R E V I E W
Hypovolemia and Dehydration
in the Oncology Patient
Lawrence Berk, MD, PhD, and Sharon Rana, PhD
D
ehydration and hypovolemia are com-
mon problems in the oncology clinic that
can be secondary to inadequate intake
(eg, due to mucositis or inanition) or
excessive loss (eg, due to vomiting or diarrhea).
However, dehydration and hypovolemia are also
problems that are often misunderstood and misdi-
agnosed by physicians. As Mange and colleagues
described,1 “Patients presenting with orthostatic
hypotension and normal plasma sodium concen-
trations are frequently admitted to the hospital
with a diagnosis of dehydration. If they are fortu-
nate, they receive fluids containing sodium chlo-
ride instead of free water to correct obvious ex-
tracellular fluid volume depletion. Confusing this
diagnosis highlights the growing and pernicious
habit of using the terms dehydration and volume
depletion interchangeably at the bedside when
the two describe clearly different disturbances.”
Unfortunately, even the Common Terminology
Criteria for Adverse Events v3.0 for dehydration,
shown in Table 1, are signs of hypovolemia and
not dehydration.2
Physiology of the Water and
Electrolyte System
WATER BALANCE
Water comprises 70%–75% of the fat-free mass
of an adult, and adipose tissue is approximately
10%–40% water.3 Figure 1 shows the distribution
of body water. For people over 50 years of age, the
total body water comprises approximately 56%
of the body weight of men and 47% of the body
weight of women.4 The water is distributed be-
tween intracellular fluid (65%) and extracellular
Manuscript submitted January 10, 2006;
accepted March 26, 2006.
Correspondence to: Lawrence Berk, MD, PhD, Radiation On-
cology, Moffitt Clinic at Tampa General Hospital, 2 Columbia
Dr., Tampa, FL 33606; e-mail: berklb@moffitt.usf.edu
J Support Oncol 2006;4:447–454 © 2006 Elsevier Inc. All rights reserved.
VOLUME 4, NUMBER 9 ■ OCTOBER 2006
Abstract Dehydration is commonly but often inappropriately diag-
nosed in cancer patients. Dehydration is the loss of water from the in-
tracellular compartment due to hypernatremia. Dehydration can occur
among patients who are hypervolemic, euvolemic, or hypovolemic.
Cancer patients are more often hypovolemic, reflecting depletion of
water from the extracellular space due to excessive loss, such as from
vomiting and diarrhea, or inadequate intake of fluids. Hypovolemia can
be hypernatremic, eunatremic, or hyponatremic. The appropriate state
of the patient should be determined prior to attempts at correcting the
problem. A hyponatremic patient would rehydrate more quickly with
a solution higher in sodium, whereas this solution could be dangerous
for a hypernatremic patient. Rapid or inappropriate treatment of hyper-
natremia can lead to death. Subjective findings, physical findings, and
laboratory values will help direct the appropriate resuscitation methods.
This paper reviews the physiologic control of extracellular volume and
electrolytes, diagnosis of sodium and water balance problems, and the
management of these concerns.
fluid (35%).3 An average 70-kg male has 42 L of Dr. Berk is Associate
total water, consisting of 29 L of intracellular and Professor, University
of South Florida, and
14 L of extracellular fluid. The extracellular fluid Medical Director of
is further distributed between the interstitial space Radiation Oncology,
and the vascular space. Of the 14 L of extracellu- H. Lee Moffitt Cancer
lar fluid, 11 L are in the interstitial space and 3 L Center Clinic at Tampa
General Hospital,
in the vascular space. These fluid distributions are Tampa, Florida. Dr. Rana
dynamic and will change in response to losses or is Assistant Professor,
gains in any one department. Water transference School of Recreation
from the extracellular fluid into or from the in- and Sport Sciences,
College of Health and
tracellular fluid is dependent on the intracellular Human Services, Ohio
and extracellular osmotic pressures. Within the University, Athens.
extracellular fluid, the majority of the water ex-
change between the interstitial and intravascular
spaces occurs at the level of the capillaries. The
transcapillary pressure determines the direction of
the flow.5
The concentration of ions in the intracellular
and extracellular compartments is equal because of
the high water permeability between the two.6 Sodi-
um (Na+), chloride (Cl–), and bicarbonate (HCO3–)
are the primary extracellular salts. Potassium (K+),
magnesium (Mg2+), and phosphates (PO43–) are the
www.SupportiveOncology.net 447
Hypovolemia and Dehydration in the Oncology Patient
Table 1
Common Terminology Criteria for Adverse
Events v3.0 Dehydration Grading
GRADE DESCRIPTION
1 Increased oral fluids indicated; dry mucous membranes;
diminished skin turgor
2 Intravenous fluids indicated < 24 hours
3 Intravenous fluids indicated ≥ 24 hours
4 Life-threatening consequence (eg, hemodynamic collapse)
5 Death
Adapted from National Cancer Institute—Common Terminology Criteria for Adverse Events.2
primary intracellular salts. A membrane-bound Na+/K+ ATPase
pump maintains the differentials. Almost all glucose is extracel-
lular because of its rapid intracellular metabolism.
Approximately 5%–10% of total body water is lost and
gained each day.7 Table 2 outlines the baseline water losses.8
Approximately 2 L of fluid are lost daily. The baseline urine
output is the amount needed to eliminate metabolic waste
products. Water loss in oncology patients may be increased
due to problems such as fever, sweating, diarrhea, and vom-
iting. Medications, such as diuretics, may also increase daily
output. Water intake is through eating and drinking, though
metabolic processes also generate a small amount of water.
RENAL PHYSIOLOGY
Water and salt balance is maintained through the kidneys
and their nephron system. Figure 2 shows the anatomy of the
nephron.9,10 Water and electrolyte balance is maintained by
the tubule system of the nephron, which functions through a
combination of active electrolyte transfer and passive, osmoti-
cally driven diffusion (Figure 3).9
The area of the distal collecting ducts is sensitive to the
presence of vasopressin (antidiuretic hormone). In a hypovo-
lemic state, the level of vasopressin rises and the aquaporins
are activated, allowing the water in the collecting ducts to be
absorbed into the interstitium; the urine becomes concentrat-
ed. Vasopressin will acutely increase the osmotic pressure of
urine over a few hours. Long-term (several days) fluid depriva-
Total body water (50%−70% body weight)
Intracellular water Extracellular water
(30%−40% body weight) (20% body weight)
Interstitial
25 L 11 L
Figure 1 Distribution of Body Water
448 www.SupportiveOncology.net
Table 2
Baseline Water Losses8
SOURCE LOSS (mL)
Kidneys 900
Skin 350
Sweat 100
Respiration 350
Feces 200
Total 1,900
Adapted from Arsenault.8
tion will then act synergistically to induce increased sensitiv-
ity to vasopressin and a higher urine osmolality. For example,
in rats, vasopressin infusion acutely raised urine osmolality to
969 mOsm/kg H2O. In contrast, fluid deprivation for 48 hours
raised the urine osmolality to 3,817 mOsm/kg H2O.11
Background
DEHYDRATION
As discussed previously, the ionic constituents of the extra-
cellular and intracellular fluids are different, with potassium,
magnesium, and phosphates predominating intracellularly,
and sodium, chloride, bicarbonate, and glucose predominat-
ing extracellularly. However, the two compartments are main-
tained in osmotic equilibrium by shifts in water. An increase
in the extracellular osmolality is compensated by a shift in wa-
ter from the intracellular compartment, causing dehydration
of the intracellular compartment. This step causes a volume
contraction of the cells. Thus, the appropriate use of the term
“dehydration” is for extracellular hyperosmotic states. The
total osmolality of the extracellular fluid is approximated by
the following formula12 (the concentration of solutes in these
equations is in mg/dL and the osmolality is in mOsm/L): 2 ×
Na+ + glucose/19 + blood urea nitrogen(BUN)/2.8. Among
some patients, this calculation may need to be corrected for
ethanol: 2 × Na+ + glucose/19 + BUN/2.8 + ethanol/4.6.
From these equations, it is clear that the extracellular os-
molality and hydration status is determined by the sodium
concentration. Intracellular dehydration, which is due to hy-
perosmotic extracellular fluid, is almost always due to hyperna-
tremia. Therefore, the term “dehydration” can almost always
be limited to the extracellular hyperosmotic, hypernatremic
state. An exception would be a severe hyperglycemic state.
Hypernatremia is any serum sodium level greater than
the defined normal range. This increase may occur due to
Transcellular
excessive sodium input (eg, intravenous supplementation
Plasma
with hypertonic saline or bicarbonate) or from excessive wa-
ter loss from the extracellular compartment (eg, excessive
diuresis). Hypernatremia can be hypovolemic, euvolemic,
or hypervolemic (Table 3).13 Hypernatremia occurs among
3L 2L oncology patients primarily in a hypovolemic state due to
gastrointestinal losses (eg, vomiting, diarrhea) or increased
insensible loss (eg, fevers).
THE JOURNAL OF SUPPORTIVE ONCOLOGY

Proximal convoluted Distal convoluted
tubule tubule
Glomerulus
Efferent
arteriole
Afferent
arteriole
Artery
Vein
Descending Ascending
limb Collecting
limb
duct
Figure 2 Anatomy of the Nephron
The flow of water out of the vascular system and into the renal tubule
collecting system (GFR) is controlled by the hydrostatic pressure drop be-
tween the afferent and efferent arterioles. Filtration occurs at the glomeru-
lar capillaries. An increase in the afferent arteriole resistance reduces both
the plasma flow (RBF) and the glomerular hydrostatic pressure. Primarily,
both local and systemic effects on the smooth muscles of the afferent
arterioles regulate the RBF and GFR; that is, an increase in tension of the
arteriole walls causes afferent arteriole contraction, whereas an increase in
flow causes vasoconstriction and a decrease causes vasodilation. This pro-
cess, known as the tubuloglomerular feedback mechanism, has increased
sensitivity in volume contraction to help conserve fluid and decreased sen-
sitivity in volume expansion to allow for loss of fluids. Angiotensin II also
increases tubuloglomerular feedback sensitivity and, therefore, diuresis.
Abbreviations: GFR = glomerular filtration rate; RBF = renal blood flow
Adapted from Mader.9
Symptoms of hypernatremia reflect cellular dysfunction in the
central nervous system13; they include lethargy, weakness, irrita-
bility, and hyperreflexia and can progress to coma. In their study
of 103 patients with hypernatremia, Palevsky et al14 reported a
mortality rate directly related to the hypernatremia of 16%.
HYPOVOLEMIA
In contrast to hypernatremia, in which the primary prob-
lem is dehydration of the intracellular fluids, hypovolemia is
an extracellular phenomenon. Specifically, it refers to the de-
creased fluid volume in the intravascular space. Hypovolemia
can occur in a hyponatremic, isonatremic, or hypernatremic
state. As discussed previously, the most common state of hy-
pernatremic dehydration is hypovolemic, due to loss of gastro-
intestinal fluids or sweating.
VOLUME 4, NUMBER 9 ■ OCTOBER 2006
Berk and Rana
Distal convoluted
tubule
Cortex
Increasing solute concentration in renal medulla
Na+Cl-
Descending limb
Ascending limb
Outer
medulla
H2O
H2O
Inner
medulla
Urea
Collecting
Loop of the
duct
nephron
Figure 3 Water Reabsorption in the Kidneys
Water diffuses out of the glomerular capillaries into the renal cortex inter-
stitium and is then passively absorbed into the renal tubules. An increasing
concentration gradient of sodium chloride, urea, and other waste products
is generated within the renal medulla focused toward the inner medulla.
This process then generates increasing osmotic pressure toward the inner
medulla. The sodium concentration gradient is created by a feedback loop.
The descending limb of the nephron is water permeable, allowing trans-
portation of water out of the descending limb and into the higher osmotic
pressure interstitium. In the ascending limb (primarily the thick ascend-
ing loop in the outer medulla), which is water impermeable, active pumps
transport sodium out of the tubule fluid, concentrating the interstitial fluid
by the ascending loop, which then draws the water out of the water-per-
meable descending loop. The counter-current arrangement magnifies this
effect to create concentrated interstitial fluid. The dilute, sodium-depleted
fluid in the ascending ducts flows into the proximal collecting ducts in the
outer medulla and finally into the distal collecting ducts.
Adapted from Mader.9
The two most common sources of gastrointestinal loss of
electrolytes and fluid are diarrhea and vomiting. Duodenal
secretions contain 1.0–11.0 mEq/L of potassium and 85–143
mEq/L sodium, whereas ileal secretions contain 11 mEq/L of
potassium and 129 mEq/L of sodium.15 The electrolyte con-
tent of diarrhea is dependent on the etiology. The small bowel
content is high in water, the reabsorption of which is driven
through osmosis by the active reabsorption of sodium. Inflam-
mation leads to dysfunction of the reabsorption pumps and loss
of both water and electrolytes, primarily sodium. For example,
the diarrhea seen with the mucosal inflammation of ulcerative
colitis is associated with dysfunction of these sodium pumps.16
Malabsorption, associated with decreased reabsorption of bile
acids, is seen in radiation-induced diarrhea.17 Experimental
models have shown an acute decrease in sodium reabsorp-
tion by the bowel after irradiation,18,19 which would lead to
hyponatremic hypovolemia. Late-onset irinotecan (Camp-
www.SupportiveOncology.net 449
Hypovolemia and Dehydration in the Oncology Patient
Table 3
Hypernatremic States
STATUS CAUSE
Extracellular volume
Hypovolemic Renal losses of hyponatremic urine
(eg, hyperglucosuria)
Excessive insensible loss (sweating, fever)
Gastrointestinal loss (diarrhea)
Euvolemic Renal loss of eunatremic urine (eg, diabetes insipidus)
Polydipsia
Hypervolemic Hypertonic solution administration
Primary hyperaldosteronism
Sodium level
Hyponatremic “Third-spacing” (CHF), renal insufficiency,
inappropriate rehydration with low-sodium fluids
Isonatremic Rapid blood loss, diarrhea, vomiting, insensible loss
Hypernatremic Diarrhea, vomiting, sweating (severe)
Abbreviation: CHF = congestive heart failure
Adapted from Fall.13
tosar)-induced diarrhea is probably related to abnormal ion
absorption from the bowel, leading to osmotic loss of fluid and
electrolytes.20 Loperamide, the most commonly used medica-
tion for radiation- and chemotherapy-induced diarrhea, has
antisecretory activity.21,22
Vomiting also induces sodium loss. Columnar cells lining
the stomach secrete sodium in exchange for hydrogen and bi-
carbonate ions. In contrast, the parietal cells secrete hydrogen
ions in exchange for potassium ions.23 Gastric juice contains
approximately 10 mEq/L of potassium and 50 mEq/L of so-
dium.15 Therefore, volume loss due to severe emesis will tend
to cause hyponatremic hypovolemia.
Diagnosis
QUANTITATIVE MEASUREMENT OF VOLUME STATUS
Precise measurements of body hydration are possible but are
often limited to the research setting (see Armstrong’s review
for a complete presentation24). One method is to administer
a compound that will distribute evenly throughout the total
body water, such as stable isotopes of oxygen (18O) or hydrogen
(2H) in water. Once equilibrium is established, measurements
of the concentration of the isotopes will reflect the total body
water. Sodium and chloride ions are chiefly found in the extra-
cellular fluid. Therefore, isotopes of these ions (24Na, 36Cl) can
also be used to distribute evenly throughout the body, though
the concentration of the isotope will reflect the extracellular
fluid. Sodium bromide (NaBr), which can be given orally, has
also been used; measurements of bromide concentration may
be taken 2–4 hours after administration.25
Another method is the measurement of the body’s bioelec-
trical impedance, which requires more assumptions and mod-
eling than do dilutional techniques. This technique models
the body as an electrical conductor system to determine the
water distribution. It is non-invasive, instantaneous, relatively
450 www.SupportiveOncology.net
Table 4
Thirst Visual Analog Scale
LOW-END HIGH-END
QUESTION QUALIFIER QUALIFIER
How thirsty do you feel now? Not at all thirsty Very thirsty
How pleasant would it be to Very unpleasant Very pleasant
drink some water now?
How dry does your mouth Not at all dry Very dry
feel now?
How would you describe the Normal Very unpleasant
taste in your mouth?
How does your stomach feel Not at all full Very full
now?
Adapted from Rolls et al.31
inexpensive, and appropriate for measuring changes in the ex-
tracellular volume/intracellular volume ratio.26
Serum osmolality is another measure of hydration status.
A 1% increase in serum osmolality induces the sensation of
thirst.24 Most clinical laboratories report a calculated serum
osmolality (Cosm) based upon the formula: Cosm = (2 ×
Na+) + BUN + glucose (in mOsm/kg). The true serum osmo-
lality is most commonly measured by freezing-point measure-
ment. A recent study showed that calculation of osmolality
overestimated measured osmolality in the lower ranges and
underestimated it in the higher ranges.27 Therefore, if accu-
rate osmolalities are required, the true osmolality, rather than
the calculated osmolality, should be obtained.
Under homeostatic conditions, the total body water has
minimal fluctuation. As described previously, the primary
mechanism for the control of hydration is through water
regulation in the kidneys. Measured urine osmolality reflects
the concentration of solutes in the urine, which should be
higher in hypovolemic conditions. However, there is no stan-
dard for directly relating the urine osmolality to the hydra-
tion state.28,29
SUBJECTIVE MEASUREMENT OF FLUID STATUS
Another potentially clinically useful measure of dehydra-
tion is the perception of thirst. In healthy individuals with
induced dehydration, thirst occurs with a rise in extracellular
fluid osmolality.30 Vasopressin release is seen at plasma os-
molalities of about 280 mOsm/kg of H2O, and thirst is felt at
about 290 mg/kg of H2O.
Rolls and colleagues31 evaluated the utility of a visual
analog scale for the measurement of thirst. They correlated
the subjective findings with serial measurements of various
laboratory parameters, including plasma sodium and plasma
osmolality (the scales used are in Table 4).31 In this study,
patients went without fluids for 24 hours and then had un-
limited access to water. Serum parameters and subjective
ratings were followed regularly. The serum osmolality corre-
lated well with the reports of the first four questions in Table
4 and inversely with the last question. Similar results were
obtained when the serum osmolality was increased using hy-
THE JOURNAL OF SUPPORTIVE ONCOLOGY

pertonic saline.32 Therefore, this rating scale is one of the few
truly validated subjective tools for measuring hydration and
may be a useful adjunct to objective measures.
Hypovolemia
SIGNS AND SYMPTOMS
McGee et al33 reviewed the literature to determine the reli-
ability of commonly used signs of hypovolemia, including a
dry mouth, dry axilla, capillary refill time, skin turgor, dizziness
on standing, systolic blood pressure fall on standing, increased
pulse on standing, and tachycardia. Of this group, the only
sensitive and specific signs were an inability to stand for the
vital signs and an increase in pulse of at least 30 beats per
minute on standing. McGee et al also emphasized that the
patient should be supine for at least 1 minute before taking the
vitals and should stand for at least 2 minutes. Patients present-
ing with hypovolemia due to severe blood loss may not show
these symptoms. The authors recommended the measurement
of serum electrolyte levels, serum BUN levels, and creatinine
levels for increased sensitivity.
LABORATORY FINDINGS
Most signs and symptoms of hypovolemia reflect the in-
ability of the body to compensate for the loss of intravascular
volume. As stated, thirst is generally felt when total body
fluid volume decreases by 0.5%–1.0%.8 However, the elderly
may have decreased sensitivity to volume depletion and re-
duced thirst.34–36
Shirreffs37 reviewed markers of volume loss from the ex-
tracellular compartment. In the acute setting, such as after
strenuous exercise, weight loss can be interpreted as reflecting
water and volume loss. This finding is less likely to be true
in the subacute and chronic changes seen among oncology
patients, although weight loss with severe vomiting or uncon-
trollable diarrhea may reflect volume loss.
The BUN level can be a marker for dehydration, but may
also be elevated for other reasons, such as blood loss within
the gastrointestinal tract or rhabdomyolysis. Sepsis, vaso-
motor nephropathy, and urinary outlet obstruction can also
cause a high BUN level.38 A study in children with acute
gastroenteritis showed that the combination of high BUN
and low bicarbonate levels best predicted fluid deficit.39
However, the utility of the bicarbonate may be related to
the secretory diarrhea of these patients, in which there will
be gastrointestinal loss of bicarbonate. This paper also high-
lights the confusion in the literature between dehydration
and volume loss. One conclusion by the authors is: “Serum
sodium did not have any significant association with the
degree of dehydration….” Because dehydration is, by defi-
nition, a hypernatremic state, this conclusion is incorrect.
Rather, the volume depletion did not correlate with the se-
rum sodium level.
In a study of athletes inducing a rapid weight loss by
strenuous activity, a 5% weight loss correlated with elevated
VOLUME 4, NUMBER 9 ■ OCTOBER 2006
Berk and Rana
serum and urine osmolality,40 a state that quickly reversed
with rehydration. The authors found that the serum osmo-
lality was a more sensitive marker than the urinary indices.
They concluded that as a field test for athletes undergoing
intense exercise, a weight loss of at least 5% and a urine os-
molality of at least 500 mOsm/kg or a urine-specific grav-
ity of at least 1.020 are reasonable markers for hypovolemia.
However, the urine-specific gravity and osmolality were not
sensitive markers by themselves.
Dehydration
SIGNS AND SYMPTOMS
The signs and symptoms of dehydration are secondary to
intracellular water loss caused by extracellular fluid hypernatre-
mia. To reduce the osmotic pressure in the extracellular com-
partment, water is transferred out of the intracellular compart-
ment. Again, one must note that dehydration is not analogous
to hypovolemia. They can have different signs and symptoms.
Common signs and symptoms of hypernatremia are anorexia,
nausea, vomiting, fatigue, and irritability. Physical findings may
include lethargy, confusion, stupor, coma, muscle twitching, hy-
perreflexia, spasticity, tremor, ataxia, or focal findings such as
hemiparesis or extensor plantar reflexes (Babinski’s reflex).41
LABORATORY FINDINGS
The unifying feature of all patients with hypernatremia
is that the serum sodium level is higher than 145 mEq/L. A
patient cannot have hypernatremia if the sodium level is not
elevated. However, the extracellular fluid in a hypernatremic
patient can be hypervolemic, euvolemic, or hypovolemic. No
laboratory test will definitively determine the patient’s state;
however, an elevated BUN level or a high urine osmolality (or
specific gravity) may reflect hypovolemia.
Clinical Effects
PERFORMANCE
Due to a decrease in renal perfusion during hypovolemia,
the juxtaglomerular apparatus increases the release of renin.42
This effect will increase the production of angiotensin I, which
is converted to angiotensin II via the angiotensin-converting
enzyme. Angiotensin II will cause an increase in vasoconstric-
tion to shunt blood to the central nervous system and heart
(therefore increasing blood pressure), leading to a decrease in
cutaneous blood flow. Angiotensin II will also stimulate the
release of aldosterone and vasopressin, both of which increase
water (and sodium) reabsorption from the distal tubule. An
increase in plasma osmolality as detected by chemoreceptors
can also cause the release of renin and vasopressin. Thus, the
body attempts to conserve fluid to increase blood pressure and
decrease plasma osmolality.42
In response to hypovolemia, the heart will have a decreased
stroke volume, which in turn lowers the cardiac output. The
aortic arch and carotid artery baroreceptors will detect the low-
www.SupportiveOncology.net 451
Hypovolemia and Dehydration in the Oncology Patient

nitive function with dehydration.49–52 The most likely popu-

Table 5 lation to experience dehydration is the elderly. Suhr et al49
Electrolyte Content in 8 oz (240 mL) determined hydration status of older (> 50 years) adults and
Per Product Labels tested cognitive function as related to hydration status. Hy-
PRODUCT SODIUM (mg) POTASSIUM (mg) dration status was expressed as percent total body water di-
Apple juice 18 240 vided by weight. After controlling for age and systolic blood
Boost (vanilla) 130 400 pressure, investigators found that those who were less hydrat-
Boost Plus (vanilla) 170 380 ed performed more slowly on several measures of psychomo-
Coca-Cola 30 NL tor processing speed and more poorly on attention/memory
Ensure (vanilla) 200 370 tasks.51,52 However, hydration status was not clinically as-
Ensure Plus (vanilla) 240 440 sessed in these investigations.
Gatorade (fruit punch) 110 30 Studies performed on younger subjects who were dehydrat-
Orange juice (Minute Maid) 8 240 ed by passive heating and exercise have shown various decreas-
Pedialyte 11 5 es in cognitive performance, including a decrease in tracking
Pepsi 25 NL tasks, a decrease in perceptual comparison performance, a de-
Powerade (fruit punch) 55 30 crease in short-term memory, an increase in decision time, and
Sprite 15 NL a possible decrease in long-term memory. Regarding long-term
Abbreviation: NL = not listed memory, it seems that fluid replacement and hyperhydration
both prevented the decline in long-term memory, since the
er cardiac output and will cause an increase in sympathetic ner- control condition (no dehydration but no fluid replacement)
vous system activity, heart rate, and heart contractility, as well also had a decrease in long-term memory performance.51,52
as suppression of atrial natriuretic peptide. As the body tries Hydration status also has the potential to affect subjective
to conserve fluid via the effects of aldosterone and vasopres- feelings. For example, Shirreffs et al50 compared subjects who
sin, there will be a reduction in sweating and cutaneous blood had a restricted fluid intake for 37 hours with those in a euhy-
flow,43 which may increase the core temperature during times of drated state. The subjects in the fluid restriction condition re-
increased physical activity. The elevated core temperature can ported increased feelings of headache and fatigue, decreased
impair work capacity and physiologic function. For example, levels of alertness, and greater difficulty concentrating. Cian
Craig and Cummings44 assessed body mass changes due to re- et al51 found that subjects dehydrated via exercise had in-
striction of water intake and found that with a decrease of 4.3% creased fatigue. In a second investigation, they found that
of body mass, walking endurance decreased by 48%; however, subjects had increased levels of tiredness as compared with a
with only a 1.9% decrease in body mass (condition of no fluid control condition whether they were dehydrated through pas-
restriction), there was still a 22% decrease in walking endur- sive heating or exercise; however, when dehydrated passively,
ance.44 It has also been shown that core temperature and heart the subjects experienced less tiredness than did those in the
rate increase in proportion to the amount of dehydration that exercise conditions.52 The authors also found that rehydrating
occurs during exercise45 and that fluid intake during prolonged after dehydration produced less fatigue.
endurance exercise (> 2 h) reduces hyperthermia.46 Thirst is another subjective measure of interest since it in-
In addition to impaired cardiovascular performance, there dicates to a patient when to replace fluids. However, when
is some initial evidence that a decrease in intracellular water subjects are fluid-restricted for 37 hours, thirst will increase
content will increase proteolysis.47 Although further study is at 13 hours after the restriction began but will not differ from
warranted, an increase in protein breakdown due to dehydra- the level of thirst at 37 hours.50 This finding indicates that the
tion could lead to muscle atrophy, and thus a decrease in criti- feeling of thirst may not a reliable indicator of hydration status
cal muscular function, especially for clinical populations that during chronic fluid restriction.
may suffer from dehydration.
Treatment
COGNITIVE EFFECTS
HYPOVOLEMIA
Severe dehydration affects cognitive function primarily
through cerebral hypoperfusion due to hypovolemia.48 Ac- Hypovolemia can be hypernatremic, hyponatremic, or
cording to the model put forth by Wilson and Morley,48 the isotonic, and therefore, the optimal treatment may differ de-
clinical consequences resulting from varying degrees of dehy- pending on clinical findings.40 Treatment is oral or intravenous
dration include 1) anxiety, panic attacks, and agitation (with depending on the severity of the condition.
persistent subclinical dehydration); 2) hallucinations, delu- Knowledge of a patient’s baseline weight is helpful in cases
sions, and inattention (with fluctuating levels of tissue dehy- of mild volume depletion. When a baseline weight is avail-
dration); and 3) somnolence, unconsciousness, and psychosis able, fluid should be replaced based on weight loss, with 100
(with progressive, untreated dehydration). mL/0.1 kg weight loss.53 For example, if a patient loses 0.5 kg
Indeed, controlled studies have shown decreases in cog- in body mass, 500 mL of fluid should be consumed. This infor-

452 www.SupportiveOncology.net THE JOURNAL OF SUPPORTIVE ONCOLOGY


mation is based on recommendations for athletic populations
in which fluid loss occurs mainly via sweat and urine, and
the clinical measures are not known54; in this population, the
fluid replaced is recommended to have approximately 60 g of
carbohydrate per liter of water to maintain performance and
prevent fatigue during practice or competition. Carbohydrate
concentrations higher than 8% slow fluid absorption into the
body. A small amount of sodium (0.3–0.7 g/L) may also be
added to rehydration solutions to enhance fluid retention and
possibly prevent hyponatremia in those who are susceptible.
Interestingly, even when exercise is not involved, oral rehy-
dration solutions that were developed mainly to treat diarrhea
also contain glucose and electrolytes.55 These solutions were
developed based on the fact that the intestinal epithelium pas-
sively absorbs water, which follows active transport of electro-
lytes; in turn, glucose stimulates electrolyte absorption due to
coupled intestinal transport.
Choosing an appropriate beverage may depend on the type
of hypovolemia. If the patient suffers from hyponatremic hy-
povolemia, beverages with higher sodium content and lower
carbohydrate content may be the best choice (such as Gato-
rade, which has 4% carbohydrate and 0.45 g/L). If the patient
suffers from hypernatremic hypovolemia, beverages with a
lower sodium content and higher carbohydrate content may
be appropriate (such as apple juice, which contains 11% car-
bohydrate and 0.07 g/L of sodium, or colas, which contain ap-
proximately 10% carbohydrate and 0.10 g/L of sodium). The
sodium and potassium contents of common replenishment
beverages are listed in Table 5. Water by itself may not always
be the best option to replace lost fluid because it decreases
osmolality and therefore the sensation of thirst.54
When oral treatment is not possible, patients may be treat-
ed intravenously. For hyponatremic hypovolemia, the patient
should be restricted from drinking free water and should in-
crease salt intake.42 However, even though water restriction
will improve all forms of hyponatremia, the sodium deficit
must be corrected if the extracellular-fluid volume is deplet-
ed.56 When hypovolemic hyponatremia is severe (serum sodi-
um level < 120 mEq/L), treatment should be immediate, with
the primary goal to raise serum sodium levels, and the second
goal aimed toward long-term correction.42 Serum sodium lev-
els should not be increased higher than 125 mEq/L over a 6-
hour period with hypertonic (3%–5%) saline to prevent dam-
age to the central nervous system.42 For long-term correction,
free water should be restricted and salt intake increased.
During hypernatremic hypovolemia, it is necessary for cli-
nicians to treat the underlying cause and distinguish between
hypovolemia and dehydration. The sodium content of medica-
tions should be minimized, and free water should be consumed,
Peer viewpoints on this article by Dr. Jean L. Holley and Dr. Tatsuya Morita appear on page 455 and page 456.
VOLUME 4, NUMBER 9 ■ OCTOBER 2006
Berk and Rana
if possible. Again, rapid correction of the condition is danger-
ous due to swelling that could occur in the central nervous
system. Sarhill et al42 suggested the following steps to correct
hypernatremic hypovolemia: 1) Calculate the water deficit;
2) Calculate the daily requirement of water; 3) Calculate the
daily sodium requirement; 4) Give half the calculated water
deficit and calculated water requirement along with the calcu-
lated daily sodium requirement in the first 24 hours; 5) Once
adequate urine output occurs, add potassium to the solution.
DEHYDRATION
Dehydration is always hypernatremic but not always hy-
povolemic and is usually due to free water loss. If sodium is
infused isotonically, water does not shift from the intracellular
to the extracellular compartments but there will be increased
fluid volume. If sodium is added hypotonically to the serum
levels, the intracellular volume increases. Since dehydra-
tion indicates that the serum sodium levels are high, isotonic
(normal) saline can be used to increase the intracellular vol-
ume. This process is done over several days to prevent abrupt
changes in brain cell volume. In emergencies (usually when
the water deficit is greater than the electrolyte deficit), half-
isotonic saline can be infused.42
As with hypovolemia, the underlying cause should be cor-
rected and fluid replacement should occur enterally, if pos-
sible, with low-sodium beverages.57 Patients with hypernatre-
mia present for more than a few hours should be corrected
slowly to avoid cerebral edema. A reasonable goal is to lower
the serum sodium concentration by 0.5 mmol/L/h or about 10
mmol/L/d.57 Inappropriate treatment of dehydration can lead
to death, and treatment of dehydration should be handled by
experienced physicians.
Conclusion
The term dehydration is often used incorrectly by oncolo-
gists. Dehydration is always accompanied by hypernatremia
and is characterized by intracellular volume loss secondary
to extracellular hyperosmolality. The more common clinical
situation is hypovolemia, which can be hyponatremic, hyper-
natremic, or eunatremic. The correct characterization of the
clinical condition is paramount before determining the ap-
propriate treatment of the patient. Hypovolemia is treated by
rehydration with the appropriate sodium-containing solution,
whereas hypernatremia is treated with a sodium-depleted so-
lution. Confusing hyponatremic hypovolemia with dehydra-
tion may harm the patient by inducing further hyponatremia.
Appropriate clinical evaluation of signs and symptoms, as well
as laboratory testing, will allow rapid diagnosis and appropri-
ate treatment.
www.SupportiveOncology.net 453
Hypovolemia and Dehydration in the Oncology Patient
References
1. Mange K, Matsuura D, Cizman B, et al. Language
guiding therapy: the case of dehydration versus vol-
ume depletion. Ann Intern Med 1997;127:848–853.
2. National Cancer Institute. Common Terminology
Criteria for Adverse Events v3.0 (CTCAE). December
12, 2003. Available at: http://ctep.cancer.gov/forms/
CTCAEv3.pdf. Accessed April 26, 2006.
3. Institute of Medicine. Dietary Reference Intakes
for Water, Potassium, Sodium, Chloride and Sulfate.
Washington, DC: National Academies Press; 2005.
4. Altman PL, Dittmer DS. Blood and Other Body
Fluids. Washington, DC: Federation of American
Societies for Experimental Biology; 1961.
5. Panel on Dietary Reference Intakes for
Electrolytes and Water: Standing Committee on the
Scientific Evaluation of Dietary Reference Intakes.
Water. Dietary Reference Intakes for Water, Potassium,
Sodium, Chloride and Sulfate. Washington, DC:
National Academies Press; 2004:73–185.
6. Blumenfeld JD, Vaughan ED Jr. Renal physiol-
ogy and pathophysiology. In: Walsh P, ed. Campbell’s
Urology. 8th ed. Philadelphia, Pa: W.B. Saunders;
2002:167–227.
7. Sawka MN, Cheuvront SN, Carter R 3rd. Human
water needs. Nutr Rev 2005;63:S30–S39.
8. Arsenault J. SparkNotes: Major Minerals–Water
and Electrolytes. October 2005. Available at: http://
www.sparknotes.com/health/minerals/major/sec-
tion1.html. Accessed April 26, 2006.
9. Mader SS. Inquiry Into Life. 10th ed. Hightstown,
NJ: McGraw-Hill Science/Engineering/Math; 2002.
10. Navar LG. Regulation of renal hemodynamics.
Advan Physiol Edu 1998;275:221S–235S.
11. Knepper MA, Gamb G. Urine concentration
and dilution. In: Brenner BM, ed. Brenner & Rector’s
The Kidney. 7th ed. Philadelphia, Pa: W. B. Saunders;
2004:599ff.
12. Hoffman RS, Smilkstein MJ, Howland MA,
Goldfrank LR. Osmol gaps revisited: normal values and
limitations. J Toxicol Clin Toxicol 1993;31:81–93.
13. Fall PJ. Hyponatremia and hypernatremia: a
systematic approach to causes and their correction.
Postgrad Med 2000;107:75–82.
14. Palevsky PM, Bhagrath R, Greenberg A.
Hypernatremia in hospitalized patients. Ann Intern
Med 1996;124:197–203.
15. Altman PL, Dittmer DS. Blood and Other Body
Fluids. Washington, DC: Federation of American
Societies for Experimental Biology; 1961.
16. Sandle GI. Pathogenesis of diarrhea in ulcer-
ative colitis: new views on an old problem. J Clin
Gastroenterol 2005;39:S49–S52.
17. Classen J, Belka C, Paulsen F, et al. Radiation-in-
duced gastrointestinal toxicity: pathophysiology, ap-
proaches to treatment and prophylaxis. Strahlenther
Onkol 1998;174(suppl 3):82–84.
18. Dublineau I, Ksas B, Griffiths NM. Functional
changes in the rat distal colon after whole-body ir-
radiation: dose-response and temporal relationships.
Radiat Res 2000;154:187–195.
19. Dublineau I, Ksas B, Aigueperse J, Gourmelon P,
Griffiths NM. In vivo alterations of fluid and electrolyte
fluxes in rat colon by gamma irradiation. Dig Dis Sci
1998;43:652–662.
20. Saliba F, Hagipantelli R, Misset JL, et al.
454 www.SupportiveOncology.net
Pathophysiology and therapy of irinotecan-induced
delayed-onset diarrhea in patients with advanced
colorectal cancer: a prospective assessment. J Clin
Oncol 1998;16:2745–2751.
21. Hughes S, Higgs NB, Turnberg LA. Loperamide
has antisecretory activity in the human jejunum in
vivo. Gut 1984;25:931–935.
22. Burleigh DE. Loperamide but not morphine has
anti-secretory effects in human colon, in vitro. Eur J
Pharmacol 1991;202:277–280.
23. Redel CA. Anatomy, histology, embryology,
and developmental anomalies of the stomach and
duodenum. Feldman M, Friedman LS, Sleisenger
MH, eds. Sleisenger & Fordtran’s Gastrointestinal and
Liver Disease. 7th ed. Philadelphia, Pa: W. B. Saunders;
2002:675–855.
24. Armstrong LE. Hydration assessment tech-
niques. Nutr Rev 2005;63:S40–S54.
25. Vaisman N, Pencharz PB, Koren G, Johnson JK.
Comparison of oral and intravenous administration
of sodium bromide for extracellular water measure-
ments. Am J Clin Nutr 1987;46:1–4.
26. Armstrong LE, Kenefick RW, Castellani JW, et
al. Bioimpedance spectroscopy technique: intra-,
extracellular, and total body water. Med Sci Sports
Exerc 1997;29:1657–1663.
27. Vialet R, Leone M, Albanese J, Martin C.
Calculated serum osmolality can lead to a systematic
bias compared to direct measurement. J Neurosurg
Anesthesiol 2005;17:106–109.
28. Armstrong LE, Soto JA, Hacker FT Jr, et al.
Urinary indices during dehydration, exercise, and
rehydration. Int J Sport Nutr 1998;8:345–355.
29. Armstrong LE, Maresh CM, Castellani JW, et al.
Urinary indices of hydration status. Int J Sport Nutr
1994;4:265–279.
30. Bouby N, Fernandes S. Mild dehydration, vaso-
pressin and the kidney: animal and human studies. Eur
J Clin Nutr 2003;57(suppl 2):S39–S46.
31. Rolls BJ, Wood RJ, Rolls ET, et al.Thirst following
water deprivation in humans. Am J Physiol 1980;239:
R476–R482.
32. Phillips PA, Rolls BJ, Ledingham JG, Forsling ML,
Morton JJ. Osmotic thirst and vasopressin release in
humans: a double-blind crossover study. Am J Physiol
1985;248:R645–R650.
33. McGee S, Abernethy WB 3rd, Simel DL. The
rational clinical examination: is this patient hypovo-
lemic? JAMA 1999;281:1022–1029.
34. Kenney WL, Chiu P. Influence of age on thirst
and fluid intake. Med Sci Sports Exerc 2001;33:1524–
1532.
35. Phillips PA, Bretherton M, Johnston CI, Gray L.
Reduced osmotic thirst in healthy elderly men. Am J
Physiol 1991;261:R166–R171.
36. Phillips PA, Rolls BJ, Ledingham JG, et al.
Reduced thirst after water deprivation in healthy
elderly men. N Engl J Med 1984;311:753–759.
37. Shirreffs SM. Markers of hydration status. Eur J
Clin Nutr 2003;57(suppl 2):S6–S9.
38. Robinson BE, Weber H. Dehydration despite
drinking: beyond the BUN/creatinine ratio. J Am Med
Dir Assoc 2004;5:S67–S71.
39. Yilmaz K, Karabocuoglu M, Citak A, Uzel N.
Evaluation of laboratory tests in dehydrated children
with acute gastroenteritis. J Paediatr Child Health
2002;38:226–228.
40. Oppliger RA, Magnes SA, Popowski LA, Gisolfi
CV. Accuracy of urine specific gravity and osmolality
as indicators of hydration status. Int J Sport Nutr Exerc
Metab 2005;15:236–251.
41. Gibbs MA, Wolfson AB, Tayal VS. Electrolyte dis-
turbances. In: Marx JA. Rosen’s Emergency Medicine.
5th ed. St. Louis, Mo: Mosby; 2002.
42. Sarhill N, Walsh D, Nelson K, Davis M. Evaluation
and treatment of cancer-related fluid deficits: volume
depletion and dehydration. Support Care Cancer
2001;9:408–419.
43. McArdle WD, Katch FL, Katch VL. Exercise
Physiology: Energy, Nutrition and Human Performance.
5th ed. Baltimore, Md: Lippincott, Williams & Wilkins;
2001.
44. Craig EN, Cummings EG. Dehydration and
muscular work. J Appl Physiol 1966;21:670–674.
45. Montain SJ, Coyle EF. Influence of graded
dehydration on hyperthermia and cardiovascular
drift during exercise. J Appl Physiol 1992;73:1340–
1350.
46. Montain SJ, Coyle EF. Fluid ingestion dur-
ing exercise increases skin blood flow indepen-
dent of increases in blood volume. J Appl Physiol
1992;73:903–910.
47. Ritz P, Salle A, Simard G, et al. Effects of changes
in water compartments on physiology and metabo-
lism. Eur J Clin Nutr 2003;57(suppl 2):S2–S5.
48. Wilson MM, Morley JE. Impaired cognitive func-
tion and mental performance in mild dehydration. Eur
J Clin Nutr 2003;57(suppl 2):S24–S29.
49. Suhr JA, Hall J, Patterson SM, Niinisto RT. The
relation of hydration status to cognitive perfor-
mance in healthy older adults. Int J Psychophysiol
2004;53:121–125.
50. Shirreffs SM, Merson SJ, Fraser SM, Archer
DT. The effects of fluid restriction on hydration
status and subjective feelings in man. Br J Nutr
2004;91:951–958.
51. Cian C, Koulmann N, Barraud PA, et al. Influences
of variations in body hydration on cognitive func-
tion: effect of hyperhydration, heat stress, and ex-
ercise-induced dehydration. J Psychophysiology
2000;14:29–36.
52. Cian C, Barraud PA, Melin B, Raphel C. Effects of
fluid ingestion on cognitive function after heat stress
or exercise-induced dehydration. Int J Psychophysiol
2001;42:243–251.
53. Baechle TR, Earle RW. Essentials of Strength
Training and Conditioning. 2nd ed. Champaign, Ill:
Human Kinetics Publishers; 2000.
54. Casa DJ, Armstrong LE, Hillman SK, et al.
National Athletic Trainers’ Association position
statement: fluid replacement for athletes. J Athl Train
2000;35:212–224.
55. Desjeux JF, Briend A, Butzner JD. Oral rehydra-
tion solution in the year 2000: pathophysiology, ef-
ficacy and effectiveness. Baillieres Clin Gastroenterol
1997;11:509–527.
56. Adrogue HJ, Madias NE. Hyponatremia. N Engl
J Med 2000;342:1581–1589.
57. Adrogue HJ, Madias NE. Hypernatremia. N Engl
J Med 2000;342:1493–1499.
THE JOURNAL OF SUPPORTIVE ONCOLOGY