Distribution of crystalloid fluid infused during onset of anesthesia-induced hypotension: a retrospective population kinetic analysis

Background Induction of anesthesia causes a drop in arterial pressure that might change the kinetics of infused crystalloid fluid. The aim of this report is to provide a mathematical view of how fluid distributes in this setting. Methods Data were retrieved from three studies where 76 patients (mean age 63 years, mean body weight 66 kg) had received approximately 1.1 L of Ringer’s solution over 60 min by intravenous infusion before and during induction of spinal, epidural, or general anesthesia. A population kinetic model was used to analyze the fluid distribution and its relationship to individual-specific factors. Frequent measurements of blood hemoglobin and the urinary excretion served as dependent variables. Results Before anesthesia induction, distribution to the extravascular space was threefold faster than elimination by urinary excretion. Both distribution and elimination of infused fluid were retarded in an exponential fashion due to the anesthesia-induced decrease in the mean arterial pressure (MAP). A decrease in MAP from 110 to 60 mmHg reduced the rate of distribution by 75% and the rate of elimination by 90%. These adaptations cause most of the infused fluid to remain in the bloodstream. Age, gender, type of anesthesia, and the use of ephedrine had no statistically significant effect on plasma volume expansion, apart from their possible influence on MAP. Conclusion The decrease in MAP that accompanies anesthesia induction depresses the blood hemoglobin concentration by inhibiting both the distribution and elimination of infused crystalloid fluid. The report provides mathematical information about the degree of these changes.

Distribution of Crystalloid Fluid Infused During Onset of Anesthesia-Induced Hypotension: A Retrospective Population Kinetic Analysis

Background. Loading with crystalloid fluid before induction of anesthesia is widely practiced but cannot reduce the accompanying drop in arterial pressure. The aim of this report is to provide a mathematical view of how fluid distributes in this setting.Methods. Data were retrieved from three studies where 76 patients (mean age 63 years, mean body weight 66 kg) had received approximately 1.1 L of Ringer’s solution over 60 min by intravenous infusion before and during induction of spinal, epidural, or general anesthesia. A population kinetic model was used to analyze the fluid distribution and its relationship to individual-specific factors. Frequent measurements of blood hemoglobin and the urinary excretion served as dependent variables.Results. Before anesthesia induction, distribution to the extravascular space was 3-fold faster than elimination by urinary excretion. Both distribution and elimination of infused fluid were retarded in an exponential fashion due to the anesthesia-induced decrease in the mean arterial pressure (MAP). A decrease in MAP from 110 to 60 mmHg reduced the rate of distribution by 75% and the rate of elimination by 90%. These adaptations cause most of the infused fluid to remain in the bloodstream. Age, gender, type of anesthesia, and the use of ephedrine had no statistically significant effect on plasma volume expansion, apart from their possible influence on MAP.Conclusion. The decrease in MAP that accompanies anesthesia induction depresses the blood hemoglobin concentration by inhibiting both the distribution and elimination of infused crystalloid fluid. The report provides mathematical information about the degree of these changes.

Predicting Residual Function in Hemodialysis and Hemodiafiltration—A Population Kinetic, Decision Analytic Approach

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of beta 2 microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations were derived entirely from computer simulations and advanced statistical modeling and had extremely high discrimination (Area Under the Curve, AUC 0.888–0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized predialysis and postdialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions for individualizing dialysis prescriptions in patients with preserved RRF.

Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates. Methods Twelve healthy volunteers, seven females and five males, mean age 28 ± 4.3 yr, underwent a randomized crossover study. Each subject participated in two separate sessions, separated by four weeks, in which they were assigned to an awake or an anesthetized arm. After a baseline period, hemorrhage (7 ml/kg during 20 min) was induced, immediately followed by a 25 ml/kg infusion during 20 min of 0.9% saline. Hemoglobin concentrations, sampled every 5 min for 60 min then every 10 min for an additional 120 min, were used for population kinetic modeling. Covariates, including body weight, sex, and study arm (awake or anesthetized), were tested in the model building. The change in dilution was studied by analyzing area under the curve and maximum plasma dilution. Results Anesthetized subjects had larger plasma dilution than awake subjects. The analysis showed that females increased area under the curve and maximum plasma dilution by 17% (with 95% CI, 1.08 to 1.38 and 1.07 to 1.39) compared with men, and study arm (anesthetized increased area under the curve by 99% [0.88 to 2.45] and maximum plasma dilution by 35% [0.71 to 1.63]) impacted the plasma dilution whereas a 10-kg increase of body weight resulted in a small change (less than1% [0.93 to 1.20]) in area under the curve and maximum plasma dilution. Mean arterial pressure was lower in subjects while anesthetized (P < 0.001). Conclusions In awake and anesthetized subjects subjected to controlled hemorrhage, plasma dilution increased with anesthesia, female sex, and lower body weight. Neither study arm nor body weight impact on area under the curve or maximum plasma dilution were statistically significant and therefore no effect can be established.

Predicting Residual Function in Hemodialysis and Hemodiafiltration – A Population Kinetic, Decision Analytic Approach

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of Beta 2 Microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations derived entirely from computer simulations and advanced statistical modeling, and had extremely high discrimination (AUC 0.888 – 0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized pre and post dialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions that for individualizing dialysis frequency in patients with preserved RRF.

Predicting Residual Function in Hemodialysis and Hemodiafiltration – A Population Kinetic, Decision Analytic Approach

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of Beta 2 Microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations derived entirely from computer simulations and advanced statistical modeling, and had extremely high discrimination (AUC 0.808 – 0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized pre and post dialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions that for individualizing dialysis frequency in patients with preserved RRF.

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.