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j.jemermed.2017.08.093

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The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–12, 2017
Ó 2017 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2017.08.093
AAEM
Position Paper
WHAT IS THE PREFERRED RESUSCITATION FLUID FOR PATIENTS WITH SEVERE
SEPSIS AND SEPTIC SHOCK?
Michael E. Winters, MD, FAAEM, FACEP,* Robert Sherwin, MD,† Gary M. Vilke, MD,‡ and Gabriel Wardi, MD, MPH‡
*University of Maryland School of Medicine, Baltimore, Maryland, †Wayne State University, Detroit, Michigan, and ‡University of California at
San Diego Medical Center, San Diego, California
Reprint Address: Michael E. Winters, MD, FAAEM, FACEP, Departments of Emergency Medicine and Medicine, University of Maryland School of
Medicine, Baltimore, MD 21201
, Abstract—Background: Current guidelines for the
management of patients with severe sepsis and septic
shock recommend crystalloids as the initial fluid solution
of choice in the resuscitation of these patients. In recent
years, there have been numerous studies published on
the type of fluid used in the resuscitation of patients
with sepsis. The primary goal of this article is to determine the preferred intravenous fluid for the resuscitation
of patients with severe sepsis and septic shock. Methods:
A MEDLINE literature review was completed to identify
studies that investigated the type of resuscitation fluid in
the management of patients with severe sepsis and septic
shock. Articles included were those published in English
between 2011 and 2016, enrolled human subjects, and
limited to the following types: randomized controlled trial,
prospective observational trial, retrospective cohort trial,
and meta-analyses. All selected articles then underwent a
structured review by the authors. Results: Nine thousand
sixty-two articles were identified in the search. After use
of predetermined criteria, 17 articles were selected for review. Eleven of these were original investigations and six
were meta-analyses and systemic reviews. Conclusion:
Crystalloids are the preferred solution for the resuscitation of emergency department patients with severe sepsis
and septic shock. Balanced crystalloids may improve
patient-centered outcomes and should be considered as
an alternative to normal saline, if available. There is
strong evidence that suggests semi-synthetic colloids
decrease survival and should be avoided. The role of albumin in the resuscitation of patients with severe sepsis and
sepsis is uncertain.
reserved.
Ó 2017 Elsevier Inc. All rights
, Keywords—sepsis; severe sepsis; septic shock; fluid
resuscitation; crystalloid; colloid; albumin; hydroxyethyl
starch; balanced solutions; normal saline
INTRODUCTION
Current management of patients who present to the
emergency department (ED) with severe sepsis or septic
shock includes early identification, aggressive fluid
resuscitation, early and appropriate antibiotic
administration, source control, lactate measurement,
and the administration of vasopressor medications, if
required, to maintain a mean arterial blood pressure of
65 mm Hg (1). Fluid resuscitation is a critical component of the ED resuscitation of patients with severe
sepsis and septic shock. Intravenous fluid (IVF) serves
to increase intravascular volume, thereby augmenting
cardiac output and improving tissue perfusion. In the
landmark early goal-directed therapy by Rivers and colleagues, patients randomized to the early goal-directed
therapy group received more IVFs within the initial
6 h compared with those randomized to standard care
(2). Although IVFs are critical in sepsis resuscitation,
there is variation in the choice of which type of
RECEIVED: 22 August 2017;
ACCEPTED: 30 August 2017
1
2
IVF is used for the resuscitation of these patients.
Resuscitation fluids are commonly classified by their
composition and whether they are a crystalloid or
colloid solution.
Crystalloid solutions are defined by the ability to
freely pass semipermeable capillary membranes and are
composed of varying amounts of sodium, chloride, and
other electrolytes (3).
Crystalloid solutions are generally divided into unbalanced and balanced solutions. The prototypical unbalanced solution is 0.9% normal saline (NS), which
contains equivalent amounts of sodium and chloride.
Importantly, the amount of chloride contained in 0.9%
NS is approximately 40% higher than the plasma chloride
concentration. In contrast to 0.9% NS, balanced solutions
are designed to better approximate the physiologic
composition of plasma. As such, balanced solutions
contain inorganic anions (i.e., lactate, gluconate, citrate,
acetate) that are rapidly converted to bicarbonate upon
administration. In addition to inorganic anions, balanced
solutions may also contain cations, such as potassium and
calcium. Finally, balanced solutions contain markedly
less chloride when compared with 0.9% NS. Common examples of balanced crystalloid solutions include Ringer’s
lactate, Ringer’s acetate, and Plasma-Lyte (Baxter
Healthcare Corporation, Deerfield, IL).
Colloid solutions are composed of substances with
higher molecular weight than crystalloids, are generally unable to cross the capillary membrane, and are
suspended within a carrier solution (3). It is commonly
taught that colloid solutions increase intravascular volume by increasing oncotic pressure within the capillary space. Colloid solutions are believed to be
beneficial for resuscitation for several reasons,
including shorter time to hemodynamic stability,
smaller volume of fluid required to achieve stability,
and the potential for a longer duration of effect
when compared with crystalloid solutions (4,5). The
prototypical colloid solution is human albumin. In
addition to albumin, a number of semi-synthetic colloids have also been developed and marketed as resuscitation fluids. Examples of these semi-synthetic
colloid products include the hydroxyethyl starch
(HES), dextran, and gelatin solutions. The most common of these are the HES solutions, which are classified based upon molecular weight and the degree of
hydroxyethylation. Semi-synthetic colloid solutions
may cause renal failure, impairment of the coagulation
system, and anaphylactoid reactions (6).
Over the past several years, numerous articles have
discussed the use of crystalloids (i.e., 0.9% NS,
balanced solutions) and colloids (i.e., albumin, HES)
in sepsis resuscitation. Current international guidelines
for the management of patients with sepsis and septic
M. E. Winters et al.
shock recommend crystalloids as the initial fluid of
choice (1). In addition, these guidelines suggest the
use of balanced fluid solutions (1). Furthermore, guidelines suggest that albumin be considered in addition to
crystalloids for initial resuscitation when patients
require a substantial amount of crystalloids (1). Importantly, these latter two recommendations are based on
low-quality evidence.
This article is a systematic review of recent evidence
regarding the impact of select types of IVF used in the
resuscitation of patients with severe sepsis and septic
shock. The primary goal of this paper is to determine
the preferred IVF for the resuscitation of ED patients
with severe sepsis and septic shock.
METHODS
A structured literature review was performed using
MEDLINE to identify articles that investigated the
type of resuscitation fluid in the management of patients with severe sepsis and septic shock. The search
was limited to studies written in English, involved
only human subjects, and were published between
January 1, 2011 and December 31, 2016. Articles
were also limited to the following design types: randomized controlled trials, meta-analyses, prospective
trials, or retrospective cohort trials. Case series, case
reports, and review articles were excluded. Abstracts
were identified in four separate literature searches,
provided in Table 1. Any abstract that met the initial
screening criteria then underwent an independent review by two authors (MW, RS) to determine if the
article should be included in this review. References
in selected articles were also evaluated to identify
any other articles of interest. All included articles underwent a ‘‘Grade of Evidence’’ review by two of the
study authors (MW, RS). This review was consistent
with the established guidelines of the Clinical Practice
Committee of the American Academy of Emergency
Medicine as listed in Table 2. All included studies
were also provided a separate ‘‘Quality Ranking
Score’’ based upon methodology and study design
(Table 3).
RESULTS
A total of 9062 articles were identified by the structured
literature review. After a thorough review of abstracts
and articles, a total of 17 articles were included in the
analysis (Table 4) (7–23). Eleven studies were original
research investigations and six studies were metaanalyses or systematic reviews. Thirteen studies evaluated the impact of colloid solutions compared with crystalloid solutions, whereas three studies compared
The Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock
3
Table 1. Literature Search
Tier 1
A. Keywords used in search: sepsis OR severe sepsis OR septic shock OR systemic inflammatory response syndrome OR sepsis
syndrome AND intravenous fluid OR fluid resuscitation OR normal saline OR balanced solution OR albumin OR colloid AND
systematic [sb]
B. Database searched: PubMed
C. Dates searched: From 2011 to 2016 with references: 639
D. Limits applied
Limit: Human
Limit: Adult
Limit: English
E. Final search results with # of references: 136
Tier 2
A. Keywords used in search: sepsis OR severe sepsis OR septic shock OR systemic inflammatory response syndrome OR sepsis
syndrome AND intravenous fluid OR fluid resuscitation OR normal saline OR balanced solution OR albumin OR colloid
B. Database searched: PubMed
C. Dates searched: From 2011 to 2016
D. Limits applied
Limit: Human
Limit: Adult
Limit: English
Limit: Randomized controlled trial
E. Final search results with # of references: 1300
Tier 3
A. Keywords used in search: sepsis OR severe sepsis OR septic shock OR systemic inflammatory response syndrome OR sepsis
syndrome AND intravenous fluid OR fluid resuscitation OR normal saline OR balanced solution OR albumin OR colloid
B. Database searched: PubMed
C. Dates searched: From 2011 to 2016
D. Limits applied
Limit: Human
Limit: Adult
Limit: English
Limit: Clinical Trial
E. Final search results with # of references: 1805
Tier 4
A. Keywords used in search: sepsis OR severe sepsis OR septic shock OR systemic inflammatory response syndrome OR sepsis
syndrome AND intravenous fluid OR fluid resuscitation OR normal saline OR balanced solution OR albumin OR colloid
B. Database searched: PubMed
C. Dates searched: From 2011 to 2016
D. Limits applied
Limit: Human
Limit: Adult
Limit: English
E. Final search results with # of references: 9062
balanced with unbalanced crystalloid solutions in the
management of patients with severe sepsis and septic
shock. One meta-analysis evaluated both topics.
Balanced vs. Unbalanced Crystalloid Fluid Solutions
We identified three original research studies that
compared the effect of balanced crystalloid solutions
with unbalanced crystalloid solutions (e.g., 0.9% NS).
Yunos and colleagues performed a prospective, openlabel, prior to-and-after study in a single-center intensive care unit (ICU) in Australia to investigate the association of a chloride-liberal fluid strategy with a
chloride-restrictive fluid strategy on the incidence of
acute kidney injury (21). Chloride-liberal IVF solutions
included 0.9% NS, albumin in NS, and a 4% succinylated gelatin solution. Chloride-restrictive IVFs include
Ringer’s lactate, Plasma-Lyte, and a 20% albumin
Table 2. Definitions of the Criteria Used in Assigning a ‘‘Grade of Evidence Review’’ to the Articles
Grade A
Grade B
Grade C
Grade D
Grade E
Grade F
Randomized clinical trials or meta-analyses (multiple clinical trials) or randomized clinical trials (smaller trials), directly
addressing the review issue
Randomized clinical trials or meta-analyses (multiple clinical trials) or randomized clinical trials (smaller trials), indirectly
addressing the review issue
Prospective, controlled, nonrandomized, cohort studies
Retrospective, nonrandomized, cohort or case-control studies
Case series, animal/model scientific investigations, theoretical analyses, or case reports
Rational conjecture, extrapolations, unreferenced opinion in literature, or common practice
4
M. E. Winters et al.
Table 3. Definitions Used to Assign a ‘‘Quality Ranking Scores’’ for the Included Articles
Ranking
Design Consideration Present
Methodology Consideration Present
Both Considerations Present
Outstanding
Good
Adequate
Poor
Unsatisfactory
Appropriate
Appropriate
Adequate with possible bias
Limited or biased
Questionable/none
Appropriate
Appropriate
Adequate
Limited
Questionable/none
Yes, both present
No, either present
No, either present
No, either present
No, either present
solution. The study was completed in three phases: a 6month control phase whereby patients were administered IVFs according to physician preference, a 6month ‘‘washout’’ period where staff were educated
on the implementation of a chloride-restrictive IVF
strategy, and a 6-month intervention period whereby
only chloride-restrictive IVFs were administered. The
authors reported a decreased rate of acute kidney injury
and the need for renal replacement therapy in patients
who received chloride-restrictive IVFs. There was no
significant difference in patient mortality. Importantly,
only 7.2% of patients in the control period and 10%
of patients in the intervention period had severe sepsis
or septic shock. Furthermore, the results of this trial
are limited by the nonrandomized design and the inclusion of observation bias.
Raghunathan and colleagues completed a retrospective study from 360 hospitals in the Premier Healthcare
Alliance to examine the association between the receipt
of balanced IVFs and isotonic saline during the resuscitation of patients with sepsis (15). Patients included in this
study were admitted to the ICU with a principle or secondary diagnosis of sepsis, had received at least 2 liters
of crystalloid by hospital day 2, and were receiving vasopressors. Patients were divided into those who received <
20%, 20% to 40%, 40% to 60%, 60% to 80%, and more
than 80% of their IVFs as balanced solutions. Of 53,448
patients enrolled in the study, 3396 patients (6.4%)
received balanced solutions. The most common balanced
solution used was Ringer’s lactate, and the majority
received < 40% of their total IVFs as balanced solutions.
Notwithstanding, the authors reported a decrease in inhospital mortality for patients who received balanced solutions compared with those patients who only received
NS (19.6% vs. 22.8%; p = 0.001). There was no change
in the incidence of acute renal failure, hospital length of
stay, or ICU length of stay between the groups. Limitations of the study included its retrospective design and
the fact that the investigators used a patient data set based
on claims. Thus, the data were dependent on physician
documentation and coding.
Shaw and colleagues performed another large retrospective cohort study in which they evaluated the impact
of volume of fluid administered and quantity of chloride
administered on mortality in over 100,000 patients
admitted with systemic inflammatory response syndrome
(23). Importantly, the investigators excluded patients who
received a colloid solution on the day prior to enrollment.
Overall, the authors reported that in-hospital mortality
was lowest in patients with a baseline serum chloride
concentration of 100 to 110 mmol/L (3.4%), compared
with those with a baseline serum chloride concentration
of 130–140 mmol/L (31.1%). The authors also noted
that patients with an increase in chloride concentration
more than 30 mmol/L from baseline also had a higher
mortality rate compared with patients who had an increase in chloride concentration of 10 mmol/L or less
(9.7% vs. 3.7%; p = 0.001).
Crystalloid vs. Semi-synthetic Colloid Fluid Solutions
We identified six original investigations and three metaanalyses that evaluated the use of crystalloids and semisynthetic colloid solutions in sepsis.
Perner and colleagues performed a multicenter,
parallel-group, randomized controlled trial across 26
ICUs in Scandinavia to assess outcomes of patients
with severe sepsis or septic shock who received 6%
HES 130/0.42 or Ringer’s acetate (14). Patients enrolled
in the study were randomized to receive either Ringer’s
acetate or 6% HES 130/0.42. The authors reported that
the group randomized to the HES solution had a statistically higher 90-day mortality when compared with patients randomized to receive Ringer’s acetate (51% vs.
43%, p = 0.03). Unfortunately, the trial was not powered
for mortality after 90 days. Patients who received HES
also had a higher need for renal replacement therapy
(22% vs. 16%, p = 0.04).
Two additional studies were published using the patient population from the Perner trial (14). The first study
evaluated the impact of fluid selection on 6-month and
1-year mortality (17). In this study, the authors found
no difference in 6-month or 1-year mortality in patients
randomized to either Ringer’s acetate or 6% HES 130/
0.42. The second study was a post hoc analysis of the
Perner trial and evaluated the effect of HES on acute kidney injury and mortality (13,14). These authors reported
that 6% HES 130/0.42 was associated with a statistically
significant increase in the rate of acute kidney injury
within the first 5 days, an increase in the need for renal
The Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock
5
Table 4. Articles Identified by the Structured Literature Review with Grade and Quality of Evidence Assignments
Publications
Grade
Quality
Patel A, Laffan MA, Waheed U, Brett SJ. Randomised
trials of human albumin for adults with sepsis:
systematic review and meta-analysis with trial
sequential analysis of all-cause mortality. BMJ
2014;349:g4561 (7).
A
Good
Rochwerg B, Ahazzani W, Sindi A, et al. Fluid
resuscitation in sepsis. A systematic review and
network meta-analysis. Ann Intern Med
2014;161:347–55 (8).
A
Good
Xu JY, Chen QH, Xie JF, et al. Comparison of the
effects of albumin and crystalloid on mortality in
adult patients with severe sepsis and septic shock: a
meta-analysis of randomized clinical trials. Crit Care
2014;18:702 (9).
A
Adequate
Zarychanski R, Abou-Setta AM, Turgeon AF, et al.
Association of hydroxyethyl starch administration
with mortality and acute kidney injury in critically ill
patients requiring volume resuscitation: a
systematic review and meta-analysis. JAMA
2013;309:678–88 (10).
B
Good
Gattas DJ, Dan A, Myburgh J, et al. Fluid resuscitation
with 6% hydroxyethyl starch (130/0.4 and 130/0.42)
in acutely ill patients: systematic review of effects on
mortality and treatment with renal replacement
therapy. Intensive Care Med 2013;39:558–68 (11).
B
Adequate
Delaney AP, Dan A, McCaffrey J, Finfer S. The role of
albumin as a resuscitation fluid for patients with
sepsis: a systematic review and meta-analysis. Crit
Care Med 2011;39:386–91 (12).
A
Poor
Müller RB, Haase N, Lange T, Wetterslev J, Perner A.
Acute kidney injury with hydroxyethyl starch 130/
E
Adequate
Comments
16 RCTs
4190 patients
3 primary trials were multicenter and designed to
investigate the endpoint of all-cause mortality in
3820 randomized patients with severe sepsis and
septic shock.
Comparison fluids were crystalloids (0.9% NS,
Ringer’s lactate) and colloids (HES, gelatin)
All-cause mortality
B Statistically similar between two fluid groups;
no publication bias
B Exclusion of studies at high risk of bias left 6
studies in 3942 patients; not statistically
significant benefit
Albumin compared with crystalloid fluids
B 7 clinical trials randomized 3878 patients
B Mortality similar for both fluid groups
B Publication bias was not detected
B Statistical heterogeneity was not present
Mortality in adults with sepsis, severe sepsis,
septic shock was not significantly reduced or
increased by the use of human albumin products
as part of fluid expansion or resuscitation in
intensive or critical care settings.
14 RCTs included
4-Node analysis
B Higher mortality with starches than
crystalloids
B Lower mortality with albumin than with
crystalloids and starches
6-Node analysis
B Balanced crystalloids are superior to saline
OR 0.78 (95% CI 0.58–1.05; low confidence)
5 studies– 3658 severe sepsis; 2180 septic shock
B 3 studies used 4% or 5% albumin; 1 used
20%; 1 used both concentrations
B Normal saline used in 2 trials; Ringer’s lactate
in 1; the remaining 2 used varying fluids
Mortality
B Severe sepsis: trend toward reduced mortality (OR 0.88) but not statistically significant
B Septic shock: decreased mortality (OR 0.81)
38 trials
B 10,880 patients
B No significant difference in mortality or AKI
When 7 studies at high risk of bias were excluded
– HES was significantly associated with
increased death (RR 1.09)
Incidence of AKI significantly higher in patients
receiving HES (RR 1.27)
35 studies; 25 of which reported on mortality
3 studies had low risk of bias – all published in
year preceding this review and comprised
majority of numbers
Mortality: RR 1.08 (95% CI 1.00–1.17)
RRT: RR 1.25 (95% CI 1.08–1.44)
17 studies– 1977 patients
8 studies in septic patients
9 studies where septic patients were subgroup
Use of albumin associated with reduction in
mortality (OR 0.82, 95% CI 0.67–1.0)
6 studies at high risk of bias were included
Post hoc analysis of 6S study (Perner et al, 2012)
to determine effect of HES on AKI and its
association with mortality (14)
(Continued )
6
M. E. Winters et al.
Table 4. Continued
Publications
Grade
Quality
0.42 in severe sepsis. Acta Anaesthesiol Scand
2015;59:329–36 (13).
Raghunathan K, Shaw A, Nathanson B, et al.
Association between the choice of IV crystalloid and
in-hospital mortality among critically ill adults with
sepsis. Crit Care Med 2014;42:1585–91 (15).
D
Poor
Caironi P, Tognoni G, Masson S, et al. Albumin
replacement in patients with severe sepsis or septic
shock. N Engl J Med 2014;370:1412–21 (16).
A
Outstanding
Perner A, Haase N, Winkel P, et al. Long-term
outcomes in patients with severe sepsis randomised
to resuscitation with hydroxyethyl starch 130/0.42 or
Ringer’s acetate. Intensive Care Med 2014;40:
927–34 (17).
E
Adequate
Annane D, Siami S, Jaber S, et al. Effects of fluid
resuscitation with colloids vs crystalloids on
mortality in critically ill patients presenting with
hypovolemic shock: the CRISTAL randomized trial.
JAMA 2013;310:1809–17 (18).
B
Poor
Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl
starch 130/0.42 versus Ringer’s acetate in severe
sepsis. N Engl J Med 2012;367:124–34 (14).
A
Outstanding
Comments
798 patients
26 ICUs in Scandinavia
Randomized to fluid resuscitation with 130/0.42
HES or Ringer’s acetate
IVF given at discretion of treating clinician
AKI: 28% in HES, 22% in Ringer’s acetate group
AKI more severe and RRT initiated earlier in first
5 days of patients who got HES
Original trial not powered to investigate AKI
Retrospective cohort
360 hospitals of health care alliance
Included adult patients with principal or
secondary diagnosis of sepsis who were
receiving vasopressors by day 2 and needed to
receive at least 2 L of crystalloid by day 2
Categorized into No Balanced IVF Group and
Balanced Group
53,448 patients
3396 patients got some form of balanced fluids
Most received < 40%
Predominant fluid was LR
Absolute in-hospital mortality for balanced group
19.6% vs. 22.8% for No Balanced group
Multicenter, open-label RCT
100 ICUs in Italy
Adult patients who met clinical criteria for severe
sepsis within previous 24 h of ICU stay
Goal was to investigate effects of
albumin + crystalloid to crystalloid alone in severe
sepsis
Patients given 20% albumin+ crystalloid to
maintain serum albumin level of 30 g/L
1818 patients
28-day mortality 31.8% in albumin group and
32% in crystalloid group
No difference in newly developed organ failure
scores or SOFA scores
Protocolized long-term follow-up of the 6S study
Long-term mortality
B 6 months: 53.3% HES vs. 47.5% in Ringer’s
acetate
B 1 year: 56% HES vs. 51.5% Ringer’s acetate
(not significant)
B Longest follow-up: 59.8% HES vs. 56.3%
Ringer’s acetate (not significant)
6S trial not powered for mortality after 90 days
Multicenter, randomized, parallel-group trial
57 ICUs in France, Belgium, Canada, Algeria,
Tunisia
Included patients with no prior IVF resuscitation
during their ICU stay that now needed IVFs for
hypovolemia
Randomized 1:1 stratified by center and
admission diagnosis (sepsis, trauma, other)
2857 patients: 1443 in crystalloid group, 1414 in
colloid group
Severe sepsis main diagnosis
28-day mortality: 25.4% in colloid group; 27% in
crystalloid group
90-day mortality: 30% in colloid group, 34% in
crystalloid group – statistically significant
Protocol violations in 20% of colloid group, took
9 years to recruit, nonblinded
Multicenter, parallel-group, blinded trial
26 ICUs in Scandinavia
Randomized patients with 6% HES 130/0.42 or
Ringer’s acetate at a dose of up to 33 mL/kg IBW
(Continued )
The Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock
7
Table 4. Continued
Publications
Grade
Quality
Myburggh JA, Finfer S, Bellomo R, et al. Hydroxyethyl
starch or saline for fluid resuscitation in intensive
care. N Engl J Med 2012;367:1901–11 (19).
B
Outstanding
Guidet B, Martinet O, Boulain T, et al. Assessment of
hemodynamic efficacy and safety of 6%
hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid
replacement in patients with severe sepsis: the
CRYSTMAS study. Crit Care 2012;16:R94 (20).
A
Adequate
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;308:1566–72
(21).
C
Poor
SAFE Study Investigators, Finfer S, McEvoy S, et al.
Impact of albumin compared with saline on organ
function and mortality of patients with severe sepsis.
Intensive Care Med 2011;37:86–96 (22).
E
Poor
Comments
Primary outcome: death or end-stage kidney
failure at 90 days
804 patients with severe sepsis
HES
B Higher 90-day mortality (51 vs. 43%)
B Increased risk of RRT (22 vs. 16%)
B More RBC transfusion (58 vs. 46%)
Multicenter, randomized, prospective trial
32 medical-surgical ICUs in Australia and New
Zealand
Patients eligible if treating physician felt they
needed fluid therapy
Patients randomized to 6% HES (130/0.4) or
0.9% saline
Primary outcome 90-day all-cause mortality
7000 patients; approx. 28% had sepsis
No difference found in 90-day all-cause mortality
(18% HES, 17% saline)
More patients in HES group required RRT (7% vs.
5.8%)
HES associated with increased risk of adverse
events (5.3% vs. 2.8%)
Prospective, multicenter, active-controlled,
double-blind, randomized trial
24 centers in France and Germany
Adult patients with severe sepsis
HES 130/0.4 vs. NS
Primary outcome was amount of IVF required to
reach hemodynamic stability;
196 patients in the ICU
Most patients got fluids and catecholamines prior
to randomization
Number of patients reaching hemodynamic
stability in 48 h similar in both groups
Less volume used in HES group
Mortality 31% HES vs. 25.3% saline (not
statistically different)
ARF or RRT not significantly different: 24.5%
HES vs. 20% saline
Study not powered for mortality or effects on
kidney function
Prospective, open-label, prior to-and-after study
22-bed multidisciplinary ICU in Melbourne
Australia
Determine if a chloride-restrictive IVF strategy
might be associated with a decreased incidence
of AKI
1533 patients: 760 in control, 773 in intervention
Severe sepsis in 7–10% of patients
Significantly lower increase in serum creatinine
during ICU say during intervention period
Decreased incidence of renal injury and failure
No change in mortality
Limitations: not blinded RCT, subject to
observation bias; lots of different solutions used
Detailed publication of the cohort of 1218
patients in the SAFE trial with severe sepsis at the
time of randomization
SAFE trial was a blinded, randomized, controlled
trial that reported no overall difference in risk of
death for heterogeneous population of patients
who received albumin or saline in the ICU
16 hospitals in Australia and New Zealand
1218 patients: 603 assigned to albumin, 615
assigned to saline
(Continued )
8
M. E. Winters et al.
Table 4. Continued
Publications
Shaw AD, Raghunathan K, Peyerl FW, et al.
Association between intravenous chloride load
during resuscitation and in-hospital mortality among
patients with SIRS. Intensive Care Med
2014;40:1897–905 (23).
Grade
D
Quality
Outstanding
Comments
No significant difference between groups in the
SOFA scores for cardiovascular, respiratory,
renal, or coagulation systems during first 7 days
Number of patients receiving RRT was the same
Mortality: 30.7% for albumin vs. 35.3% for saline
(not significant)
After adjustment for potential confounding
variables, albumin independently associated with
decreased odds of death at 28 days (OR 0.71;
95% CI 0.52–0.97; p = 0.03)
Subgroup analysis – sample size not predetermined, trial not designed to examine albumin and
saline in sepsis; not all patients included in the
multivariate analysis
Retrospective analysis of a prospectively
collected EHR database of 109,836 adult
patients with SIRS from 124 hospitals
Examined change in serum chloride, fluid volume
and chloride administration
Lowest mortality (2.6%) when volume adjusted
chloride load was 105–115 mmol/L
In-hospital mortality was lowest among patients
with baseline chloride concentrations of
100–110 mmol/L (3.4 %) and highest among
patients with 130–140 mmol/L baseline
concentrations (31.1 %)
Larger positive shifts in serum chloride from
baseline were associated with increased
in-hospital mortality
Patients with the smallest increase in serum
chloride concentration (0–10 mmol/L) had the
lowest observed in-hospital mortality (3.7 %),
and mortality increased significantly as the
change in serum chloride increased.
Mortality rate was 7.2 % in patients with shifts of
10–20 mmol/L, 9.2 % in patients with shifts of
20–30 mmol/L and 9.7 % in patients with shifts of
30–40 mmol/L (p = 0.001)
RCT = randomized controlled trial; NS = normal saline; HES = hydroxyethyl starch; OR = odds ratio; CI = confidence interval; AKI = acute
kidney injury; RR = relative risk; RRT = renal replacement therapy; ICU = intensive care unit; IVF = intravenous fluid; LR = lactated Ringer’s
solution; SOFA = Sequential Organ Failure Assessment; IBW = ideal body weight; RBC = red blood cells; ARF = acute renal failure;
SAFE = Saline versus Albumin Fluid Evaluation; EHR = electronic health record; SIRS = systemic inflammatory response syndrome.
replacement therapy, and a longer duration of renal
replacement therapy.
Myburgh and colleagues performed a randomized,
prospective, controlled trial to evaluate the impact of
6% HES 130/0.4 and NS on 90-day mortality in patients
admitted to the ICU (19). Patients were randomized to
receive either 6% HES 130/0.4 or 0.9% NS for resuscitative IVF in the ICU. Resuscitative IVFs were defined as a
bolus of fluid above the amount required for maintenance
of replacement fluids. A total of 7000 patients were
enrolled from 32 ICUs across Australia and New Zealand, of which 1937 had sepsis. The authors reported no
difference in 90-day mortality in patients who received
HES compared with 0.9% NS (18% vs. 17%, p = 0.26).
A statistically significant difference in the percentage of
patients who required renal replacement therapy was
observed in patients who received HES compared with
0.9% NS (7% vs. 5.8%, p = 0.04). In addition, more
patients who received HES had an adverse event,
compared with those who received 0.9% NS (4.6% vs.
3.3%, p = 0.006).
Guidet and colleagues performed a prospective, multicenter, double-blind, randomized, controlled trial in 24
centers in France and Germany to assess the impact of
fluid quantity in patients with severe sepsis (20). The authors enrolled 196 patients and randomized them to
receive either 6% HES 130/0.4 or 0.9% NS. The
maximum amount of fluid allowed for both solutions
was 50 mL/kg/day on the first day, followed by 25 mL/
kg/day on days 2 through 4. The primary endpoint of
this study was the amount of study fluid required to
achieve initial hemodynamic stability, defined as a
mean arterial blood pressure > 65 mm Hg and at least
two of the following: central venous pressure between 8
The Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock
and 12 cm H2O, urine output > 2 mL/kg, and central
venous oxygen saturation > 70%. Overall, the authors reported that patients who received HES required less fluid
to achieve hemodynamic stability when compared with
those who received 0.9% NS (1.379 L vs. 1.709 L,
p = 0.0185). The incidence of acute renal failure was
24.5% in patients who received HES, compared with
20% in patients who received 0.9% NS. Unfortunately,
the study was not powered to detect differences in mortality, percent of patients with acute kidney injury, or the
number of adverse events.
Annane and colleagues performed a multicenter, randomized, parallel-group trial in 57 centers in France,
Belgium, Canada, Algeria, and Tunisia to assess the effects of fluid resuscitation with colloids or crystalloids
on mortality of patients with hypovolemic shock (18). Patients were stratified by center and according to the etiology of shock as sepsis, trauma, or hypovolemia without
sepsis or trauma. Colloid IVFs administered in this study
included gelatins, dextrans, HESs, or albumin. Crystalloid IVFs included NS and Ringer’s lactate. Patients
were included only if they had evidence of acute hypovolemia without any preceding fluid resuscitation. A total of
2857 patients were included in this study, 1443 in the
crystalloid group and 1414 in the colloid group. Overall,
the authors found no difference in 28-day mortality in
those who received a colloid fluid compared with those
patients who received a crystalloid fluid (25.4% vs.
27%, p = 0.26). When evaluating the number of patients
with sepsis as the etiology of hypovolemia (54%), there
was also no difference in 28-day mortality for those
that received a colloid fluid, compared with those who
received a crystalloid fluid (29% vs. 27.8%, odds ratio
0.95). Importantly, protocol violations occurred in
approximately 20% of patients assigned to the colloid
group. In addition, the study was nonblinded and took
9 years to complete.
The three meta-analyses identified during this review
included those by Gattas and colleagues, Zarychanski
and colleagues, and Rochwerg and colleagues
(8,10,11). Gattas and colleagues reported on 35 studies
that assessed fluid resuscitation with 6% HES (130/0.4
and 130/0.42) in critically ill patients (11). These authors
found a relative risk for mortality of 1.08 (95% confidence interval [CI] 1.00–1.17) and a relative risk for renal
replacement therapy of 1.25 (95% CI 1.08–1.44) for patients who receive these 6% HES solutions (11). Zarychanski and colleagues reported on 38 trials comparing
HES with other IVFs in the acute resuscitation of critically ill patients (10). The authors found an increased
relative risk of death (1.09, 95% CI 1.02–1.17) and an
increased relative risk of acute kidney injury (1.27,
95% CI 1.09–1.47) in patients receiving HES solutions
(10). Finally, Rochwerg and colleagues performed a
9
network meta-analysis evaluating all types of fluid used
in the resuscitation of patients with severe sepsis and septic shock (8). The authors included 14 studies in the study
and, using a four-node level network analysis, found a
higher mortality with starch solutions (i.e., HES)
compared with crystalloids.
Crystalloid vs. Albumin Fluid Solutions
The most recent Surviving Sepsis Campaign guidelines
recommend the use of albumin for patients with severe
sepsis or septic shock requiring significant crystalloid
administration (1). We identified five studies that evaluated the use of albumin: two were original research studies
and three were systemic reviews and meta-analyses.
Caironi and colleagues performed the Albumin
Replacement in Patients with Severe Sepsis or Septic
Shock (ALBIOS) Trial (16). The ALBIOS trial was a
multicenter, randomized, controlled, open-label trial conducted in 100 ICUs in Italy to compare the effects of crystalloid fluids with crystalloids plus albumin in patients
with severe sepsis or septic shock (16). An additional
objective of the study was to maintain a serum albumin
concentration of 30 g/L. Over 1800 patients where
enrolled in the trial and randomized to receive either crystalloids alone or crystalloids plus 20% albumin to maintain the target serum albumin concentration. The
administration of semi-synthetic solutions was prohibited. The authors found no statistically significant difference in 28-day mortality between those patients who
received crystalloids alone and those who received crystalloids and albumin (32% vs. 31.8%; relative risk in the
albumin group 1.00, 95% CI 0.87–1.14, p = 0.94). No differences were found between the groups with respect to
the secondary outcomes of 90-day mortality, number of
patients with organ dysfunction, and ICU and hospital
length of stay. Post hoc univariate and multivariate analyses did demonstrate improved survival for patients
with septic shock who received albumin, however,
outcome was worse for those patients without septic
shock who received albumin. The authors concluded
that there was no mortality benefit at 28 and 90 days in
patients with severe sepsis receiving albumin to target a
level of 3 g per liter compared with a resuscitation strategy using only crystalloids.
The SAFE Study Investigators performed a predefined
subgroup analysis of the Saline versus Albumin Fluid
Evaluation (SAFE) trial to compare the effect of albumin
and NS on organ function and mortality (22). Using the
original SAFE trial data set, the authors identified 603 patients with severe sepsis who received albumin and 615
patients who received NS. No statistically significant difference was found between the groups in the number of
patients who required renal replacement therapy. In
10
univariate analysis, the relative risk of death was not
significantly different between the two groups. However,
multivariate analysis revealed an odds ratio of 0.71 (95%
CI 0.52–0.97, p = 0.03) for mortality in patients who
received albumin. Importantly, the SAFE trial was not designed to evaluate septic patients.
Patel and colleagues performed a systematic review
and meta-analysis to assess the safety and efficacy of human albumin as part of the fluid resuscitation strategy in
critically ill patients with sepsis of any severity (7). The
authors included prospective, randomized clinical trials
that reported on adults in a critical care or ICU setting, trials or subgroups of patients that were diagnosed with
sepsis of any severity prior to randomization, had at least
one exposure group that received human albumin of any
concentration, had at least one control group that received
IVF of any strength or type, and had all-cause mortality
data. The authors included 16 trials in the metaanalysis. Seven clinical trials comprising over 3800 patients compared albumin with crystalloid fluids. There
was no difference in mortality when albumin was
compared with crystalloids (relative risk 0.93; 95% CI
0.86–1.01, p = 0.07). Evaluation of these trials did not
reveal evidence of publication bias or statistical heterogeneity. The authors concluded that mortality in adults with
sepsis of any severity was not significantly reduced by the
use of human albumin products as part of the fluid resuscitation strategy in the ICU setting.
Xu and colleagues performed a meta-analysis of randomized clinical trials to examine whether albumin
reduced mortality when used in the resuscitation of adult
patients with severe sepsis or septic shock compared with
crystalloids (9). The authors included randomized or
parallel-group trials performed in adults with severe
sepsis or septic shock who were given albumin for fluid
therapy, compared with patients who received crystalloids, and evaluated all-cause, 28-day, or 90-day mortality. Five studies with a total of 3658 patients with severe
sepsis and 2180 patients with septic shock were included
in the meta-analysis. Three trials used 4% or 5% albumin,
one trial used 20%, and the remaining trial used both concentrations. Regarding crystalloid solutions, two trials
used NS, one trial used Ringer’s lactate, and the remaining two trials used varying crystalloid solutions. For patients with severe sepsis, the authors reported a
nonstatistically significant trend toward reduced mortality (odds ratio 0.88; 95% CI 0.76–1.01, p = 0.08) in patients who received albumin. This result was even more
pronounced, and statistically significant, in patients
with septic shock (odds ratio 0.81; 95% CI 0.67–0.97,
p = 0.03).
Delaney and colleagues performed a systematic review and meta-analysis to evaluate the impact of albumin
as a resuscitation fluid on mortality for patients with
M. E. Winters et al.
sepsis (12). A total of 17 studies with a total of 1977 patients were included in this meta-analysis. Although the
authors concluded that the use of albumin was associated
with reduction in mortality, nine of the studies were not
specifically designed to directly evaluate patients with
sepsis. In addition, six of the studies included in this analysis were from the same author. Finally, this metaanalysis was published in 2011 and did not include
more recent original research on the use of albumin in
sepsis.
DISCUSSION
The initial description of the use of IVF for resuscitation is
credited to Dr. Thomas Latta, when he administered an alkalized salt solution to patients suffering from cholera in
1832 in London, England (24). Since that time, numerous
types of IVF have been developed and used in the resuscitation of critically ill patients. Although the importance
of timing and quantity of IVF used in resuscitation is well
recognized, there is increasing effort to identify the ideal
type of resuscitative fluid to use in the care of acutely ill
patients. In this paper we evaluated the type of IVF used
in the resuscitation of patients with severe sepsis or septic
shock. Specifically, we evaluated current evidence on the
use of crystalloids (balanced vs. NS), albumin, and semisynthetic fluids used in sepsis care.
Based on current evidence, crystalloids solutions
remain the preferred IVF for ED patients with severe sepsis
and septic shock. Though both balanced and unbalanced
crystalloid solutions are acceptable IVFs for sepsis resuscitation, it is important to recognize the potential deleterious
effects of 0.9% NS. NS was first used by Dutch physiologist Hartog Hamburger in 1882, when he studied the lysis
of red blood cells (25). He erroneously concluded that
the concentration of salt in the human body was 0.9%.
As a result of this miscalculation, 0.9% saline became
known as ‘‘normal saline.’’ As previously discussed,
0.9% NS contains supraphysiological amounts of chloride.
In fact, the amount of chloride in 0.9% NS is approximately
40% higher than the concentration of chloride in plasma.
This supraphysiological amount of chloride has been associated with increased renal vasoconstriction, decreased
renal blood flow, and decreased glomerular filtration (26–
28). In addition, increased chloride with 0.9% NS has
been shown to increase mortality among patients with
renal transplantation (29). There is also evidence that demonstrates an increase in systemic inflammation and adverse
effects upon the gastrointestinal, pulmonary, cardiovascular, and hematologic systems when large volumes of
sodium chloride are administered to human subjects
(30–34). When administered in large volumes, 0.9% NS
also reliably induces a hyperchloremic metabolic
acidosis. Given the potential deleterious effects of 0.9%
The Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock
NS, there has been increasing interest in the use of balanced
crystalloid fluids in the resuscitation of patients with sepsis.
Current evidence suggests that balanced crystalloid
solutions may be preferred to 0.9% NS in the
resuscitation of patients with sepsis. This evidence,
however, is limited to retrospective and observational
trials. There is currently no randomized controlled trial
that compares the use of balanced solutions with 0.9%
NS for fluid resuscitation in patients with sepsis.
Notwithstanding, the most recent guidelines from the
Surviving Sepsis Campaign suggest the use of balanced
fluid solutions or saline for fluid resuscitation (1).
The clinical benefit of colloid fluid solutions compared
with crystalloid fluid solutions continues to remain
controversial. It has traditionally been taught that colloid
solutions provide intravascular volume expansion at a ratio of 1:3 when compared with crystalloid solutions. This
ratio was challenged by the results of the SAFE trial,
which found the actual ratio may be closer to 1:1.6 (35).
In addition, recent evidence has highlighted the importance of the endothelial glycocalyx, a complex network
of proteoglycans that may be responsible for the ‘‘leakiness’’ of the endothelium in critically ill states such as
sepsis (36–39). Though research continues with respect
to the function of the endothelial glycocalyx and the
benefit of select colloid solutions, it is clear from the
current evidence that HES solutions may be harmful to
patients and should be avoided. Based on current
evidence, the use of human albumin has not been clearly
shown to improve patient-centered outcomes in patients
with severe sepsis or septic shock. The current guidelines
from the Surviving Sepsis Campaign suggest the use of albumin in addition to crystalloids for initial resuscitation
and subsequent volume expansion when patients require
substantial amounts of crystalloids (1). This suggestion,
however, is based on a low quality of evidence.
RECOMMENDATION
Crystalloids are the preferred solution for the resuscitation of ED patients with severe sepsis and septic shock.
Balanced crystalloids may improve patient-centered outcomes and should be considered as an alternative to 0.9%
NS, if available. There is strong evidence that HES solutions decrease survival and should be avoided. The role of
albumin in the resuscitation of patient with severe sepsis
and sepsis is uncertain.
LEVEL OF RECOMMENDATION: B
Limitations
We acknowledge certain limitations are inherent to this
review. Although we identified over 9000 articles in the
11
initial literature search, it is possible that certain relevant
articles were missed, including those written in foreign
languages and those published prior to and after the
time frame of the literature review. We also recognize
there are relatively few, albeit well-designed trials to evaluate the impact of fluid type upon outcome in patients
with severe sepsis and septic shock, particularly those addressing the topic of balanced and unbalanced crystalloid
solution, which may limit our findings and thus our recommendations.
CONCLUSION
After a review of recent literature, we recommend that patients with severe sepsis and septic shock receive a crystalloid solution during the initial resuscitation. Balanced
solutions may be better than 0.9% NS and can be used
when available; however, additional trials are needed to
confirm this premise. HES solutions should be avoided
in patients with severe sepsis or septic shock, as they
have been associated with adverse outcomes. Recent evidence has not demonstrated any patient-centered benefit
to the use of albumin as a resuscitative fluid in sepsis.
Nonetheless, the current guidelines on severe sepsis and
septic shock from the Surviving Sepsis Campaign provide a weak recommendation for its use with crystalloids
when large volumes of crystalloids are administered.
REFERENCES
1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis
Campaign: international guidelines for management of sepsis and
septic shock: 2016. Intensive Care Med 2017;43:304–77.
2. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in
the treatment of severe sepsis and septic shock. N Engl J Med 2001;
345:1368–77.
3. Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med 2013;
369:1243–51.
4. Estrada CA, Murugan R. Hydroxyethyl starch in severe sepsis: end
of starch era? Crit Care 2013;17:310.
5. Severs D, Hoorn EJ, Rookmaaker MB. A critical appraisal of intravenous fluids: from the physiological basis to clinical evidence.
Nephrol Dial Transplant 2015;30:178–87.
6. Mitra S, Khandelwal P. Are all colloids same? How to select the
right colloid? Indian J Anaesth 2009;53:592–607.
7. Patel A, Laffan MA, Waheed U, Brett SJ. Randomised trials of human albumin for adults with sepsis: systematic review and metaanalysis with trial sequential analysis of all-cause mortality. BMJ
2014;349:g4561.
8. Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in
sepsis. A systematic review and network meta-analysis. Ann Intern
Med 2014;161:347–55.
9. Xu JY, Chen QH, Xie JF, et al. Comparison of the effects of albumin
and crystalloid on mortality in adult patients with severe sepsis and
septic shock: a meta-analysis of randomized clinical trials. Crit Care
2014;18:702.
10. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of
hydroxyethyl starch administration with mortality and acute kidney
injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013;309:678–88.
12
11. Gattas DJ, Dan A, Myburgh J, et al. Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal
replacement therapy. Intensive Care Med 2013;39:558–68.
12. Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a
resuscitation fluid for patients with sepsis: a systematic review and
meta-analysis. Crit Care Med 2011;39:386–91.
13. Müller RB, Haase N, Lange T, Wetterslev J, Perner A. Acute kidney
injury with hydroxyethyl starch 130/0.42 in severe sepsis. Acta
Anaesthesiol Scand 2015;59:329–36.
14. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/
0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 2012;
367:124–34.
15. Raghunathan K, Shaw A, Nathanson B, et al. Association between
the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 2014;42:1585–91.
16. Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients
with severe sepsis or septic shock. N Engl J Med 2014;370:1412–21.
17. Perner A, Haase N, Winkel P, et al. Long-term outcomes in patients
with severe sepsis randomised to resuscitation with hydroxyethyl starch
130/0.42 or Ringer’s acetate. Intensive Care Med 2014;40:927–34.
18. Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with
colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial.
JAMA 2013;310:1809–17.
19. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012;367:
1901–11.
20. Guidet B, Martinet O, Boulain T, et al. Assessment of hemodynamic
efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9%
NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study. Crit Care 2012;16:R94.
21. 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;
308:1566–72.
22. Finfer S, McEvoy S, et al., S.A.F.E. Study Investigators. Impact of
albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 2011;37:86–96.
23. Shaw AD, Raghunathan K, Peyerl FW, et al. Association between
intravenous chloride load during resuscitation and in-hospital
mortality among patients with SIRS. Intensive Care Med 2014;
40:1897–905.
24. Latta TA. Malignant cholera. Documents communicated by the
Central Board of Health, London, relative to the treatment of
cholera by the copious injection of aqueous and saline fluids into
the veins. Lancet 1832;18:274–80.
25. Awad S, Allison SP, Lobo DN. The history of 0.9% saline. Clin Nutr
2008;27:179–88.
M. E. Winters et al.
26. Bullivant EM, Wilcox CS, Welch WJ. Intrarenal vasoconstriction
during hyperchloremia: role of thromboxane. Am J Physiol 1989;
256:152–7.
27. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized,
controlled, double-blind crossover study on the effect of 2-L infusion of 0.9% saline and plasma-lyte 148 on renal blood flow velocity
and renal cortical tissue perfusion in healthy volunteers. Ann Surg
2012;256:18–24.
28. Eisenhut M. Causes and effects of hyperchloremic acidosis. Crit
Care 2006;10:413.
29. Hadimioglu N, Saadawy I, Saglam T, et al. The effect of
different crystalloid solutions on acid-base balance and early
kidney function after kidney transplantation. Anesth Analg
2008;107:264–9.
30. Handy JM, Soni N. Physiological effects of hyperchloraemia and
acidosis. Br J Anaesth 2008;101:141–50.
31. Kellum JA, Song M, Almasri E. Hyperchloremic acidosis increases
circulating inflammatory molecules in experimental sepsis. Chest
2006;130:962–7.
32. Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce
different patterns of inflammatory response in LPS-stimulated
RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol 2004;
286:R686–92.
33. Rackow EC, Falk JL, Fein IA, et al. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic
and septic shock. Crit Care Med 1983;11:839–50.
34. Kiraly LN, Differding JA, Enomoto TM, et al. Resuscitation with
normal saline (NS) vs. lactated ringers (LR) modulates hypercoagulability and leads to increased blood loss in an uncontrolled hemorrhagic shock swine model. J Trauma Acute Care Surg 2006;61:
57–65.
35. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and
saline for fluid resuscitation in the intensive care unit. N Engl J Med
2004;350:2247–56.
36. Reitsma S, Slaaf DW, Vink H, et al. The endothelial glycocalyx:
composition, functions, and visualization. Pflügers Arch 2007;
454:345–59.
37. Woodcock TE, Woodcock TM. Revised Starling equation and the
glycocalyx model of transvascular fluid exchange: an improved
paradigm for prescribing intravenous fluid therapy. Br J Anaesth
2012;108:384–94.
38. Torres LN, Sondeen JL, Ji L, et al. Evaluation of resuscitation fluids
on endothelial glycocalyx, venular blood flow, and coagulation
function after hemorrhagic shock in rats. J Trauma Acute Care
Surg 2013;75:759–66.
39. Chappell D, Westphal M, Jacob M. The impact of the glycocalyx on
microcirculatory oxygen distribution in critical illness. Curr Opin
Anesthesiol 2009;22:155–62.
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