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.

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.

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.

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.

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.

Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.

Should a fistula first policy be revisited in elderly haemodialysis patients?

Life-sustaining haemodialysis requires a durable vascular access (VA) to the circulatory system. The ideal permanent VA must provide longevity for use with minimal complication rate and supply sufficient blood flow to deliver the prescribed dialysis dosage. Arteriovenous fistulas (AVFs) have been endorsed by many professional societies as the VA of choice. However, the high prevalence of comorbidities, particularly diabetes mellitus, peripheral vascular disease and arterial hypertension in elderly people, usually make VA creation more difficult in the elderly. Many of these patients may have an insufficient vasculature for AVF maturation. Furthermore, many AVFs created prior to the initiation of haemodialysis may never be used due to the competing risk of death before dialysis is required. As such, an arteriovenous graft and, in some cases, a central venous catheter, become a valid alternative form of VA. Consequently, there are multiple decision points that require careful reflection before an AVF is placed in the elderly. The traditional metrics of access patency, failure and infection are now being seen in a broader context that includes procedure burden, quality of life, patient preferences, morbidity, mortality and cost. This article of the European Dialysis (EUDIAL) Working Group of ERA-EDTA critically reviews the current evidence on VA in elderly haemodialysis patients and concludes that a pragmatic patient-centred approach is mandatory, thus considering the possibility that the AVF first approach should not be an absolute.

Pros and cons of antithrombotic therapy in end-stage kidney disease: a 2019 update.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High- and Low-Flux Hemodialyzers.

The aim of this study was to examine the relationship between hydrostatic trans-membrane pressure (TMPh ) and colloid osmotic pressure (COP) in low-flux (LF) and high-flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg) under constant dialysate flow and variable blood flow (Qb ) ranging from 0 to 400 mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted, undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit, all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly increased with increasing Qb . The intercept of the linear TMPh to Qb relationship correlated with measured COP with an average bias of 1.00 ± 2.26 mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear TMPh to Qb relationship increased with increasing sample viscosity and was much larger in HF dialyzers under otherwise identical operating conditions, most likely because of increased internal filtration. The TMPh to Qb relationship measured in dialyzers in absence of UF can be described by the intercept related to measured COP and the slope related to internal filtration. This relationship could be of interest to estimate internal filtration and COP under in vivo conditions.

Hemodialysis Ultrafiltration Rate Targets Should Be Scaled to Body Surface Area Rather than to Body Weight.

The association between higher ultrafiltration rates and poor outcomes in hemodialysis patients has received increased attention, to the point that various regulatory entities are considering adding ultrafiltration rate as a quality measure to be monitored and controlled. Most of the discussion to date has focused on ultrafiltration rate scaled to body weight, or more correctly, body mass (ml/hour per kg). One outcome study suggests that ultrafiltration rate might best be not scaled at all to body size, as modestly higher ultrafiltration rate in very small-size patients may be associated with some survival benefit, probably via increased dietary intake. Outcomes studies also suggest that the risk of exceeding a weight-scaled ultrafiltration target may be magnified in very large patients, and that body weight-scaled ultrafiltration targets in such patients should be set a lower level. Here, we present an analysis, based on physiological hemodynamic arguments, that it would be better to scale ultrafiltration rate to body surface area rather than to body mass. Whatever ultrafiltration rate is scaled to, attempts to restrict ultrafiltration rate by limiting interdialytic weight gain in small, possibly malnourished patients, should be done cautiously, to prevent an inadvertent lowering of intake of calories and dietary protein.

Vascular Refilling Is Not Reduced in Dialysis Sessions with Morbid Events.

BACKGROUND: It is commonly believed that insufficient vascular refilling leads to hypovolemia during hemodialysis and contributes to intradialytic morbid events (IME). But data of refilling volumes at the time of IME are lacking. METHODS: We compared the vascular refilling in 10 patients with IME with 14 stable patients with normal blood volume at the dialysis end (66-80 mL/kg). RESULTS: The refilling characteristics in patients with IME did not differ from those in stable patients. The refilling fraction (refilling/ultrafiltration [UF] ratio) was 73.8 ± 9.4% in patients with IME, and 70.2 ± 6.4% in patients with normal blood volume at the end of the treatment. Refilling volume strongly correlated with UF volume in both patient groups (r2 = 0.93 and r2 = 0.81, respectively). CONCLUSION: IME are associated with a specific blood volume below 65 mL/kg. Vascular refilling is a constant fraction of UF in stable as well as in symptomatic dialysis sessions.

Loss of antimicrobial effect of trisodium citrate due to 'lock' spillage from haemodialysis catheters.

BACKGROUND: Due to its reported antimicrobial effects, hypertonic citrate (46.7%) is a widely used catheter lock solution, but following instillation, citrate inevitably spills into the systemic circulation. This process is mainly driven by hydraulic effects during instillation and density differences between blood and lock solution. Hence, in haemodialysis catheters, intra-luminal citrate concentration ranges from 0% (at the tip in catheters with side holes), 3% (between the side holes and the highest point of the catheter) to 46.7% (at the Luer end) with possible differences in antimicrobial effects. We investigated in vitro the antimicrobial effect of pure citrate 46.7%, citrate 46.7% diluted with saline and blood to a net concentration of 3% (=citrate 3%), and of citrate-free blood, simulating in vivo conditions in different catheter sections. METHODS: Time-kill studies measuring the antimicrobial effect of citrate 46.7%, citrate 3% and citrate-free blood were performed with overnight cultures of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). RESULTS: Citrate 46.7% reduced the number of E. coli by 2 log units but after 24 h, 10(6) CFU/mL were still present. Citrate 3% and citrate-free blood had no antimicrobial effect on E. coli. Citrate 46.7%, citrate 3% and citrate-free blood had scarce antimicrobial effect on S. aureus within 24 h. CONCLUSIONS: Spillage of catheter lock solution leading to reduced intra-luminal citrate concentrations considerably reduces the antimicrobial effect of citrate 46.7% on E. coli. As none of the solutions tested had relevant antimicrobial effect on S. aureus, the antimicrobial effect of 46.7% citrate lock solution in vivo has to be seriously questioned.

Prevalence of detectable venous pressure drops expected with venous needle dislodgement.

Venous needle dislodgement (VND) is a potentially fatal complication during hemodialysis (HD) treatment and the venous pressure monitor is the most widely used device for its detection. VND can only be detected by the venous sensor if the resulting pressure drop exceeds the difference between the actual venous pressure and the lower alarm limit. In clinical practice, the lower alarm limit is usually set 30-40 mmHg below the actual venous pressure to avoid a disproportionate high number of nuisance alarms. The aim of this study was to quantify the number of fistulas and grafts in a group of HD patients where venous pressure monitoring can be expected to detect VND. We determined intra-access pressures in 99 chronic HD patients. Sixty-five (65.7%) had a fistula and 34 (34.3%) had a prosthetic graft as a vascular access. Mean intra-access pressure (Pa ) in fistulas was 32.6 ± 23.5 mmHg, whereas in grafts mean Pa was 60.9 ± 19.5 mmHg. Nineteen (29.2%) of the fistulas and 32 (94.1%) of the grafts exhibited an intra-access pressure above 40 mmHg. Therefore, in our study nearly all grafts but only 29% of fistulas would fulfill the requirement for venous pressure monitoring to detect VND.

Continuous veno-venous hemofiltration to adjust fluid volume excess in septic shock patients reduces intra-abdominal pressure.

OBJECTIVE: To analyze the effect and the time course of continuous veno-venous hemofiltration (CVVH) with net ultrafiltration (UF) on intra-abdominal pressure (IAP) body fluid volumes in septic shock patients with acute kidney injury (AKI). METHODS: Patients were studied at baseline and after 6, 12, 24, 48, 72, and 96 hours of CVVH treatment. IAP was measured via the bladder, and abdominal perfusion pressure (APP) was calculated as mean arterial pressure minus IAP. Fluid volume excess (VE), total body water (TBW), extracellular body water (ECW), and intracellular body water (ICW) were derived from wholebody bioimpedance analysis (BIA). RESULTS: 30 patients entered final analysis, of which 6 died during CVVH (non-survivors). Fluid VE, TBW, ECW, ICW, and IAP significantly decreased in 24 survivors, whereas these variables remained essentially unchangedin non-survivors. APP slowly increased in survivors, while it did not change in nonsurvivors. IAP strongly correlated with VEin survivors: The lower the IAP, the lower the fluid volume excess. CONCLUSION: CVVH with net UF successfully reduced IAP, TBW, ECW, and ICW in critically ill patients who survived 96 h of CVVH. Failure to increase APP was associated with fatal outcome, and, finally, IAP correlated with fluid volume excess. BIA could be helpful to monitor fluid status in patients with AKI.

A simple and feasible method to determine absolute blood volume in hemodialysis patients in clinical practice.

BACKGROUND: We developed a simple method to determine the absolute blood volume (V) during hemodialysis in everyday clinical practice and examined its relationship with volume overload, clinical relevance, and accuracy. METHODS: The increase in relative blood volume (RBVpost - RBVpre) measured before and after infusion of 240 ml of ultra-pure dialysate using the bolus function of a commercial online hemodiafiltration machine incorporating a relative blood volume monitor was applied to determine absolute blood volume. The specific blood volume (Vs, blood volume per kg body mass at dry weight, in ml/kg) was compared to volume status as assessed by bioimpedance analysis and clinical criteria. RESULTS: The blood volume measured in 30 stable hemodialysis patients was 6.51 ± 1.70 l at the beginning, corresponding to a specific blood volume of 80.1 ± 12.8 ml/kg, and dropped to 5.84 ± 1.61 l or 72.0 ± 12.1 ml/kg at the end of the dialysis session, respectively. Specific blood volume correlated with volume status assessed both clinically and by bioimpedance analysis. Intradialytic morbid events occurred only in treatments where specific blood volume fell below 65 ml/kg. The reproducibility of the technique was better than 4% and the in vitro accuracy corresponds to a resolution in Vs of better than 1 ml/kg. CONCLUSION: Absolute blood volume can be easily measured at the beginning of the dialysis session using the current dialysis technology. Information about V and Vs could be a promising tool to avoid intradialytic morbid events. This technique could be completely automated without altering the hardware of currently available online dialysis devices. Therefore, it is recommended that this technique be integrated into all hemodiafiltration machines.

Volume excess in chronic haemodialysis patients--effects of treatment frequency and treatment spacing.

BACKGROUND: The main objective of this study was to theoretically quantify the fluctuations of fluid volume excess for different modes of intermittent ultrafiltration schedules and to compare the prediction for the typical and asymmetric thrice-weekly schedule to clinical, physiological and biophysical markers of volume expansion in a group of stable haemodialysis patients. METHODS: Overall volume excess (V(OVE)) was described as the sum of a time-independent (V(0)) and a time-dependent component (V). An exact relationship was developed to relate V to variable treatment frequency, treatment spacing and net volume accumulation rate. In a single-centre haemodialysis population, body mass profiling was combined with volume state evaluation by bioimpedance analysis, N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels, clinical signs, a volume questionnaire and blood pressure levels. RESULTS: In 23 patients following the typical thrice-weekly schedule, the time-averaged volume excess (V) during the whole week (1.1 ± 0.5 L) was significantly larger than that during the midweek interval (0.9 ± 0.4 L) (P < 0.002) by a factor comparable to that of 1.21 obtained from the theoretical analysis. V(OVE) was 1.3 ± 1.7 L and significantly related to pre- (P < 0.001) and post-dialysis levels of NT-pro BNP (P < 0.001). CONCLUSION: Asymmetric treatment spacing such as with the typical thrice-weekly treatment schedule leads to a significant increase in time-averaged volume excess. The theoretical analysis allows for comparison of time-averaged volume excess in treatments varying with regard to treatment frequency and regularity and could be helpful to prescribe post-treatment volume (target weight) for such variable treatment modes.