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Intensive Care Med (2014) 40:17951815

DOI 10.1007/s00134-014-3525-z CONFERENCE REPORTS AND EXPERT PA NEL

Maurizio Cecconi
Daniel De Backer
Consensus on circulatory shock
Massimo Antonelli and hemodynamic monitoring. Task force
Richard Beale
Jan Bakker of the European Society of Intensive Care
Christoph Hofer
Roman Jaeschke Medicine
Alexandre Mebazaa
Michael R. Pinsky
Jean Louis Teboul
Jean Louis Vincent
Andrew Rhodes

R. Jaeschke literature and evidence. These ques-


Received: 17 October 2014 McMaster University, Hamilton, ON,
Accepted: 18 October 2014 tions were: (1) What are the
Canada epidemiologic and pathophysiologic
Published online: 13 November 2014
 The Author(s) 2014. This article is features of shock in the intensive care
published with open access at A. Mebazaa
Springerlink.com Department of Anesthesiology and Critical unit? (2) Should we monitor preload
Care Medicine, U942 INSERM, Universite and fluid responsiveness in shock? (3)
Paris Diderot, PRES Sorbonne Paris Cite How and when should we monitor
M. Cecconi ())  A. Rhodes and APHP, Saint Louis Lariboisie`re stroke volume or cardiac output in
Anaesthesia and Intensive Care, St Georges University Hospitals, Paris, France shock? (4) What markers of the
Hospital and Medical School, SW17 0QT regional and microcirculation can be
London, UK M. R. Pinsky
Department of Critical Care Medicine, monitored, and how can cellular
e-mail: mcecconi@sgul.ac.uk; function be assessed in shock? (5)
m.cecconi@nhs.net University of Pittsburgh, Pittsburgh, PA
15261, USA What is the evidence for using
Tel.: ?44-208-7250879
hemodynamic monitoring to direct
D. De Backer  J. L. Vincent J. L. Teboul therapy in shock? Four types of
Department of Intensive Care, Erasme Hopital de Bicetre, Service de Reanimation statements were used: definition,
University Hospital, Universite Libre de Medicale, AP-HP, Hopitaux Universitaires recommendation, best practice and
Bruxelles, Brussels, Belgium Paris-Sud, Le Kremlin-Bicetre, France
statement of fact. Results: Forty-
four statements were made. The main
M. Antonelli
Abstract Objective: Circulatory new statements include: (1) state-
Department of Intensive Care Medicine and
Anesthesiology, Catholic UniversityA. shock is a life-threatening syndrome ments on individualizing blood
Gemelli University Hospital, Rome, Italy resulting in multiorgan failure and a pressure targets; (2) statements on the
high mortality rate. The aim of this assessment and prediction of fluid
R. Beale consensus is to provide support to the responsiveness; (3) statements on the
Department of Critical Care, Kings College bedside clinician regarding the diag- use of echocardiography and hemo-
London, Guys and St Thomas Foundation nosis, management and monitoring of dynamic monitoring.
Trust, Westminster Bridge Road, London
shock. Methods: The European Conclusions: This consensus pro-
SE1 7EH, UK
Society of Intensive Care Medicine vides 44 statements that can be used
J. Bakker invited 12 experts to form a Task at the bedside to diagnose, treat and
Department of Intensive Care Adults, Force to update a previous consensus monitor patients with shock.
Erasmus University Medical Center, (Antonelli et al.: Intensive Care Med
Rotterdam, The Netherlands 33:575590, 2007). The same five Keywords Circulatory shock 
questions addressed in the earlier Intensive care unit 
C. Hofer Hemodynamic monitoring 
Department of Transversal Medicine,
consensus were used as the outline for
Institute of Anesthesiology and Intensive the literature search and review, with Echocardiography 
Care Medicine, Triemli City Hospital, the aim of the Task Force to produce Consensus statement/guidelines
Zurich, Switzerland statements based on the available
1796

Introduction time and resources to formal evidence review, best


practice statements were issued.
Guidelines for the hemodynamic management of patients A modified Delphi approach was used to achieve con-
with circulatory shock and their implications for manage- sensus. For each of the five questions included in the 2006
ment [1] were developed in 2006 by a team of 25 experts in guidelines [1], five pairs of experts of the consensus group
the field of shock and a jury of 11 individuals representing were assigned the task of reviewing the new clinical trial
five critical care societies. In these guidelines, five specific data and presenting their findings at a consensus confer-
questions were addressed: (1) What are the epidemiologic ence. During the conference, held in Brussels in March
and pathophysiologic features of shock in the intensive 2014, the evidence and recommendations were reviewed
care unit (ICU)? (2) Should we monitor preload and fluid and discussed by the entire group and consensus reached.
responsiveness in shock? (3) How and when should we A medical writer (Sophie Rushton-Smith) was present
monitor stroke volume or cardiac output in shock? (4) at the conference in Brussels and recorded the minutes of
What markers of the regional and microcirculation can be the discussion. These were used to complete the contri-
monitored, and how can cellular function be assessed in butions of the authors and to draft the first version of the
shock? (5) What is the evidence for using hemodynamic manuscript.
monitoring to direct therapy in shock? A conference call was held in August 2014. To com-
Since the publication of the 2006 guidelines [1], data plete the process by taking into account the latest papers
from several observational and randomized clinical trials published (up to 1 October 2014), members of the Task
(RCTs) have been published that provide new evidence Force communicated with each other via emails and
for the optimal management of patients with circulatory telephone conversations. The findings are presented in
shock. In this paper, the term shock refers to circulatory this report. While the same five questions of 2006 were
shock. used as the basis to search and discuss available literature,
the present report has been written without retaining the
order of the answers to the five questions of the 2006
consensus. This decision was based on the obvious
Consensus methodology overlap between answers to the different questions and to
provide a more readable manuscript. The main differ-
An international team of 12 experts in the field of shock ences between the 2007 report of Antonelli et al. [1] and
was invited by the European Society of Intensive Care this consensus are summarized in Tables 1 and 2. The
Medicine to form a Task Force to evaluate new evidence statements issued in 2014 by the Task Force are sum-
and to revise the guidelines as judged appropriate. Four marized in Tables 3, 4, 5 and 6.
types of statements were used for the consensusstate-
ments of facts, recommendations, best practice and
definitions (for example, definition of shock).
Statements of facts are used to summarize an Definition, pathophysiology, features
important topic discussed in the consensus when facts, and epidemiology of shock
rather than actions, are discussed and agreed. Definition
Indications to act or not to act on a specific issue are
written in the form of a recommendation or best Shock is best defined as a life-threatening, generalized
practice statement. Although the formal GRADE form of acute circulatory failure associated with inade-
(Grading of Recommendations Assessment, Development quate oxygen utilization by the cells. It is a state in which
and Evaluation) system of evidence review with the the circulation is unable to deliver sufficient oxygen to
generation of evidence profiles was not conducted, in meet the demands of the tissues, resulting in cellular
making their recommendations the Task Force members dysfunction. The result is cellular dysoxia, i.e. the loss of
took into account the principles of the GRADE system. the physiological independence between oxygen delivery
This system classifies recommendations as strong (Level and oxygen consumption, associated with increased lac-
1) or weak (Level 2) [2] based on the certainty of Task tate levels. Some clinical symptoms suggest an impaired
Force members that following given recommendation will microcirculation, including mottled skin, acrocyanosis,
result in more good than harm. Panelists were also aware slow capillary refill time and an increased central-to-toe
that strength of the GRADE system recommendation temperature gradient.
depends on the quality of underlying evidence (certainty
in the estimates of effects), balance of benefits and harms,
costs and values and preferences of the interested parties. Pathophysiology and features of shock
When the panel judged that a specific recommendation
should be issued, but there was either no reasonable Shock is a clinical state of acute circulatory failure [3]
alternative or sufficient indirect reasoning not to commit that can result from one, or a combination, of four
1797

Table 1 Main differences between the 2006 and 2014 consensus papers in terms of definition of shock, blood pressure statements and
fluid responsiveness statements

Topic ICM Antonelli 2007 ICM Cecconi 2014

Definition We recommend that shock be defined as a life- We define circulatory as a life-threatening, generalized
threatening, generalized maldistribution of blood form of acute circulatory failure associated with
flow resulting in failure to deliver and/or utilize inadequate oxygen utilization by the cells. Ungraded
adequate amounts of oxygen, leading to tissue
dysoxia. Level 1; QoE moderate (B)
Blood pressure We recommend a target blood pressure during We recommend individualizing the target blood
statements initial shock resuscitation of: pressure during shock resuscitation. Level 1; QoE
For uncontrolled hemorrhage due to trauma: MAP moderate (B)
of 40 mmHg until bleeding is surgically controlled. We recommend to initially target a MAP
Level 1; QoE moderate (B) of C65 mmHg. Level 1; QoE low (C)
For TBI without systemic hemorrhage: MAP of We suggest to tolerate a lower level of blood pressure
90 mmHg. Level 1; QoE low (C) in patients with uncontrolled bleeding (i.e. in patients
For all other shock states: MAP [65 mmHg. with trauma) without severe head injury. Level 2; QoE
Level 1; QoE moderate (B) low (C)
We suggest a higher MAP in septic patients with
history of hypertension and in patients that show clinical
improvement with higher blood pressure. Level 2; QoE
moderate (B)
Fluid responsiveness We do not recommend the routine use of dynamic We recommend using dynamic over static variables to
statements measures of fluid responsiveness (including but predict fluid responsiveness, when applicable. Level
not limited to pulse pressure variation, aortic 1; QoE moderate (B)
flow changes, systolic pressure variation, When the decision for fluid administration is made we
respiratory systolic variation test and collapse of recommend to perform a fluid challenge, unless in cases
vena cava). Level 1; QoE high (A) of obvious hypovolemia (such as overt bleeding in a
There may be some advantage to these ruptured aneurysm). Level 1; QoE low (C)
measurements in highly selected patients. Level 1; We recommend that even in the context of fluid-
QoE moderate (B) responsive patients, fluid management should be titrated
carefully, especially in the presence of elevated
intravascular filling pressures or extravascular lung
water. Ungraded best practice
ICM, Intensive Care Medicine; QoE, Quality of experience, MAP, mean arterial pressure; TBI, traumatic brain injury

avoided. Shock can be categorized according to the


mechanisms [4]. The first of these is a decrease in venous
return due to a loss of circulating volume (i.e. due to underlying cause, including septic shock, cardiogenic
shock, anaphylactic shock and shock associated with
internal or external loss of fluids). The second is a failure
burns, trauma and hemorrhage. In the 1,679 ICU patients
of the pump function of the heart that results from a loss
of contractility (resulting from ischemia, infarction, in the European Sepsis Occurrence in Acutely Ill Patients
myopathy, myocarditis) or a major arrhythmia (such as II (SOAP II) trial, septic shock was the most frequent
ventricular tachycardia or a high degree A-V block). The cause of shock, accounting for 62 % of cases, followed by
third is an obstruction due to pulmonary embolism, ten- cardiogenic shock (17 %) and hypovolemia (16 %) [8].
sion pneumothorax or cardiac tamponade. The fourth is Septic shock is the most severe manifestation of sep-
loss of vascular tone that results in maldistribution of sis, with reported case-fatality rates in the range of
blood flow (due to sepsis, anaphylaxis or spinal injury).4050 %, reaching as high as 80 % [9]. Limited data are
The features of each of these four types of shock often available on the epidemiology of septic shock, particu-
overlap, and patients admitted with one type of shock canlarly in low-income countries [9], but the literature
develop other types of shock. For example, patients hos- suggests that its incidence is increasing [1020]. The
pitalized with hemorrhagic shock due to trauma or with reported incidence of septic shock in patients admitted to
cardiogenic shock occasionally develop septic shock [5, the ICU varies between 6.3 and 14.7 % [1, 21].
6]. Cardiogenic shock has most commonly been studied
in the setting of acute myocardial infarction; the incidence
in this population has remained fairly constant at between
Epidemiology 6 and 9 %, over the past several decades [6, 2225]. In a
multinational observational study of 65,119 patients
Up to one-third of patients admitted to the ICU are in hospitalized for an acute coronary syndrome between
circulatory shock [7], and early recognition of the con- 1999 and 2007, 4.6 % developed cardiogenic shock, and
dition is vital if subsequent tissue injuries are to be the in-hospital case-fatality rate was 59.4 % [26].
1798

Table 2 Main differences between the 2006 and 2014 consensus papers in terms of hemodynamic monitoring

Topic ICM Antonelli 2007 ICM Cecconi 2014

Hemodynamic We do not recommend routine measurement of CO for We recommend further hemodynamic assessment (such as
monitoring patients with shock. Level 1; QoE moderate (B) assessing cardiac function) to determine the type of
We suggest considering echocardiography or shock if the clinical examination does not lead to a clear
measurement of CO for diagnosis in patients with clinical diagnosis. Ungraded best practice
evidence of ventricular failure and persistent shock with We suggest that, when further hemodynamic assessment
adequate fluid resuscitation. Level 2 (weak); QoE moderate is needed, echocardiography is the preferred modality to
(B) initially evaluate the type of shock as opposed to more
We do not recommend the routine use of the pulmonary invasive technologies. Level 2; QoE moderate (B)
artery catheter for patients in shock. Level 1; QoE high (A) In complex patients we suggest to additionally use
pulmonary artery catheterization or transpulmonary
thermodilution to determine the type of shock. Level 2;
QoE low (C)
We do not recommend routine measurement of cardiac
output for patients with shock responding to the initial
therapy. Level 1; QoE low (C)
We recommend measurements of cardiac output and
stroke volume to evaluate the response to fluids or
inotropes in patients that are not responding to initial
therapy. Level 1; QoE low (C)
We suggest sequential evaluation of hemodynamic status
during shock. Level 1; QoE low (C)
Echocardiography can be used for the sequential
evaluation of cardiac function in shock. Statement of fact
We do not recommend the routine use of the pulmonary
artery catheter for patients in shock. Level 1; QoE high (A)
We suggest pulmonary artery catheterization in patients
with refractory shock and right ventricular dysfunction.
Level 2; QoE low (C)
We suggest the use of transpulmonary thermodilution or
pulmonary artery catheterization in patients with severe
shock especially in the case of associated acute respiratory
distress syndrome. Level 2; QoE low (C)
We recommend that less invasive devices are used,
instead of more invasive devices, only when they have been
validated in the context of patients with shock. Ungraded
best practice

The definition, pathophysiology, features and epidemi- signs. The clinical signs of shock typically include
ology of shock arterial hypotension (although this is not always pres-
We define circulatory shock as a life-threatening, general- ent), associated with signs of altered tissue perfusion,
ized form of acute circulatory failure associated with visualized through the three windows of the body
inadequate oxygen utilization by the cells. Definition. [27]: the peripheral window (skin that is cold, clammy
As a result, there is cellular dysoxia, associated with and blue, pale or discolored); the renal window
increased blood lactate levels. Statement of fact. (decreased urine output: \0.5 mL/kg/h); the neurologic
Shock can be associated with four underlying patterns, of window (altered mental characterized by obtundation,
which three are associated with a low flow state (hypo- disorientation and confusion). The presence of low
volemic, cardiogenic, obstructive) and one is associated blood pressure should not be a prerequisite for defining
with a hyperkinetic state (distributive). Statement of fact. shock: compensatory mechanisms may preserve blood
Shock can be due to a combination of processes. pressure through vasoconstriction [28], while tissue
Statement of fact. perfusion and oxygenation are already decreased sig-
nificantly [29].

Diagnosis of shock General considerations

General considerations Shock is typically associated with evidence of inade-


quate tissue perfusion on physical examination. The
The diagnosis of acute circulatory failure is based on a three organs readily accessible to clinical assessment of
combination of clinical, hemodynamic and biochemical tissue perfusion are the:
1799

skin (degree of cutaneous perfusion); Plasma lactate, mixed venous oxygen saturation
kidneys (urine output); and central venous oxygen saturation and other
brain (mental status). perfusion markers

Statement of fact. In experimental models of acute circulatory failure


induced by arterial hypoxemia, low hemoglobin levels,
We recommend routine screening of patients at risk to obstructive shock and septic shock, the onset of decreased
allow earlier identification of impending shock and oxygen utilization relative to oxygen demand is charac-
implementation of therapy. Recommendation. Level 1; terized by increasing lactate levels [33, 34] and decreased
QoE low (C). regional and microcirculatory perfusion [35, 36]. Addi-
We recommend frequent measurement of heart rate, tionally, the results of limited clinical studies have shown
blood pressure, body temperature and physical exam- that inadequate oxygen is associated with increased lac-
ination variables (including signs of hypoperfusion, tate levels [3739].
urine output and mental status) in patients with a Hyperlactatemia is indeed typically present in cases of
history and with clinical findings suggestive of shock. acute circulatory failure, indicating abnormal metabolism.
Best practice. The usual cut-off value is 2 mEq/L (or mmol/L), but
lactate levels of [1.5 mmol/L in patients with septic
shock are associated with increased mortality [40].
Hypotension and shock Although generally increased lactate levels are associated
with abnormal oxidative phosphorylation and inadequate
The diagnostic accuracy of a systolic blood pressure of oxygen utilization [38, 39], other mechanisms may also
\95 mmHg associated with acute blood loss was asses- increase lactate levels in the presence of adequate tissue
sed by Stern et al. in a systematic evaluation of physical oxygenation [4143].
findings in patients with hypovolemia [30]. A random The prognostic value of lactate levels exceeds that of
effects model produced a sensitivity of 13 % for moderate blood pressure [32, 44, 45]. While hyperlactatemia is
blood loss and 33 % for severe blood loss. The authors associated with worse outcome in any type of shock, a
therefore concluded that a systolic blood pressure of correct interpretation also depends on the type of shock,
\95 mmHg is not a sensitive measure for ruling out i.e. septic shock versus hemorrhagic shock [46].
moderate or significant blood loss. A decrease in cardiac From a metabolic perspective, elevations in blood
output is associated with significant vasoconstriction, lactate concentration may be due to increased production,
leading to decreased peripheral perfusion to maintain a decreased clearance or a combination of the two. As
arterial pressure [28]. The presence of hypotension is elevated plasma lactate forms part of the definition of
generally included in the diagnosis of septic shock, but shock, the argument to measure it as a diagnostic marker
several studies have actually shown that preserved blood of shock is circular. Many studies have confirmed the
pressure can be associated with markers of inadequate association between initial serum lactate level and mor-
tissue perfusion, such as decreased central venous oxygen tality independently of clinical signs of organ dysfunction
saturation (ScvO2) and significantly increased concentra- in patients not only with severe sepsis [47], but also those
tions of blood lactate [31]. In addition, persistent in cardiogenic shock [48].
hypotension in patients with septic shock without An early decrease in blood lactate levels may indicate
increased lactate levels may a have limited impact on the resolution of global tissue hypoxia and has been
mortality [32]. associated with a decreased mortality rate [49]. Two
The definition of circulatory shock emerging from this studies proposed lactate-based management of ICU
consensus conference does not therefore require the pre- patients [50, 51]. Jones et al. [50] studied 300 patients, of
sence of hypotension. Rather, the definition of shock as whom more than 80 % had septic shock, who were
life-threatening, generalized form of acute circulatory treated to normalize central venous pressure (CVP) and
failure associated with inadequate oxygen utilization by MAP; additional management to normalize lactate clear-
the cells usually includes, but is not limited to, the pre- ance compared with management to normalize ScvO2 did
sence of hypotension. not result in different rates of hospital mortality. Jansen
et al. [51] showed, in patients with hyperlactatemia
Hypotension and shock ([3.0 mEq/L) on ICU admission, that lactate-guided
We recommend that the presence of arterial hypoten- therapy (with the aim of decreasing lactate by C20 %
sion [defined as systolic blood pressure of \90 mmHg, every 2 h for the initial 8 h) in comparison with no lac-
or mean arterial pressure (MAP) of \65 mmHg, or a tate-guided therapy (in which the treatment team had no
decrease of C40 mmHg from baseline], while com- knowledge of lactate levels other than the admission
monly present, should not be required to define shock. level) reduced hospital mortality when predefined risk
Recommendation. Level 1; QoE moderate (B). factors were adjusted (hazard ratio 0.61, 95 % confidence
1800

Table 3 Summary of the consensus statementspart 1

No. Statement/recommendation GRADEa level of Type of


recommendation; statement
quality of evidence

1 We define circulatory as a life-threatening, generalized form of acute Ungraded Definition


circulatory failure associated with inadequate oxygen utilization by the
cells
2 As a result, there is cellular dysoxia, associated with increased blood Ungraded Statement of fact
lactate levels
3. Shock can be associated with four underlying patterns: three associated Ungraded Statement of fact
with a low flow state (hypovolemic, cardiogenic, obstructive) and one
associated with a hyperkinetic state (distributive)
4. Shock can be due to a combination of processes Ungraded Statement of fact
5. Shock is typically associated with evidence of inadequate tissue Ungraded Statement of fact
perfusion on physical examination. The three organs readily accessible
to clinical assessment of tissue perfusion are the:
-skin (degree of cutaneous perfusion);
kidneys (urine output); and
brain (mental status)
6. We recommend frequent measurement of heart rate, blood pressure, Ungraded Best practice
body temperature and physical examination variables (including signs
of hypoperfusion, urine output and mental status) in patients with a
history and clinical findings suggestive of shock
7. We recommend not to use a single variable (for the diagnosis and/or Ungraded Best practice
management of shock
8. We recommend efforts to identify the type of shock to better target Ungraded Best practice
causal and supportive therapies
9. We recommend that the presence of arterial hypotension (defined as Level 1; QoE moderate (B) Recommendation
systolic blood pressure of \90 mmHg, or MAP of \65 mmHg, or
decrease of C40 mmHg from baseline), while commonly present,
should not be required to define shock
10. We recommend routine screening of patients at risk, to allow earlier Level 1; QoE low (C) Recommendation
identification of impending shock and implementation of therapy
11. We recommend measuring blood lactate levels in all cases where shock Level 1; QoE low (C) Recommendation
is suspected
12. Lactate levels are typically [2 mEq/L (or mmol/L) in shock states Ungraded Statement of fact
Statements in this table are related to the initial diagnosis and recognition of shock. These are also presented in the main text together with
the rationale. The order of presentation in the table has been changed from that in the main text to allow for better reading in the table
a
GRADE refers to the Grading of Recommendations Assessment, Development and Evaluation system of evidence review

interval 0.430.87; P = 0.006). These authors demon- outcome than a different protocolized treatment not using
strated a reduced rate of organ failurebut no reduced this measurement to guide therapy [31]. In their study, the
mortalityin the lactate group compared with the control mean baseline values of ScVO2 were 49 and 48 % for the
group in the early observation period (between 9 and control and EGDT groups, respectively. Two recent
72 h). Lactate levels between the control and lactate multicenter RCTs, the ProCESS and the ARISE trials,
groups were similar over a 3-day period. In clinical failed to reproduce similar results. In these studies,
practice, we suggest serial measurements of lactates and/ patients had a lower mortality and higher mean baseline
or base deficit to evaluate not only the outcome and ScvO2 values (71 % for the ProCESS trial and 73 % for
prognosis but also to guide therapy; lactate measurements ARISE trial) [52, 53] compared to the Rivers et al. study
can be performed every 2 h in the first 8 h and every [31]. In addition, in both the ProCESS and ARISE trials,
812 h thereafter. clinicians well trained in management of septic shock and
In the context of hyperlactatemia and mixed venous well aware of available resuscitation goals and techniques
oxygen saturation (SvO2), ScvO2 can provide important treated the control groups.
information about the balance between oxygen transport In practice, a high ScvO2 value in the context of hy-
and oxygen demand. For example, in the context of septic perlactatemia is of limited use. One of the limitations of
shock, low ScVO2 indicates an inadequacy of oxygen ScvO2 is that normal/high values cannot discriminate if
transport, especially in the context of hyperlactatemia. In the oxygen transport is adequate, as it may remain blind
patients with low ScVO2 values (\70 %), Rivers et al. to local hypoperfusion.
showed that early goal-directed therapy (EGDT) aimed at The venoarterial carbon dioxide difference (pCO2
increasing the ScVO2 to [70 % was associated to a better gap), which measures the difference in the partial pressure
1801

Table 4 Summary of the consensus statementspart 2

No. Statement/recommendation GRADE level of Type of


recommendation; statement
quality of evidence

13. We recommend further hemodynamic assessment (such as assessing cardiac Ungraded Best practice
function) to determine the type of shock if the clinical examination does not
lead to a clear diagnosis
14. We suggest that, when further hemodynamic assessment is needed, Level 2; QoE moderate (B) Recommendation
echocardiography is the preferred modality to initially evaluate the type of
shock as opposed to more invasive technologies
15. In complex patients, we suggest to additionally use pulmonary artery Level 2; QoE low (C) Recommendation
catheterization or transpulmonary thermodilution to determine the type of
shock
16. We recommend early treatment, including hemodynamic stabilization (with Ungraded Best practice
fluids and vasopressors if needed) and treatment of the shock etiology, with
frequent reassessment of response
17. We recommend arterial and central venous catheter insertion in shock not Ungraded Best practice
responsive to initial therapy and/or requiring vasopressor infusion
18. In patients with a central venous catheter, we suggest measurements of ScvO2) Level 2; QoE moderate (B) Recommendation
and V-ApCO2 to help assess the underlying pattern and the adequacy of
cardiac output as well as to guide therapy
19. We recommend serial measurements of blood lactate to guide, monitor, and Level 1; QoE low (C) Recommendation
assess
20. We suggest the techniques to assess regional circulation or microcirculation for Level 2; QoE low (C) Recommendation
research purposes only
V-ApCO2, Veno-arterial partial pressure of carbon dioxide; ScvO2, central venous oxygen saturation
Statements in this table are related to the assessment of perfusion. These are also presented in the main text together with the rationale.
The order of presentation in the table has been changed from that in the main text to allow for better reading in the table

of carbon dioxide (pCO2) between mixed or central Lactate levels are typically [2 mEq/L (or mmol/L) in
venous blood and arterial blood, is a marker that can be shock states. Statement of fact.
used to identify patients who are under-resuscitated. We recommend serial measurements of blood lactate.
Values of[6 mmHg suggest an insufficient blood flow in The rationale is to guide, monitor and assess. Recom-
the tissues even when the ScvO2 is [70 % [54, 55]. mendation. Level 1; QoE low (C).
Although all shock states are associated with systemic In patients with a central venous catheter (CVC), we
inflammation either early or later in the course of circu- suggest measurements of central venous oxygen satu-
latory failure, and markers of systemic inflammation have ration (ScvO2) and venoarterial difference in PCO2 (V-
been associated with mortality in such cases, the levels of ApCO2) to help assess the underlying pattern and the
these mediators are generally higher in septic patients [56 adequacy of cardiac output as well as to guide therapy.
59]. However, even in patients with septic shock, lactate Recommendation. Level 2; QoE moderate (B).
levels have a better prognostic value than other markers
[60]. There is a lack of evidence that other biomarkers of
an early hyper-inflammatory response (e.g. interleukin-1
receptor agonist, intercellular adhesion molecule 1, tumor How and when to monitor cardiac function
necrosis factor-a, caspase 3 and interleukin-8) predict and hemodynamics in shock
early complications, particularly in septic shock [61].
Good animal and human data are available on the role The three main reasons for monitoring cardiac function in
of mediators in the evolution of shock, but current out- circulatory shock are for:
come data do not support the routine use of these
mediators as biomarkers in the diagnosis and staging of Identifying the type of shock.
shock. Selecting the therapeutic intervention.
Evaluating the patients response to therapy.
Plasma lactate, mixed venous oxygen saturation and
central venous oxygen saturation and other perfusion
markers Identification of the type of shock
We recommend measuring blood lactate levels in all
cases where shock is suspected. Recommendation. Identifying the main mechanism responsible for shock
Level 1; QoE low (C). hypovolemic, cardiogenic, obstructive, or distributive [4,
1802

Table 5 Summary of the consensus statementspart 3

No. Statement/recommendation GRADE level of Type of


recommendation; statement
quality of evidence

21. We recommend individualizing the target blood pressure during shock Level 1; QoE moderate (B) Recommendation
resuscitation
22. We recommend to initially target a MAP of C65 mmHg Level 1; QoE low (C) Recommendation
23. We suggest to tolerate a lower level of blood pressure in patients with Level 2; QoE low(C) Recommendation
uncontrolled bleeding (i.e. in patients with trauma) without severe head
injury
24. We suggest a higher MAP in septic patients with history of hypertension and in Level 2; QoE moderate (B) Recommendation
patients that show clinical improvement with higher blood pressure
25. Optimal fluid management does improve patient outcome; hypovolemia and Ungraded Statement of fact
hypervolemia are harmful
26. We recommend to assess volume status and volume responsiveness Ungraded Best practice
27 We recommend that immediate fluid resuscitation should be started in shock Ungraded Best practice
states associated with very low values of commonly used preload parameters
28. We recommend that commonly used preload measures (such as CVP or PAOP Level 1; QoE moderate (B) Recommendation
or end diastolic area or global end diastolic volume) alone should not be used
to guide fluid resuscitation
29. We recommend not to target any absolute value of ventricular filling pressure Level 1; QoE moderate (B) Recommendation
or volume
30. We recommend that fluid resuscitation should be guided by more than one Ungraded Best practice
single hemodynamic variable
31. We recommend using dynamic over static variables to predict fluid Level 1; QoE moderate (B) Recommendation
responsiveness, when applicable
32. When the decision for fluid administration is made we recommend to perform a Level 1; QoE low (C) Recommendation
fluid challenge, unless in cases of obvious hypovolemia (such as overt
bleeding in a ruptured aneurysm)
33. We recommend that even in the context of fluid-responsive patients, fluid Ungraded Best practice
management should be titrated carefully, especially in the presence of
elevated intravascular filling pressures or extravascular lung water
34. We suggest that inotropic agents should be added when the altered cardiac Level 2; QoE low (C) Recommendation
function is accompanied by a low or inadequate cardiac output, and signs of
tissue hypoperfusion persist after preload optimization
35. We recommend not to give inotropes for isolated impaired cardiac function Level 1; QoE moderate (B) Recommendation
36. We do not recommend targeting absolute values of oxygen delivery in patients Level 1; QoE high (A) Recommendation
with shock
CVP, Central venous pressure; PAOP, pulmonary artery occlusion pressure
Statements in this table are related to therapeutic strategies, blood pressure targets, fluid management and inotropes. These are also
presented in the main text together with the rationale. The order of presentation in the table has been changed from that in the main text to
allow for better reading in the table

62]is of paramount importance. Context analysis form of obstructive shock, is associated with compression
(trauma, infection, chest pain, etc.) and clinical evaluation of all cavities, and thus with elevated intracardiac pres-
which focuses on skin perfusion and jugular vein disten- sures but small cardiac volumes. In general,
sion usually orient diagnosis to the type of shock, but hemodynamic variables such as CVP can be useful in
complex situations may exist (e.g. cardiac tamponade in a identifying the type of shock. However, unless in the
patient with trauma or septic shock in a patient with extreme ranges of the variables (such as a CVP of
chronic heart failure) in which a diagnosis is more diffi- 0 mmHg in the case of a history of bleeding), they should
cult. Hence, additional hemodynamic measurements are always be interpreted together with other variables.
often needed to ascertain the type of shock, especially in Evaluation of cardiac output, cardiac function and
complex situations or in patients with comorbidities. preload is essential when attempting to identify the type
Distributive shock is usually characterized by an elevated of shock and can be obtained using various techniques.
cardiac output, while the other types of shock are asso- Echocardiography allows rapid characterization of the
ciated with low cardiac output. Hypovolemic shock is type of shock and is now proposed as the first-line eval-
associated with low blood pressures and volumes, while uation modality [4]. This information can be obtained
these are increased in cardiogenic shock. Obstructive rapidly, usually in less than 2 min, even by physicians
shock is associated with increased pulmonary artery with minimal training [63]. The situation may evolve
pressure and dilated right-sided cavities. Tamponade, a over time, however, and repeated echocardiographic
1803

Table 6 Summary of the consensus statementspart 4

No. Statement/recommendation GRADE level of Type of


recommendation; statement
quality of evidence

37. We do not recommend routine measurement of cardiac output for patients with Level 1; QoE low (C) Recommendation
shock responding to the initial therapy
38. We recommend measurements of cardiac output and stroke volume to evaluate Level 1; QoE low (C) Recommendation
the response to fluids or inotropes in patients that are not responding to initial
therapy
39. We suggest sequential evaluation of hemodynamic status during shock Level 1; QoE low (C) Recommendation
40. Echocardiography can be used for the sequential evaluation of cardiac function Ungraded Statement of fact
in shock
41. We do not recommend the routine use of the pulmonary artery catheter for Level 1; QoE high (A) Recommendation
patients in shock
42. We suggest pulmonary artery catheterization in patients with refractory shock Level 2; QoE low (C) Recommendation
and right ventricular dysfunction
43. We suggest the use of transpulmonary thermodilution or pulmonary artery Level 2; QoE low (C) Recommendation
catheterization in patients with severe shock especially in the case of
associated acute respiratory distress syndrome
44. We recommend that less invasive devices are used, instead of more invasive Ungraded Best practice
devices, only when they have been validated in the context of patients with
shock
Statements in this table are related to cardiac function and cardiac output assessment and monitoring. These are also presented in the main
text together with the rationale. The order of presentation in the table has been changed from that in the main text to allow for better
reading in the table

evaluations are not always feasible. Hence, a combination Selection of the therapeutic intervention
of echocardiography with other technologies is often
Target for blood pressure in the management of shock
warranted. Advanced hemodynamic monitoring may not
be needed in non-severe episodes of shock that rapidly
Aggressive fluid resuscitation should be avoided and
respond to initial therapy based on clinical evaluation and
hypotension tolerated in trauma patients with penetrating
echocardiography. In cases of severe shock and in com-
injuryuntil the bleeding is surgically stopped [64]. No
plex conditions, advanced hemodynamic monitoring is
equivalent guidelines are available for patients with blunt
useful for identifying the factor(s) which contrib-
trauma. Regarding cardiogenic shock, no clinical studies
ute(s) most to the hemodynamic disturbances and on
have investigated the optimal blood pressure level, and
which therapy should focus. Continuous or semi-contin-
guidelines no longer recommend a target blood pressure
uous measurements of cardiac output and/or SvO2 are
[65]. Blood pressure should be individualized for all
particularly useful as these can be nurse driven.
patients. There is evidence, however, that a mean MAP of
around 65 mmHg is sufficient in most patients with septic
Identification of the type of shock
shock [51, 6669], although in patients with a history of
We recommend efforts to identify the type of shock to
hypertension, a higher MAP is associated with a lower
better target causal and supportive therapies. Best
risk of acute kidney injury [70]. Therefore, clearly the
practice.
arterial blood pressure level must be individualized. Va-
We recommend further hemodynamic assessment (such
sopressors may have to be used if fluid resuscitation is not
as assessing cardiac function) to determine the type of
sufficient, or they may be indicated to maintain the
shock if the clinical examination does not lead to a
desired value of MAP. In-dwelling arterial catheters allow
clear diagnosis. Best practice.
continuous arterial blood pressure monitoring and at the
We suggest that, when hemodynamic assessment is
same time allow for regular blood gas analysis. This is
needed, echocardiography is the preferred modality to
particularly important in patients not responding to the
initially evaluate the type of shock as opposed to more
initial therapy. Central venous access may be required and
invasive technologies. Recommendation. Level 2; QoE
preferred to peripheral venous access when patients
(B).
admitted to the ICU require vasopressor infusions [71].
We recommend not to use a single variable for the
diagnosis and/or management of shock. Best Practice.
Target blood pressure in circulatory shock
In complex patients we suggest to additionally use
We recommend individualizing the target blood
pulmonary artery catheterization or transpulmonary
pressure during shock resuscitation. Recommendation.
thermodilution to determine the type of shock. Recom-
Level 1; QoE moderate (B).
mendation. Level 2; QoE low (C).
1804

We recommend to initially target a MAP of occurred in 34 (74 %) of the patients, but that the eval-
C65 mmHg. Recommendation. Level 1; QoE low (C). uation of LVEF suggested the use of inotropic agents in
We suggest to tolerate a lower level of blood pressure 11 patients for whom the SSC guidelines suggested
in patients with uncontrolled bleeding (i.e. bleeding otherwise. The reverse situation occurred in only one
patients from a road traffic accident) without severe patient. These authors therefore suggested that resuscita-
head injury. Recommendation. Level 2; QoE low (C). tion should be guided by measurements of LVEF rather
We suggest a higher MAP in septic patients with a than by the SSC criteria. These data should, however, be
history of hypertension and in patients who improve interpreted with caution as no analysis of patient outcome
with higher blood pressure. Recommendation. Level 2; was performed. The study simply illustrates that LVEF
QoE moderate (B). and oxygen saturation evaluate two different aspects of
We recommend arterial and CVC insertion in cases of the hemodynamic state, with LVEF evaluating myocar-
shock unresponsive to initial therapy and/or requiring dial contractility and ScvO2 evaluating the adequacy of
vasopressor infusion. Best practice. cardiac output according to oxygen utilization. Hence,
inotropic agents should be given only when the altered
cardiac function is accompanied by a low or inadequate
Therapeutic interventions to improve perfusion cardiac output and signs of tissue hypoperfusion are
present. The aim of the therapeutic options mentioned
When tissue perfusion is judged inadequate, interventions above is to increase oxygen delivery (DO2) to improve
aimed at improving perfusion can be considered. Vaso- tissue perfusion. It therefore needs to be emphasized that
pressors (together with fluid resuscitation) are often the ultimate goal is the improvement of tissue perfusion
needed to restore blood pressure. The question then is not the achievement of any specific DO2 value, which
how to select between the manipulation of preload (flu- ultimately could lead to patients harm [76].
ids), inotropic stimulation and modulation of afterload to
improve flow and perfusion? Clinical examination is often Therapeutic interventions to improve perfusion
of limited value. The detection of preload responsiveness We recommend early treatment, including hemody-
can be achieved through the use of several different namic stabilization (with fluid resuscitation and
indices [72], but the presence of preload responsiveness vasopressor treatment if needed) and treatment of the
does not imply that fluids can be administered safely or shock etiology. Best practice.
that they should be administered at all. Determination of We suggest that inotropic agents should be added when
filling pressures, measured invasively by pulmonary the altered cardiac function is accompanied by a low or
artery catheter (PAC) or estimated non-invasively by inadequate cardiac output and signs of tissue hypoper-
echocardiography, and measurements of extravascular fusion persist after preload optimization.
lung water with transpulmonary thermodilution provide Recommendation. Level 2; QoE low (C).
important information on the risks associated with fluid We recommend not to give inotropes for isolated
administration (see Monitoring Preload and Fluid impaired cardiac function. Recommendation. Level 1;
Responsiveness for further details). QoE moderate (B).
Evaluation of cardiac function is crucial when decid- We recommend not to target absolute values of oxygen
ing on whether inotropic agents have a place in the delivery in patients with shock. Recommendation.
therapy of a given patient. Cardiac function may be Level 1; QoE high (A).
altered when cardiac output is normal or even when ele-
vated, as is often the case in myocardial depression in
sepsis. In a trial involving more than 200 patients with Evaluation of response to therapy
septic shock, Vieillard-Baron et al. [73] observed that
several patients presented a left ventricular ejection The aim of providing hemodynamic support in cases of
fraction (LVEF) of close to 40 % even though their car- acute circulatory failure is often to increase cardiac output
diac index was higher than 3 L/min/m2. Conversely, in order to improve tissue perfusion or decrease pul-
several patients had a low cardiac output but preserved monary capillary pressure. What measurements should
cardiac functionand inotropic stimulation should not be therefore be performed to evaluate the effects of these
used in these patients. In 46 patients with septic shock, interventions? While the ultimate goal is resolution of the
Bouferrache et al. [74] observed that echocardiographic signs of tissue hypoperfusion (e.g. oliguria, lactate levels),
assessment of myocardial function and preload respon- these may lack sensitivity or take time to improve.
siveness often led to different interventions than those The evaluation of cardiac output and cardiac function
guided by the resuscitation goals proposed by the Sur- can be helpful in evaluating the impact of therapeutic
viving Sepsis Campaign (SSC) [75]. In this study, the interventions.
authors found that agreement on the indication (or How can the effect of fluids be evaluated? Fluids are
absence of indication) for inotropic administration expected to improve the hemodynamic state by increasing
1805

stroke volume and cardiac output. Accordingly, changes Therefore, the first questions physicians should ask
in cardiac output by at least 1015 % (to ascertain that themselves are: (1) whether the clinical problem at hand
these changes are not due to measurement variability) are can be (partially) resolved by increasing cardiac output
used to define a positive response to fluids [77]. When and (2) whether fluid resuscitation will be effective to
cardiac output is not measured, surrogate measurements achieve this target.
can be used, such as changes in end-tidal CO2 in Preload, along with afterload and cardiac contractility,
mechanically ventilated patients [78, 79]. Alternatively, is an important determinant of cardiac output. Preload has
resolution of the signs of preload dependency indicates a been defined as myocardial stretch imposed by ventricular
positive response to fluids. Changes in arterial pressure filling at the end of the diastole. While fluid resuscitation
are unpredictable [80, 81] and depend on vascular tone should not be delayed, efforts should be made to assess if
[82]. Even though pulse pressure is related to stroke a patient will respond to fluids. Ideally, in cases of shock,
volume, changes in pulse pressure cannot reliably predict a clinician should be able to use a measure of preload to
response to fluids [81]. Of note, an increase in CVP or in determine whether a patient requires additional fluids to
end-diastolic volume only reflects the fact that preload increase cardiac output. CVP and pulmonary artery
was effectively manipulated, but these measurements are occlusion pressure (PAOP) are the most commonly used
not helpful in identifying patients who experience an estimates of right ventricular (RV) and LV preloads,
increase in cardiac output in response to fluid respectively. Volumetric parameters, assessed by trans-
administration. pulmonary thermodilution, and end-diastolic ventricular
Evaluation of the response to inotropic agents in volumes, determined by echocardiography, are also used
patients who do not respond to the initial therapy requires to evaluate preload [72]. However, each of these pressure
assessment of cardiac function and/or measurements of and volume measurements has their limitations. Dynamic
cardiac output. When present, a rise in SvO2 suggests an measures of assessing whether a patient requires addi-
increase in cardiac output, but an increase can also occur tional fluid to increase stroke volume (i.e. assessing fluid
with significant alterations in SvO2, especially when the responsiveness) have been proposed in an effort to
SvO2 is close to the normal range and/or when oxygen improve fluid management. The principle behind dynamic
consumption (VO2) concomitantly increases, which is the measures is that changes in intrathoracic pressure
typical pattern of response in shock states characterized imposed by mechanical ventilation impact on venous
by VO2 dependency [83, 84]. Under these conditions, return and subsequent cardiac output. During a positive
changes in pulse pressure also do not relate to changes in pressure breath, RV filling has been shown to decrease by
cardiac output [80]. 2070 %, leading to a decrease in stroke volume that can
be amplified by an increasing degree of hypovolemia [85,
Evaluation of response to therapy1 86]. This finding indicates that dynamic measures allow
We do not recommend routine measurement of cardiac the discrimination of preload-dependent and preload-
output for patients with shock responding to the initial independent hemodynamic situations (i.e. these measures
therapy. Recommendation. Level 1; QoE low (C). identify the position of a patients individual Frank
We recommend measurements of cardiac output and Starling curve). Different dynamic measures are currently
stroke volume to evaluate the response to fluids or available and can be routinely assessed at the bedside
inotropes in patients that are not responding to initial using standard and minimally invasive hemodynamic
therapy. Recommendation. Level 1; QoE low (C). monitoring systems. These include the assessment of
We suggest sequential evaluation of hemodynamic pulse pressure variation (PPV) and stroke volume varia-
status during shock. Recommendation. Level 1; QoE tion (SVV) via the arterial line or non-invasively by
low (C). plethysmography, as well as of aortic flow variation and
vena cava collapsibility or distensibility determined by
Doppler and other modalities of echocardiography [87
89]. The need for additional fluid may also be evaluated
Monitoring preload and fluid responsiveness by observing the response to a volume challenge. Fol-
lowing the rapid administration of a bolus of intravenous
Optimal fluid management is one of the cornerstones of fluid (i.e. 500 mL in\30 min) or a passive leg-raising test
hemodynamic management in shock. Both hypovolemia (which is akin to a fluid load, as venous return increases),
and hypervolemia are harmful states, and attempts have to cardiac output immediately increases in patients who are
be made to administer the fluids in the best possible way. fluid-responsive [3, 77, 90].
Despite the fact that current guidelines as well as
1
Refers also to the statements related to general considerations important clinical trials have used measures of preload to
and plasma lactate, mixed venous oxygen saturation and central guide fluid resuscitation, clinicians should be cautious
venous oxygen saturation and other perfusion markers discussed in when using such measures. Importantly, any measure of
the section Diagnosis of shock) preload, particularly if it is a one-time measurement,
1806

should not be taken out of context with respect to the Monitoring preload and fluid responsiveness
measures of other variables and the patients overall Optimal fluid management does improve patient out-
clinical condition. For example, a normal individual with come; hypovolemia and hypervolemia are harmful.
a normal vascular volume has a very low CVP and does Statement of fact.
not require additional fluid; alternatively, some patients We recommend to assess volume status and volume
with high measures of preload pressure may benefit from responsiveness. Best practice.
additional fluids. Thus, changes in these parameters fol- We recommend that immediate fluid resuscitation
lowing interventions may be much more useful than a should be started in shock states associated with very
single measurement. Unfortunately, poor correlations low values of commonly used preload parameters. Best
between estimates of preload (whether pressures or vol- practice.
umes) and predictions of fluid responsiveness have been We recommend that commonly used preload measures
widely reported. For example, in normal healthy volun- (such as CVP or PAOP or global end diastolic volume
teers, both CVP and PAOP are poor predictors of preload, or global end diastolic area) alone should not be used to
cardiac performance and changes in cardiac performance guide fluid resuscitation. Recommendation. Level 1;
following fluid loading compared with measurements of QoE moderate (B).
end-diastolic ventricular volumes. End-diastolic ventric- We recommend not to target any ventricular filling
ular volumes have also been found to provide superior pressure or volume. Recommendation. Level 1; QoE
estimates of preload compared with CVP and PAOP in moderate (B).
diverse groups of critically ill patients [91]. Nonetheless, We recommend that fluid resuscitation should be
there may be clinical settings, such as severe congestive guided by more than one single hemodynamic variable.
heart failure or hypovolemia, where titration of fluid Best practice.
therapy based on CVP and PAOP may be helpful [92]. We recommend using dynamic over static variables to
Notably, measurements of ventricular volumes are not predict fluid responsiveness, when applicable. Recom-
always easy to obtain (especially on the right side of the mendation. Level 1; QoE moderate (B).
heart), are associated with costs and time delays and are When the decision for fluid administration is made, we
operator-dependent. A number of studies have shown that recommend to perform a fluid challenge, unless in
dynamic measures of fluid responsiveness are better pre- cases of obvious hypovolemia (such as overt bleeding
dictors of fluid responsiveness than static parameters in in a ruptured aneurysm). Recommendation, Level 1;
mechanically ventilated patients. PPV and SVV, for QoE low (C).
example, have proven to be good predictors of fluid We recommend that even in the context of fluid-
responsiveness in sedated mechanically ventilated responsive patients, fluid management should be
patients without spontaneous breathing activities and in titrated carefully, especially in the presence of elevated
sinus rhythm. Dynamic measures do have several limi- intravascular filling pressures or extravascular lung
tations, however. Importantly, patients must be on fully water. Best practice.
controlled mechanical ventilation without spontaneous
efforts, which is seldom the case in ICU patients. In
addition, these parameters are affected by the magnitude
of the employed tidal volume. Finally, most of the eval- Monitoring cardiac function and cardiac output
uations involving dynamic measures have included
relatively stable patients, such as post-cardiac surgery Echocardiography
patients, and the extent to which these measures are useful
in other potentially unstable populations is uncertain. Few Echocardiography cannot provide continuous hemody-
studies evaluating measures of fluid responsiveness have namic data. Nevertheless, it is the best bedside method to
specifically focused on the spontaneously breathing assess cardiac function repeatedly. Echocardiography can
patient. Not surprisingly, the measurement of PPV had no help the ICU physician in three ways: (1) better charac-
predictive value in the subgroup of patients with sponta- terization of the hemodynamic disorders; (2) selection of
neous breathing activity [93]. However, reductions in the best therapeutic options (intravenous fluids, inotropes
right atrial pressures by at least 1 mmHg during a spon- and ultrafiltration); (3) assessment of the response of the
taneous inspiration have been shown to be a reasonable hemodynamic disorders to therapy.
predictor of fluid responsiveness [9496]. Passive leg- Doppler echocardiography provides an estimation of
raising (e.g. 45 elevation for 4 min while maintaining the stroke volume and hence cardiac output using the calcu-
trunk supine) results in an increase in RV and LV preload. lation of the velocitytime integral (VTI) of the subaortic
Such a test may help in predicting individual fluid blood flow and the area of the duct crossed by this flow.
responsiveness during spontaneous and positive pressure Since the area of the subaortic tract does not change over
breaths while avoiding the hazards of unnecessary fluid time, it is sufficient to follow short-term changes in VTI
loading [97, 98]. in order to assess changes in stroke volume.
1807

Doppler echocardiography provides measurements of pressure, pulmonary artery pressure (PAP), PAOP and
LVEF, which depends mainly on LV contractility and LV cardiac output) and tissue perfusion variables (e.g. SvO2,
afterload. Thus, LVEF is not a precise marker of LV oxygen utilization, oxygen delivery, oxygen extraction
contractility but rather reflects the way the heart is able to
and PvCO2]. All of these variables can be useful in the
adapt to the actual loading conditions with its intrinsic
management of patients with shock.
contractility. This is particularly important in shock Right atrial pressure and PAP are particularly useful
patients in whom LV afterload can change markedly over for managing patients with shock associated with RV
a short period. Therefore, the LVEF must be correctly dysfunction and/or acute respiratory distress syndrome
interpreted to take into account the systolic arterial pres-
(ARDS). PAOP is assumed to reflect the LV end-diastolic
sure. Visual estimation of LVEF provides values very pressure. Correct measurements and appropriate inter-
close to those measured by the orthogonal plan method pretation of PAOP represent a difficult challenge,
[99], and this measurement can be obtained by most ICU especially in patients receiving positive end-expiratory
physicians, even those who are moderately experienced pressure (PEEP) [112, 113] or in the presence of intrinsic
with echocardiography [100]. PEEP [113], where the measured PAOP overestimates the
LV filling pressures are best evaluated using analysis of
transmural PAOP.
the transmitral flow with pulsed Doppler echocardiography Cardiac output can be measured intermittently
and the tissue Doppler imaging of the mitral annulus [101].
according to the thermodilution principle after cold bolus
Analysis of transmitral flow allows measurement of the injections. This is classically considered as the reference
peak Doppler velocities of early (E) and late diastolic flow
method, although it suffers from a number of methodo-
(A). The E/A ratio has been proposed as an estimation of
logical limitations, such as tricuspid regurgitation. The
the LV filling pressure [102], but this measurement is semi-continuous thermodilution method is based on the
affected by diastolic function. Early diastolic mitral intermittent and automatic heating of blood by means of a
annular velocity (E0 ) measured with tissue Doppler imag-
proximal thermal filament and the recording of the tem-
ing evaluates diastolic function in a load-independent perature changes using a distal thermistor. The results
manner [103]. The combination of tissue Doppler imagingobtained with continuous thermodilution agree with those
and pulsed Doppler echocardiography of transmitral flowprovided by the intermittent technique, except for high
allows calculation of the E/E0 ratio, which is considered to
values of cardiac output, which can be underestimated by
be one of the best echocardiographic estimates of LV the continuous method [114]. This technique presents the
filling pressure [103, 104]. However, echocardiography advantage of a continuous display of cardiac output and
avoids repeated manipulations of the catheters and bolus
provides only a semi-quantitative estimate of LV filling
pressures. Although an E/E0 value of\8 is a good predictor
injections. The major limitation is that it does not enable
of low LV filling pressure and an E/E0 value of [15 is a
real-time monitoring of cardiac output as it averages
several successive cardiac output measurements.
good predictor of high LV filling pressure, a value between
8 and 15 cannot reliably predict the LV filling pressure The PAC can also provide intermittent or continuous
[105]. This is not a minor issue as most E/E0 values are
measurements of SvO2 and intermittent measurements of
between 8 and 15 in critically ill patients [104, 106].PvCO2; both variables are helpful in assessing the ade-
Echocardiography also provides dynamic parameters quacy of the cardiac output for oxygen (O2) utilization
of preload responsiveness through analysis of the respi-
and for the clearance of carbon dioxide (CO2) produced
ratory variability of VTI [88] or the inferior or superior
by cellular metabolism.
vena cava diameter [88, 107] or through the response of The main limitation of the PAC is its invasiveness,
VTI to passive leg-raising [98, 108]. which explains in part the decline in its use during the
Doppler echocardiography provides an estimation ofpast decade when less invasive hemodynamic techniques
RV function through comparison of the RV end-diastolic have been developed. Nevertheless, the PAC can still be
area (RVEDA) with the LV end-diastolic area (LVEDA). helpful for the management of shock states refractory to
A RVEDA/LVEDA ratio of between 0.6 and 1 suggests the initial treatment, especially those with RV dysfunction
the presence of moderate RV dilatation, and a ratio [1 or with complex circulatory conditions in which the
suggests the presence of severe RV dilatation. Some knowledge of PAP, PAOP and oxygenation parameters is
authors have defined acute cor pulmonale as the combi- believed to be important for identifying the main disor-
nation of a RVEDA/LVEDA ratio [0.6 and the presence ders. Monitoring with a PAC is commonplace in the ICU
of a paradoxical septal motion [109111]. setting despite the lack of high-quality data to support its
benefits [115]. While the availability of cardiac output
and other hemodynamic variables obtained using a PAC
Pulmonary artery catheter can improve the diagnosis and management of circulatory
instability, the device can also cause complications and
The PAC provides the ICU physician with information on provide inaccurate measurements, and the data can be
important hemodynamic variables [e.g. right atrial difficult to interpret [116].
1808

Published evidence on the use of PACs in the ICU is injection into a central vein and detection of changes in
conflicting, with some early non-randomized trials sug- the blood temperature in the femoral artery. The tech-
gesting increased rates of mortality and morbidity and nique has been compared favorably with pulmonary
longer hospital stays. The results of a prospective study thermodilution in critically ill patients, including some in
with propensity-matched groups showed that patients shock [126]. Transpulmonary thermodilution also pro-
receiving a PAC had a higher rate of 30-day death, higher vides intermittent measurements of: (1) global end-
hospital costs and increased duration of ICU stay com- diastolic volume, a volumetric marker of cardiac preload;
pared with patients who did not receive a PAC [116]. (2) cardiac function index, a marker of systolic function
Analysis of data from an observational study in over of the heart; (3) extravascular lung water, a quantitative
4,000 patients undergoing non-cardiac surgery revealed index of pulmonary edema.
an increase in the rate of postoperative major cardiac and Arterial pulse wave analysis measures cardiac output
non-cardiac complications in those who underwent peri- by placing sensors placed directly into the femoral artery
operative right heart catheterization [117]. In contrast, catheter which record the arterial pressure waveform
two recent studies, both of which used propensity scores through the femoral artery catheter. Determination of
to account for illness severity, reported similar outcomes pulse contour cardiac output uses proprietary algorithms
in critically ill patients with or without a PAC [118, 119]. based on the relationship between stroke volume and
In a retrospective study of 119 consecutive patients with arterial pressure waveform, which is influenced by the
ARDS, monitoring with a PAC was not an independent resistive and elastic characteristics of the arterial system.
predictor of death [120]. Intermittent transpulmonary thermodilution cardiac out-
The impact of PAC on mortality and morbidity in put measurements are used to calibrate the pulse contour
critically ill patients has also been reported in several, cardiac output, and good agreement with thermodilution
more recent RCTs [121124]. One study involving 201 cardiac output has been reported in hemodynamically
patients reported no difference in mortality related to unstable patients [127]. However, there is a potential drift
PAC use, but more fluids were given in the first 24 h to with time, making recalibration mandatory. After a 1-h
the PAC group, and the rates of acute renal failure and calibration-free period, recalibration may be encouraged
thrombocytopenia 3 days after randomization were in patients with septic shock who are receiving vaso-
greater in this group [121]. Similarly, in 676 patients with pressors [128].
shock and/or ARDS, the use of a PAC did not signifi- The clinical interest for such real-time cardiac output
cantly improve morbidity or reduce mortality [122]. monitoring is to improve diagnostics so that patients in
Harvey et al. reported that they found no evidence of whom cardiac output is dropping can be identified early
benefit or harm with the use of a PAC in a study of 1,041 and to be able to follow the short-term changes in cardiac
ICU patients [123]. Wheeler et al. conducted a random- output during dynamic tests or therapeutic challenges.
ized trial in 1,000 patients with ARDS or acute lung Because such devices provide numerous important
injury with the aim of comparing hemodynamic man- hemodynamic variables, transpulmonary thermodilution
agement guided by PAC and by CVC [124]. These can be helpful in patients with shock refractory to ini-
authors reported that there were no differences in 60-day tial treatment and especially in cases of associated
mortality, time on the ventilator or days spent in the ICU, ARDS because of the assessment of extravascular lung
but the PAC group did have a higher rate of catheter- water.
related complications, largely arrhythmias [124]. Shah
et al., in a meta-analysis of the efficacy and safety of the
PAC in 5,051 critically ill patients (13 RCTs) [125], Lithium dilution monitor
reported that the use of a PAC was not associated with an
increased rate of death or length of hospitalization, but the This system uses the lithium dilution method to calibrate
results also failed to demonstrate improved survival an arterial waveform analysis system. The technique has
associated with PAC use. been validated against pulmonary artery thermodilution
in humans [129], and agreement remains acceptable for
up to 4 h after calibration in critically ill patients [130].
Transpulmonary thermodilution devices The system needs a lithium bolus injection for its cali-
bration. The best calibrations are achieved, as is true for
Transpulmonary thermodilution devices are considered to any intermittent technique, by averaging more mea-
be less invasive than the PAC, but they still require surements (i.e. 23 boluses) [131]. The device can be
insertion of a CVC and femoral arterial catheter. These used to measure and track cardiac output continuously in
devices combine transpulmonary thermodilution and patients with shock. In complex patients it has the
pulse contour analysis. limitation of measuring fewer hemodynamic variables
Transpulmonary thermodilution provides intermittent than the PAC and the transpulmonary thermodilution
measurements of cardiac output after a cold bolus systems.
1809

Uncalibrated arterial pulse contour analysis monitors limitation of the technique is that the probe moves easily
into the esophagus when the patient is moving. Thus,
Several devices provide real-time cardiac output mea- continuous monitoring of cardiac output requires frequent
surements by deriving the arterial pressure waveform replacement of the probe. Esophageal Doppler is more
recorded from an artery catheter (radial or femoral). These suitable for the operating theater than for the ICU. Unfor-
devices use proprietary algorithms that analyze the char- tunately, esophageal Doppler can only provide blood flow
acteristics of the arterial pressure waveform and use this measurements, which limits its potential for hemodynamic
analysis, along with patient-specific demographic infor- monitoring in the context of shock in comparison with
mation, to determine continuous cardiac output and PPV other monitoring devices, such as the PAC or transpul-
and/or SVV. A theoretical advantage is that these devices monary thermodilution.
can be used with a radial artery catheter and do not need
calibration. However, the reliability of uncalibrated devi-
ces is still debated in the case of shock, particularly septic Bioreactance
shock [132134]. More importantly, the fact that these
devices do not provide important variables, such as filling Bioreactance is a non-invasive technique used for moni-
pressures or transpulmonary thermodilution variables toring cardiac output in real-time which uses skin surface
(global end-diastolic volume, extravascular lung water, electrodes placed on the patients chest and neck that
etc.), represents a disadvantage compared with PAC or apply a low-amplitude, high-frequency electrical current
transpulmonary thermodilution devices. which traverses the thorax. The signal is recorded by other
Recently developed systems use the pulse contour electrodes on the skin surface, with a time delay called a
analysis and the volume clamp method to monitor cardiac phase shift. The underlying scientific rationale is that the
output in real-time using an inflatable cuff wrapped around higher the cardiac stroke volume, the more significant
a finger connected to a monitor. This non-invasive method these phase shifts become. In critically ill patients,
should be used during the perioperative period. However, including those with shock, a poor agreement between
the value of this technique in the context of shock patients thermodilution cardiac output and bioreactance cardiac
and/or patients receiving vasopressors is questionable, as output has been reported in two studies [138, 139].
confirmed by results from clinical studies which showed no
agreement with thermodilution cardiac output [135] or Monitoring cardiac function and cardiac output
velocity time integral [136] for estimating either absolute Echocardiography can be used for the sequential
values of cardiac output or for tracking changes in cardiac evaluation of cardiac function in shock Statement of
output during therapy. In addition, patients with shock often fact.
need an arterial catheter for their routine management. We do not recommend the routine use of the pulmonary
artery catheter for patients in shock. Recommendation.
Level 1; QoE high (A).
Esophageal Doppler We suggest PAC in patients with refractory shock and
RV dysfunction. Recommendation. Level 2; QoE low
The use of esophageal Doppler is aimed at monitoring (C).
cardiac output by continuously measuring the blood flow We suggest the use of transpulmonary thermodilution
in the descending thoracic aorta. This method takes or PAC in patients with severe shock especially in the
advantage of the anatomical proximity of the thoracic case of associated acute respiratory distress syndrome.
descending aorta and the esophagus. With this technique, Recommendation. Level 2; QoE low (C).
a flexible probe of small diameter is introduced into the We recommend that less invasive devices are used,
esophagus. The tip of the probe is equipped with a instead of more invasive devices, only when they have
Doppler transducer that records the velocity of red blood been validated in the context of patients with shock.
cells passing into the descending thoracic aorta. To obtain Best practice.
flow from velocity measurements, the diameter of the
descending aorta must be taken into account.
Most commercialized devices do not measure the aortic
diameter, but rather they estimate it from nomograms based Monitoring the microcirculation
on the patients height, weight and age. With these devices,
the aortic diameter is thus considered to be a constant in a Several techniques are available to evaluate the micro-
particular patient. In patients with shock receiving resus- circulation in critically ill patients. These show some
citation, this assumption represents an important limitation relation between altered microcirculation and poor out-
of using such devices because the aortic diameter depends come. In experimental conditions, shock states have been
on the transmural aortic pressure, such that changes in associated with a decrease in perfused capillary density
MAP result in changes in aortic diameter [137]. A practical and an increase in the heterogeneity of microcirculatory
1810

perfusion, with non-perfused capillaries in close vicinity conditions, have been observed in patients with septic
to perfused capillaries [140]. [145], cardiogenic [146], and hemorrhagic [147] shock.
The use of metabolic parameters for the assessment of One goal of the management of patients with shock
regional microcirculatory perfusion is promising. Tissue within the first hours after admission is to ensure adequate
CO2 represents the balance between local production and tissue perfusion and cellular metabolism. In a prospective
removal; thus, a rising value likely reflects a decrease in observational study, early improvement in microvascular
local blood flow rather than an increased local production of perfusion in response to goal-directed therapy was asso-
CO2. When associated with arterial CO2, tissue CO2 allows ciated with an improvement in organ function [148].
determination of the gradient or the PCO2 gap, which is These data strongly suggest that microcirculatory altera-
inversely related to the proportion of perfused capillaries tions are implicated in the development of organ failure.
[141]. An occlusion test with near-infrared spectroscopy In a randomized, double-blind, crossover study by Her-
may help to evaluate indirectly the dynamic response of the nandez et al. [149] in patients with pressor-dependent
microcirculation to an occlusion, even if the link between septic shock and hyperlactatemia, increasing oxygen
vasoreactivity, microcirculation and tissue oxygenation is delivery for 90 min by infusion of dobutamine did not
still not clearly established. The evaluation of StO2 [tissue alter lactate clearance, regional flow (measured by gastric
(muscle) oxygen saturation] changes in response to a vas- tonometry PCO2) or microcirculatory flow (measured by
cular occlusion test provides two additional parameters: the sublingual imaging
StO2-deoxygenation rate (DeOx), which has been related to The use of microcirculatory markers of tissue perfu-
the local metabolic rate and local blood flow distribution, sion will require further large-scale studies to assess their
and the StO2-reoxygenation rate (ReOx). In a population of potential benefit in microcirculation-oriented or micro-
septic shock patients with restored MAP, decrements in circulation-guided management and/or therapy of early
DeOx and ReOx were found to be associated with a longer shock resuscitation. In summary, these techniques need
ICU stay, and impaired DeOx was associated with no further exploration and are not presently recommended as
improvement in organ failures after 24 h [142]. The ReOx targets for resuscitation.
rate seen on reperfusion is an measure of both the limbs
oxygen content and the capacity to recruit arterioles and Monitoring microcirculation
venules (microvascular reserve) [143]. We suggest the techniques to assess regional circulation
Microvideoscopic techniques, such as orthogonal or microcirculation for research purposes only. Rec-
polarization spectral and sidestream dark field imaging, ommendation. Level 2; QoE low (C).
can directly evaluate microvascular networks covered by
a thin epithelium, such as the sublingual microcirculation. Acknowledgments Prof Alexandre Mebazaa acknowledges the
They take into account the heterogeneity of microvascular contribution of Anais Caillard for the literature search.Prof Roman
Jaeschke acknowledges Bram Rochwerg and Waleed Alhazzani for
perfusion. The following parameters have been suggested their help in reviewing the statements in view of the literature and
[144]: (1) a measure of vessel density (total or perfused the GRADE system.
vessel density); (2) two indices of vascular perfusion
(proportion of perfused vessels and microcirculatory flow Conflicts of interest None.
index); (3) a flow heterogeneity index. These indices
evaluate how many vessels are perfused, the quality of the Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which permits
flow and whether non-perfused areas are located next to any noncommercial use, distribution, and reproduction in any medium,
well-perfused areas. Using these techniques, microvas- provided the original author(s) and the source are credited.
cular alterations, similar to those reported in experimental

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