REVIEW

CURRENT
OPINION Optimizing fluid therapy in shock
Paul E. Marik a and Maxwell Weinmann b

Purpose of review
Shock, best defined as acute circulatory failure is classified into four major groups, namely hypovolemic,
cardiogenic, obstructive, and distributive (vasodilatory). The purpose of this review is to provide a practical
approach to fluid optimization in patients with the four types of shock.
Recent findings
Large-volume fluid resuscitation has traditionally been regarded as the cornerstone of resuscitation of
Downloaded from https://journals.lww.com/co-criticalcare by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD33gDmupaxCIwyEJpJx6k1zyCCMd8jcZ+Ayt3PLaO9JSw= on 09/11/2019

shocked patients. However, in many instances, aggressive fluid resuscitation may be harmful, increasing
morbidity and mortality.
Summary
We believe that the approach to fluid therapy must be individualized based on the cause of shock as well
as the patient’s major diagnosis, comorbidities and hemodynamic and respiratory status. A conservative,
physiologically guided approach to fluid resuscitation likely improves patient outcomes.
Keywords
crystalloid, fluid responsiveness, fluid therapy, sepsis, shock

INTRODUCTION from shock. The source of this wisdom is difficult to

The current article provides a practical common-
sense approach to fluid resuscitation in patients
with shock. At the outset, it should be recognized
that the definition of shock is somewhat confusing.
However, shock is best described as a life-threaten-
ing condition of acute circulatory failure. Shock
should be recognized and treated immediately to
prevent progression to irreversible organ failure.
discern; however, ‘Early Goal Directed therapy’
(EGDT) as championed by Rivers et al. [2] appears
to have established this as the irrefutable truth.
However, over the last decade, it has become clear
that aggressive fluid resuscitation is associated with
increased morbidity and mortality across diverse
groups of patients, including those with sepsis,
burns, pancreatitis, trauma, and patients undergo-
&

Four major categories of shock are recognized,
namely vasodilatory (distributive), cardiogenic,
hypovolemic, and obstructive, although some
degree of overlap may occur between each type of
shock. Acute circulatory failure is most commonly
manifested as hypotension, although some patients
with cardiogenic shock may be normotensive. From
a pragmatic point of view, shock should be diag-
nosed in any patient with sustained hypotension.
Multiple studies have reproducibly demonstrated
that the risk of organ injury increases when the
mean arterial pressure (MAP) falls below 65 mmHg
[1]. A sustained MAP of less than 65 mmHg should,
therefore, be considered diagnostic of circulatory
failure/shock. It should, however, be appreciated
that patients who are chronically hypotensive
may tolerate a MAP below 65 mmHg without evi-
dence of organ dysfunction.
Traditionally large volume fluid resuscitation
has been considered the cornerstone of resuscitation
ing surgery [3,4 ,5]. Consequently, a more conser-
vative, thoughtful and physiologic approach to fluid
resuscitation has emerged. The argument is no lon-
ger ‘wet or dry’ but ‘just the right amount of fluid.’
Whenever evaluating the role of fluid resuscita-
tion in shock, recognition of several guiding prin-
ciples are critically important. These principles are
listed below:
(1) The only reason to give a patient a fluid chal-
lenge (fluid bolus) is to increase the patient’s
a
Division of Pulmonary and Critical Care Medicine, Eastern Virginia
Medical School, Norfolk and bDirector Acute Respiratory Intensive Care
Unit, Emory University Hospital, Atlanta, USA
Correspondence to Paul E. Marik, MD, Chief, Division of Pulmonary and
Critical Care Medicine, Eastern Virginia Medical School, 825 Fairfax Ave,
Suite 410, Norfolk VA 23507, USA. E-mail: marikpe@evms.edu
Curr Opin Crit Care 2019, 25:246–251
DOI:10.1097/MCC.0000000000000604

www.co-criticalcare.com Volume 25  Number 3  June 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Emerging data suggests that in most patients with (6)
shock, an aggressive approach to fluid resuscitation
increases the risks of organ dysfunction and death.
 The approach to fluid therapy must be individualized
based on the type of shock as well as the patient’s
major diagnosis, comorbidities, and hemodynamic and
respiratory status. (7)
 A conservative, physiologically guided approach to
fluid resuscitation likely improves patient outcomes.
stroke volume. This concept is referred to as
fluid responsiveness, which is best defined as
an increase in the stroke volume index (SVI) of
greater than 10% following a 500 ml fluid
&
bolus (see also below) [6 ].
(2) Clinical studies across heterogenous popula-
tions of patients including those with sepsis,
trauma, pancreatitis, burns as well as intra-
operative and postoperative patients have con-
sistently and reproducibly demonstrated that
only about 50% of hemodynamically unstable
&
patients are fluid responsive [5,6 ]. This implies
that approximately 50% of hemodynamically
unstable patients will not benefit from a fluid
bolus and that a fluid bolus could potentially
be harmful.
(3) Both noninvasive as well as minimally invasive (8)
cardiac output monitors are useful in deter-
mining fluid responsiveness in shocked
patients by assessing the response to a passive
&
leg raising maneuver (PLR) or fluid bolus [6 ,7].
The SVI (or cardiac output) should be moni-
tored dynamically and in real-time as the max-
imal change in SVI has been reported to occur
after 1.2 min with return to the baseline hemo- (9)
dynamic profile after 10 min [8].
(4) Goal-directed fluid management based on
fluid responsiveness has been shown to reduce
mortality, as well as duration of mechanical
&&
ventilation [9 ,10]. Paradoxically, this
approach may reduce the risk of acute kidney
injury and the duration of vasopressor support
[10]. In critically ill patients with renal, car-
diac, or respiratory failure, transpulmonary
thermodilution monitoring with measure-
ment of the extravascular lung water index
(EVLWI) and global end-diastolic volume
index (GEDI) will provide additional data to
guide fluid resuscitation [11].
(5) Static ‘preload’ parameters, such as the central
venous pressure (CVP), pulmonary capillary
wedge pressure (PCWP), venal caval diameter,
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Fluid therapy and shock Marik and Weinmann
and so forth are unreliable and should not be
used to guide fluid management [3,12,13].
Crystalloids ‘resuscitate’ predominantly the
interstitial compartment with less than 20%
remaining intravascular after about 2 h [14].
Consequently, the hemodynamic benefit, as
reflected by the SVI and MAP, is short lived,
typically lasting for less than 1 h [5,8,15].
The major category of shock must be rapidly
determined; this is based on a focused history
and clinical examination. Within a few
minutes, the presumptive category of shock
should be ‘clinically obvious’ in the vast majorly
of patients with shock. A bed-side-focused
transthoracic echocardiographic examination
is a simple, readily available intervention that
can provide vital information in supporting the
clinical diagnosis. Bed-side echocardiography
allows for the rapid determination of left and
right ventricular function, as well the detection
of cardiac tamponade, major valvular disease,
and hypertrophic obstructive cardiomyopathy
(HOCM). Although echocardiography can usu-
ally support a diagnosis of severe volume deple-
tion, it is less useful in assessing volume status
and fluid responsiveness. In the modern ICU,
echocardiography (as performed by intensivist)
plays a major role in the initial and ongoing
assessment of patients with hemodynamic
instability [16].
A one-size-fits-all fluid treatment strategy is
exceedingly dangerous and will increase
patient morbidity and mortality [17]. The
approach to the resuscitation of any patient
with shock must be individualized and based
on the type of shock, the patient’s comorbid-
ities (and hemodynamic reserve) as well as the
patients’ hemodynamic and respiratory status.
The ideal volume of a fluid bolus/fluid chal-
lenge is somewhat controversial. The FENICE
study was a global inception cohort study,
which evaluated fluid challenges in 2213
patients in 311 centers in 46 countries [18].
In this study, the median (interquartile range)
amount of fluid given during a fluid challenge
&
was 500 ml (500–1000). Aya et al. [19 ] studied
the hemodynamic effect of different doses of
fluids in postcardiac surgery patients. These
investigators reported that the predicted mini-
mal volume required for a fluid challenge was
between 321 and 509 ml and that at least 4 ml/
kg was required to reliably increase the mean
circulating filling pressure and to distinguish
fluid responders from nonresponders. On
the basis of this data, and for simplicity and
standardization we suggest that fluid is best
www.co-criticalcare.com 247
Cardiopulmonary monitoring
administered as 500 ml boluses of crystalloid
with repeat boluses as clinically indicated. The
patient’s physiologic response to a fluid bolus
should be closely monitored and only those
who have shown a beneficial effect should
cautiously receive further boluses of fluid.
(10) Under almost all circumstances, a balanced
crystalloid (e.g. Lactated Ringers solution) is
the crystalloid of choice; this includes patient
with diabetic ketoacidosis, burns, trauma, sep-
&& &
sis, pancreatitis, and so forth [20 ,21 ].
Taking these basic principles into consideration,
the resuscitation of patients with hypovolemic,
obstructive and distributive shock will be briefly
reviewed. Patients with acute cardiogenic shock
frequently require cardiac-assist devices; this topic
is beyond the scope of this article and the reader is
referred to contemporary reviews on this subject
[22–24].
HYPOVOLEMIC SHOCK
Hypovolemic shock is because of reduced intravas-
cular volume (i.e. reduced preload), which, in turn,
reduces cardiac output and blood pressure. Hypo-
volemic shock can be divided into hemorrhagic and
nonhemorrhagic shock. This distinction is usually
clinically obvious and influences the treatment
strategy.
Hemorrhagic shock
The most important causes of hemorrhagic shock
include traumatic injuries, gastrointestinal bleed-
ing, ruptured aneurysm, and less commonly post-
operative hemorrhage. In patients who have lost
blood, fluid moves from the interstitial to the intra-
vascular compartment to restore blood volume; the
hemoglobin concentration falls by hemodilution.
Therefore, both the intravascular and extravascular,
extra-cellular compartments are decreased follow-
ing blood loss. Experimental hemorrhage models
have demonstrated a higher mortality when ani-
mals are resuscitated with blood alone, as compared
with blood and crystalloids. Patients who have lost
blood should, therefore, be resuscitated with crys-
talloid (Lactated Ringers solution), followed by
blood. Trauma-induced coagulopathy occurs within
minutes of injury and is associated with an increased
mortality [25]. Large-volume crystalloid resuscita-
tion should be avoided as this will compound the
coagulopathy of trauma and lead to increased bleed-
ing [25,26]. Several studies show a stepwise increase
in coagulopathy associated with the volume of crys-
talloid administered [27,28]. The main strategy to
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
treat trauma-induced coagulopathy is to provide
volume replacement that augments coagulation.
Current consensus is that fresh frozen plasma
(FFP) and platelets should be given from the begin-
ning of the resuscitation, alongside transfusions
of packed red blood cells [25,26]. The target hemo-
globin should be about 7 g/dl [29]. Furthermore,
‘permissive hypotension’ (MAP 50–55 mmHg) is
suggested until surgical, coil embolization, or endo-
scopic control of the bleeding has been achieved
[30].
Nonhemorrhagic hypovolemic shock
Nonhemorrhagic hypovolemic shock is perhaps the
‘easiest’ category of shock to treat. This category
includes patients who have lost bodily fluids from
diarrhea, vomiting, diabetic osmotic diuresis, and so
forth. These patients have lost both intravascular
and extravascular, extracellular fluid. Volume
replacement with crystalloids will resuscitate both
compartments. The choice of crystalloid (Lactated
Ringers solution or isotonic saline) will depend on
the patients’ serum sodium concentration; how-
ever, in most circumstances, Lactated Ringers solu-
&
tion is the crystalloid of choice [21 ]. These patients
may require large volumes of fluid. Tests of fluid
responsiveness are less valuable in these patients
and fluid resuscitation is best guided by hemody-
namic parameters and clinical examination. Never-
theless, overzealous resuscitation and fluid overload
should be avoided.
OBSTRUCTIVE SHOCK
This category includes patients with a pericardial
effusion with cardiac tamponade, those with mas-
sive pulmonary embolism and patients with HOCM
with left ventricular outflow obstruction (LVOT).
Fluid management is important in these conditions,
although the approach differs quite considerably.
In cardiac tamponade, cardiac output is reduced
because of underfilling and collapse of the right
ventricle whereas in massive pulmonary embolism,
cardiac output is reduced because of severe enlarge-
ment and failure of the right ventricle. In patients
with cardiac tamponade, a fluid bolus may increase
right ventricular filling and thereby increase SVI.
However, in patients with a massive pulmonary
embolism and right ventricular (RV) failure, a fluid
bolus may further increase right ventricular size
(without an increase in SVI) and compromise left
ventricular filling because of the phenomenon of
ventricular interdependence. Fluids should be used
with extreme caution in patients with massive pulmo-
nary embolism. When RV afterload is significantly
Volume 25  Number 3  June 2019

increased, even a relatively small increase in blood
volume may result in RV dysfunction.
In patients with HOCM dynamic left ventricular
outflow obstruction (LVOT) may occur leading to
decreased cardiac output with hemodynamic com-
promise [31]. In these patients, volume depletion
tends to decrease stroke volume and worsen the
LVOT gradient, leading to hypotension, syncope,
and hemodynamic collapse. Acute hemodynamic
collapse in the setting of LVOT obstruction should
be treated with a fluid bolus (repeated as required)
and an infusion of phenylephrine (increases after-
load and decreases LVOT obstruction) [31]. Ino-
tropes that may worsen LVOT obstruction should
be avoided.
SEPTIC SHOCK
A rational approach to the treatment of patients
with septic shock requires a basic understanding
of the pathophysiology of this disease [32,33]. Ignor-
ing these concepts and/or basing treatment on
unproven dogma will increase the morbidity and
mortality of patients with septic shock. Firstly,
although it is widely assumed that the microcircu-
latory dysfunction in sepsis leads to tissue and cel-
lular hypoxia, there is no credible evidence to
support this concept. An emerging body of evidence
suggests that the organ dysfunction of sepsis is a
consequence of metabolic failure and the failure to
generate ATP. This occurs at the mitochondrial level
because of abnormities of the Krebs cycle and elec-
tron transport chain [34,35]. This suggests that the
traditional approach of increasing oxygen delivery
to improve organ function, may be both counterin-
tuitive and harmful. Secondly, severe sepsis and
septic shock are not volume-depleted states; the
patient has not lost fluid, it has just been redistrib-
uted (in vasodilatory shock).
The first step in the management of patients
with septic shock is to determine if the patient has
distributive (vasodilatory) shock or ‘cold’ shock.
Approximately, 20% of patients with septic shock
present/develop a ‘septic cardiomyopathy’ with
markedly reduced left ventricular function and
compensatory vasoconstriction. The distinction
between ‘warm’ and ‘cold’ septic shock is important
as the treatment differs with norepinephrine being
the pressor of choice in the former with dobut-
amine/milrinone and low-dose norepinephrine
preferable in those with cold septic shock [36].
Patients with vasodilatory shock have severe veno-
dilatation with a large increase in the unstressed
venous volume; this results in a decrease in venous
return and stroke volume. The hypotension is com-
pounded by loss of arterial tone and arterial
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Fluid therapy and shock Marik and Weinmann
vasodilatation. It is important to recognize that
although some patients with sepsis may have pre-
existing dehydration (because of decreased oral
intake, vomiting, diarrhea, etc.) sepsis per se is
not a volume-depleted state and that large volumes
of fluid resuscitation may be harmful. Norepineph-
rine is a potent venoconstrictor, which will increase
the stressed blood volume in patients with vaso-
dilatory shock, thereby increasing venous return
and cardiac output [37,38]. Unless the patient is
truly volume-depleted, fluid boluses will have a less
pronounced or no effect on the stressed blood vol-
ume with little improvement in venous return and
cardiac output. Furthermore, fluid boluses may par-
adoxically cause further vasodilatation and decrease
adrenergic responsiveness [10,39]. This concept is
supported by an elegant experimental model per-
&&
formed by Byrne et al. [40 ]. In an ovine endotoxic
shock model, these authors compared fluid resusci-
tation with 40 ml/kg of isotonic saline followed
by norepinephrine versus hemodynamic support
with protocolized noradrenaline and vasopressin
without a fluid bolus. Paradoxically, the fluid resus-
citation group required greater vasopressor require-
ments than vasopressor group to achieve the same
hemodynamic goals. Furthermore, fluid resuscita-
tion was associated with an increase in plasma atrial
natriuretic peptide (ANP) and the glycocalyx glycos-
aminoglycan hyaluronan, suggesting that large-
volume fluid resuscitation resulted in iatrogenic
damage to the glycocalyx. These concepts may
explain the results of the FEAST study, which com-
pared a fluid management strategy consisting of a
40 ml/kg fluid bolus as compared with no fluid bolus
&&
in African children with severe sepsis [41 ]. The
fluid bolus group had a significantly higher mortal-
ity largely because of early hemodynamic collapse.
The current paradigm promoted by the Surviv-
ing Sepsis Campaign is to resuscitate patients with
large volumes of fluid (beginning with a 30 ml/kg
fluid bolus) and to commence vasopressors once
fluids have failed to reach to hemodynamic goals
[17]. We favor an individualized, conservative, and
physiologically guided fluid strategy with the early
use of norepinephrine [42]. These two differing
approaches are outlined in Fig. 1. The conservative
approach to fluid management in sepsis is supported
by the ever-expanding number of studies, which
have demonstrated a strong association between a
positive fluid balance and adverse outcomes in
&
patients with sepsis [4 ,43–45]. The CLOVERS trial
is a multicenter, randomized, clinical trial being
conducted by the NHLBI PETAL Network, which
is essentially comparing these two treatment strate-
gies; that is, liberal fluid followed by pressors versus
&
early pressors and limited fluid [46 ]. Although the
www.co-criticalcare.com 249
Cardiopulmonary monitoring
FIGURE 1. Paradigm change in the management of sepsis and septic shock. Reproduced with permission from [42].
CLOVERS trial will likely provide useful informa-
tion, it is unlikely to provide the definitive approach
to the management of all patients with septic shock.
CONCLUSION
We strongly believe that the treatment approach to
every patient with shock must be individualized
based on the type of shock, the patient’s diagnoses,
comorbidities, hemodynamic and respiratory sta-
tus, and degree of fluid responsiveness and guided
by the thoughtful intensivist at the patient’s
bed-side.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
P.E.M. has received consulting fees and an honorarium
for Baxter Healthcare. He has no other conflicts of
interest to declare. M.W. has no conflicts of interest.
250 www.co-criticalcare.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Both authors contributed to this manuscript. Both
authors have reviewed the final draft of this manuscript
and approved it for publication.
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& and NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL)
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early septic shock: rationale for a randomized trial. Ann Emerg Med 2018;
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This article outlines the rationale of the CLOVERS study, which is comparing a fluid
restrictive to a fluid liberal strategy in the management of patients with septic
shock.
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