Fluid Management in Shock

Greg S. Martin, M.D., M.Sc.1 and Charmaine A. Lewis, M.D.1

ABSTRACT

Shock is a broad category of injury to the human body caused by a variety of

insults. Fluid resuscitation is the cornerstone of initial therapy for nearly all forms of shock.
This article reviews the basic physiology determining body fluid composition, the goals of
fluid resuscitation in shock, the types of fluids available for use, and clinical evidence for use
of specific fluids based on etiology of the insult.

KEYWORDS: Shock, ARDS, sepsis, trauma, hemorrhage, colloid, crystalloid

Objectives: Upon completion of this article, the reader should be able to: (1) understand the physiology governing fluid management;
and (2) apply clinical evidence when choosing fluids for use in resuscitation of critically ill patients.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor
continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for a maximum of 1 category 1 credit toward the AMA
Physician’s Recognition Award.

S hock is a broad category of ailments that arise
from specific disturbances but cause global insult to the
human body. The most common forms of shock are
sepsis, hypovolemic with or without hemorrhage, car-
diogenic, anaphylactic, and neurological. This diverse
group of conditions is unified by the common thread of
therapy: fluid resuscitation. Despite the differences in
pathophysiology apparent from these forms of shock and
the attendant physiological derangements, all require
fluid resuscitation. Interestingly, no one technique has
ever been determined to be more effective than others,
and indeed, even the most basic of resuscitation strate-
gies, such as the choice of type of fluid, has been hotly
debated. And rightly so. Millions of patients are diag-
nosed with shock in small community hospitals and large
academic centers alike. These patients are often the
sickest of hospitalized patients and require prolonged
maximal intensive care. The health care burden for these
patients is immense, costing billions of dollars in direct
health care costs alone. Thus it is a rational goal for the
medical community to strive to discover the optimal
therapy for these patients.
PHYSIOLOGY
The human body is functionally divided into compart-
ments that permit volume buffering during times of
physiological stress. (Fig. 1.) Water is an important
component of all tissues and constitutes 50 to 70% of
total body weight, present in inverse proportion to age
and body fat. The distribution of total body water
(TBW) is two thirds (40%) to the intracellular compart-
ment and one third (20%) to the extracellular compart-
ments. The extracellular fluid (ECF) is then subdivided
into an interstitial component, constituting 75% of the
ECF, and an intravascular component, constituting 25%
of the ECF and representing the effective plasma
volume. The fluid in the interstitium and plasma are

Management of Shock; Editor in Chief, Joseph P. Lynch, III, M.D.; Guest Editors, Arthur P. Wheeler, M.D., Gordon R. Bernard, M.D. Seminars
in Respiratory and Critical Care Medicine, volume 25, number 6, 2004. Address for correspondence and reprint requests: Greg S. Martin, M.D.,
M.Sc., Pulmonary, Allergy, and Critical Care, Emory University School of Medicine, 69 Jesse Hill Jr Dr. SE, Rm. 2D-004, Atlanta, GA 30303.
E-mail: Greg_Martin@emory.org. 1Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University School of
Medicine, Atlanta, Georgia. Copyright # 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Tel: +1(212) 584-4662. 1069-3424,p;2004,25,06,683,693,ftx,en;srm00339x.
683
684 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6
Figure 1 Depiction of body fluid compartments and distribution of body water for an average 70 kg male. TBW, total body water; RBC
volume, red blood cell volume, normally 2 L. Plasma volume normally occupies 3.5 L, or 8% of TBW.
interchangeable, with only the endothelial junctions of
the thin capillary wall regulating the passage of large
molecules such as plasma proteins and blood cells.
The rate of filtration across a capillary membrane
may be quantified by the balance of forces described from
the Starling equation1 (Fig. 2). The first term of Star-
ling’s equation represents the hydrostatic pressure gra-
dient (the hydrostatic pressure in the capillary minus the
hydrostatic pressure in the interstitium), and drives fluid
out of the capillary under normal conditions. The second
term of Starling’s equation represents the colloid osmotic
pressure (COP) gradient across the capillary wall
(plasma COP minus interstitial fluid COP), which
normally favors movement of fluid into the vessel. The
effect of COP on fluid flux is modulated by the protein
reflection coefficient (!), which decreases as the capillary
becomes permeable to proteins. Reducing plasma COP
has twice the effect on fluid flux from the vasculature to
Figure 2 The Starling equation describing filtration of fluid
across a semipermeable membrane, often applied clinically to
predict forces responsible for edema fluid accumulation across
the vascular endothelium.
2004
the interstitial space than does an equivalent increase in
capillary hydrostatic pressure.2 Lymphatic clearance and
intrinsic resistance to flow across the capillary (Kf) are
also determinants of fluid flux between the intravascular
space and the interstitial space.
Albumin constitutes 60% of circulating protein in
the human body, with ! 60% of it located in the
interstitial space. Fibrinogen and globulins contribute
the remainder of the protein. COP is produced by the
total effect of these endogenous proteins, and although
albumin contributes ! 80% of plasma COP, it is total
protein that best predicts plasma COP. Because COP is
produced by the number of molecules and not by
molecular size, 1 g of albumin, at 69,000 daltons, will
exert twice the oncotic force as 1 g of globulin averaging
150,000 daltons and more than five times the force as 1 g
of fibrinogen 490,000 daltons. It is noteworthy that
oncotic pressure becomes osmotic pressure as the nega-
tive charges surrounding the protein molecules attract
sodium and water.
An imbalance in the Starling forces may lead to
edema formation in a given tissue or organ. Common
clinical examples include ‘‘cardiogenic’’ pulmonary
edema when pulmonary capillary hydrostatic pressure
is increased and acute respiratory distress syndrome
(ARDS) when pulmonary capillary permeability is in-
creased. When the oncotic pressure gradient is dimin-
ished, as in states of hypoalbuminemia (e.g., cirrhosis),
edema formation may occur at lower hydrostatic pres-
sures.3 Experimental models have shown that pulmonary
edema begins to form at left atrial pressures > 24 mm
Hg when COP is normal, whereas edema may form at
11 mm Hg when COP is reduced.4 This finding has
been replicated with varying success in critically ill
patients, simplified to the COP-hydrostatic pressure

gradient, in which filtration and edema formation are
proportional to the difference between plasma COP and
pulmonary artery occlusion pressure (PAOP).5
TYPES OF FLUIDS
Perhaps the largest controversy in the management of
shock patients centers on the type of fluid chosen for
intravascular volume resuscitation. This has resulted in a
myriad of physiological studies, several meta-analyses,
and one of the largest clinical trials ever conducted in
critically ill patients.
Crystalloids
Crystalloid solutions are composed of various physiolo-
gical combinations of electrolytes and have advantages in
acquisition cost, shelf life, and ease of administration.
For these reasons, normal saline and lactated Ringer’s
(LR) solution are often the preferred agents for volume
resuscitation. See Table 1 for a comparative description
of common intravenous solutions. Crystalloid solutions
rapidly redistribute to the ECF compartment and re-
quire larger infusions to expand intravascular volume, in
addition to diluting serum protein concentrations and
packed red cell volume. One may expect a higher rate of
pulmonary edema formation with less intravascular vo-
lume expansion from these solutions, and normal saline
particularly may cause hypernatremia and hyperchlore-
mic metabolic acidosis.
Hyper-tonic crystalloid solutions are increasingly
recognized as an alternative resuscitation fluid in hypo-
volemic shock. They are characterized by a high tonicity
and work by rapidly increasing plasma osmolality, which
subsequently creates a high osmotic gradient across
cellular membranes. This gradient encourages volume
expansion by movement of fluid from the intracellular
and interstitial compartments to the intravascular com-
partment. Hyper-tonic solutions increase plasma volume
by 2 to 4 times the volume infused, depending on
tonicity of the chosen fluid. This effect is short-lived,
however, as fluid rapidly redistributes into all compart-
ments. Hyper-tonic solutions may favorably influence
capillary permeability,6 whereas the addition of a colloid
component to the hyper-tonic solution may prolong and
augment the volume expansion effect of the hyper-tonic
solution alone.7 An advantage of hyper-tonic solutions is
the ability to facilitate field transport of small-volume
resuscitation solutions.
Hyper-tonic agents are not without risk. The first
concern for hyperosmolarity has not materialized; pa-
tients treated in clinical trials were not found to have
prolonged hyperosmolarity nor did they experience ad-
verse effects from infusion.8 The second concern rests on
the hyper-tonic electrolyte load. In a study of trauma
patients given 7.5% NaCl with dextran, significant
FLUID MANAGEMENT/MARTIN, LEWIS 685
hypernatremia was rare and without clinical conse-
quence. Other risks include hypokalemia, metabolic
acidosis, hemolysis, hemoglobinuria, and impaired pla-
telet aggregation.9
Colloids
As already mentioned, colloid solutions more rapidly
expand the intravascular compartment with about one
fourth to one half the volume required from iso-tonic
crystalloid solutions. Because of the smaller infusion
volume, they may restore circulating volume more ra-
pidly.10 Colloids cause less plasma protein and red blood
cell dilution, and they have a longer-lasting effect on
intravascular volume than crystalloids. In addition,
maintenance of normal COP may limit extravascular
fluid accumulation in the lungs, as described by Starling’s
equation.11 This is particularly important in patients
with shock requiring fluid resuscitation and who are at
risk for protein leak across the injured alveolar–capillary
membrane. Clinically, a low serum albumin concentra-
tion is a marker for increased mortality, but increasing
serum levels with administration of albumin does not in
and of itself improve survival.12 See Table 1 for a
comparative description of common intravenous solu-
tions.
ALBUMIN
Albumin is the final product in the Cohn fractionation
and precipitation process from pooled human plasma,
thus some Jehovah’s Witnesses refuse albumin infusions.
Albumin was first used clinically at Pearl Harbor and was
approved for use in the United States in 1943. It is
diluted with physiological quantities of sodium and is
available in two primary forms: iso-oncotic (4–5% solu-
tion) and hyper-oncotic (20–25% solution). There have
been no reports of serious viral illnesses transmitted via
albumin.
In one of the largest critical care trials to date,
investigators from the Australia and New Zealand In-
tensive Care Society randomized 7,000 critically ill pa-
tients requiring fluid resuscitation to receive iso-oncotic
albumin or iso-tonic crystalloid solutions. There was no
overall difference in morbidity or mortality, although
traumatically injured patients with brain injuries ap-
peared to fare better with crystalloids, while septic shock
patients may have fared better with colloids.12a
STARCHES
Starches, such as hydroxyethyl starch (HES) and penta-
starch, are synthetic polymers derived from the starch
amylopectin. HES is a polydispersed molecular weight
substance composed of D-glucose units linked by a
branching polysaccharide backbone. It is predominantly
renally excreted but is distributed throughout the body,
including deposition in the reticuloendothelial system
 686

Table 1 Characteristics of Commonly Used Intravenous Fluids

Albumin Solutions Starches Dextrans Gelatins Crystalloids

Iso-oncotic Hyper-oncotic Heta-starch Penta-starch Dextran-40 Iso-tonic Hyper-tonic
Common Formulations 5% 25% 6% 10% 10% Dextran-70 6% 3% 0.9% 3%, 7.5%
Osmolality (mOsm/L) 300 300 325 280–325 300 250–310 900–2400
Molecular weight (avg, kDa) 69 450 280 40 70 30 0
Colloid osmotic pressure (mm Hg) 20 100 30 60 30 24 20 0
Volume expansion* (%) 100 500 100 150 150 100 75 25 200–400
Duration of volume expansion (h) 12–24 8–36 12–24 1–2 " 8–24 4–6 0.5–4
Potential for adverse reactions þ þþ þþþ þþþ þ
Possible side effects Allergic reactions Renal dysfunction Anaphylactoid reactions High calcium content Metabolic Hyper-tonicity,
Transmitted infection Coagulopathy Allergic reactions (urea-linked forms) acidosis metabolic
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6

Pruritus Anaphylactoid Interference Anaphylactoid acidosis

reactions with blood cross-matching reactions
2004

*Expressed as a percentage of administered volume.


and skin where it may cause prolonged pruritis.
Although relatively unpopular in the United States,
these agents are among the most common volume
expanders used in European intensive care units.13
Limitations to the widespread use of starch preparations
lie in their association with altered coagulation, includ-
ing increases in prothrombin time, partial thromboplas-
tin time, and bleeding time as well as a decrease in
platelet aggregation.14
DEXTRANS
Dextrans are large glucose polymers, available as
dextran-40 (molecular weight 40,000 daltons) or
dextran-70 (70,000 daltons). Dextrans alter platelet
and red blood cell function and interfere with blood
cross-matching. They are associated with a moderate
risk for anaphylaxis and thus may require antigen-bind-
ing premedication. Dextrans improve microvascular cir-
culation by decreasing blood viscosity and minimizing
platelet and red blood cell aggregation. Because of their
low molecular weight and short half-life, they are rarely
used as volume expanders except when combined with
hypertonic crystalloid solutions.
GELATINS
Gelatins are colloidal solutions derived from bovine
sources. The most common gelatin formulation has a
mean molecular weight of 30,000 daltons, is relatively
inexpensive, and has a long shelf-life. Gelatins have a
short half-life in the circulation and may induce a
coagulopathy, limiting their usefulness in critically ill
patients with shock. In addition, they have the highest
rates of anaphylactoid reactions of any colloid.15 There
are no U.S. Food and Drug Administration (FDA)-
approved gelatin formulations.
Blood Products
The amount of oxygen available to the tissues is related
to cardiac output, hemoglobin levels, and dissolved
arterial oxygen content. In patients with normal physiol-
ogy, adaptive mechanisms prevent decompensation from
acute moderate anemia.16 In critically ill individuals,
anemia may have systemic consequences of reduced
tissue oxygen delivery that are further complicated by
coincident inflammatory processes.17 However, mainte-
nance of normal hemoglobin concentration has not
shown clinical benefit, and blood products carry a finite
risk of infection, allergic reaction, immunosuppres-
sion,18,19 and microcirculatory dysfunction.20,21
A large, controlled trial randomized 838 critically
ill patients to a standard ‘‘liberal’’ red blood cell transfu-
sion strategy (hemoglobin concentration of 10.0 g/dL)
or a ‘‘restrictive’’ transfusion strategy at a hemoglobin
concentration of 7.0 g/dL.22 Although there was no
FLUID MANAGEMENT/MARTIN, LEWIS 687
overall outcome difference, there was a significant survi-
val benefit for the restrictive transfusion strategy in
patients who were younger (age < 55 years) and less
severely ill [acute physiology and chronic evaluation
(APACHE II) score " 20]. The restrictive transfusion
strategy may be safe for general patients with cardiovas-
cular disease, though patients with active coronary vas-
cular disease may benefit from a higher hemoglobin
concentration.23,24 Prevention of anemia in the intensive
care unit may be the best way to conserve blood, through
either minimized phlebotomy or use of erythropoietin.25
Meta-analyses
For 40 years, the crystalloid-or-colloid question has been
hotly debated without a satisfactory conclusion. At least
12 meta-analyses have evaluated the issue of colloid
administration and mortality or morbidity in critically
ill patients. The first meta-analysis in 1989 examined
data from eight clinical studies and reported discordant
results according to patient type: mortality favored
crystalloids for trauma patients and favored colloids for
nontrauma patients.26 These findings highlight the
conflicts in underlying evidence and reinforce the het-
erogeneity of critically ill patients.
A large meta-analysis comparing colloids and
crystalloids in critically ill patients was published in
1998 and reignited the controversy.27 In this review,
data from 19 of the 48 identified studies were examined
with respect to mortality (N ¼ 1315). A heterogeneous
group of crystalloids were analyzed together and com-
pared with a heterogeneous colloid group that included
hyper-tonic solutions. The authors concluded that col-
loid resuscitation is associated with a relative risk for
death of 1.16, thus increasing the risk of death by 4% for
critically ill patients. Shortly thereafter, the Cochrane
Injuries Group published a meta-analysis of albumin
administration in critically ill patients.28 Twenty-four
trials (N ¼ 1204) were separated according to use of
albumin with or without globulins, or any formulation
of crystalloid. They observed a 6% increased mortality in
the albumin % globulin group that was most significant
for thermally injured patients.
Two subsequent meta-analyses have not quieted
the conflict. Choi et al analyzed 17 studies (N ¼ 814)
comparing iso-tonic crystalloids to colloids.29 They
reported no overall difference in outcome, yet a reduc-
tion in mortality for the subgroup of trauma patients
receiving crystalloids. To explore reasons for the appar-
ent mortality difference in prior meta-analyses, they also
analyzed adverse outcomes such as the occurrence of
pulmonary edema and hospital length of stay, but found
no difference. Most recently, Wilkes and Navickis re-
ported the largest meta-analysis to date, specifically
examining albumin compared with crystalloids in criti-
cally ill patients.30 In analyzing a total of 42 trials
688 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6
(N ¼ 2958) for differences in mortality, the investigators
found no significant outcome difference according to
fluid type.
Some of these meta-analyses have been criticized
for omission of relevant trials, heterogeneity of included
trials with intrinsic study design flaws, improper meta-
analytic techniques, lack of mortality data as the primary
endpoint, and difficulty comparing studies in which
resuscitation goals were different.31 Unfortunately, the
discrepant results in primary trials and systematic reviews
preclude a uniform statement about the effect of crystal-
loids and colloids on outcome.32
GOALS OF FLUID RESUSCITATION
The goals of fluid resuscitation for patients with shock
are: (1) to rapidly replace intravascular volume and
restore tissue perfusion, and (2) to minimize organ
dysfunction through timely interventions that either
halt or reverse the physiological derangements. Tradi-
tionally, the achievement of these goals is measured by
numeric parameters that have been arbitrarily chosen; in
addition, clinicians must determine whether these para-
meters are better monitored via invasive or noninvasive
methods (see Thompson article on monitoring). Invasive
methods, such as pulmonary artery catheters (PACs),
may produce complications such as pneumothorax, ar-
terial puncture, infection, or bleeding. Furthermore,
these catheters require a significant amount of skill
from the nursing staff and the clinician to use them
effectively.33 PAC use has been associated with worsened
survival,34 thus it remains to be proven that invasive
monitoring methods may improve patient outcomes
despite the fact that they may provide a more precise
understanding of individual patient hemodynamics. It
may be argued that conventional hemodynamics are less
important endpoints for forms of shock dominated by
dysregulation of the immune system in septic shock.35
Two recently published studies addressed the use
of the PAC in patients with shock. The first used an
observational design comparing sepsis patients who
underwent PAC placement to those without a PAC
and adjusted for the risk of receiving a PAC by a
propensity score.36 By these methods, there was no
difference in resource consumption or mortality attribu-
table to the PAC. The second study randomized 681
patients with shock or ARDS to standard intensive care
unit monitoring with or without a PAC.37 The investi-
gators did not impose a strict treatment protocol, leaving
patient management to the discretion of the clinician.
They found no evidence of a mortality benefit at 28 days
between groups, nor did they find evidence of increased
morbidity or significant complications in the PAC
group. Thus there remains no firm evidence that invasive
monitoring either improves or worsens outcomes for
patients with shock.
2004
Most clinicians agree that the maintenance of
tissue perfusion is tantamount to patient survival, but
there is still controversy regarding the strict use of
hemodynamic optimization in resuscitation. Rivers
et al conducted a study in which 263 severe sepsis and
septic shock patients were randomized upon arrival in
the emergency department to either standard therapy or
‘‘goal-directed therapy’’ guided by central venous oxygen
saturation.38 A strict protocol governed the use of fluid
boluses, vasoactive drug use, and red blood cell transfu-
sions during the 6-hour treatment period. Patients as-
signed to the early goal-directed group received 40%
more intravenous fluids and more vasoactive drugs and
red blood cell transfusions, and were more likely to
achieve hemodynamic goals during the 6-hour treat-
ment. These differences translated into reduced illness
severity at 72 hours and improved survival at 28 days
compared with patients in the standard care group.
Although it is unclear which component of the proto-
colized care produced the benefits, this study highlights
our inability to assess hypoperfusion and suggests that, at
a minimum, septic shock patients should receive greater
fluid resuscitation than is required to reach traditional
endpoints.
A more extensive discussion of the methods and
goals of hemodynamic monitoring may be found in the
Monitoring section of this volume.
SPECIFIC STRATEGIES
Septic Shock
Like antimicrobial therapy, fluid resuscitation is a key
component to improving outcomes for septic shock and
must be administered early and appropriately. The
choice of fluid for resuscitation of patients with septic
shock is hotly debated. The nature of sepsis as an
immunologic insult and the preponderance of vascular
leakage introduce a new element to the resuscitation
question: is there a fluid replacement strategy that
improves intravascular volume and tissue perfusion and
also offers biochemical advantages?
The distribution of intravenous fluids can be
predicted by knowledge of the body fluid compartments
discussed previously. Iso-tonic fluids, such as normal
saline or Ringer’s lactate, will distribute into the ECF.
Thus, 1 L of iso-tonic fluid will provide ! 250 mL of
intravascular volume expansion, with the remainder
distributing to the interstitial space. Similar calculations
may be performed for colloids, though they are con-
founded by our inability to measure the oncotic reflec-
tion coefficient (!) that determines colloid distribution
between the vasculature and the interstitium. Studies of
patients with sepsis show that administration of iso-
oncotic albumin results in plasma volume expansion
equal to the volume infused, with an equivalent

expansion of the interstitial space.39 Thus, even when
capillary permeability is compromised, colloids are more
effective volume expanders per unit administered than
crystalloids.
Experimental sepsis models support colloids as
the superior fluid for intravascular resuscitation. Colloids
demonstrate superiority in speed of resuscitation and
tissue perfusion,40,41 primarily because oncotic solutions
achieve similar resuscitation goals with less than half the
infusion volume of crystalloids.42–44 Resuscitation spe-
cifically with albumin may have benefits for the myo-
cardial depression of sepsis by altering nitric oxide
expression and increasing myocyte contractility.45 Albu-
min may also confer benefits to patients with sepsis by
improving redox balance and thus preventing oxidative
cellular damage.46 After acute resuscitation, albumin
administration in experimental sepsis preserves micro-
vascular surface area for tissue oxygen exchange, result-
ing in less tissue injury.47 This may relate to a direct
albumin-mediated effect on capillary permeability,48
though this has not been confirmed in humans.49 HES
solutions have been similarly shown to reduce capillary
permeability, apparently by starch macromolecules ‘‘seal-
ing’’ the injured endothelial gaps.50
The individual side-effect profiles may best dif-
ferentiate colloids. In a randomized trial of patients with
severe sepsis comparing HES to gelatin resuscitation,
HES recipients were more likely to develop acute renal
failure.51 This finding is consistent with observations of
renal dysfunction in HES-treated cadaveric kidney
transplants.52 In addition, starch solutions and dextrans
have potent effects on the coagulation system and may
increase the risk of bleeding in susceptible pa-
tients.14,53,54 Although there have not been adequate
studies specifically in patients with septic shock, drugs
that increase the risk of bleeding are concerning in this
condition where activation of the coagulation system is
universal and disseminated intravascular coagulation is
common.55
There are insufficient clinical data to proclaim
superiority of a given intravenous solution. The best level
of evidence for the importance of fluid resuscitation in
septic shock comes from the study by Rivers et al,38
mentioned earlier, in which patients identified in the
emergency department and aggressively resuscitated ac-
cording to goal-directed hemodynamic therapy achieved
better survival than patients randomized to standard
resuscitation endpoints. Both colloids and crystalloids
were allowed in this study protocol, precluding con-
trolled analysis and failing to provide evidence of benefit
for a given intravenous solution. It is clear, however,
that crystalloid solutions require two to four times
greater volume to achieve similar hemodynamic resusci-
tation endpoints in patients with septic shock.56,57
Albumin and synthetic colloids are equivalent for these
purposes.56,58
FLUID MANAGEMENT/MARTIN, LEWIS 689
The hypothesis that maintenance of COP
through colloid administration will reduce pulmonary
edema in patients with septic shock remains unproven.56
Reductions in COP are generally associated with pul-
monary edema5,59–61 and ARDS,62 whereas increases in
COP reduce tissue-directed fluid flux in the lung.11
Although the data are not conclusive in states of im-
paired capillary integrity, available evidence suggests that
crystalloid administration produces more pulmonary
edema than colloids.56,63 Importantly, colloid adminis-
tration does not exacerbate edema formation in states of
capillary permeability if hydrostatic pressures are un-
changed.64 For patients with established respiratory
dysfunction (e.g., ARDS), colloid administration shifts
Starling forces in favor of lung fluid resorption65 and
reduces intrapulmonary shunt.66 This nonresuscitation
effect of colloids may be more potent when combined
with diuretics.67,68
Hypovolemic Shock
TRAUMATIC HEMORRHAGE
Fluids used in resuscitation of patients with traumatic
injuries need to be readily available and capable of rapidly
restoring plasma volume. Fluid resuscitation should
typically be initiated upon recognition of unstable he-
modynamic parameters, or in anticipation of instability.
However, a controlled delay in resuscitation may benefit
certain patients with trauma-related shock. In a study of
hemorrhagic shock from penetrating torso injuries, 598
patients were randomized to receive standard prehospital
fluid resuscitation or resuscitation that was delayed until
arrival in the operating room.69 Subjects randomized to
delayed resuscitation had improved survival, shorter
hospital stay, and probably fewer postoperative compli-
cations. The magnitude of this effect has been disputed
in other prospective studies,69a making confirmation of
these benefits difficult in a systematic review.70
Although unproven, the theoretical benefit lies in per-
missive controlled hypotension that avoids resuscitation-
induced loss of blood and clotting factors, until mechan-
ical control of bleeding can be achieved.
Similar to experimental models of sepsis, colloid
administration in hemorrhagic shock is superior in
rapidity of resuscitation and tissue perfusion.71–73
Furthermore, albumin specifically reduces inflammatory
cytokine expression after hemorrhagic shock.44,72 By
comparison, crystalloid solutions promote adhesion mo-
lecule expression74 and cellular apoptosis.75–77
Is there a clinical advantage to a particular in-
travenous solution? Historically, iso-tonic crystalloids
have been used for trauma resuscitation, requiring infu-
sion of seven to 10 times the volume of blood lost.78 The
physiological aspects of colloids are similar to its use in
sepsis: a smaller infusion volume may be achieved with
690 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6
colloids,56,79 although the impact of colloids on the
development of respiratory failure80,81 or ARDS79 re-
mains uncertain. However, colloids have been shown to
resuscitate traumatically injured patients more rapidly
due to smaller infusion volumes10 and to produce greater
increases in oxygen delivery than crystalloid solutions.82
Alternatively, hyper-tonic–colloid combination solu-
tions may benefit trauma patients with hemorrhagic
shock. A multicenter trial randomizing traumatic injury
patients to hyper-tonic saline plus dextran (HSD) or iso-
tonic crystalloid suggested benefit of the former for the
subset of hemorrhagic shock patients requiring sur-
gery.83 A subsequent smaller trial in this population
found a survival benefit for HSD84 that has been
supported by meta-analysis of the literature.85
GASTROINTESTINAL BLEEDING
Massive gastrointestinal hemorrhage is a common clin-
ical scenario in the intensive care unit. Similar to patients
who sustain penetrating traumatic wounds, patients with
gastrointestinal bleeding lose whole blood and are ap-
propriately resuscitated with a combination of blood
products. There have been no trials that have compared
resuscitation strategies in patients with gastrointestinal
bleeding. Although serum albumin is often subnormal, it
is an independent predictor of mortality.86,87
NONHEMORRHAGIC, HYPOVOLEMIC SHOCK
Dialysis-related hypotension may result in the adminis-
tration of volume expanders and vasopressors, thus
hindering the goals of fluid and electrolyte removal
necessary for optimal patient management. In ambula-
tory patients, albumin priming for dialysis results in
more stable hemodynamics and greater filtration vo-
lume.88 Both albumin and HES successfully restore
intravascular volume and prevent subsequent hemody-
namic compromise compared with hyper-tonic or iso-
tonic crystalloid solutions.89,90 Extrapolation of these
results to critically ill patients is physiologically sound
but requires confirmation in clinical trials.
Anaphylactic Shock
A section of this volume is devoted to anaphylaxis
and the reader is referred there for a detailed discussion
of pathophysiology and treatment. Regarding fluid
resuscitation in this condition, published practice para-
meters state: ‘‘Hypotension should be addressed by . . .
infusion of large volumes of intravenous fluids/colloid to
compensate for peripheral vasodilation and for intravas-
cular fluid loss caused by third spacing.’’91 Randomized
clinical trials from which to draw evidence are
absent, though some advocate colloids as the fluid of
choice in resuscitating patients from anaphylactic
shock.92
2004
Cardiogenic Shock
There are no studies intended to define the best type of
fluid in cardiogenic shock. As in other critical illnesses,
Starling forces predict the development and resolution
of pulmonary edema.93 Care of patients with this
condition is discussed in depth in the article devoted to
this subject.
CONCLUSION
Shock represents one of the most common clinical
scenarios in the intensive care unit. Patients with this
condition require prolonged and intensive hospital care,
consuming tremendous health care resources. Fluid
management for these patients is the cornerstone of
therapy and must be administered early and judiciously.
The ideal intravenous resuscitation fluid in shock would
be immediately available, would rapidly restore both
global and microvascular hemodynamics, and would
favorably influence the nature of the insult (i.e., promote
hemostasis in hemorrhage or abrogate inflammation in
sepsis). Although colloids, and in particular albumin,
may possess some of these characteristics, their acquisi-
tion costs are greater and there is no conclusive evidence
that any physiological benefit described here may trans-
late into improved outcomes. Unfortunately, there are
inadequate data on which to build consensus for the best
strategies regarding the type of intravenous fluid. Ran-
domized, controlled trials with clinical endpoints are
needed to optimize care for these patients.
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