American Journal of Therapeutics 0, 1–6 (2017)
Intravenous Fluid Therapy in Hospitalized Patients
Pramod Reddy, MD*
INTRODUCTION
Blood is a complex fluid composed of plasma (water,
proteins, and electrolytes) and formed elements (red
blood cells, white blood cells, and platelets). Blood
uniquely represents both the intracellular compart-
ment (the fluid inside the blood cells) and the extracel-
lular compartment (the plasma). The volume of blood
in the blood vessels in an average human adult is
about 5 L. Venous circulation makes up 85% of the
total blood volume and arterial circulation accounts
for the rest. The arterial blood perfuses all the tissues
through the capillary network embedded in a colla-
gen-rich interstitium. Interstitial fluid has access to
the lymphatic vasculature for the subsequent venous
return. On average, a person has approximately 10 L
of interstitial fluid providing the cells of the body with
nutrients.
Because the arterial blood perfuses all the vital tis-
sues, it is also referred to as the effective circulating
volume or effective arterial blood volume (EABV).
Normal EABV depends on several factors like fluid
intake versus losses, cardiac output, hydrostatic pres-
sure, peripheral vascular resistance, and the oncotic
pressure. In patients with decreased EABV, renal
sodium and water retention occur as a compensatory
mechanism to maintain arterial perfusion to the vital
organs. Kidneys only respond to the changes in EABV,
irrespective of the venous circulation overload (eg,
edema). Hydrostatic pressure is generated by the sys-
tolic force of the heart, which pushes fluid out of the
capillaries. Albumin accounts for ;80% of the oncotic
pressure, which drives fluid back into the vessels.
Albumin has a half-life of 17 days and a total body
turnover time of ;25 days. Most (;84%) of the albu-
min is removed by catabolism in the skin and muscle,
Division of General Internal Medicine, UF Health Jacksonville,
Jacksonville, FL.
The author has no conflicts of interest to declare.
*Address for correspondence: 653-1 West Eight St, 3rd Floor
Faculty Clinic, Jacksonville, FL 32209. E-mail: pramod.reddy@
jax.ufl.edu
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and the combined renal and gastrointestinal losses
account to less than 6%.1
Each day ;5 L of fluid are secreted by the pancreas,
gallbladder, stomach, and bowel into the lumen of the
gastrointestinal tract and only 100–200 mL are lost in
the stool. Volume depletion results from poor oral
intake and loss of sodium and water from the gastro-
intestinal tract (eg, vomiting and diarrhea), kidneys,
and skin. Volume depletion can also occur through
the loss of fluid into a third space that is not in equi-
librium with the extracellular fluid (eg, fractured hip,
intestinal obstruction, severe pancreatitis, peritonitis,
and crush injuries).
Shock is defined by circulatory failure due to
decreased EABV, manifesting as hypotension, and
decreased urine output. Etiology of shock can be mul-
tifactorial but most causes are due to either decreased
EABV (eg, hypovolemia, decreased cardiac output) or
excessive vasodilation out of proportion to the cardiac
output (eg, sepsis, anaphylaxis). In patients with
shock, rapid volume repletion is indicated because de-
layed therapy can lead to multiorgan system failure. It
is a common practice to administer resuscitative fluids
to shock patients in boluses ranging from 1 to 2 L in
the form of crystalloids (eg, 0.9% saline) or colloids (eg,
albumin).
CLINICALLY AVAILABLE
INTRAVENOUS FLUID
PREPARATIONS
Crystalloids
Isotonic crystalloids have a 25% intravascular and 75%
interstitium distribution and are effective in treating
hypovolemia and shock. Physicians should choose
between the available crystalloids based on concurrent
abnormalities in serum sodium, chloride, and bicar-
bonate. Chloride liberal isotonic crystalloids (0.9%
saline) have a sodium concentration of 154 mEq/L,
but 1.5 times the normal serum concentration of chlo-
ride (154 mEq/L), which makes it ideal to treat pa-
tients with hypochloremic metabolic alkalosis (eg,
vomiting and loop diuretic overuse). When 0.9% saline
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 2 Reddy
is given in large volumes for resuscitation, it can lead
to hyperchloremic metabolic acidosis. Saline (0.45%)
has 500 mL of free water and is the ideal solution to
treat dehydrated patients with hypernatremia and
concomitant acute kidney injury (AKI). Chloride
restrictive crystalloids (Ringer lactate) contain 28
mEq/L of lactate which metabolizes in the liver to
generate bicarbonate. They are best used to treat con-
ditions with hyperchloremic metabolic acidosis (eg,
diarrhea).2,3
Colloids
Albumin solutions are typically available either as iso-
oncotic (4% or 5%) or as hyperoncotic (20%–25%) sol-
utions. Four percentage and 24% albumin solutions are
not readily available in the United States. Hyperon-
cotic albumin is sometimes called “salt poor albumin”
when the Na concentration is reduced at 130 mmol/L.
Binding sites for drugs are usually lost in the produc-
tion process of human albumin solutions. Albumin
solutions are considerably more expensive when com-
pared with crystalloids. Hospital cost for a 12.5 gram
vial of 25% albumin is ;$60 when compared with the
crystalloids (;$1). Typically, 5–10 times the value will
be charged to the patient to cover various administra-
tive costs, so the final cost of a daily dose of albumin (1
g/kg of body weight) may exceed $1000 in hospital-
ized patients.
Mechanism of action
Colloids tend to draw the fluid from the interstitial
spaces of the body. When 25% albumin is injected, it
will draw additional 3 times the fluid from the inter-
stitial spaces into the circulation in adequately
hydrated patients. For example, a 100 cc infusion of
25% albumin solution theoretically could be the equiv-
alent of a 300 cc bolus of 0.9% saline (1:3 ratio). But
larger studies (Saline versus Albumin Fluid Evaluation
study) observed a ratio of 1:1.4, so it should no longer
be considered the determining factor. In general, 4%–
5% albumin is used to treat shock states associated
mainly with a volume deficit, and 20%–25% albumin
is used in edematous patients with hypoalbuminemia
(oncotic deficit) to maintain the effective intravascular
volume (Table 1).
Four to five percent albumin mortality benefits
So far, randomized control studies of 4%–5% albumin
(Saline versus Albumin Fluid Evaluation and Colloids
Versus Crystalloids for the Resuscitation of the Criti-
cally Ill) reveal no mortality benefits when compared
with crystalloids, and increased rate of death was
American Journal of Therapeutics (2017) 0(0)
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observed in patients with traumatic brain injury4–7
(Table 2).
Twenty to twenty-five percent albumin mortality benefits
Twenty to twenty-five percent albumin has the most
proven use in patients with decompensated liver fail-
ure (Table 1), but it has also been studied in other
disease states with possible benefits.8–13 In noncirrhotic
patients, several randomized trials of intravenous albu-
min (Colloids Versus Crystalloids for the Resuscitation
of the Critically Ill, Early Albumin Resuscitation Dur-
ing Septic Shock, and Albumin Italian Outcome Sepsis
[ALBIOS]) have been performed. All the trials except
ALBIOS recruited both hypovolemic and septic shock
patients, and several subset analysis studies were con-
ducted in septic patients (Table 2). A 28- and 90-day
mortality reduction was observed in subset analysis
of patients with severe sepsis and septic shock (Table 2).
It is reasonable to use 20%–25% albumin during the
first few days of intensive care unit stay in selective
hypoalbuminemic critically ill septic patients. Of all
the studies to date, only ALBIOS study maintained
a serum albumin level of .3 g/dL with albumin
infusion.
COMMON LABORATORY
DERANGEMENTS IN ACUTELY ILL
PATIENTS
Hypoalbuminemia
Despite the long serum, half-life serum albumin levels
tend to drop rapidly (;1–1.5 g/dL during 3–7 days) in
critically ill patients (sepsis, trauma, or mental strain),
most likely from redistribution and increased catabo-
lism.14 Sepsis is known to increase the capillary perme-
ability of albumin by 13-fold, and the hepatic albumin
synthesis is suppressed by the inflammatory cytokines
(eg, interleukin 6 and tumor necrosis factor–a).
Hypoalbuminemia may worsen the edema, pulmo-
nary congestion, and pleural effusions by causing intra-
vascular fluid shifts to the interstitial space.
Hypoalbuminemia also falsely lowers the serum calcium
levels and anion gap, which should be corrected before
interpretation. For every 1 gram decrease in serum albu-
min, calcium level decreases by 0.8 mg/dL and anion
gap decreases by 2.5 mEq/L. Hypoalbuminemia in-
creases the free serum levels of several drugs, but the
unbound fraction of the drug is rapidly cleared from the
intravascular space resulting in no toxic tissue effects.
Acute hypoalbuminemia in ill patients may persist
despite adequate protein calorie nutrition until pa-
tients are clinically improved. Serum albumin levels
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IVF and Albumin 3

Table 1. Clinical uses of 25% albumin.

Condition Dosing of albumin Comments

Large volume 20%–25% albumin at a dose of 8–10 g for Albumin significantly reduces the incidence
paracentesis (.5 L) every liter of ascitic fluid removed. of postparacentesis circulatory
dysfunction, hyponatremia, and mortality.
In patients with SBP to 20%–25% albumin at a dose of 1.5 g/kg of Renal failure develops in 30%–40% of
prevent renal failure body weight at the time of diagnosis, patients with SBP and is a major cause of
followed by 1 g/kg of body weight on day 3. death. Albumin use significantly decreases
the risk of AKI (33% in antibiotic only group
vs. 10% in albumin + antibiotics group) and
3-month mortality (41% vs. 22%).
Treatment of type 1 HRS 20%–25% albumin at a dose of 1 g/kg of body Use albumin with other vasoconstrictors
weight on day 1, followed by 20–40 g/d. (octreotide/terlipressin and midodrine).
HRS reversal seen in 77% of patients
receiving vasoconstrictor and albumin
compared with only 25% of those receiving
vasoconstrictor alone.
Critically ill patients with 20%–25% albumin Albumin use has been shown to improve
cirrhosis (high circulatory dysfunction and survival in
mortality rates of patients with cirrhosis. Prospective
;30%) randomized studies are needed before
using albumin as the primary resuscitative
fluid.
Critically ill patients with 20%–25% albumin at doses of 1.0 g/kg/d with Limit albumin use to the first few days of ICU
severe sepsis and a target serum albumin of 3 g/dL. stay.
septic shock
Improve organ function 20%–25% albumin at doses of 1.0 g/kg/d Organ function (respiratory, cardiovascular,
in critically ill patients and central nervous system) improved
more in the albumin than in the control
group. Mean fluid gain was almost 3 times
higher in the control group despite
identical diuretic use.
Hepatic encephalopathy 20%–25% albumin at doses of 1.5 g/kg at day Albumin use was associated with improved 3
1 and 1.0 g/kg at day 3. month survival, but without improvement
in hepatic encephalopathy symptoms.
Acute respiratory 20%–25% albumin. Addition of albumin therapy to loop diuretics
distress syndrome improves early oxygenation but without
(ARDS) a mortality benefit.
Treatment of refractory 20%–25% albumin. Infusion of the Lack of efficacy of infused albumin was
edema furosemide–albumin complex is thought to demonstrated in patients with mean serum
increase diuretic delivery to the kidney by albumin levels of ;3 g/dL. Patients with
keeping furosemide within the vascular severe hypoalbuminemia (,2 g/dL) may
space. have a benefit but need further studies.

HRS, hepatorenal syndrome; ICU, intensive care unit; SBP, spontaneous bacterial peritonitis.

in hospitalized patients are not a good measure of Hyponatremia

overall nutritional status. Hypoalbuminemia is known
to negatively impact mortality in medical and surgical
patients, but it is not the albumin concentration per se,
but the underlying pathologic condition that affects
the prognosis. Preadmission albumin levels should
be screened in critically ill patients before attempting
a work up of unexplained hypoalbuminemia.
Syndrome of inappropriate antidiuretic hormone
(SIADH) is the most common cause of hyponatremia
in hospitalized patients. Acutely ill patients have sev-
eral disease states (eg, pneumonia) associated with an
excess of ADH release. Other common physiological
stimuli for ADH secretion include pain, stress, nausea,
hypoxemia, and hypercapnia. Hyponatremia may

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 4 Reddy

Table 2. Large randomized control studies comparing colloids to crystalloids.

Study No. of patients Exclusion criteria Results Comments

SAFE study: 4% 6997 patients with Cardiac surgery, No significant difference The ratio of the volumes
albumin and 0.9% hypovolemia and liver transplant, with respect to the rate of albumin to the
saline sepsis. and burns. of death or the volumes of normal
development of new saline is 1:1.4.
organ failure at 28 days.
SAFE study Subset of 1218 Same Decrease in the adjusted Albumin was not
additional patients only with risk of death at 28 days administered to achieve
analysis severe sepsis (CI, 0.52–0.97). a particular serum
albumin concentration.
Most patients did not
attain a serum albumin
concentration of .3
g/dL.
SAFE study—post Subset of 460 Same Patients who received 4% May be due to the
hoc 2-year follow- patients only with albumin had increase in intracranial
up traumatic brain a significant increase in pressure within the first
injury the rate of death week after albumin
compared with the 0.9% therapy.
saline (CI 1.17–2.26).
CRISTAL study: 4% 2857 patients with Chronic liver and No difference in 28-day Of 1414 patients in the
and 20% albumin sepsis, trauma. or renal failure, mortality. Patients colloid group, 973
compared with hypovolemia. burns treated with colloids patients received
0.9% saline and had 1 more day free of hetastarch (69%), 494
Ringer lactate mechanical ventilation patients received
(13.5 vs. 14.6 days) and gelatins (35%), 201
vasopressor therapy received 20% albumin
(15.2 vs. 16.2 days), but (14%), and only 87 (6%)
a lower 90-d mortality received 4% albumin.
(31 vs. 34 percent).
EARSS study: 100 798 patients within Severe heart failure, No significant differences
mL of 20% 6 hrs of septic neutropenia, in 28-day mortality but
albumin versus shock (most with cirrhosis, primary a greater number of
100 mL of 0.9% hypoalbuminemia peritonitis, and catecholamine-free
saline Q8 hr 3 3 ;2 g/dL) severe burns. days in the albumin
days. group.
ALBIOS study: 20% 1818 patients with Cirrhosis, nephrotic No differences between An initial bolus of 300 mL
albumin plus severe sepsis and syndrome, both the groups for 28- 20% albumin was given
crystalloids or shock advanced heart d mortality rate. in the albumin group,
crystalloids alone. failure, and burns followed by a daily
administration of 20%
albumin from day 1
until day 28 to maintain
a serum albumin level
of at least 3 g/dL.
ALBIOS: subset 1121 patients only Same Significantly lower 90-d
analysis with septic shock mortality rate with
albumin treatment
compared with
crystalloid treatment
(CI, 0.77–0.99)

CI, confidence interval; CRISTAL, effects of fluid resuscitation with colloids versus crystalloids on mortality in critically ill patients
presenting with hypovolemic shock; EARSS, the efficacy and tolerance of hyperoncotic albumin administration in septic shock pa-
tients; SAFE, Saline versus Albumin Fluid Evaluation.

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IVF and Albumin
acutely develop in marathon runners who drink too
much water with inadequate sodium intake. Acute
symptomatic hyponatremia may also occur after tran-
surethral prostate resection syndrome and ecstasy use.
Hyponatremia should be considered chronic when
there are no previous laboratory values are available
or when persistent for more than 48 hours. Patients
with chronic hyponatremia are more prone to develop
osmotic demyelination syndrome and sodium
correction should be gradual not exceeding 10 mEq/L
per day.
Patients with mild hyponatremia are best treated
with free water restriction and avoiding free water
containing intravenous fluid (IVF) (eg, 0.45% saline
and D5W). Urine osmolality is relatively fixed in
SIADH and is helpful to guide the choice between
0.9% (154 mEq/L sodium and 308 osmolality) and
3% (513 mEq/L sodium and 1027 osmolality) saline
therapy. When urine osmolality exceeds the 0.9%
saline osmolality of 308, saline infusion may worsen
the hyponatremia.15 Because SIADH patients are eu-
volemic, the entire administered sodium is excreted in
the urine but the daily consumed water is retained
because of the persistent action of ADH. To prevent
this effect, sometimes loop diuretics are combined with
0.9% saline and they work by lowering the urine
osmolality through inhibition of ADH effect on collect-
ing tubule.16 Saline (3%) typically exceeds the average
urinary osmolality induced by SIADH and is able to
draw the excess free water into the urine. Small vol-
ume of 3% saline administered at low infusion rate is
recommended in the management of any symptomatic
hyponatremia while frequently monitoring the serum
sodium.
AKI
It is common to see AKI in critically ill patients from both
dehydration and acute tubular necrosis (ATN). Prerenal
azotemia resolves rapidly with 1–2 L of IVF therapy
unless ATN has developed. Indiscriminate use of IVF
may lead to fluid overload in many patients and should
be avoided. Ischemic ATN is due to prolonged dehydra-
tion, hypotension, and toxic ATN occurs from sepsis,
radiocontrast media, and adverse effect of medications.
It is common to see volume overloaded patients (edema
and hypoxia) with AKI, which further complicates the
choice of IVF therapy. One should not continue bolus
fluids till creatinine levels are normalized because the
resolution of renal injury is typically gradual in patients
with ATN. Patients may remain oliguric during ATN
and their total fluid intake should be restricted to the
amount of urine output and an additional 500 mL for
insensible losses. Patients with AKI should be carefully
monitored for signs of fluid overload.
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5
Sodium overload with IVF administration
Prolonged use of IVF results in retention of sodium
and water, frequently leading to fluid overload (eg,
edema and hypoxia). It is important to understand
the amount of sodium infused with resuscitative flu-
ids after converting sodium from mmol to mg/L.
Both 0.9% saline and albumin solutions contain
3.2–3.3 mg sodium per ml of solution (1 L 0.9% saline
has 3335 mg sodium). For example, a hospitalized
septic patient with pneumonia receives intravenous
0.9% saline 150 cc/h on day 1, followed by 125 cc/h
on days 2 and 3. Over a 72-hour period, he would
have received a total of 1478 mEq (34,000 mg) of
sodium.
CONCLUSIONS
IVF therapy in a dehydrated patient should be tailored
based on history, physical examination, and abnormal-
ities in serum urea, creatinine, sodium, chloride, and
bicarbonate. Crystalloids remain the choice of therapy
in hypovolemic patients. Although colloid solutions
theoretically should remain in the vascular space in
contrast to saline, most of the infused albumin is dis-
tributed into the extravascular space within 1–2 days.
Routine use of 20%–25% albumin as the fluid of choice
in edematous hypoalbuminemic patients should be
avoided. Administration of human albumin to
improve the transport capacity for drugs is not recom-
mended. Albumin (4%–5%) has no particular benefits
and can increase mortality in traumatic brain injury
patients. Albumin (20%–25%) is best used in the man-
agement of cirrhosis complications and may have
a mortality benefit in critically ill septic patients with
severe hypoalbuminemia.
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