wedge pressure and central venous pressure responded to IV fluid with an increase that correlated with accompanying plasma dilution. Six of 10 patients showed a decrease in cardiac output that was probably secondary to an increase in peripheral vascular resistance (nonresponders), whereas the rest increased cardiac output (responders). Volume kinetic analysis suggested that 54% of the infused fluid resided in the central fluid space at the end of the infusion and 25% at the end of the study in the responders compared with 25% and 3%, respectively, in nonresponders. In conclusion, half of the patients undergoing open abdominal surgery responded to crystalloid fluid with a decrease in cardiac output. Pulmonary artery wedge pressure and central venous pressure responded more consistently to different degrees of plasma dilution, which can be simulated for various fluid regimens using volume kinetics.

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.

Background: The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep. Methods: Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep. Results: kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01). Conclusions: Elimination from the central fluid space of large, rapidly infused volumes of saline solution is independent of infused volume. Larger volumes are apparently cleared from the central fluid space (V1) by expansion of a peripheral volume (V2) as renal excretion fails to increase in proportion to the volume of infused fluid.