Reappraisal of Factors Disturbing the Relationship between Body Water Volumes and Total Body Electrical Resistance in Patients on Hemodialysis

Research Article

Int J Nutr Sci. 2021; 6(2): 1052.

Reappraisal of Factors Disturbing the Relationship between Body Water Volumes and Total Body Electrical Resistance in Patients on Hemodialysis

Schotman JM1*, van Borren MMGJ2, Wetzels JFM3, Kloke HJ3, Reichert LJM1, Doorenbos CJ4 and de Boer H1

1Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands

2Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands

3Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands

4Department of Internal Medicine, Deventer Hospital, Deventer, The Netherlands

*Corresponding author: Schotman JM, Department of Internal Medicine, Rijnstate Hospital, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands

Received: April 27, 2021; Accepted: May 24, 2021; Published: May 31, 2021


Background: Measurements of Total Body Electrical Resistance (TBER) are used to improve fluid balance management in patients on Hemodialysis (HD). This approach is based on the inverse relation that exists between TBER and body water volumes. Interpretation errors may occur if TBER measurements are affected by factors that are not related to changes in body water. Aim of this paper was to provide an overview of the methodological artifacts commonly encountered in a clinical setting, and to strengthen current evidence of their disturbing effects by performing additional experiments.

Methods: This study includes an analysis of available literature data, supplemented with additional experiments in healthy adults and patients. A cutoff of 2.7% was used to classify changes in TBER as significant within individual subjects.

Results: Electrode position, electrode interference, differences of measurements performed at the right or left side of the body, presence of orthopedic prosthesis located in the limbs, fluid redistribution induced by longterm changes in body position, and electrolyte abnormalities were the main disturbing factors that can induce a significant change in TBER. Other factors either had no significant disturbing effect or could be easily avoided.

Conclusion: TBER measurements require a high degree of standardization to minimize interpretation errors.

Keywords: Bioimpedance; Hemodialysis; Single-frequency; Measurement errors; Standardization


Whole-body Bioelectrical Impedance Analysis (BIA) can be used for fluid balance monitoring in patients on Hemodialysis (HD) and has been shown to have significant clinical benefits, such as improvements in fluid status and blood pressure, reduction of antihypertensive medication, and a reduced number of intradialytic hemodynamic events [1-5]. Nevertheless, clinicians remain reluctant to use the BIA technique in clinical practice, probably because of concerns about the accuracy of volume estimations in individual patients. In the present paper, we will discuss the potential sources of these inaccuracies, based on findings described in the literature as well as data from additional experiments.

BIA is an umbrella term used to encompass a number of different technologies, of which Single-Frequency BIA (SF-BIA), Multifrequency BIA (MF-BIA), and Bioimpedance Spectroscopy (BIS) are the most commonly used methodologies. It is important to note that they are all based on a two-step procedure. The first step is measurement of Total Body Electrical Resistance (TBER) by skin electrodes positioned on the hand and foot or a predefined body segment. The second step includes translation of the measured TBER into body water volumes, either based on empirically derived algorithms or more complex models [6-10]. Therefore, inaccuracies may either be related to factors that only affect the measurement of TBER itself, or to computation errors caused by invalid assumptions in the algorithms translating TBER into body water volumes.

The electrical measurement of TBER itself is very precise, with an analytical coefficient of variation ranging from 0.07 to 0.30%, and therefore this cannot account for the observed inaccuracies in patients [11-14]. In a well-controlled setting, changes in TBER observed during HD are tightly correlated with the changes in body water volume induced by Ultrafiltration (UF) [14-16], indicating that TBER measurements are useful to monitor hydration and to guide UF. However, this does not exclude the possibility that methodical errors or specific clinical conditions can induce changes in TBER that have no relation with changes in body water volume. If these disturbing factors are not recognized, a non-volume related decrease or increase in TBER will be incorrectly translated into an increase or decrease in calculated body water, respectively. This will lead to either over- or underestimation of the actual hydration status, and patients may receive the wrong treatment.

Knowledge of all factors affecting TBER in any specific situation is required to avoid interpretation errors. This applies to all BIA approaches using algorithms to calculate body water, as well as all BIA methods that are based on raw data analysis. Several studies already provided an overview of sources of error affecting TBER and recommended ways to minimize or avoid them [11,17-21]. Examples of factors that were addressed are electrode placement, body position during measurement, and the impact of food and beverage. However, other issues commonly encountered during HD, like blood pressure measurements coinciding with TBER measurements, HD related changes in body temperature, and the impact of posture dependent fluid redistribution have received limited attention. Moreover, the safety of TBER measurements in patients with implanted electronic cardiac devices also remains subject of debate.

Most data about TBER disturbances have been derived from studies in healthy subjects. It is not well known to what extent these results are applicable in patients on HD. The aim of this study was to extend the currently available information on methodological factors and conditions that disturb the relationship between TBER and body water volume in patients on HD, in order to minimize errors in hydration status assessment.



This study was performed in various subgroups of healthy adults and patients visiting either Rijnstate Hospital (Arnhem, the Netherlands) or Deventer Hospital (Deventer, the Netherlands). The studies were approved by the local ethics committee of both institutions, and all subjects gave their informed consent prior to participation.

TBER measurements

Literature results and additional experiments were based on TBER measured at a frequency of 50kHz, unless stated otherwise. This choice was made because 50kHz BIA was the earliest proposed method for the estimation of body water, and because the majority of research on interfering factors has been performed at this particular current frequency. The BIA101 Anniversary (Akern bioresearch srl, Pontassieve, Italy) was used to measure whole-body TBER in additional experiments, using skin-gel electrodes. In fact, TBER is not measured directly, but calculated from measured total body impedance and phase. Under normal conditions, TBER was measured at the right body side in controls and at the non-shunt side in patients on HD, with subjects in semi-recumbent position and with limbs slightly abducted from the body. Current injection electrodes were placed below the phalangeal-metacarpal joints of the index and middle finger, and below the phalangeal-metatarsal joints of the second and third toe. Detection electrodes were placed in the middle of the posterior aspect of the wrist proximal from the imaginary line at level of the styloid process of the radius, and at the ventral side of the ankle joint distal from the imaginary line at level of the lateral malleolus.

Critical difference

The concept of critical difference of TBER measurements was used as an objective criterium to quantify the impact of the investigated error for individual patients. It is defined as the smallest difference needed to consider a change in TBER significant within a single subject, with a confidence interval of 95% [22]. The critical difference of a TBER measurement in adults is 2.7%, and is based on analytical precision of the TBER instrument and biological variation within subjects [7,14,23]. For example, in patients with an ECW volume of 18L, a critical difference of 2.7% implies that the volume change has to be at least 0.49L in order to become detectable within a single subject. In this study the critical difference is used as a cutoff to describe the impact magnitude for each disturbing factor separately. However, in a clinical setting more than one disturbing factor may occur. In such cases the errors need to be added up. To avoid a significant disturbance, it should be realized that the sum of the all errors factors should not exceed 2.7%.

Statistical analysis

Results of additional experiments were presented as mean ± standard deviation (SD). Differences between groups were tested by a student’s t-test and intra-individual changes in TBER by paired twotailed t-test. Linear regression was performed to explore the relation between TBER and UF volume (temperature study). A P-value of <0.05 was considered statistically significant.

Experiments and Results

Impact of alcohol cleaning

TBER is measured by four adhesive electrodes applied to the skin. To achieve a good signal quality, the skin has to be proper and dry. In case of dirty or oily skin, impeding proper attachment of the electrodes, the skin can be cleaned with alcohol prior to attachment of the electrodes. However, it has been suggested that alcohol might dehydrate the skin and, thereby, increase the electrodeskin impedance [24]. Evans et al. investigated the impact of alcohol cleaning on the TBER in only two patients. TBER measured before and directly after alcohol cleaning, showed an increase in TBER of 1.3% (7.0Ω) and 1.5 % (7.2Ω), respectively [11]. A similar study in 46 adults found a small but significant increase of 0.4% [25]. Because of the limited data available we decided to study this aspect in a group of 18 healthy subjects (9 men and 9 women). In this study, alcohol cleaning was associated with a very small, non-significant decrease in TBER of 0.5 ± 2.1 Ω or 0.1 ± 0.4% (P=0.29). Changes within subjects ranged from -6.0 to 3.4 Ω (-1.0 to 0.6%) and never exceeded the critical difference. Note that this topic is only relevant for skingel electrode type devices. It does not apply for stand-on devices or devices using tactile electrodes.

In conclusion: Cleaning of the skin with alcohol does not affect TBER.

Shielding of the cables

When performing TBER measurements it is important to know the degree of shielding of the electrode cables. If shielding is incomplete, electrical interference may occur between the cables or between the cables and metallic bed frames, which will disturb the measurement of TBER. A study in 46 adults showed a small error of 0.2% related to the use of a metallic hospital bed [21]. To extent current knowledge, we studied further this aspect with BIA 101 cables in 20 healthy controls (9 men and 11 women). Cables were attached to the skin electrodes placed at the standard anatomical positions on the hand and foot. Initially, TBER was measured with the cables clearly separated, and then while holding the cables in parallel contact to each other. Interference was found to be negligible with the cables in parallel contact, with a mean decrease in TBER of 1.0 ± 0.7 Ω or 0.2 ± 0.1% (P <0.001). Impact at individual level was far below the critical difference of 2.7%, with values ranging from -3.1 to -0.3 Ω (-0.4 to -0.1%).

In conclusion: The cables of the BIA101 device are well shielded. When measurements are performed with other devices and at other frequencies, shielding check is recommended.

Impact of detection electrode position

TBER measurements are often used for long-term monitoring. Since TBER is directly related to length of the segment that is measured [8], electrode position should be the same at each occasion to obtain comparable data. In a study of two subjects, Evans et al. reported that a decrease of the hand-to-foot detection electrode distance was associated with a decline in TBER of about 1.7% per cm proximalization of the hand electrode pair and of 1.2 % per cm proximalization of the foot electrode pair [11]. Gartner et al. studied 8 subjects and confirmed that proximalization of the detection electrode was associated with a linear decrease in TBER [26].

To extend current evidence, we evaluated the impact of electrode displacement in 20 healthy subjects (9 men and 11 women). TBER measurements were first performed with electrode pairs applied to standard anatomical positions, and then after shifting the detection electrode in steps of 1cm, up to either 3cm distally or 3cm proximally, while maintaining the baseline position of the injection electrodes.

TBER proved very sensitive to detection electrode displacement (Figure 1). It decreased by 11.1 ± 2.3 Ω/cm (2.1 ± 0.3 %/cm) for proximal shifts of the hand detection electrode and by 8.3 ± 2.0 Ω/cm (1.5 ± 0.2 %/cm) for proximal shifts of the foot detection electrode. At individual level, the impacts ranged from 7.5 to 14.4 Ω/cm (1.6 to 2.6 %/cm) for shifts of the hand electrode and from 4.7 to 11.8 Ω/cm (1.0 to 1.9 %/cm) for shifts of the foot electrode. In 7 of 20 subjects (35%), one centimeter distalization of the hand detection electrode caused an increase in TBER that exceeded the critical difference.