Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Abstract

In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer's lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer's lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer's lactate solution. A two-volume model best described the pharmacokinetics of Ringer's lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance (k r ) and central volume of distribution at baseline (V c0 ), respectively. The parameter estimates were as follows: k r (mL/min) = 124 + (MAP/70) 14.2 , V c0 (mL) = 0.95 + 3440 × (WT/63), V t0 (mL) = 2730, and k t (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.

Understanding volume kinetics

“…The most commonly studied covariates in drug research are age, gender, and body weight. In anesthesia, the arterial pressure is also an important covariate …”

“…Based on the urine flow rate, the elimination is approximately 10 times longer during general anesthesia . The main cause appears to be the lowered mean arterial pressure . Stimulating the alpha‐1‐receptors with phenylephrine and blocking the beta‐1‐receptors with esmolol triples the urinary excretion during surgery, but it is still far from being as effective as elimination in the conscious state.…”

“…16 The main cause appears to be the lowered mean arterial pressure. 8,9 Stimulating the alpha-1-receptors with phenylephrine and blocking the beta-1-receptors with esmolol triples the urinary excretion during surgery, 17 but it is still far from being as effective as elimination in the conscious state. The patient's capacity to handle infused fluid in the post-operative setting appears to be much better.…”

Population-based volume kinetics of crystalloids and colloids in healthy volunteers

“…Crystalloid solutions are used in most situations, but in cases which volume expansion is necessary, colloid solutions are used 1 . Plasma volume expansion and interstitial edema following administration of crystalloid or colloid solutions can be quantified using volume kinetics, a method used to analyze the disposition of infusion fluids 2–4 . Moreover, population analysis can be used to measure the interindividual variability of volume kinetic parameters 4,5 .…”

“…Plasma volume expansion and interstitial edema following administration of crystalloid or colloid solutions can be quantified using volume kinetics, a method used to analyze the disposition of infusion fluids 2–4 . Moreover, population analysis can be used to measure the interindividual variability of volume kinetic parameters 4,5 . Accurate quantification of the distribution and elimination of crystalloids or colloids used in clinical practice would contribute to the development of a more effective fluid therapy strategy.…”