Circulatory Shock - Review Article

This review article discusses the pathophysiological mechanisms, differential diagnosis, and initial approach to the patient in shock. It also covers the use of vasopressors and fluid resuscitation in the treatment of shock.

review article
T h en e w e ngl a nd j o u r na lo f m e dic i n e
n engl j med 369;18nejm.org october 31, 20131726
critical care medicine
Simon R. Finfer, M.D., and Jean-Louis Vincent, M.D., Ph.D., Editors
Circulatory Shock
Jean-Louis Vincent, M.D., Ph.D., and Daniel De Backer, M.D., Ph.D.
From the Department of Intensive Care,
Erasme Hospital, Université Libre de Brux-
elles, Brussels. Address reprint requests to
Dr. Vincent at the Department of Intensive
Care, Erasme University Hospital, Rte. de
Lennik 808, B-1070 Brussels, Belgium, or
at [e-mail].
N Engl J Med 2013;369:1726-34.
DOI: 10.1056/NEJMra1208943
Copyright © 2013 Massachusetts Medical Society.
Shock is the clinical expression of circulatory failure that
results in inadequate cellular oxygen utilization. Shock is a common condi-
tion in critical care, affecting about one third of patients in the intensive ca
unit (ICU).1 A diagnosis of shock is based on clinical, hemodynamic, and bio-
chemical signs, which can broadly be summarized into three components. First,
systemic arterial hypotension is usually present, but the magnitude of the hypo
sion may be only moderate, especially in patients with chronic hypertension. Ty
cally, in adults, the systolic arterial pressure is less than 90 mm Hg or the mean
arterial pressure is less than 70 mm Hg, with associated tachycardia. Second, th
are clinical signs of tissue hypoperfusion, which are apparent through the three
“windows” of the body2: cutaneous (skin that is cold and clammy, with vasocon-
striction and cyanosis, findings that are most evident in low-flow states), renal
(urine output of <0.5 ml per kilogram of body weight per hour), and neurologic
(altered mental state, which typically includes obtundation, disorientation,
confusion). Third, hyperlactatemia is typically present, indicating abnormal cellu
oxygen metabolism. The normal blood lactate level is approximately 1 mmol pe
but the level is increased (>1.5 mmol per liter) in acute circulatory failure.
Pathoph ysiol o gic a l Mech a nisms
Shock results from four potential, and not necessarily exclusive, pathophysiolog
mechanisms3: hypovolemia (from internal or external fluid loss), cardiogenic fac-
tors (e.g., acute myocardial infarction, end-stage cardiomyopathy, advanced va
heart disease, myocarditis, or cardiac arrhythmias), obstruction (e.g., pulmonar
embolism, cardiac tamponade, or tension pneumothorax), or distributive factors
(e.g., severe sepsis or anaphylaxis from the release of inflammatory mediators)
(Fig. 1A and the interactive graphic, available at NEJM.org). The first three mech
anisms are characterized by low cardiac output and, hence, inadequate oxygen
port. In distributive shock, the main deficit lies in the periphery, with decreased
systemic vascular resistance and altered oxygen extraction. Typically, in such c
cardiac output is high, although it may be low as a result of associated myocard
depression. Patients with acute circulatory failure often have a combination of t
mechanisms. For example, a patient with distributive shock from severe pancre
anaphylaxis, or sepsis may also have hypovolemia and cardiogenic shock from
myocardial depression.
Differ en ti a l Di agnosis
Septic shock, a form of distributive shock, is the most common form of shock
among patients in the ICU, followed by cardiogenic and hypovolemic shoc
obstructive shock is relatively rare (Fig. 1B and 1C). In a trial involving more tha
An interactive
graphic showing
initial assessment of
shock is available
at NEJM.org
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Critical Care Medicine
n engl j med 369;18nejm.org october 31, 2013 1727
1600 patients with shock who were randomly as-
signed to receive either dopamine or norepineph-
rine, septic shock occurred in 62% of the patients,
cardiogenic shock in 16%, hypovolemic shock in
16%, other types of distributive shock in 4%, and
obstructive shock in 2%.4
The type and cause of shock may be obvious
from the medical history, physical examination,
or clinical investigations. For example, shock
after traumatic injury is likely to be hypovolemic
(due to blood loss), but cardiogenic shock or
distributive shock may also occur, alone or in
combination, caused by such conditions as car-
diac tamponade or spinal cord injury. A full clini-
cal examination should include assessment of
skin color and temperature, jugular venous dis-
tention, and peripheral edema. The diagnosis
can be refined with point-of-care echocardio-
graphic evaluation, which includes assessment
for pericardial effusion, measurement of left and
right ventricular size and function, assessment for
respiratory variations in vena cava dimensions,
and calculation of the aortic velocity–time inte-
gral, a measure of stroke volume. Whenever pos-
sible, focused echocardiography should be per-
formed as soon as possiblein any patient
presenting with shock (Fig. 1A).5,6
Ini ti a l A pproach
t o the Patien t in Sho ck
Early, adequate hemodynamic support of patients
in shock is crucial to prevent worsening organ
dysfunction and failure. Resuscitation should be
started even while investigation of the cause is
ongoing. Once identified, the cause must be cor-
rected rapidly (e.g., control of bleeding, percuta-
neous coronary intervention for coronary syn-
dromes, thrombolysis or embolectomy for massive
pulmonary embolism, and administration of anti-
biotics and source control for septic shock).
Unless the condition is rapidly reversed, an
arterial catheter should be inserted for monitor-
ing of arterial blood pressure and blood sam-
pling, plus a central venous catheter for the infu-
sion of fluids and vasoactive agents and to guide
fluid therapy. The initial management of shock
is problem-oriented, and the goals are therefore
the same, regardless of the cause, although the
exact treatments that are used to reach those
goals may differ. A useful mnemonic to describe
the important components of resuscitation is the
VIP rule7: ventilate (oxygen administration), in-
fuse (fluid resuscitation), and pump (administra-
tion of vasoactive agents).
Ventilatory Support
The administration of oxygen should be started im-
mediately to increase oxygen delivery and prevent
pulmonary hypertension. Pulse oximetry is often
unreliable as a result of peripheral vasoconstric-
tion, and precise determination of oxygen require-
ments will often require blood gas monitoring.
Mechanical ventilation by means of a mask
rather than endotracheal intubation has a lim-
ited place in the treatment of shock because
technical failure can rapidly result in respiratory
and cardiac arrest. Hence, endotracheal intuba-
tion should be performed to provide invasive
mechanical ventilation in nearly all patients with
severe dyspnea, hypoxemia, or persistent or wors-
ening acidemia (pH, <7.30). Invasive mechanical
ventilation has the additional benefits of reduc-
ing the oxygen demand of respiratory muscles
and decreasing left ventricular afterload by in-
creasing intrathoracic pressure. An abrupt de-
crease in arterial pressure after the initiation of
invasive mechanical ventilation strongly suggests
hypovolemia and a decrease in venous return.
The use of sedative agents should be kept to a
minimum to avoid further decreases in arterial
pressure and cardiac output.
Fluid Resuscitation
Fluid therapy to improve microvascular blood
flow and increase cardiac output is an essential
part of the treatment of any form of shock. Even
patients with cardiogenic shock may benefit
from fluids, since acute edema can result in a
decrease in the effective intravascular volume.
However, fluid administration should be closely
monitored, since too much fluid carries the risk
of edema with its unwanted consequences.
Pragmatic end points for fluid resuscitation
are difficult to define. In general, the objective is
for cardiac output to become preload-indepen-
dent (i.e., on the plateau portion of the Frank–
Starling curve), but this is difficult to assess
clinically. In patients receiving mechanical ventila-
tion, signs of fluid responsiveness may be identi-
fied either directly from beat-by-beat stroke-volume
measurements with the use of cardiac-output
monitors or indirectly from observed variations
in pulse pressure on the arterial-pressure tracing
during the ventilator cycle. However, such bedside
inferences have some limitations8 — notably,
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1
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Signs of tissue hypoperfusion
Chronic
hypotension?
Syncope
(if transient)
PresentAbsent
Normal
or high
Low
CVP
Distributive shock Hypovolemic shock
Small cardiac
chambers and normal
or high contractility
Normal cardiac
chambers and (usually)
preserved contractility
Cardiogenic shock
Large ventricles and
poor contractility
In tamponade: pericardial
effusion, small right and
left ventricles, dilated
inferior vena cava; in
pulmonary embolism or
pneumothorax: dilated right
ventricle, small left ventricle
Obstructive shock
Distributive shock Hypovolemic shock Cardiogenic shock Obstructive shock
HighLow
Obstruction
Pericardial
tamponade
Loss of
plasma or
blood
volume
Vasodilatation
Ventricular
failure
C
A
Estimate cardiac
output or SvO2
Arterial hypotension
Circulatory
shock
Echocardiography
Brain
Altered mental
state
Skin
Kidney
Mottled,
clammy
Oliguria
Tachycardia
Elevated
blood
lactate
B Types of shock
ObstructiveDistributive
(nonseptic)
4% 2%
Hypovolemic
16%
62%
Distributive (septic)
Cardiogenic
16%
Figure 1. Initial Assessment of Shock States.
Shown is an algorithm for the initial assessment of a patient in shock (Panel A), relative frequencies of the main types of shock (Pan
and schematic representations of the four main types of shock (Panel C). The algorithm starts with the most common presentation
(i.e., arterial hypotension), but hypotension is sometimes minimal or absent. CVP denotes central venous pressure, and Sv O2 mixed
venous oxygen saturation.
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Critical Care Medicine
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that the patient must receive ventilation with
relatively large tidal volumes, have no spontane-
ous breathing effort (which usually requires the
administration of sedatives or even muscle relax-
ants), and be free of major arrhythmia and right
ventricular dysfunction. A passive leg-raising test
is an alternative method9 but requires a rapid-
response device, since the effect is transient.
Regardless of the test used, there remains a gray
zone in which it is difficult to predict a patient’s
response to intravenous fluids.
A fluid-challenge technique should be used to
determine a patient’s actual response to fluids,
while limiting the risks of adverse effects. A fluid
challenge incorporates four elements that should
be defined in advance.10 First, the type of fluid
must be selected. Crystalloid solutions are the
first choice, because they are well tolerated and
cheap. The use of albumin to correct severe hy-
poalbuminemia may be reasonable in some pa-
tients.11 (A detailed examination of the choice of
resuscitation fluids was provided in a previous
article in this series12 and thus is not included in
this review.) Second, the rate of fluid adminis-
tration must be defined. Fluids should be in-
fused rapidly to induce a quick response but not
so fast that an artificial stress response develops;
typically, an infusion of 300 to 500 ml of fluid
is administered during a period of 20 to 30 min-
utes.13 Third, the objective of the fluid challenge
must be defined. In shock, the objective is usu-
ally an increase in systemic arterial pressure,
although it could also be a decrease in heart rate
or an increase in urine output. Finally, the safety
limits must be defined. Pulmonary edema is the
most serious complication of fluid infusion. Al-
though it is not a perfect guideline, a limit in
central venous pressure of a few millimeters of
mercury above the baseline value is usually set to
prevent fluid overload.13
Stimulation of the patient and any other
change in therapy should be avoided during the
test. Fluid challenges can be repeated as required
but must be stopped rapidly in case of non-
response in order to avoid fluid overload.
Vasoactive Agents
Vasopressors
If hypotension is severe or if it persists despite
fluid administration, the use of vasopressors is
indicated. It is acceptable practice to administer
a vasopressor temporarily while fluid resuscita-
tion is ongoing, with the aim of discontinuing it,
if possible, after hypovolemia has been corrected.
Adrenergic agonists are the first-line vaso-
pressors because of their rapid onset of action,
high potency, and short half-life, which allows
easy dose adjustment. Stimulation of each type
of adrenergic receptor has potentially beneficial
and harmful effects. For example, β-adrenergic
stimulation can increase blood flow but also in-
creases the risk of myocardial ischemia as a result
of increased heart rate and contractility. Hence, the
use of isoproterenol, a pure β-adrenergic agent, is
limited to the treatment of patients with severe
bradycardia. At the other extreme, α-adrenergic
stimulation will increase vascular tone and blood
pressure but can also decrease cardiac output
and impair tissue blood flow, especially in the
hepatosplanchnic region. For this reason, phenyl-
ephrine, an almost pure α-adrenergic agent, is
rarely indicated.
We consider norepinephrine to be the vaso-
pressor of first choice; it has predominantly
α-adren ergic properties, but its modest β-adrener-
gic effects help to maintain cardiac output.
Administration generally results in a clinically
significant increase in mean arterial pressure,
with little change in heart rate or cardiac output.
The usual dose is 0.1 to 2.0 μg per kilogram of
body weight per minute.
Dopamine has predominantly β-adrenergic
effects at lower doses and α-adrenergic effects at
higher doses, but its effects are relatively weak.
Dopaminergic effects at very low doses (<3 μg per
kilogram per minute, given intravenously) may
selectively dilate the hepatosplanchnic and renal
circulations, but controlled trials have not shown
a protective effect on renal function,14 and its
routine use for this purpose is no longer recom-
mended. Dopaminergic stimulation may also
have undesired endocrine effects on the hypo-
thalamic–pituitary system, resulting in immuno-
suppression, primarily through a reduction in
the release of prolactin.
In a recent randomized, controlled, double-
blind trial, dopamine had no advantage over nor-
epinephrine as the first-line vasopressor agent;
moreover, it induced more arrhythmias and was
associated with an increased 28-day rate of
death among patients with cardiogenic shock.4
Administration of dopamine, as compared with
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T h en e w e ngl a nd j o u r na lo f m e dic i n e
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norepinephrine, may also be associated with
higher rates of death among patients with septic
shock.15 Hence, we no longer recommend dopa-
mine for the treatment of patients with shock.
Epinephrine, which is a stronger agent, has
predominantly β-adrenergic effects at low doses,
with α-adrenergic effects becoming more clini-
cally significant at higher doses. However, epi-
nephrine administration can be associated with
an increased rate of arrhythmia16,17and a decrease
in splanchnic blood flow16 and can increase blood
lactate levels, probably by increasing cellular me-
tabolism.16,18Prospective, randomized studies have
not shown any beneficial effects of epinephrine
over norepinephrine in septic shock.17,18We re-
serve epinephrine as a second-line agent for se-
vere cases.13
The use of other strong vasopressor agents as
continuous infusions (e.g., angiotensin or meta-
raminol) has largely been abandoned. Nonselec-
tive inhibition of nitric oxide has not been shown
to be beneficial in patients with cardiogenic
shock19 and is detrimental in patients with sep-
tic shock.20
Vasopressin deficiency can develop in pa-
tients with very hyperkinetic forms of distribu-
tive shock, and the administration of low-dose
vasopressin may result in substantial increases
in arterial pressure. In the Vasopressin and Sep-
tic Shock Trial (VASST), investigators found that
the addition of low-dose vasopressin to norepi-
nephrine in the treatment of patients with septic
shock was safe21 and may have been associated
with a survival benefit for patients with forms of
shock that were not severe and for those who
also received glucocorticoids.22 Vasopressin should
not be used at doses higher than 0.04 U per min-
ute and should be administered only in patients
with a high level of cardiac output.
Terlipressin, an analogue of vasopressin, has
a duration of action of several hours, as com-
pared with minutes for vasopressin. For this
reason, we do not believe it offers an advantage
over vasopressin in the ICU. Vasopressin deriva-
tives with more selective V1-receptor activity are
currently being studied.
Inotropic Agents
We consider dobutamine to be the inotropic
agent of choice for increasing cardiac output, re-
gardless of whether norepinephrine is also being
given. With predominantly β-adrenergic proper-
ties, dobutamine is less likely to induce tachycar-
dia than isoproterenol. An initial dose of just a
few micrograms per kilogram per minute may
substantially increase cardiac output. Intravenous
doses in excess of 20 μg per kilogram per minute
usually provide little additional benefit. Dobuta-
mine has limited effects on arterial pressure, al-
though pressure may increase slightly in patients
with myocardial dysfunction as the primary ab-
normality or may decrease slightly in patients
with underlying hypovolemia. Instead of routine
administration of a fixed dose of dobutamine to
increase oxygen delivery to supranormal, prede-
termined levels, the dose should be adjusted on
an individual basis to achieve adequate tissue
perfusion. Dobutamine may improve capillary
perfusion in patients with septic shock, indepen-
dent of its systemic effects.23
Phosphodiesterase type III inhibitors, such as
milrinone and enoximone, combine inotropic and
vasodilating properties. By decreasing the me-
tabolism of cyclic AMP, these agents may rein-
force the effects of dobutamine. They may also
be useful when β-adrenergic receptors are down-
regulated or in patients recently treated with
beta-blockers. However, phosphodiesterase type
III inhibitors may have unacceptable adverse ef-
fects in patients with hypotension, and the long
half-lives of these agents (4 to 6 hours) prevent
minute-to-minute adjustment. Hence, intermit-
tent, short-term infusions of small doses of
phosphodiesterase III inhibitors may be prefer-
able to a continuous infusion in shock states.
Levosimendan, a more expensive agent, acts
primarily by binding to cardiac troponin C and
increasing the calcium sensitivity of myocytes,
but it also acts as a vasodilator by opening ATP-
sensitive potassium channels in vascular smooth
muscle. However, this agent has a half-life of
several days, which limits the practicality of its
use in acute shock states.
Vasodilators
By reducing ventricular afterload, vasodilating
agents may increase cardiac output without in-
creasing myocardial demand for oxygen. The
major limitation of these drugs is the risk of de-
creasing arterial pressure to a level that compro-
mises tissue perfusion. Nevertheless, in some
patients, prudent use of nitrates and possibly
other vasodilators may improve microvascular
perfusion and cellular function.24
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Critical Care Medicine
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Mech a nic a l Support
Mechanicalsupportwith intraaorticballoon
counterpulsation (IABC) can reduce left ventricu-
lar afterload and increase coronary blood flow.
However, a recent randomized, controlled trial
showed no beneficial effect of IABC in patients
with cardiogenic shock,25 and its routine use in
cardiogenic shock is not currently recommended.
Venoarterial extracorporeal membrane oxygena tion
(ECMO) may be used as a temporary lifesaving
measure in patients with reversible cardiogenic
shock or as a bridge to heart transplantation.26
G oa l s of Hemody na mic Support
Arterial Pressure
The primary goal of resuscitation should be not
only to restore blood pressure but also to provide
adequate cellular metabolism, for which the cor-
rection of arterial hypotension is a prerequisite.
Restoring a mean systemic arterial pressure of
65 to 70 mm Hg is a good initial goal, but the
level should be adjusted to restore tissue perfu-
sion, assessed on the basis of mental status, skin
appearance, and urine output, as described above.
In patients with oliguria, in particular, the effects
of a further increase in arterial pressure on urine
output should be assessed regularly, unlessacute
renal failure is already established. Conversely,a
mean arterial pressure lower than 65 to 70 mm Hg
may be acceptable in a patient with acute bleeding
who has no major neurologic problems, with the
aim of limiting blood loss and associated coagu-
lopathy, until the bleeding is controlled.
Cardiac Output and Oxygen Delivery
Since circulatory shock represents an imbalance
between oxygen supply and oxygen requirements,
maintaining adequate oxygen delivery to the tis-
sues is essential, but all the strategies to achieve
this goal have limitations. After correction of hy-
poxemia and severe anemia, cardiac output is the
principal determinant of oxygen delivery, but the
optimal cardiac output is difficult to define. Car-
diac output can be measured by means of various
techniques, each of which has its own benefits
and drawbacks.6 Absolute measures of cardiac
output are less important than monitoring trends
in response to interventions such as a fluid chal-
lenge. The targeting of a predefined cardiac out-
put is not advisable, since the cardiac output that
is needed will vary among patients and in the
same patient over time.
Measurements of mixed venous oxygen satu-
ration (SvO2) may be helpful in assessing the
adequacy of the balance between oxygen de-
mand and supply; SvO2 measurements are also
very useful in the interpretation of cardiac out-
put.27 SvO2 is typically decreased in patients with
low-flow states or anemia but is normal or high
in those with distributive shock. Its surrogate,
central venous oxygen saturation (ScvO2), which
is measured in the superior vena cava by means
of a central venous catheter, reflects the oxygen
saturation of the venous blood from the upper
half of the body only. Under normal circumstances,
ScvO2 is slightly less than SvO2, but in critically
ill patients it is often greater. Rivers et al.28 found
A
B
Figure 2. Sidestream Dark-Field Images of Sublingual
Microcirculation in a Healthy Volunteer and a Patient
with Septic Shock.
The microcirculation in the healthy volunteer is charac-
terized by dense capillaries that are consistently perfused
(Panel A, arrows), whereas in the patient with septic
shock, the density of the capillaries is diminished, and
many of the capillaries have stopped or intermittent
flow (Panel B, arrows).
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T h en e w e ngl a nd j o u r na lo f m e dic i n e
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that in patients presenting to the emergency
department with septic shock, a treatment algo-
rithm targeting an ScvO2 of at least 70% during
the first 6 hours was associated with decreased
rates of death. The robustness of this finding is
currently being evaluated in three multicenter
trials. (ClinicalTrials.gov numbers, NCT00975793
and NCT00510835; and Current Controlled Trials
number, ISRCTN36307479).
Blood Lactate Level
An increase in the blood lactate level reflects ab-
normal cellular function. In low-flow states, the
primary mechanism of hyperlactatemia is tissue
hypoxia with development of anaerobic metabo-
lism, but in distributive shock, the pathophysiol-
ogy is more complex and may also involve increased
glycolysis and inhibition of pyruvate dehydroge-
nase. In all cases, alterations in clearance can be
due to impaired liver function.
The value of serial lactate measurements in
the management of shock has been recognized
for 30 years.29 Although changes in lactate take
place more slowly than changes in systemic arte-
rial pressure or cardiac output, the blood lactate
level should decrease over a period of hours with
effective therapy. In patients with shock and a
blood lactate level of more than 3 mmol per liter,
Jansen et al.24 found that targeting a decrease
of at least 20% in the blood lactate level over a
2-hour period seemed to be associated with re-
duced in-hospital mortality.
Microcirculatory Variables
The development of handheld devices for orthog-
onal polarization spectral (OPS) imaging and its
successor, sidestream dark-field (SDF) imaging,
is providing new means of directly visualizing
the microcirculation and evaluating the effects of
interventions on microcirculatory flow in easily
accessible surfaces, such as the sublingual area.30
Microcirculatory changes, including decreased
capillary density, a reduced proportion of perfused
capillaries, and increased heterogeneity of blood
flow, have been identified in various types of circu-
latory shock (Fig. 2), and the persistence of these
alterations is associated with worse outcomes.31
Near-infrared spectroscopy is a technique that
uses near-infrared light to determine tissue oxy-
gen saturation from the fractions of oxyhemo-
globin and deoxyhemoglobin. Analysis of the
changes in tissue oxygen saturation during a
brief episode of forearm ischemia can be used to
quantify microvascular dysfunction32; such altera-
tions are associated with worse outcomes.33 Vari-
ous therapeutic interventions have been shown
to have an effect on these microcirculatory vari-
ables, but whether therapy that is guided by
monitoring or targeting the microcirculation
can improve outcomes requires further study
and cannot be recommended at this time.
Ther a peu tic Pr ior i ties
a nd G oa l s
There are essentially four phases in the treatment
of shock, and therapeutic goals and monitoring
need to be adapted to each phase (Fig. 3). In the
first (salvage) phase, the goal of therapy is to
achieve a minimum blood pressure and cardiac
output compatible with immediate survival. Mini-
mal monitoring is needed; in most cases, invasive
monitoring can be restricted to arterial and cen-
tral venous catheters. Lifesaving procedures (e.g.,
surgery for trauma, pericardial drainage, revascu-
larization for acute myocardial infarction, and anti-
biotics for sepsis) are needed to treat the under-
lying cause. In the second (optimization) phase, the
goal is to increase cellular oxygen availability, and
there is a narrow window of opportunity for inter-
ventions targeting hemo dynamic status.28 Ade-
quate hemodynamic resuscitation reduces inflam-
mation, mitochondrial dysfunction, and caspase
activation.34,35Measurements of SvO2 and lactate
levels may help guide therapy, and monitoring of
cardiac output should be considered. In the third
3
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Author
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DE
Artist
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COLOR FIGURE
Draft 6
Vincent
Knoper
Obtain a
minimal
acceptable
blood pressure
Perform
lifesaving
measures
Provide
adequate
oxygen
availability
Optimize
cardiac output,
SvO2, lactate
Provide organ
support
Minimize
complications
Wean from
vasoactive
agents
Achieve a
negative
fluid balance
Salvage Optimization Stabilization De-escalation
Phase Focus
Figure 3. Four Phases in the Treatment of Shock.
The salvage phase focuses on achieving a blood pressure and cardiac out-
put compatible with immediate survival and performing lifesaving proce-
dures to treat the underlying cause of shock. The optimization phase focus-
es on promoting cellular oxygen availability and monitoring cardiac output,
mixed venous oxygen saturation (SvO2), and lactate levels. The stabilization
phase focuses on preventing organ dysfunction, even after hemodynamic
stability has been achieved. The de-escalation phase focuses on weaning
the patient from vasoactive agents and providing treatments to help
achieve a negative fluid balance.
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Critical Care Medicine
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(stabilization) phase, the goal is to prevent organ
dysfunction, even after hemodynamic stability has
been achieved. Oxygen supply to the tissues is no
longer the key problem, and organ support be-
comes more relevant. Finally, in the fourth (de-
escalation) phase, the goal is to wean the patient
from vasoactive agents and promote spontaneous
polyuria or provoke fluid elimination through the
use of diuretics or ultrafiltration to achieve a neg-
ative fluid balance.
Conclusions
Circulatory shock is associated with high mor-
bidity and mortality. Prompt identification is es-
sential so that aggressive management can be
started. Appropriate treatment is based on a good
understanding of the underlying pathophysiolog-
ical mechanisms. Treatment should include cor-
rection of the cause of shock and hemodynamic
stabilization, primarily through fluid infusion
and administration of vasoactive agents. The pa-
tient’s response can be monitored by means of
careful clinical evaluation and blood lactate mea-
surements; microvascular evaluation may be fea-
sible in the future.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
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