The relationship between symptoms and blood pressure during maintenance hemodialysis

Intradialytic hypotension (IDH) is a detrimental complication of maintenance hemodialysis, but how it is defined and reported varies widely in the literature. European Best Practice Guideline and Kidney Disease Outcomes Quality Initiative guidelines require symptoms and a mitigating intervention to fulfill the diagnosis, but morbidity and mortality outcomes are largely based on blood pressure alone. Furthermore, little is known about the incidence of asymptomatic hypotension, which may be an important cause of hypoperfusion injury and impaired outcome. Seventy‐seven patients were studied over 456 dialysis sessions. Blood pressure was measured at 15‐minute intervals throughout the session and compared with post‐dialysis symptom questionnaire results using mixed modeling to adjust for repeated measures in the same patient. The frequency of asymptomatic hypotension was estimated by logistic regression using a variety of commonly cited blood pressure metrics that describe IDH. In 113 sessions (25%) where symptoms were recorded on the questionnaire, these appear not to have been reported to dialysis staff. When symptoms were reported (293 sessions [64%]), an intervention invariably followed. Dizziness and cramp were strongly associated with changes in systolic blood pressure (SBP), but not diastolic blood pressure. Nausea occurred more frequently in younger patients but was not associated with falls in blood pressure. Thresholds that maximized the probability of an intervention rather than a session remaining asymptomatic were SBP <100 mmHg or a 20% reduction in SBP from baseline. The probability of SBP falling to <100 mmHg in an asymptomatic session was 0.23. Symptoms are frequently not reported by patients who are hypotensive during hemodialysis, which leads to an underestimation of IDH if symptom‐based definitions are used. A revised definition of IDH excluding patient‐reported symptoms would be in line with literature reporting morbidity and mortality outcomes and include sessions in which potentially detrimental asymptomatic hypotension occurs.     

Hydration abnormalities in Nigerian patients on chronic hemodialysis

The state of hydration affects the outcomes of chronic dialysis. Bioelectrical impedance analysis (BIA) provides estimates of body water (V), extracellular volume (ECFV), and fat-free mass (FFM) that allow characterization of hydration. We compared single-frequency BIA measurements before and after 14 hemodialysis sessions in 10 Nigerian patients (6 men, 4 women; 44+/-7 years old) with clinical evaluation (weight removed during dialysis, presence of edema) and with estimates of body water obtained by the Watson, Chertow, and Chumlea anthropometric formulas. Predialysis and postdialysis values of body water did not differ between BIA and anthropometric estimates. However, only the BIA estimate of the change in body water during dialysis (-0.8+/-2.9 L) did not differ from the corresponding change in body weight (-1.3+/-3.0 kg), while anthropometric estimates of the change in body water were significantly lower, approximately one-third of the change in weight. Bioelectrical impedance analysis correctly detected the intradialytic change in body water content (the ratio V/Weight) in 79% of the cases, while anthropometric formula estimates of the same change were erroneous in each case. Compared with patients with clinical postdialysis euvolemia (n=7), those with postdialysis edema (n=5) had higher values of postdialysis BIA ratios V/FFM (0.77+/-0.01 vs. 0.72+/-0.03, p<0.01) and ECFV/V (0.53+/-0.02 vs. 0.47+/-0.06, p<0.05), respectively. Bioelectrical impedance analysis appeared to underestimate body water and extracellular volume in a patient with massive ascites and bilateral pleural effusions. Anthropometric formulas are not appropriate for evaluating the state of hydration in patients on chronic hemodialysis. In contrast, BIA provides estimates of hydration agreeing with clinical estimates in the same patients, although it tends to underestimate body water and extracellular volume in patients with large collections of fluid in central body cavities.     

Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis

Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra-HD hemodynamic stability. We first questioned whether BVT also improves post-HD blood pressure stability in hypotension-prone patients and second, whether BVT is effective in reducing the post-HD weight as many hypotension-prone patients are overhydrated because of an inability to reach dry weight. After a 3-week period on standard HD, 12 hypotension-prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post-HD target weight was kept identical compared with the standard HD period (BVT-constant weight; BVT-cw). During the second BVT period of 6 weeks, we gradually tried to lower the post-HD target weight (BVT-reduced weight; BVT-rw). In the last week of each period, we studied intra-HD and 24 hr post-HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre- and post-HD weight did not differ between standard HD and either BVT-cw or BVT-rw. Heart size on a standing pre-dialysis chest X-ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post-HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension-prone patients is associated with higher systolic blood pressures for as long as 16 hr post-HD. BVT was not effective in reducing the post-HD target weight in this patient group.     

Radioisotope blood volume measurement in hemodialysis patients

Accurate assessment of blood volume (BV) may be helpful for prescribing hemodialysis (HD) and for reducing complications related to hypovolemia and volume overload. Monitoring changes in relative BV (RBV) using hematocrit, e.g., Crit‐Line Monitor (CLM‐III), an indirect method, cannot be used to determine absolute BV. We report the first study of BV measurement for assessing volume status in HD patients using the indicator dilutional method. Ten adult HD patients were enrolled in this prospective observational study. BV measurement was performed before and after HD using BV analysis (BVA)‐100 (Daxor Corporation, New York, NY, USA). BVA‐100 calculates BV using radiolabeled albumin (Iodine‐131) followed by serial measures of the radioisotope. Fluid loss from the extravascular space was calculated by subtracting the change in BV from total weight loss. Intradialytic changes in RBV were measured by CLM‐III. Eight out of 10 cases had significant hypervolemia, two cases were normovolemic. The range of BV variation from predicted normal was 156 to 1990 mL. Significant inter‐individual differences in extravascular space fluid loss ranged from 54% to 99% of total weight loss. Spearman correlation showed a good correlation in the measurement of RBV by BVA‐100 and CLM‐III in 8 out of 10 patients (r² = 0.64). BV measurement using BVA‐100 is useful to determine absolute BV as well as changes in BV and correlates reasonably well with CLM‐III measurements. Individual refilling ability can be determined as well. This may prove useful in prescribing and monitoring ultrafiltration rates, establishment of optimal BV in HD patients and reducing morbidity and mortality associated with chronic HD.     

Comparison of stroke volume measurements during hemodialysis using bioimpedance cardiography and echocardiography

Background: Fluid management remains a major challenge of hemodialysis (HD) care, with serious implications for morbidity and mortality. Intradialytic fluid management is typically guided by blood pressure, an indirect resultant of hemodynamics status. Direct measurements of hemodynamic parameters may improve cardiovascular outcomes by providing rational bases for intervention. We compare stroke volume (SV) measurements using a noninvasive, regional biompedance cardiography device (NiCaS) with Doppler echocardiography (Echo) in HD setting. Methods: Stroke volumes were simultaneously measured using the devices in 17 patients receiving maintenance HD. Measurements were made during 2 weekly HD treatments, and twice within each HD treatment during the first and last hour of each treatment, for a total of 64 SV measurements. Agreement between devices was assessed using linear regression, a Pearson's correlation coefficient, and a Bland‐Altman plot all adjusted for repeated measures within patients. Results: Echo and NiCaS SV mean and 95% CIs were 58.0 (50.1, 65.8) and 56.7 (49.4, 64.0) mL, respectively. NiCaS SV correlated strongly with Echo SV during the first and last hours of treatments (r = 0.93, P < 0.001 and r = 0.92, P < 0.001, respectively). Linear regression of NiCaS on Echo showed a slope of 0.97, 95% CI (0.91, 1.02) which did not differ from 1, P = 0.20. A Bland‐Altman plot and 4‐Quadrant plot confirmed that the 2 methods produced comparable measurements. Conclusion: NiCaS SV measurements are similar to and strongly correlated with Echo SV measurements. This suggests that noninvasive NiCaS technology may be a practical method for measuring SV during HD.     

An evaluation of blood volume changes during ultrafiltration pulses and natriuretic peptides in the assessment of dry weight in hemodialysis patients

Changes in blood volume (BV) during dialysis as well as plasma levels of brain natriuretic peptide (BNP) and N-terminal (NT) pro-BNP levels are possible tools to assess dry weight in hemodialysis (HD) patients. The aim of the study was to compare these parameters with other non-invasive techniques used to assess dry weight in HD patients, and to study their relation with intradialytic hypotension (IDH) and the presence of cardiovascular disease BV changes during HD, both during regular dialysis and during an ultrafiltration pulse, plasma levels of NT pro-BNP and BNP, and vena cava diameter index (VCDI) were assessed in a cohort of 66 HD patients, which was subdivided according to tertiles of total body water (TBW) corrected for body weight, assessed by bioimpedance analysis. Parameters were also related to the presence of IDH and history of cardiovascular disease. The decline in BV during regular dialysis and during an ultrafiltration pulse, as well as VCDI and BNP were significantly different between the tertiles of normalized TBW, but refill after the ultrafiltration pulse and NT pro-BNP were not. Only VCDI and the decline in BV during regular dialysis were significantly different between patients with or without IDH. Vena cava diameter index, BNP, and NT pro-BNP were significantly higher in patients with cardiovascular disease. Using bioimpedance as the reference method, changes in BV, either during regular dialysis or during an ultrafiltration pulse, as well as VCDI and BNP are all indicative of hydration state in dialysis patients, but refill after an ultrafiltration pulse is not. Only VCDI and BV changes were related to IDH. The presence of cardiovascular disease appears to influence both VCDI as well as BNP.     

The effects of single hemodialysis session on arterial stiffness in hemodialysis patients

Increased arterial stiffness in hemodialysis patients is a strong predictor of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) and augmentation index (AIx), which are markers of arterial stiffness, were used to determine the severity of vascular damage noninvasively. This study aimed to investigate the effects of solute volume removal and hemodynamic changes on PWV and AIx of a single hemodialysis session. Thirty hemodialysis patients were enrolled in the study. Before initiation of hemodialysis, every 15 minutes during hemodialysis, and 30 minutes after the completion of the session, measurements of PWV and AIx@75 (normalized with heart rate 75 bpm) were obtained from each patient. Body composition was analyzed by bioimpedance spectroscopy device before and 30 minutes after completion of the hemodialysis session. During the hemodialysis, no significant change was observed in AIx@75. However, PWV decreased steadily during the session reaching statistically significant level at 135th minute (P = 0.026), with a maximal drop at 210th minute (P < 0.001). At 210th minute, decrease in PWV correlated positively with the decrease in central systolic blood pressure, central diastolic blood pressure, central pulse pressure, augmentation pressure, and AIx@75. Multiple regression analysis showed that decrease in PWV at 210th minute was associated with decrease in central systolic blood pressure and central pulse pressure. Ultrafiltration during hemodialysis had no significant effect on PWV and AIx@75. Delta urea correlated positively with delta PWV at 240th minute. A significant decrease in PWV was observed during hemodialysis and correlated with urea reduction; however, we were unable to document any effect of volume removal on arterial stiffness.     

Interactions between intradialytic central venous oxygen saturation,relative blood volume,and all-cause mortality in maintenance hemodialysis patients

Introduction

In maintenance hemodialysis (HD) patients, low central venous oxygen saturation (ScvO₂) and small decline in relative blood volume (RBV) have been associated with adverse outcomes. Here we explore the joint association between ScvO₂ and RBV change in relation to all-cause mortality.

Methods

We conducted a retrospective study in maintenance HD patients with central venous catheters as vascular access. During a 6-month baseline period, Crit-Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO₂ and hematocrit-based RBV. We defined four groups per median change of RBV and median ScvO₂. Patients with ScvO₂ above median and RBV change below median were defined as reference. Follow-up period was 3 years. We constructed Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO₂ and RBV and all-cause mortality during follow-up.

Findings

Baseline comprised 5231 dialysis sessions in 216 patients. The median RBV change was −5.5% and median ScvO₂ was 58.8%. During follow-up, 44 patients (20.4%) died. In the adjusted model, all-cause mortality was highest in patients with ScvO₂ below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37–29.06), followed by patients with ScvO₂ below median and RBV change below median (HR 5.04; 95% CI 1.14–22.35), and ScvO₂ above median and RBV change above median (HR 4.52; 95% CI 0.95–21.36).

Discussion

Concurrent combined monitoring of intradialytic ScvO₂ and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO₂ and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload.     

Intradialytic changes of serum magnesium and their relation to hypotensive episodes in hemodialysis patients on different dialysates

Magnesium is a crucial mineral, involved in many important physiological processes. Magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients. Intradialytic hypotension is a common complication of dialysis and it is more common with acetate dialysate. The significance of the intradialytic changes of magnesium and their relation to parathyroid hormone (PTH) level and calcium changes during dialysis, and their relation to hypotensive episodes during dialysis are interesting. The aim of this work is to investigate the intradialytic changes of serum magnesium in chronic hemodialysis patients with different hemodialysis modalities and the relation to other electrolytes and to PTH, and also the relation to intradialytic hypotension. The present study was conducted on 20 chronic renal failure patients. All patients were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate-based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH during a hemodialysis session, the same patients were shifted to bicarbonate dialysis (group II). All patients were subjected to full history and clinical examination, predialysis laboratory assessment of blood urea nitrogen (BUN), serum creatinine, albumin, and hemoglobin, serial assessment of magnesium, calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis session, 2 hr later, and at the end of the session, blood pH, and electrocardiogram (ECG) presession and postsession. All patients were urged to fix their dry weight, diet, and current medications. None of the patients had diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on magnesium-containing drugs or previously parathyroidectomized. Hemodialysis sessions were performed by volumetric dialysis machines using the same electrolyte composition. Magnesium level significantly increased in the bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1, and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33 mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate group (p=0.024) but not in the acetate group. Phosphorus level significantly decreased in both acetate and bicarbonate groups. PTH level did not significantly change in either group, p value > or =0.05. Blood pH significantly increased, changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG showed no significant changes during sessions with either type of dialysate. Hypotension was significantly higher in group I compared with group II (p=0.01), and this hypotension was positively correlated with a decrease in serum magnesium level in group I. Intradialytic changes in serum magnesium have no correlation with intradialytic changes in serum calcium or with PTH level. However, it was significantly correlated with hypotension during the dialysis session, especially with acetate dialysate. Further investigations are needed to determine whether or not this is true in patients using bicarbonate dialysis.     

Comparison of intradialytic blood pressure variability between conventional thrice‐weekly hemodialysis and short daily hemodialysis

Intradialytic blood pressure (BP) variability may be associated with increased mortality. We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice‐weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed‐effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP<90/55 mmHg at any time during HD). In addition to a predictor and outcomes, the demographics, estimated dry weight, and ultrafiltration ratio were examined. The median (range) age of the patients was 48 (34–77); all had hypertension, and 4 (33%) had diabetes. By a mixed effects linear regression model, the intradialytic systolic BP variability was 13.2 (quartile range 9.5–14.0) mmHg and 10.0 (8.3–10.9) mmHg for CHD and SDHD, respectively (P<0.006). Intradialytic diastolic BP variability was also significantly reduced (7.7 [6.4–9.2] vs. 6.1 [5.5–6.6] mmHg, P=0.005). Relative to CHD, less hypotension was observed during treatment on SDHD: the odds ratio (95% confidence interval) was 0.36 (0.16–0.81; P=0.008). In this retrospective study, SDHD was associated with less intradialytic BP variability and with fewer episodes of hypotension during treatments. Further studies are necessary to generalize these findings.     

The source of net ultrafiltration during hemodialysis is mostly the extracellular space regardless of hydration status

Fluid shifts are common in patients undergoing chronic hemodialysis (HD) during the intradialytic periods, as several liters of fluid are removed during ultrafiltration (UF). Some patients have experienced frequent intradialytic hypotension (IDH). However, the characteristics of fluid shifts and which fluid space is affected remain controversial. Therefore, we designed this study to evaluate the fluid spaces most affected by UF and to determine whether hydration status influences the fluid shifts during HD. This was a prospective cohort study of 40 patients undergoing HD. We measured the patient's fluid spaces using a whole‐body bioimpedance apparatus to evaluate the changes in the fluid spaces before HD and 1–4 hours of HD and 30 minutes after HD. UF achieved during HD by the 40 patients (age, 60.0 ± 5.2 years; 50% men; 50% of patients with diabetes; body weight, 61.3 ± 10.5 kg) was 2.18 ± 0.78 L (measured fluid overload, 2.15 ± 1.24 L). 1) Mean relative reduction of total body water and extracellular water was reduced from the start to the end of HD. 2) However, mean relative reduction of intracellular water was not reduced from the start to the end of HD. 3) No significant differences in fluid shifts were observed according to hydration status. The source of net UF during HD is mostly the extracellular space regardless of hydration status. Thus, IDH may be related to differences in the interstitial fluid shift to the vascular space.     

The pivotal role of sodium balance in control of blood pressure in dialysis patients

In hemodialysis patients, as in patients with normal kidney function, sodium balance is the major determinant of changes in extracellular volume, and extracellular volume is an important determinant of blood pressure. The osmotic thresholds for thirst and ADH release are normal in kidney failure; pre‐dialysis serum sodium concentration shows a high index of individuality in oliguric hemodialysis patients. Non‐osmotic storage of sodium in vascular walls may also amplify the volume‐sensitivity of blood pressure. The variable relationship between volume removal and change in blood pressure described in clinical studies reflects a state of permanent volume expansion in those whose blood pressure does not fall, or rises, during dialysis, whereas those whose blood pressure falls during dialysis are those who approach normovolemia. Rigorous control of extracellular volume often results in perfect blood pressure control, but may be difficult to achieve safely other than with long, slow dialysis combined with dietary salt restriction.     

Pulse contour-derived cardiac output in hemodialysis patients

Reliable methods for cardiac output determination are essential for studying the pathophysiology of intradialytic hypotension. Use of the current gold standard, the Transonic^® monitor, requires an arteriovenous fistula. We wished to verify the accuracy of a method based on finger pulse contour analysis, namely the Finometer^® monitor (FNM) for further use on patients dialyzing on a central vascular catheter. Fifty simultaneous cardiac output measurements were obtained during hemodialysis sessions in 25 patients. The internal variability of the FNM measurements was assessed by comparing 24 pairs of immediately successive measurements. The variability of successive FNM measurements was small (bias 0.28%, SD ± 6.1%; NS). The absolute cardiac output values reported by the FNM were unreliable (bias 20.1%, SD ± 35.3%; P<0.001) as were the relative intradialytic changes (r²=0.01). Excluding participants from the analysis due to old age, high dialysis vintage or a suspicion of atherosclerosis did not improve the results. Our findings do not support the use of pulse contour analysis for measuring cardiac output in hemodialysis patients. Uremic vascular disease may be the cause of the observed inaccuracy.     

Interdialytic blood pressure obtained by ambulatory blood pressure measurement and left ventricular structure in hypertensive hemodialysis patients

Unlike in subjects with normal renal function, the relationship between hypertension and cardiovascular morbidity and mortality in dialysis patients is still being debated. In order to clarify this issue, we performed 44-hour ambulatory blood pressure measurements (ABPM) during the interdialytic period in a group of 164 hypertensive patients, the blood pressure (BP) control based on conventional antihypertensive strategy previously, on chronic hemodialysis treatment in the Mediterranean region of Turkey. These results were then compared with their echocardiographic data. This is a cross-sectional analysis. The mean ABPM during 44 hours was close to the manually measured predialysis value, but there was a gradual increase in the ABPM values in the interdialytic period. When divided into a group with mild or no left ventricular hypertrophy (LVH) (45 patients) and severe LVH (119 patients), the latter had significantly higher BP levels in all separate periods, while the difference in predialysis BP was not significant. Patients with severe LVH had larger left atrium and left ventricular diameters, and consumed more antihypertensive drugs. Systolic BP during the night before dialysis showed the strongest relation to LVH, but interdialytic weight gain was also independently related to LVH. Yet, 56% of the patients with systolic BP <135 had severe LVH. There is not only an association between BP and presence of LVH, but it is shown that volume expansion is also an important independent determinant of LVH. This may explain the difficulty in identifying hypertension as a cardiac risk factor in these patients.