Intensive Care Med
DOI 10.1007/s00134-017-4989-4
WHATS NEW IN INTENSIVE CARE
The dark sides offluid administration
inthe critically ill patient
DanielA.Reuter1*, DanielChappell2 andAzrielPerel3
2017 Springer-Verlag GmbH Germany, part of Springer Nature and ESICM
The administration of intravenous fluids is probably the
most frequently initiated therapy in critically ill patients.
With very few exceptions, such as severe congestive heart
failure, IV fluids are considered as a safe and generalistic
therapeutic approach. Indeed, IV fluids save lives in many
clinical situations and often the benefits outweigh the
potential harm. Really?
All of our interventions, even those that were initially
considered to have a safe therapeutic rangesooner or
laterrevealed to have a dark side. In highly complex,
critically ill patients, these dark sides become even
more relevant, invoking therapeutic conflicts that neces-
sitate an individual risk assessment of each decision.
Fluid administration often presents us with the clas-
sic therapeutic conflict, between the need for hemody-
namic stabilizationmeaning restoration of end-organ
microcirculatory perfusionversus the dangers of fluid
overload.
An increasing number of sub-analyses of sepsis stud-
ies demonstrate that aggressive fluid administration aim-
ing to achieve CVP values even within the physiological
range, in the sickest patients in particular, turns out to be
more harmful than beneficial [1]. But why?
Edema formation: The main mechanism of edema for-
mation is the degradation of the endothelial glycocalyx,
which is mainly responsible for the regulation of perme-
ability and for fluid shifting towards the interstitial space.
Even with an intact endothelial glycocalyx, there is nor-
mally a shift of protein-free fluid and electrolytes out
of the vasculature. Only when the capacity of the lym-
phatic system to drain this fluid shift is overwhelmed,
tissue edema occurs. During critical illness, frequently
substantial physical and functional alterations of the
*Correspondence: Daniel.reuter@med.unirostock.de
1
Department ofAnesthesiology andIntensive Care Medicine, University
Medical Center, Rostock, Schillingallee 35, 18057Rostock, Germany
Full author information is available at the end of the article
glycocalyx lead to a pathological shift of protein-rich
plasma towards the interstitium, the so-called capillary
leakage. This type of edema formation may occur even
before hemodynamic fluid overload [2].
Dilutional coagulopathy: Fluid loading may induce
dilutional coagulopathy, which can increase the risk of
(re-)bleeding in the trauma or the surgical patient. The
administration of cold fluids may further aggravate such
coagulopathy by inducing hypothermia [3].
Dilutional anemia: IV fluid administration causes a rel-
ative, but not absolute, reduction in hemoglobin concen-
tration. Similarly, fluid accumulation may decrease serum
creatinine levels and thus lead to a delayed diagnosis or
underestimation of acute kidney injury. Hemodilution
may also result in a loss of erythrocyte-filled capillaries,
leading to a reduction in the oxygen-carrying capacity
and effective microcirculatory oxygen delivery with the
possible development of organ dysfunction [4]. Iatrogenic
hemodilution may cause a paradoxical decrease in oxy-
gen delivery, which in turn may lead clinicians to admin-
ister catecholamines or even more fluids. The decrease of
hemoglobin levels to below the transfusion threshold due
to excessive fluid loading may also trigger administration
of blood transfusions that are potentially avoidable [5].
This may explain why patients who received more fluids
perioperatively also received significantly more blood
transfusions [6].
Electrolyte imbalance: All clinically applied solutions
contain un-physiological concentrations of electrolytes
and, at times, artificial substances. Fluid administration
may therefore lead to a dose-dependent electrolyte and
acidbase imbalance such as hyperchloremic acidosis
and to functional, or even physical, organ damage [7].
Pathophysiological consequences: The above-men-
tioned and, possibly, other side effects of excessive fluid
Table1 Prevalent iatrogenic dark sides offluid administration
Dark side Pathophysiological mechanisms
Edema formation Hydrostatic intravascular pressures
Destruction of endothelial glykokalix
Organ congestion Hydrostatic intravascular pressures
Intra-organ/capsular/compartmental pressures
Dilutional coagulopathy Relative decrease of thrombocytes and coagulation factors
Hypothermia Application of cold infusions
Dilutional anemia Relative decrease of Hb: O2 transport capacity
Electrolyte imbalance Chloride-rich infusions induce hyperchloremic acidosis
administration may cause the dysfunction of many organ
systems including the heart, lungs, kidneys, gut and
brain. [8].
Practical conclusions: The first step toward better fluid
management is the recognition that it needs to be physi-
ologically justified, individually adjusted, and critically
questioned. We have to constantly remind ourselves of
the repeatedly shown finding that only half of surgical
and critically ill patients actually respond to fluid admin-
istration by increasing their cardiac output (CO) [9]. Even
when fluid loading does increase CO, this effect is fre-
quently of short duration only, and may not necessarily
be accompanied by microcirculatory improvement. This
sobering reality should make us admit how uncertain
we are regarding optimal fluid management, and should
serve as an incentive to assess the fluid responsiveness
status of each patient, preferably before fluids are actually
administered. In mechanically ventilated patients, the
information supplied by continuous dynamic parameters
like the PPV, SVV, and PVI may be helpful, when appro-
priate [10]. Other intermittent dynamic parameters,
like passive leg raising, may be helpful in some circum-
stances, though continuous CO has to be measured in
order to get a reliable result. Multiparametric, automated
analysis of physiological variables derived from hemody-
namics, ventilation and other modalities will hopefully
further increase accuracy in the detection of fluid respon-
siveness. When still in doubt, and especially in patients
where an error may be detrimental, a low-volume fluid
challenge should be administered, again under CO moni-
toring, as the response of the blood pressure, heart rate
and CVP alone can often be misleading. A status of fluid
responsiveness per se does not automatically mean that
fluids should be administered. However, the most impor-
tant aspect in the assessment of fluid responsiveness is
the identification of fluid non-responders. These are the
Clinical consequence
Oxygen delivery to end organs
End organ dysfunction (e.g. lungs, brain, kidney, gut)
Risk for infections
Risk for GI anastomotic breakdown
End organ dysfunction (e.g. kidney, liver, heart)
Risk of bleeding
Coagulopathy
Need for compensatory increase in CO endogenous cat-
echolamines /exogenous application of catecholamines;
need for transfusions
End organ (kidney) dysfunction/damage
patients who will sustain most harm from unnecessary
fluid loading as the associated dilution may lead to a par-
adoxical decrease in oxygen delivery [11]. Fluid admin-
istration necessitates an ever-present search for signs of
its dark sides, i.e. of fluid overload. Echocardiography,
the measurement of extravascular lung water, point-of-
care thrombelastography, and a continuously measured
hemoglobin which may alert the development of pos-
sible dilution may all be useful clinical tools in selected
groups of patients [3, 12, 13]. When aggressive fluid
administration seems to be clinically indicated, we have
to bear in mind that by the time the full extent of fluid
overload becomes incontrovertible, it may be already too
late to mount effective therapeutic measures. This means
that after a justified fluid resuscitation for acute stabiliza-
tion, and as soon as hemodynamically tolerable, fluid de-
resuscitation strategies should be initiated [14]. Among
other beneficial effects, such fluid removal may facilitate
weaning from mechanical ventilation [15].
In conclusion, we have to realize that fluid administra-
tion has very real and prevalent iatrogenic dark sides
(Table 1). In order to minimize the occurrence of fluid
overload and minimize its deleterious effects, we need
to either prevent it or identify it as early as possible.
When the risk associated with possible fluid overload is
increased in the individual patient, more focused moni-
toring efforts should be employed. Or, with the words of
Yoda in Star Wars III, the Revenge of the Sith: In a dark
place we find ourselves and a little more knowledge lights
our way.
Author details
1
Department ofAnesthesiology andIntensive Care Medicine, University
Medical Center, Rostock, Schillingallee 35, 18057Rostock, Germany. 2Depart-
ment ofAnesthesiology, Ludwig Maximilians University, University Hospital
Munich, Munich, Germany. 3Department ofAnesthesiology andIntensive
Care, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.
Received: 9 September 2017 Accepted: 31 October 2017
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