Changes in major blood components after adopting the supine position during haemodialysis

Hitoshi Inagaki1, Masahiro Kuroda1, Shiro Watanabe2 and Tomohito Hamazaki,2

1 Asanagi Hospital, Takaoka-shi, Toyama, and 2 Department of Clinical Application, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama-shi, Toyama, Japan



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. In Japan, haemodialysis (HD) is usually performed with patients in the supine position. However, the effects of changing posture on major blood components have not been investigated in HD patients. It is possible that several fluid components change rapidly when patients change from the upright to the supine position. We therefore investigated the effects of posture on blood component analysis.

Methods. A first blood sample was taken from 10 HD patients 5 min after they adopted a supine position; HD was begun immediately after sampling. Additional blood samples were collected 15 and 30 min later while patients remained in the supine position. On an alternate day, blood samples were taken from these same patients in the supine position, but not during HD. The same procedure was performed in 10 healthy volunteers.

Results. Haematocrit significantly decreased in patients undergoing HD at 15 and 30 min into the HD session. Similar decreases were observed in HD patients not undergoing HD and in normal control subjects. Haematocrit changes at 15 min were not significantly different between the three groups. Serum albumin concentrations decreased in the same way as haematocrit. Consequently, the reductions in haematocrit and albumin concentrations in HD patients during the HD session were not attributable to the HD procedure or to end-stage renal disease, but rather were due to the supine position and consequent haemodilution caused by redistribution of water from the extra- to the intravascular space. Finally, WBC counts decreased significantly at 15 min in both HD patient groups and in normal controls. The relative decrease at 15 min was significantly greater in HD patients undergoing HD (61.4% of baseline) than in those not undergoing HD (88.0%) or in normal controls (94.7%). These differences were probably due to previously reported WBC sequestration in the lungs during the early phase of HD.

Conclusions. This study suggests that the change from the upright to the supine positions during HD causes changes in blood components that are critical for quality control determinations.

Keywords: albumin; haematocrit; haemodialysis; plasma refilling; posture change; white blood cells



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
For optimal chronic maintenance haemodialysis (HD), numerous parameters must be monitored. Among them, haematocrit is regularly measured during each HD session. Because red blood cells are non-diffusible, they can be used as a simple and reliable indicator of the circulating blood volume [1]. Haematocrit is also important for monitoring the inevitable anaemia of end-stage renal disease and the effects of erythropoietin. Consequently, the method of monitoring haematocrit should be rigid, and various conditions that affect haematocrit should be controlled. The same is true for serum albumin, since albumin concentrations are a good predictor of mortality risk in HD patients [2].

Recently a newly developed optical device has enabled the continuous monitoring of haematocrit [3,4]. This technique allows real-time estimation of circulating blood volume during HD sessions. Since in Japan HD is usually performed with patients lying down, HD patients must change their posture shortly before each HD session. If changes in posture affect blood components, postural effects should be carefully investigated in HD patients. However, there are no reports of changes in blood components as a result of postural changes prior to HD. In the present study we measured changes in haematocrit and serum albumin in supine HD patients during the first 30 min of HD, and compared these changes with data from the same patients in the same position without HD treatment, and also in normal controls. Additionally we studied white blood cell (WBC) counts, whose responses were different from haematocrit, depending on the biocompatibility of the dialyser membranes used [5,6]. Here we emphasize the importance of controlling blood-sampling times during HD when patients change postures.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Subjects
The protocol and purpose of the study was explained to patients undergoing chronic maintenance HD thrice weekly at the night HD sessions of the Hemodialysis Center, Asanagi Hospital. Ten male HD patients volunteered to enter the study. Their ages were 50±12 years (mean±SD); the mean duration of HD therapy was 12 years, range 2–22 years. Reasons for HD treatment were chronic glomerulonephritis (8), urolithiasis (1), and unknown (1). Diabetic patients were not included because of the risks of diabetic neuropathy (autonomic imbalance) and possible increased permeability of blood vessels to albumin. From a previous investigation it had been established that no patient suffered from recirculation of dialysed blood around the shunt. Dry weights were 54±6 kg. Ten normal male volunteers were recruited from staff members of the Center and Toyama Medical and Pharmaceutical University. They were 47±8 years old and weighed 66±7 kg. None of the HD patients or normal subjects suffered from autonomic disorders.

Dialysers and blood lines
Dialyser membranes were made of ethylene vinyl alcohol (membrane area 1.8 m2, 3 patients), polyester polymer alloy (1.5 m2, 3 patients), cuprammonium rayon (1.8 and 2.0 m2, 2 patients), and polysulphone (1.5 m2, 2 patients). The capacity of each dialyser with connected blood lines was 252–290 ml.

Study protocol
Blood samples were taken from patients on their last HD of the week between 4 and 6 p.m., before dinner. When patients came to the centre, they were asked to remain standing for at least 15 min. Then they adopted a supine position and continued supine during the entire experimental period (about 35 min). Before the first blood samples, the following preparations were made: blood lines for HD were connected, an appropriate amount of priming saline (102–140 ml) was discarded when the blood front went through the dialyser so that exactly 150 ml of saline was infused into each patient. The first blood sample (0 min) was collected from the artery line exactly 5 min after the patient took a supine position. HD was begun immediately after the first blood sampling. The second and third arterial blood samples were collected 15 and 30 min after the first sampling, while subjects remained supine. Ultrafiltration was applied to all patients for the first 15 min to remove an amount equivalent to the priming saline. By using a dialysate containing 140 mEq sodium, serum sodium concentrations of HD patients were not changed (values before and after HD sessions were 139±3 and 139±1 mEq respectively). The sodium balance of HD patients during the first 30 min of HD was therefore considered stable.

One to 6 weeks later, similar sampling was performed on the same patients on the last HD day of the week, just before routine HD sessions started. On this occasion a heparin-locked needle was inserted into the shunt. The first, second, and third samples were taken as previously described but without HD. The first few millilitres of blood from the heparin-locked needle were discarded to prevent contamination of heparin-containing saline. Regular HD was begun only after blood sampling had been completed. Blood samples from normal volunteers were taken exactly as in HD patients not undergoing HD treatment, except that a heparin-locked needle was inserted into an antecubital vein.

Written informed consent was obtained from each subject, and the protocol was approved by the ethics committee of Toyama Medical and Pharmaceutical University.

Measurements
EDTA-anticoagulated whole blood and serum prepared from each sample were immediately sent to a clinical laboratory (BML Hokuriku, Toyama) for measurement of haematocrit, white blood cells, and serum albumin.

Statistical analysis
Data are expressed as means±SD. Comparison among the three time points within the same group was performed by the paired t-test with Bonferroni's adjustment after ANOVA. Baseline values under the three different conditions were compared with Bonferroni's adjustment by the paired t-test within the patient group and by the unpaired t-test between the patient groups and the normal control group. The relative changes (%) of the data at 15 min (and 30 min) vs baseline were compared as in the case of comparison of baseline values. Differences were considered significant at the P<0.05 level.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Haematocrit
Baseline haematocrit was significantly lower (P<0.001) in the HD groups than in the control group. Changes of haematocrit in each group are shown in Figure 1Go. Decreases in haematocrit from 15 to 30 min were significant only in the HD groups, independent of HD treatment. There were no differences in haematocrit decrease at 15 min between HD patients undergoing HD (95.6±2.2% of baseline), not undergoing HD (94.8±1.7%), and normal controls (96.7±1.4%). The haematocrit decreases at 30 min were significantly greater in HD patients, whether undergoing HD (93.6±2.9%, P=0.006) or not (92.8±2.8%, P<0.001), than in the normal control group (96.7±1.2%).



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Fig. 1. Changes in haematocrit in the supine position. Blood samples were collected from 10 HD patients (open squares) at the start of HD (0 min), and 15 min and 30 min into HD. HD was begun 5 min after subjects adopted a supine position. The second and third samples were collected while subjects continued in the supine position. For control studies, blood samples were similarly collected from the same HD patients not undergoing HD (solid squares) and from 10 normal volunteers (open circles). (a) Significantly different from baseline (P<0.001); (b) significantly different from 15 min (P<0.01); (c) significantly different from 15 min (P<0.001).

 

Albumin concentrations
Baseline values of serum albumin concentrations were significantly lower (P<0.001) in the HD patient group than in the normal control group. Changes in serum albumin concentrations in each group are shown in Figure 2Go. Relative changes in albumin concentrations were very similar to those for haematocrit (data not shown).



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Fig. 2. Changes in albumin concentration in the supine position. See legend to Figure 1Go for protocol and explanation of symbols. (a) Significantly different from baseline (P<0.001); (b) significantly different from 15 min (P<0.001).

 

WBC counts
Baseline WBC counts were not different between the HD and normal control groups. Changes in WBC counts are shown in Figure 3Go. WBC counts significantly decreased in each group at 15 min compared with baseline. There was no significant difference between 15 and 30 min in either group. The relative decrease at 15 min in the HD group undergoing HD (61.4±16.8% of baseline) was significantly greater than the decrease in HD patients not undergoing HD (88.0±8.9%, P<0.001) and in normal controls (94.7±4.4%, P<0.001). Mean ratios of relative changes at 15 min in the HD group undergoing HD vs the changes in the HD group not undergoing HD were 61% for ethylene vinyl alcohol, 79% for polyester polymer alloy, 52% for cuprammonium rayon, and 89% for polysulphone, producing a total mean of 70±19%. There was no significant difference in the relative changes at 15 or 30 min between the HD patients not undergoing HD and the normal controls. The relative changes at 30 min were still greater in the HD patients undergoing HD than in the normal control group (data not shown).



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Fig. 3. Changes in WBC counts in the supine position. See legend to Figure 1Go for protocol and explanation of symbols. (a), (b), (c) and (d), Significantly different from baseline (P<0.02, 0.01, 0.002, and 0.001 respectively).

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The first blood sampling was taken 5 min after subjects assumed a supine position. In most HD centres this is a typical timing for blood sampling because blood lines are connected to patients after they adopt the supine position. In addition 5 min are required to start HD after a patient lies down. Accordingly the results obtained in the present study are comparable with and can be applied to daily HD treatment and measurement.

In the present study, arterial blood samples were not collected from normal controls. However, differences in haematocrit and albumin concentrations between arterial and venous blood samples were negligible in normal volunteers (unpublished data).

Haematocrit was markedly lower in the HD group than in the normal control group, even though one-half of the patients were treated with erythropoietin. The reduction in haematocrit at 15 and 30 min in the HD group undergoing HD was not due to HD itself, since relative changes in haematocrit during HD were essentially the same as in HD patients not undergoing HD (Figure 1Go). During the first 15 min there was no difference between the HD groups and the normal control group. Consequently, the decreases in the HD group during the first 15 min could not be attributed to end-stage renal disease. Infusion of primer saline at the beginning of HD and extracorporeal circulation are necessary during HD treatment. They influence plasma refilling in opposite ways by increasing and decreasing blood volume, respectively. Furthermore, infusion of saline dilutes blood components. In the present study we infused only about one-half of the fluid (150 ml of saline) that the dialysers and blood lines contained. In this way we were able to attenuate the effects of the primer, but at the same time HD patients could not receive the fully compensatory amount for extracorporeal circulation at the beginning of HD. Ultrafiltration of 150 ml during the first 15 min nullified the effects of the primer at the time of the second blood sampling. The effects of extracorporeal circulation were apparently minimal, since no significant differences were observed in haematocrit or albumin concentrations between HD groups undergoing HD or not.

The influence of posture changes on blood components has long been known [7,8]. Recently Maw et al. [9] measured body fluid redistribution during postural manipulations by utilizing a simultaneous radionuclide dilution technique, in which serum fibrinogen, erythrocytes, and water were radiolabelled. In their experiments, blood volume increased by 89 ml when supine, and decreased by 407 ml while standing compared to seated volume. These shifts were primarily the result of plasma movement. Maw et al. concluded that intravascular fluid loss during standing was caused by filtration of plasma into the interstitium, whereas during supine rest, intravascular volume increased, reflecting fluid flux from the interstitium into the circulation. In the present study, during standing before HD or blood sampling, plasma filtered through the capillary walls into the interstitial compartment by increased hydrostatic pressure. After adopting a supine position, the opposite occurred. Additional fluid flux from the interstitium into the circulation occurred in the HD groups between 15 and 30 min but not in the normal control group (Figures 1Go, 2Go). This difference was probably due to overhydration in the HD patients, since these patients probably had more water in the extravascular space than normal controls had. In fact, increases in body weights of 2.0–3.0 kg occurred at the start of HD. Thus it appears that 15 min was insufficient for excess water in the extravascular compartment of HD patients to be redistributed into the circulation.

We could have extended the experimental period beyond 30 min to determine whether haemodilution by plasma refilling would continue after the third sampling point (30 min) in HD patients. However, the experiment was stopped at 30 min because the ultrafiltration that is necessary during HD would make the interpretation of results difficult.

We experienced certain paradoxical changes in haematocrit. In some HD patients there was a decrease in haematocrit after HD, even when slight ultrafiltration was applied to them. In others, haematocrit increased after a meal during HD even though circulating blood volume should increase through influx of water contained in a meal. These apparently paradoxical phenomena may be explained by changes in posture. In the first case, if fluid amounts refilling the plasma volume induced by postural changes are greater than the volume to be ultrafiltered, haematocrit may decrease. In the second case, plasma may filter into the interstitium of the legs when patients change from the supine to the sitting position to have a meal. There are previous reports of plasma refilling and changes in blood volume during HD [10,11]. However, those reports did not consider the effects of postural changes. Incorporation of postural effects into their discussion would have increased the accuracy of their explanations of changes in blood volume components.

The pattern of decreasing albumin concentration was essentially identical to that of haematocrit in each group. This finding indicated that albumin had a similar stability as red cells during HD, which was in marked contrast to the WBC findings. Changes at 15 min in WBC counts in the HD group undergoing HD were different from the haematocrit and albumin results in the same group. The sequestration of granulocytes in pulmonary vascular beds after blood contact with dialyser membranes probably explains a sharp drop in WBC counts at 15 min [12]. This phenomenon has been shown repeatedly since 1968 [13]. Before the availability of reasonably biocompatible membranes for dialysers, about 75% of WBC were sequestered from the circulation in the first 15 min of HD [13,14]. The sequestration of WBC at 15 min has recently been reduced, and some membranes cause only a negligible drop in WBC [6]. In the present study, ratios of relative changes in WBC at 15 min in the HD group undergoing HD were variable according to the biocompatibility of dialysers. However, these data should be interpreted with caution, since, as shown in Figure 3Go, WBC counts fell to 89±9% at 15 min even in the HD group not undergoing HD. The reduction in WBC attributable directly to HD must be adjusted using values from HD patients not undergoing HD. In our case the adjusted relative changes were 70±19% as a whole, which were different from the apparent reduction of 61±17%. To our knowledge, previous studies calculating WBC sequestration ratios neglected the effects of changes in the posture of patients [6,1315].

In conclusion, red blood cells and albumin levels decreased significantly during the first 15–30 min of HD even after exclusion of the effects of priming volumes. Similar phenomena were observed in normal volunteers and in HD patients not undergoing HD after they assumed a supine position. Consequently the redistribution of water between the intra- and extravascular spaces following changes in posture may, at least in part, explain these phenomena. Thus, when monitoring these blood components, the effects of posture must be taken into consideration. The period of supine posture, before blood is sampled, is a critical factor to assure quality control during measurement of blood components.



   Acknowledgments
 
We are grateful to Ms Hiroko Hamatani for her technical assistance.



   Notes
 
Correspondence and offprint requests to: Tomohito Hamazaki MD PhD, Department of Clinical Application, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama-shi, Toyama 930-0194, Japan Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 21.12.99
Revision received 9.10.00.