The n e w e ng l a n d j o u r na l of m e dic i n e

review article

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.

S
From the Department of Intensive Care, hock is the clinical expression of circulatory failure that
Erasme Hospital, Universit Libre de Brux- results in inadequate cellular oxygen utilization. Shock is a common condi-
elles, Brussels. Address reprint requests to
Dr. Vincent at the Department of Intensive tion in critical care, affecting about one third of patients in the intensive care
Care, Erasme University Hospital, Rte. de unit (ICU).1 A diagnosis of shock is based on clinical, hemodynamic, and bio-
Lennik 808, B-1070 Brussels, Belgium, or chemical signs, which can broadly be summarized into three components. First,
at [email protected].
systemic arterial hypotension is usually present, but the magnitude of the hypoten-
N Engl J Med 2013;369:1726-34. sion may be only moderate, especially in patients with chronic hypertension. Typi-
DOI: 10.1056/NEJMra1208943
Copyright 2013 Massachusetts Medical Society.
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, there
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, and
confusion). Third, hyperlactatemia is typically present, indicating abnormal cellular
oxygen metabolism. The normal blood lactate level is approximately 1 mmol per liter,
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, pathophysiological
mechanisms3: hypovolemia (from internal or external fluid loss), cardiogenic fac-
tors (e.g., acute myocardial infarction, end-stage cardiomyopathy, advanced valvular
heart disease, myocarditis, or cardiac arrhythmias), obstruction (e.g., pulmonary
embolism, cardiac tamponade, or tension pneumothorax), or distributive factors
(e.g., severe sepsis or anaphylaxis from the release of inflammatory mediators)
An interactive (Fig.1A and the interactive graphic, available at NEJM.org). The first three mech-
graphic showing anisms are characterized by low cardiac output and, hence, inadequate oxygen trans-
initial assessment of
shock is available
port. In distributive shock, the main deficit lies in the periphery, with decreased
at NEJM.org systemic vascular resistance and altered oxygen extraction. Typically, in such cases
cardiac output is high, although it may be low as a result of associated myocardial
depression. Patients with acute circulatory failure often have a combination of these
mechanisms. For example, a patient with distributive shock from severe pancreatitis,
anaphylaxis, or sepsis may also have hypovolemia and cardiogenic shock from
myocardial depression.

Differ en t i 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 shock;
obstructive shock is relatively rare (Fig. 1B and 1C). In a trial involving more than

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 Critical Care Medicine

1600 patients with shock who were randomly as- fuse (fluid resuscitation), and pump (administra-
signed to receive either dopamine or norepineph- tion of vasoactive agents).
rine, septic shock occurred in 62% of the patients,
cardiogenic shock in 16%, hypovolemic shock in Ventilatory Support
16%, other types of distributive shock in 4%, and The administration of oxygen should be started im-
obstructive shock in 2%.4 mediately to increase oxygen delivery and prevent
The type and cause of shock may be obvious pulmonary hypertension. Pulse oximetry is often
from the medical history, physical examination, unreliable as a result of peripheral vasoconstric-
or clinical investigations. For example, shock tion, and precise determination of oxygen require-
after traumatic injury is likely to be hypovolemic ments will often require blood gas monitoring.
(due to blood loss), but cardiogenic shock or Mechanical ventilation by means of a mask
distributive shock may also occur, alone or in rather than endotracheal intubation has a lim-
combination, caused by such conditions as car- ited place in the treatment of shock because
diac tamponade or spinal cord injury. A full clini- technical failure can rapidly result in respiratory
cal examination should include assessment of and cardiac arrest. Hence, endotracheal intuba-
skin color and temperature, jugular venous dis- tion should be performed to provide invasive
tention, and peripheral edema. The diagnosis mechanical ventilation in nearly all patients with
can be refined with point-of-care echocardio- severe dyspnea, hypoxemia, or persistent or wors-
graphic evaluation, which includes assessment ening acidemia (pH, <7.30). Invasive mechanical
for pericardial effusion, measurement of left and ventilation has the additional benefits of reduc-
right ventricular size and function, assessment for ing the oxygen demand of respiratory muscles
respiratory variations in vena cava dimensions, and decreasing left ventricular afterload by in-
and calculation of the aortic velocitytime inte- creasing intrathoracic pressure. An abrupt de-
gral, a measure of stroke volume. Whenever pos- crease in arterial pressure after the initiation of
sible, focused echocardiography should be per- invasive mechanical ventilation strongly suggests
formed as soon as possible in any patient hypovolemia and a decrease in venous return.
presenting with shock (Fig. 1A).5,6 The use of sedative agents should be kept to a
minimum to avoid further decreases in arterial
pressure and cardiac output.
Ini t i a l A pproach
t o the Pat ien t in Sho ck
Fluid Resuscitation
Early, adequate hemodynamic support of patients Fluid therapy to improve microvascular blood
in shock is crucial to prevent worsening organ flow and increase cardiac output is an essential
dysfunction and failure. Resuscitation should be part of the treatment of any form of shock. Even
started even while investigation of the cause is patients with cardiogenic shock may benefit
ongoing. Once identified, the cause must be cor- from fluids, since acute edema can result in a
rected rapidly (e.g., control of bleeding, percuta- decrease in the effective intravascular volume.
neous coronary intervention for coronary syn- However, fluid administration should be closely
dromes, thrombolysis or embolectomy for massive monitored, since too much fluid carries the risk
pulmonary embolism, and administration of anti- of edema with its unwanted consequences.
biotics and source control for septic shock). Pragmatic end points for fluid resuscitation
Unless the condition is rapidly reversed, an are difficult to define. In general, the objective is
arterial catheter should be inserted for monitor- for cardiac output to become preload-indepen-
ing of arterial blood pressure and blood sam- dent (i.e., on the plateau portion of the Frank
pling, plus a central venous catheter for the infu- Starling curve), but this is difficult to assess
sion of fluids and vasoactive agents and to guide clinically. In patients receiving mechanical ventila-
fluid therapy. The initial management of shock tion, signs of fluid responsiveness may be identi-
is problem-oriented, and the goals are therefore fied either directly from beat-by-beat stroke-volume
the same, regardless of the cause, although the measurements with the use of cardiac-output
exact treatments that are used to reach those monitors or indirectly from observed variations
goals may differ. A useful mnemonic to describe in pulse pressure on the arterial-pressure tracing
the important components of resuscitation is the during the ventilator cycle. However, such bedside
VIP rule7: ventilate (oxygen administration), in- inferences have some limitations8 notably,

n engl j med 369;18nejm.orgoctober 31, 2013 1727

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 The n e w e ng l a n d j o u r na l of m e dic i n e

A B Types of shock
Arterial hypotension
62%
Distributive (septic)

Absent Signs of tissue hypoperfusion Present

Brain
Altered mental
Chronic
state
hypotension?
Syncope Circulatory
(if transient) shock 4% 2%
Distributive Obstructive
Tachycardia (nonseptic)
16% 16%
Skin Elevated Estimate cardiac Cardiogenic Hypovolemic
blood output or SvO2
Mottled,
clammy lactate

Normal Low
or high
Kidney
Oliguria CVP

Low High

Echocardiography In tamponade: pericardial

effusion, small right and
Normal cardiac Small cardiac left ventricles, dilated
Large ventricles and
chambers and (usually) chambers and normal inferior vena cava; in
poor contractility
preserved contractility or high contractility pulmonary embolism or
pneumothorax: dilated right
ventricle, small left ventricle

Distributive shock Hypovolemic shock Cardiogenic shock Obstructive shock

Distributive shock Hypovolemic shock Cardiogenic shock Obstructive shock

Loss of Obstruction
Vasodilatation plasma or
blood
volume

Ventricular Pericardial
failure tamponade

Figure 1. Initial Assessment of Shock States.

COLOR FIGURE
Shown is an algorithm for the initial assessment of a patient in shock (Panel A), relative frequencies of the main types of shock (Panel B),
and schematic representations of the four main types of shock (Panel C). The algorithm starts with the most common Draft 9presentation 10/10/13
Author Vincent
(i.e., arterial hypotension), but hypotension is sometimes minimal or absent. CVP denotes central venous pressure, Fig #
and
1
SvO2 mixed
venous oxygen saturation. Title

ME
DE Drazen
Artist Knoper
AUTHOR PLEASE NOTE:
Figure has been redrawn and type has been reset

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Please check carefully

10/31/13

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 Critical Care Medicine

that the patient must receive ventilation with a vasopressor temporarily while fluid resuscita-
relatively large tidal volumes, have no spontane- tion is ongoing, with the aim of discontinuing it,
ous breathing effort (which usually requires the if possible, after hypovolemia has been corrected.
administration of sedatives or even muscle relax- Adrenergic agonists are the first-line vaso-
ants), and be free of major arrhythmia and right pressors because of their rapid onset of action,
ventricular dysfunction. A passive leg-raising testhigh potency, and short half-life, which allows
is an alternative method9 but requires a rapid- easy dose adjustment. Stimulation of each type
response device, since the effect is transient. of adrenergic receptor has potentially beneficial
Regardless of the test used, there remains a gray and harmful effects. For example, -adrenergic
zone in which it is difficult to predict a patients
stimulation can increase blood flow but also in-
response to intravenous fluids. creases the risk of myocardial ischemia as a result
A fluid-challenge technique should be used to of increased heart rate and contractility. Hence, the
determine a patients actual response to fluids, use of isoproterenol, a pure -adrenergic agent, is
while limiting the risks of adverse effects. A fluid
limited to the treatment of patients with severe
challenge incorporates four elements that should bradycardia. At the other extreme, -adrenergic
be defined in advance.10 First, the type of fluid stimulation will increase vascular tone and blood
must be selected. Crystalloid solutions are the pressure but can also decrease cardiac output
first choice, because they are well tolerated and and impair tissue blood flow, especially in the
cheap. The use of albumin to correct severe hy- hepatosplanchnic region. For this reason, phenyl
poalbuminemia may be reasonable in some pa- ephrine, an almost pure -adrenergic agent, is
tients.11 (A detailed examination of the choice of rarely indicated.
resuscitation fluids was provided in a previous We consider norepinephrine to be the vaso-
article in this series12 and thus is not included in
pressor of first choice; it has predominantly
this review.) Second, the rate of fluid adminis- -adrenergic properties, but its modest -adrener
tration must be defined. Fluids should be in- gic effects help to maintain cardiac output.
fused rapidly to induce a quick response but not Administration generally results in a clinically
so fast that an artificial stress response develops;
significant increase in mean arterial pressure,
typically, an infusion of 300 to 500 ml of fluid with little change in heart rate or cardiac output.
is administered during a period of 20 to 30 min- The usual dose is 0.1 to 2.0 g per kilogram of
utes.13 Third, the objective of the fluid challengebody weight per minute.
must be defined. In shock, the objective is usu- Dopamine has predominantly -adrenergic
ally an increase in systemic arterial pressure, effects at lower doses and -adrenergic effects at
although it could also be a decrease in heart rate higher doses, but its effects are relatively weak.
or an increase in urine output. Finally, the safetyDopaminergic effects at very low doses (<3 g per
limits must be defined. Pulmonary edema is the kilogram per minute, given intravenously) may
most serious complication of fluid infusion. Al- selectively dilate the hepatosplanchnic and renal
though it is not a perfect guideline, a limit in circulations, but controlled trials have not shown
central venous pressure of a few millimeters of a protective effect on renal function,14 and its
mercury above the baseline value is usually set to routine use for this purpose is no longer recom-
prevent fluid overload.13 mended. Dopaminergic stimulation may also
Stimulation of the patient and any other have undesired endocrine effects on the hypo-
change in therapy should be avoided during the thalamicpituitary system, resulting in immuno
test. Fluid challenges can be repeated as required suppression, primarily through a reduction in
but must be stopped rapidly in case of non the release of prolactin.
response in order to avoid fluid overload. In a recent randomized, controlled, double-
blind trial, dopamine had no advantage over nor
Vasoactive Agents epinephrine as the first-line vasopressor agent;
Vasopressors moreover, it induced more arrhythmias and was
If hypotension is severe or if it persists despite associated with an increased 28-day rate of
fluid administration, the use of vasopressors is death among patients with cardiogenic shock.4
indicated. It is acceptable practice to administer Administration of dopamine, as compared with

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 The n e w e ng l a n d j o u r na l of m e dic i n e

norepinephrine, may also be associated with ties, dobutamine is less likely to induce tachycar-
higher rates of death among patients with septic dia than isoproterenol. An initial dose of just a
shock.15 Hence, we no longer recommend dopa- few micrograms per kilogram per minute may
mine for the treatment of patients with shock. substantially increase cardiac output. Intravenous
Epinephrine, which is a stronger agent, has doses in excess of 20 g per kilogram per minute
predominantly -adrenergic effects at low doses, usually provide little additional benefit. Dobuta-
with -adrenergic effects becoming more clini- mine has limited effects on arterial pressure, al-
cally significant at higher doses. However, epi- though pressure may increase slightly in patients
nephrine administration can be associated with with myocardial dysfunction as the primary ab-
an increased rate of arrhythmia16,17 and a decrease normality or may decrease slightly in patients
in splanchnic blood flow16 and can increase blood with underlying hypovolemia. Instead of routine
lactate levels, probably by increasing cellular me- administration of a fixed dose of dobutamine to
tabolism.16,18 Prospective, randomized studies have increase oxygen delivery to supranormal, prede-
not shown any beneficial effects of epinephrine termined levels, the dose should be adjusted on
over norepinephrine in septic shock.17,18 We re- an individual basis to achieve adequate tissue
serve epinephrine as a second-line agent for se- perfusion. Dobutamine may improve capillary
vere cases.13 perfusion in patients with septic shock, indepen-
The use of other strong vasopressor agents as dent of its systemic effects.23
continuous infusions (e.g., angiotensin or meta- Phosphodiesterase type III inhibitors, such as
raminol) has largely been abandoned. Nonselec- milrinone and enoximone, combine inotropic and
tive inhibition of nitric oxide has not been shown vasodilating properties. By decreasing the me-
to be beneficial in patients with cardiogenic tabolism of cyclic AMP, these agents may rein-
shock19 and is detrimental in patients with sep- force the effects of dobutamine. They may also
tic shock.20 be useful when -adrenergic receptors are down-
Vasopressin deficiency can develop in pa- regulated or in patients recently treated with
tients with very hyperkinetic forms of distribu- beta-blockers. However, phosphodiesterase type
tive shock, and the administration of low-dose III inhibitors may have unacceptable adverse ef-
vasopressin may result in substantial increases fects in patients with hypotension, and the long
in arterial pressure. In the Vasopressin and Sep- half-lives of these agents (4 to 6 hours) prevent
tic Shock Trial (VASST), investigators found that minute-to-minute adjustment. Hence, intermit-
the addition of low-dose vasopressin to norepi- tent, short-term infusions of small doses of
nephrine in the treatment of patients with septic phosphodiesterase III inhibitors may be prefer-
shock was safe21 and may have been associated able to a continuous infusion in shock states.
with a survival benefit for patients with forms of Levosimendan, a more expensive agent, acts
shock that were not severe and for those who primarily by binding to cardiac troponin C and
also received glucocorticoids.22 Vasopressin should increasing the calcium sensitivity of myocytes,
not be used at doses higher than 0.04 U per min- but it also acts as a vasodilator by opening ATP-
ute and should be administered only in patients sensitive potassium channels in vascular smooth
with a high level of cardiac output. muscle. However, this agent has a half-life of
Terlipressin, an analogue of vasopressin, has several days, which limits the practicality of its
a duration of action of several hours, as com- use in acute shock states.
pared with minutes for vasopressin. For this
reason, we do not believe it offers an advantage Vasodilators
over vasopressin in the ICU. Vasopressin deriva- By reducing ventricular afterload, vasodilating
tives with more selective V1-receptor activity are agents may increase cardiac output without in-
currently being studied. creasing myocardial demand for oxygen. The
major limitation of these drugs is the risk of de-
Inotropic Agents creasing arterial pressure to a level that compro-
We consider dobutamine to be the inotropic mises tissue perfusion. Nevertheless, in some
agent of choice for increasing cardiac output, re- patients, prudent use of nitrates and possibly
gardless of whether norepinephrine is also being other vasodilators may improve microvascular
given. With predominantly -adrenergic proper- perfusion and cellular function.24

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 Critical Care Medicine

Mech a nic a l Supp or t A

Mechanical support with intraaortic balloon
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 oxygenation
(ECMO) may be used as a temporary lifesaving
measure in patients with reversible cardiogenic
shock or as a bridge to heart transplantation.26
B
G oa l s of Hemody na mic Supp or t
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. Figure 2. Sidestream Dark-Field Images of Sublingual
In patients with oliguria, in particular, the effects Microcirculation in a Healthy Volunteer and a Patient
of a further increase in arterial pressure on urine with Septic Shock.
output should be assessed regularly, unless acute The microcirculation in the healthy volunteer is charac-
renal failure is already established. Conversely, a terized by dense capillaries that are consistently perfused
mean arterial pressure lower than 65 to 70 mm Hg (Panel A, arrows), whereas in the patient with septic
shock, the density of the capillaries is diminished, and
may be acceptable in a patient with acute bleeding many of the capillaries have stopped or intermittent
who has no major neurologic problems, with the flow (Panel B, arrows).
aim of limiting blood loss and associated coagu-
lopathy, until the bleeding is controlled.
is needed will vary among patients and in the
Cardiac Output and Oxygen Delivery same patient over time.
Since circulatory shock represents an imbalance Measurements of mixed venous oxygen satu-
between oxygen supply and oxygen requirements, ration (SvO2) may be helpful in assessing the
maintaining adequate oxygen delivery to the tis- adequacy of the balance between oxygen de-
sues is essential, but all the strategies to achieve mand and supply; SvO2 measurements are also
this goal have limitations. After correction of hy- very useful in the interpretation of cardiac out-
poxemia and severe anemia, cardiac output is the put.27 SvO2 is typically decreased in patients with
principal determinant of oxygen delivery, but the low-flow states or anemia but is normal or high
optimal cardiac output is difficult to define. Car- in those with distributive shock. Its surrogate,
diac output can be measured by means of various central venous oxygen saturation (ScvO2), which
techniques, each of which has its own benefits is measured in the superior vena cava by means
and drawbacks.6 Absolute measures of cardiac of a central venous catheter, reflects the oxygen
output are less important than monitoring trends saturation of the venous blood from the upper
in response to interventions such as a fluid chal- half of the body only. Under normal circumstances,
lenge. The targeting of a predefined cardiac out- ScvO2 is slightly less than SvO2, but in critically
put is not advisable, since the cardiac output that ill patients it is often greater. Rivers et al.28 found

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Microcirculatory Variables

Salvage Optimization Stabilization De-escalation The development of handheld devices for orthog-
onal polarization spectral (OPS) imaging and its
Obtain a Provide Provide organ Wean from successor, sidestream dark-field (SDF) imaging,
is providing new means of directly visualizing
Phase Focus

minimal adequate support vasoactive

acceptable oxygen agents
blood pressure availability
the microcirculation and evaluating the effects of
interventions on microcirculatory flow in easily
Perform Optimize Minimize Achieve a accessible surfaces, such as the sublingual area.30
lifesaving cardiac output, complications negative
measures SvO2, lactate fluid balance
Microcirculatory changes, including decreased
capillary density, a reduced proportion of perfused
Figure 3. Four Phases in the Treatment of Shock. capillaries, and increased heterogeneity of blood
COLOR FIGURE

The salvage phase focuses on achieving a blood pressure and cardiac out- flow, have been identified in various types of circu-
Draft 6 10/15/13
put compatible with immediate survival and performing
Author Vincent
lifesaving proce- latory shock (Fig. 2), and the persistence of these
dures to treat the underlying cause of shock. The Fig
optimization
# 3 phase focus- alterations is associated with worse outcomes.31
es on promoting cellular oxygen availability and monitoring
Title cardiac output, Near-infrared spectroscopy is a technique that
mixed venous oxygen saturation (SvO2), and lactate levels. The stabilization
ME uses near-infrared light to determine tissue oxy-
phase focuses on preventing organ dysfunction, even
DE after
Drazen hemodynamic
stability has been achieved. The de-escalation phase
Artist focuses
Knoper on weaning
gen saturation from the fractions of oxyhemo-
the patient from vasoactive agents and providing treatmentsAUTHOR PLEASEto help NOTE: globin and deoxyhemoglobin. Analysis of the
Figure has been redrawn and type has been reset
achieve a negative fluid balance. Please check carefully changes in tissue oxygen saturation during a
Issue date 10/31/13
brief episode of forearm ischemia can be used to
quantify microvascular dysfunction32; such altera-
that in patients presenting to the emergency tions are associated with worse outcomes.33 Vari-
department with septic shock, a treatment algo- ous therapeutic interventions have been shown
rithm targeting an ScvO2 of at least 70% during to have an effect on these microcirculatory vari-
the first 6 hours was associated with decreased ables, but whether therapy that is guided by
rates of death. The robustness of this finding is monitoring or targeting the microcirculation
currently being evaluated in three multicenter can improve outcomes requires further study
trials. (ClinicalTrials.gov numbers, NCT00975793 and cannot be recommended at this time.
and NCT00510835; and Current Controlled Trials
number, ISRCTN36307479).
Ther a peu t ic Pr ior i t ie s
a nd G oa l s
Blood Lactate Level
An increase in the blood lactate level reflects ab- There are essentially four phases in the treatment
normal cellular function. In low-flow states, the of shock, and therapeutic goals and monitoring
primary mechanism of hyperlactatemia is tissue need to be adapted to each phase (Fig. 3). In the
hypoxia with development of anaerobic metabo- first (salvage) phase, the goal of therapy is to
lism, but in distributive shock, the pathophysiol- achieve a minimum blood pressure and cardiac
ogy is more complex and may also involve increased output compatible with immediate survival. Mini-
glycolysis and inhibition of pyruvate dehydroge- mal monitoring is needed; in most cases, invasive
nase. In all cases, alterations in clearance can be monitoring can be restricted to arterial and cen-
due to impaired liver function. tral venous catheters. Lifesaving procedures (e.g.,
The value of serial lactate measurements in surgery for trauma, pericardial drainage, revascu-
the management of shock has been recognized larization for acute myocardial infarction, and anti-
for 30 years.29 Although changes in lactate take biotics for sepsis) are needed to treat the under-
place more slowly than changes in systemic arte- lying cause. In the second (optimization) phase, the
rial pressure or cardiac output, the blood lactate goal is to increase cellular oxygen availability, and
level should decrease over a period of hours with there is a narrow window of opportunity for inter-
effective therapy. In patients with shock and a ventions targeting hemodynamic status.28 Ade-
blood lactate level of more than 3 mmol per liter, quate hemodynamic resuscitation reduces inflam-
Jansen et al.24 found that targeting a decrease mation, mitochondrial dysfunction, and caspase
of at least 20% in the blood lactate level over a activation.34,35 Measurements of SvO2 and lactate
2-hour period seemed to be associated with re- levels may help guide therapy, and monitoring of
duced in-hospital mortality. cardiac output should be considered. In the third

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 Critical Care Medicine

(stabilization) phase, the goal is to prevent organ sential so that aggressive management can be
dysfunction, even after hemodynamic stability has started. Appropriate treatment is based on a good
been achieved. Oxygen supply to the tissues is no understanding of the underlying pathophysiolog-
longer the key problem, and organ support be- ical mechanisms. Treatment should include cor-
comes more relevant. Finally, in the fourth (de- rection of the cause of shock and hemodynamic
escalation) phase, the goal is to wean the patient stabilization, primarily through fluid infusion
from vasoactive agents and promote spontaneous and administration of vasoactive agents. The pa-
polyuria or provoke fluid elimination through the tients response can be monitored by means of
use of diuretics or ultrafiltration to achieve a neg- careful clinical evaluation and blood lactate mea-
ative fluid balance. surements; microvascular evaluation may be fea-
sible in the future.
C onclusions
No potential conflict of interest relevant to this article was
reported.
Circulatory shock is associated with high mor- Disclosure forms provided by the authors are available with
bidity and mortality. Prompt identification is es- the full text of this article at NEJM.org.

References

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