The elimination half-life of crystalloid fluid is shorter in female than in male volunteers: a retrospective population kinetic analysis

Abstract

Background: A recent review article suggests that elimination of infused crystalloid fluid might occur faster in females than in males. To study this question, a population kinetic analysis was performed to compare the turnover of buffered Ringer's solution when infused at different rates in males and females.

Methods: Data were retrieved from seven series of experiments where 44 intravenous infusions of Ringer's acetate had been given to female volunteers and 67 to male volunteers. Frequent measurements of the blood hemoglobin and the urinary excretion were used as input in a kinetic two-volume model with micro-constants and covariates, using a nonlinear mixed effects software. The key outcome measure was the rate of irreversible elimination of infused fluid, which was expressed as the half-life, obtained as the excreted urine divided by the modeled plasma volume expansion over time.

Results: The half-life amounted to 24 min (95 % confidence interval, 21-27) in the females and 38 min (33-42) in the males. The urinary excretion differed somewhat less than suggested by these figures during the experimental period (3-4 h) because the plasma volume became less expanded in the females. This was due to that fluid that had been distributed peripheral tissues (the interstitium) returned slightly more slowly to the central fluid space (the plasma) in the females. Gender did not serve as a statistically significant covariate to other rate constants in the kinetic model.

Conclusions: The half-life of infused Ringer's acetate was 60 % longer in healthy male volunteers than in female volunteers.

Keywords: Crystalloid fluid; Kinetic model; Sex differences.

Fig. 1

Kinetic model and goodness-of-fit. a Schematic drawing of the volume kinetic model. b Plasma dilution as predicted by the base model versus the measured plasma dilution for all data points in the 111 experiments. Hence, the predictions are based only on the mean values of V _c, k ₁₂, k ₂₁, k ₁₀, and k _b for all experiments. c Same plot as b but after correction of the predicted plasma dilution for covariates, which gives different values to k ₂₁ and k ₁₀ depending on gender. Random distribution around the solid line of unity indicates a good goodness-of-fit. d Predicted versus measured urinary excretion for all 111 infusions according to the base model. Each point represents one patient. e Same plot as d but after correction for covariates (i.e., gender). Comparing d with e shows how important gender is when predicting the diuretic response to infused fluid

Fig. 2

Covariate effects. V _c and the rate constants k ₂₁ and k ₁₀ obtain different values depending on gender. The mean (solid line) and the median (irregular line) are displayed within the box, which ends indicate the 25th and 75th percentile limits. The whiskers indicate the maximum and minimum values except for extreme outliers, which are not shown (if any)

Fig. 3

Distribution of infused fluid. Computer simulations of the distribution of fluid between body fluid compartments (V _c, V _t, and urine) when Ringer’s acetate is infused at two different rates in males and females. Fluid distribution is expressed in proportion to the body weight, which averaged 82 kg in the males and 63 kg in the females. The smaller volume expansion of V _c in the females, which was mostly due to greater accumulation in V _t, limited the short-term impact of the difference in crystalloid fluid half-life on the urinary excretion