?????
Intensive Care Med
https://doi.org/10.1007/s00134-024-07369-9
GUIDELINES
European Society of?Intensive Care Medicine
clinical practice guideline on?fluid therapy
in?adult critically ill patients. Part 1: the choice
of?resuscitation fluids
1 2 3 4 5,6
Yaseen M. Arabi , Emilie Belley?Cote , Andrea Carsetti , Daniel De Backer , Katia Donadello ,
7 8,9 10 11 12
Nicole P. Juffermans , Naomi Hammond , Jon Henrik Laake , Dawei Liu , Kathryn Maitland ,
13,14 15,16 17 18 19
Antonio Messina , Morten Hylander M?ller , Daniele Poole , Rob Mac Sweeney , Jean?Louis Vincent ,
20 21
Fernando G. Zampieri and Fayez AlShamsi on behalf of European Society of Intensive Care Medicine
? 2024 Springer Verlag GmbH Germany, part of Springer Nature
Abstract
Purpose: This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care
Medicine (ESICM) on resuscitation fluids in adult critically ill patients. This part addresses fluid choice and the other
two will separately address fluid amount and fluid removal.
Methods: This guideline was formulated by an international panel of clinical experts and methodologists. The Grad
ing of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was applied to evaluate
the certainty of evidence and to move from evidence to decision.
Results: For volume expansion, the guideline provides conditional recommendations for using crystalloids rather
than albumin in critically ill patients in general (moderate certainty of evidence), in patients with sepsis (moderate
certainty of evidence), in patients with acute respiratory failure (very low certainty of evidence) and in patients in the
perioperative period and patients at risk for bleeding (very low certainty of evidence). There is a conditional recom
mendation for using isotonic saline rather than albumin in patients with traumatic brain injury (very low certainty of
evidence). There is a conditional recommendation for using albumin rather than crystalloids in patients with cirrhosis
(very low certainty of evidence). The guideline provides conditional recommendations for using balanced crystalloids
rather than isotonic saline in critically ill patients in general (low certainty of evidence), in patients with sepsis (low
certainty of evidence) and in patients with kidney injury (very low certainty of evidence). There is a conditional recom
mendation for using isotonic saline rather than balanced crystalloids in patients with traumatic brain injury (very low
certainty of evidence). There is a conditional recommendation for using isotonic crystalloids rather than small volume
hypertonic crystalloids in critically ill patients in general (very low certainty of evidence).
Correspondence: arabi@mngha.med.sa
1
Intensive Care Department, King Abdulaziz Medical City, Ministry
of National Guard—Health Affairs, King Abdullah International Medical
Research Center, College of Medicine, King Saud Bin Abdulaziz University
for Health Sciences, Riyadh, Saudi Arabia
Full author information is available at the end of the article????
Conclusions: This guideline provides eleven recommendations to inform clinicians on resuscitation fluid choice in
critically ill patients.
Keywords: Albumin, Crystalloid solutions, Colloid solutions, Practice guidelines, Critical care, Fluid therapy
Take?home message
Introduction
Administration of resuscitation fluids is common in the
For volume expansion, the guideline provides conditional recom
management of critically ill patients [1]. The European
mendations for using crystalloids rather than albumin in critically
Society of Intensive Care Medicine (ESICM) convened
ill patients in general, in patients with sepsis, in patients with acute
respiratory failure and in patients in the perioperative period and
a group of content and method experts to issue a clini-
patients at risk for bleeding. There are conditional recommenda
cal practice guideline (CPG) on fluid management in
tions for using isotonic saline rather than albumin in patients with
adult critically ill patients. This CPG was divided into
traumatic brain injury and for using albumin rather than crystalloids
in patients with cirrhosis. The guideline provides conditional rec
three parts: the choice of resuscitation fluids (part 1), the
ommendations for using balanced crystalloids rather than isotonic
amount of resuscitation fluids (part 2), and fluid removal
saline in critically ill patients in general, in patients with sepsis and in
in the de-escalation phase (part 3). The full list of contrib-
patients with kidney injury. There are conditional recommendations
for using isotonic saline rather than balanced crystalloids in patients
utors is presented in the online electronic supplementary
with traumatic brain injury and for using isotonic crystalloids rather
material (ESM). In this manuscript, the guideline on the
than small volume hypertonic crystalloids in critically ill patients in
choice of resuscitation fluid will be presented.
general.
Resuscitation fluids are categorized into crystalloids,
including isotonic saline and balanced crystalloids, and
colloids, with albumin as the reference colloid solution The roles of the panel members are outlined in the online
[2]. In clinical practice, the choice of resuscitation fluids electronic supplementary material (ESM).
varies according to fluid availability, understanding of the
physiologic characteristics of different fluids, clinician
Conflict of?interest management
preferences, practice setting and region [3].
We applied the principles of management of conflict of
The aim of this CPG from ESICM was to provide evi-
interest (COI) as previously described [5]. Panelists were
dence-based guidance regarding the choice of resusci-
requested to declare any intellectual or financial COI that
tation fluid in adult critically ill patients supported by a
may influence their participation in the guideline by com-
critical analysis of the literature.
pleting a special form per the ESICM procedures. A sum-
mary of individual declarations is provided at the end of
the document under the COI section. Panelists received
Methods
no financial incentives for their participation. In addition,
Guideline scope and?target audience
no funding or input from the industry was incorporated
The scope of this guideline was to provide evidence-
into the guideline.
based guidance regarding the choice of early resusci-
tation fluid in adult critically ill patients due to various
etiologies. The target audience for this guideline is front- Development of?questions and?outcomes selection
line clinicians (medical and nursing), allied healthcare This guideline addressed the use of commonly used
workers and policymakers in both high- and low-to-mid- resuscitation fluids in adult critically ill patients: crys-
dle-income contexts. talloids (isotonic saline and balanced crystalloids) and
albumin. One question addressed small-volume hyper-
tonic or isotonic crystalloids. This guideline did not
Panel selection and?organization
address other colloids, such as hydroxyethyl starch
Panel members were appointed with consideration of
(HES) or gelatin. In addition, these guidelines did not
diversity and inclusivity as previously described [4]. The
address fluid choice for managing burns, the use of
panel consisted of two ESICM Guidelines Co-chairs, one
hypertonic solutions for the management of increased
Clinical Chair, two Methods Co-Chairs from ESICM and
intracranial pressure or the use of albumin solutions to
Guidelines in Intensive Care, Development and Evalua-
increase serum albumin levels [6, 7].
tion (GUIDE)?group, the Chairperson of the Methodol-
At the beginning of the process of the guideline
ogy Group of ESICM, and 11 experts, including clinicians
development, the panel proposed several questions
specialized in critical care, anesthesia, infectious diseases
according to the Population, Intervention, Comparison,
and emergency medicine as well as critical care nursing.
and Outcomes (PICO) format. After deliberations, assessed mainly on a clinical basis. All analyses were
the panel prioritized eleven questions, which were performed using Review Manager (RevMan) [Version
approved by the guideline leadership. These questions 5.4, The Cochrane Collaboration, 2020] [18]. Updated
included the following areas: (A) albumin vs. crystal- RevMan data from Lewis et?al?were?used [9]. In addi-
loids (six questions; in critically ill patients in general, tion, published results from Bayesian meta-analysis or
patients with sepsis, patients with acute respiratory individual patient data meta-analysis were also included
failure, patients with ? traumatic brain injury (TBI), when evaluating the evidence. The results of systematic
patients in the perioperative period and in patients reviews were reported according to the Grading of Rec-
with bleeding or at risk for bleeding and patients with ommendations Assessment, Development, and Evalua-
cirrhosis); (B) balanced crystalloids vs. isotonic saline tion (GRADE) guidance, considering the size of effect
(four questions; in critically ill patients in general, and certainty of evidence [19].
patients with sepsis, patients with TBI, and patients
with acute kidney injury); (C) one question for small- Risk of?bias and?certainty of?evidence
volume hypertonic vs. isotonic crystalloids. The Cochrane Collaboration Risk of Bias (ROB) 1.0 tool
Panelists selected and prioritized outcomes for each was used to assess the risk of bias of individual RCTs.
PICO on a scale from 1 to 9 (ranging from unimpor- The GRADE methodology was applied to evaluate the
tant to critical) [8]. The following outcomes judged as certainty of evidence [20]. Accordingly, the certainty
being critical were included: short-term mortality, need of evidence from randomized controlled trials for each
for renal replacement therapy, ventilator-free days/ critical outcome started with a high rating, but it could
duration of mechanical ventilation, intensive care unit be downgraded by one or two points for each of the fol-
(ICU)-free days/ICU length of stay, hospital-free days/ lowing domains: risk of bias, inconsistency, indirectness,
hospital length of stay, quality of life and functional imprecision, and publication bias [21]. If the evidence
outcomes. For the questions regarding patients with was primarily based on study subgroups, the validity of
TBI, the additional critical outcome of the extended the findings was deliberated during the panel discus-
Glasgow Outcome Scale (GOSE) was used. sions. The certainty of evidence for each recommenda-
tion was determined considering the totality of evidence
Literature search across all outcomes including the critical outcome with
Methodologists searched for relevant systematic the lowest certainty [22]. In addition and in line with the
reviews and meta-analyses and updated them when GRADE methodology, the panel also considered the rela-
needed. When neither was available, we searched for tive importance of each outcome so that the whole body
randomized controlled trials in MEDLINE & EMBASE of evidence is not downgraded based on the lower confi-
from inception to April 2022,?and any relevant trials dence in estimates of the effects of a less critical outcome.
published subsequently were also included. We used For each PICO, we reported the level of certainty for each
and updated the search, as relevant, from the reviews outcome, the level of certainty for the whole body of evi-
by Lewis et?al., Tseng et?al. and Bai et?al. for the ques- dence and the domains that were involved in downgrad-
tions related to albumin vs. crystalloids [9–11], by ing in the corresponding Summary of Evidence section,
Hammond et?al., Zampieri et?al. and Wan et?al. for the and provided a more detailed description in the Evidence
questions related to balanced crystalloids vs. isotonic Profile tables in the ESM. The GRADEpro GDT (GRA-
saline [12–14] and by Orbegozo et?al. for small-volume DEpro Guideline Development Tool [Software], McMas-
hypertonic vs. isotonic crystalloids [15]. Although not ter University and Evidence Prime, 2022. Available from
included in the grading process, data from observa- w w w .g rade pr o.or g) was used to create evidence profiles
tional studies were deliberated in panel meetings, as for each PICO.
applicable.
Recommendation formulation
Data analysis The panel met online monthly and used the Evidence-
The DerSimonian and Laird random-effects model was to-Decision (EtD) Framework to formulate recommen-
used when pooling results of effect sizes across rand- dations [23]. As described in the GRADE methodology,
omized controlled trials (RCTs) [16, 17]. Relative risks the panel considered the following factors: magnitude
(RRs) with corresponding 95% confidence intervals of effect, certainty of evidence, patient values and pref-
(CIs) were used for binary outcomes, while mean dif- erences, resources and cost, equity, acceptability, and
ferences (MDs) and 95% CIs were used for continu- feasibility when deciding the direction and strength of
2
ous outcomes. The I statistic was used?for descriptive recommendations. A strong recommendation in favor of
and not inferential purposes, and heterogeneity was an intervention (reported as “we recommend”) implies ??
that the desirable benefit of the intervention outweighs in maintaining circulating volume has been challenged
undesirable effects, that most patients and clinicians by physiologists, pointing toward a possible regulating
would choose the recommendation, and that it can be role for filtration in micro-vessels [25]. Potentially in line
adopted as a policy. On the other hand, a conditional rec- with this view, recent RCTs have failed to demonstrate
ommendation in favor of an intervention (reported as “we any advantage of albumin over crystalloids on patient-
suggest”) implies that the desirable benefit of the interven- centered outcomes. The volume-sparing effect of albu-
tion outweighs the undesirable effects but with a low con- min is probably less pronounced and shorter-lasting than
fidence. It implies that a majority, but not all, individuals initially thought. In the SAFE (the Saline versus Albumin
will likely be best served by the recommended course of Fluid Evaluation) trial, a double-blind RCT, the ratios of
action [23], and that most patients and clinicians, but not the albumin volume to the saline volume ranged from
all, would accept the suggested action from a conditional 1:1.2 to 1:1.6 [26].
recommendation, and for policymakers, it would not be
appropriate to be adopted as a policy. To provide practi- Summary of?the evidence
cal guidance to critical practitioners, we presented the A pooled analysis of RCTs showed that albumin com-
recommendations in favor of a particular approach rather pared with crystalloids in critically ill patients resulted in
than against an alternative [24]. The panel used consensus little to no difference in mortality [16 trials, n = 11,896,
2
to formulate recommendations and all members approved RR 0.98, 95% CI 0.93, 1.04, I 0%, high certainty of evi-
the final recommendations. A family member of a criti- dence, Fig.? 1 and ESM]. Albumin versus crystalloids
cally ill patient reviewed the recommendations, provided might have not resulted in a difference in renal replace-
feedback and supported all eleven recommendations. For ment therapy (5 trials, n = 3508, RR 1.04, CI 0.88, 1.24,
2
each PICO, the panel identified unresolved questions and I 29%, low certainty of evidence). In critically ill patients
research gaps as relevant. in general, albumin versus crystalloids did not result in
a difference in the duration of mechanical ventilation
(high certainty of evidence), might have not affected ICU
Results
length of stay (low certainty of evidence), and might have
Albumin vs. crystalloids
had little to no effect on hospital length of stay but the
evidence was very uncertain. There was no data on albu-
Question 1: Should albumin vs. crystalloids be used
min versus crystalloids’ impact on quality of life (ESM).
for?volume expansion in?adult critically ill patients in?general?
The balance of effects did not favor albumin over?crystal-
loids for volume expansion in critically ill patients, and
Recommendation
the certainty of the whole body of evidence across all out-
We suggest using crystalloids rather than albumin for volume expansion
comes was moderate (downgraded for imprecision).
in adult critically ill patients in general.
The panel considered additional issues when formu-
Conditional recommendation, moderate certainty of evidence.
lating recommendations for using albumin versus crys-
Remark
talloid solutions (EtD framework, ESM). First, the cost
of albumin is higher than that of crystalloids [27, 28]. In
Questions 2, 3, 4, 5 and 6 address the use of albumin vs. crystalloids
in adult critically ill patients with sepsis , adult critically ill patients an international survey, albumin was approximately 27
with acute respiratory failure, adult critically ill patients with TBI, adult
times more costly than an equivalent dose of isotonic
critically ill patients in the perioperative period and those with bleed
saline, with 1 mL of 4% albumin being considered an
ing or at risk for bleeding and adult critically ill patients with cirrho
sis, respectively. equivalent dose to 1.4?mL of saline based on data from
the SAFE trial [26, 28]. Data on cost-effectiveness are
limited, but some studies have demonstrated that albu-
Background
min use might be cost-effective in selected populations
[29, 30]. Other studies have shown that albumin is not
Albumin has been advocated as a more effective fluid
cost-effective, especially in low-resource settings [31, 32].
for expanding intravascular volume than crystalloids
Second, the widespread use of albumin may negatively
because it is believed to be more effectively retained
impact the equitable use of healthcare resources. Third,
within the intravascular space and that it?maintains the
albumin is not available in many resource-limited set-
intravascular oncotic pressure [3]. Based on early physi-
tings. Fourth, albumin is procured from human blood
ologic considerations, albumin has been considered vol-
and, as such, is a limited resource. Fifth, regarding patient
ume-sparing, expanding intravascular volume at a ratio
values and preferences, the panel felt that most patients
of 1:3 compared to crystalloids [3]. Albumin has been
would likely find albumin administration acceptable.
associated with less interstitial edema compared to crys-
However, some patients who avoid blood products may
talloids [3]. However, the importance of oncotic pressure ?
Fig. 1 Forest plots for mortality for albumin compared to crystalloids for questions 1 to 6 in adult critically ill patients in general (Panel A), adult critically ill patients with sepsis (Panel B), adult criti
cally ill patients with acute respiratory failure (Panel C), adult critically ill patients with traumatic brain injury (TBI) (Panel D), adult critically ill patients in the perioperative period and patients with
bleeding or at risk for bleeding (Panel E) and adult critically ill patients with cirrhosis (Panel F)Table 1 Summary of?clinical questions and?recommendations for?albumin vs. crystalloids
a
Specific recommendations are made for adult critically ill patients with sepsis (Question 2), acute respiratory failure (Question 3), traumatic brain injury (Question 4),
patients in the perioperative period and patients with bleeding or at risk for bleeding (Question 5) or cirrhosis (Question 6)
b
Existing data compares isotonic saline, but not balanced crystalloids, to albumin
c
A specific recommendation is made for the use of balanced crystalloids vs. isotonic saline in adult critically ill patients with traumatic brain injury (Question 9)
not accept the use of albumin [3]. Rare allergic reactions Question 2: Should Albumin vs. crystalloids be used
may also cause some to prefer to avoid albumin [33, 34]. for?volume expansion in?adult critically ill patients
With all these considerations, the panel made a condi- with?sepsis?
tional recommendation for using crystalloids rather than
Recommendation
albumin for volume expansion in critically ill patients in
general (Table?1).
We suggest using crystalloids rather than albumin for volume expansion
in adult critically ill patients with sepsis.
Conditional recommendation, moderate certainty of evidence.
Unresolved questions and?research gaps
Studies are needed for albumin solutions in differ-
ent concentrations, and for the interaction of albu-
Background
min effect with the volume of crystalloids administered
Patients with sepsis have decreased vascular tone,
contemporaneously.
increased venous capacitance, and capillary leak, and
may respond to fluid resuscitation [35]. However, resuscitation fluids will eventually distribute into the the?role of albumin in?these groups?remains an?area of
interstitial and intracellular spaces, especially if endothe- uncertainty. A sub-study from the SAFE trial evaluated
lial integrity is impaired, leading to a gradual loss of whether outcomes of resuscitation with albumin or iso-
effect of fluid administration [35, 36]. In addition, the tonic saline in critically ill patients depend on patients’
resulting interstitial edema has been associated with baseline serum albumin concentration [42]. In this sub-
organ dysfunction in sepsis. Albumin may have potential study, which included 6045 patients, 25% of whom had
advantages over crystalloids in patients with sepsis and sepsis on admission, the odds ratios for death for albu-
is believed to afford greater plasma-expanding capacity min compared with saline for patients with a baseline
than crystalloids by maintaining the oncotic pressure in serum albumin concentration of 25 g/l or less and more
the intravascular compartment [3]. In addition, albumin than 25 g/l were 0.87 and 1.09, respectively (ratio of odds
has several pleiotropic properties not related to fluid vol- ratios 0.80, 95% CI 0.63–1.02, P value = 0.08 for hetero-
ume [37–40]. geneity) [42]. Given the limited existing data, there were
different views among the panelists?about using albumin
Summary of?the evidence for volume expansion for patients with hypo-albumine-
For patients with sepsis, the pooled analysis demon- mia, patients who received large volumes of crystalloids
strated that albumin versus crystalloids in patients with and patients with septic shock. Therefore, no recommen-
sepsis did not result in a difference in mortality (9 tri- dations for or against using albumin in these groups were
2
als, n = 5725, RR 0.96, 95% CI 0.89–1.02, I 0%, high issued.
certainty of evidence, Fig.? 1 and ESM). In the CRIS-
TAL (Colloids Versus Crystalloids for the Resuscita- Unresolved questions and?research gaps
tion of the Critically Ill) trial, patients were randomized The choice of fluid in different phases of sepsis therapy
to receive colloids (gelatines, dextrans, hydroxyethyl (resuscitation, optimization, stabilization, and evacu-
starches, or 4% or 20% of albumin) or crystalloids [41]. ation) is still largely unclear and requires further study
Because randomization was not stratified according to [43]. The role of concentrated albumin as a resuscita-
the type of colloid, we conducted a sensitivity analysis tion fluid in patients with sepsis is unclear. Further stud-
excluding the patients from this trial, and the results ies need to evaluate whether there are specific groups
did not change. Albumin versus crystalloids prob- of patients with sepsis in which albumin improves out-
ably?did not result in a difference in renal replacement comes. Fluid choice in resource-limited settings needs
2
therapy (5 trials, n = 3508, RR 1.04, CI 0.88, 1.24, I 29%, to be evaluated. Cost-effective analyses of using albu-
moderate certainty of evidence). In patients with sepsis, min in patients with sepsis are required across different
albumin versus crystalloids probably did not affect ICU settings and patient populations, including those with
length of stay (moderate certainty of evidence), might hypoalbuminemia.
not have?resulted in a difference in ventilator-free days
(low certainty of evidence), and might have had little to
Question 3: Should albumin vs. crystalloids be used
no effect on mechanical ventilation duration and hospi-
for?volume expansion in?adult critically ill patients with?acute
tal length of stay but the evidence was very uncertain.
respiratory failure?
The balance of effects did not favor albumin over?crys-
talloids for volume expansion in patients with sepsis.
Recommendation
The certainty of the whole body of evidence was mod-
We suggest using crystalloids rather than albumin for volume expansion
erate (downgraded for imprecision).
in adult critically ill patients with acute respiratory failure.
Considering the increased cost and limited availability
Conditional recommendation, very low certainty of evidence.
of albumin and the additional considerations listed ear-
lier (under question 1), the panel made a conditional rec-
Background
ommendation for using crystalloids rather than albumin
Acute respiratory distress syndrome (ARDS) is a major
for volume expansion in patients with sepsis (Table?1).
cause of acute respiratory failure [44, 45]. One of the
Does albumin have a role in selected groups of patients
hallmark features of ARDS is the increased alveolar-
with sepsis? The panel discussed thoroughly the potential
capillary permeability resulting in the accumulation
role of albumin in the following selected groups: patients
of fluids into the alveolar space [46]. Fluid filtration
with hypo-albuminemia, patients who received large vol-
across the alveolar-capillary barrier has traditionally
umes of crystalloids and patients with septic shock. Trials
been viewed according to the classic Starling model
in these specific patient groups have been limited; hence, ?
Question 4: Should albumin vs. crystalloids be used
[47]. In this model, fluid filtration is mainly determined
for?volume expansion in?adult critically ill patients
by the hydrostatic gradient and oncotic gradient, and
with?traumatic brain injury?(TBI)?
the interstitial space is considered to have a low pro-
tein concentration. It is now recognized that the inter-
Recommendation
stitial space has a high protein concentration, limiting
the oncotic gradient and reducing fluid return to the
We suggest using isotonic saline rather than albumin for volume expan
plasma compartment and that much of the residual
sion in adult critically ill patients with TBI.
Conditional recommendation, very low certainty of evidence.
fluid in the interstitial space is removed through the
lymphatic system [47].
Remark
The optimal fluid for patients with acute respiratory
Existing RCT data compares isotonic saline, but not balanced crystalloids,
failure (including ARDS) is a fluid that corrects hemody-
to albumin.
namic instability and improves tissue perfusion without
Question 9 addresses the use of balanced crystalloids vs isotonic saline in
inducing pulmonary interstitial edema and compromis-
adult critically ill patients with TBI.
ing pulmonary function. There are data suggesting that
albumin used concurrently with furosemide improves
Background
oxygenation in patients with ARDS compared to crystal-
Current management of severe TBI is centered on main-
loids [48].
taining adequate cerebral perfusion pressure, necessitat-
ing treatment with intravenous fluids and vasopressors
Summary of?the evidence
[51]. Concerns about the safety of 4% albumin were
The literature search identified 3 RCTs, with a total of
raised based on the subgroup analysis from the SAFE
197 participants randomized to receive either albumin
trial [26].
or crystalloids in acute respiratory failure (ARF). This
included data from a subgroup in the SAFE trial [26],
Summary of?the evidence
comprised of only 123 of 6997 randomized patients
In the literature review of RCTs comparing albumin
(1.8%, not stratified by ARF) and two other small stud-
with crystalloids in patients with TBI, we identified
ies (46 and 24 patients randomized) [49, 50]. The pooled
only the subgroup analysis from the SAFE trial [10,
analysis demonstrated that albumin, compared to crys-
52]. The analysis demonstrated that using 4% albu-
talloids, in patients with acute respiratory failure had no
min compared to isotonic saline for volume expan-
effect on mortality, but the evidence was very uncertain
sion in the subgroup of patients with TBI might
2
(RR 1.01, 95% CI 0.73–1.39, I 0%, very low certainty
have?increased mortality at day 28, but the evidence
of evidence, Fig.? 1 and ESM). No other outcomes were
was very uncertain (26.1% vs. 15.7%, RR 1.68, 95% CI
reported for this population (ESM). The balance of ben-
1.16–2.43, P value = 0.005, very low certainty of evi-
efits and harms of either strategy did not favor albumin
dence Fig.? 1 and ESM). A long-term follow-up study
or crystalloids, and the certainty of the whole body of
demonstrated that mortality at two years might have
evidence was very low (downgraded for risk of bias and
remained higher in the albumin group, but the evi-
imprecision, ESM).
dence was very uncertain (420 patients, 33.2% vs.
Considering the factors discussed earlier, including
20.4%, RR 1.63, 95% CI 1.17–2.26, P value = 0.003,
the cost, equity, availability, and patient preferences, the
very low certainty of evidence,?Fig.? 1 and ESM) [52].
panel made a conditional recommendation for using
Patients in the albumin group might less likely have
crystalloids rather than albumin for volume expansion in
had? favorable neurologic outcomes as measured by
patients with ARF (Table?1).
the GOSE, but the evidence was very uncertain (ESM)
[52]. This effect was driven by patients with severe
Unresolved questions and?research gaps
TBI (Glasgow Coma Scale (GCS) score < 9) [52]. A
There are no published clinical trials that have evalu-
mechanistic study [53] ascribed the excess mortal-
ated the effect of albumin or other types of fluids on
ity observed in SAFE-TBI to cerebral edema based
patient-centered outcomes in ARDS. There is also a
on observed higher intracranial pressure in patients
need to investigate the cost-effectiveness of albumin
in the albumin group compared to the isotonic saline
and its effects on long-term outcomes in patients with
group at the end the first week (19.2 ± 1.07 versus
ARDS.
15.4 ± 1.06 mmHg, P value = 0.01). The balance of
benefits and harms favored isotonic saline over albu-
min, the certainty of the whole body of evidence Summary of?the evidence
across all outcomes was very low (downgraded for the
Based on a recent systematic analysis by Tseng et?al., we
risk of bias and imprecision).
identified nine trials comparing albumin with crystalloids
The finding was based on a post hoc subgroup analy-
in adult critically ill patients in the perioperative period
sis. However, subsequent studies suggested the physi-
and in patients with bleeding or at risk for bleeding [10].
ologic plausibility of the finding. The 4% albumin solution
Of these, six trials were performed in patients under-
used in the study was hypotonic (260 mOsm/L), raising
going major vascular surgery and three were in trauma
the question of whether excess mortality was due to the
patients. All studies but one were conducted > 15 years
hypotonic carrier fluid or to the albumin itself. An animal
ago. Albumin, compared to crystalloids had no effect on
study designed to answer this question suggested that the
mortality, but the evidence was very uncertain (9 trials,
albumin solution’s hypotonicity might have been a con-
2
n = 1754, RR 0.96, 95% CI 0.57–1.62, I 0%, Fig.? 1 and
tributing factor [54]. The panel noted that the balance of
ESM). Acute kidney injury was assessed in one study:
effects, cost and equity considerations all favored using
albumin, compared to crystalloids, had no effect on acute
isotonic saline over albumin. Therefore, the panel made
kidney injury, but the evidence was very uncertain. Those
a conditional recommendation for using isotonic saline
receiving albumin had a numerically smaller blood trans-
rather than albumin in TBI patients requiring fluid resus-
fusion volume, which was not statistically significant and
citation (Table?1).
the evidence was very uncertain (mean difference ? 224
2
ml, 95% CI ? 490, 42, I 95%, ESM). The balance of ben-
Unresolved questions and?research gaps
efits and harms did not favor albumin or crystalloids, and
No robust data are addressing the safety and efficacy
the certainty of the whole body of evidence across all out-
of hyperoncotic (20–25%) human albumin solution in
comes was very low (downgraded for risk of bias, indi-
patients with severe TBI [55].
rectness, and imprecision).
Given the balance of effect, in addition to the consid-
Question 5: Should albumin vs. crystalloids be used
erations of albumin versus crystalloids discussed earlier
for?volume expansion in?adult critically ill patients in?the
about the cost, equity, availability and patient prefer-
perioperative period and?in patients with?bleeding or at?risk
ences, the panel made a conditional recommendation for
for?bleeding?
using crystalloids rather than albumin for volume expan-
Recommendation sion in patients with or at risk of bleeding (Table?1).
We suggest using crystalloids rather than albumin for volume expansion
in critically ill patients in the perioperative period and patients with
Unresolved questions and?research gaps
bleeding or at risk for bleeding.
The available evidence is mostly based on relatively old
Conditional recommendation, very low certainty of evidence.
RCTs, which had limited evaluation of outcomes of
interest. More contemporary RCTs are needed to better
Background
understand the effect of fluid choice in this population
Intravenous infusion of resuscitation fluids not contain-
and evaluate the presence of differential effects across
ing coagulation factors impairs coagulation by diluting
patients’ subgroups.
the plasma [56, 57]. This non-specific dilutional effect
on coagulation is determined by the fluid’s volume effi-
Question 6: Should albumin vs. crystalloids be used
cacy, which explains why crystalloids, especially when
for?volume expansion in?adult critically ill patients
given in large volumes, are more likely than albumin to
with?cirrhosis?
cause dilutional coagulopathy [56]. In a matched con-
trolled study of trauma patients, low-compared with
Recommendation
high-volume crystalloid replacement was associated
We suggest using albumin rather than crystalloids for volume expansion
with reduced coagulopathy, blood transfusion, and
in adult critically ill patients with cirrhosis.
mortality, suggesting that the effect is volume-depend-
Conditional recommendation, very low certainty of evidence.
ent [58]. In addition to the dilutional effect, colloids in
general, induce derangements in specific coagulation
Background
factors, although these effects are observed the least
Advanced cirrhosis is associated with complex hemo-
with albumin compared with other colloids [56].
dynamic changes, characterized by increased splanch-
nic blood volume and relative central hypovolemia [59]. Unresolved questions and?research gaps
Infusion of albumin is widely used in cirrhotic patients
Given the limited available data, future work is needed to
for intravascular volume expansion. In addition, stud-
evaluate the question of albumin vs. crystalloids for vol-
ies suggest that the administration of albumin may have
ume expansion in adult critically ill patients with cirrho-
beneficial effects through its antioxidant and anti-inflam-
sis. The role of albumin 20% vs 5% in this population for
matory effects as well as its binding properties for endog-
volume expansion requires further study.
enous and exogenous toxins [59, 60].
In managing patients with cirrhosis, albumin is used
for various indications, including decompensated cir-
rhosis, ascites, encephalopathy, infections, hepatorenal Balanced crystalloids vs. isotonic saline
syndrome and hypoalbuminemia [61–63]. Several sys-
tematic reviews and CPGs have been published over the
Question 7: Should balanced crystalloids vs. isotonic saline
years, addressing these indications based on the existing
be used for?volume expansion in?adult critically ill patients
data that varied in settings (mainly hospitalized patients)
in?general?
and comparisons [11, 61–69]. Many of the conducted tri-
als, for example, those evaluating hepatorenal syndrome, Recommendation
included albumin in both study arms, indicating the lack
We suggest using balanced crystalloids rather than isotonic saline for
of equipoise in the medical community in some of these
volume expansion in adult critically ill patients.
indications. Conditional recommendation, low certainty of evidence.
Remarks
In settings with a limited supply of balanced crystalloids, it is advised
Summary of?the evidence
to prioritize using balanced crystalloids rather than isotonic saline in
A literature review identified three relevant RCTs based
patients who require large volumes of resuscitation fluids and those
on a recent systematic review by Bai et?al., addressing the
with hyperchloremia or acidosis.
question of albumin versus crystalloids [11]. One trial
In settings where balanced crystalloids are unavailable, isotonic saline is
an acceptable alternative.
was performed on critically ill patients with cirrhosis,
Conversely, isotonic saline should be considered in patients with
while the other two included all hospitalized patients with
hypochloremia or metabolic alkalosis.
cirrhosis [70–72]. The studies compared hyper-oncotic
Questions 8, 9 and 10 address the use of balanced crystalloids vs isotonic
albumin in different doses and concentrations. Aggregate
saline in adult critically ill patients with sepsis , traumatic brain injury ,
data from the three trials on 464 patients showed no sta-
and acute kidney injury, respectively.
tistically significant difference in mortality between albu-
min and crystalloids, with the point estimate favoring
albumin, but the evidence was very uncertain (RR 0.89,
Background
2
95% CI 0.75–1.07, I 11%, very low certainty of evidence,
Isotonic saline (normal saline, 0.9% saline) is tradition-
Fig.?1 and ESM). Similar findings were shown when eval-
ally the most commonly used crystalloid solution world-
uating the need for renal replacement therapy, ICU and
wide [2, 73]. Because isotonic saline contains sodium
hospital lenght of stay (LOS) (all very low certainty of
and chloride in equal concentrations (each 154 mmol/l),
evidence, only one trial included, ESM) [72]. The balance
the strong ion difference is zero [3, 74]. As a result, rapid
of benefits and harms favored albumin over crystalloids,
administration of a large volume of isotonic saline can
and the certainty of the whole body of evidence across all
cause hyperchloremic metabolic acidosis. It is recognized
outcomes was very low (downgraded for indirectness and
now that hyperchloremia may be associated with acute
imprecision).
kidney injury [3, 74, 75].
Cost-effectiveness data are limited. One study from
The use of balanced crystalloids has risen over the last
Germany, Italy, and Spain demonstrated that albumin
few years because of concerns about the adverse effects
was cost-effective in the treatment of decompensated
of isotonic saline [2]. Compared to isotonic saline, bal-
cirrhosis [27]. However, data from low-middle-income
anced crystalloids have lower chloride concentrations by
countries are lacking. Despite increased costs and
substituting some chloride with an organic anion, such
reduced equity (EtD framework, ESM), the panel made
as lactate, acetate, gluconate and malate [3, 74]. Addi-
a conditional recommendation for using albumin rather
tionally, balanced crystalloids contain cations other than
than crystalloids for volume expansion in critically ill
sodium (potassium, calcium and magnesium) [3, 74].
patients with cirrhosis (Table?1).Summary of?the evidence
a seven-fold variation in the cost of balanced crystalloids
Our literature review, including the recent systematic
across countries, ranging from 0.14 to 1.04 USD/100 mL
review and meta-analysis on the topic by Hammond
[28]. The panel acknowledged the unavailability or limited
et? al. [13] identified 11 studies with a total of 35,884
availability and the higher cost of balanced crystalloids
participants, of which 9 RCTs with 35,644 participants
compared to isotonic saline in many settings worldwide,
reported the mortality outcome. The pooled estimate
especially in low-income countries [28]. In settings where
demonstrated that balanced crystalloids compared with
there is a limited supply of balanced crystalloids, the panel
isotonic saline in adult critically ill patients did not result
advised to prioritize using balanced crystalloids rather
in a statistically significant difference in mortality (RR
than isotonic saline in patients who require large volumes
2
0.93, 95% CI 0.76–1.15, I 88.44%). In the same system-
of resuscitation fluids and in those with hyperchloremia
atic review, the risk ratio (RR) for 90-day mortality with
or acidosis. A good practice could be to monitor chloride
balanced crystalloids versus saline in a pooled analysis
levels and switch from saline to balanced crystalloids if
from six trials (34,450 participants) with a low risk of
hyperchloremia develops. In? situations where balanced
2
bias was 0.96 (95% CI 0.91–1.01, I 12.1%). In a Bayes-
crystalloids are unavailable, isotonic saline was consid-
ian analysis using vague priors, the posterior probability
ered an acceptable alternative. Conversely, isotonic saline
that balanced crystalloids reduced mortality was 91.69%
should be considered in patients with hypochloremia or
for all trials and 89.5% for low-risk of bias trials [13]. In
metabolic alkalosis.
an individual patient data meta-analysis (six RCTs, 34 653
patients) using a Bayesian regression model, the odds
Unresolved questions and?research gaps
ratio for 90-day mortality with balanced crystalloids ver-
There is a need to compare the effect of different bal-
sus saline was 0.962 (95% credible interval 0.909–1.019),
anced solutions, e.g., PlasmaLyte, Ringer’s lactate or
with an absolute difference –0.4 percentage points [–1.5
acetate and others on patient-centered outcomes. Trials
to 0.2]) and a posterior probability that balanced solu-
of guided therapy with balanced crystalloids and isotonic
tions reduced mortality of 89.5% [14]. These findings
saline are an important next step for critically ill patients.
were generally aligned with the findings of a systematic
Such trials could, for example, include regular chloride
review that included observational studies and RCTs
measurements, allowing for prompt intervention in case
[76]. Collectively, the existing data showed that balanced
of hyperchloremia. Additionally, such trials could con-
crystalloids compared with isotonic saline probably
sider cost variations of fluids and laboratory tests across
resulted in a slight reduction in mortality (moderate cer-
different settings.
tainty of evidence). Balanced crystalloids compared with
isotonic saline probably did not result in a difference in
Question 8: Should balanced crystalloids vs. isotonic saline
renal replacement therapy (low certainty of evidence),
be used for?volume expansion in?adult critically ill patients
might not have changed ventilation-free days (moder-
with?sepsis?
ate certainty of evidence), did not affect vasopressor-free
Recommendation
days or ICU LOS (high certainty of evidence for both
outcomes) and probably did not change hospital length
We suggest using balanced crystalloids rather than isotonic saline for
of stay (moderate certainty of evidence, ESM). The bal-
volume expansion in adult critically ill patients with sepsis.
Conditional recommendation, low certainty of evidence.
ance of benefits and harms favored balanced crystalloids
over isotonic saline, and the certainty of the whole body
of evidence across all outcomes was low (downgraded for
risk of bias, imprecision and inconsistency). Background
Because the balance of benefits and harms favored Isotonic saline was globally the most commonly used
balanced crystalloids over isotonic saline in critically ill resuscitation fluid in patients with sepsis until data
patients, the panel issued a conditional recommenda- emerged suggesting that isotonic saline might increase
tion for using balanced crystalloids rather than isotonic the risk of acute kidney injury due to the high chloride
saline for volume expansion in adult critically ill patients content [77–80]. As a result, balanced crystalloids have
(Table?2). gained popularity as the fluid of choice due to their lower
In a 2014 study conducted in 426 ICUs from 27 coun- chloride content, which mimics human physiologic levels
tries, the average cost for crystalloids overall was less than [2].
1 United States Dollars (USD) per 100 mL, with isotonic
saline being the least costly [28]. There was an 11-fold Summary of?the evidence
variation in the cost of isotonic saline across countries, All recent trials comparing balanced crystalloids to saline
ranging from 0.09 to 1.04 USD/100 mL [28]. There was evaluated subgroups of patients with sepsis [81–85]. Six Table 2 Summary of?clinical questions and?recommendations for?balanced crystalloids vs. isotonic saline
a
Specific recommendations are made for adult critically ill patients with sepsis (Question 8), traumatic brain injury (Question 9), or acute kidney injury (Question 10)
studies contributed to the mortality outcome, including Balanced crystalloids compared with isotonic saline
6914 participants with sepsis [13]. The pooled estimate might not have?resulted in differences in renal replace-
demonstrated that balanced solutions compared with ment therapy or ventilation-free days (low certainty of
isotonic saline in adult critically ill patients with sepsis evidence for both outcomes) and probably did not affect
probably?did not result in a statistically significant reduc- vasopressor-free days (moderate certainty of evidence)
2
tion in mortality (RR 0.93, 95% CI 0.85–1.01, I 19.26%). (ESM). The balance of benefits and harms favored bal-
In an individual patient data meta-analysis using a Bayes- anced crystalloids over isotonic saline, and the certainty
ian regression model, the odds ratio for 90-day mortal- of the whole body of evidence across all outcomes was
ity among patients with sepsis with balanced crystalloids low (downgraded for inconsistency and imprecision).
versus isotonic saline was 0.935 (95% credible interval Based on the available evidence, the panel issued a
0.847–1.040) with a posterior probability that balanced conditional recommendation for using balanced crystal-
solutions reduced mortality of 89.3% [14]. Collectively, loids rather than isotonic saline for volume expansion in
the existing data showed that balanced crystalloids com- patients with sepsis (Table?2).
pared with isotonic saline probably resulted in a slight
reduction in mortality (moderate certainty of evidence). ?
Unresolved questions and?research gaps
mortality [14]. Collectively, the existing data showed
There is a need for trials comparing the effects of differ-
that balanced crystalloids compared with isotonic saline
ent balanced crystalloids on patient-centered outcomes
might have?resulted in an increase in mortality (low cer-
in patients with sepsis.
tainty of evidence). Balanced crystalloids, compared to
isotonic saline, had little to no effect on renal replace-
Question 9: Should balanced crystalloids vs. isotonic saline
ment therapy but the evidence was very uncertain (very
be used for?volume expansion in?adult critically ill patients
low certainty of evidence) (ESM). There were no reported
with?traumatic brain injury (TBI)?
data on neurologic outcomes. However, a secondary
analysis of the SMART trial (Isotonic Solutions and
Recommendation
Major Adverse Renal Events trial) demonstrated that bal-
anced crystalloids compared with isotonic saline? were
We suggest using isotonic saline rather than balanced crystalloids for
associated with worse discharge disposition (death or
volume expansion in adult critically ill patients with TBI.
Conditional recommendation, very low certainty of evidence.
discharge to another medical facility) in critically injured
patients with TBI? (adjusted odds ratio [aOR] 1.38, 95%
Remarks
CI 1.02–1.86, P value = 0.04) [89]. The balance of benefits
Most of the evidence is based on data from RCTs that used balanced
and harms favored isotonic saline over balanced crystal-
crystalloids with nearnormal osmolarity.
loids, and the certainty of the whole body of evidence
More hypotonic balanced crystalloids, such as Ringer’s lactate (or
across all outcomes was very low (downgraded for risk of
acetate), probably should be avoided in patients with TBI.
bias, inconsistency, indirectness, and imprecision).
Based on the available evidence, the panel issued a con-
Background
ditional recommendation for using isotonic saline rather
Fluid osmolarity is an important consideration in patients
than balanced crystalloids for volume expansion in adult
with TBI, as low fluid osmolality has been linked to the
critically ill patients with TBI (Table?2). Because most of
development of cerebral edema [86]. Isotonic saline is
the evidence is based on data from RCTs that used bal-
considered the reference solution because it has an osmo-
anced crystalloids with near-normal osmolarity and
larity of 308 mOsmol/L, which is slightly higher than that
because of observational data demonstrating harm of
of the plasma. Balanced crystalloids vary in osmolarity,
Ringer’s lactate in patients with TBI, the panel advised
but they have an osmolarity slightly lower than isotonic
avoiding Ringer’s lactate (or acetate), in patients with
saline. Ringer’s lactate (or acetate) is slightly hypotonic
TBI.
(osmolarity of Ringer’s lactate 273 mOsmol/L) [87] and
has been associated with higher mortality among patients
Question 10: Should balanced crystalloids or isotonic saline
with TBI compared to isotonic saline in observational
be used for?volume expansion in?adult critically ill patients
data [88]. However, even other balanced crystalloids that
with?kidney injury?
have an osmolality near to the serum osmolality, such
as Plasma-Lyte 148 (osmolarity of 294 mOsmol/L), have
Recommendation
been linked to increased mortality in recent RCTs (see
below).
We suggest using balanced crystalloids rather than isotonic saline for
volume expansion in adult critically ill patients with kidney injury.
Conditional recommendation, very low certainty of evidence.
Summary of?the evidence
Based on a recent systematic review, we identified sub-
group data from 3 RCTs with a low risk of bias that
Background
compared balanced crystalloids with isotonic saline and
Volume expansion in patients with acute kidney injury
reported data on mortality for patients with TBI [13, 81,
(AKI) aims to improve tissue perfusion and maintain
83, 85, 89]. The balanced crystalloid in two trials was
fluid balance without further compromising kidney
Plasma-Lyte, and in one trial Plasma-Lyte or Ringer’s
function.
lactate [89]. The pooled analysis (n = 1896 participants)
demonstrated an increase in mortality with balanced
Summary of?the evidence
crystalloids compared with isotonic saline (RR 1.25, 95%
2 Our literature review identified only one small relevant
CI 1.01–1.54; I = 7%). In an individual patient data meta-
RCT (n = 38) comparing balanced crystalloids or iso-
analysis using a Bayesian regression model, the odds
tonic saline in prerenal AKI with pre-established chronic
ratio for mortality among patients with TBI with bal-
kidney disease (CKD) [90]. Administration of Ringer’s
anced crystalloids compared to isotonic saline was 1.424
lactate or isotonic saline did not result in a significant
(95% credible interval 1.1–1.818) with a high posterior
probability (97.5%) that balanced crystalloids increased ??
difference in short or long-term kidney function, and functional outcomes of TBI patients [95]. It has been
none of the patients required dialysis [90]. We also iden- shown that hypertonic saline solution, compared to iso-
tified indirect evidence from RCTs on patients with renal tonic saline, was associated with improved hemodynam-
transplantation, including the recently published BEST- ics [96]. Hypertonic saline solution may have favorable
Fluids (Better Evidence for Selecting Transplant Fluids) anti-inflammatory effects [97]. Because smaller volumes
trial [12, 91–93]. In this population, pooled data (8 RCTs, of hypertonic saline are needed to expand intravascu-
n = 1526 patients) demonstrated that balanced crystal- lar volume, it has an advantage as a resuscitation fluid
loids compared to isotonic saline might have? reduced on the battlefield and in pre-hospital settings [98–100].
2
renal replacement therapy (RR 0.85, 95% CI 0.73–0.99, I However, the high chloride content of hypertonic saline
0%, low certainty of evidence) and the?need for mechani- may have adverse effects, including acidosis, coagulopa-
cal ventilation (low certainty of evidence) and probably thy, and impaired renal function [101]. Of note, the use
have?reduced delayed graft function (moderate certainty of hypertonic saline in patients with traumatic brain
of evidence). There were no significant differences in hos- injury?(TBI) as a bolus in a pre-hospital setting or as a
pital LOS, but the evidence was very uncertain (ESM). continuous infusion in the ICU has not improved either
The certainty of the whole body of evidence across all short-term or long-term outcomes compared to patients
outcomes was very low (downgraded for inconsistency, who received conventional fluids [100, 102].
indirectness, and imprecision).
The costs of balanced crystalloids solutions are mod-
Summary of?the evidence
est; their availability varies and is probably limited in
Our literature search, including reviewing existing sys-
resource-poor settings. Taking all the above in consid-
tematic reviews [15, 103–107] identified 17 RCTs com-
eration, the panel issued a conditional recommendation
paring hypertonic saline solution to isotonic crystalloids
for using balanced crystalloids rather than isotonic saline
in patients with trauma, hypovolemia, sepsis, and sur-
for volume expansion in adult critically ill patients with
gery. Pooled analysis suggested that hypertonic saline
acute kidney injury (Table?2).
solution compared to isotonic crystalloids in adult
critically ill patients did not reduce mortality (17 trials,
Unresolved questions and?research gaps
2
n = 2195, RR 0.99, 95% CI 0.88–1.12, I 0%, low certainty
There is a need for more data on the choice of balanced
of evidence, Fig.?2 and ESM). The analysis also suggested
crystalloids or isotonic saline for volume expansion in
that hypertonic saline solution compared to isotonic
adult critically ill patients with acute kidney injury.
crystalloids did not result in a difference in renal replace-
ment therapy, ventilation-free days, ICU length of stay,
Small?volume hypertonic or isotonic crystalloids or functional outcomes (low certainty of evidence for the
four outcomes) and the evidence about hospital length of
Question 11: Should small?volume hypertonic or isotonic stay was very uncertain (very low certainty of evidence,
crystalloids be used for?volume expansion in?adult critically ESM). The balance of benefits and harms did not favor
ill patients? small-volume hypertonic or isotonic crystalloids, and the
certainty of the whole body of evidence across all out-
Recommendation
comes was very low (downgraded for risk of bias, incon-
sistency, and imprecision).
We suggest using isotonic crystalloids rather than small volume hyper
The balance of effects did not favor either hypertonic
tonic fluids for volume expansion in adult critically ill patients.
Conditional recommendation, very low certainty of evidence.
saline solution to isotonic crystalloids. However, given
the variable availability, the additional cost, and the lim-
ited acceptability of hypertonic saline among critical care
Background
practitioners, the panel issued a conditional recommen-
Hypertonic saline solution (3%, 5%, 7.5%, 20% or other
dation for using isotonic crystalloids rather than small
concentrations) has been investigated in animal mod-
volume hypertonic fluids for volume expansion (Table?3).
els as an alternative to isotonic crystalloids as for the
management of hypovolemic, hemorrhagic and septic
Unresolved questions and?research gaps
shock. The hypertonic saline solution provides immedi-
Further research is required to identify if there are sub-
ate intravascular volume expansion but with a reduced
groups of adult critically ill patients who may benefit
amount of administered volume [94]. Limited evidence
from hypertonic saline for volume expansion [108].
from observational cohorts showed that a positive fluid
balance was associated with worse ICU mortality and ??
Fig. 2 Forest plots for mortality for small volume hypertonic compared to isotonic crystalloids in adult critically ill patients
Table 3 Summary of?the clinical question and?recommendation for?smallvolume hypertonic or isotonic crystalloids??? ?????? ?? ? ? ? ? ? ? ???? ??
Anaesthesiologica Scandinavia (regarding the use of starches (HES)). DL: none.
Conclusions
KM: none. AM received a lecture fee from Baxter. MHM: none. DP: participated
In conclusion, these guidelines present 11 evidence-
in guidelines focused on fluid management in cerebral injury. RMS: none. JLV:
based recommendations (summarized in Tables?1, 2 and
none. FGZ received consulting fees from Baxter International and is the PI of
the BaSICS trial that received logistic support and fluid donation from Baxter
3) regarding the use of albumin, balanced crystalloids
Hospitalar (Brazil). FA: none.
and isotonic saline as resuscitation fluid in adult critically
ill patients. In addition, research priorities were identified
for future studies.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub
Supplementary Information
lished maps and institutional affiliations.
The online version contains supplementary material available at https://doi.
or g/10.1007/s00134 024 073699.
Received: 13 November 2023 Accepted: 20 February 2024
Author details
1
Intensive Care Department, King Abdulaziz Medical City, Ministry of National
Guard—Health Affairs, King Abdullah International Medical Research Center,
References
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences,
1. Vincent JL, De Backer D (2013) Circulatory shock. N Engl J Med
2
Riyadh, Saudi Arabia. Divisions of Cardiology and Critical Care, McMaster Uni
369:1726–1734
3
versity, Riyadh, Saudi Arabia. Department of Biomedical Sciences and Public
2. Hammond NE, Taylor C, Finfer S, Machado FR, An Y, Billot L, Bloos F,
4
Health, Università Politecnica delle Marche, Ancona, Italy. Department
Bozza F, Cavalcanti AB, Correa M, Du B, Hjortrup PB, Li Y, McIntryre L,
of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels,
Saxena M, Schortgen F, Watts NR, Myburgh J, Fluid TRIPS and Fluidos
5
Belgium. Department of Surgery, Dentistry, Gynaecology and Paediatrics,
Investigators; George Institute for Global Health, The ANZICS Clinical
6
University of Verona, Verona, Italy. Anaesthesia and Intensive Care B Unit,
Trials Group, BRICNet, and the REVA research Network (2017) Patterns
7
AOUIUniversity Hospital Integrated Trust of Verona, Verona, Italy. Depart
of intravenous fluid resuscitation use in adult intensive care patients
ment of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands.
between 2007 and 2014: an international crosssectional study.
8
Critical Care Program, The George Institute for Global Health and UNSW,
PLoS One 12:e0176292
9
Sydney, Australia. Malcolm Fisher Department of Intensive Care, Royal
3. Myburgh JA, Mythen MG (2013) Resuscitation fluids. N Engl J Med
10
North Shore Hospital, Sydney, Australia. Department of Anaesthesiology
369:2462–2463
and Intensive Care Medicine, Division of Emergencies and Critical Care, Oslo
4. Cecconi M, Kesecioglu J, Azoulay E, European Society of Intensive Care
11
University Hospital, Oslo, Norway. Department of Critical Care Medicine,
Medicine (2021) Diversity and inclusivity: the way to multidisciplinary
12
Peking Union Medical College Hospital, Beijing, China. Institute of Global
intensive care medicine in Europe. Intensive Care Med 47:598–601
Health and Innovation, Division of Medicine, Imperial College, London, UK.
5. Alhazzani W, Lewis K, Jaeschke R, Rochwerg B, Moller MH, Evans L,
13
IRCCS Humanitas Research Hospital, Department of Anesthesia and Inten
Wilson KC, Patel S, Coopersmith CM, Cecconi M, Guyatt G, Akl EA (2018)
14
sive Care Medicine, Rozzano, Italy. Department of Biomedical Sciences,
Conflicts of interest disclosure forms and management in critical care
15
Humanitas University, Pieve Emanuele, Milan, Italy. Department of Intensive
clinical practice guidelines. Intensive Care Med 44:1691–1698
Care, Copenhagen University Hospital—Rigshospitalet, K?benhavn, Denmark.
6. SAFE Study Investigators, Finfer S, McEvoy S, Bellomo R, McArthur C,
16
Department of Clinical Medicine, University of Copenhagen, Copenhagen,
Myburgh J, Norton R (2011) Impact of albumin compared to saline on
17
Denmark. Operative Unit of Anesthesia and Intensive Care, S. Martino Hospi
organ function and mortality of patients with severe sepsis. Intensive
18
tal, Belluno, Italy. Regional Intensive Care Unit, Royal Victoria Hospital, Belfast,
Care Med 37:86–96
19
Northern Ireland. Department of Intensive Care, Erasme Hospital, Université
7. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M,
20
libre de Bruxelles, Brussels, Belgium. Department of Critical Care Medicine,
Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M,
21
University of Alberta, Edmonton, Canada. Department of Internal Medicine,
Parrini V, Fiore G, Latini R, Gattinoni L, ALBIOS Study Investigators (2014)
College of Medicine and Health Sciences, United Arab Emirates University, Al
Albumin replacement in patients with severe sepsis or septic shock. N
Ain, United Arab Emirates.
Engl J Med 370:1412–1421
8. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, Alderson P,
Acknowledgements
Glasziou P, Falck Ytter Y, Schunemann HJ (2011) GRADE guidelines: 2.
We thank Jade Shyvers, a patient relative for reviewing the recommendations
Framing the question and deciding on important outcomes. J Clin
and providing feedback.
Epidemiol 64:395–400
9. Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, Rob
Funding
erts I (2018) Colloids versus crystalloids for fluid resuscitation in critically
Panelists received no financial incentives for their participation. In addition, no
ill people. Cochrane Database Syst Rev 8:CD000567
funding or input from the industry was incorporated into the guideline.
10. Tseng CH, Chen TT, Wu MY, Chan MC, Shih MC, Tu YK (2020) Resuscita
tion fluid types in sepsis, surgical, and trauma patients: a systematic
Declarations
review and sequential network metaanalyses. Crit Care 24:693
11. Bai Z, Wang L, Wang R, Zou M, MendezSanchez N, Romeiro FG, Cheng
Conflicts of interest
G, Qi X (2022) Use of human albumin infusion in cirrhotic patients: a
YMA: none. EB C: None. AC: none. DDB: received remuneration from Fresenius,
systematic review and metaanalysis of randomized controlled trials.
Baxter, Pfizer, Edwards, Philips, and has published and presented on the topic.
Hepatol Int 16:1468–1483
KD: none. NPJ received unrestricted funding from Octaphrama for investiga
12. Wan S, Roberts MA, Mount P (2016) Normal saline versus lower chloride
tor driven research on development of fluids for shock treatment that are
solutions for kidney transplantation. Cochrane Database Syst Rev.
associated with reduced vascular permeability, and reported publishing
https://doi.or g/10.1002/14651858.CD010741.pub2
on the topic. NH reported that her institute, the George Institute for Global
13. Hammond NE, Zampieri FG, Tanna GLD, Garside T, Adigbli D, Cavalcanti
Health, has received research and travel funding from Baxter, Fresenius Karbi,
AB, Machado FR, Micallef S, Myburgh J, Ramanan M, Rice TW, Semler
Grifols and CSL. She has several publications related to the topic including
MW, Young PJ, Venkatesh B, Finfer S, Delaney A, (2022) Balanced Crystal
Crystalloid vs Hydroxyethyl Starch Trial (CHEST); Fluid TRIPS; PlasmaLyte vs
loids versus Saline in Critically Ill Adults — A Systematic Review
saline trial (PLUS) and has presented research findings in relation to fluid
with MetaAnalysis. NEJM Evidence 1: EVIDoa2100010
therapy at national and international critical care conferences. JHL presented
14. Zampieri FG, Cavalcanti AB, Di Tanna GL, Damiani LP, Hammond NE,
on the topic at national and international meetings, one opinion piece in Acta
Machado FR, Micallef S, Myburgh J, Ramanan M, Venkatesh B, Rice TW, ??? ??? ?? ? ????? ? ? ? ? ? ? ? ??????? ? ? ? ? ? ? ???? ? ? ? ? ? ?
Semler MW, Young PJ, Finfer S (2024) Balanced crystalloids versus saline 33. Vincent JL, Wilkes MM, Navickis RJ (2003) Safety of human albumin–
for critically ill patients (BESTLiving): a systematic review and individual serious adverse events reported worldwide in 1998–2000. Br J Anaesth
patient data metaanalysis. Lancet Respir Med 12(3):237–246 91:625–630
15. Orbegozo D, Vincent JL, Creteur J, Su F (2019) Hypertonic saline in 34. von Hoegen I, Waller C (2001) Safety of human albumin based on spon
human sepsis: a systematic review of randomized controlled trials. taneously reported serious adverse events. Crit Care Med 29:994–996
Anesth Analg 128:1175–1184 35. Zampieri FG, Bagshaw SM, Semler MW (2023) Fluid therapy for critically
16. DerSimonian R, Laird N (2015) Metaanalysis in clinical trials revisited. Ill adults with sepsis: a review. JAMA 329:1967–1980
Contemp Clin Trials 45:139–145 36. Hahn RG (2020) Understanding volume kinetics. Acta Anaesthesiol
17. DerSimonian R, Laird N (1986) Metaanalysis in clinical trials. Control Scand 64:570–578
Clin Trials 7:177–188 37. Kremer H, BaronMenguy C, Tesse A, Gallois Y, Mercat A, Henrion D,
18. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring incon Andriantsitohaina R, Asfar P, Meziani F (2011) Human serum albumin
sistency in metaanalyses. BMJ 327:557–560 improves endothelial dysfunction and survival during experimental
19. Santesso N, Glenton C, Dahm P, Garner P, Akl EA, Alper B, Brignardello endotoxemia: concentration dependent properties. Crit Care Med
Petersen R, CarrascoLabra A, De Beer H, Hultcrantz M, Kuijpers T, Meer 39:1414–1422
pohl J, Morgan R, Mustafa R, Skoetz N, Sultan S, Wiysonge C, Guyatt G, 38. Hogue B, Chagnon F, Lesur O (2012) Resuscitation fluids and endotoxin
Schunemann HJ, Group GW (2020) GRADE guidelines 26: informative induced myocardial dysfunction: is selection a loadindependent
statements to communicate the findings of systematic reviews of differential issue? Shock 38:307–313
interventions. J Clin Epidemiol 119:126–135 39. Vincent JL, De Backer D, Wiedermann CJ (2016) Fluid management
20. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck Ytter Y, Alonso Coello P, in sepsis: the potential beneficial effects of albumin. J Crit Care
Schunemann HJ, Group GW (2008) GRADE: an emerging consensus 35:161–167
on rating quality of evidence and strength of recommendations. BMJ 40. Semler MW, Rice TW (2016) Sepsis resuscitation: fluid choice and dose.
336:924–926 Clin Chest Med 37:241–250
21. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek 41. Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declere AD, Preiser JC,
J, Vist GE, Falck Ytter Y, Meerpohl J, Norris S, Guyatt GH (2011) GRADE Outin H, Troche G, Charpentier C, Trouillet JL, Kimmoun A, Forceville X,
guidelines: 3. Rating the quality of evidence. J Clin Epidemiol Darmon M, Lesur O, Reignier J, Abroug F, Berger P, Clec’h C, Cousson J,
64:401–406 Thibault L, Chevret S, Investigators C (2013) Effects of fluid resuscitation
22. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso Coello P, with colloids vs crystalloids on mortality in critically ill patients present
Atkins D, Kunz R, Montori V, Jaeschke R, Rind D, Dahm P, Akl EA, Meer ing with hypovolemic shock: the CRISTAL randomized trial. JAMA
pohl J, Vist G, Berliner E, Norris S, Falck Ytter Y, Schunemann HJ (2013) 310:1809–1817
GRADE guidelines: 11. Making an overall rating of confidence in effect 42. SAFE Study Investigators, Finfer S, Bellomo R, McEvoy S, Lo SK, Myburgh
estimates for a single outcome and for all outcomes. J Clin Epidemiol J, Neal B, Norton R (2006) Effect of baseline serum albumin concentra
66:151–157 tion on outcome of resuscitation with albumin or saline in patients
23. Andrews J, Guyatt G, Oxman AD, Alderson P, Dahm P, Falck Ytter Y, in intensive care units: analysis of data from the saline versus albumin
Nasser M, Meerpohl J, Post PN, Kunz R, Brozek J, Vist G, Rind D, Akl EA, fluid evaluation (SAFE) study. BMJ 333:1044
Schunemann HJ (2013) GRADE guidelines: 14. Going from evidence to 43. Malbrain M, Van Regenmortel N, Saugel B, De Tavernier B, Van Gaal
recommendations: the significance and presentation of recommenda PJ, JoannesBoyau O, Teboul JL, Rice TW, Mythen M, Monnet X (2018)
tions. J Clin Epidemiol 66:719–725 Principles of fluid management and stewardship in septic shock: it is
24. GRADE Handbook. https://gdt.g radepr o .or g/app/handb ook/handbook . time to consider the four D’s and the four phases of fluid therapy. Ann
html#:~:t ex t=I n%20general%2C%20it%20seems%20pr ef erable%20t o% Intensive Care 8:66
20pr esent%20r ecommendations%20in%20fa v or%20of%20a%20par 44. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L,
ticular%20management%20appr oach%20rather%20than%20against% van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson
20an%20alt er nativ e. Accessed March 24–2024 BT, Wrigge H, Slutsky AS, Pesenti A, LUNG SAFE Investigators; ESICM
25. Michel CC, Woodcock TE, Curry FE (2020) Understanding and extending Trials Group (2016) Epidemiology, patterns of care, and mortality for
the Starling principle. Acta Anaesthesiol Scand 64:1032–1037 patients with acute respiratory distress syndrome in intensive care units
26. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R, SAFE Study in 50 countries. JAMA 315:788–800
Investigators (2004) A comparison of albumin and saline for fluid resus 45. Pisani L, Algera AG, Neto AS, Azevedo L, Pham T, Paulus F, de Abreu
citation in the intensive care unit. N Engl J Med 350:2247–2256 MG, Pelosi P, Dondorp AM, Bellani G, Laffey JG, Schultz MJ, ERICC study
27. Runken MC, Caraceni P, Fernandez J, Zipprich A, Carlton R, Bunke M investigators; LUNG SAFE study investigators; PRoVENT study investiga
(2019) The cost effectiveness of albumin in the treatment of decom tors; PRoVENTiMiC study investigators (2022) Geoeconomic variations
pensated cirrhosis in Germany, Italy, and Spain. Health Econ Rev 9:22 in epidemiology, ventilation management, and outcomes in invasively
28. Taylor C, Yang L, Finfer S, Machado FR, YouZhong A, Billot L, Bloos F, ventilated intensive care unit patients without acute respiratory distress
Bozza F, Cavalcanti AB, Correa M, Du B, Hjortrup PB, McIntyre L, Saxena syndrome: a pooled analysis of four observational studies. Lancet Glob
M, Schortgen F, Watts NR, Myburgh J, Thompson K, Hammond NE, Health 10:e227–e235
Fluid TRIPS and Fluidos Investigators, The George Institute for Global 46. Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat
Health, The ANZICS Clinical Trials Group, BRICNet, and the REVA A, Herridge M, Randolph AG, Calfee CS (2019) Acute respiratory distress
Research Network (2021) An international comparison of the cost of syndrome. Nat Rev Dis Primers 5:18
fluid resuscitation therapies. Aust Crit Care 34:23–32 47. Mendes RS, Pelosi P, Schultz MJ, Rocco PRM, Silva PL (2020) Fluids in
29. Farrugia A, Bansal M, Balboni S, Kimber MC, Martin GS, Cassar J (2014) ARDS: more pros than cons. Intensive Care Med Exp 8:32
Choice of fluids in severe septic patients—a cost effectiveness analysis 48. Uhlig C, Silva PL, Deckert S, Schmitt J, de Abreu MG (2014) Albumin ver
informed by recent clinical trials. Rev Recent Clin Trials 9:21–30 sus crystalloid solutions in patients with the acute respiratory distress
30. Guidet B, Mosqueda GJ, Priol G, Aegerter P (2007) The COASST study: syndrome: a systematic review and metaanalysis. Crit Care 18:R10
cost effectiveness of albumin in severe sepsis and septic shock. J Crit 49. Metildi LA, Shackford SR, Virgilio RW, Peters RM (1984) Crystalloid versus
Care 22:197–203 colloid in fluid resuscitation of patients with severe pulmonary insuf
31. Tigabu B, Davari M, Kebriaeezadeh A, Mojtahedzadeh M, Sadeghi K, ficiency. Surg Gynecol Obstet 158:207–212
JahangardRafsanjani Z (2019) Is albuminbased resuscitation in severe 50. van der Heijden M, Verheij J, van Nieuw Amerongen GP, Groeneveld AB
sepsis and septic shock justifiable? An evidence from a cost effective (2009) Crystalloid or colloid fluid loading and pulmonary permeability,
ness evaluation. Ethiop J Health Sci 29:869–876 edema, and injury in septic and nonseptic critically ill patients with
32. Tigabu BM, Davari M, Kebriaeezadeh A, Mojtahedzadeh M, Sadeghi hypovolemia. Crit Care Med 37:1275–1281
K, Najmeddin F, JahangardRafsanjani Z (2019) A cost effectiveness 51. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Brat
analysis of albumin in septic shock: a patientlevel data analysis. Clin ton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker
Ther 41(2297–2307):e2292 RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J (2017) Guidelines ?????????????????????????????????
for the management of severe traumatic brain injury, fourth edition. 70. Simon Talero M, GarciaMartinez R, Torrens M, Augustin S, Gomez S,
Neurosurgery 80:6–15 Pereira G, Guevara M, Gines P, Soriano G, Roman E, SanchezDelgado
52. SAFE Study Investigators; Australian and New Zealand Intensive Care J, Ferrer R, Nieto JC, Sunye P, Fuentes I, Esteban R, Cordoba J (2013)
Society Clinical Trials Group; Australian Red Cross Blood Service; George Effects of intravenous albumin in patients with cirrhosis and episodic
Institute for International Health; Myburgh J, Cooper DJ, Finfer S, Bel hepatic encephalopathy: a randomized doubleblind study. J Hepatol
lomo R, Norton R, Bishop N, Kai Lo S, Vallance S (2007) Saline or albumin 59:1184–1192
for fluid resuscitation in patients with traumatic brain injury. N Engl J 71. Philips CA, Maiwall R, Sharma MK, Jindal A, Choudhury AK, Kumar G,
Med 357:874–884 Bhardwaj A, Mitra LG, Agarwal PM, Sarin SK (2021) Comparison of 5%
53. Cooper DJ, Myburgh J, Heritier S, Finfer S, Bellomo R, Billot L, Murray L, human albumin and normal saline for fluid resuscitation in sepsis
Vallance S, SAFE TBI Investigators; Australian and New Zealand Intensive induced hypotension among patients with cirrhosis (FRISC study): a
Care Society Clinical Trials Group (2013) Albumin resuscitation for trau randomized controlled trial. Hepatol Int 15:983–994
matic brain injury: is intracranial hypertension the cause of increased 72. Maiwall R, Kumar A, Pasupuleti SSR, Hidam AK, Tevethia H, Kumar
mortality? J Neurotrauma 30:512–518 G, Sahney A, Mitra LG, Sarin SK (2022) A randomized controlled trial
54. Iguchi N, Kosaka J, Bertolini J, May CN, Lankadeva YR, Bellomo R (2018) comparing 20% albumin to plasmalyte in patients with cirrhosis and
Differential effects of isotonic and hypotonic 4% albumin solution on sepsisinduced hypotension [ALPS trial]. J Hepatol 77:670–682
intracranial pressure and renal perfusion and function. Crit Care Resusc 73. Freitas FGR, Hammond N, Li Y, Azevedo LCP, Cavalcanti AB, Taniguchi
20:48–53 L, Gobatto A, Japiassu AM, Bafi AT, Mazza BF, Noritomi DT, DalPizzol
55. Wiedermann CJ (2022) Use of hyperoncotic human albumin solution F, Bozza F, Salluh JIF, Westphal GA, Soares M, Assuncao MSC, Lisboa T,
in severe traumatic brain injury revisited—a narrative review and meta Lobo SMA, Barbosa AR, Ventura AF, Souza AF, Silva AF, Toledo A, Reis
analysis. J Clin Med 11:2662 A, Cembranel A, Rea Neto A, Gut AL, Justo APP, Santos AP, Albuquer
56. KozekLangenecker SA (2015) Fluids and coagulation. Curr Opin Crit que ACD, Scazufka A, Rodrigues AB, Fernandino BB, Silva BG, Vidal BS,
Care 21:285–291 Pinheiro BV, Pinto BVC, Feijo CAR, Abreu Filho C, Bosso C, Moreira CEN,
57. Rasmussen KC, Secher NH, Pedersen T (2016) Effect of perioperative Ramos CHF, Tavares C, Arantes C, Grion C, Mendes CL, Kmohan C, Piras
crystalloid or colloid fluid therapy on hemorrhage, coagulation compe C, Castro CPP, Lins C, Beraldo D, Fontes D, Boni D, Castiglioni D, Paisani
tence, and outcome: a systematic review and stratified metaanalysis. DM, Pedroso DFF, Mattos ER, Brito Sobrinho E, Troncoso EMV, Rodrigues
Medicine (Baltimore) 95:e4498 Filho EM, Nogueira EEF, Ferreira EL, Pacheco ES, Jodar E, Ferreira ELA,
58. Hussmann B, Lefering R, Waydhas C, Touma A, Kauther MD, Ruchholtz Araujo FF, Trevisol FS, Amorim FF, Giannini FP, Santos FPM, Buarque
S, Lendemans S, Trauma Registry of the German Society for Trauma F, Lima FG, Costa F, Sad F, Aranha FG, Ganem F, Callil F, Costa Filho FF,
Surgery (2013) Does increased prehospital replacement volume lead Dall Arto FTC, Moreno G, Friedman G, Moralez GM, Silva GAD, Costa G,
to a poor clinical course and an increased mortality? A matchedpair Cavalcanti GS, Cavalcanti GS, Betonico GN, Betonico GN, Reis H, Araujo
analysis of 1896 patients of the Trauma Registry of the German Society HBN, Hortiz Junior HA, Guimaraes HP, Urbano H, Maia I, Santiago Filho
for Trauma Surgery who were managed by an emergency doctor at the IL, Farhat Junior J, Alvarez JR, Passos JT, Paranhos J, Marques JA, Moreira
accident site. Injury 44:611–617 Filho JG, Andrade JN, Sobrinho JOC, Bezerra JTP, Alves JA, Ferreira J,
59. Durand F, Kellum JA, Nadim MK (2023) Fluid resuscitation in patients Gomes J, Sato KM, Gerent K, Teixeira KMC, Conde KAP, Martins LF, Figue
with cirrhosis and sepsis: a multidisciplinary perspective. J Hepatol iredo L, Rezegue L, Tcherniacovsk L, Ferraz LO, Cavalcante L, Rabelo
79:240–246 L, Miilher L, Garcia L, Tannous L, Hajjar LA, Paciencia LEM, Cruz Neto
60. Valerio C, Theocharidou E, Davenport A, Agarwal B (2016) Human LMD, Bley MV, Sousa MF, Puga ML, Romano MLP, Nobrega M, Arbex M,
albumin solution for patients with cirrhosis and acute on chronic liver Rodrigues ML, Guerreiro MO, Rocha M, Alves MAP, Alves MAP, Rosa MD,
failure: beyond simple volume expansion. World J Hepatol 8:345–354 Dias MD, Martins M, Oliveira M, Moretti MMS, Matsui M, Messender O,
61. Best LM, Freeman SC, Sutton AJ, Cooper NJ, Tng EL, Csenar M, Hawkins Santarem OLA, Silveira P, Vassallo PF, Antoniazzi P, Gottardo PC, Correia
N, Pavlov CS, Davidson BR, Thorburn D, Cowlin M, Milne EJ, Tsochatzis P, Ferreira P, Torres P, Silva P, Foernges R, Gomes R, Moraes R, Nonato
E, Gurusamy KS (2019) Treatment for hepatorenal syndrome in people Filho R, Borba RL, Gomes RV, Cordioli R, Lima R, Lopez RP, Gargioni RRO,
with decompensated liver cirrhosis: a network metaanalysis. Cochrane Rosenblat R, Souza RM, Almeida R, Narciso RC, Marco R, Waltrick R,
Database Syst Rev 9:CD013103 Biondi R, Figueiredo R, Dutra RS, Batista R, Felipe R, Franco R, Houly S,
62. Benmassaoud A, Freeman SC, Roccarina D, Plaz Torres MC, Sutton AJ, Faria SS, Pinto SF, Luzzi S, Sant’ana S, Fernandes SS, Yamada S, Zajac S,
Cooper NJ, Iogna Prat L, Cowlin M, Milne EJ, Hawkins N, Davidson BR, Vaz SM, Bezerra SAB, Farhat TBT, Santos TM, Smith T, Silva UVA, Dama
Pavlov CS, Thorburn D, Tsochatzis E, Gurusamy KS (2020) Treatment for sceno VB, Nobre V, Dantas VCS, Irineu VM, Bogado V, Nedel W, Campos
ascites in adults with decompensated liver cirrhosis: a network meta Filho W, Dantas W, Viana W, Oliveira Filho W, Delgadinho WM, Finfer S,
analysis. Cochrane Database Syst Rev 1:CD013123 Machado FR (2021) Resuscitation fluid practices in Brazilian intensive
63. Simonetti RG, Perricone G, Nikolova D, Bjelakovic G, Gluud C (2019) care units: a secondary analysis of Fluid TRIPS. Rev Bras Ter Intensiva
Plasma expanders for people with cirrhosis and large ascites treated 33:206–218
with abdominal paracentesis. Cochrane Database Syst Rev 6:CD004039 74. Finfer S, Myburgh J, Bellomo R (2018) Intravenous fluid therapy in criti
64. Leao GS, John Neto G, Jotz RF, Mattos AA, Mattos AZ (2019) Albumin cally ill adults. Nat Rev Nephrol 14:541–557
for cirrhotic patients with extraperitoneal infections: a metaanalysis. J 75. Soussi S, Ferry A, Chaussard M, Legrand M (2017) Chloride toxicity in
Gastroenterol Hepatol 34:2071–2076 critically ill patients: what’s the evidence? Anaesth Crit Care Pain Med
65. Bombassaro IZ, Tovo CV, de Mattos AZ, Ahlert M, Chiesa T, de Mattos 36:125–130
AA (2021) Albumin in the management of hepatic encephalopathy: a 76. Hammond DA, Lam SW, Rech MA, Smith MN, Westrick J, Trivedi AP, Balk
systematic review and metaanalysis. Ann Hepatol 26:100541 RA (2020) Balanced crystalloids versus saline in critically ill adults: a
66. Teh KB, Loo JH, Tam YC, Wong YJ (2021) Efficacy and safety of albumin systematic review and metaanalysis. Ann Pharmacother 54:5–13
infusion for overt hepatic encephalopathy: a systematic review and 77. Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C,
metaanalysis. Dig Liver Dis 53:817–823 Myburgh J, Investigators ST (2010) Resuscitation fluid use in critically ill
67. Ashour AA, Atta MA, Sadek KW, Obaid KR, Ashour MA, Ashour A, Dan adults: an international crosssectional study in 391 intensive care units.
juma MI, Doi SA, ElZouki AN (2021) Albumin administration in patients Crit Care 14:R185
with decompensated liver cirrhosis: a metaanalytic update. Eur J 78. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Associa
Gastroenterol Hepatol 33:479–486 tion between a chlorideliberal vs chloride restrictive intravenous fluid
68. Xu T, Liu W, Huang R (2023) Can albumin reduce the mortality of administration strategy and kidney injury in critically ill adults. JAMA
patients with cirrhosis and ascites? A metaanalysis of randomized 308:1566–1572
controlled trials. Eur J Gastroenterol Hepatol 35:80–88 79. Brown RM, Wang L, Coston TD, Krishnan NI, Casey JD, Wanderer JP,
69. Zaccherini G, Tufoni M, Bernardi M (2020) Albumin administration is Ehrenfeld JM, Byrne DW, Stollings JL, Siew ED, Bernard GR, Self WH, Rice
efficacious in the management of patients with cirrhosis: a systematic TW, Semler MW (2019) Balanced crystalloids versus saline in sepsis. a
review of the literature. Hepat Med 12:153–172????????????????????????????????????
secondary analysis of the SMART clinical trial. Am J Respir Crit Care Med Laurence JM, Lim WH, McTaggart SJ, O’Connell PJ, Pilmore HL, Wong
200:1487–1495 G, Chadban SJ, BESTFluids Investigators; Australasian Kidney Trials
80. Raghunathan K, Shaw A, Nathanson B, Sturmer T, Brookhart A, Stefan Network (2023) Balanced crystalloid solution versus saline in deceased
MS, Setoguchi S, Beadles C, Lindenauer PK (2014) Association between donor kidney transplantation (BESTFluids): a pragmatic, double blind,
the choice of IV crystalloid and inhospital mortality among critically ill randomised, controlled trial. Lancet 402:105–117
adults with sepsis. Crit Care Med 42:1585–1591 94. Drobin D, Hahn RG (2002) Kinetics of isotonic and hypertonic plasma
81. Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, volume expanders. Anesthesiology 96:1371–1380
McGuinness S, Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R, 95. Wiegers EJA, Lingsma HF, Huijben JA, Cooper DJ, Citerio G, Frisvold S,
Investigators S, ANZICS CTG (2015) Effect of a buffered crystalloid solu Helbok R, Maas AIR, Menon DK, Moore EM, Stocchetti N, Dippel DW,
tion vs saline on acute kidney injury among patients in the intensive Steyerberg EW, van der Jagt M, CENTER TBI; OzENTER TBI Collaboration
care unit: the SPLIT randomized clinical trial. JAMA 314:1701–1710 Groups (2021) Fluid balance and outcome in critically ill patients with
82. Semler MW, Wanderer JP, Ehrenfeld JM, Stollings JL, Self WH, Siew ED, traumatic brain injury (CENTER TBI and OzENTER TBI): a prospec
Wang L, Byrne DW, Shaw AD, Bernard GR, Rice TW, SI, the Pragmatic tive, multicentre, comparative effectiveness study. Lancet Neurol
Critical Care Research G, Investigators S (2017) Balanced crystalloids 20:627–638
versus saline in the intensive care unit the SALT randomized trial. Am J 96. Oliveira RP, Velasco I, Soriano FG, Friedman G (2002) Clinical review:
Respir Crit Care Med 195:1362–1372 hypertonic saline resuscitation in sepsis. Crit Care 6:418–423
83. Semler MW, Self WH, Rice TW (2018) Balanced crystalloids versus saline 97. Pascual JL, Khwaja KA, Ferri LE, Giannias B, Evans DC, Razek T, Michel RP,
in critically ill adults. N Engl J Med 378:1951 Christou NV (2003) Hypertonic saline resuscitation attenuates neutro
84. Finfer S, Micallef S, Hammond N, Navarra L, Bellomo R, Billot L, Delaney phil lung sequestration and transmigration by diminishing leukocyte
A, Gallagher M, Gattas D, Li Q, Mackle D, Mysore J, Saxena M, Taylor C, endothelial interactions in a twohit model of hemorrhagic shock and
Young P, Myburgh J, PLUS Study Investigators and the Australian New infection. J Trauma 54:121–130
Zealand Intensive Care Society Clinical Trials Group (2022) Balanced 98. Dubick MA, Atkins JL (2003) Small volume fluid resuscitation for the
multielectrolyte solution versus saline in critically ill adults. N Engl J Med farforward combat environment: current concepts. J Trauma 54:S4345
386:815–826 99. Smith JE, Hall MJ (2004) Hypertonic saline. J R Army Med Corps
85. Zampieri FG, Machado FR, Biondi RS, Freitas FGR, Veiga VC, Figueiredo 150:239–243
RC, Lovato WJ, Amendola CP, SerpaNeto A, Paranhos JLR, Guedes 100. Cooper DJ, Myles PS, McDermott FT, Murray LJ, Laidlaw J, Cooper
MAV, Lucio EA, Oliveira Junior LC, Lisboa TC, Lacerda FH, Maia IS, Grion G, Tremayne AB, Bernard SS, Ponsford J, Investigators HTSS (2004)
CMC, Assuncao MSC, Manoel ALO, Silva Junior JM, Duarte P, Soares RM, Prehospital hypertonic saline resuscitation of patients with hypotension
Miranda TA, de Lima LM, Gurgel RM, Paisani DM, Correa TD, Azevedo and severe traumatic brain injury: a randomized controlled trial. JAMA
LCP, Kellum JA, Damiani LP, Brandao da Silva N, Cavalcanti AB, BaSICS 291:1350–1357
investigators and the BRICNet members (2021) Effect of intravenous 101. Orbegozo Cortes D, Rayo Bonor A, Vincent JL (2014) Isotonic crystal
fluid treatment with a balanced solution vs 0.9% saline solution on loid solutions: a structured review of the literature. Br J Anaesth
mortality in critically ill patients: the BaSICS randomized clinical trial. 112:968–981
JAMA 326:1–12 102. Roquilly A, Moyer JD, Huet O, Lasocki S, Cohen B, DahyotFizelier C,
86. Ramming S, Shackford SR, Zhuang J, Schmoker JD (1994) The relation Chalard K, Seguin P, Jeantrelle C, Vermeersch V, Gaillard T, Cinotti R,
ship of fluid balance and sodium administration to cerebral edema Demeure Dit Latte D, Mahe PJ, Vourc’h M, Martin FP, Chopin A, Lere
formation and intracranial pressure in a porcine model of brain injury. J bourg C, Flet L, Chiffoleau A, Feuillet F, Asehnoune K (2021) Effect of
Trauma 37:705–713 continuous infusion of hypertonic saline vs standard care on 6month
87. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ (1999) The effect neurological outcomes in patients with traumatic brain injury: the COBI
of intravenous lactated Ringer’s solution versus 0.9% sodium chloride randomized clinical trial. JAMA 325:2056–2066
solution on serum osmolality in human volunteers. Anesth Analg 103. Li B, Zhao H, Zhang J, Yan Q, Li T, Liu L (2020) Resuscitation fluids in
88:999–1003 septic shock: a network metaanalysis of randomized controlled trials.
88. Rowell SE, Fair KA, Barbosa RR, Watters JM, Bulger EM, Holcomb Shock 53:679–685
JB, Cohen MJ, Rahbar MH, Fox EE, Schreiber MA (2016) The impact 104. Bunn F, Roberts I, Tasker R, Akpa E (2004) Hypertonic versus near iso
of pre?hospital administration of lactated ringer’s solution versus tonic crystalloid for fluid resuscitation in critically ill patients. Cochrane
normal saline in patients with traumatic brain injury. J Neurotrauma Database Syst Rev 2004:CD002045
33:1054–1059 105. Safiejko K, Smereka J, Pruc M, Ladny JR, Jaguszewski MJ, Filipiak KJ,
89. Lombardo S, Smith MC, Semler MW, Wang L, Dear ML, Lindsell CJ, Yakubtsevich R, Szarpak L (2022) Efficacy and safety of hypertonic saline
Freundlich RE, Guillamondegui OD, Self WH, Rice TW, Isotonic S, Major solutions fluid resuscitation on hypovolemic shock: a systematic review
Adverse Renal Events Trial I, Vanderbilt Learning Healthcare System and metaanalysis of randomized controlled trials. Cardiol J 29:966–977
Platform I (2022) Balanced crystalloid versus saline in adults with trau 106. Pfortmueller CA, Schefold JC (2017) Hypertonic saline in critical
matic brain injury: secondary analysis of a clinical trial. J Neurotrauma illness—a systematic review. J Crit Care 42:168–177
39:1159–1167 107. Wu MC, Liao TY, Lee EM, Chen YS, Hsu WT, Lee MG, Tsou PY, Chen SC,
90. Papasotiriou M, Mpratsiakou A, Georgopoulou G, Ntrinias T, Balta L, Lee CC (2017) Administration of hypertonic solutions for hemorrhagic
Pavlakou P, Goumenos DS, Papachristou E (2023) Normal saline versus shock: a systematic review and metaanalysis of clinical trials. Anesth
balanced crystalloids in patients with prerenal acute kidney injury and Analg 125:1549–1557
pre existing chronic kidney disease. Rom J Intern Med 61:98–105 108. Shrum B, Church B, McArthur E, Burns KE, Znajda T, McAlister V
91. Jahangir A, Sahra S, Niazi MRK, Siddiqui FS, Anwar MY, Jahangir A, (2016) Hypertonic salt solution for peri operative fluid management.
El Charabaty EJ (2021) Comparison of normal saline solution with low Cochrane Database Syst Rev 2016:CD005576
chloride solutions in renal transplants: a metaanalysis. Kidney Res Clin
Pract 40:484–495
92. Wagener G, Bezinover D, Wang C, Kroepfl E, Diaz G, Giordano C, West
J, Kindscher JD, Moguilevitch M, NicolauRaducu R, Planinsic RM,
Rosenfeld DM, Lindberg S, Schumann R, Pivalizza EG (2021) Fluid
management during kidney transplantation: a consensus statement
of the committee on transplant anesthesia of the American Society of
Anesthesiologists. Transplantation 105:1677–1684
93. Collins MG, Fahim MA, Pascoe EM, Hawley CM, Johnson DW, Varghese
J, Hickey LE, Clayton PA, Dansie KB, McConnochie RC, Vergara LA, Kiri
wandeniya C, Reidlinger D, Mount PF, Weinberg L, McArthur CJ, Coates
PT, Endre ZH, Goodman D, Howard K, Howell M, Jamboti JS, Kanellis J, |
|
