Volume disorders and assessment

1. What is meant by volume?

Physicians use the terms “volume” and “extracellular fluid volume” interchangeably. Because sodium is largely restricted to the extracellular fluid (ECF), total body sodium determines the ECF volume. Therefore changes in total body sodium lead to changes in ECF volume. A typical Westerner consumes about 150 mmol of sodium chloride per day. Let’s consider the hypothetical case of adding 150 mmol of sodium chloride to the ECF of a normal human. The resultant rise in the plasma sodium concentration and plasma osmolality will stimulate thirst and antidiuretic hormone (ADH) secretion. Ingestion of water and reabsorption of water by the collecting ducts will restore the plasma sodium concentration and plasma osmolality to normal. The end result is that 1 L of an isosmotic solution has been added to the ECF compartment; an increase in total body sodium has led to an increase in ECF volume.

2. How is ECF volume regulated?

If ECF volume is to remain constant, the amount of sodium ingested must be matched by the amount of sodium excreted by the kidneys. In the example above, expansion of the ECF volume must somehow be sensed. What is sensed is not ECF volume, but rather a portion of ECF called effective arterial volume. Effective arterial volume (also called effective circulating volume or sensed volume) is that portion of the ECF that is in the arterial tree and effectively perfusing tissues. An increase in effective arterial volume is sensed by baroreceptors in the aortic arch, carotid sinus, central veins, cardiac chambers, and afferent arterioles. In addition, an increase in effective arterial volume leads to an increase in renal tubular flow, which is sensed by the macula densa. Signals (suppression of renal sympathetic nerve activity and suppression of the renin angiotens in aldosterone system) are then sent to the kidneys, which lead to diminished sodium reabsorption by the renal tubules and increased sodium excretion by the kidneys. In the example above, 150 mmol of sodium will be excreted by the kidneys, returning ECF volume to normal.

3. What is hypervolemia?

Hypervolemia is due to an excess of total body sodium and water, which leads to expansion of the ECF compartment. Hypervolemia is therefore synonymous with ECF volume overload. Hypervolemia is typically due to kidney retention of sodium and water. This kidney retention may be primary or secondary. Primary kidney sodium retention may be caused by kidney failure; in this setting the diseased kidneys may be unable to match sodium excretion with sodium intake. Drugs may also lead to primary kidney retention. The direct vasodilator minoxidil and the thiazolidinedioines commonly cause kidney sodium retention and edema. The dihydropyridine calcium channel blockers may cause edema; with these drugs, capillary leak plays an important role in the development of edema. Secondary kidney retention occurs when there is a reduction in effective arterial volume. The most common causes of reduced effective arterial volume are congestive heart failure (CHF) and cirrhosis. In these conditions, the reduction in sensed volume leads to enhanced kidney sympathetic nerve activity, enhanced activity of the renin-angiotensin-aldosterone system, and enhanced secretion of ADH. Avid kidney sodium and water reabsorption ensue. In the case of the nephrotic syndrome, both primary and secondary kidney sodium retention may contribute to varying degrees. The kidney disease itself may lead to primary sodium retention (overfill hypothesis). The low plasma oncotic pressure from hypoalbuminemia may lead to movement of fluid from the intravascular compartment to the interstitial compartment. The contraction of the intravascular volume leads to secondary kidney sodium retention (underfill hypothesis).

4. What are the manifestations of hypervolemia?

The ECF compartment is composed of the vascular compartment (one-fourth of ECF volume) and the interstitial compartment (three-fourths of ECF volume). Patients with hypervolemia have expansion of the interstitial compartment; they may or may not have expansion of the vascular compartment.

• Patients with primary kidney sodium retention may have elevated jugular venous pressure, pulmonary edema, and peripheral edema.

• Patients with CHF may also have elevated jugular venous pressure, pulmonary edema, and peripheral edema.

• Patients with cirrhosis may develop portal hypertension and splanchnic vasodilatation. Portal hypertension leads to an increase in hydraulic pressure in the hepatic sinusoids. Fluid in the sinusoids moves across the hepatic capsule into the peritoneum. Ascites formation and splanchnic vasodilatation lead to a state of low effective arterial volume, which in turn leads to avid reabsorption of ingested sodium and water. Kidney retention of sodium and water serves to increase effective arterial volume—but also augments ascites formation. Patients with cirrhosis may also have lower extremity edema. Jugular venous pressure, however, is usually not elevated, and patients with cirrhosis do not develop pulmonary edema.

• Patients with the nephrotic syndrome typically have peripheral edema. If primary kidney sodium retention is predominant in an individual patient with the nephrotic syndrome, jugular venous pressure may be elevated. If vascular underfilling from movement of fluid from the intravascular to the interstitial compartment is predominant, the jugular venous pressure will not be elevated.

5. Is the history and physical exam reliable for the detection of hypervolemia?

The history and physical exam is neither sensitive nor specific for diagnosing hypervolemia. No one exam finding or historical feature is 100% accurate in the determination of volume status. There may be false negatives. A patient with kidney disease or heart failure may not have crackles or edema on exam, yet have significant extracellular volume expansion. Moreover, a patient may have no dyspnea by history, yet still harbor significant pulmonary congestion. Nor are certain physical exam findings entirely specific for hypervolemia (false positives). For instance, a patient may have edema related to venous stasis or pulmonary crackles from atelectasis despite intravascular effective arterial volume depletion. Some physical exam signs are technically challenging and have variable interoperator reliability. Obesity, valvular heart disease, and impaired right heart function make interpretation of jugular venous distention contentious. These difficulties have led to the proliferation of innumerable techniques to aid in assessment of volume status.

6. What are some adjuvant techniques to enhance the history and physical in assessing hypervolemia?

Given the association of volume overload with excess mortality and readmissions in heart failure and kidney disease, a variety of methods have been developed for noninvasively assessing volume overload. These methods take advantage of changes in physical properties as ECF volume increases. As with the history and physical exam, each method has limitations and their utility may be in the aggregate. This chapter will look at the noninvasive techniques with availability in inpatient or outpatient settings that have the best validation and most clinical utility:

• Bioimpedance spectroscopy (BIS)

• Lung-water ultrasound

• Intradialytic blood volume monitoring (BVM) devices

7. What is bioimpedance spectroscopy and how is it used?

Bioelectrical impedance analysis refers to several related techniques for determining body composition based on measuring electrical impedance or opposition to flow of a small alternating current applied to the body. Electrical impedance is the alternating current corollary to resistance in direct current circuits and is composed of resistance as well as reactance, which is made up itself of inductance (current induced by magnetic fields) and capacitance (the ability of circuit components to store charge). Body composition is determined by modeling the human body as an alternating current circuit using estimation equations derived from physical properties of the human body. Fat-free mass has lower impedance given its higher electrolyte-rich water content, whereas fat mass is relatively anhydrous and has higher impedance. In general, the greater the fluid content, the lower the impedance.

Whole-body BIS is the most validated of these methods. In this method, electrodes are placed on a hand and foot and alternating currents over a broad band of frequencies are applied to the body to estimate impedance. BIS has been validated against deuterium, bromide, and radioactive potassium radioisotope dilution techniques for determination of total body water (TBW), ECF, and intracellular fluid (ICF), respectively. BIS appears to have value in detecting occult fluid overload patients with end-stage kidney disease (ESKD) on HD. In retrospective cohort analysis, fluid overload as measured by BIS has been associated with increased all-cause mortality. In a large prospective cohort, fluid overload as measured by BIS was strongly and independently associated with all-cause mortality. Duration of exposure to fluid overload was associated with all-cause mortality in a dose-dependent fashion. These effects were durable across blood pressure tertiles. In two small clinical trials, estimation of dry weight enhanced by BIS showed improvement in all-cause mortality versus clinical evaluation alone. Similarly, in heart failure literature, one study validated transthoracic impedance to specifically measure ECF in the lung and found improvements in cardiovascular outcomes, all-cause mortality, and readmission. However, a multi-center randomized-controlled trial including 50 patients with fluid overload of 15% or more as demonstrated by BIS comparing three methods of dry weight reduction showed a high (31%) rate of dialysis-related complications across all groups demonstrating the difficulty of fluid removal in the dialysis population.

8. What is the role of thoracic ultrasound?

Formerly, ultrasound of the lung was thought to be valueless apart from the easy identification of pleural effusions. The lung is composed of numerous air-filled alveoli that represent multiple air-fluid interfaces. These interfaces reflect sound waves and generate reverberation artifacts that impair accurate tomographic visualization of normal lung parenchyma. These artifacts are termed A-lines and can be visualized as serial, equally spaced reflections of the pleural line ( Fig. 71.1 ).

In patients with kidney disease or heart failure, fluid accumulates in the interlobular septa separating alveoli and the A-line pattern gives way to a B-line pattern ( Fig. 71.2 ) with more B-lines corresponding with increasing fluid overload. The B-line pattern is visualized as radially oriented hyperechoic (bright) lines emanating perpendicularly from the pleural line running to the edge of the field. Counting B-lines serially over a predefined pattern of 28 intercostal spaces yields a B-line score.

B-line score has been validated using gravimetry in a post-mortem pig model and using invasive techniques available in the intensive care unit, such as transpulmonary thermodilution. B-line score correlates well with volume overload, outperforming the chest radiograph in detection of pulmonary edema, with higher score correlating with increased lung water. In patients with ESKD on HD, B-lines were demonstrated to disappear dynamically on dialysis correlating with ultrafiltration volume. In these patients, B-line score correlates with cardiovascular outcomes, death, and readmissions in retrospective data. A large, prospective, multi-center randomized controlled trial (Lung Water by Ultrasound Guided Treatment in Hemodialysis Patients or LUST Study) is ongoing to determine whether measurement of B-line score enhances estimation of dry weight and improves cardiovascular outcomes in patients with ESKD on HD and comorbid cardiac disease. Preliminary data from this trial has shown that the prevalence of asymptomatic pulmonary congestion is high and often goes undetected by the physical exam.

Lung ultrasound is easy to learn. Inter-observer reliability has been demonstrated using web-based tutorials and image review by expert trainers. There are limitations to lung ultrasound. A full 28-point exam takes about 5 minutes to perform and requires the patient to disrobe. Importantly, other disease processes can present as a diffuse B-line pattern, including the acute respiratory distress syndrome, diffuse interstitial lung diseases, and multifocal pneumonias.

9. What is the role of intradialytic BVM devices?

Patients undergoing ultrafiltration therapy have sodium and water removed from the intravascular compartment, leading to hemoconcentration as red cell mass is distributed in less volume. This is matched by mobilization of retained salt and water from the ECF compartment, termed capillary refill. The movement of water results in hemodilution, a fall in hematocrit. If the rate of ultrafiltration exceeds capillary refill, the patient develops effective arterial volume depletion. This can lead to intradialytic hypotension, decreased tissue perfusion, and myocardial and cerebral stunning.

The principle behind intradialytic BVM devices is to noninvasively estimate the hematocrit in real time during dialysis in order to avoid overaggressive ultrafiltration and prevent intradialytic hypotension.

Initial studies using intradialytic BVM devices showed improvement in intradialytic hypotension. However, a larger randomized controlled trial (the Crit-Line Intradialytic Monitoring Benefit or CLIMB Study) comparing these devices with standard of care demonstrated a significantly higher adverse event rate and mortality with intradialytic BVM. Further study is ongoing.