18/02/2021 Treatment of severe hypovolemia or hypovolemic shock in adults - UpToDate

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Treatment of severe hypovolemia or hypovolemic shock in adults

Authors: Jess Mandel, MD, Paul M Palevsky, MD
Section Editors: Richard H Sterns, MD, Scott Manaker, MD, PhD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2021. | This topic last updated: Aug 29, 2019.

INTRODUCTION

Fluid resuscitation is the mainstay of therapy in patients with severe hypovolemia. Although no clear definition exists,
severe hypovolemia may be present when loss of blood or extracellular fluids results in decreased peripheral
perfusion. Hypovolemic shock is considered present when severe hypovolemia results in organ dysfunction as the
result of inadequate tissue perfusion. In patients with severe hypovolemia or hypovolemic shock, delayed fluid
therapy can lead to ischemic injury and irreversible shock with multiorgan system failure.

Treatment of severe hypovolemia and hypovolemic shock are discussed here. Etiologies, manifestations, and
diagnosis of volume depletion are discussed separately. (See "Etiology, clinical manifestations, and diagnosis of
volume depletion in adults".)

PRINCIPLES OF MANAGEMENT

Management of hypovolemia involves assessing and treating the underlying cause, identifying electrolyte and acid-
base disturbances, and assessing and treating the volume deficit, all of which influence the choice of fluid and rate at
which it should be administered.

Identify and treat the etiology — Clinicians should identify the etiology (or etiologies) contributing to hypovolemia
so that therapies can be directed at the underlying cause of volume loss. Potential etiologies of hypovolemia include
gastrointestinal, renal, skin, hemorrhage, and third-space losses. Therapies may include anti-emetics to treat
vomiting, cessation of diuretics, or controlling bleeding. Further details regarding etiology and diagnosis of
hypovolemia are discussed separately. (See "Etiology, clinical manifestations, and diagnosis of volume depletion in
adults".).

Identify electrolyte and acid-base disturbances — Biochemical analysis will alert the clinician to electrolyte (eg,
hypo- or hypernatremia, hypo- or hyperkalemia) and acid-base disturbances (eg, contraction alkalosis, metabolic
acidosis) which may affect choice of replacement fluid and rate of repletion. In some cases, an arterial blood gas may
be needed if mixed acid-base disturbance is suspected. (See "Overview of the treatment of hyponatremia in adults"
and "Treatment of hypernatremia in adults" and "Clinical manifestations and treatment of hypokalemia in adults" and
"Treatment and prevention of hyperkalemia in adults" and "Simple and mixed acid-base disorders" and "Potassium
balance in acid-base disorders".)

Assess the volume deficit — Clinical assessment involves estimating pre- and post-deficit body weight, if known, as
well as assessment of clinical and laboratory parameters including the blood pressure, jugular venous pressure, urine
sodium concentration, urine output, lactate, and, if bleeding has not occurred, the hematocrit. Ultrasonographic
assessment of collapse of the inferior vena cava on inspiration may be useful in some situations. Assessing volume
deficit is discussed separately. (See "Maintenance and replacement fluid therapy in adults", section on 'Volume deficit'
and "Novel tools for hemodynamic monitoring in critically ill patients with shock", section on 'Vena cava assessment'.)

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CHOICE OF REPLACEMENT FLUID

For patients with hypovolemic shock, the three major classes of replacement fluids are:

● Crystalloid solutions (eg, saline solutions, buffered [ie, also known as balanced or chloride-restrictive] solutions
[eg, lactated Ringer's, Plasma-Lyte, bicarbonate buffered 0.45% saline]). Hartmann's solution is the same as
lactated Ringer’s, although small differences in the sodium, chloride, and calcium concentrations may exist
across commercial formulations.

● Colloid-containing solutions (eg, albumin solutions, hyperoncotic starch, dextran, gelatin).

● Blood products (eg, packed red blood cells) or blood substitutes.

The choice of replacement fluid depends in part upon the type of fluid that has been lost [1]. For example, blood
components are indicated in patients who are bleeding. Isotonic crystalloids are generally preferred for the
management of patients with severe volume depletion not due to bleeding. (See "Indications and hemoglobin
thresholds for red blood cell transfusion in the adult" and "Massive blood transfusion" and "Initial management of
NON-hemorrhagic shock in adult trauma".)

The components and physiologic effects of commonly administered fluids are provided in the tables ( table 1 and
table 2 and table 3).

Hemorrhagic shock

Packed red blood cells — The mainstay of therapy for patients with intravascular volume depletion due to
bleeding is the replacement of volume loss with blood products, typically packed red blood cells. Patients may receive
fluid replacement, usually with crystalloid (eg, 0.9 percent saline), while waiting for blood products to be delivered to
the bedside. The management of patients with hemorrhagic shock is discussed separately. (See "Initial management
of moderate to severe hemorrhage in the adult trauma patient".)

Blood substitutes — Acellular, oxygen carrying resuscitation fluids may be an alternative when blood transfusion
is not immediately available or when patients refuse blood products due to religious beliefs. This subject is discussed
separately. (See "Oxygen carriers as alternatives to red blood cell transfusion".)

Nonhemorrhagic shock — In patients with nonhemorrhagic shock, isotonic or near-isotonic crystalloids (eg, 0.9
percent saline solutions with or without dextrose, buffered crystalloids [eg, lactated Ringer's, Plasma-Lyte,
bicarbonate buffered 0.45 percent saline]) and colloid-containing solutions (eg, albumin solution, hyperoncotic
starch, dextran, gelatin) can be used to effectively replace the extracellular fluid deficit. Hyperoncotic starch solutions,
although effective, should be avoided since they increase the risk of acute kidney injury, need for renal replacement
therapy, and mortality [2-6].

First line: Crystalloid solutions — In general, for patients with severe volume depletion or hypovolemic shock not
due to bleeding, crystalloids are typically preferred over colloid-containing solutions. Among the crystalloids, normal
saline (ie, 0.9 percent saline) is the most commonly used solution for initial repletion since data have failed to show
consistent superiority of buffered crystalloids when compared with saline, especially when volumes ≤2 L are being
administered. However, several factors influence the choice between 0.9 percent saline and buffered crystalloids,
which are discussed below. (See 'Choosing between 0.9 percent saline and buffered crystalloid' below.)

Data that support the value of crystalloid solutions over colloid-containing solutions include the following:

● In a 2013 nine-year, multicenter, open-label trial (CRISTAL), 2857 patients with hypovolemic shock due to any
cause were randomly assigned to resuscitation with intravenous crystalloid (mostly 0.9 percent saline) or colloid
solutions (eg, albumin, gelatin, hetastarch) [7]. There was no difference in 28-day mortality or need for renal
replacement therapy between the groups. However, patients treated with colloids had more days free of

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mechanical ventilation (13.5 versus 14.6 days) and vasopressor therapy (15.2 versus 16.2 days), as well as a lower
90-day mortality (31 versus 34 percent). The open-label design, lengthy study period (2003 to 2012), and
heterogeneity of fluids that were compared between the groups, limit confidence in a possible benefit of colloid
solutions in this population. (See 'Second line: Colloid solutions' below.)

● A 2006 multicenter trial (SAFE) randomly assigned nearly 7000 hypovolemic medical and surgical intensive care
unit (ICU) patients to fluid resuscitation using either 4 percent albumin solution (colloid) or 0.9 percent saline
(crystalloid) [8]. All-cause mortality at 28 days, multiorgan failure, the duration of hospitalization, and effect upon
systemic pH were similar in both groups [9]. No differences were observed in subgroup analyses of patients with
and without sepsis [10]. However, in patients with head trauma, resuscitation with albumin was associated with
higher mortality than resuscitation with 0.9 percent saline [11]. (See 'Albumin' below.)

● Meta-analyses of studies older than SAFE confirm a similar lack of benefit and/or harm from colloid-containing
solutions compared with crystalloids. For example, one analysis reported a 4 percent increase in mortality [12]
and another reported no difference in mortality [13] in patients given albumin compared with crystalloids (mostly
0.9 percent saline).

Choosing between 0.9 percent saline and buffered crystalloid — Normal saline (0.9 percent saline) is
hyperchloremic relative to plasma, such that large volume resuscitation using 0.9 percent saline may be associated
with the development of a hyperchloremic metabolic acidosis ( table 1) [14-16]. This has led to suggestions that
isotonic fluids with lower chloride concentration be used instead of 0.9 percent saline for large volume resuscitation;
such fluids are termed buffered, balanced, or chloride-restrictive crystalloids and include fluids such as lactated
Ringer’s solution (or Hartmann’s solution), 0.45 percent saline solution with 75 mmol/L of sodium bicarbonate, or
Plasma-Lyte. A list of commonly administered crystalloids and their electrolyte content relative to plasma can be
viewed in the table ( table 1).

Among crystalloids, normal saline (0.9 percent saline) is the most commonly used initial resuscitation solution since it
is inexpensive and other solutions have not consistently been proven to be superior, especially when smaller volumes
(eg, ≤2 L) are administered. However, the choice between buffered solutions and normal saline is individualized and
informed by factors including patient chemistries, estimated volume of resuscitation, potential adverse effect of the
solution used (eg, hyponatremia [Ringer's lactate] and hyperchloremic acidosis [normal saline]) as well as institutional
and physician preference. The clinician should have a low threshold to re-evaluate the type of fluid administered
depending upon the patient's response and development of adverse effects. The rationale for this recommendation
is based upon the lack of an ideal standard crystalloid resuscitation solution, and data from randomized trials that are
conflicting but may suggest potential benefit from buffered crystalloids in those in whom large volumes of fluids are
administered (eg, >2 L). As an example, patients with hypernatremia from hypovolemia may benefit from fluids with
lower concentrations of sodium or free water while those with symptomatic acute hyponatremia may benefit from
hypertonic saline. Similarly, in patients with hyperchloremic acidosis, buffered crystalloids may be preferred while 0.9
percent saline may be preferred in those with hypochloremic contraction alkalosis. Potassium-containing solutions
such as lactated ringers are traditionally avoided in patients with hyperkalemia; however, data in patients undergoing
renal transplantation suggest that lactated ringers does not significantly increase the potassium level when
compared with normal saline [17,18]. (See "Treatment of hypernatremia in adults" and "Overview of the treatment of
hyponatremia in adults" and "Clinical manifestations and treatment of hypokalemia in adults" and "Treatment and
prevention of hyperkalemia in adults" and "Treatment of metabolic alkalosis".)

Data to support an individualized approach to this choice include the following:

● Earlier studies [19,20] and meta-analyses [21] reported a reduced incidence of acute kidney injury and renal
replacement therapy in critically ill patients in whom a chloride–restrictive strategy was used (eg, Hartman's
solution, chloride-poor albumin, Plasma-Lyte 148) compared with standard intravenous fluids (typically 0.9
percent saline). In contrast, several subsequent randomized trials found no difference in the risk of acute kidney
injury, renal replacement therapy, or composite outcome of death, dialysis, or kidney dysfunction [22,23].

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However, interpretation of these data is limited due to issues such as low severity of illness scores and low or
variable volumes of resuscitation fluid.

● Two subsequent trials reported modest benefit from the use of balanced crystalloids in critically ill and non-
critically ill patients. A trial including 15,802 adults in five intensive care units in one institution found that
balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) resulted in a modest reduction in a composite
outcome of death from any cause at 30 days, new renal replacement therapy, or persistent renal dysfunction,
when compared with 0.9 percent saline (14.35 versus 15.4 percent), but no significant difference in the rates of
the individual components of the outcome were found [24]. The response was variable among subgroups. For
example, a pre-specified analysis of patients with sepsis (who received higher volumes than the median of
approximately 1 L) found infusion of balanced crystalloids to be associated with a lower 30-day mortality (25.2
versus 29.4 percent; adjusted odds ratio 0.8, 95% CI 0.67 to 0.94), while minimal benefit was seen in other
subpopulations. No differences in in-hospital death, ICU- ventilator- or vasopressor-free days, rates of stage-2 or
higher AKI, or creatinine levels before discharge were reported. Another parallel trial including 13,347 non-
critically ill patients treated in the emergency department and subsequently hospitalized outside the ICU found
that compared with 0.9 percent saline, buffered crystalloids did not affect the number of hospital-free days but
did result in a modest reduction in the composite outcome of death from any cause, new renal replacement
therapy, or persistent renal dysfunction (4.7 versus 5.6 percent) without significant difference in the individual
outcomes [25]. Although well-conducted, both of these studies were criticized for issues including small median
volumes of infusion, heterogeneity of the populations studied, and a response in a composite outcome that was
marginal [26].

● A meta-analysis of 21 randomized controlled trials (over 20,000 patients), eight of which were of high
methodologic quality, found no convincing evidence of an effect of buffered solutions (balanced crystalloids) on
in-hospital mortality or acute kidney injury, when compared with 0.9 percent saline (odds ratio [OR] 0.92, 95% CI
0.84-1.00; OR 0.80, 95% CI 0.40-1.62, respectively) [27]. The certainty of evidence that buffered solutions are no
better than 0.9 percent saline in preventing in-hospital mortality was considered high, indicating that further
research would detect little or no difference in mortality. The certainty of evidence showing that buffered
solutions and 0.9 percent saline are similar in preventing acute kidney injury was considered low, so that further
research could change this conclusion.

Normal saline (crystalloid) — For most patients, normal saline (0.9 percent saline) ( table 1), which contains
154 mEq/L of sodium chloride, is an effective and inexpensive initial resuscitation fluid for the management of
patients with hypovolemia and hypovolemic shock not due to bleeding [7,8,12,13,28,29]. This assessment is based
upon several trials and meta-analyses which consistently report that although colloids expand plasma volume more
effectively than isotonic crystalloids, clinically meaningful outcomes are similar [7-13,28,29]. Data that compare
buffered crystalloids and 0.9 percent saline and the factors that influence the decision regarding the choice between
0.9 percent saline and buffered crystalloids are discussed above. (See 'First line: Crystalloid solutions' above and
'Choosing between 0.9 percent saline and buffered crystalloid' above.)

Complications of 0.9 percent saline include hyperchloremic acidosis and peripheral edema.

● Hyperchloremic acidosis is due to the high concentrations of chloride relative to that in plasma and may be
resolved by the administration of buffered crystalloid, provided continued fluid resuscitation is required.
Hyperchloremia associated with 0.9 percent saline has also been associated with hyperkalemia due to
transcellular shifts of potassium. For example, in patients undergoing renal transplantation, 0.9 percent saline
administration has been associated with more cases of hyperkalemic acidosis than lactated Ringer’s [17,18].

● Peripheral edema occurs because of the significant extravascular distribution of normal saline when compared
with colloids ( table 2 and table 3); for this reason, it has been estimated that 1.5 to 3 times as much saline
must be given when compared with colloid-containing solutions [8,30-32]. However, this is not necessarily
deleterious, since fluid loss also leads to an interstitial fluid deficit that is repaired by saline administration.

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Buffered crystalloid — Buffered crystalloids are a reasonable alternative as either the initial resuscitation fluid
or as a secondary fluid to be used if large volumes of resuscitation fluids are necessary or if hyperchloremic acidosis
is a concern. Several buffered crystalloids are available ( table 1). Some of these have a lower sodium concentration
than 0.9 percent saline, and were associated with greater hyponatremia than saline in the SMART/SALT-ED trials
[24,25]. Although buffered fluids also contain small amounts of potassium, their contribution to extracellular
potassium concentration is small unless very large volumes are infused. Buffered crystalloids have nearly the same
plasma-expanding properties as isotonic crystalloid solutions ( table 2 and table 3).

As with 0.9 percent saline, administration of buffered crystalloids may be associated with the development of
peripheral edema. Because the available buffered crystalloids are modestly hypotonic, they are more commonly
associated with development of hyponatremia. Data that compare buffered crystalloids and 0.9 percent saline and
the factors that influence the decision regarding the choice between 0.9 percent saline and buffered crystalloids are
discussed above. (See 'Choosing between 0.9 percent saline and buffered crystalloid' above.)

Second line: Colloid solutions — Colloid-containing solutions are rarely used as first line resuscitative fluids for
the management of hypovolemia and hypovolemic shock not due to bleeding. However, some clinicians advocate the
administration of colloid solutions, particularly albumin, in those with limited response to crystalloid solutions or
those in whom hypoalbuminemia is thought to be contributing to shock, although data to support these indications
are limited. Hyperoncotic starch should, in general, be avoided since its use is associated with an increased risk of
kidney dysfunction and mortality. (See 'Fluids to avoid: hyperoncotic starch (colloid)' below.)

The rationale for the administration of colloid is that colloids result in more rapid plasma volume expansion than
saline, since the colloid solution is more likely to remain in the vascular space (in contrast to saline, three-quarters of
which enters the interstitium) ( table 2 and table 3). Although rapid plasma expansion can be achieved with
colloid-containing solutions, randomized trials and meta-analyses have failed to convincingly demonstrate a
consistent clinically meaningful benefit derived from this advantage [7-9,12,13,28,30,33-39] and some older studies
suggest possible harm [11,12]. Data to support this lack of clear benefit from the administration of colloid-containing
solutions are discussed above. (See 'First line: Crystalloid solutions' above.)

Albumin — Several formulations of albumin are available. Intravenous albumin can expand the intravascular
volume effectively but it is expensive and data have not shown consistent benefit with its use as an initial
resuscitation fluid compared with crystalloids (see 'First line: Crystalloid solutions' above). While it was originally
thought that albumin might avoid the dilutional hypoalbuminemia typically seen with isotonic crystalloid [40] and
therefore protect against the effect of pulmonary edema, this advantage has not been proven to be true [41-43].

The use of hyper-oncotic (20 to 25 percent) albumin has been used in individuals with intravascular volume depletion
but total body volume overload, such as patients with cirrhosis. However, little data exists to support this strategy.
Details regarding the management of cirrhosis are discussed separately. (See 'Chronic liver disease' below and
"Ascites in adults with cirrhosis: Initial therapy" and "Cirrhosis in adults: Overview of complications, general
management, and prognosis" and "Hyponatremia in patients with cirrhosis".)

Others — While colloid-containing solutions other than albumin and hyperoncotic starch (eg, dextran, gelatin),
are effective expanders of intravascular volume, they have not been sufficiently studied for recommendations to be
made regarding their administration. While in the past dextran has been used to inhibit platelet function, they are no
longer used to treat hypovolemia [44].

Fluids to avoid: hyperoncotic starch (colloid) — Hyperoncotic starch solutions are not recommended for
patients with hypovolemia. Concern has been raised about risks associated with the use of hyperoncotic starch
solutions (eg, pentastarch, hydroxyethyl starch [HES]) ( table 2 and table 3). Use of hyperoncotic starch solutions
has been associated with increased risk of acute kidney injury (AKI), and in some studies, increased mortality [2-
5,39,45-50]. The lack of benefit and potential adverse effects of starch solutions for critically ill patients, including the
subgroup with septic shock, are illustrated by the following:

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● In a randomized trial, 7000 ICU patients were assigned to receive 6 percent HES or 0.9 percent saline for all fluid
resuscitation until ICU discharge [48]. Compared with patients resuscitated with 0.9 percent saline, there was an
increased risk of AKI requiring renal replacement therapy in the HES group (7 versus 5.8 percent), but not an
increased mortality risk.

● In two subsequent meta-analyses, one of which excluded seven trials that were retracted due to scientific
misconduct of one investigator, compared to conventional fluid resuscitation regimens, HES was associated with
increased risk of mortality (relative risk ranging from 1.08 to 1.09), and treatment with renal replacement therapy
(relative risk ranging from 1.09 to 1.25) [4,5].

● Similarly, in the randomized 6S trial that compared HES with the colloid, Ringer's lactate, for volume expansion in
patients with severe sepsis and septic shock, patients receiving HES had a higher mortality and a greater
likelihood of needing renal replacement therapy [50]. This trial is discussed in more detail separately. (See
"Evaluation and management of suspected sepsis and septic shock in adults", section on 'Intravenous fluids (first
three hours)'.)

INITIAL RATE OF FLUID REPLETION

The rate of fluid repletion should be individualized depending upon the underlying etiology and rate of fluid loss,
estimated total body deficit, underlying electrolyte abnormalities, and predicted future losses, which can be hard to
predict if fluid loss continues from persistent bleeding or third space sequestration. While there is no one ideal initial
rate, many clinicians model the rate of fluid administration on rates similar to those recommended in patients with
sepsis and septic shock, although data to support this strategy is lacking. Further details on rate of fluid repletion in
patients with sepsis are provided separately (See "Evaluation and management of suspected sepsis and septic shock
in adults", section on 'Volume'.)

Ensuring adequate intravenous access for fluid resuscitation is important and for those with massive hemorrhage
adhering to massive transfusion protocols is advised. Further details are provided separately. (See "Evaluation and
management of suspected sepsis and septic shock in adults", section on 'Establish venous access' and "Initial
management of moderate to severe hemorrhage in the adult trauma patient", section on 'Predicting the need for
massive transfusion'.)

MONITORING THE RESPONSE

Following the response to fluid administration is necessary to prevent irreversible shock and to prevent over
resuscitation and iatrogenic hypervolemia. Irreversible shock is associated with loss of vascular tone, a drop in
systemic vascular resistance, pooling of blood in the capillaries and tissues, an impaired response to vasoactive
medications, and multiorgan failure. Clinical parameters including heart rate, blood pressure, urine output, skin
turgor, mucus membrane integrity, and mental status should be continuously followed during fluid replacement to
assess the efficacy of volume replacement. For most patients, the period of observation lasts for the duration of fluid
resuscitation (eg, 6 to 48 hours, longer for ongoing fluid loss). While there are no recommended ideal measurable
targets for patients with hypovolemia, many clinicians use parameters extrapolated from patients with sepsis and
septic shock (eg, mean arterial pressure 65 to 70 mmHg, no greater than 70 mmHg, urine output >0.5 mL/kg/hour),
the details of which are discussed separately. (See "Evaluation and management of suspected sepsis and septic shock
in adults", section on 'Clinical'.)

Measuring laboratory parameters including chemistries and lactate level within 6 hours and urinary sodium within 24
hours of replacement may also be useful. If, for example, the urine sodium concentration remains below 15 mEq/L
(15 mmol/L), then the kidney is sensing persistent volume depletion and more fluid should be given. Use of the urine
sodium concentration does not apply to edematous patients with heart failure or cirrhosis in whom the urine sodium
concentration is a marker of effective circulating volume depletion but not of the need for more fluid or more salt.

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FOLLOW-UP

Patients who respond to therapy — In most patients, an immediate clinical response to fluid administration is
appreciated by clinical examination and laboratory findings. The decision to maintain or stop fluids is dependent
upon the robustness of the clinical response as well as any predicted continued loss of fluids and the ability of the
patients to maintain their own oral fluid intake.

Maintenance — Once clinically stable, fluid repletion is often maintained for a short period at a rate lower than
the initial rate, and occasionally with a different solution, depending upon complications of fluid resuscitation that
may be evident. Further details regarding maintenance fluids are discussed separately. (See "Maintenance and
replacement fluid therapy in adults".)

Cessation — Once fluids have been adequately repleted (usually 3 to 48 hours) and it has been determined that
maintenance fluids are not needed, fluids may be stopped.

Over resuscitation — Some patients may show evidence of over resuscitation such as pulmonary edema.
Although peripheral edema is a marker of fluid overload, it should not be used as the sole marker for adequate fluid
resuscitation or fluid overload since peripheral edema is often due to acute dilutional hypoalbuminemia. The decision
to diurese patients should be individualized and depends upon several factors including the need for supplemental
oxygen, presence of respiratory failure, or lower extremity discomfort from edema.

Patients who fail therapy — While most patients respond to fluid resuscitation, some patients demonstrate a poor
or no improvement in clinical or biochemical parameters within the first 1 to 6 hours of treatment. Such patients may
require additional testing and/or monitoring (to investigate other potential etiologies for shock and to assess for
fluid-responsiveness), or an empiric trial of alternative resuscitation fluid such as albumin. Rarely, when hypovolemic
shock is refractory to aggressive fluid administration, vasopressors are added to maintain tissue perfusion.

Alternative resuscitation fluid — For those who initially fail with or develop a complication from 0.9 percent
crystalloid, some experts may empirically switch to or add a colloid, such as albumin, although data to support this
strategy are lacking.

Additional testing and monitoring — Additional testing may be needed to revisit the diagnosis of hypovolemic
shock and to investigate contributions from other etiologies of shock (eg, vasogenic from sepsis or cardiogenic from
heart failure). (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and
shock".)

Additional monitoring may also be appropriate. For example, measurement of the central venous pressure (CVP) may
help direct therapy. Alternative methods of monitoring volume status and fluid-responsiveness may also be
considered including pulmonary arterial venous catheterization (eg, patients with underlying cardiopulmonary
disease), pulse contour analysis, passive leg raising, and point-of-care ultrasonography, all of which require intensive
care unit admission. Details of CVP and alternate forms of measuring volume status are provided separately. (See
"Evaluation and management of suspected sepsis and septic shock in adults", section on 'Hemodynamic' and "Novel
tools for hemodynamic monitoring in critically ill patients with shock" and "Pulmonary artery catheterization:
Indications, contraindications, and complications in adults".)

Vasopressors — Vasopressors (eg, norepinephrine) generally should not be administered, since they do not
correct the primary problem and, in the absence of adequate resuscitation, tend to further reduce tissue perfusion
[51]. However, in patients with refractory shock, vasopressors may be administered while ongoing measures are
being taken to treat hypovolemia. (See "Use of vasopressors and inotropes".)

SPECIAL POPULATIONS

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Individual populations of patients with hypovolemia due to specific etiologies may need special attention.

Acute pancreatitis — Patients with acute pancreatitis can lose significant volumes of fluid into the third space such
that aggressive fluid resuscitation with crystalloid is the cornerstone of therapy. Details regarding fluid choice and
rate of repletion are discussed separately. (See "Management of acute pancreatitis", section on 'Fluid replacement'.)

Sepsis — Most patients with sepsis are treated with crystalloids and a similar lack of clear benefit for the colloid,
albumin, has been demonstrated in that population, the details of which are discussed separately. (See "Evaluation
and management of suspected sepsis and septic shock in adults", section on 'Choice of fluid'.)

Lactic acidosis — Patients with marked hypoperfusion may develop lactic acidosis, leading to a reduction in
extracellular pH below 7.10. Some have advocated addition of sodium bicarbonate to the replacement fluid in this
setting, in an attempt to correct both the acidemia and the volume deficit, although the optimal approach is
controversial. Data to support bicarbonate therapy in lactic acidosis are discussed separately. (See "Bicarbonate
therapy in lactic acidosis".)

Acute respiratory distress syndrome — Patients with acute respiratory distress syndrome (ARDS) commonly have
hypovolemia in association with the etiology inducing ARDS (eg, pancreatitis). Fluid management in patients with
ARDS is discussed separately. (See "Acute respiratory distress syndrome: Supportive care and oxygenation in adults",
section on 'Fluid management'.)

Trauma — Fluid resuscitation in patients with hypovolemic shock due to trauma is discussed separately. (See "Initial
management of moderate to severe hemorrhage in the adult trauma patient", section on 'Intravenous fluid
resuscitation'.)

Diabetic ketoacidosis — Fluid management in patients with diabetic ketoacidosis and hyperosmolar hyperglycemic
state is discussed separately. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults:
Treatment".)

Chronic liver disease — Fluid management in patients with intravascular hypovolemia who have chronic liver
disease is challenging, since most are also total body sodium and fluid overloaded with interstitial edema and/or
ascites. In general, these patients should be managed using a similar strategy to that in noncirrhotic patients.
However, particular attention needs to be paid to avoiding and managing hyponatremia and to managing third space
sequestration with diuresis and paracentesis. The intermittent administration of hyperoncotic (20 to 25 percent)
albumin as a resuscitative fluid is poorly studied but used by experts to limit fluid retention in this population [52].
(See "Hyponatremia in patients with cirrhosis" and "Ascites in adults with cirrhosis: Initial therapy".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient
education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five
key questions a patient might have about a given condition. These articles are best for patients who want a general
overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics
to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info"
and the keyword(s) of interest.)

● Basics topic (see "Patient education: Dehydration in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

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● Rapid volume repletion is indicated in patients with severe hypovolemia or hypovolemic shock. Delayed therapy
can lead to ischemic injury and possibly to irreversible shock and multiorgan system failure. Management of
hypovolemia involves assessing and treating the underlying cause, identifying electrolyte and acid-base
disturbances, and assessing the volume deficit, all of which influence the choice of fluid and rate at which it
should be administered. (See 'Introduction' above and 'Principles of management' above.)

● For patients with intravascular volume depletion due to bleeding, fluid loss is repleted with blood products,
typically packed red cells. Patients may receive fluid replacement with crystalloid (eg, 0.9 percent saline), while
waiting for blood products. (See "Initial management of moderate to severe hemorrhage in the adult trauma
patient" and 'Hemorrhagic shock' above.)

● For patients with severe non-hemorrhagic hypovolemia or non-hemorrhagic hypovolemic shock:

• We recommend initial fluid replacement with an isotonic crystalloid solution rather than a colloid-containing
solution (Grade 1B) based upon the rationale that randomized trials and meta-analyses have demonstrated
no consistent clinically meaningful benefit from colloids when compared with crystalloids. (See 'First line:
Crystalloid solutions' above.)

• Among crystalloids, normal (0.9 percent) saline is the most commonly used initial resuscitation solution since
it is inexpensive and other solutions have not consistently been proven to be superior, especially when
smaller volumes (eg, ≤2 L) are administered. However, the choice between buffered solutions and normal
saline is individualized and informed by factors including patient chemistries, estimated volume of
resuscitation, potential adverse effect of the solution used (eg, hyponatremia [Ringer's lactate] and
hyperchloremic acidosis [normal saline]) as well as institutional and physician preference. The clinician
should have a low threshold to re-evaluate the type of fluid administered depending upon the patient's
response and development of adverse effects. The rationale for this recommendation is based upon the lack
of an ideal standard crystalloid resuscitation solution, and data from randomized trials that are conflicting
but may suggest potential benefit from buffered crystalloids in those in whom large volumes of fluids are
administered (eg, >2 L). (See 'Choosing between 0.9 percent saline and buffered crystalloid' above.)

• Colloid-containing solutions are rarely used as first-line resuscitative fluids for the management of non-
hemorrhagic hypovolemia and hypovolemic shock. However, some clinicians advocate the administration of
colloid solutions, particularly albumin, in those with a limited response to crystalloid solutions or those in
whom hypoalbuminemia is thought to be contributing to shock, although data to support these indications
are limited. (See 'Second line: Colloid solutions' above.)

• For patients with severe hypovolemia and hypovolemic shock, we recommend against the use of
hyperoncotic starch solutions due to an increased risk of acute kidney injury and death (Grade 1B). (See
'Fluids to avoid: hyperoncotic starch (colloid)' above.)

● The rate of fluid repletion should be individualized depending upon the underlying etiology and rate of fluid loss,
estimated total body deficit, predicted future losses, and underlying electrolyte abnormalities. While there is no
one ideal initial rate, many clinicians model the rate of fluid administration on rates similar to those
recommended in patients with sepsis and septic shock, although data to support this strategy are lacking. (See
'Initial rate of fluid repletion' above and "Evaluation and management of suspected sepsis and septic shock in
adults", section on 'Volume'.)

● Clinical parameters including heart rate, blood pressure, urine output, skin turgor, mucus membrane integrity,
and mental status should be continuously followed during fluid replacement to assess the efficacy of volume
replacement and avoid over resuscitation. Chemistries, lactate, and urinary sodium should also be intermittently
followed (within 6 to 24 hours). While there are no recommended ideal measurable targets for patients with
hypovolemia, many clinicians use parameters extrapolated from patients with sepsis and septic shock. (See

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'Monitoring the response' above and "Evaluation and management of suspected sepsis and septic shock in
adults", section on 'Monitor response'.)

● In most patients, an immediate clinical response to fluid administration is appreciated, such that fluids can be
weaned and/or stopped. However, for patients who fail to respond, additional testing and monitoring (to
investigate other potential etiologies for shock and/or to assess for fluid-responsiveness), or an empiric trial of an
alternative resuscitation fluid such as albumin may be required. Rarely, vasopressors are added in shock
refractory to aggressive fluid resuscitation so that tissue perfusion can be maintained. (See 'Follow-up' above.)

● Individual populations of patients with hypovolemia due to specific etiologies may need special attention
including patients with acute pancreatitis, sepsis, lactic acidosis, acute respiratory distress syndrome, trauma,
diabetic ketoacidosis, hyperosmolar hyperglycemic state, and chronic liver disease. (See 'Special populations'
above.)

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15. O'Dell E, Tibby SM, Durward A, Murdoch IA. Hyperchloremia is the dominant cause of metabolic acidosis in the
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18. Khajavi MR, Etezadi F, Moharari RS, et al. Effects of normal saline vs. lactated ringer's during renal
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19. Yunos NM, Bellomo R, Hegarty C, et al. Association between a chloride-liberal vs chloride-restrictive intravenous
fluid administration strategy and kidney injury in critically ill adults. JAMA 2012; 308:1566.

20. Yunos NM, Bellomo R, Glassford N, et al. Chloride-liberal vs. chloride-restrictive intravenous fluid administration
and acute kidney injury: an extended analysis. Intensive Care Med 2015; 41:257.
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perioperative and critical care fluid resuscitation. Br J Surg 2015; 102:24.
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Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA 2015; 314:1701.
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27. Antequera Martín AM, Barea Mendoza JA, Muriel A, et al. Buffered solutions versus 0.9% saline for resuscitation
in critically ill adults and children. Cochrane Database Syst Rev 2019; 7:CD012247.
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29. Alderson P, Schierhout G, Roberts I, Bunn F. Colloids versus crystalloids for fluid resuscitation in critically ill
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30. Virgilio RW, Rice CL, Smith DE, et al. Crystalloid vs. colloid resuscitation: is one better? A randomized clinical
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32. Drobin D, Hahn RG. Volume kinetics of Ringer's solution in hypovolemic volunteers. Anesthesiology 1999; 90:81.
33. Weaver DW, Ledgerwood AM, Lucas CE, et al. Pulmonary effects of albumin resuscitation for severe hypovolemic
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34. Choi PT, Yip G, Quinonez LG, Cook DJ. Crystalloids vs. colloids in fluid resuscitation: a systematic review. Crit Care
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36. Roberts I, Blackhall K, Alderson P, et al. Human albumin solution for resuscitation and volume expansion in
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:CD001208.

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38. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane
Database Syst Rev 2013; :CD000567.
39. Opperer M, Poeran J, Rasul R, et al. Use of perioperative hydroxyethyl starch 6% and albumin 5% in elective joint
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350:h1567.

40. Rackow EC, Falk JL, Fein IA, et al. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory
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41. Taylor AE. Capillary fluid filtration. Starling forces and lymph flow. Circ Res 1981; 49:557.

42. Gallagher TJ, Banner MJ, Barnes PA. Large volume crystalloid resuscitation does not increase extravascular lung
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43. Zarins CK, Rice CL, Peters RM, Virgilio RW. Lymph and pulmonary response to isobaric reduction in plasma
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44. Ts'ao CH, Krajewski DV. Effect of dextran on platelet activation by polymerizing fibrin. Am J Pathol 1982; 106:1.
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46. Wiedermann CJ. Systematic review of randomized clinical trials on the use of hydroxyethyl starch for fluid
management in sepsis. BMC Emerg Med 2008; 8:1.
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of randomized trials. Crit Care 2010; 14:R191.
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Engl J Med 2012; 367:1901.

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Cochrane Database Syst Rev 2013; :CD007594.
50. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N
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51. Nordin AJ, Mäkisalo H, Höckerstedt KA. Failure of dobutamine to improve liver oxygenation during resuscitation
with a crystalloid solution after experimental haemorrhagic shock. Eur J Surg 1996; 162:973.
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Topic 1607 Version 44.0

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GRAPHICS

Comparison of plasma with commonly used intravenous solutions

  Sodium Potassium Calcium Magnesium Chloride Acetate Lactate Gluconate Bicarbonate Osmo

Plasma 135-145 3.5-5.0 mEq/L 2.2-2.6 0.8-1.0 mEq/L 94-111 – 1-2 mEq/L – – 275-295
mEq/L mEq/L 1.0-1.2 mg/dL mEq/L mOsm/
4.4-5.2 0.4-0.5 mmol/L
mg/dL
1.1-1.3
mmol/L

Plasma water* 145-156 3.8-5.4 mEq/L 2.4-2.8 0.9-1.1 mEq/L 101-119 – 1.1-2.2 – – 295-317
mEq/L mEq/L 1.1-1.3 mg/dL mEq/L mEq/L mOsm/
4.8-5.6 0.5-0.6 mmol/L
mg/dL
1.2-1.4
mmol/L

Intravenous solutions

Sodium chloride 154 – – – 154 mEq/L – – – – 308 mO

injection, mEq/L
USP [1]

Lactated 130 4.0 mEq/L 2.7 mEq/L – 109 mEq/L – 28 mEq/L – – 273 mO
Ringer's mEq/L 5.4 mg/dL
injection,
1.4
USP [2]
mmol/L

Plasma-Lyte 140 5.0 mEq/L – 3.0 mEq/L 98 mEq/L 27 mEq/L – 23 mEq/L – 294 mO
A [3] mEq/L 3.7 mg/dL
1.5 mmol/L

0.45% Sodium 141 – – – 72 mEq/L – – – 70 mEq/L 283 mO

chloride mEq/L
injection,
USP [1] with
added sodium
bicarbonate [4] ¶

* Plasma is approximately 93% aqueous; concentrations in plasma water calculated as plasma concentration ÷ 0.93.
¶ This solution can be mixed by adding 75 mL of 8.4% sodium bicarbonate (NaHCO 3 ) to 1 liter of 0.45% normal saline.

Data from:
1. Sodium Chloride Injection, USP. Baxter Healthcare Corporation. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/016677s137lbl.pdf (Accessed on
April 23, 2018).
2. Lactated Ringer's Injection, USP. Baxter Healthcare Corporation. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/016679s104,016682s105,016692s095,019367s026lbl.pdf (Accessed on April 23, 2018).
3. PLASMA-LYTE 148 Injection (Multiple Electrolytes Injection, Type 1, USP). Baxter Healthcare Corporation. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017451s060,017378s065lbl.pdf (Accessed on April 23, 2018).
4. Sodium Bicarbonate Injection, USP. Baxter Healthcare Corporation. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/077394lbl.pdf (Accessed on
April 24, 2018).

Graphic 117769 Version 1.0

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Physiological characteristics and clinical effects of commonly used intravenous solutions

Available solutions
  Albumin solutions Starches

4, 5 percent 20, 25 percent 3, 6, 10 percent Hetastarch 10 percent Pentastarch

Molecular weight, average (kD) 69 69 450 280

Osmolality, mOsm/L 290 310 300-310 326

COP, mm Hg 20-30 70-100 23-50 23-50

Maximum volume expansion,* percent 70-100 300-500 100-200 100-200

Duration of volume expansion, h 12-24 12-24 8-36 12-24

Plasmatic half-life, h 16-24 16-24 50 2-12

Potential for adverse reactions + + ++ ++

Possible side effects Allergic reactions Allergic reactions Renal dysfunction Renal dysfunction

Transmitted infection Transmitted infection Coagulopathy Coagulopathy

Pruritus Pruritus

Anaphylactoid reactions Anaphylactoid reactions

COP: colloid osmotic pressure.

* Expressed as a percentage of administered volume.

Am J Respir Crit Care Med Vol 170. pp 1247-1259, 2004.

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Physiological characteristics and clinical effects of commonly used intravenous solutions, continued

Available solutions

  Dextrans Gelatins Crystalloids

3 percent Dextran-60, 6 Succinylated and cross-linked: 2.5, 3, 4 Ringer's

10 percent Dextran-70 Normal saline
percent Dextran-70 percent Urea-linked: 3.5 percent lactate

Molecular weight, 40 70 30-35 0 0

average (kD)

Osmolality, mOsm/L 280-324 280-324 300-350 285-308 250-273

COP, mm Hg 20-60 20-60 25-42 0 0

Maximum volume 100-200 80-140 70-80 20-25 20-25

expansion,* percent

Duration of volume 1-2 8-24 4-6 1-4 1-4

expansion, h

Plasmatic half-life, h 4-6 12 2-9 0.5 0.5

Potential for adverse +++ +++ ++ + +

reactions

Possible side effects Anaphylactoid Anaphylactoid reactions High calcium content (urea-linked forms) Hyperchloremic Hyperkalemia
reactions Allergic reactions Anaphylactoid reactions metabolic acidosis
Allergic reactions Interference with blood
Interference with blood crossmatching
crossmatching

COP: colloid osmotic pressure; maximum volume expansion: the degree of expansion of circulatory volume divided by infused volume.
* Expressed as a percentage of administered volume.

Am J Respir Crit Care Med Vol 170. pp 1247-1259, 2004.

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Contributor Disclosures
Jess Mandel, MD Nothing to disclose Paul M Palevsky, MD Grant/Research/Clinical Trial Support: Dascena [Informatics;
prediction of AKI]. Richard H Sterns, MD Nothing to disclose Scott Manaker, MD, PhD Equity Ownership/Stock Options (Spouse):
Johnson & Johnson; Pfizer. Consultant/Advisory Boards: Expert witness in workers' compensation and in medical negligence
matters [General pulmonary and critical care medicine]. Other Financial Interest: National Board for Respiratory Care
[Director]. Geraldine Finlay, MD Consultant/Advisory Boards: LAM Board of directors, LAM scientific grant review committee for
The LAM Foundation.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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