Magnitude and precision of absolute blood volume estimated during hemodialysis.

Background: Management of body fluid volumes and adequate prescription of ultrafiltration (UF) remain key issues in the treatment of chronic kidney disease patients.Objective: This study aims to estimate the magnitude as well as the precision of absolute blood volume (Vb) modeled during regular hemodialysis (HD) using standard data available with modern dialysis machines.Methods: The estimation utilizes a two-compartment fluid model and a mathematical optimization technique to predict UF-induced changes in hematocrit measured by available on-line techniques. The method does not rely on a specific hematocrit sensor or a specific UF or volume infusion protocol and uses modeling and prediction tools to quantify the error in Vb estimation.Results: The method was applied to 21 treatments (pre-UF body mass: 65.57±13.44 kg, UF-volume: 3.99±1.14 L) obtained in ten patients (4 female). Pre-HD Vb was 5.4±0.53 L with an average coefficient of variation of 9.8% (range 1 to 22%). A significant moderate correlation was obtained when Vb was compared to a different method applied to the same data set (r = 0.5). Specific blood volumes remained above the critical level of 65 mL/kg in 17 treatments (80.9%).Conclusion: The method offers the opportunity to detect critical blood volumes during HD and to judge the quality and reliability of that information based on the precision of the Vb estimate.

Day-to-day variability in euvolemic body mass.

Short-term variability in body mass is a common, everyday phenomenon; however, data on body mass variability are scarce. While the physiological variability of body mass is negligible in healthy individuals, it could have implications for therapy in patients with impaired volume homeostasis, for example, patients with kidney failure undergoing kidney replacement therapy. We analyzed a long-term dataset comprising 9521 days of standardized body mass measurements from one healthy male individual and assessed the variability in body mass as a positive or negative relative difference in body mass measured on subsequent days. The average and median relative differences were zero, with a standard deviation (SD) of 0.53% for the one-day interval, increasing to 0.69% for the 7-day interval, and this variability was constant throughout the observation period. A body mass variability of approximately 0.6% (±450 mL in a 75-kg patient) should be taken into consideration when weight-dependent treatment prescriptions, e.g. the ultrafiltration rates in patients on hemodialysis, are being set. Consequently, a "soft target weight", considering the longitudinal variation of volume markers, such as body mass, might improve treatment quality.

Feasibility of continuous intra-uterine pressure measurements during amnioreduction in twin-to-twin transfusion syndrome therapy.

INTRODUCTION: This work explores the feasibility of simultaneous and continuous intra-abdominal, intra-uterine, and arterial blood pressure measurements to examine the hemodynamic perturbation expected during therapeutic amnioreduction and to better understand the protective role of the placenta during that treatment. METHODS: Patients with twin-to-twin transfusion syndrome were treated with fetoscopic laser ablation followed by amnioreduction. Intra-abdominal, intra-uterine, and mean arterial pressures were simultaneously recorded during amnioreduction performed in steps of 200 mL. Placental thickness and uterine dimensions were measured before and after amnioreduction by ultrasonography. RESULTS: Useful pressure recordings were obtained between volume reduction steps and short hands-off periods in four studies. Median amnioreduction volume was 1400 mL corresponding to a median uterine volume reduction of 1121 mL. Mean intra-uterine pressure significantly fell from 24.8 to 13.6 mmHg (p = 0.011) and intra-abdominal pressure significantly decreased from 13.4 to 9.2 mmHg after amnioreduction (p = 0.015). Uterine pressure recordings revealed transient contractions (A, in mmHg) following individual amnioreduction steps, which increased with fractional amnioreduction (F, no dimension) (A = 17.23*F + 11.81; r = 0.50, p = 0.001). DISCUSSION: Simultaneous and continuous measurement of intra-abdominal, intra-uterine, and arterial blood pressures during amnioreduction is feasible. The dynamics reveal transient uterine contractions reaching levels comparable to those seen during childbirth which seem to oppose impending maternal hypovolemia by placental steal at the expense of temporarily reducing placental perfusion pressure and underline the importance of uterine and placental interaction.

Differences in bioimpedance-derived fluid status between two versions of the Body Composition Monitor.

OBJECTIVES: The Body Composition Monitor (BCM) (Fresenius Medical Care) measures body impedances in alternating currents to subsequently calculate fat and lean tissue mass, fluid compartments, and overhydration (OH). The aim of this study was to investigate differences between two versions of the BCM (an older version, 3.2.5, and a newer version, 3.3.3). METHODS: Between September 2021 and December 2021, 28 hemodialysis patients were included to undergo BCM measurements before each of 14 consecutive dialysis sessions with versions 3.2.5 and 3.3.3 devices. Measurements were performed according to instructions provided by the manufacturer. Differences between BCM devices were tested for statistical significance using paired Wilcoxon tests, neglecting clustering. RESULTS: A total of 288 measurement pairs of 27 patients were left after exclusion of 43 flawed data points. The mean difference in OH between both BCM devices was 0.548 L (higher for version 3.2.5). Analysis of impedance data revealed differences in the high-frequency spectrum, quantifiable by the intracellular resistance, Ri (median Ri version 3.2.5 = 1750.3 Ω; Ri version 3.3.3 = 1612.45 Ω; P < 0.001), and the time delay, Td (median Td version 3.2.5 = 1.85 ns; Td version 3.3.3 = 8.88 nanoseconds; P < 0.001). CONCLUSIONS: This study finds that results between the two versions of the BCM differed in a clinically meaningful fashion and that the newer version 3.3.3 device had a bias toward less OH. Circulating BCM devices should be checked for versions and only devices of the same version should be used for each patient to ensure better within-patient consistency.

Intradialytic techniques for automatic and everyday access monitoring.

Vascular access dysfunction is associated with reduced delivery of dialysis, unplanned admissions, patient symptoms, and loss of access, making assessment of vascular access a fundamental part of routine care in dialysis. Clinical trials to predict the risk of access thrombosis based on accepted reference methods of access performance have been disappointing. Reference methods are time-consuming, affect the delivery of dialysis, and therefore cannot repeatedly be used with every dialysis session. There is now a new focus on data continuously and regularly collected with every dialysis treatment, directly or indirectly associated with access function, and without interrupting or affecting the delivered dose of dialysis. This narrative review will focus on techniques that can be used continuously or intermittently during dialysis, taking advantage of methods integrated into the dialysis machine and which do not affect the delivery of dialysis. Examples include extracorporeal blood flow, dynamic line pressures, effective clearance, dose of delivered dialysis, and recirculation which are all routinely measured on most modern dialysis machines. Integrated information collected throughout every dialysis session and analyzed by expert systems and machine learning has the potential to improve the identification of accesses at risk of thrombosis.

Comparable Hemodilution with Hypertonic Glucose in Patients with and without Type-2 Diabetes Mellitus during Hemodialysis.

(1) Background: It was examined whether glucose-induced changes in the relative blood volume are suitable to identify subjects with and without type-2 diabetes mellitus (T2D) during hemodialysis. (2) Methods: The relative blood volume was continuously recorded during hemodialysis and perturbed by the infusion of glucose comparable to the dose used for intravenous glucose tolerance tests. Indices of glucose metabolism were determined by the homeostatic model assessment (HOMA). Body composition was measured by a bioimpedance analysis. The magnitude and the time course of hemodilution were described by a modified gamma variate model and five model parameters. (3) Results: A total of 34 subjects were studied, 14 with and 20 without T2D. The magnitude of the hemodilution and the selected model parameters correlated with measures of anthropometry, body mass index, absolute and relative fat mass, volume excess, baseline insulin concentration, and HOMA indices such as insulin resistance and glucose disposition in a continuous analysis, but were not different in a dichotomous analysis of patients with and without T2D. (4) Conclusions: Even though the parameters of the hemodilution curve were correlated with measures of impaired glucose metabolism and body composition, the distinction between subjects with and without T2D was not possible using glucose-induced changes in the relative blood volume during hemodialysis.

Fluid volume management in hemodialysis: never give up!

Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward. Clinical reasoning demands that as much information as possible should be gathered on the fluid status of patients undergoing dialysis. Besides body weight and blood pressure, measurements of bioimpedance and dialysate bolus-derived absolute blood volume can in principle be automatized, whereas lung ultrasound can be obtained routinely. In the era of machine learning, fluid management could consist of flexible target weight prescriptions, adjusted on a daily basis and accounting even for fluctuations in fluid-free body mass. In view of all the negative prospective results surrounding fluid management in hemodialysis, we propose this as a "never-give-up" approach.

Changes of Hemodynamic Parameters after Intradialytic Glucose Injection.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis (HD). Current methods of IDH prevention are insufficient. METHODS: We analyzed the intradialytic time course of systolic (SBP), diastolic (DBP), mean arterial (MAP), pulse pressure (PP), and heart rate (HR) in a group of chronic kidney disease (CKD) patients. First, 30 min into HD, a 40% glucose solution was injected into the venous line of the extracorporeal circulation at a dose of 0.5 g/kg of dry weight. Pressures and HR were measured in frequent intervals. Relative volume overload was determined by bioimpedance spectroscopy. RESULTS: Thirty-five participants were studied. SBP increased after 5, 10, and 20 min of glucose infusion. DBP increased after 2 and 3 h and also at the end of HD. PP increased after 5, 10, and 20 min of glucose infusion and fell after the 2nd and 3rd hour and also at the end of HD. MAP increased after 2 and 3 h of glucose injection and at the end of HD. Significant interactions of the time course of SBP, DBP, MAP, with HR at baseline and of the time course of PP with fluid overload were observed. Symptomatic hypotensive episodes were absent. CONCLUSIONS: Glucose infusions during HD prevent symptomatic IDH and do not cause severe hypertensive episodes.

Ultrafiltration-induced decrease in relative blood volume is larger in hemodialysis patients with low specific blood volume: Results from a dialysate bolus administration study.

INTRODUCTION: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI). METHODS: This retrospective analysis comprised 77 patients who had their dialysate bolus-based absolute blood volume extracted routinely with an automated method. Patient-specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two-group comparisons, and correlation analyses. FINDINGS: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (rs  = -0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (rs  = -0.299, p = 0.008). DISCUSSION: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus-based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs.

Revisiting the concept of constant tissue conductivities for volume estimation in dialysis patients using bioimpedance spectroscopy.

RATIONALE: Current estimation of body fluid volumes in hemodialysis patients using bioimpedance analysis assumes constant specific electrical characteristics of biological tissues despite a large variation in plasma Na+ concentrations [Na+], ranging from 130 to 150 mmol/L. Here, we examined the potential effect of variable [Na+] on bioimpedance-derived volume overload. METHOD: Volumes were calculated from published whole-body extra- and intracellular resistance data and relationships using either "standard" or "revised" specific electrical characteristics modeled as functions of [Na+]. RESULT: With "standard" assumptions, volumes increased with increasing [Na+]. The increase in volume overload was about 0.5 dm3 and 3% of extracellular volume per 10 mmol/dm3 of [Na+] in a 75 kg patient. This increase was abolished when the same bioimpedance data were analyzed under "revised" conditions. DISCUSSION: The overestimation in extracellular volume overload in the range of 0.5 dm3 per 10 mmol/dm3 [Na+] perfectly matches the positive relationship determined in a large cohort of hemodialysis patients. The bias may be considered moderate when interpreting data of individual patients, but may become important when comparing data of larger patient groups. The bias disappears when analysis of bioimpedance data accounts for differences in tissue electrical properties, using individual [Na+].

Cardiovascular Response to Intravenous Glucose Injection during Hemodialysis with Assessment of Entropy Alterations.

BACKGROUND: The quality of autonomic blood pressure (BP) control can be assessed by the entropy of serial BP data. The aim of this study was to evaluate the effect of hemodialysis (HD) and glucose infusion (GI) on amplitude aware permutation entropy (AAPE) of hemodynamic variables during HD in chronic kidney disease patients with and without type-2 diabetes mellitus (DM). METHODS: Twenty-one patients without DM (NDO) and ten with DM were studied. Thirty minutes after the start of HD, a 40% glucose solution was administered. Hemodynamic data were extracted from continuous recordings using the Portapres® system. RESULTS: AAPE decreased during HD in all patients and all hemodynamic signals with the exception of AAPE of mean and diastolic BP in DM patients. GI led to an increase in AAPE for cardiac output in all patients, while AAPE for heart rate and ejection time increased only in DM studies, and AAPE for systolic, diastolic, and mean arterial pressure, as well as total peripheral resistance, increased only in NDO patients. CONCLUSIONS: The reduction in entropy during HD indicates impaired autonomic control in response to external perturbations. This state is partially reversed by the infusion of glucose with differences in central and peripheral responsiveness in DM and NDO patients.

Dynamics of vascular refilling in extended nocturnal hemodialysis.

INTRODUCTION: Long dialysis treatments are generally assumed to mitigate the ultrafiltration (UF) induced volume perturbation and to improve vascular refilling because of reduced UF rates and sufficient time for volume re-equilibration. The time course of vascular refilling was therefore examined during extended nocturnal dialysis. METHODS: For each hour of dialysis, vascular refilling volume was calculated from the absolute blood volume changes and UF volume removed. Absolute blood volume was estimated by indicator dilution at the beginning of dialysis and then tracked with a relative blood volume monitor. The refilling fraction was defined as the ratio of refilling volume to UF volume. FINDINGS: Ten stable chronic hemodialysis (HD) patients were studied during extended (7 h) nocturnal treatment sessions. Specific UF rate was 4.8 ± 1.8 ml/kg/h. In the 1 h, refilling volume amounted to only 23% of UF volume. Thereafter, refilling fraction steeply increased and reached maximum values in the 2, 3 and 4 h at about mean 90% (91.5%, 88.7%, and 91.1% respectively). From the 5 h on, refilling volume decreased (5 h 81.3%, 6 h 72.5%, 7 h 70.0% of UF volume). Cumulative refilling reached 73.6% of UF volume after 4 h of treatment time. This did not change during the further course of HD. Cumulative refilling volume showed a strong correlation (r = 0.94; p < 0.001) with UF volume. The ratio of blood volume to extracellular volume (Rbex ) was 0.306 ± 0.029 before and slightly but significantly increased to 0.326 ± 0.030 after UF. DISCUSSION: In spite of low-UF rates and extended treatment times, overall refilling fraction reached only 74% and was not different from the refilling fraction observed in regular HD. This value seems to represent a point where UF-induced volume perturbation is adequately compensated by physiologic control mechanisms.

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

BACKGROUND: Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, "before-" and "after-bolus"; (iii) assess ABV-variation. METHODS: We used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients. RESULTS: Regarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L. CONCLUSIONS: We demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple "abridged" calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.

An improved method to estimate absolute blood volume based on dialysate dilution.

Online hemodiafiltration machines equipped with a blood volume monitor and the possibility to rapidly infuse exact amounts of ultrapure dialysate into the extracorporeal circulation can be used to determine absolute blood volume in clinical practice. The aim of the present study was to evaluate the reproducibility of such measurements. Intra-individual reproducibility was evaluated in four measurements taken in hourly intervals within the same dialysis treatment. Ten patients were studied. Absolute blood volumes measured at the beginning and after 1 hour of dialysis were significantly different (80.6 ± 14.5 and 63.9 ± 14.3 mL/kg, P < .001) and highly reproducible between the last three measurements (63.9 ± 14.3, 61.4 ± 13.8, and 60.9 ± 13.9 mL/kg, P = n.s.). Measurement of absolute blood volume after 1 hour of treatment is more precise than earlier measurements and might be better suited for guidance of ultrafiltration.

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis.

AIMS: The disposal of a glucose bolus was studied to identify glucose metabolism in patients with and without type 2 diabetes mellitus (T2DM) during their regular hemodialysis (HD) treatment. METHODS: Plasma glucose, insulin, and c-peptide concentrations were measured during a 60 min observation phase following a rapid glucose infusion (0.5 g/kg dry weight). Glucose disposition and elimination rates were determined from kinetic analysis, and insulinogenic index was calculated. Insulin resistance (RHOMA) was determined by homeostatic model assessment (HOMA). RESULTS: 35 HD patients (14 with T2DM) distinguished by a higher age (median: 70 vs. 55 y, p < 0.01) in T2DM patients were studied. Glucose kinetic data showed only small differences between patients with or without T2DM, but as RHOMA measured in all patients increased, a larger fraction of glucose was removed by the extracorporeal system (r = 0.430, p = 0.01). One hour after glucose bolus injection the glucose level was not different from that before HD also in patients with T2DM (p = 0.115). CONCLUSIONS: The larger glucose amount recovered in dialysate in patients with increasing RHOMA indicates that impaired glucose disposal could be measured during HD using a non-invasive dialysis quantification approach without blood sampling. Glucose infusion during HD is safe also in patients with T2DM.

Sudden cardiac death in dialysis patients: different causes and management strategies.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.