Renal Research Institute, New York, USA
Keywords: bioimpedance; dry weight; extracellular volume; fluid removal; haemodialysis; hydration
Introduction
Patients undergoing regular dialysis therapy for end-stage renal disease retain fluid during the interdialytic period, which is removed during dialysis. The aim of such fluid removal is to maintain a dry or target weight in the patient. This weight was defined as the lowest weight that the patient could tolerate without any intradialytic symptoms or hypotension at the termination of the treatment session. It may be more accurately defined as the weight at which there is no excess extracellular hydration in the tissues. The accurate assessment of patient dry weight can pose considerable difficulties due to the shape of the pressurevolume curve of the interstitial fluid spaces such that oedema may not be detectable until the interstitial volume has risen by 30% above normal, corresponding to 45 l. The interdialytic weight gain seen in patients may not simply be a result of hypervolaemia; gain in body weight as a result of improved nutrition, particularly following the initiation of regular dialysis therapy, may also contribute. With the trend towards shorter treatment sessions, a more restrained approach to the interdialytic control of sodium intake and the treatment of older patients, the tolerance of the high ultrafiltration rates required to remove the interdialytic weight gain is impaired in many patients, preventing the attainment of dry weight by the end of the treatment session. These factors result in overhydration and increased blood pressure and contribute to cardiac complications and mortality in dialysis patients [13].
Considerable technological advances have occurred in the equipment used for the treatment of renal failure, but a technique for establishing patient's dry weight and ensuring that it is maintained over extended periods remains elusive. A number of different approaches have been tried to assess dry weight but have failed to gain popularity arising from limitations in using them in a routine manner [47]. In a recent publication, Chamney et al. [8] described the use of whole body bioimpedance utilizing the principle of intersecting slopes based on normovolaemia in healthy subjects and hypervolaemia in dialysis patients. This showed that quantification of dry weight using this approach was within ±1.58 kg of the best clinical estimate for dry weight. The purpose of this review is to critically examine the use of bioimpedance as a tool for dry-weight prediction and the optimization of fluid removal during dialysis, thereby maintaining the patient in a normal or near normal hydration state.
What is bioimpedance and what does it measure?
Electrical bioimpedance methods have been in existence since the beginning of the 20th century when experiments investigating the electrical properties of biological matter were undertaken [9]. These early experiments demonstrated that when an alternating current is passed through biological tissues the resistance consists of two components: the electrical resistance of the material and a second component, due to the capacitive reactance of the cell membrane. This latter component was shown to vary with the frequency of the applied current such that at low frequencies (<10 kHz) the cell membrane acts as an insulator and prevents the penetration of electric current into the cell so that current flows predominantly through the extracellular spaces of the tissues. At high frequencies the current penetrates the cell membrane enabling it to pass through both the intracellular and extracellular spaces. In bioimpedance measurements, a small alternating current is usually applied via two electrodes to the body. The voltage produced is detected by a second pair of electrodes. The impedance generated is a function of the conductor geometry, which is generally assumed to be a cylinder. A number of different positions may be used for the current injection and detection. Measurements may be based upon a single frequency or multiple frequencies. The conversion of the impedance measurements into volumes is generally achieved by use of the dielectric theory of electrical conduction through mixed emulsified solutions, which is used to derive the resistances of the extracellular and intracellular fluid compartments coupled with a set of reference coefficients for extracellular conductivity and tissue density derived from isotope dilution measurements in non-uraemic subjects [10,11].
The assumption that the body could be approximated to a single conducting cylinder results in the inability of whole-body bioimpedance measurements to accurately assess regional accumulation of fluid, such as may be seen in renal patients, therefore underestimating the changes in volumes [12]. This arises from the fact that the limbs, due to their physical dimensions, make a greater contribution to the overall impedance than the trunk. With refinements using a segmental concept in which the body is taken as being formed from five cylinders representing the trunk and the limbs, the true whole body impedance taken as the sum of the individual components overcomes this limitation but practical issues arising from patient movement during dialysis remain [1315].
Dry weight and bioimpedance measurements in dialysis patients
Kushner et al. [16] reviewed the use of bioelectrical impedance in the clinical management of patients undergoing dialysis and identified four areas in which it might be used: the assessment of volume status, monitoring of fluid shifts during treatment, the provision of a value for total body water and the assessment of nutritional status. Discussions will be confined to the use of bioimpedance in the assessment of dry weight.
An early use of bioimpedance to establish dry weight was by Kouw et al. [17] who measured the intracellular and extracellular volumes of dialysis patients before and after dialysis and compared them with those of normal controls. The authors noted that in patients who were at their dry weight the extracellular volumes were comparable with those of normal controls. A similar approach was used in a recent study by Lopot et al. [18]. In the absence of changes in the lean body mass, the majority of the fluid gained in between treatments resides in the extracellular compartment [19]. Adjustment of dry weight based on the adjustment of extracellular volume in dialysis patients has also been undertaken by Chen et al. [20]. This study measured the extracellular volume of both normals and dialysis patients and noted that in hypertensive patients the ratio of extracellular to total body water was higher than in normotensives. Reduction of the extracellular volume by the lowering of the post-dialysis weight resulted in a reduction in blood pressure, an observation that has also been seen in our own unpublished data on patients undergoing daily dialysis. These observations are consistent with the observations made on the Tassin group of patients by Katzarski et al. [21].
Piccoli et al. [22,23] utilized an alternative approach to evaluate the hydration status without any assumptions based on body composition. They plotted the components of impedance measurements, resistance (R) and reactance (Xc), normalized to height of both normal controls and patients undergoing dialysis. Measurements were plotted as bivariate vectors with their confidence and tolerance intervals, which are in the form of ellipses. Measurements from dialysis patients taken pre- and post-treatment were overlaid and a definite, cyclical, backwardforward displacement of impedance corresponding to the wet (pre-dialysis) and dry (post-dialysis) weight cycling of the patients was noted. In patients subject to haemodialysis-related hypotension the changes were less steep and more often shifted to the right, out of the reference 75% tolerance ellipse, compared with asymptomatic patients. A wetdry weight prescription, based on bioimpedance indications, resulted in the restoration of bioimpedance into the normal range. This approach was also used by Guida et al. [24] who compared assessment of volume status by conventional bioelectrical impedance analysis and the resistancereactance (RXc) graph method in patients achieving their target dry weight determined on clinical criteria. The authors demonstrated that removal of body fluid during treatment was associated with a progressive increase in both impedance vector components, R and Xc.
Spiegel et al. [25] measured the resistances of the intracellular and extracellular fluid compartments in normal subjects and used these to define a normal physiologic ratio that was used for comparison with dialysis patients, both pre- and post-dialysis. The authors noted that in patients who had reached their dry weight, as determined by clinical criteria, the ratio of resistances still remained outside the normal range, suggesting that these patients were not yet at their physiologic dry weight.
Bioimpedance may also be used to characterize fluid shifts during dialysis. Shulman et al. [26] demonstrated that during dialysis, plasma refilling to preserve central blood volume is more dynamic from the leg than from elsewhere. A similar approach whereby the hydration status of the calf was monitored during dialysis using a low frequency (5 kHz) alternating current has been used by Zhu at the Renal Research Institute and these measurements indicated that patients who have reached their dry weight extracellular resistivity stabilized towards the end of dialysis, signifying the attainment of a dry state. The attainment of such a state may explain the frequent occurrence of cramps towards the end of dialysis.
What are the limitations of bioimpedance measurements?
There remains uncertainty regarding certain technical aspects of bioimpedance measurements [27,28]. Nevertheless, bioimpedance studies in which hydration status is compared with normal groups have universally demonstrated that the hydration status of the patients exceeds that of a normal group and manipulation of the post-dialysis weight results in a normalization of hydration status and improves blood pressure. One could make the argument that when determining dry weight there is no need to convert the measurements into volumes. As the majority of the changes occur in the extracellular compartment, the monitoring of extracellular resistance or resistivity may be more appropriate. A further limitation of using volumes is the fact that the underlying equations rely upon constants derived from non-uraemic control groups. During dialysis the fluid shifts are associated with changes in electrolyte, red cell and protein concentrations and patient temperature homeostasis may also be perturbed, all of which are known to influence bioimpedance [2931]. Measurement of resistivity in biological tissue through which blood flows is influenced by erythrocyte orientation in the flowing blood [32]. Red cell dimensions change when the osmotic pressure of plasma changes, further confounding measurements [33]. Uncertainty surrounds the clinical significance of these changes relative to the changes induced by volumetric changes. It is of note that Chamney and colleagues [8] adopted a pragmatic approach to these effects by stating the effect of fluid must overwhelm other factors such as electrolyte variation, otherwise the technology would be of very little value in the dialysis setting. Additional studies are required to establish the relevance of confounding factors. Many of the measurements comparing pre- and post-dialysis values described in the literature are non-standardized. Postural changes are known to influence fluid distribution and complete fluid equilibrium may take up to 30 min to achieve. Serial measurements using the whole-body approach over a dialysis session restrict patient movement. The application of segmental or regional measurements, such as in the patient's calf, are less restrictive and may be preferable, particularly as they have been shown to be representative of true whole body measurements [34].
Conclusions
Historically, patients underwent longer dialysis sessions than used today; they dialysed against lower dialysate sodium concentrations and were subject to a more rigorous control of their interdialytic sodium intake. When starting dialysis, such patients were progressively dried out by a systematic reduction of their post-dialysis weight until they became hypotensive in the latter part of the treatment. The weight at which this occurred plus the amount of fluid needed to restore blood pressure to normal values was taken as dry weight. These historic approaches have been largely forgotten and would be difficult to achieve with the currently used shorter treatment sessions. Patients may experience hypotension long before they reach their dry weight. It is, however, instructive to reflect on the data relating to the Tassin group of patients where such an approach remains.
Bioimpedance measurements are able to establish the hydration status of patients and thus distinguish between those at their dry weight and those who are overhydrated. Normalization of overhydration has been shown to result in an improvement in blood pressure. Longer studies are needed to establish if routine monitoring of hydration and the maintenance of the patient at normal hydration using this approach translates to improved cardiovascular status and improved treatment outcome. Regional measurements, such as those in the calf, are simpler to perform and are better tolerated by patients than whole body or segmental measurements. Their use to the point at which normal hydration is reached may also contribute to the minimization of intradialytic morbidity. Assessment of accuracy relative to more established approaches over the longer term are currently in progress. The availability of this information will enable the appropriate technology to be developed either as a stand alone hydration meter or incorporated into the next generation of haemodialysis equipment, possibly with feedback architecture. The availability of such instrumentation will go a considerable way to ensure that patients are not over-hydrated and are at their dry weight.
Notes
Correspondence and offprint requests to: Dr N. A. Hoenich, Nephrology, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK. Email: Nicholas.hoenich{at}ncl.ac.uk
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