The continuous measurement of the relative blood volume is a standard feature of modern dialysis devices enabling feedback guidance of ultrafiltration and dialysate conductivity. The blood volume and its changes are noninvasively determined according to the principle of mass conservation. Given that the “solid” blood components remain stable in the vascular space during the hemodialysis session, changes in their concentration signify changes in the plasma volume.
Currently available dialysis systems of the Gambro-Hospal group (Integra, AK 200, Artis) and the Nikkiso DBB series feature a blood volume monitor based on optical methods. The dialysis machines 4008 and 5008, FMC, perform blood volume monitoring with an ultrasonic method.1 In the Gambro system, an optoelectronic instrument measures the absorption of near-infrared monochromatic light (wavelength 810 nm) transmitted through blood. The amount of absorption is directly related to the hemoglobin concentration. Removal of plasma volume leads to an increase in the relative hemoglobin concentration, thus causing an increased absorption of light.2
In the Nikkiso system, near-infrared monochromatic light (wavelength 805 nm) is transmitted through blood likewise. The blood volume is deduced from the reflected light measured by a light-receiving element. The degree of reflection depends on the surface of red blood cells and correlates with the hematocrit (Hct) value.3
Using the ultrasonic method, blood volume is assessed by measuring the transit time of an ultrasonic pulse transmitted through blood. The speed of sound in whole blood depends on the total protein concentration (TPC), which is the sum of plasma proteins and hemoglobin. The relative blood volume finally is determined from changes in the TPC.1
An excellent correlation between all three methods and direct measurements of hemoglobin and hematocrit has been shown previously by means of linear regression analysis.3–5 No deviations from the reference method could be correlated with concentrations of blood components, such as lipids, glucose, proteins, or electrolytes.5 The optical method measuring Hb-dependent light absorption (Gambro/Hospal) has been proven to be less susceptible to sodium changes from 136 to 154 mmol/L. However, this was only tested at steady sodium concentrations.4
During routine dialysis treatments with a step sodium profile, we repeatedly noted rapid changes in the blood volume measured with the optical absorbance method (AK 200). Changes in blood volume appeared to be inversely related to changes in dialysate sodium concentration. This reaction has not been directly described or investigated yet. Only Mercadal et al.6 referred indirectly to this phenomenon. They described spikes of the blood volume curve that occurred during rapid modifications of the dialysate conductivity being set automatically by the monitor for ionic dialysance measurement. This phenomenon was only observed in patients with access recirculation.
On the occasion of these findings, we systematically investigated the data of blood volume monitors working with the optical Hb-dependent absorbance method and the ultrasonic method in relation to rapid sodium changes.
Patients and Methods
We recruited six clinically stable chronic hemodialysis patients, three women and three men, to participate in the study. Their median age was 75 years (range, 54–79 years) and time on hemodialysis averaged 49 months (range, 12–146 months). Renal failure resulted from nephrosclerosis (four), glomerulonephritis (one), and pyelonephritis (one). In all patients, vascular access was a native arteriovenous fistula. The local ethics committee approved the study, and all patients gave written informed consent.
All six patients underwent 4 hours of hemodialysis, with a step sodium profile in their mid-week session for two consecutive weeks using two different dialysis systems. Dialysis systems used were the AK 200 (Gambro) and the FMC 5008, both continuously recording the relative blood volume. The AK 200 (Gambro) machine features a blood volume monitor detecting Hb-dependent light absorption (optical method).4 The FMC 5008 machine performs blood volume monitoring with the ultrasonic method.1 The following step sodium profile was applied: during the first hour of treatment, dialysate sodium concentration was kept at 140 mmol/L; during the second hour, dialysate sodium concentration was kept at 150 mmol/L; in the third hour, sodium concentration was set at 130 mmol/L; and finally set at 140 mmol/L in the fourth hour of treatment. All patients were treated in sitting position. The ultrafiltration rate was kept constant during the hemodialysis sessions. With the AK 200 and the FMC 5008, the mean ultrafiltration rate was 480 and 495 ml/h, respectively. The other treatment conditions (blood flow rate, dialysate flow rate and temperature, other dialysate contents, dialyzer, and anticoagulation) were identical in both dialysis sessions. The changes in relative blood volume were manually recorded from the monitor every 15 minutes.
Sodium Chloride Bolus
All patients underwent another dialysis session with both the AK 200 and the FMC 5008 machine. The dialysate sodium concentration was kept constant at 140 mmol/L. The other treatment conditions were also identical in both sessions. Ten milliliters of hypertonic saline (20% NaCl), meaning 34 mmol sodium and chloride, respectively, was administered as a bolus injection lasting 15 seconds to the venous blood line after 2 hours of treatment. The data recorded by the blood volume monitors of both dialysis devices were compared every minute during the first 5 minutes, and then at 5 minute intervals.
All statistical analyses were performed with SPSS Statistics 18 (SPSS Inc., Chicago, IL). The data concerning relative blood volume were tested nonparametrically with the Wilcoxon test for related samples. Data are presented as appropriate.
Changes in serum sodium levels of the patients during the profile are displayed in Table 1. During the step sodium profile, the ultrasonic method showed a near-constant rate of decline in blood volume (Figure 1A). The optical method (AK 200) on the contrary recorded a rapid inverse change in blood volume with every change in dialysate sodium (Figure 1B).
One hour after increasing the dialysate sodium to 150 mmol/L, the optical Hb-dependent monitor showed a 5.2% reduction in the blood volume. One hour after decreasing the dialysate sodium to 130 mmol/L, the monitor detected an increase in blood volume by 4.4%. Fifteen minutes after each change in dialysate sodium, the corresponding values of blood volume measured by the two devices differed significantly (Table 2). At the end of the 4 hour dialysis session, the change in blood volume recorded by the optical and the ultrasonic device was −6.4% (±2.4%) and −10.6% (±2.6%), respectively. The difference was significant (p = 0.028).
Sodium Chloride Bolus
One minute after injecting 10 ml of hypertonic saline (20% NaCl), the serum sodium concentration of the patients had risen from 139.7 ± 1.9 to 148.8 ± 7.2 mmol/L. After 5 minutes, the serum sodium was 142.0 ± 1.5 mmol/L. One minute after the sodium injection, the ultrasonic monitor recorded a 0.8% (±0.9%; range from −1.8% to +0.5%) reduction in blood volume (Figure 2). As of minute 3, the ultrasonic device detected an increase in blood volume by 1.2% (±0.3%). The monitor using the optical Hb-dependent absorbance method showed a distinct 8.7% (±4.6%, range from −17.4% to −5.3%) decrease in blood volume 1 minute after the bolus injection (p = 0.028). Not before 5 minutes, the measured blood volume was at baseline value again. After 20 minutes, the differences were still significant (p = 0.046).
Preservation of blood volume plays a major role in maintaining intradialytic hemodynamic stability. Blood volume monitors and feedback control systems have been devised for optimum guidance of ultrafiltration and dialysate conductivity basically by adjusting plasma and dialysate sodium concentration. Blood volume monitors provide important data for these systems, thus determining their reliability. The two blood volume monitoring devices that we used in the present study are frequently incorporated in feedback control systems especially the one using the optical Hb-dependent absorbance method. Dasselaar et al.7 compared the data of the ultrasonic monitor, the optical hemoglobin absorbance method, and the Crit-Line stand-alone device, which are based on an optical hematocrit measurement. They found considerable differences between the three devices. However, at the end of the treatment, only the difference between the Crit-Line device and the optical Hb-dependent absorbance method reached significance. In their study, the dialysate sodium concentration was kept constant at 139 mm/L. But the effect of varying sodium concentration on blood volume measurement has not been investigated systematically yet.
The analysis of our study showed that rapid osmotic alterations lead to instantaneous changes in the measured blood volume. With the optical Hb-dependent absorbance method, these changes are much more pronounced. Especially after administering the sodium chloride bolus, the apparent change in blood volume as detected by the optical AK 200 device is not in accordance with what is expected. Increasing the blood osmolality by injecting hypertonic saline resulted in a considerable drop in measured blood volume by nearly 9% within 1 minute. A sudden loss of 8.7% of the circulating volume meaning 350–500 ml would alter hemodynamic stability to the state of shock. Therefore, we consider this phenomenon to be an artifact of the optical hemoglobin method becoming evident with rapid alterations of the blood osmolality. This is in accordance with Mercadals description of small downward spikes in the blood volume curve induced by short-term modifications of the dialysate conductivity.6 These modifications of conductivity were less pronounced than in our study and the artifact of the blood volume curve only became evident in the presence of recirculation. Admittedly alterations of blood osmolality as substantial as produced by the sodium chloride bolus represent an experimentally created exceptional condition and are not likely to occur in clinical settings.
It is remarkable though that none of these changes could be observed when blood volume was measured with the ultrasonic method. In our study, the ultrasonic blood volume monitor recorded a 1.2% increase in blood volume 3 minutes after the sodium bolus injection. Applying comparable conditions, Nette et al.8 found a similar increase in blood volume recorded by the ultrasonic system. The accuracy of this system seems to be less affected by changes in osmolality. However, the ultrasonic system has not been systematically validated, yet under conditions of changing osmolality using a reference method such as direct hemoglobin measurement. In our study, we neither did.
A possible explanation for our findings can be deduced from the fact that the erythrocyte volume is not constant. Fleming et al.9 found a near 4% reduction in erythrocyte volume after increasing the dialysate sodium from 140 to 154 mmol/L. The smaller erythrocyte volume causes a relative gain in mean corpuscular hemoglobin concentration. This could account for an increased absorption of light and would be translated into a drop in relative blood volume by the blood volume monitor. Furthermore, any change in the red blood cell volume contributes to the optical phenomenon of scattering meaning a multiple reflection of light on the cellular walls.4 The attenuation of light in whole blood as measured by the photodetector is the result of both absorption and scattering. Changing the red cell surface by osmotic influences therefore would alter the ratio of scattered and crossing light.4 Steuer et al.10 found an 8% decrease in the optical density of blood at 805 nm when increasing the serum sodium from 140 to 130 mmol/L. Most of this evidence derives from developing studies on the blood volume monitoring systems. Potentially incorrect deviations of the optical method have been pointed out than already.4,5,11 But nevertheless the method has never been systematically and critically tested in the presence of major osmotic changes.
However, our findings have only been obtained with the optical Hb-dependent absorbance method and certainly cannot be applied to other optical methods by implication. It is of note that the artifact we described cannot be found with the optical Nikkiso system, which primarily measures the reflected light. But these data are observational findings only. Controlled comparative studies are needed to address the influence of sodium changes on different optical systems. The optical hematocrit-based Crit-Line device that can be externally attached to blood lines offers an elegant practical approach for performing simultaneous measurements with different systems as it has been shown by Dasselaar et al.7 As a clinical consequence of our findings, issues concerning sodium profiling in hemodialysis have to be judged differently. The mode of decreasing sodium, that is, stepwise or linearly has been a controversy for long. Only few studies investigated high-low sodium profiles when ultrafiltration rate was kept constant. It is remarkable that some evidence favoring a high-low sodium profile over constant dialysate sodium because of smaller changes in blood volume has been created using the optical Hb-dependent absorbance monitor.12,13 These data would certainly have been influenced by the artifact we described. On the contrary, studies using the direct hematocrit measurement14 or ultrasonic method15 failed to establish an effect of sodium profiling on blood volume preservation.
Considerations concerning blood volume monitoring with the optical method have to be extended to feedback control systems featuring the blood volume monitor. In the feedback process, dialysate conductivity is adjusted according to blood volume data.16 The systems reliability is challenged if the feedback action itself (change in conductivity) might distort the recording of the target value. The feedback control system Hemocontrol (Gambro/Hospal) features the optical Hb-dependent absorbance monitor and is incorporated in the hemodialysis devices Artis and Integra. Winkler et al.17 performed a meta-analysis of 15 controlled trials on the Hemocontrol system involving 287 patients. Comparing feedback control and standard dialysis, they attributed a 12% reduction in intradialytic hypotension to the feedback-guided preservation of blood volume. This reduction is rather lower than what has been found in studies using different feedback control systems.18–21 The inducible deviation of the optical monitor we described could serve as an explanation. It bears the risk of recording an increase in blood volume when actually there is a reduction.
In conclusion, blood volume monitors using the optical absorbance device are influenced by changes in blood osmolality. An increase in osmolality produces a paradox drop in the measured blood volume. Reducing the osmolality leads to recording an artificial gain in blood volume. This osmotic interference renders the monitor inappropriate for use in sodium profiling. Data of feedback control systems featuring this optical monitor have to be critically reviewed. The ultrasonic system seems to be less susceptible to osmotic changes. Further studies are needed and comparative data on other optical systems, that is, the Hct-dependent Nikkiso system and the Crit-Line device, remain to be created.
1. Schneditz D, Pogglitsch H, Horina J, Binswanger U. A blood protein monitor for the continuous measurement of blood volume changes during hemodialysis. Kidney Int. 1990;38:342–346
2. Mancini E, Santoro A, Spongano M, Paolini F, Rossi M, Zucchelli P. Continuous on-line optical absorbance recording of blood volume changes during hemodialysis. Artif Organs. 1993;17:691–694
3. Yoshida I, Ando K, Ando Y, et al.BVM Study Group. A new device to monitor blood volume in hemodialysis patients. Ther Apher Dial. 2010;14:560–565
4. Santoro A, Mancini E, Paolini F, Zucchelli P. Blood volume monitoring and control. Nephrol Dial Transplant. 1996;11(suppl 2):42–47
5. Johner C, Chamney PW, Schneditz D, Krämer M. Evaluation of an ultrasonic blood volume monitor. Nephrol Dial Transplant. 1998;13:2098–2103
6. Mercadal L, Coevoet B, Albadawy M, et al. Analysis of the optical concentration curve to detect access recirculation. Kidney Int. 2006;69:769–771
7. Dasselaar JJ, Huisman RM, DE Jong PE, Franssen CF. Relative blood volume measurements during hemodialysis: comparisons between three noninvasive devices. Hemodial Int. 2007;11:448–455
8. Nette RW, Krepel HP, van den Meiracker AH, Weimar W, Zietse R. Specific effect of the infusion of glucose on blood volume during haemodialysis. Nephrol Dial Transplant. 2002;17:1275–1280
9. Fleming SJ, Wilkinson JS, Aldridge C, et al. Dialysis-induced change in erythrocyte volume: Effect on change in blood volume calculated from packed cell volume. Clin Nephrol. 1988;29:63–68
10. Steuer RR, Bell DA, Barrett LL. Optical measurement of hematocrit and other biological constituents in renal therapy. Adv Ren Replace Ther. 1999;6:217–224
11. Johnson DW, McMahon M, Campbell S, et al. Non-invasive, optical measurement of absolute blood volume in hemodialysis patients. Kidney Int. 1996;49:255–260
12. Movilli E, Camerini C, Viola BF, Bossini N, Strada A, Maiorca R. Blood volume changes during three different profiles of dialysate sodium variation with similar intradialytic sodium balances in chronic hemodialyzed patients. Am J Kidney Dis. 1997;30:58–63
13. Brummelhuis WJ, van Geest RJ, van Schelven LJ, Boer WH. Sodium profiling, but not cool dialysate, increases the absolute plasma refill rate during hemodialysis. ASAIO J. 2009;55:575–580
14. Iselin H, Tsinalis D, Brunner FP. Sodium balance-neutral sodium profiling does not improve dialysis tolerance. Swiss Med Wkly. 2001;131:635–639
15. Zhou YL, Liu HL, Duan XF, Yao Y, Sun Y, Liu Q. Impact of sodium and ultrafiltration profiling on haemodialysis-related hypotension. Nephrol Dial Transplant. 2006;21:3231–3237
16. Santoro A, Mancini E, Paolini F, Cavicchioli G, Bosetto A, Zucchelli P. Blood volume regulation during hemodialysis. Am J Kidney Dis. 1998;32:739–748
17. Winkler RE, Grandi F, Santoro APenido MG. Blood volume regulation, Technical Problems in Patients on Hemodialysis. 2011:235–250 Available at: www.intechopen
18. Schmidt R, Roeher O, Hickstein H, Korth S. Prevention of haemodialysis-induced hypotension by biofeedback control of ultrafiltration and infusion. Nephrol Dial Transplant. 2001;16:595–603
19. Gabrielli D, Krystal B, Katzarski K, et al. Improved intradialytic stability during haemodialysis with blood volume-controlled ultrafiltration. J Nephrol. 2009;22:232–240
20. Colì L, La Manna G, Comai G, et al. Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: A noncontrolled multicenter trial. Am J Kidney Dis. 2011;58:93–100
21. Locatelli F, Stefoni S, Petitclerc T, et al. Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study. Nephrol Dial Transplant. 2012;27:3935–3942