Urinary excretion as an input variable in volume kinetic analysis of Ringer's solution

Area of Science:

• Pharmacokinetics and Biopharmaceutics
• Physiology and Medicine

Background:

• Intravenous fluid infusion studies utilize kinetic models to analyze dilution of blood components.
• The two-volume kinetic model, while informative, often yields high standard errors for peripheral fluid space (V2) estimation.
• Investigating methods to stabilize V2 estimation in kinetic modeling is crucial for accurate fluid disposition analysis.

Purpose of the Study:

• To assess if a fixed elimination rate constant (kr), determined by urinary excretion, enhances the stability of the two-volume kinetic model.
• To evaluate the impact of a fixed kr on the accuracy and error of one- and two-volume kinetic models in fluid disposition studies.
• To determine the conditions under which a fixed kr improves the estimation of the peripheral body fluid space (V2).

Main Methods:

• Infusion of Ringer's acetate (25 ml kg-1 over 30 min) in 15 healthy adult male volunteers.
• Application of one- and two-volume kinetic models to fractional dilution data of blood hemoglobin and serum albumin.
• Curve-fitting analysis with a fixed elimination rate constant (kr) derived from urinary excretion, compared to model-generated kr values.

Main Results:

• A fixed kr increased total residual error in the one-volume model.
• The two-volume model demonstrated improved stability and V2 estimation when a strong within-patient covariance between kr and V2 existed (r2 ≤ -0.98).
• The peripheral fluid space (V2) was estimated at 10 liters when fixed and model-generated kr values showed full agreement.

Conclusions:

• Fixing the elimination rate constant (kr) does not universally improve fluid kinetic models; it can increase error in simpler models.
• The two-volume kinetic model's stability is significantly enhanced by incorporating a fixed kr, particularly when strong covariance with V2 is present.
• Accurate estimation of V2 in fluid disposition studies can be achieved by integrating urinary excretion data to fix kr, especially when model-generated and fixed kr values align.