1 Department of Nephrology, University Hospital Freiburg and 2 Deutsche Klinik für Diagnostik, Division of Nephrology, Wiesbaden, Germany
Correspondence and offprint requests to: Dr Johannes Donauer, Medizin IV, Universitätsklinik Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. Email: donauer{at}med1.ukl.uni-freiburg.de
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Abstract |
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Methods. Seventeen patients with a history of frequent hypotensive episodes during dialysis sessions were studied, each patient serving as his or her own control. The first 25 HD treatments in comparison with 25 o-HDF sessions were evaluated using identical dialysate temperature. In the second part of the study, o-HDF (n = 25) was compared with Temp-HD (n = 25). In the latter method, the temperature of the dialysate was adjusted to result in identical energy transfer rates to those in the corresponding o-HDF. The number of hypotensive episodes, blood temperature and blood volume regulation were assessed.
Results. Symptomatic hypotension was much more frequent during HD (40%) than during o-HDF (4%) (P < 0.001). During o-HDF, an enhanced energy loss within the extracorporeal system occurred (o-HDF, 16.6 ± 4.0 W; HD, 5.4 ± 5.1 W; P < 0.0001), despite identical temperature settings for dialysate and substitution fluid. As a result, the blood returning to the patient was cooler during o-HDF than during HD (o-HDF 35 ± 0.2°C vs HD 36.5 ± 0.3°C; P < 0.0001). In o-HDF, even in the patients circulation, the mean blood temperature was lower (o-HDF 36.7 ± 0.2°C vs HD 36.9 ± 0.3°C; P < 0.0001) and blood volume was significantly more reduced (o-HDF, 91.8 ± 3.1%; HD, 94.0 ± 3.2%; P < 0.05). Energy transfer rates and blood temperature did not differ significantly between o-HDF and Temp-HD. The rate of hypotensive episodes was low and not different between o-HDF (4%) and Temp-HD (4%). Neither was there any significant difference in blood volume reduction.
Conclusions. O-HDF showed a significant reduction of hypotensive episodes compared with HD. Surprisingly, o-HDF resulted in cooling of the blood via enhanced thermal energy losses within the extracorporeal system, despite use of replacement fluid prepared from pre-warmed dialysate. The incidence of symptomatic hypotension was reduced to that of o-HDF by using cooler Temp-HD. Thus, unexpected blood cooling appears to be the main blood pressure-stabilizing factor in o-HDF.
Keywords: blood volume monitoring; dialysis-induced hypotension; dialysate temperature; haemodiafiltration; haemodialysis; relative blood volume
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Introduction |
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The influence of blood temperature on hypotension during HD treatments has been studied extensively. It is well documented that HD leads to a substantial increase in body temperature [1]. Several factors have been discussed in the literature as contributing to hypotension during HD treatments: bloodmembrane interaction induces cytokine release, which may act as a pyrogen increasing core temperature; a non-sterile dialysate could enhance this effect [2]. The core temperature of many dialysis patients is lower than normal, and inappropriate high dialysate temperature (e.g. 37°C) may cause a transfer of heat from dialysate to the blood [1]. In addition, reduced heat losses via the skin due to peripheral vasoconstriction in response to ultrafiltration may increase body temperature [3]. As a consequence of this heat accumulation, a loss of vascular tone may take place, resulting in hypotension [4].
It has been reported that patients with cardiovascular instability during conventional HD treatments may experience fewer side effects if treatments based on convective solute and water transport are used [5]. Several mechanisms could be responsible for this phenomenon: differences in convective and diffusive solute clearance [5], differences in sodium removal [6,7], different vascular reactivity [8] or simply cooling of the blood [9,10]. Recent data favour the latter explanation, because conventional haemofiltration (HF) as well as haemodiafiltration (HDF) using replacement fluids at room temperature were shown to stabilize blood pressure [10]. However, it is still unclear, how online-HDF (o-HDF) may stabilize blood pressure, since in this treatment, in contrast to conventional HDF, substitution fluid is prepared from pre-warmed dialysate and thus one would not expect thermal energy losses to occur.
To clarify the effects of o-HDF on patient stability, blood temperature and blood volume changes, this study compares o-HDF with conventional HD and with temperature-controlled HD (Temp-HD).
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Subjects and methods |
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Symptomatic hypotension was defined as a reduction of the systolic blood pressure below 100 mmHg associated with reactions of the patient prompting nurse intervention, such as placing the patient in Trendelenburgs position, reducing the ultrafiltration rate or infusing intravenous fluids. An asymptomatic fall of blood pressure is not believed to be of clinical relevance and therefore was not evaluated.
Experimental protocol
Patients eligible to participate were studied according to two different protocols: in the first part of the study (study A), 11 patients underwent three o-HDF treatments over 1 week followed by three HD sessions during the next week. In the second part (study B), nine patients were subjected to three o-HDF treatments, followed by three Temp-HD sessions. Three patients participated in both studies. The observation period of 1 week for each treatment modality was chosen in order to compare treatments with nearly identical weight losses. For each patient, pairs of treatments were selected which had to fulfil the following matching criteria: (i) the difference of weight losses between matched treatments had to be < 500 g, since it is well known that weight loss during dialysis is a major determinant of side effects and temperature changes [4]; (ii) dry weight had to be reached during all sessions; (iii) treatment time had to be identical in corresponding treatments; and (iv) dialysate temperature was the same for corresponding treatments, except for Temp-HD, where dialysate temperature was changed in order to cool the blood.
Patients with significant shunt recirculation [>10%, measured using the blood temperature monitor (BTM)] were excluded, as recirculation may affect blood temperature and blood volume measurements [11].
Each patient served as his or her own control. Based on the above-mentioned criteria, 25 matched treatment pairs were identified for final analysis in both parts of the study.
Dialysis prescription
All treatments were performed using a volume-controlled dialysis machine with optional online-HDF mode (4008H, Fresenius Medical Care, Bad Homburg, Germany). For all treatments, polysulfone hollow-fibre dialysers, F50 or F60 for HD or HF80 for o-HDF (Fresenius Medical Care), were used. Dialysate and substituate composition was 35 mmol/l bicarbonate, 135140 mmol/l sodium, 1.75 mmol/l calcium, 24 mmol/l potassium, 0.5 mmol/l magnesium, 109.5 mmol/l chloride, 1 g/l glucose. Dialysate sodium concentration of an individual patient was not changed and was kept constant throughout the study period. All dialysate was sterile filtered. O-HDF produces sterile replacement fluid from the pre-warmed dialysate. The replacement fluid was infused in post-dilution mode with a substitution rate of 50 ml/min. Blood flow rate and treatment time were prescribed individually for each patient aiming at a Kt/V of at least 1.3 per treatment. Dry weight was determined by clinical judgement, chest X-ray or ultrasound of vena cava collapse, and was not changed during the study period. Detailed data of the dialysis prescription are given in Table 2.
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Blood temperature measurement and control
The BTM [12] measures blood temperature in the arterial and venous line and calculates the energy transfer (ET) rate between the extracorporeal system and the blood at 15 s intervals. Based on the temperature of the arterial line, the BTM calculates the patients core temperature by correcting for fistula and cardiopulmonary recirculation. Recirculation is measured by inducing a temporary change in dialysate temperature. The ensuing temperature change of the blood passing through the dialyser is detected by the venous temperature sensor head of the BTM and later by the sensor head at the arterial line. Recirculation can be calculated from the ratio of the amplitudes of the temperature transients in the arterial and the venous blood line, respectively [13].
The BTM calculates extracorporeal arterio-venous temperature gradients (Tav) and ET rates. ET is the amount of thermal energy that is transferred from the extracorporeal system to the patient, or vice versa. ET (in kJ/h) is calculated using the following formula: c x p x Qb x (Tart-Tven), where c = the specific thermal capacity (3.64 kJ/kg); Qb = extracorporeal blood flow; and p = density of the blood (1052 kg/m3)]. For a detailed description, see Rosales et al. [4]. In Temp-HD treatments, dialysate temperature was modified to achieve the same ET rate as seen before in the corresponding o-HDF treatments. ET values are given in Watts (1 W = 3.6 kJ/h).
Monitoring of relative blood volume
Relative blood volume (RBV) was measured with a commercially available blood volume monitor (BVM, Fresenius Medical Care). This monitor measures the transient time of short ultrasonic pulses, which are sent through the blood column in the arterial line. On the basis of these measurements, total protein concentration of the blood and RBV are calculated consecutively. The changes in RBV during dialysis treatment are assessed every 10 s, starting from 100% at the beginning (for details, see Schneditz et al. [14]).
Data collection and graphical depiction of the RBV and BTM curves were done with graphical software provided by Fresenius Medical Care.
Data analysis and statistics
Statistical analysis was performed using Sigmastat statistical software (SPSS Science, Chicago, IL). For comparison of blood temperature and blood volume between treatment modalities within study A or B, the paired Students t-test or Wilcoxon signed rank test were used as appropriate. Comparison of temperature and blood volume between HD (study A) and Temp-HD (study B) was performed using unpaired Students t-test. Comparison of the frequencies of dialysis-associated side effects between o-HDF and HD (study A) or o-HDF and Temp- HD (study B) was done using McNemars test. For comparison of the rates of hypotensive episodes in HD (study A) and Temp-HD (study B), the z-test was used.
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Results |
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Frequency of hypotensive episodes during o-HDF, HD and Temp-HD
In study A, there was a significantly lower rate of hypotensive episodes during o-HDF (4%) compared with HD (40%, P < 0.001). Blood pressure declined significantly during HD, but not during o-HDF treatments (see Table 3). In study B, no difference in the frequency of hypotensive episodes was seen between o-HDF and Temp-HD treatments (4% in both, NS), and decline of systolic blood pressure during treatments, although present, did not reach statistical significance (see Figure 1 and Table 3). The rate of symptomatic hypotensive side effects was significantly lower in Temp-HD (study B) than in conventional HD (study A) (P < 0.001, see Table 3).
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Blood temperature in the venous outlet of the dialyser
In study A, the temperature of the dialysate was between 36.5 and 37°C during all treatments. Temperature settings were adopted from previous sessions. For each patient, HD and the corresponding o-HDF treatments were performed at the same dialysate temperature.
Despite identical temperature settings for the dialysate, o-HDF treatments resulted in significantly lower blood temperatures in the venous line compared with HD (mean venous blood temperature: o-HDF, 35.49 ± 0.23°C; HD, 36.51 ± 0.31°C; P < 0.0001; see Figure 2). In study B, blood temperature in the venous line did not differ significantly between Temp-HD and o-HDF (Temp-HD 35.50 ± 0.4°C vs o-HDF 35.51 ± 0.43°C, NS).
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Relative blood volume (RBV) measurements
Mean RBV values of all treatments were significantly higher during HD than during o-HDF (study A: HD 97.18 ± 3.37%; o-HDF, 95.2 ± 2.86%; P < 0.05). In study B, there was no significant difference in mean RBV between o-HDF and Temp-HD (o-HDF, 95.5 ± 3.79%; HD, 96.69 ± 3.63%; NS).
Minimal RBV values (see Table 3) also were higher in conventional HD compared with o-HDF (study A, P < 0.005), whereas Temp-HD and o-HDF in study B showed no significant difference in minimal RBV. During hypotensive episodes, RBV values are influenced by artefacts e.g. increased fistula recirculation or fluid infusion, hence minimal RBVs in Table 3 were compared only for asymptomatic treatments.
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Discussion |
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HF and HDF are dialysis procedures using convective solute transport. It has been reported that these treatments provide superior cardiovascular stability compared with standard HD, which uses mainly diffusive transport of solutes [5]. However, the main stabilizing factor in isolated HF seems to be the cooling of the blood [15] with use of relatively cold substitution fluid. It is also well known that use of cool dialysate during HD can reduce the number of hypotensive episodes [1,4]. In contrast to HF and HD, there is little information about heat balance and occurrence of symptomatic hypotension in HDF procedures [15], and no data are available concerning o-HDF. Comparing HDF vs HD, one study over 6 months of treatment noted a decrease of hypotensive episodes from 18% (HD) to 14% (HDF) [16]. A second study did not find significant differences between HDF and HD regarding hypotensive episodes [17]. However, the frequency of hypotensive episodes was low, and, therefore, considering the sample size differences between treatment modalities, could hardly be detected. A recently published investigation [10] followed changes in blood pressure and temperature during HDF and HD. A more stable blood pressure was seen in HDF using replacement fluids at room temperature. As this study did not focus on hypotension-prone patients, it did not address the question of whether cooling by HDF can prevent symptomatic hypotension. Therefore, our study included only patients known to be hypotension prone, while other treatment variables (e.g. intradialytic weight loss, dialysate and infusate composition, dialysate and room temperature) were kept constant. Focusing on patients at risk, this selected group had an unusually high rate of hypotensive episodes (40%) with conventional HD at a dialysate temperature set at 36.537°C. The rate of hypotensive episodes was significantly lowered with o-HDF (4%) despite the same dialysate temperature settings. In addition, we could show that systolic blood pressure remained stable during o-HDF treatments, whereas it dropped significantly during HD.
Since in o-HDF the substitution fluid is prepared from the same pre-warmed fluid that is also used as dialysate, one would expect identical temperature profiles and ET rates during HD and o-HDF. Interestingly, o-HDF reduced blood temperature significantly and increased ET. Loss of thermal energy in the extracorporeal circuit could cause this effect, as in o-HDF blood temperature in the venous tube was >1°C lower than in the arterial tube. We suggest that substitution of cold fluid may explain this finding. During o-HDF, the substitution fluid initially has the same temperature as the dialysate. Due to the post-dilution mode, it subsequently cools down while passing through an additional tube and sterile filter before it reaches the venous drip chamber. The amount of thermal energy loss during o-HDF in this study reaches 16.6 W, which is 22% of the estimated resting energy expenditure of an adult person. It should be emphasized, however, that patients were not cooled to temperatures lower than their initial blood temperature, instead o-HDF merely prevented some of the patients temperature increase typically seen with conventional HD.
To prove that the observed cooling of the venous blood during o-HDF was responsible for better haemodynamic tolerance, the second part of the study compared o-HDF treatments with cooler HD treatments. In order to imitate the temperature course of the previous o-HDF, we used the E-control option of the BTM, which automatically reduced the dialysate temperature as needed to ensure identical ET in both treatments. As blood flow was unchanged, this resulted in identical venous and arterial blood temperature profiles during Temp-HD and o-HDF, respectively. Under these conditions, the rate of hypotensive episodes during Temp-HD was significantly lower than during conventional HD treatments in study A and was no longer different compared with o-HDF sessions. Maggiore et al. showed in a recently published, randomized, crossover trial that the incidence of dialysis-induced symptomatic hypotension during HD could be reduced from 50 to 25% in hypotension-prone patients using isothermic HD [18]. The reduction of side effects in our study seems to be more pronounced (40 to 4%), but this may be explained by a different definition of the term symptomatic hypotension and different patient inclusion criteria. In our study, body temperature rises up 0.26°C in HDF and Temp-HD. Despite this increase, a significant reduction of hypotension takes place. We conclude that patients tolerate a slight increase of body temperature well. However, isothermic dialysis may be the more physiological treatment procedure and therefore should be recommended.
The study design (short-term single centre interventional study) may limit the interpretation, but we believe that the highly significant reduction of side effects with o-HDF and Temp-HD sufficiently validates the data presented here. It should be mentioned that comparison between HD treatment in study A and Temp-HD treatment in study B has to be made with caution, since different patients were followed in both studies. However, our findings prove sufficiently that mainly temperature effects are responsible for the reduced incidence of hypotensive episodes during o-HDF. Moreover, they also indicate that increases in body temperature should be avoided during HD in order to prevent unnecessary symptomatic hypotensive episodes. As shown for example in Figure 3, the patients blood temperature at the beginning is clearly lower than the venous temperature, but later continues to rise above venous temperature levels. Thus, warming the blood within the extracorporeal circuit only partly explains the increase of patients core temperature at the beginning of the treatment. In accordance with other studies [18], we found that the body temperature (measured in the arterial line) continues to rise despite cooler blood returning to the patient (measured in the venous line). Thus, it is obvious that endogenous heat accumulation also contributes to the temperature increase during HD. As shown by Rosales et al. [4], this is most probably due to peripheral vasoconstriction in response to ultrafiltration. Overall, even during conventional HD, the blood is cooled in the extracorporeal circuit as indicated by ET balance.
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In summary, the blood pressure-stabilizing effect of o-HDF is due to blood cooling despite the administration of replacement fluids which are prepared from warm dialysate. In this case, cooling may be due to heat loss from longer extracorporeal fluid lines, as o-HDF was performed in post-dilution mode. HD has the same low rate of side effects as o-HDF provided that blood temperature measurements and use of appropriately cooler dialysate prevent warming of the patient.
Conflict of interest statement. J.B. has repeatedly served as a consultant for Fresenius Medical care. J.D., C.S., B.R. and B.K. declare no conflict of interest.
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References |
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