ACKD

Fluid Resuscitation: Principles of Therapy and

“Kidney Safe” Considerations
Ajay Srivastava

Fluid resuscitation in the acutely ill must take into consideration numerous elements, including the intravenous solution itself,
the phase of resuscitation, and the strategies toward volume management which are paramount. With the advancement in the
understanding and implementation of aggressive fluid resuscitation has also come a greater awareness of the resultant fluid
toxicity, especially in those that suffer acute kidney injury, and the realization that there is continued ambiguity with regard
to volume mitigation and removal in the resuscitated patient. As such, the discussion regarding intravenous solutions con-
tinues to evolve especially as it pertains to their effect on kidney and metabolic function, electrolytes, and ultimately patient
outcome. In the section below, we review the foundations of fluid resuscitation in the critically ill patient and the different so-
lutions available in this context, including their composition, physiologic properties, and safety and efficacy including the avail-
able data regarding “renal-safe” options.
Q 2017 by the National Kidney Foundation, Inc. All rights reserved.
Key Words: Fluid, Resuscitation, Solution, Volume

INTRODUCTION was approximately the same in both. Since 2001, there

Despite its absolute pervasiveness in the management of
the acutely ill patient, there remains large practice varia-
tions with regard to the selection and administration of
IV fluids, not only by geographic location and between
medical specialties but even between providers within
the same specialty.1 As such, given that these variations
may actually be related more to clinician preference
rather than a physiological basis,2 questions abound not
only as to the optimal composition and administration
of IV fluids (including fluid dose, timing, and rate) but
also as to the relative morbidity attributable to fluid
toxicity and whether there are “kidney safe” options.
This has led to a greater push in ascribing the same
caution toward IV fluid administration as any other
medication2,3 in the hopes of optimizing patient-
centered outcomes. However, the challenges of standard-
izing fluid administration are notably apparent when
considering the numerous patient-related clinical vari-
ables (including organ failure, infection, nutrition, and
electrolyte derangements) in the context of a wide range
of clinical settings related to hemodynamic instability in
which IV fluid therapy is administered (including sepsis,
trauma, and hemorrhage).
FOUNDATIONS OF VOLUME RESUSCITATION
The mainstay of therapy for the modern-day management
of sepsis is aggressive IV fluid resuscitation whose efficacy
with regard to mortality was first demonstrated in the
landmark study by Dr. Emmanuel Rivers.4 The foundation
of this early goal-directed therapy (EGDT) was to maxi-
mize preload to augment cardiac output for optimal organ
perfusion and included a number of specific interventions
geared toward specific hemodynamic and physiological
targets (Table 1). This study was the first to emphasize
the utility of such measures allowing for a protocolized
EGDT in sepsis. The patients were followed for 60 days
or until death with the in-hospital mortality significantly
lower in the EGDT arm (30.5%) vs the standard therapy
(46.5%) as was the amount of overall fluid used in the
EGDT arm in the first 6 hours, although by 72 hours, it
have been at least 12 studies that have evaluated variations
of the River’s study and despite some of their challenges to
specific bundled components of the study’s protocols,
most subsequent studies have considered the administra-
tion of 25 to 50 mL/kg (average of 30 mL/kg) of isotonic
fluid within the first 6 to 8 hours as defining the EGDT.5
As such, initiated in 2002, the Surviving Sepsis Campaign
was a product of the joint collaboration between the Soci-
ety of Critical Care Medicine and European Society of
Intensive Care Medicine with the inherent goal of reducing
mortality due to sepsis (Surviving Sepsis Campaign:
http://www.survivingsepsis.org). The collaboration’s orig-
inal treatment algorithm was adopted from Rivers and col-
leagues4 and was designed into treatment “bundles.”
These “bundles” represent core elements of care designed
to ensure timely administration of treatments with known
benefit to maximize patient outcome while simplifying
and reducing the variability in the early management of
septic patients. The most recent algorithm (updated April
2015) now provides 3- and 6-hour bundles for the initial
resuscitation of patients in septic shock (Fig 1). Recently,
in an effort to advance the modern-day understanding of
acute fluid resuscitation, the Acute Dialysis Quality Initia-
tive workgroup conceptualized fluid management in the
setting of critical illness. Originally formed in 2000 to re-
view emerging evidence and formulate consensus with re-
gard to the management of kidney diseases, the Acute
Dialysis Quality Initiative framed their concept of fluid
management in the acutely ill population as a dynamic
From the Division of Nephrology, Kidney C.A.R.E. Program, University of Cin-
cinnati, Cincinnati, OH.
Financial Disclosure: The authors declare that they have no relevant finan-
cial interests.
Address correspondence to Ajay Srivastava, MD, FASN, Associate Professor
of Medicine, Division of Nephrology, Kidney C.A.R.E. Program, University of
Cincinnati, 231 Albert Sabin Way, ML 0585, Cincinnati, OH 45267. E-mail:
srivasay@ucmail.uc.edu
Ó 2017 by the National Kidney Foundation, Inc. All rights reserved.
1548-5595/$36.00
http://dx.doi.org/10.1053/j.ackd.2017.05.002

Adv Chronic Kidney Dis. 2017;24(4):205-212 205

206 Srivastava

Table 1. Original Early Goal-Directed Therapy Interventions and traditionally been used to evaluate the resolution of tissue
Targets underperfusion, thus marking the end point of aggressive
500 mL IV bolus crystalloid q30 min to achieve CVP 8-12 mm Hg fluid resuscitation.11-13 In Rivers and others,4 ScvO2
and MAP 65 mm Hg increased with fluid resuscitation which suggested a paral-
Vasopressor if BP goal not achieved lel increase in cardiac output and, therefore, was consid-
PRBCs if ScvO2 ,70% with target goal HCT .30% ered a surrogate for cardiac output. However, the
Dobutamine if ScvO2 remains ,70% (until .70% or maximum baseline value for ScvO2 in the study was about 50%,
dose) which is much lower than a normal value of about
Minimum 6 h therapy (EGDT) 70%,14 and the ScvO2 and SvO2 are actually characteristi-
**Antibiotic therapy at clinician discretion**
cally normal or higher in septic shock patients due to
Abbreviations: BP, blood pressure; CVP, central venous pressure; decreased oxygen extraction15,16 and, therefore, does not
EGDT, early goal directed therapy; HCT, hematocrit; MAP, mean necessarily suggest adequate tissue oxygenation. In fact,
arterial pressure; PRBC, packed red blood cells; ScvO2, central only Rivers and others4 found such a low ScvO2 as more
venous oxygen saturation.
recent studies have found much higher ScvO2 values in
septic shock patients, either in the emergency department
process which was divided into 4 phases with the goals of or on admission to the ICU,17,18 which suggests that other
fluid administration dependent on the phase of illness factors such as pre-existing co-morbidities or late arrival to
(Table 2).6-8 Within each phase of therapy and dependent the hospital were responsible. Additionally, measuring
on numerous factors, both the requirements of and ScvO2 is characteristically invasive and requires specific
response to fluid resuscitation can have considerable equipment which is not readily available in many facilities
variation over the course of the illness. Although patients globally.19 However, there is no single absolute physical,
may be perceived as biochemical, or imaging
progressing through each CLINICAL SUMMARY measurement that will suffi-
phase of resuscitation in a ciently represent the status
linear fashion, they do not  The evaluation of a fluid’s safety and effectiveness must of a critically ill patient
all start at the same point take into account its composition and properties and the suffering from variable co-
and certainly do not follow a clinical features of the population that is receiving it. morbidities.3 Therefore,
temporal pattern, such as continued assessment and
the patient who may present  Standardized approaches to fluid resuscitation and
reassessment of volume re-
maintenance therapy should utilize and integrate multiple
with hypotension but does quirements and responsive-
objective measures of clinical targets and end points.
not require vasoactive ness with any concurrent or
support or who may acutely  Although there are no solutions to date that show clear occult tissue hypoperfusion
decompensate while superiority, it is recognized that hetastarch should be utilizing multiple parame-
mobilizing excessive fluid, avoided as a volume expander. ters and targets is ideal to
therefore requiring repeat  Although there has been much advancement in the avoid toxic accumulation,
resuscitation. This variability understanding of aggressive fluid resuscitation and including those that have
presents continued resultant fluid toxicity, there is continued ambiguity with developed acute kidney
challenges to the design and regard to accumulated volume removal in the injury (AKI) and, therefore,
implementation of resuscitated patient. remain susceptible to pro-
standardized protocols gressive and unnecessary
regarding fluid management. accumulation, designated as
“fluid creep.”20 A larger degree of fluid overload at the
APPROACH TO VOLUME RESUSCITATION initiation of kidney replacement therapy is associated
During initial attempts to rapidly reverse the shock state with a higher mortality21 and lower likelihood of kidney
and throughout the patient’s clinical course, it is impera- recovery22 and quantitative fluid toxicity will lead to a
tive that volume responsiveness be continually evaluated, longer intubation period and hospital stay.23 To date,
utilizing, and integrating a number of different physical, however, there is no applicable data to direct what degree
biochemical, and/or imaging parameters comprising static of fluid mitigation or removal is optimal as the patient
and dynamic variables. When used in conjunction with progresses toward the de-escalation phase.
static variables (such as central venous pressure, mean
arterial pressure, heart rate, urine output, and pulmonary SOLUTION COMPOSITION
artery wedge pressure/pulmonary artery occlusion pres- Modern-day medicine has availed itself of numerous types of
sure) that are surrogates for preload and routinely used fluid compositions in each class of solution available for deliv-
as the customary indicators of volume status, dynamic ery in multiple clinical scenarios (Table 3).24-28 IV fluid
measures (such as stroke volume variation, pulse pressure distribution within the body fluid compartments can vary
variation, end-expiratory occlusion test, and passive leg considerably depending on the acute illness that the patient
raise), which represent preload responsiveness, may help is suffering, and therefore, any resuscitative fluid can
avoid over-resuscitation (Fig 2).7,9,10 Markers, such as contribute to the formation of interstitial edema especially
ScvO2 or SvO2 (central venous or mixed venous oxygen in septic or inflammatory conditions.3 Crystalloid solutions
saturation) and clearance of arterial lactate, have are sterile aqueous solutions comprising mineral salts or other

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 Fluid resuscitation: Principles of Therapy 207

Figure 1. Three- and 6-hour treatment bundles for initial resuscitation of severe sepsis and septic shock. The 3- and 6-hour
time designation begins at the time of presentation in the emergency department triage or the earliest chart documentation
whose elements signify severe sepsis or septic shock. Abbreviations: CV, cardiovascular; CVP, central venous pressure; MAP,
mean arterial pressure; IVF, intravenous fluid; PE, physical exam; VS, vital signs; ScvO2, central venous oxygen saturation.

water-soluble molecules freely allowing distribution through
the capillaries and into the extracellular space made up of
both the intravascular and interstitial compartments.29 Col-
loids offer an alternative approach to intravascular volume
resuscitation given their macromolecular composition that
are high in molecular weight and, thus, during initial admin-
istration tend to remain primarily in the intravascular
compartment, thereby generating an oncotic pressure.30
Blood products or substitutes are used for specific clinical in-
dications. There are a number of advantages to both crystal-
loid and colloid solutions (Table 4).
Crystalloid Solutions
Because only 1/3 of IV-administered isotonic crystalloid
solution is distributed to the extracellular fluid (of which,
only 25% is intravascular), a patient must receive at least
3 times the volume in the setting of blood loss.31 Accord-
ingly, for a 20% loss of blood volume (ie., approximately
1 L), a patient may require a 3 or 4 L (or more) infusion
of isotonic crystalloid.26 “Balanced” solutions were origi-
nally defined as those having compositions approximating
that of plasma which would, therefore, theoretically not
significantly alter the acid-base balance.27 More recently,
hyperchloremia has come to be associated with negative
renal effects and in that setting “balanced” has come to
designate those solutions that are low in chloride con-
tent.27 Ringer’s solution refers to the saline component
without the bicarbonate precursor lactate, which is termed
lactated Ringer’s (LR) solution, whose composition is very
similar to that of Hartmann’s solution.32 The hepatic meta-
bolism of lactate ultimately yields an equivalent amount of
bicarbonate.28 To sustain electrical neutrality, the sodium
concentration in both these buffered solutions is reduced
to balance (in conjunction with the ionic potassium con-
centration which approximates that of plasma and also
that of ionized calcium which is slightly higher) the anionic
chloride and lactate concentration.3,27 As such, with the
addition of lactate to these solutions, there is a decrease
in the chloride concentration which approaches that of
plasma as opposed to 0.9% saline whose sodium and
chloride concentrations are 154 mEq/L each.27,33 Because
the negative anion lactate is delivered with sodium
instead of hydrogen (ie, lactic acid), it will not contribute
to the development of acidosis. Although the buffered
solutions are seemingly more physiological, there are no
large-scale randomized controlled trial data suggesting
any superiority or buffering capacity as opposed to 0.9%
saline. Furthermore, the bioavailability of certain drugs
can be reduced due to the calcium in LR and Hartmann’s
solutions and, consequently, also cannot be used with
blood products as calcium would bind with the citrated
anticoagulant and cause blood clot formation.33 Plasma-

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208 Srivastava

Table 2. Phases of Fluid Resuscitation

Phase Characterization
Rescue  Life-threatening shock represented by low BP and
impaired organ perfusion
 Vasopressors generally initiated should hypotension
persist after administration of .30 mL/kg of crystalloid
or equivalent
Optimization  No longer at impending risk for life-threatening shock
marking improved oxygen delivery to tissues
 Vasopressor support may still be required although
dose is constant or reduced
Stabilization  Adequate tissue perfusion achieved
De-escalation  Final phase
 Ongoing recovery observed such that patient can be
weaned from ventilator and vasoactive support indi-
cating hemodynamic stability and optimal tissue
perfusion
 Negative fluid balance maintained
Management Strategy
 Rapid fluid administration with close hemodynamic
monitoring and evaluation of fluid responsiveness
 Optimization of cardiac function and tissue perfusion,
mitigating organ dysfunction
 Achieve measured physiological endpoints (traditional
markers have included ScvO2 and arterial lactate clear-
ance)
 Promote continued hemodynamic stability
 Prevent iatrogenic complications including excessive
fluid administration
 May administer fluid challenges if patient fluid respon-
sive with aim of reducing vasopressor requirements;
Avoid fluid challenges if patient not exhibiting evidence
of hypoperfusion even if fluid responsive
 Weigh fluid volume administered with medication and
nutrition against insensible loss and output for mainte-
nance fluid therapy to avoid unnecessary volume
accumulation
 Fluid restrict with consideration of diuresis if clinical
evidence of volume overload apparent and/or patient
unable to achieve negative fluid balance independently

Abbreviations: BP, blood pressure; ScvO2, central venous oxygen saturation.

Lyte 148 and Normosol-R also contain bicarbonate precur-
sors in the form of acetate, gluconate, and magnesium,2,4,33
which the LR and Hartmann’s solutions do not.
Additionally, given their composition, the resultant
electroneutrality balance requires that the chloride
concentration be reduced even further to 98 mEq/L and
arguably has an electrolyte composition that is more
physiologically similar in comparison with the other
crystalloid solutions.
Colloid Solutions
Dextrans are glucose polymers that are produced by a
gram-positive bacteria (Leuconostoc mesenteroides) that are
incubated in a sucrose medium.25 Like albumin, dextrans
were also introduced in the 1940s but have fallen into
disfavor in the United States because of their propensity
to cause adverse reactions, such as severe anaphylactic re-
actions and inhibition of platelet aggregation leading to
dose-related bleeding tendencies.30 The 2 most common
preparations are the 10% dextran-40 and the 6% dextran-
70 which are both diluted in isotonic saline25 but are hyper-
oncotic to plasma (which has a colloid osmotic pressure of
about 28 mm Hg) with a colloid osmotic pressure of up to
60 mm Hg.34,35 Although dextran-40 causes a larger in-
crease in plasma volume than dextran-70, dextran-70 has
a protracted action time.25,35
Gelatins are created through the hydrolysis of collagen
tissue and are high–molecular weight proteins of
approximately 100,000 kDa which allows them to pro-
vide significant oncotic effect.30 Although they can pro-
mote up to an 80% volume expansion, are cost effective,
have not been known to cause AKI, and do not have an
infusion ceiling, their duration of action is shorter as
opposed to albumin and hetastarch (HES) and can
induce anaphylaxis.30
Derived from maize or potato starch, HES is a polymeric
glucose that is available in 6% (iso-oncotic) and 10% (hy-
peroncotic) concentrations.36 They are usually designated
by their concentration (%), molecular weight (low [#70
kDa], medium [130-200 kDa], and high [450-670 kDa]), de-
gree of molar substitution (which delineates the propor-
tion of modified glucose units with hydroxyethyl
[typically around 0.35 to 0.5]), and the C2/C6 ratio (which
determines their half-life).25 HES elimination occurs in the
urine for molecules ,60 kDa, whereas those greater in size
are metabolized by plasma a-amylase before urinary
excretion and can, thus, accumulate in the skin and tissue
where it can last for many years.25 Studies with HES in crit-
ically ill patients as described below have clearly shown se-
vere adverse effects with regard to the use of HES and is
not currently supported for use in the critically ill in the
United States.
In the United States, the available 5% (iso-oncotic) and
25% albumin (hyper-oncotic) solutions are isotonic with
plasma, contain 130 to 160 mEq/L of sodium, and are
based on 12.5 g and 25 g components: With 5% comprising
12.5 g in 250 mL or 25 g in 500 mL and 25% comprising
12.5 g in 50-mL and 25 g in 100-mL volume.

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 Fluid resuscitation: Principles of Therapy 209

Figure 2. Integrating parameters of volume status and responsiveness. Abbreviations: BP, blood pressure; CVP, central
venous pressure; EEOT, end-expiratory occlusion test; FeNa, fractional excretion of sodium; FeUrea, fractional excretion of
urea; HR, heart rate; MAP, mean arterial pressure; UOP, urine output; PAOP, pulmonary artery occlusion pressure; PAP, pul-
monary artery pressure; PAWP, pulmonary artery wedge pressure; PLR, passive leg resistance; PPV, pulse pressure variation;
ScvO2, central venous oxygen saturation; SVO2, mixed venous oxygen saturation; SVV, stroke volume variation; IVC, inferior
vena cava; SVC, superior vena cava.

SOLUTION EFFICACY double-blind trial with a heterogeneous ICU population

Overall, the efficacy of isotonic saline solutions in acute
resuscitation appears to be as effective as other crystalloids
as well as colloids37 and is available at an immensely lower
cost.29 Although hyperoncotic colloids can expand the
plasma compartment with much less volume and propen-
sity toward extravascular distribution vs crystalloids, vol-
ume loss also leads to interstitial loss which theoretically is
restored with crystalloid. Additionally, colloid solutions
do not carry any advantage over crystalloids in preserving
pulmonary function38 because of the fact that the alveolar
capillaries are highly permeable to albumin and any gain
or loss of albumin will not affect the transcapillary oncotic
pressure gradient.39,40 Although animal models suggest
significant volume expansion with colloid solutions
compared with crystalloid, clinical trials suggest a far
less difference as indicated by an approximately 1.5:1
crystalloid-to-colloid volume ratio,41 signifying the sub-
stantial effect of capillary leak in critically ill clinical sce-
narios, regardless of solution composition. Recently,
there have been 6 notable trials comparing colloid and
crystalloid solutions. The Saline versus Albumin Fluid
Evaluation (SAFE) trial38 was the first high-quality ran-
domized control trial comparing 4% albumin in 0.9% sa-
line and 0.9% saline and was designed as a multicenter,
that included patients with severe sepsis, trauma, and
acute respiratory distress syndrome. There was no differ-
ence in 28-day mortality, mean ICU and hospital length
of stay, and number of days on mechanical ventilation
and kidney replacement therapy, whereas a subgroup
analysis and post hoc long-term analysis showed
increased mortality in trauma patients (especially head)
in the colloid group. A large issue with the study was
that unlike Rivers and colleagues4 the rate and volume
of solution administration were at the discretion of the
treating clinician, based on their interpretation of the pa-
tient’s clinical status and treatment response. Furthermore,
in addition to the study solutions, the treating clinicians
also decided on the replacement and maintenance fluids,
nutrition (both enteral and parenteral), and blood prod-
ucts. Albumin Italian Outcomes Sepsis (ALBIOS) was a
multicenter, open-label trial that compared 20% albumin
plus crystalloid (targeting serum albumin concentration
of $3 g/dL) vs crystalloid alone in over 1800 patients
with severe sepsis.42 The study investigators adhered
closely to a standardized goal-directed protocol utilizing
predefined hemodynamic targets. There were no differ-
ences between the groups with regard to survival although
the albumin group received less overall fluid and had a

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210 Srivastava

Table 3. Examples of Available Crystalloid Solutions ature consisted of small and low-quality trials that did not
Composition Osmolality fully elucidate the toxicity involved with HES. Three fairly
Solution (in 1 L) (mOsm/L) recent trials, Efficacy of Volume Substitution and Insulin
Therapy in Severe Sepsis (VISEP),44 Crystalloid versus
0.9% Saline or Na 154 mEq 308 Hydroxy-Ethyl Starch Trial (CHEST),45 and 6S,46 clearly
normal saline Cl 154 mEq
indicated the increased risk involved with HES solutions
3% Saline Na 513 mEq 1026
Cl 513 mEq
including AKI, need for RRT, and mortality and have since
0.45% Saline Na 77 mEq 154 led the European Society of Intensive Care Medicine to
Cl 77 mEq recommend against the use of HES in those at increased
5% Dextrose in water Dextrose 50 g 278 risk for AKI or severe sepsis.47 The US Food and Drug
Lactated Ringers Na 130 mEq 273 Administration also issued a black box (November 2013)
K 4 mEq warning against the use of HES in critically ill patients
Cl 109 mEq given its associated increased risk of AKI and death. It is
Ca 3 mEq unclear whether these data regarding the adverse effects
Lactate 28 mEq of HES can be applied to other semisynthetic colloids,
Hartmann’s solution Na 131 mEq 280
such as gelatin, as there are currently no high-quality ran-
K 5 mEq
Cl 111 mEq
domized control trials evaluating them.
Ca 4 mEq Although primarily observational data have suggested
Lactate 29 mEq that high chloride solutions contribute to kidney vasocon-
Normosol-R Na 140 mEq 295 striction,48 decreased GFR,49 hyperchloremic metabolic
Plasma-lyte 148 K 5 mEq acidosis,50-52 and increased risk of AKI and need for
Cl 98 mEq RRT,50,53 there has been no demonstrable consistent
Mg 3 mEq benefit in using buffered or balanced solutions instead.
Acetate 27 mEq Although a recent meta-analysis54 did show a slight signif-
Gluconate 23 mEq icant association between hyperchloremic solutions vs
chloride-restrictive solutions with regard to the develop-
ment of AKI, the solutions within the chloride-restrictive
group had differing compositions, and there was no differ-
shorter time on vasopressors or inotropes. Colloids versus ence with regard to mortality.
Crystalloids for the Resuscitation of the Critically Ill To date, there has been 1 large (and the first) randomized
(CRISTAL) was a recent multicenter, open-label, random- control trial comparing the effects of 2 different types of
ized trial evaluating “any” colloid (ie, gelatins, dextrans, crystalloids: The 0.9% Saline versus Plasma-Lyte 148
HES, or 4% or 20% albumin) vs “any” crystalloid (ie, (PL-148) for ICU fluid Therapy (SPLIT) trial55 was a
isotonic or hypertonic saline and buffered solutions) in a double-blind, cluster-randomized, double crossover trial
case-mix population (ie, sepsis [54%], trauma [6.2%], hy- conducted in 4 ICUs in New Zealand evaluating 0.9%
povolemic shock without sepsis or trauma [39%]) of over saline solution vs Plasma-Lyte 148 with regard to AKI (pri-
2800 patients.43 As with the other 2 studies, there were mary outcome) and the use of RRT and in-house mortality
no mortality differences and also no differences in kidney (secondary outcomes) with no significant differences
replacement therapy use although there were some noted between either group. Although the study adhered
notable design issues including the inclusion of solutions to rigorous methodology and studied patients in the ICU
with significantly different properties especially within environment, the therapy itself was at the clinician’s discre-
the colloid group in addition to the clinician choosing at tion and the patients were mainly elective and postopera-
their discretion the actual solution to be administered. tive cardiac patients with only ,5% representing septic or
As noted earlier, HES has been deemed unsafe for use in trauma patients. Additionally, there was no indication that
the critically ill population, although before 2008 the liter- vasopressors were used as the Acute Physiology and
Chronic Health Evaluation (APACHE II) scores were low
indicating a lower acuity level for the patients. Conse-
Table 4. Advantages of Crystalloid and Colloid Solutions quently, low fluid volumes (median of 2 L for the entire
Crystalloid Advantages Colloid Advantages
ICU stay) were used, and therefore, the data cannot be
extrapolated with regard to large-volume resuscitation in
Inexpensive Fluid sparing patients with sepsis for example. The study also did not
Offer effective resuscitation More rapid volume expansion evaluate the effect of the solutions on serum chloride,
fluid Hyperoncotic formulations therefore rendering any assessment on its effect on the
Readily available allow fluid shift from
outcomes impossible.
Low incidence of adverse interstitial space to
reactions intravascular space
Although the available data do not suggest superiority
Compatibility testing not with regard to fluid or chloride composition, there are
required fundamental methodologies that clinicians should
No religious objections to use consider when evaluating future studies regarding solu-
Easy storage and long half-life tions, which would also benefit the planning of subsequent
studies: (1) ensuring the study population is homogenous

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 Fluid resuscitation: Principles of Therapy
and with a significant mortality rate, eg, using an entirely
septic population rather than including trauma patients,
(2) standardization of the resuscitative efforts and using
data-driven and objective targets instead of solely relying
on clinician discretion, (3) utilization of patient-centered
primary outcomes, such as disease-free survival, mortality,
and use of kidney replacement therapy, in a population
with significant mortality risk/rate (such as sepsis), and
(4) comparison of 2 specific fluids rather than a compen-
dium with differing properties making comparison impos-
sible. For example, when comparing a crystalloid against a
colloid, including HES, albumin based, and dextran solu-
tions as the colloid group will not offer insight into efficacy
given the significant differences inherent to the solution
properties within the colloid group.
CONCLUSION
The evaluation of a fluid’s safety and effectiveness must
take into account its composition and properties and the
clinical features of the population that is receiving it, how-
ever, just as important is the standardization of fluid resus-
citation and maintenance therapy that ideally uses and
integrates multiple objective measures of clinical targets
and end points. As such, based on the available data, there
are no solutions to date that show superiority, although it
is clear that HES should be avoided as a volume expander.
Additionally, there are clinical scenarios where certain so-
lutions would not be feasible, such as those containing cal-
cium, which would preclude its use with blood products
and certain drugs. Although there has been much
advancement in the understanding of aggressive fluid
resuscitation and resultant fluid toxicity, there is continued
ambiguity with regard to accumulated volume removal in
the resuscitated patient. Therefore, concentration of oblig-
atory fluids and tube feeds and other approaches to limit
fluid accumulation should be strategized at the time of
initial patient evaluation and throughout the course of
treatment. Ultimately, a co-ordinated approach between
clinicians, support staff, and caregivers will be key to
achieving these goals and optimizing patient outcomes.
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