REVIEW

CURRENT
OPINION The ideal crystalloid – what is ‘balanced’?
Thomas J. Morgan

Purpose of review
This review explores the contemporary definition of the term ‘balanced crystalloid’ and outlines optimal
design features and their underlying rationale.
Recent findings
Crystalloid interstitial expansion is unavoidable, but also occurs with colloids when there is endothelial
glycocalyx dysfunction. Reduced chloride exposure may lessen kidney dysfunction and injury with a
possible mortality benefit. Exact balance from an acid–base perspective is achieved with a crystalloid
strong ion difference of 24 mEq/l. This can be done simply by replacing 24 mEq/l of chloride in 0.9%
sodium chloride with bicarbonate or organic anion bicarbonate substitutes. Potassium, calcium and
magnesium additives are probably unnecessary. Large volumes of mildly hypotonic crystalloids such as
lactated Ringer’s solution reduce extracellular tonicity in volunteers and increase intracranial pressure in
nonbrain-injured experimental animals. A total cation concentration of 154 mmol/l with accompanying
anions provides isotonicity. Of the commercial crystalloids, Ringer’s acetate solution is close to balanced
from both acid–base and tonicity perspectives, and there is little current evidence of acetate toxicity in the
context of volume loading, in contrast to renal replacement.
Summary
The case for balanced crystalloids is growing but unproven. A large randomized controlled trial of
balanced crystalloids versus 0.9% sodium chloride is the next step.
Keywords
acid–base, balanced crystalloid, strong ion difference, tonicity

INTRODUCTION even reliably reduced by colloids [4 ,5]. At low

&&

The advent of the Stewart approach has allowed
greater insight into important design features of a
‘balanced’ crystalloid from the acid–base perspec-
tive [1]. However, if the broader aim of balancing
crystalloids is to minimize all perturbations of the
extracellular milieu when large volumes are admin-
capillary hydrostatic pressures, transcapillary fluid
losses for both crystalloids and colloids are similar.
Furthermore, the integrity of the endothelial glyco-
calyx layer, an active interface moderating macro-
molecular transcapillary transit, is damaged by a
variety of insults including inflammatory states
&&

istered rapidly, acid–base is one of several consider- and simple hypervolaemia [2,4 ]. The result is
ations. Accordingly, this review will focus on the higher than expected volume requirements for
&

following areas: colloids in various forms of critical illness [5,6,7 ],

(1) Interstitial ‘spillover’
(2) Acid–base and chloride
(3) Ancillary cations: potassium, calcium and mag-
nesium
(4) Tonicity.
INTERSTITIAL ‘SPILLOVER’
Eighty percent of a crystalloid volume load ends up
in the interstitium [2]. The result can be tissue and
organ oedema, and even in health this fluid takes
days to be excreted [3]. However, it is now apparent
that interstitial expansion is neither eliminated nor
almost identical to those of crystalloids in early
blunt trauma [5].
Some ‘context-specific’ drawbacks of colloids
versus crystalloids may be connected to their failure
Mater Medical Research Institute and University of Queensland, Mater
Health Services, Stanley Street, South Brisbane, Brisbane, Queensland,
Australia
Correspondence to Dr T.J. Morgan, Intensive Care Unit, Mater Adult
Hospital, Mater Health Services, Raymond Terrace, South Brisbane,
Queensland 4101, Australia. Tel: +61 7 3163 8111; fax: +61 7 3163
1503; e-mail: t.morgan@uq.edu.au
Curr Opin Crit Care 2013, 19:299–307
DOI:10.1097/MCC.0b013e3283632d46

1070-5295 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-criticalcare.com

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Intravenous fluids
KEY POINTS
 The ideal balanced crystalloid is normotonic with a
strong ion difference of 24 mEq/l.
 This can be achieved by excising 24 mEq/l of chloride
from 0.9% sodium chloride and substituting
bicarbonate or organic anions, which disappear
rapidly on infusion, such as L-lactate or acetate.
 Interstitial expansion is inevitable on volume loading
but colloids also have this problem to a varying extent.
 A large randomized controlled trial is required to
determine whether balanced crystalloids are superior to
0.9% sodium chloride as suggested by current
evidence.
to target the intravascular space selectively. For
example, 4% albumin resuscitation is associated
with increased mortality in traumatic brain injury
[8]. Starch-based colloids administered to general
ICU patients are linked to renal injury and excess
&
blood product requirements [7 ,9] plus an increased
&
mortality rate in severe sepsis [10 ], and there are
renal toxicity concerns with gelatine-based fluids
&
[11 ,12].
Accordingly, crystalloids can be expected to
retain a prominent role in rapid volume expansion
in the foreseeable future despite interstitial ‘spill-
over’ [13].
ACID–BASE
Several litres of intravenous 0.9% saline infused over
a few hours will reliably cause hyperchloraemia
accompanied on most occasions by a normal anion
gap metabolic acidosis [14–17]. Identical phenom-
ena occur during cardiopulmonary bypass [18–20]
and following other forms of normovolaemic hae-
modilution [21]. The Stewart approach provides a
useful model framework on which to understand
the underlying mechanism, as well as a practical
tool for designing fluids with predefined acid–base
properties [22].
Stewart modelled the acid–base behaviour of
plasma using a series of simultaneous equations
expressing the laws of mass action, mass conserva-
tion and electrical neutrality as applied to aqueous
solutions [23]. Expressions for Gibbs Donnan
transmembrane forces were added in subsequent
iterations, as the equilibrating environment deter-
mining the arterial PCO2/pH relationship is a com-
posite domain consisting of the interstitium plus
plasma plus erythrocytes (IPE) [24,25]. Any final
equilibrium is a function of three independent
300 www.co-criticalcare.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
variables referenced to this IPE space. They are the
strong ion difference (SID), the total concentration
of nonvolatile weak acid (Atot) and PCO2.
SID is the net charge (milliequivalents per litre)
of all fully dissociated cations (sodium, potassium,
calcium, magnesium) and anions (chloride, lactate,
keto-acids and all other organic anions with pKa
values <4.0). Strong cationic charge exceeds strong
anionic charge such that the normal plasma SID is
approximately 40 mEq/l. Atot in plasma consists
mainly of albumin and phosphate (again measured
in milliequivalents per litre), whereas haemoglobin
is the predominant nonvolatile weak acid in red
cells. Isolated SID increases/decreases move the
acid–base equilibrium towards metabolic alkalo-
sis/acidosis, respectively. Conversely isolated
increases/decreases in Atot shift the equilibrium
towards metabolic acidosis/alkalosis, respectively.
From the Stewart perspective, the acid–base
properties of a given intravenous fluid are deter-
mined by its SID and Atot. Rapid fluid adminis-
tration is modelled as an equilibration with
extracellular (more correctly IPE) fluid. Because all
crystalloids have zero Atot, they reduce extracellular
Atot by simple dilution of albumin and phosphate,
whereas corresponding SID values are driven
towards those of the administered fluid.
The SID of saline is zero (equal concentrations of
the strong cation Naþ and the strong anion Cl
).
When saline is administered rapidly and in large
volumes (for example 4 l in 2 h), it forces simul-
taneous reductions in SID (metabolic acidosis) and
Atot (metabolic alkalosis). If there is no pre-existing
acid–base disturbance, the net result is always
metabolic acidosis.
CHLORIDE
Although hyperchloraemia is inevitable in any
metabolic acidosis induced by 0.9% sodium
chloride, an identical acidosis without hyperchlor-
aemia can arise from fluids containing low chloride
concentrations [26]. This is because the relevant
crystalloid property is the SID rather than the
chloride concentration alone. If crystalloids with
low chloride concentrations cause metabolic acido-
sis, there may even be a fall in plasma chloride. The
reduction in extracellular SID will then be caused by
a still greater fall in sodium.
IS FLUID-INDUCED METABOLIC ACIDOSIS
HARMFUL?
Saline-induced acidosis is characteristically mild to
moderate. Standard base excess values are unlikely
to fall below
10 mEq/l even with administered
Volume 19  Number 4  August 2013

volumes as high as 50 ml/kg over 2 h [27]. After
respiratory compensation, arterial pH rarely strays
below 7.3, a value unlikely to induce the classic
complications of severe acidemia such as myo-
cardial depression, dysrhythmias or pulmonary
hypertension.
There are even theoretical benefits including the
Bohr effect [28] and acidemic protection against
hypoxic stress [29,30]. Acidosis caused by chloride
accumulation certainly appears less harmful than
acidosis caused by strong anions other than chloride,
as evidenced by a retrospective study of 851 ICU
patients with metabolic acidosis in whom arterial
lactate concentrations were measured [31]. Inde-
pendent predictors of hospital mortality did not
include chloride or acidosis severity, but did include
lactate concentrations and the strong ion gap (which
quantifies nonchloride anions other than lactate).
On the contrary, there is a spectrum of cell
culture, animal, human volunteer and clinical data
implicating hyperchloraemic metabolic acidosis
as a proinflammatory stimulus causing pulmonary,
renal, splanchnic, circulatory and coagulation
dysfunction [32–40]. Recent evidence includes the
following: In a human volunteer study compar-
ing responses to 2-l infusions of 0.9% saline
[(Cl-) ¼ 154 mmol/l, Table 1] versus Plasma-Lyte
148 [(Cl-) ¼ 98 mmol/l, Table 1] administered over
1 h, saline generated more severe and sustained
hyperchloraemia and SID reduction, along with
more prominent extravascular expansion plus sig-
nificant reductions in renal arterial flow velocity
&
and cortical perfusion [41 ]. The authors speculated
that afferent arteriolar resistance was increased in
response to the action of chloride on the macula
Table 1. Five commercial crystalloids
0.9% Sodium chloridea
Sodium 154
Chloride 154
Potassium
Calcium
Magnesium
L-lactate
Acetate
Gluconate
Citrate
Malate
In-vivo SID 0 50
All concentrations are in mEq/l. SID, strong ion difference.
a
Baxter Healthcare Corporation, Deerfield, Illinois, USA.
b
Sterofundin, B Braun, Melsungen, Germany.
c
McGaw, Irvine, California, USA.
1070-5295 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The ideal crystalloid -- what is ‘balanced’? Morgan
densa, although an alternative explanation was
simple compression of renal cortical vessels by
raised intracapsular pressure.
A retrospective study analysed data extracted
from nearly 500 000 patient records in a US hospital
&&
claims database [42 ]. Selection was on the basis
that patients had undergone emergency abdominal
surgery for nontrauma. A further requirement was
that on the day of surgery either 0.9% saline or
Plasma-Lyte 148 had been administered exclusively.
After propensity score matching to minimize con-
founders, patients given saline suffered a higher
mortality and were more prone to investigations
for acidosis and to complications, which included
infection, renal failure requiring dialysis, blood
transfusion and electrolyte disturbances.
One important question is: Are perturbations
associated with fluid-induced metabolic acidosis a
response to the acid–base disturbance itself or
simply because of hyperchloraemia [43]? A defini-
tive answer is elusive, partly because studying
sodium reduction instead of hyperchloraemia as a
way of reducing SID causes unacceptable hypoto-
nicity. Even when chloride is actively restricted,
concentrations tend to rise in critical illness. A
6-month low chloride fluid policy in a single ICU
failed to prevent steady plasma chloride increases in
the days following ICU admission [44]. Chloride was
restricted by banning gelatine-based colloids, sub-
stituting 20% for 4% albumin, and administering
Hartmann’s solution or Plasma-Lyte 148 instead of
0.9% saline. As expected, chloride elevations were
more marked when chloride was unrestricted, and
the increased rates of acute kidney injury reported in
this period along with a greater need for renal
Plasma-Lyte 148a Compound sodium lactatea Ringer’s acetateb Isolyte Ec
140 129 145 140
98 109 103 103
5 5 4 10
4 5 5
3 2 3
29
27 24 49
23
8
5
29 29 57
www.co-criticalcare.com 301
 Intravenous fluids
replacement therapy might therefore have been
&&
because of higher chloride concentrations [45 ].
However, there was also differential colloid
exposure with administration of gelatine-based
colloids and 4% albumin virtually eliminated in
the chloride-restricted period.
HOW CAN FLUID-INDUCED METABOLIC
ACID–BASE DISTURBANCES BE
PREVENTED?
If SID is held constant during crystalloid fluid
loading, Atot dilution will be the sole consequence
and progressive metabolic alkalosis will result.
Balanced crystalloids must therefore lower SID in
parallel with Atot at a rate that counteracts the
&
alkalosis. Assuming normocarbia [46 ], exact
balance occurs with a crystalloid SID of 24 mEq/l,
demonstrable theoretically at infinite dilution
(Atot ¼ zero) [1], in haemodilution simulations
[47] and in actual haemodilutions of varying
severity [48,49]. Chloride will still increase as SID
falls with haemodilution, although not to the same
extent as with 0.9% saline.
Saline is therefore balanced from an acid–base
viewpoint by replacing 24 mEq/l of Cl
with OH
,
HCO3
or CO32
. HCO3
is the desirable option, as
OH
generates a severely alkaline fluid pH
(pH ¼ 12.4 at 258C), and CO32
increases the risk
of calcium precipitation. Unfortunately, HCO3
is
problematic for manufacturers because a high PCO2
must be maintained within the fluid to prevent even
slight dissociation to CO32
. CO2-impermeable con-
tainers are therefore required to block CO2 egress
during fluid preparation, autoclaving and storage.
Glass is the ultimate CO2-impervious material.
Flexible diffusion-retardant materials such as multi-
layer polyvinyl chloride are more ‘user-friendly’
but have a limited shelf life and introduce extra
cost. Small supplementary concentrations of citrate
or L-lactate may be needed to inhibit precipitation
once traces of CO32
appear [50].
THE STANDARD COMMERCIAL
APPROACH
To circumvent the problem of atmospheric CO2
loss, most manufacturers of ‘balanced’ salt solutions
substitute organic anions for HCO3
. Examples
include L-lactate, acetate, gluconate, malate and
citrate (Table 1). The ex-vivo SID of all such fluids
is zero because bicarbonate substitutes are either
strong or borderline strong anions. However, pro-
vided they disappear promptly on administration
their preinfusion concentrations can be regarded as
the effective in-vivo crystalloid SID.
302 www.co-criticalcare.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Some years ago, the Shimizu Pharmaceutical
Company Ltd developed a ‘bicarbonated Ringer’s
solution’ of potential interest. It contained
25 mEq/l of bicarbonate and 5 mEq/l of citrate,
giving it an in-vivo SID of 30 mEq/l [50–52].
CHOICE OF ORGANIC ANION
Terms such as ‘bicarbonate precursor’ or ‘bicarbon-
ate as lactate’ can be misleading. The final common
metabolic pathway of substitute organic anions is a
variable split between glycolysis and gluconeogen-
esis. Their role is not to generate HCO3
but simply
to disappear rapidly. Hence, the important attri-
butes of any potential bicarbonate substitute are
that it should be nontoxic, efficiently metabolized
and should maintain a fluid pH, which minimizes
haemolysis and endothelial damage on peripheral
infusion. Exact pH requirements are unclear. In
commercial preparations, pH values are usually
within the range pH ¼ 4.0–8.0.
L-lactate administered at doses up to 100 mmol/h
will not accumulate unless there is severe liver dys-
function [53,54] or major liver resection [55]. To put
this in context, compound sodium lactate infused at
3.3 l/h delivers 100 mmol/h of L-lactate. Up to 70% of
infused L-lactate undergoes gluconeogenesis follow-
ing conversion to pyruvate, potentially destabilizing
glucose control. The remainder traverses the Krebs
cycle via acetyl CoA with ultimate generation of CO2.
If L-lactate accumulates, glycolysis is retarded at the
glyceraldehyde-3-phosphate dehydrogenase step,
&
reducing ATP generation [56 ].
Acetate has several advantages over L-lactate.
Because of its rapid metabolism, 300 mmol/h can
be tolerated without significant accumulation.
Acetate is unlikely to cause hyperglycaemia and
has less effect on oxygen consumption and carbon
dioxide elimination. Unlike L-lactate, acetate is
metabolized in several extrahepatic tissues, particu-
larly muscle, and thus is subject to less accumulation
in shock states or severe liver dysfunction. These
favourable properties have made acetate a popular
component of ‘balanced’ crystalloids (Table 1). It is
also a common constituent of cardioplegia and total
parenteral nutrition solutions.
On the contrary, sustained high acetate concen-
trations during renal replacement have been linked
to hypotension, direct myocardial toxicity [57,58]
and complex metabolic disturbances [59]. As a
result, acetate-based haemodialysis has been discon-
tinued in Australia and elsewhere, even in supple-
mentary concentrations. Transient acetate surges
approaching 9 mmol/l have been documented on
commencement of cardiopulmonary bypass with
Plasma-Lyte 148 as the 2-L pump prime [60]. There
Volume 19  Number 4  August 2013

has also been one report of lactic acidosis during
resuscitation with a sodium acetate-containing fluid
[61].
Gluconate is metabolized more slowly than
L-lactate [62], but there is no evidence of toxicity
based on limited clinical and experimental data. On
the contrary, gluconate at plasma concentrations of
2.4 and 4.8 mmol/l may protect against postischae-
mic myocardial dysfunction and oxidative injury
[63]. Plasma gluconate elevations following
Plasma-Lyte 148 administration can cause false-
positive tests for galactomannan antigenemia, a
biomarker for invasive pulmonary aspergillosis
[64].
Citrate has been limited to supplementary con-
centrations in commercial crystalloids (Table 1) pre-
sumably to avoid ionized calcium chelation. Malate
has also been used, again in smaller concentrations
(Table 1). Succinate has received experimental
attention [65], but apart from malate and citrate,
no other Krebs cycle intermediates have appeared in
commercial balanced salt solutions.
OTHER POTENTIAL BICARBONATE
SUBSTITUTES
Pyruvate has toxic breakdown products and is too
unstable for inclusion in commercial preparations.
Pyruvate can be rendered water-soluble as an enolate
in the presence of calcium (‘Ringer’s Ethyl Pyruvate
Solution’) [66] and is without toxic metabolites.
Although showing promise as an anti-inflammatory
agent and reactive oxygen species scavenger [67],
ethyl pyruvate infused during cardiopulmonary
bypass proved disappointing in patients undergoing
high-risk cardiac surgery [68].
The novel carotenoid molecule trans-sodium
crocetinate is of interest. Its unusual property of
increasing oxygen diffusivity in aqueous media
may be beneficial in conditions of restricted oxygen
delivery [69,70]. D-b-Hydroxybutyrate is another
potential bicarbonate substitute (Ringer ketone
solution) [71]. Described as a neuronal ‘superfuel’,
D-b-hydroxybutyrate is stable at room temperature,
bypasses insulin resistance, is rapidly metabolized
on administration and has neuroprotective proper-
&
ties at high plasma concentrations [56 ,72,73].
ANCILLARY CATIONS
Sodium is the principle cation in balanced salt
solutions. In many commercial fluids we find
additional cations such as Kþ, Ca2þ and Mg2þ
(Table 1). In each case the net benefit is debatable.
Because potassium requirements in critical illness
are highly variable, separate administration via a
1070-5295 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The ideal crystalloid -- what is ‘balanced’? Morgan
dedicated infusion line is a more precise approach.
The same can be said of calcium and magnesium,
which also introduce drug and blood product
incompatibilities particularly in the case of calcium
[74], plus a tendency to precipitate in CO2-contain-
ing solutions.
The inclusion of calcium dates back to the clas-
sic experiments of Sydney Ringer on ex-vivo beating
frog hearts [75]. Preservation of coagulation is a
more recent argument, although in thromboelasto-
graphic studies the hypocalcaemic threshold for
coagulopathy verges on extreme (<0.56 mmol/l)
[76]. There are limited in-vivo data supporting
calcium inclusion. In one small study (n ¼ 66) of
patients undergoing abdominal aortic aneurysm
repair, those administered 0.9% saline (calcium free)
required more blood products than those receiving
lactated Ringer’s solution [35]. In a haemorrhagic
shock model, isotonic saline resuscitation was again
associated with increased blood loss versus lactated
Ringer’s solution [77].
Although calcium was conceivably a factor, the
elimination of metabolic acidosis with lactated
Ringer’s solution is an alternative explanation for
the reduced blood loss in both cases, especially
because a hypercoagulable state occurs with both
Hartmann’s solution and 0.9% saline after in-vitro
haemodilution [78]. The driver for including mag-
nesium in fluids such as Plasma-Lyte 148 is presum-
ably prevention of hypomagnesaemia associated
with shock states and critical illness. In one haemor-
rhagic shock model, there was no evident benefit
[79].
TONICITY
In the late 19th century, Hamburger [80] concluded
after observing the effects of various diluents on
plasma haemolytic thresholds and freezing points
that 0.9% aqueous sodium chloride is isotonic with
the plasma of ‘warm-blooded animals’. More than
a century later, 0.9% sodium chloride (NaCl
154 mmol/l, measured osmolality 284 mOsm/kg)
remains the normotonic standard [81].
Tonicity or ‘effective osmolality’ is an important
property of body fluids because it determines the
partitioning of water between intracellular and extra-
cellular compartments, the driver being the resol-
ution of transmembrane tonicity gradients [82,83].
Normal plasma osmolality is 275–295 mOsm/kg
[84]. Tonicity can be defined as osmolality
[urea]
because urea is a permeant solute with no influence
on water partitioning. Normal plasma tonicity is
approximately 270–290 mOsm/kg. Sudden changes
in extracellular tonicity generate compartmental
water shifts, which can have neurological
www.co-criticalcare.com 303
 Intravenous fluids
consequences, for example cerebral oedema in acute
hypotonic hyponatraemia, or osmotic demyelina-
tion after its subsequent correction [85–87].
Even a mildly hypotonic solution such as
compound sodium lactate (measured osmolality
259 mOsm/kg, Table 1) can reduce extracellular
tonicity enough to affect water partitioning if large
volumes are administered rapidly. For example,
50 ml/kg of lactated Ringer’s solution (similar to
compound sodium lactate) infused over 1 h into
healthy volunteers reduced mean measured
plasma osmolality by 4 mOsm/kg [34]. In non-
brain-injured mammals, equivalent tonicity
reductions increased mean intracranial pressure
by >5 mmHg [88]. In a large randomized study of
two resuscitation fluids, patients with traumatic
brain injury administered 4% albumin solution
were found to have a higher mortality at 2 years
than patients administered 0.9% saline [8]. There
was a greater increase in intracranial pressure in the
albumin group in the first postinjury week, based
on available pressure measurements [89]. The
measured osmolality of the 4% albumin solution
was 260 mOsm/kg, approximately 24 mOsm/kg
below that of the alternative study fluid 0.9% saline,
and similar to that of compound sodium lactate.
The cause of the intracranial pressure discrepancy
may thus have been the relative hypotonicity of
the albumin preparation rather than colloid extra-
vasation [89].
Tonicity equilibrations after fluid gain or loss
occur throughout the total body water [90–92]. For
tonicity ‘balance’ calculations, an administered
crystalloid can be represented as a mixture of iso-
tonic saline (0.9% sodium chloride) and electrolyte-
free water [91]. The contribution of infused potass-
ium to plasma sodium concentrations and tonicity
is considered identical to that of infused sodium.
Hence, a solution consisting of a mixture of NaCl
150 mmol/l and KCl 4 mmol/l should have effects
on plasma sodium concentrations and tonicity
similar if not identical to those of isotonic NaCl
(154 mmol/l).
THE IDEAL BALANCED CRYSTALLOID
Figure 1 illustrates the author’s concept of an ideal
balanced crystalloid. It is normotonic, has an in-
vivo SID of 24 mEq/l, contains no ancillary cations,
and uses HCO3
in preference to bicarbonate
‘substitutes’. Given a commercial imperative for
bicarbonate substitutes, L-lactate is preferred. With
inclusion of potassium (not recommended), the
sodium concentration should be reduced by an
equal amount to ensure that the total cation con-
centration remains at 154 mEq/l.
304 www.co-criticalcare.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
HCO3–
24
Na+ PCO2 760 mmHg
154
Cl–
130 pH 6.04
FIGURE 1. ‘Gamblegram’ of the ideal balanced crystalloid
(author’s opinion). L-lactate can be substituted for
bicarbonate if required for manufacturing reasons. All
concentrations are in mEq/l.
CHOOSING FROM AVAILABLE
‘BALANCED’ CRYSTALLOIDS
Recommendation 1 of The British Consensus Guide-
lines on Intravenous Fluid Therapy for Adult
Surgical Patients [93] reads as follows: ‘Because of
the risk of inducing hyperchloraemic acidosis in
routine practice, when crystalloid resuscitation or
replacement is indicated, balanced salt solutions, for
example Ringer’s lactate acetate or Hartmann’s
solution should replace 0.9% saline except in cases
of hypochloraemia, for example from vomiting or
gastric drainage’.
From an acid–base perspective, these fluids are
appropriate choices. In fact, at 29 mEq/l, their
in-vivo SID should be slightly alkalinizing. This is
as intended by Dr Alexis Hartmann for his original
target group – children with gastroenteritis and
dehydration [94]. On available evidence, volume
replacement with compound sodium lactate and
its congeners reduces or eliminates infusion-related
metabolic acidosis [34,35,79,95,96]. Although post-
infusion alkalosis has been evident in pig haemodi-
&
lution experiments [33,46 ], these animals have a
&
baseline metabolic alkalosis [46 ]. The lactate in
compound sodium lactate and congeners, originally
racemic [94], now consists solely of L-lactate.
Ringer’s acetate solution with its increased total
cation concentration (Table 1) has the added
advantage of normotonicity, and there is no current
evidence of acetate toxicity after volume resuscita-
tion.
Fluids with higher in-vivo SID values, for
example Plasma-Lyte 148 and Isolyte E (Table 1),
should force more rapid correction of a pre-existing
acidosis. In diabetic ketoacidosis, both Plasma-
Lyte 148 and its congener Plasma-Lyte A pH 7.4
clearly accelerate the rate of resolution of metabolic
Volume 19  Number 4  August 2013

acidosis compared with 0.9% saline by reducing the
&
postinfusion normal anion gap acidosis [97,98 ].
Times to ketoacidosis resolution (as quantified by
the strong ion gap) and total insulin requirements
& 11. Bayer O, Reinhart K, Kohl M, et al. Effects of fluid resuscitation with synthetic
are similar [98 ]. However, higher SID solutions in
large volume are more likely to cause overshoot
metabolic alkalosis [47], which may be undesirable
at times of impaired tissue oxygen delivery [99].
CONCLUSION
By applying principles laid down by the late Peter
Stewart, we can now design fluids for specific acid–
base outcomes. For balanced electrolyte solutions,
the rules are relatively simple. They should be well
tolerated to administer peripherally, and apart from
unavoidable interstitial expansion should inflict
minimal acid–base and tonicity disturbances. They
should be isotonic, with an ‘in-vivo’ SID of 24 mEq/l
and a pH unlikely to cause haemolysis or endo-
thelial damage. The case for balanced crystalloids
is growing but unproven. A large randomized con-
trolled trial of balanced crystalloids versus 0.9%
sodium chloride is the next step.
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 370).
1. Morgan TJ. Fluid resuscitation. In: Kellum JA, Elbers PWG, editors. Stewart’s
Textbook of acid base. Amsterdam: AcidBase.org; 2009. pp. 351–363.
2. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational approach to
perioperative fluid management. Anesthesiology 2008; 109:723–740.
3. Drummer C, Gerzer R, Heer M, et al. Effects of an acute saline infusion on fluid
and electrolyte metabolism in humans. Am J Physiol 1992; 262:F744–F754.
4. 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; 108:384–394.
This study canvases new concepts of transendothelial fluid dynamics and reviews
the need to modify the original Starling equation to incorporate the important roles
of the endothelial glycocalyx, basement membrane and interstitial matrix.
5. James MF, Michell WL, Joubert IA, et al. Resuscitation with hydroxyethyl
starch improves renal function and lactate clearance in penetrating trauma in a
randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe
Trauma). Br J Anaesth 2011; 107:693–702.
6. 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–
2256.
7. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid
& resuscitation in intensive care. N Engl J Med 2012; 367:1901–1911.
This is an important study on many levels. On the current topic, it provides evidence
for retaining crystalloids as volume agents in preference to starch-based colloids.
8. Myburgh J, Cooper DJ, Finfer S, et al. Saline or albumin for fluid resuscitation
in patients with traumatic brain injury. N Engl J Med 2007; 357:874–
884.
1070-5295 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The ideal crystalloid -- what is ‘balanced’? Morgan
9. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentas-
tarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125–139.
10. 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; 367:124–134.
&
This is an important study on many levels. On the current topic, it provides evidence
for retaining crystalloids as volume agents in preference to starch-based colloids.
& colloids or crystalloids alone on shock reversal, fluid balance, and patient
outcomes in patients with severe sepsis: a prospective sequential analysis.
Crit Care Med 2012; 40:2543–2551.
This study provides evidence for retaining crystalloids as volume agents in
preference to starch and gelatine-based colloids.
12. Mahmood A, Gosling P, Vohra RK. Randomized clinical trial comparing the
effects on renal function of hydroxyethyl starch or gelatine during aortic
aneurysm surgery. Br J Surg 2007; 94:427–433.
13. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in
critically ill patients. Cochrane Database Syst Rev 2011; CD000567.
14. McFarlane C, Lee A. A comparison of Plasmalyte 148 and 0.9% saline for
intra-operative fluid replacement. Anaesthesia 1994; 49:779–781.
15. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion
produces hyperchloremic acidosis in patients undergoing gynecologic
surgery. Anesthesiology 1999; 90:1265–1270.
16. Waters JH, Miller LR, Clack S, Kim JV. Cause of metabolic acidosis in
prolonged surgery. Crit Care Med 1999; 27:2142–2146.
17. Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable
consequence of intraoperative infusion of 0.9% saline. Anesthesiology 1999;
90:1247–1249.
18. Hayhoe M, Bellomo R, Liu G, et al. The aetiology and pathogenesis of
cardiopulmonary bypass-associated metabolic acidosis using polygeline
pump prime. Intensive Care Med 1999; 25:680–685.
19. Liskaser FJ, Bellomo R, Hayhoe M, et al. Role of pump prime in the etiology
and pathogenesis of cardiopulmonary bypass-associated acidosis. Anesthe-
siology 2000; 93:1170–1173.
20. Himpe D, Neels H, De Hert S, Van Cauwelaert P. Adding lactate to the prime
solution during hypothermic cardiopulmonary bypass: a quantitative acid-
base analysis. Br J Anaesth 2003; 90:440–445.
21. Rehm M, Orth V, Scheingraber S, et al. Acid-base changes caused by 5%
albumin versus 6% hydroxyethyl starch solution in patients undergoing acute
normovolemic hemodilution: a randomized prospective study. Anesthesiology
2000; 93:1174–1183.
22. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Phar-
macol 1983; 61:1444–1461.
23. Morgan TJ. The Stewart approach–one clinician’s perspective. Clin Biochem
Rev 2009; 30:41–54.
24. Wolf MB, Deland EC. A mathematical model of blood-interstitial acid-base
balance: application to dilution acidosis and acid-base status. J Appl Physiol
2011; 110:988–1002.
25. Morgan TJ. Partitioning standard base excess: a new approach. J Clin Monit
Comput 2011; 25:349–352.
26. Makoff DL, da Silva JA, Rosenbaum BJ, et al. Hypertonic expansion: acid-base
and electrolyte changes. Am J Physiol 1970; 218:1201–1207.
27. Rehm M, Finsterer U. Treating intraoperative hyperchloremic acidosis with
sodium bicarbonate or tris-hydroxymethyl aminomethane: a randomized pro-
spective study. Anesth Analg 2003; 96:1201–1208.
28. Handy JM, Soni N. Physiological effects of hyperchloraemia and acidosis. Br J
Anaesth 2008; 101:141–150.
29. Bonventre JV, Cheung JY. Effects of metabolic acidosis on viability of cells
exposed to anoxia. Am J Physiol 1985; 249:C149–159.
30. Heijnen BH, Elkhaloufi Y, Straatsburg IH, Van Gulik TM. Influence of acidosis
and hypoxia on liver ischemia and reperfusion injury in an in vivo rat model. J
Appl Physiol 2002; 93:319–323.
31. Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus nonlactate metabolic
acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care
2006; 10:R22.
32. Lobo DN. Intravenous 0.9% saline and general surgical patients: a problem,
not a solution. Ann Surg 2012; 255:830–832.
33. Phillips CR, Vinecore K, Hagg DS, et al. Resuscitation of haemorrhagic shock
with normal saline vs. lactated Ringer’s: effects on oxygenation, extravascular
lung water and haemodynamics. Crit Care 2009; 13:R30.
34. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intra-
venous lactated Ringer’s solution versus 0.9% sodium chloride solution on
serum osmolality in human volunteers. Anesth Analg 1999; 88:999–1003.
35. Waters JH, Gottlieb A, Schoenwald P, et al. Normal saline versus lactated
Ringer’s solution for intraoperative fluid management in patients undergoing
abdominal aortic aneurysm repair: an outcome study. Anesth Analg 2001;
93:817–822.
36. Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus saline-
based hetastarch and crystalloid solutions on acid-base and electrolyte status
and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 2001;
93:811–816.
37. Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest
1983; 71:726–735.
38. Pedoto A, Caruso JE, Nandi J, et al. Acidosis stimulates nitric oxide production
and lung damage in rats. Am J Respir Crit Care Med 1999; 159:397–402.
www.co-criticalcare.com 305
 Intravenous fluids
39. Pedoto A, Nandi J, Oler A, et al. Role of nitric oxide in acidosis-induced
intestinal injury in anesthetized rats. J Lab Clin Med 2001; 138:270–276.
40. Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer’s solution reduces
systemic inflammation compared with saline in patients with acute pancrea-
titis. Clin Gastroenterol Hepatol 2011; 9:710–717; e711.
41. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled,
& double-blind crossover study on the effects of 2-L infusions of 0.9% saline
and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue
perfusion in healthy volunteers. Ann Surg 2012; 256:18–24.
This is an open-label cross-over set of volunteer experiments demonstrating
important renal and extravascular perturbations after 2-l infusions of 0.9% saline
but less so after Plasma-Lyte 148. These data provide further support for a
randomized controlled trial of balanced crystalloids versus 0.9% saline.
42. Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality,
&& and resource utilization after open abdominal surgery: 0.9% saline compared
to Plasma-Lyte. Ann Surg 2012; 255:821–829.
Thisisalargeretrospectiveobservationalstudyof0.9%salineversusPlasma-Lyte148
inabdominalsurgeryrelyingonpropensityscoringtoeliminateconfounders.Important
differences in mortality and morbidity favouring Plasma-Lyte 148 provide yet more
support for a randomized controlled trial of balanced crystalloid versus 0.9% saline.
43. Yunos NM, Bellomo R, Story D, Kellum J. Bench-to-bedside review: chloride in
critical illness. Crit Care 2010; 14:226.
44. Yunos NM, Kim IB, Bellomo R, et al. The biochemical effects of restricting
chloride-rich fluids in intensive care. Crit Care Med 2011; 39:2419–2424.
45. 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; 308:1566–1572.
A well-conducted single centre open-label sequential study of chloride restriction
versus nonrestriction, important primarily from the perspective of hypothesis gen-
eration. The data strongly support the need for a large randomized trial to test the
hypothesis that exposure of critically ill patients to fluids high in chloride increases the
risk of kidney injury, either directly or via resultant acid–base disturbances.
46. Langer T, Carlesso E, Protti A, et al. In vivo conditioning of acid-base
& equilibrium by crystalloid solutions: an experimental study on pigs. Intensive
Care Med 2012; 38:686–693.
This interesting article adds new information concerning the arterial and renal
acid–base and electrolyte responses to infused fluids with widely differing SID and
electrolyte compositions.
47. Omron EM, Omron RM. A physicochemical model of crystalloid infusion on
acid-base status. J Intensive Care Med 2010; 25:271–280.
48. Morgan TJ, Venkatesh B, Hall J. Crystalloid strong ion difference determines
metabolic acid-base change during in vitro hemodilution. Crit Care Med
2002; 30:157–160.
49. Morgan TJ, Venkatesh B, Hall J. Crystalloid strong ion difference determines
metabolic acid-base change during acute normovolaemic haemodilution.
Intensive Care Med 2004; 30:1432–1437.
50. Satoh K, Ohtawa M, Katoh M, et al. Pharmacological study of BRS, a new
bicarbonated Ringer’s solution, in haemorrhagic shock dogs. Eur J Anaes-
thesiol 2005; 22:703–711.
51. Shimada Y, Kitamura A, Nakanishi K, et al. Effect of bicarbonated Ringer’s
solution on the acid-base balance in patients undergoing abdominal aortic
aneurysm repair. Journal of Nippon Medical School ¼ Nippon Ika Daigaku
zasshi 2005; 72:364–369.
52. Satoh K, Ohtawa M, Okamura E, et al. Pharmacological study of BRS, a new
bicarbonated Ringer’s solution, in partially hepatectomized rabbits. Eur J
Anaesthesiol 2005; 22:624–629.
53. McLean AG, Davenport A, Cox D, Sweny P. Effects of lactate-buffered and
lactate-free dialysate in CAVHD patients with and without liver dysfunction.
Kidney Int 2000; 58:1765–1772.
54. Kierdorf HP, Leue C, Arns S. Lactate- or bicarbonate-buffered solutions in
continuous extracorporeal renal replacement therapies. Kidney Int Suppl
1999; S32–36.
55. Shin WJ, Kim YK, Bang JY, et al. Lactate and liver function tests after living
donor right hepatectomy: a comparison of solutions with and without lactate.
Acta Anaesthesiol Scand 2011; 55:558–564.
56. Robert Valeri C, Veech RL. The unrecognized effects of the volume and
& composition of the resuscitation fluid used during the administration of blood
products. Transfus Apher Sci 2012; 46:121–123.
This study is an opinion piece from two National Institute of Health researchers,
one of whom raised the alarm about acetate in dialysis fluids in the 1980s. It is
relevant because of comments on some of the positive and negative effects of
organic anion bicarbonate substitutes. In particular, it outlines properties of D-b-
hydroxybutyrate, which might be advantageous during periods of metabolic stress.
57. Selby NM, Fluck RJ, Taal MW, McIntyre CW. Effects of acetate-free double-
chamber hemodiafiltration and standard dialysis on systemic hemodynamics
and troponin T levels. ASAIO J 2006; 52:62–69.
58. Jacob AD, Elkins N, Reiss OK, et al. Effects of acetate on energy metabolism
and function in the isolated perfused rat heart. Kidney Int 1997; 52:755–760.
59. Veech RL, Gitomer WL. The medical and metabolic consequences of
administration of sodium acetate. Adv Enzyme Regul 1988; 27:313–343.
60. Davies PG, Venkatesh B, Morgan TJ, et al. Plasma acetate, gluconate and
interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of
Plasma-Lyte 148 with a bicarbonate-balanced solution. Crit Care 2011;
15:R21.
306 www.co-criticalcare.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
61. McCague A, Bowman N, Wong DT. Lactic acidosis after resuscitation with
sodium acetate. J Surg Res 2012; 173:362–364.
62. Naylor JM, Forsyth GW. The alkalinizing effects of metabolizable bases in the
healthy calf. Can J Vet Res 1986; 50:509–516.
63. Murthi SB, Wise RM, Weglicki WB, et al. Mg-gluconate provides superior
protection against postischemic dysfunction and oxidative injury compared to
Mg-sulfate. Mol Cell Biochem 2003; 245:141–148.
64. Petraitiene R, Petraitis V, Witt JR 3rd, et al. Galactomannan antigenemia after
infusion of gluconate-containing Plasma-Lyte. J Clin Microbiol 2011;
49:4330–4332.
65. Levin GS, Shevchenko LI, Gubaev SA. [Comparative evaluation of the effects
of crystalloid solutions containing sodium lactate and sodium succinate on the
hemodynamic indicators in different types of hemorrhage]. Gematologiia i
transfuziologiia 1991; 36:25–28.
66. Sims CA, Wattanasirichaigoon S, Menconi MJ, et al. Ringer’s ethyl pyruvate
solution ameliorates ischemia/reperfusion-induced intestinal mucosal injury in
rats. Crit Care Med 2001; 29:1513–1518.
67. Fink MP. Ethyl pyruvate. Curr Opin Anaesthesiol 2008; 21:160–167.
68. Bennett-Guerrero E, Swaminathan M, Grigore AM, et al. A phase II multicenter
double-blind placebo-controlled study of ethyl pyruvate in high-risk patients
undergoing cardiac surgery with cardiopulmonary bypass. J Cardiothorac
Vasc Anesth 2009; 23:324–329.
69. Mohler ER 3rd, Gainer JL, Whitten K, et al. Evaluation of trans sodium
crocetinate on safety and exercise performance in patients with peripheral
artery disease and intermittent claudication. Vasc Med 2011; 16:346–353.
70. Manabe H, Okonkwo DO, Gainer JL, et al. Protection against focal ischemic
injury to the brain by trans-sodium crocetinate. Laboratory investigation.
J Neurosurg 2010; 113:802–809.
71. Koustova E, Rhee P, Hancock T, et al. Ketone and pyruvate Ringer’s solutions
decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock
and resuscitation. Surgery 2003; 134:267–274.
72. White H, Venkatesh B. Clinical review: ketones and brain injury. Crit Care
2011; 15:219.
73. Valeri CR, Ragno G, Veech RL. Effects of the resuscitation fluid and the
hemoglobin based oxygen carrier (HBOC) excipient on the toxicity of the
HBOC: Ringer’s D,L-lactate, Ringer’s L-lactate, and Ringer’s ketone solu-
tions. Artif Cells Blood Substit Immobil Biotechnol 2006; 34:601–606.
74. Gin A, Walker S. Notice to hospitals regarding ceftriaxone-calcium incompat-
ibility: what’s a clinician to do? Can J Hosp Pharm 2009; 62:157–158.
75. Toledo-Pereyra LH. Sydney Ringer and the origins of cardioplegia. Surg
Gynecol Obstet 1986; 163:183–190.
76. James MF, Roche AM. Dose-response relationship between plasma ionized
calcium concentration and thrombelastography. J Cardiothorac Vasc Anesth
2004; 18:581–586.
77. 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 2006; 61:57–64.
78. Roche AM, James MF, Bennett-Guerrero E, Mythen MG. A head-to-head
comparison of the in vitro coagulation effects of saline-based and balanced
electrolyte crystalloid and colloid intravenous fluids. Anesth Analg 2006;
102:1274–1279.
79. Traverso LW, Lee WP, Langford MJ. Fluid resuscitation after an otherwise
fatal hemorrhage: I. Crystalloid solutions. J Trauma 1986; 26:168–175.
80. Hamburger HJ. A discourse on permeability in physiology and pathology.
Lancet 1921; 198:1039–1045.
81. Awad S, Allison SP, Lobo DN. The history of 0.9% saline. Clin Nutr 2008;
27:179–188.
82. McManus ML, Churchwell KB, Strange K. Regulation of cell volume in health
and disease. N Engl J Med 1995; 333:1260–1266.
83. Strange K. Regulation of solute and water balance and cell volume in the
central nervous system. J Am Soc Nephrol 1992; 3:12–27.
84. Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water
balance in hospitalized patients. Can J Anaesth 2009; 56:151–167.
85. Adrogue HJ, Madias NE. Management of life-threatening acid-base disorders.
First of two parts. N Engl J Med 1998; 338:26–34.
86. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy
in menstruant women. Ann Intern Med 1992; 117:891–897.
87. Sterns RH, Cappuccio JD, Silver SM, Cohen EP. Neurologic sequelae after
treatment of severe hyponatremia: a multicenter perspective. J Am Soc
Nephrol 1994; 4:1522–1530.
88. Tommasino C, Moore S, Todd MM. Cerebral effects of isovolemic hemodilu-
tion with crystalloid or colloid solutions. Crit Care Med 1988; 16:862–
868.
89. Cooper DJ, Myburgh J, Finfer S, et al. Albumin resuscitation for traumatic brain
injury: is intracranial hypertension the cause of increased mortality? J Neuro-
trauma 2013; 30:512–518.
90. Rose BD. New approach to disturbances in the plasma sodium concentration.
Am J Med 1986; 81:1033–1040.
91. Carlotti AP, Bohn D, Mallie JP, Halperin ML. Tonicity balance, and not
electrolyte-free water calculations, more accurately guides therapy for acute
changes in natremia. Intens Care Med 2001; 27:921–924.
92. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000; 342:1581–
1589.
Volume 19  Number 4  August 2013

93. British consensus guidelines on intravenous fluid therapy for adult surgical
patients. 2011. http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf
[Accessed 30 January 2013]
94. Hartmann AF, Senn MJ. Studies in the metabolism of sodium r-lactate. I.
Response of normal human subjects to the intravenous injection of sodium
r-lactate. J Clin Invest 1932; 11:327–335.
95. Reid F, Lobo DN, Williams RN, et al. (Ab)normal saline and physiological
Hartmann’s solution: a randomized double-blind crossover study. Clin Sci
(Lond) 2003; 104:17–24.
96. Takil A, Eti Z, Irmak P, Yilmaz Gogus F. Early postoperative respiratory
acidosis after large intravascular volume infusion of lactated ringer’s solution
during major spine surgery. Anesth Analg 2002; 95:294–298.
1070-5295 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The ideal crystalloid -- what is ‘balanced’? Morgan
97. Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation with balanced
electrolyte solution prevents hyperchloremic metabolic acidosis in patients
with diabetic ketoacidosis. Am J Emerg Med 2011; 29:670–674.
98. Chua HR, Venkatesh B, Stachowski E, et al. Plasma-Lyte 148 vs 0.9% saline for
& fluid resuscitation in diabetic ketoacidosis. J Crit Care 2012; 27:138–145.
A small observational retrospective multicenter data analysis demonstrating likely
advantages of Plasma-Lyte 148 over 0.9% saline in diabetic ketoacidosis, includ-
ing acid–base and improved maintenance of cardiovascular performance and
renal function.
99. Morgan TJ, Venkatesh B, Beindorf A, et al. Acid-base and bio-energetics
during balanced versus unbalanced normovolaemic haemodilution. Anaesth
Intensive Care 2007; 35:173–179.
www.co-criticalcare.com 307