During hemodialysis with ultrafiltration, blood volume generally decreases as a result of an imbalance between the ultrafiltration rate and the plasma refilling rate.1 In the past decade, optical devices have become available that allow noninvasive monitoring of relative blood volume changes (ΔRBV) during hemodialysis.2–4 The use of such devices has been propagated for two closely related purposes. First, continuous intradialytic monitoring of ΔRBV has been advocated as a tool to maintain an adequate volume of the intravascular compartment to avoid dialysis hypotension.5,6 According to this concept, dialysis hypotension can be prevented by keeping the ΔRBV on the safe side of an individual critical ΔRBV threshold.6–8 Second, ΔRBV at the end of the hemodialysis session has been reported to reflect posthemodialysis volume status, and the measurement of this parameter may thus be helpful to fine-tune dry weight in individual patients.9,10
We found no mention in the literature that ΔRBV results should be interpreted differently for the first, second, or third hemodialysis session of the week in patients on a thrice-weekly hemodialysis schedule. This is surprising because the impact of intradialytic ultrafiltration volume/ultrafiltration rate on the course of ΔRBV is well-known.11–14 Because the length of the interdialytic interval is a major determinant of fluid accumulation between hemodialysis sessions, most patients on a thrice-weekly hemodialysis schedule are more overhydrated at the start of the first than at the start of the second and third hemodialysis sessions of the week. Consequently, the prescribed ultrafiltration volume/ultrafiltration rate, in order to reach dry weight, is usually higher at the first than at the second and third hemodialysis sessions of the week. To elucidate whether ΔRBV indeed varies systematically over the week, we separately analyzed this parameter for the first, second, and third hemodialysis sessions of the week in 13 chronic hemodialysis patients on a thrice-weekly hemodialysis schedule. In addition, we studied whether normalizing the ΔRBV level at the end of the hemodialysis session for the ultrafiltration volume during that particular hemodialysis session (ΔRBV/ultrafiltration ratio) would render a parameter that is not influenced by the total ultrafiltration volume as has been suggested previously.15,16
Written informed consent was obtained from all participating patients. The study was performed in accordance with the principles of the Declaration of Helsinki, and was approved by the local Medical Ethical Committee.
We recruited nonhospitalized patients from our institution who fulfilled the following criteria: 1) standard bicarbonate hemodialysis for more than 6 months; 2) three times a week, 4 hours/day hemodialysis schedule; 3) low incidence of dialysis hypotension, defined as less than three episodes of dialysis hypotension in the preceding month. Dialysis hypotension was defined as a drop in systolic BP of more than 40 mm Hg from the prehemodialysis value in combination with a treatment intervention by the dialysis nurse (temporary stop of ultrafiltration and/or infusion of IV fluids).
Exclusion criteria were: 1) absence of informed consent; 2) history of frequent (more than two occasions per month) transfusions with packed red blood cells because this interferes with the calculation of ΔRBV.
Patients were prospectively studied for a total of 17 weeks. Each hemodialysis session was evaluated for pre- and posthemodialysis body weight, pre- and posthemodialysis blood pressure, heart rate, ultrafiltration volume, occurrence of hypotensive episodes, treatment interventions, and ΔRBV. All data were registered on a run sheet or stored electronically using the Exalis system (Gambro-Hospal, Lyon, France). Blood pressure and heart rate were measured with an automated oscillometric monitor that was incorporated in the hemodialysis apparatus. ΔRBV was measured with a Hemoscan (Gambro-Hospal) incorporated in the dialysis apparatus that measures ΔRBV every minute based on assessment of hemoglobin concentration variations.3 The end-hemodialysis ΔRBV/ultrafiltration ratio was calculated from ΔRBV at the end of the hemodialysis session and the ultrafiltration volume during that hemodialysis session.
Patients were either dialyzed on Monday, Wednesday, and Friday or on Tuesday, Thursday, and Saturday. Monday and Tuesday were defined as the first hemodialysis sessions of the week; Wednesday and Thursday as the second hemodialysis sessions of the week; Friday and Saturday as the third hemodialysis sessions of the week.
For each patient, data from a total of 51 hemodialysis sessions were recorded (17 weeks times three hemodialysis sessions per week). Hemodialysis sessions in which IV fluids had been given were excluded from the analysis because IV administration of fluids interferes with accurate calculation of ΔRBV. Patients in whom more than 3 out of the 17 hemodialysis sessions per day of the week had to be excluded were completely removed from the study. Thus, for each patient, the results of a minimum of 14 hemodialysis sessions per day of the week are presented.
Prescriptions regarding dry weight and antihypertensive medication were made solely by the nephrologists during their weekly visit to the participating patients. Dry weight was evaluated clinically (peripheral edema, signs of pulmonary congestion, intra and extradialytic blood pressure course, muscle cramps) and by changes of the cardiopulmonary radiological aspect. To compare the use of antihypertensive medication at the start and the end of the study, we calculated the average defined daily dose for each individual patient according to reference.17
At the start and at the end of the study, prehemodialysis bioimpedance analysis was performed to detect a possible change in volume status during the course of the study. Extracellular water (ECW) was determined by single-frequency (50 kHz) bioimpedance analysis using a BIA-101 (Akern System, Florence, Italy). Bioimpedance was performed just before the start of the hemodialysis session on the nonaccess side.18 ECW was corrected for body weight.
All patients were dialyzed with bicarbonate dialysis with the Integra Physio hemodialysis apparatus (Gambro-Hospal) three times a week for 4 hours with a low-flux polysulfon hollow-fiber dialyzer, F8 (Fresenius Medical Care, Bad Homburg, Germany). Blood flow rates were 250–350 ml/min and dialysate flow rate was 500 ml/min. Blood flow was kept constant in the individual patients. All patients were dialyzed with a constant dialysate sodium concentration (dialysate conductivity 13.9 mS/cm) and a linear ultrafiltration rate. Dialysate temperature was 36.0°C. Dialysate composition was as follows: sodium 139 mmol/l, potassium 1.0 mmol/l, calcium 1.5 mmol/l, magnesium 0,5 mmol/l, chloride 108 mmol/l, bicarbonate 34 mmol/l, acetate 3 mmol/l, glucose 1.0 g/l. Patients received a light lunch and two cups of coffee or tea during hemodialysis. Patients were dialyzed in the supine position during most of the treatment.
All data were analyzed using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, CA). Data are presented as mean ± SD unless otherwise stated. Comparisons of weight, blood pressure, ultrafiltration volume, ΔRBV, and the ΔRBV/ultrafiltration ratio between the first, second, and third day of the week were made with a paired Student’s t test. Intrapatient coefficients of variation were calculated for all hemodialysis sessions together as well as separately for the first, second, and third hemodialysis session of the week. Correlation was assessed by Pearson’s correlation coefficient. p values of <0.05 were considered significant.
Fourteen patients were included and all finished the study protocol. In compliance with the study protocol, one of these patients was removed from the analysis because more than 3 of 17 hemodialysis sessions per day of the week had to be excluded because of IV fluid administration during hemodialysis. The patient characteristics of the remaining 13 patients were as follows. The male/female ratio was 6/7. The mean (±SD) age of the patient group was 65 ± 13 years (range 44 to 84 years). The mean time (±SD) on dialysis was 2.5 ± 1.2 years (range 0.5 to 4.5 years). The cause of renal failure was hypertension (n = 5), diabetes (n = 1), focal segmental glomerulosclerosis (n = 2), immunoglobulin A nephropathy (n = 2), membranoproliferative glomerulonephritis (n = 1), and unknown (n = 2). Two patients had diabetes mellitus (both type II). Mean (±SD) hemoglobin and albumin levels were 7.6 ± 0.5 mmol/l (12.2 ± 0.8 g/dl) and 40 ± 2.6 g/l, respectively. Mean Kt/V was 1.3 ± 0.1 per week. Hemodialysis access was an arteriovenous fistula or polytetrafluoroethylene graft in 12 patients and a tunneled central venous catheter in one patient.
All patients were on a correct posthemodialysis dry weight during the study, and posthemodialysis dry weight remained constant throughout the study. None of the patients had peripheral edema or pulmonary congestion on chest x-ray at any time during the study. As shown in Table 1, pre- and posthemodialysis weight, blood pressure, and heart rate did not change significantly from the start to the end of the 17-week study period. The number of patients that used antihypertensive medication and the mean defined daily dose of antihypertensive medication did not change significantly from the start to the end of the study. The midweek prehemodialysis ECW/body weight was comparable for the first (0.25 ± 0.04 l/kg) and the last week (0.25 ± 0.03 l/kg) of the study.
Weight, Ultrafiltration Volume, ΔRBV, and ΔRBV/Ultrafiltration Ratio
As shown in Table 2, the mean prehemodialysis weight was significantly higher (p < 0.01) at the first hemodialysis session of the week in comparison with the second and third hemodialysis session of the week. The posthemodialysis weight was slightly, but significantly (p < 0.01), higher at the first hemodialysis session in comparison with both the second and third hemodialysis sessions of the week.
The data for ultrafiltration volume, ΔRBV, and the ΔRBV/ultrafiltration ratio are shown in Figure 1 and Table 2. As shown in Figure 1, ultrafiltration volume, ΔRBV and the ΔRBV/ultrafiltration ratio showed some random fluctuation over time, but overall, these parameters were rather stable during the 17-week study period. As expected, the mean ultrafiltration volume during the 17-week study period was significantly (p < 0.001) higher during the first session than during the second and third hemodialysis sessions of the week (Table 2). ΔRBV at the end of the hemodialysis session was significantly (p < 0.01) lower at the first session than at the second and third hemodialysis sessions of the week (Table 2). The ΔRBV/ultrafiltration ratio was significantly (p < 0.01) higher at the first session than at the second and third hemodialysis sessions of the week (Table 2).
Intrapatient Variability of Ultrafiltration Volume, ΔRBV, and ΔRBV/Ultrafiltration Ratio
The individual intrapatient coefficients of variation of ultrafiltration volume, ΔRBV, and the ΔRBV/ultrafiltration ratio are shown in Figure 2. Coefficients of variation for ultrafiltration volume and ΔRBV were significantly lower for the first hemodialysis session in comparison with the second and third hemodialysis sessions of the week. Intraindividual coefficients of variation of the ΔRBV/ultrafiltration ratio were significantly lower for the first hemodialysis session of the week in comparison with the second hemodialysis session of the week but not in comparison with the third hemodialysis session of the week (p = 0.10).
Relation Between Ultrafiltration Volume and ΔRBV
Figure 3 shows the relation between ultrafiltration volume and ΔRBV for the first, second, and third day of the week, respectively. The correlation between ultrafiltration volume and ΔRBV was significant for the first, second, and third hemodialysis session of the week (all p < 0.0001).
This study shows that both ΔRBV and the ΔRBV/ultrafiltration ratio differ significantly between the first and the second or third hemodialysis session of the week in patients on a thrice-weekly hemodialysis schedule. The differences in ΔRBV and the ΔRBV/ultrafiltration ratio are most likely explained by different ultrafiltration volumes between the first and the second or third hemodialysis session of the week.
Our findings have several practical implications. First, the use of both ΔRBV and its derivative, the ΔRBV/ultrafiltration ratio, have previously been proposed as a tool to assess posthemodialysis volume status and, thus, to fine-tune dry weight.9,10,15,16 The present study shows that the ΔRBV at the end of the hemodialysis session as well as the ΔRBV/ultrafiltration ratio vary systematically over the week. With regard to ΔRBV, this finding is not surprising because the relation between higher ultrafiltration volumes/ultrafiltration-rates and an overall greater reduction in ΔRBV is well-known.11–14 Regarding the ΔRBV/ultrafiltration ratio, it was previously suggested that normalizing ΔRBV for intradialytic ultrafiltration volume would provide a parameter that is not being influenced by ultrafiltration volume.16 In the present study, however, the ΔRBV/ultrafiltration ratio was found to be significantly higher (less negative) at the first hemodialysis session of the week with higher ultrafiltration volumes than at the second and third hemodialysis sessions of the week. This observation is in accordance with our previous study that showed that the ΔRBV/ultrafiltration ratio of an individual patient varies systematically with ultrafiltration volume.19 Previously, Koomans et al.20 and Wizeman et al.21 have clearly shown that the more overhydrated a patient, the smaller the observed decrease in blood volume per unit of ultrafiltration volume. This can be explained by a higher refill rate from the interstitial tissues in a more overhydrated state.20,21 In our opinion, the dependence on total ultrafiltration volume limits the use of ΔRBV and the ΔRBV/ultrafiltration ratio for the assessment of the posthemodialysis volume status. Monitoring of intradialytic ΔRBV levels has been advised for the prevention of dialysis hypotension. According to this concept, dialysis hypotension can be prevented by keeping the ΔRBV on the safe side of an individual critical ΔRBV threshold.6–8 The present study shows that spontaneous ΔRBV levels vary systematically over the week in patients on a thrice-weekly hemodialysis schedule. As a practical consequence, it may be advisable to use different settings for the critical ΔRBV level for the first hemodialysis session as compared with the second and third hemodialysis sessions of the week and/or to adjust the critical ΔRBV level for the prescribed ultrafiltration volume. At present, however, it is not clear which adjustment would be most suitable. Notably, using different settings for the critical ΔRBV level might encounter difficulties when one observes the considerable intrapatient variations in ΔRBV in relation to the, from a clinical point of view, relatively small mean ΔRBV difference at the end of the session between the first and second or third hemodialysis session of the week (10.1% vs. 9.3%). An adjustment using the ΔRBV level normalized for ultrafiltration volume (ΔRBV/ultrafiltration ratio) is not correct because this ratio is not constant over the week and is being influenced by prehemodialysis hydration status.19–21
We observed considerable intrapatient variations in ultrafiltration volume, ΔRBV, and the ΔRBV/ultrafiltration ratio. The variability of the ΔRBV level cannot be explained by postural changes,22,23 exercise,24 or food intake,25 because these factors were standardized in this study. A comparable wide degree of intrapatient variability of the spontaneous ΔRBV course has been reported previously.14,19 The considerable intrapatient variability may well explain why the predictive value of ΔRBV reductions for the occurrence of dialysis hypotension is poor in most studies [reviewed in4,21]. The present study suggests that part of the ΔRBV variability results from variations in ultrafiltration volume. However, normalizing the ΔRBV level for ultrafiltration volume does not result in markedly lower intraindividual coefficients of variation, probably because additional variation is introduced as a result of the dependence of the ΔRBV/ultrafiltration ratio on total ultrafiltration volume (vide supra). Interestingly, intrapatient variability of ΔRBV at the end of the hemodialysis sessions was significantly lower for the first session than for the other hemodialysis sessions of the week. This coincided with a lower intrapatient variability for ultrafiltration volume at the first hemodialysis session of the week. This observation can be explained by a more “narrow window” of ultrafiltration-volume at the first hemodialysis session of the week in comparison with the other hemodialysis sessions (Figure 3). Very low ultrafiltration volumes are rare because of the preceding longer interdialytic interval; at the same time, relatively more patients are repeatedly at or close to their prescribed “maximum ultrafiltration volume/ ultrafiltration rate” at the first hemodialysis session of the week.
This study has some drawbacks. First, posthemodialysis weight was slightly but significantly higher at the first session then at the second and third hemodialysis sessions of the week. We can not rule out that ΔRBV would have been lower (more negative) if posthemodialysis weight would have been lower at the first hemodialysis session of the week. In that case, the ΔRBV/ultrafiltration ratio would probably also have been lower (more negative). However, it is a clinical reality that many hemodialysis patients, and especially those who display high interdialytic weight gains, only reach the prescribed posthemodialysis target weight (dry weight) at the second or third hemodialysis session of the week. Second, we studied patients with a relatively low frequency of dialysis hypotension and, therefore, our results may not be extrapolated to hypotension-prone patients. It would be interesting to study the relation between ΔRBV and ultrafiltration volume in hypotension-prone patients. This would also give the opportunity to study if the so-called individual critical ΔRBV threshold at which dialysis hypotension is thought to occur varies with ultrafiltration volume. Such a study, however, will be difficult to perform because ΔRBV results are not reliable from the moment that IV fluids have been administered, e.g., for the symptomatic treatment of dialysis hypotension.
ΔRBV and the ΔRBV/ultrafiltration ratio differ significantly between the first and the other hemodialysis sessions in patients on a thrice-weekly hemodialysis schedule, most likely because of differing ultrafiltration volumes. The systematic changes in ΔRBV level and ΔRBV/ultrafiltration ratio with variations in intradialytic ultrafiltration volume limit the use of these parameters to prevent dialysis hypotension and as an aid to assess volume status in hemodialysis patients.
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