Various methods have been developed to help determine if patients have achieved their “dry weight.”

 

The standard goal of ultrafiltration (UF) is the achievement of “dry weight,” defined as the lowest weight a patient can tolerate without intradialytic symptoms or hypotension. It is well accepted that while body weight varies with total body water (TBW), weight alone does not provide comprehensive in-formation about the relationships between intravascular, interstitial, and intracellular fluid (ICF).

 

Furthermore, change in weight does not distinguish fluid change from gain or loss of muscle mass or fat. If there is an imbalance between compartments, a patient may achieve a prescribed weight yet still be hy-pervolemic or hypovolemic.

 

Often, signs and symptoms are used to evaluate the limits of UF. Since both systolic hypotension (systolic blood pressure [BP] less than 110 mm Hg) and systolic hypertension (systolic BP higher than 170 mm Hg) lead to early death, the definition of, and the trial-and-error approach to, “dry weight” should be revisited, and more objective and accurate methods for measuring fluid status and guiding UF should be explored.

 

More objective measurements should be incorporated into the clinical definition of dry weight including consideration of the volumes of each compartment, with particular attention to their dynamic properties and factors that influence these properties. Each patient should achieve optimal pre-dialysis and post-dialysis fluid balance or “steady state.” This is defined clinically as an asymptomatic, normotensive clinical status, on minimum BP medications with preservation of organ perfusion and existing residual renal function.

 

While a variety of tools have been proposed for evaluating “dry weight,” there is no agreed-upon gold standard for what objective measurements best indicate an optimal pre- and post-dialysis fluid status, or what methods are safest, most effective, and feasible to guide UF. This article briefly reviews the current fluid conundrum and proposes a multi-compartment, targeted fluid assessment approach to view-ing and investigating UF adequacy. The article will discuss three promising assessment methods: vector-bioelectrical impedance analysis (BIA), hematocrit-guided intradi-alytic blood volume monitoring (Hct-BVM) and radiotracer dilution blood volume analysis (BVA).

 

Volume excess and depletion

In hemodialysis (HD) patients, both volume excess and depletion are independent risk factors for increased cardiovascular and cerebrovascular morbidity and mortality. Chronic volume excess likely contributes to hypertension,1 left ventricular dysfunction, and left ventricular hypertrophy (LVH)2-6—all independent risk factors for increased cardiovascular and cerebrovascular morbidity and mortality in the dialysis population.7 Furthermore, LVH predicts an increased incidence of myocardial infarction,4,8 congestive heart failure (CHF),3,4,9 and sudden death in HD patients.10,11

 

Conversely, volume depleted HD patients may develop signs and symptoms of volume depletion.12-15 In a recent multicenter, prospective study of 1,206 patients, Shoji et al. found that patients' two-year mortality risk was increased twofold when intradialytic systolic hypotension and orthostatic hypotension were present.15

 

Correction of volume excess or depletion requires accurate assessment of the patient's fluid volume. Clinical examination alone is insufficient to make this determination.

 

Moreover, HD patients may not exhibit physical signs of volume overload because edema is not detectable until the interstitial fluid volume has risen to 30% above normal (4-5 kg of body weight).16 In addition, cardiac dysfunction and peripheral vasodilatation from calcium antagonists, venous insufficiency (structural or neurogenic) or permeability, and low serum albumin may manifest as peripheral edema in patients whose intravascular volume is appropriate for organ perfusion and for whom additional fluid ex-traction could lead to significant hypotension.

 

However, it is recognized that UF rates/volume, in excess of vascular refilling capacity (rate or volume), predispose to UF-associated hypotension and related symptoms. In addition, severe dehydration can develop before clinical signs and symptoms emerge.

 

HD delivery methods

The most effective and physiologic HD delivery methods currently available are frequent or long dialysis sessions. By maintaining a strict control of patient fluid volume through eight-hour dialysis sessions and strict limitation of salt and fluid intake, Charra et al. have reported an impressive 10-year patient survival of 75% associated with excellent BP control without BP medication.17,18 Every study of both short daily 19-23 and long nocturnal24 treatments has found a decrease in systolic and mean arterial pressure, often with reduction of all BP medications, reduction of extracellular fluid (ECF), or regression of LVH.

 

For reasons of economics, quality of life, and patient compliance, thrice-weekly HD remains the norm in the United States. Therefore, dynamic, objective measures of fluid compartments with more controlled changes in plasma volume may play an important role in improving HD outcomes when frequent or longer treatments cannot be implemented.

 

Compartment evaluations

Recent efforts have evaluated the use of non-invasive technologies to monitor intra- and extravascular fluid volumes independently. Methods for evaluating intravascular fluid include ultrasound assessment of inferior vena cava diameter 25-30 and several biochemical parameters, such as the natriuretic peptides.31-35

 

These methods have been proposed to guide fluid management and have been shown in certain studies to limit intradialytic morbidity. Their use is limited by interpatient variability, test variability, intra-operator ability, the presence of right-sided heart failure, and cost.

 

Radiotracer dilution methods provide quantitative measurement of the intravascular compartment. These methods are not suitable for intra-dialysis testing but may lend themselves to better analyze the intravascular volume at steady state. Their application may enable the clinician to better control blood volumes over long time intervals and assist in the prevention of chronic hypo- and hypervolemia.

 

A semi-automated, FDA-approved, blood volume analyzer (BVA) has made it possible to obtain rapid direct measurement of intravascular fluid, eliminating many of the previous time-consuming steps of other dilution techniques. This method may help further validate tools such as the continuous hematocrit measurements by providing quantitative intravascular compartments measurements at pre- and post-dialysis steady states.

 

BIA is a noninvasive method for assessing electrical tissue properties, predominantly of the limbs. Hundreds of BIA methods derived from models and regression equations have been used successfully to estimate soft-tissue hydration and have been validated by isotope dilution.

 

Using different single frequency, multi-frequency and bioimpedance spectroscopy (BIS) methods, compartments of ECF, TBW and ICF have been measured in healthy individuals. The concept is based on the assumption that TBW can be measured with single frequency (50 KHz) and formulas using the resistance. Low frequencies (1-5 kHz) pass through ECF whereas high frequencies (50-500 kHz) pass through both ECF and ICF, hence the TBW. Unfortunately, these methods fall short in HD patients who are malnourished, have active inflammation, or have abnormal tissue hydration.

 

In addition, an unknown and variable amount of low frequency current passes through cells due to anisotropy, particularly through muscle fibers in parallel to the current. Prediction errors are comprised of the sum of measurement error, variability among subjects, and the large bias introduced by the many assumptions that are necessary when using the equations. In contrast, vector-BIA uses direct measurements of a patient's impedance (Z). This method has been shown to have a precision error of only 2%, with subject variability the only potential source of additional error.

 

High UF rates are required to achieve desired fluid removal during thrice-weekly HD treatments. This increases the likelihood of an imbalance between UF and vascular refilling, frequently resulting in intradialytic hypovolemia. To address this important issue, hematocrit-guided blood volume monitoring (Hct-BVM) has been advocated and used to guide intradialytic volume removal, both by assessing changes in relative blood volume or hematocrit, vascular refilling, and central oxygen saturation. The promising individual methodologies are reviewed below.

 

Vector-bioimpedance analysis

The RXc graph 36 classifies an individual patient's fluid and nutritional status (by means of vector with length and direction according to the distance of the vector from the mean value of a reference population). Vector-BIA is a method for measuring the voltage drop as an 800 mAmps alternating current at 50 KHz is sent through the body by way of peripheral electrodes placed on the skin of a patient's ipsilateral hand and foot.

 

The impedance is made up of the sum of height-standardized R and Xc measurements, where R is the opposition to the flow of the current as it flows through an electrolyte solution—as the percentage of water in the body rises, current flows more freely, and the impedance falls. Xc is the shift in the phase angle of the current as it passes through cell membranes and tissue interfaces, which act as capacitors—the larger and healthier the cell membranes and proteoglycan meshwork, the greater the Xc. The phase angle is the arctangent of the Xc over the R, and it is visualized as the angle made by the vector and the X axis. At a fixed resistance, the phase angle increases with an increase in cell mass, and decreases with a decrease in cell mass. Simply, vector-BIA is a method for converting the body's electrical properties into clinically useful information, analogous to an electrocardiogram (ECG).

 

In 1998, vector-BIA was assessed in 1,367 chronic HD patients from more than 40 dialysis centers across Italy, and compared to results from 726 healthy subjects. Asymptomatic HD patients tended to stay within the 75% tolerance (ellipse) interval of the normal population, whereas symp-tomatic patients had smaller phase angles, outside of the 75% reference tolerance intervals for normal healthy population.37

 

These results were consistent with the study by Chertow et al., which showed that low phase angles were associated with an increased relative risk of death in chronic HD patients.38 Pillon et al. found that shorter vector lengths, indicating greater soft tissue hydration, were associated with an increased one-year relative risk of death, even after adjustment for case mix and several nutritional and inflam-matory indicators.39

 

Vector-BIA provides a promising direct approach for interpreting soft tissue fluid status in dialysis patients. Longitudinal studies evaluating the clinical effectiveness of using vector-BIA to guide UF has yet to be performed. One of the perceived drawbacks of vector-BIA is that it does not directly indicate an easily understood physical property. This problem is largely one of familiarity. With continued use of vector-BIA and the development of clear protocols for incorporating results into adjustment of UF by the nursing staff, the method will be more globally understood and more easily integrated into treatment.

 

Hct-BVM

Hct-BVM (Crit Line III, Hemametrics) is an optical density monitor that can detect and visually

display the continuous recording of changes in hematocrit, relative blood volume and oxygen saturation in real time during HD. It uses a transmissive photometric technique to measure the Hct on the basis of both the absorptive properties of hemoglobin and the scattering properties of red blood cells passing through the blood chamber.

 

During UF, intravascular blood volume is inversely and linearly correlated to hematocrit changes: as fluid is removed, the Hct rises. If the UF rate exceeds the vascular refill rate, hematocrit rises sharply. Intradialytic symptoms are often preceded by a rapid rise in hematocrit (fall in relative blood volume)40 or fall in central oxygen saturation.41 Timely intervention by the nurses has been shown to reduce symptoms and prevent morbidity.

 

Several small, observational studies have supported this hypothesis. They showed improved outcomes when Hct-BVM is used to guide dialysis.40,42 In contrast to these studies,  however, the multi-center, randomized, controlled CLIMB study did not demonstrate improved patient outcome when using Hct-BVM to guide dialysis.43 This study, however, should be interpreted with caution for several reasons.

 

First, the use of Hct-guided BVM was encouraged but not mandated or monitored. The study only evaluated the availability of Hct-BVM, not its implementation. Second, the annualized mortality rate in the patients treated without Hct-guided BVM was extremely low (6.4%), substantially lower than for average patients within the United States (23.7%).

 

This suggests that, as often occurs with randomized trials, the healthier patients tend to be enrolled and results cannot be generalized to the average American population. Third, all-cause mortality was reported instead of volume-related death. This study cannot be used to discount the potential benefits of using Hct-BVM, although it does emphasize the need for developing clear and effective protocols for the use of this methodology. Baseline BVA coupled with Hct-BVM changes has potential to provide quantitative intravascular volume measurements.

 

BVA

Radioisotope BVA (BVA-100, Daxor Co.) uses a single tracer dilution technique to measure plasma volume. Red cell mass is calculated utilizing the hematocrit and the plasma volume in the intravascular space. Total blood volume then, can be calculated. BVA has been used to assess volume requirements in heart failure44,45 with promising results. If used in conjunction with vector-BIA and Hct-BVM, the three combined tools may provide more objective measures of fluid status in all body compartments.

 

The Future

Vector-BIA, Hct-BVM, and BVA provide complementary volume meas- urements. At the New York University School of Medicine's VA New York Harbor Health Care System dialysis unit, we have been developing strategies using a combination of vector-BIA (TBW), BVA (intravascular blood volume), and Hct-BVM (dynamic, intradialytic response to volume removal) to define dynamic fluid compartment volumes in adults and the elderly.

 

By using more objective, accurate methods to dynamically evaluate fluid status in the different compartments, we ultimately hope to develop an improved method to guide ultrafiltration during thrice weekly hemodialysis.

 

Dr. Pillon is assistant professor of medicine (Nephrology) at the New York University School of Medicine, Director of Dialysis at the VA New York Harbor Health Care System. Dr. Feldschuh is President and CEO of Daxor Corporation. 

 

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