50TH ANNIVERSARY ARTICLE

Hemodynamic Monitoring and Support

Jean-Louis Vincent, MD, PhD,
KEY WORDS: arterial pressure; blood lactate; cardiac output; fluid FCCM1
responsiveness; microcirculation; oxygen delivery; pulmonary artery catheter Alexandre Joosten, MD, PhD2,3
Bernd Saugel, MD4

C
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ritically ill patients are carefully and closely monitored to assess the
nature and severity of their disease process and to assess the need for
and impact of different therapies. All organs can be monitored, some
more easily than others, with hemodynamic monitoring of the cardiovascular
system being the most frequent. Hemodynamic monitoring techniques have
progressed immensely since the very early days of intensive care and perhaps
particularly over the past 50 years, moving from the very earliest, bulky sphyg-
mographs to measure arterial pressure, to invasive catheters to assess cardiac
output, to the more recent development of noninvasive, digital monitors pro-
viding continuous values of multiple hemodynamic variables. Concepts have
also changed as we move from global macrohemodynamic monitoring toward
a more regional, microcirculatory perfusion approach and from maximal mon-
itoring for all, to a much more individualized approach. Here, we will briefly
review these changes.

SOME KEY STEPS IN THE HISTORY OF HEMODYNAMIC

MONITORING
From Pressures to Blood Flow
Monitoring of a patient’s hemodynamic status initially concentrated on meas-
uring arterial pressure. The fundamental hemodynamic principle that pressure
is determined by flow and vascular tone (or vascular resistance) soon became
evident and had a major impact on the development of hemodynamic moni-
toring. As technology advanced, the ability to perform more advanced hemo-
dynamic assessment enabled better description and characterization of the
different types of shock (hypovolemic, cardiogenic, distributive, and obstruc-
tive) as proposed by Weil and Henning in 1979 (1, 2). A clear separation was
identified between shock with high systemic vascular resistance (SVR) (hypo-
volemic, cardiogenic, obstructive) and shock with low SVR (distributive), but
it became apparent that the vascular resistance concept had major limitations.
First, physiologically the line on a graph representing the relationship between
intravascular pressure (on the y-axis) and flow (on the x-axis) does not start
from the origin, as pressure is still positive in the absence of flow. Second, va-
sopressor therapy targeting an increase in SVR may result in an increase in
arterial pressure but also a reduction in blood flow. Third, septic shock is not
Copyright © 2021 by the Society of
always associated with low SVR. These observations were the basis for the his- Critical Care Medicine and Wolters
torical separation of septic shock into “cold” and “warm” types, possibly related Kluwer Health, Inc. All Rights
to different types of organism—Gram+ve and Gram-ve—in particular (3), but, Reserved.
although still sometimes used in pediatric shock, these distinctions are not DOI: 10.1097/CCM.0000000000005213

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Vincent et al
reliable. Patients with circulatory shock often present
with a combination of several different types of shock;
for example, in septic shock, cardiac output can be lim-
ited by hypovolemia and/or sepsis-related myocardial
depression. In patients with acute respiratory failure,
the effects of high airway pressures on right ventricular
function can further complicate the hemodynamic
pattern (4). Hence, the concept of characterizing shock
according to vascular resistance lost popularity, and we
have rather stayed focused on the primary variables of
pressures and cardiac output.
The Importance of Cardiac Output
The first measurements of cardiac output, using indicator
dilution techniques, were complicated and cumbersome
(5) but helped us recognize the large variability in car-
diac output that can exist in patients. The development of
the balloon-tipped pulmonary artery catheter (PAC) by
Swan et al (6) in 1970, just before the Society for Critical
Care Medicine was founded in 1971, revolutionized our
approach to the monitoring of cardiac output enabling
the simpler pulmonary artery thermodilution technique
(7). The PAC had the additional benefit of enabling mul-
tiple hemodynamic variables (pulmonary artery pres-
sures, pulmonary artery occlusion pressure [PAOP],
SVR and pulmonary vascular resistance, core body tem-
perature, mixed venous oxygen saturation [Svo2]) to be
measured and monitored simultaneously.
Measurement of the central venous pressure (CVP)
had been introduced in the late 1960s, and already
provided information on hemodynamic status, no-
tably on right heart filling pressures and thus guid-
ance for rapid fluid administration. However, the
CVP does not correlate well with blood volume, as it
reflects right ventricular function and venous compli-
ance as well. Use of the PAC helped understand the
differences between the CVP and the pulmonary ar-
tery wedge or occlusion pressure, which reflects left-
sided filling pressures. Interpretation of the pressure
waveforms was also promoted, enabling assessment of
different conditions affecting the cardiac cycle.
The Concept of Oxygen Delivery/Oxygen
Consumption Relationships and the
Importance of Svo2
Over the years, the emphasis in hemodynamic moni-
toring has moved progressively from the central
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to the peripheral circulation, getting closer to the
cells. Tissue oxygen consumption (Vo2) varies with
a patient’s clinical condition (inflammatory response,
body temperature, mechanical ventilation, to name
a few), and it is essential that sufficient oxygen can
be delivered to meet differing cellular needs. Oxygen
delivery (Do2) is determined by cardiac output and
the arterial oxygen content. The concept of providing
supranormal amounts of oxygen to avoid the so-
called “oxygen debt” was promoted in the early 1990s
by Shoemaker (8, 9) to prevent complications in
high-risk surgical patients. However, the excess treat-
ments (e.g., fluids and inotropic therapy) necessary to
achieve the marked increase in Do2 could be harmful
in some patients. This was illustrated in a study by
Hayes et al (10) in 1994 using massive doses of dobu-
tamine to achieve the Do2 goal.
The pendulum therefore shifted toward a more
personalized approach, considering the needs of in-
dividual patients by using appropriate monitoring. A
first strategy consisted of constructing individual Vo2/
Do2 curves. Such an approach may make sense be-
cause physiologic studies have clearly shown the pres-
ence of a Vo2/Do2 dependency phenomenon in shock
states (11, 12). Furthermore, the fall in Do2 below a
critical value (the so-called Do2crit) is associated with
an abrupt increase in blood lactate levels (Fig. 1). The
clinical application of the experimental data was nicely
illustrated in the observation by Ronco et al (13) in
1993 that the same relationship can be documented in
patients who die following withdrawal of life-support.
However, the individual construction of Vo2/Do2 dia-
grams in patients has several difficulties. First, it could
lead to spurious Vo2/Do2 relationships because of the
presence of so-called “mathematical coupling of data,”
in which cardiac output, hemoglobin concentration,
and arterial oxygen saturation (Sao2) are present on
both axes of the graph. To avoid this, it was suggested
that Vo2 be determined by indirect calorimetry, but
this does not really provide a “measured” Vo2 just a
value estimated using another technique and is prone
to other technical limitations (14). Second, the Vo2 can
change quite rapidly with changes in patient condition
or environmental factors.
The relationship between Vo2 and Do2 essentially
represents oxygen extraction (the ratio of Vo2/Do2) or
more simply the Svo2 when Sao2 is close to 100%. The
use of the PAC enables easy collection of mixed venous
XXX 2021 • Volume XX • Number XXX

Figure 1. The relationship between oxygen consumption (Vo2)
and oxygen delivery (Do2). A, Blood lactate levels increase
abruptly when Do2 falls below a critical value (Do2crit). Please note
that Vo2 does not fall to the same extent as Do2 below Do2crit,
indicating that oxygen extraction can still increase, although to a
much lesser extent. B, The same concepts can be represented by
a cardiac output/oxygen extraction diagram.
blood from the tip of the catheter in the pulmonary
artery. Reference Svo2 values in acutely ill patients may
be a bit lower than the normal value of 75% in healthy
humans, because the hemoglobin value in the critically
ill is usually lower. Measurement of central venous ox-
ygen saturation (Scvo2) through a central venous cath-
eter has been proposed as a surrogate for Svo2, but is
only an approximation, as venous saturations are not
the same in the superior and the inferior parts of the
body, and this relationship can be altered by the clin-
ical situation (15). Hence, Scvo2 can only be consid-
ered as a gross approximation of Svo2. Nevertheless,
Scvo2 can still provide valuable information to guide
patient management.
Critical Care Medicine
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50th Anniversary Article
A suggested approach to interpreting S(c)vo2 is
given in Figure 2. Svo2 can decrease in the presence
of decreased arterial oxygen content (due to hypox-
emia and/or anemia), an inadequate cardiac output or
a significant increase in Vo2 (e.g., during exercise). It
thus became evident that a cardiac output value cannot
be correctly interpreted without a simultaneous Svo2
measurement and vice versa. Importantly, just as a low
cardiac output does not need to be corrected in every
case, a low Svo2 should not be corrected in every crit-
ically ill patient. This was documented in a large ran-
domized controlled trial (RCT) by Gattinoni et al (16),
in which bringing cardiac output and Svo2 to normal
values did not influence mortality rates.
The observation that S(c)vo2 was low at the time
of diagnosis of septic shock in many patients despite
traditionally expected to be normal or high following
initial resuscitation, led Rivers et al (17), in 2001, to
propose to rapidly (in 6 hr) restore the Scvo2 to at least
70% in the early resuscitation of such patients. The
so-called “early goal-directed therapy (EGDT)” was
achieved by more aggressive fluid resuscitation and
more than three times more patients receiving a blood
transfusion compared with control patients. Applied
in 130 patients versus 133 in the control group, EGDT
was associated with substantially and significantly
lower mortality, from 46.5% to 30.5%. This single-cen-
ter study stimulated strong interest but also some crit-
icism. Three large multicenter RCTs published in 2014
and 2015 (18–20) were unable to reproduce the results
but were not true comparator studies of the original
Figure 2. Interpretation of mixed (central) venous oxygen
saturation (S(c)vo2). In ovals: things to do—in italic: treatment to
consider. CO = cardiac output, PEEP = positive end-expiratory
pressure, Sao2 = arterial oxygen saturation, Vo2 = oxygen
consumption.
www.ccmjournal.org     3
Vincent et al
study by Rivers et al (17), notably including patients
who were less severely ill and most of the patients in
the EGDT group had normal S(c)vo2 values at the start
of the EGDT strategy (21). Hence, application of this
strategy cannot be considered as evidence-based, but it
does not invalidate the importance of S(c)vo2 in inter-
preting hemodynamic status in patients who do not
improve promptly (22).
The addition of the venoarterial Pco2 (VAPco2) gra-
dient may be useful in the presence of persisting he-
modynamic alterations when the Svo2 is normal or
high. In these conditions, an increased VAPco2 gra-
dient greater than 6 mm Hg may indicate that periph-
eral blood flow is still inadequate (23).
Blood Lactate Concentrations
In shock, falling tissue oxygen concentrations result in
anaerobic metabolism with the increased formation of
lactate, making blood lactate concentration a useful
index of altered tissue perfusion (24). This recognition
was an important step in the evolution of hemody-
namic monitoring. Based on the fundamental stud-
ies of Huckabee on the relationship between pyruvate
and lactate (25–27), Broder and Weil (28) proposed in
1969 that excess lactate should be measured to assess
the role of “oxygen debt” in prognostication of shock
states. The concept of oxygen debt was challenged,
however, as it is more relevant to the field of strenuous
exercise, and the measurements of pyruvate are too
complex and cumbersome to become routinely used
in clinical practice. Numerous articles have focused on
the pathophysiology of lactic acidosis in septic shock,
emphasizing that hyperlactatemia is not due only to
cellular hypoxia, but other cellular derangements can
be involved (24). Nevertheless, blood lactate concen-
trations are well-established as an index of the severity
of shock (29) and hyperlactatemia (> 1.5–2 mmol/L)
as a marker of poor outcome.
The concept of measuring serial blood lactate con-
centrations over time to monitor patient response to
treatment and evolution soon emerged. In early stud-
ies in the 1980s, blood lactate concentrations were
shown to decrease by 10% over one hour in the most
straightforward patients with circulatory shock who
responded to fluid administration (30). Further stud-
ies confirmed that a rapid decrease in lactate con-
centration is associated with a better prognosis in
various groups of critically ill patients (31). As lactate
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concentrations reflect the balance between production
and clearance (primarily by the liver), the term “lac-
tate clearance” is not appropriate to describe lactate
kinetics (32). Development of rapid bedside analyzers
has simplified measurement of lactate concentrations.
Treatment based primarily on lactate kinetics (33) has
been attempted but this approach is not entirely con-
vincing, because the changes in lactate concentrations
are slow (31). Hence, the assessment of serial blood
lactate levels is considered as helpful to assess the re-
sponse to therapy rather than to precisely guide it (24).
The Importance of Peripheral Perfusion
The attempt to selectively increase the regional blood
flow to some organs has led to increased interest in
monitoring regional blood flow, but this is difficult in
the clinical setting. Measurements of blood flow in the
hepatosplanchnic circulation are possible but quite
invasive (34). Gastric tonometry became popular in
the 1990s. This minimally invasive technique assesses
gastric mucosal perfusion via a modified nasogastric
tube equipped with a balloon including some saline or
even Co2. Monitoring of critically ill patients using this
technique was shown to decrease mortality in a study
published in 1992 (35), but the existence of many arti-
facts leading to inconsistent results led to this approach
being abandoned. More recently, measurements of ure-
thral perfusion have also been proposed (36). Studying
the peripheral blood flow to the extremities could be
valuable. Joly and Weil (37) proposed already in 1969
to monitor the toe temperature, but this strategy is
limited in the presence of peripheral arteriopathy. The
assessment of skin perfusion has been pursued by dif-
ferent techniques, from the simple capillary refill time
(38) to the more complex use of Doppler techniques
(39). Assessment of peripheral perfusion has been, and
will remain, an important component of the clinical
evaluation of the critically ill.
The Importance of the Microcirculation
Restoring and maintaining adequate tissue oxygen-
ation is the ultimate goal of hemodynamic resuscita-
tion and management. Estimation of Do2 includes the
components cardiac output, hemoglobin, and Sao2,
but this neglects not only the distribution of cardiac
output to the various organs but also distribution
within the organs. Several methods exist to explore
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 50th Anniversary Article

the microcirculation (40), including laser Doppler TABLE 1.

that measures RBC speed in small tissues, intravital Some Hemodynamic Strategies That Have
microvideo-surface microscopy applied directly on Been Studied in Randomized Controlled
organs, microvideo-surface microscopy by orthogonal Trials in Critically Ill Patients But Failed to
polarization spectral or sidestream darkfield imaging, Show a Reduction in Mortality
and nail capillarovideoscopy. For clinical practice, one Strategy References
needs the devices to be reliable and reproducible, easy
to use, and which provide data that are easy to inter- In critically ill patients (in general)
pret by most medical and paramedical staff (41). Higher vs lower mixed venous Gattinoni et al (16)
Handheld vital microscopy assessing the sublingual  oxygen saturation targets in
critically ill patients
microcirculation has been the most widely studied
Higher vs lower cardiac output Gattinoni et al (16)
approach and has enabled persistent microcirculatory in critically ill patients
alterations to be depicted in critically ill patients with
Higher vs lower hemoglobin Hébert et al (50)
sepsis (42). The time course of these changes has been targets for blood transfusion
associated with organ dysfunction and mortality (43) The pulmonary artery catheter Sandham et al (48),
and microvascular changes are frequently observed Richard et al (51),
even after global variables have normalized (43, 44). Harvey et al (52)
This approach has been used to assess the effects of var- Colloids vs crystalloids Myburgh et al (53),
ious interventions on the microcirculation, including Annane et al (54)
the titration of vasopressor support (45). Whether In septic patients (in particular)
these measurements can be used to adjust treatment Vasopressin administration Russell et al (55),
such that they have an impact on patient outcome re- Gordon et al (56)
mains to be proven. Higher vs lower hemoglobin Holst et al (57)
targets for blood transfusion
The Move Toward Less Invasive Techniques Higher vs lower arterial Asfar et al (58)
pressure targets
Decreasing Use of the PAC. The use of the PAC has Early goal-directed therapy Yealy et al (18),
decreased worldwide over the last 2 decades. One ar- Peake et al (19),
gument to support this trend was that RCTs have not Mouncey et al (20)
consistently shown a reduction in mortality asso- Levosimendan administration Gordon et al (59)
ciated with the use of PACs (46–48). However, a re-
duction in mortality has not been shown with other PAC-derived monitoring, PAC-derived variables re-
monitoring techniques (Table 1), such as the electro- main of value in certain complex patients, particularly
cardiogram or pulse oximetry (49), for example, but those with severe cardiorespiratory failure (60).
these are still widely used. Gastric tonometry was The Development of Echo-Doppler. It is beyond
shown to influence mortality (35), and yet this tech- the scope of this review to discuss the echo-Doppler
nique has been abandoned. Furthermore, a monitor- technique in detail. Echo-Doppler, first developed in
ing technique can only improve outcomes if the data the 1950s but only becoming more widely used clin-
generated can be used to influence management in ically in the 1970s (61), was initially reserved for use
a way that can reduce mortality. Hence, the negative in cardiology, but the development of simplified, more
observations from the RCTs suggest that PAC-derived mobile devices and availability of training programs
measurements cannot influence patient management around the globe have enabled echo-Doppler to be
and/or that the changes in management do not influ- used routinely in many ICUs. It is not necessary to be
ence mortality. The reduced use of the PAC in recent an expert in echo-Doppler to use it in the management
years is likely explained more by the greater availability of critically ill patients; knowledge and expertise can
and use of echo-Doppler techniques and other newer, be relatively limited, covering just the necessary basics
less invasive hemodynamic monitoring techniques. to perform a so-called focused cardiac ultrasound
Although these newer devices have reduced the use of (62); cardiologists can still be called if more complex

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Vincent et al
evaluations are needed. Echocardiography can differ-
entiate between the different types of shock (2) and se-
rial examination can be used to monitor response to
treatment.
Availability of Less Invasive Methods for Cardiac
Output Measurement. Other indicator dilution meth-
ods to measure cardiac output were developed to avoid
the need for a PAC (Fig. 3), including transpulmo-
nary thermodilution and lithium dilution (63–65).
However, a (central) venous catheter is still required
for indicator injection and an arterial catheter to detect
changes in indicator temperature or concentration.
Pulse wave analysis, which uses a mathematical anal-
ysis of the arterial blood pressure waveform to estimate
cardiac output, has also been proposed (66, 67). With
pulse wave analysis, cardiac output is estimated continu-
ously, with a rapid response time; it can therefore be used
to assess fluid responsiveness during, for example, a fluid
challenge maneuver or a passive leg raising test. However,
estimation of cardiac output using pulse wave analysis
relies on theoretical assumptions and measurement per-
formance is limited in patients with rapid changes in
vasomotor tone, either spontaneous or drug-induced.
Different pulse wave analysis devices—invasive, min-
imally invasive, and noninvasive—are available for this
purpose, and may use external, internal, or no calibra-
tion to calibrate the estimated cardiac output values (66).
Each has benefits and limitations, but detailed discussion
is beyond the scope of this article (Table 2).
Other less invasive methods for cardiac output
monitoring, including noninvasive pulse wave analysis
(e.g., finger cuff method), pulse wave transit time, Co2
rebreathing, thoracic bioimpedance and bioreactance,
Figure 3. Timeline showing the development of some techniques to measure or estimate cardiac output sure alone may be sufficient
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are not reliable enough for routine use in critically ill
patients.
HEMODYNAMIC MONITORING DURING
ADMINISTRATION OF KEY THERAPEUTIC
INTERVENTIONS IN SHOCK
As proposed by Weil and Shubin (68) many years ago,
the patient with shock should be managed according
to the Ventilate, Infuse, Pump approach. Each of these
management components requires close and specific
hemodynamic monitoring.
Ventilate
It may not seem intuitive that hemodynamic manage-
ment requires an initial focus on ventilation, but an
adequate oxygen supply is essential to restore an ade-
quate Do2. The use of invasive mechanical ventilation
can decrease the oxygen demand of the respiratory
muscles, thus facilitating achievement of adequate tis-
sue Do2. Optimal timing of endotracheal intubation
is thus an important part of the resuscitation process.
Infuse
Fluid administration remains an essential component
of the management of all forms of shock. Initially re-
served for hypovolemic states, and to some extent
septic shock, fluid administration is also essential in
cardiogenic shock, because the vasoconstrictive state
results in extravasation of fluid into the interstitium.
Hence, management of cardiogenic shock using pru-
dent fluid administration has become a standard, even
when cardiogenic lung edema is present (69).
How much fluid should
be given has been a topic
of intense discussion.
Attempts to predeter-
mine the amount of fluid
required have been un-
successful in all subsets
of patients. Hence, the
amount of fluid to be given
should be guided by ap-
propriate and adequate
hemodynamic monitor-
ing in individual patients.
Monitoring arterial pres-
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 50th Anniversary Article

TABLE 2.
Advantages and Limitations of Techniques for Cardiac Output Determination
Method Advantages Limitations

Pulmonary artery Clinical reference method Invasiveness, catheter-related major complications

thermodilution Additional variables: cardiac Sources of error including the temperature and volume
filling pressures and mixed of the injectate, timing of indicator injection during
venous oxygen saturation respiratory cycle
Measurement error in patients with intracardiac
shunts and tricuspid valve abnormalities
Transpulmonary indicator dilution
Thermodilution Good performance Invasiveness, complications associated with central
Additional variables: volumetric preload venous and (femoral) arterial catheters
variables, extravascular lung water and
pulmonary vascular permeability index
Lithium dilution Good performance Invasiveness
Response time
Costs
Not available everywhere
Minimally invasive No external calibration Depends on impeccable blood pressure waveform quality
pulse wave Beat-to-beat continuous monitoring Stroke volume algorithms based on theoretical assumptions
analysis
Operator independent Marked alterations or rapid changes in systemic vascular
Plug and play (easy to set up) resistance make cardiac output estimations unreliable
(e.g., in patients with shock)
Additional variables: stroke volume
variation/pulse pressure variation
Transesophageal Beat-to-beat continuous cardiac Operator dependent
Doppler output monitoring Probe not fixed: frequent need for repositioning
Sedation and mechanical ventilation required
Assumes constant distribution of arterial blood flow
between the upper and lower parts of the body
Depends on the correct estimation of the diameter of the aorta
Finger cuff method No external calibration Not reliable in presence of finger edema and poor
(noninvasive pulse peripheral perfusion
wave analysis) Beat-to-beat continuous cardiac Poor performance, especially in the presence of
output monitoring vasoconstriction
Operator independent
Plug and play (easy to set up)
Additional variables: SVV/PPV
Pulse wave No need for calibration Not reliable in the presence of arrhythmia
transit time Operator independent Not reliable if vasoconstriction
Plug and play (easy to set up) Does not provide SVV/PPV
Thoracic bioimpedance No calibration Unreliable in many cases of arrhythmia, electrical
and bioreactance interference, internal or external pacemakers, movement
(motion artifacts), anatomic shunts, pleural and pericardial
effusions, foreign bodies in the chest, pulmonary edema
Operator independent Electrode positioning (interference with some
Plug and play (easy to set up) surgical sites)

PPV = pulse pressure variation, SVV = stroke volume variation.

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Vincent et al
when vascular tone is well preserved, but in septic
shock the cardiac output may increase much more
than the arterial pressure (70), so that a cardiac output
measurement is desirable. Although a low CVP can in-
crease confidence that fluid administration will be safe,
a single CVP measurement is not a reliable indicator
of fluid requirements (71). Changes in CVP during
the administration of a fluid bolus provide more use-
ful information about the tolerance to fluids. The ben-
efit (increase in cardiac output) versus risk (of edema
formation) of fluid is the basis for the fluid challenge
technique, in which a relatively small amount of fluids
(usually around 200 mL) is given over a relatively short
period of time (usually around 10 min) while carefully
monitoring safety limits (72).
In patients treated with controlled mechanical ven-
tilation, the effects of intermittent positive pressure
ventilation on preload and stroke volume were pro-
posed to detect fluid responsiveness. If mechanical
ventilation induces respiratory variations in stroke
volume (SVV) or in arterial pulse pressure (PPV), it
is more likely that the patient is preload-dependent.
During fluid administration, the decrease in PPV in-
versely correlates with the increase in cardiac output
(73). However, first introduced in the late 1990s, these
dynamic measures of fluid responsiveness based on
cardiopulmonary interactions have their limitations.
PPV is only reliable in mechanically ventilated patients
who are profoundly sedated (no spontaneous breath-
ing) receiving a relatively large tidal volume, with
modestly altered lung compliance, and no right ven-
tricular failure, intra-abdominal hypertension, or se-
vere arrhythmias. Conditions for its use are usually
met during surgical interventions, where goal-directed
fluid management strategies based on such indices
(PPV or SVV) have been shown to reduce postopera-
tive complications (74); however, in the ICU, very few
patients fulfill optimal conditions (75, 76). Additional
tests that rely on the dynamics of PPV have been pro-
posed, including the positive end-expiratory pressure
or the tidal volume challenge (77).
A passive leg raising test was proposed as an alter-
native method (78), avoiding, in principle, the fluid
bolus of a fluid challenge. However, there are two key
limitations: one is that the test may represent a stim-
ulus in the unsedated patient, resulting in an adren-
ergic response regardless of the fluid status; the other is
that if there is a positive response (i.e., indicating fluid
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responsiveness), the increase in stroke volume is very
transient, and appropriate monitoring must be used to
ensure any change is identified reliably.
Type of Fluid and Blood Transfusions. A compre-
hensive discussion on the different effects of different
colloids and crystalloids (albumin or hydroxyethyl
starch, saline or balanced solutions) is beyond the
scope of the present review, but fluid choices remain a
highly controversial topic.
Transfusion strategies have also evolved with time.
When a patient should be transfused remains a matter
of debate. There is no doubt that the maintenance of he-
moglobin levels greater than 10 g/dL resulted in excess
transfusions, but the pendulum may have swung too far
in the other direction following RCTs showing similar
outcomes when transfusions are given only when hemo-
globin falls less than 7 g/dL (57). A recent review of the
available data indicated that blood transfusion may in-
crease Vo2 in critically ill patients (79), and there is now
broad consensus that the decision to transfuse should
not be based on a hemoglobin level alone but also on
other factors, including patient age, hemodynamic
status, and cardiovascular comorbidity (80). A reason-
able approach today would be that blood transfusion
can be safely withheld when the hemoglobin is above
9 g/dL and should be given when hemoglobin is below
7 g/dL; decisions to transfuse should be individualized
when the hemoglobin is between these two values.
Pump
Various vasopressor agents have been proposed, in-
cluding norepinephrine, dopamine, phenylephrine,
metaraminol, mephentermine, and others, but norep-
inephrine is now established as the initial vasopressor
of choice (81). Importantly, administration of vaso-
pressors can decrease blood flow to nonvital organs,
in particular to the kidneys. The pharmacology of do-
pamine was particularly appealing for its use as a va-
sopressor, because dopaminergic receptors are more
numerous in the splanchnic and renal circulations.
However, the administration of low-dose dopamine,
although initially promoted by MacCannell et al (82)
in the 1960s, was later shown not to be associated with
renal protective effects in patients with shock (83). The
use of dopamine has been shown to be associated with
higher mortality rates than norepinephrine in shock
states (81, 84) and use of dopamine as a vasopressor
has been largely abandoned.
XXX 2021 • Volume XX • Number XXX

The place of other vasopressor agents remains unde-
fined. The risk with these agents is a decrease in cardiac
output. Vasopressin has been widely used without ev-
idence of clinical benefit. Benefit may be found when
vasopressin is administered early to prevent capillary
leakage, but the risk is that it may decrease blood flow,
especially in the hepatosplanchnic and the coronary
circulations. Hence, close hemodynamic monitoring is
required to ensure that cardiac output is well preserved
(85). Similarly, administration of selepressin, a vaso-
pressin derivative, was not found to be beneficial in a
study where cardiac output was not monitored (86).
Angiotensin II has been reintroduced as a vasopressor
(87), but its indications are not well defined.
Although in the past, vasopressor therapy was initi-
ated only when it was considered that the patient was
not responding to fluids, more recent studies have indi-
cated that arterial hypotension should be avoided in all
cases. Even transient hypotension can be associated with
an increase in organ failure (88) or mortality (89) and
early norepinephrine administration to restore arterial
pressure seems to have beneficial effects on outcomes
(90). The optimal arterial pressure target in shock states
has been a topic of intense investigation (58, 91), but
no globally acceptable ideal value has been identified
because arterial pressure targets should be personalized
taking into account various factors, including, among
others, history of chronic hypertension, current disease
process, and hemodynamic status (92).
Dobutamine has been considered as the inotropic
agent of choice in case of myocardial failure. Initially
considered as inappropriate for use in septic shock, it
has found a place when response to fluids is limited.
Since optimization of hemodynamic variables is usu-
ally considered as standard of care, conduct of a large
RCT to evaluate the potential benefit or harm of dobu-
tamine would be difficult.
Although their long half-life is not particularly de-
sirable, phosphodiesterase inhibitors (like milrinone)
and levosimendan can find a place in the management
of cardiogenic shock, but their vasodilating effects have
limited their place in the management of septic shock.
There is no place for routine administration of any ino-
tropic agent in these patients, even levosimendan (93).
The Future of Hemodynamic Monitoring
Medical and scientific technology continues to ad-
vance at an extraordinary pace, and this will continue
Critical Care Medicine
Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
50th Anniversary Article
to impact the field of hemodynamic monitoring in
shock. New tiny, flexible noninvasive sensors that can
be attached to the skin or items of clothing are already
available and can provide continuous monitoring of
multiple variables (94). These values can be transmitted
wirelessly to central computers or systems or to health-
care workers’ smartphones or smartwatches. Artificial
intelligence will increasingly be used to interpret such
signals and suggest or even start appropriate therapy.
There is already renewed interest in clinical automa-
tion with automated closed-loop control systems (95).
The integration of feedback control systems and arti-
ficial intelligence into medical device systems has the
potential to improve adherence to prescribed treat-
ment regimens and protocols, and enable rapid adap-
tation to new or changing therapeutic strategies. In the
future, it is likely that personalized titration of drugs
will be administered by automated systems using data
previously gathered from patients with similar demo-
graphics and disease patterns. These systems would be
able to more accurately predict the response of a given
patient to specific drugs and use these predictive mod-
els within their treatment protocols, thus facilitating a
personalized medicine approach. Echocardiography
probes will also become even smaller and even more
widely available and used. Although costs remain high
at present, these will decrease as such tools become
more widespread. However, further study needs to de-
termine how best such innovations can be used in the
critically ill to improve outcomes before they become a
routine presence on our ICUs.
CONCLUSIONS
Hemodynamic monitoring and management have
improved greatly in critical care and perioperative
medicine over the past 50 years. Monitoring tech-
nology has evolved to enable very invasive devices to
be replaced by much less invasive (and even totally
noninvasive) equipment—even though we may lose
some accuracy. Simultaneously, our whole approach to
monitoring has shifted from using a few static, single
measures to a functional, dynamic, and multivari-
able approach. Hemodynamic monitoring in the ICU
needs to include more than simply blood pressure,
heart rate, and urine output. Furthermore, any var-
iable on its own provides relatively little information
of a patient’s hemodynamic status, particularly in the
www.ccmjournal.org     9
Vincent et al
complex critically ill patient with shock. Rather the
results from monitoring of several different variables
need to be considered together to provide a complete
hemodynamic picture for that particular patient at that
moment in time (15). The ability to monitor regional
blood flow would be helpful but is not currently feasible
clinically. We also have no ideal monitoring system for
cell function, and monitoring of the microcirculation
is still a work in progress. Yet, these areas could rep-
resent important targets for successful resuscitation in
the future. Finally, we are moving from standard, pro-
tocolized hemodynamic strategies to a more person-
alized approach to ensure appropriate management of
each patient according to his/her specific requirements
during their disease trajectory (92).
1 Department of Intensive Care, Erasme Hospital, Université
libre de Bruxelles, Brussels, Belgium.
2 Department of Anesthesiology, Erasme Hospital, Université
Libre de Bruxelles, Brussels, Belgium.
3 Department of Anesthesiology and Intensive Care, Hôpitaux
Universitaires Paris-Sud, Université Paris-Sud, Université
Paris-Saclay, Paul Brousse Hospital, Assistance Publique
Hôpitaux de Paris (APHP), Villejuif, France.
4 Department of Anesthesiology, Center of Anesthesiology
and Intensive Care Medicine, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany.
Dr. Vincent drafted the article. Drs. Joosten and Saugel revised
it for critical content. All authors read and approved the final
version.
Dr. Joosten’s institution received funding from Edwards
Lifesciences (Irvine, CA). Dr. Saugel has received honoraria
for consulting, honoraria for giving lectures, and refunds of
travel expenses from Edwards Lifesciences (Irvine, CA); he
has received honoraria for consulting, institutional restricted
research grants, honoraria for giving lectures, and refunds of
travel expenses from Pulsion Medical Systems SE (Feldkirchen,
Germany); he has received institutional restricted research grants,
honoraria for giving lectures, and refunds of travel expenses from
CNSystems Medizintechnik GmbH (Graz, Austria); he has re-
ceived institutional restricted research grants from Retia Medical,
LLC (Valhalla, NY); he has received honoraria for giving lectures
from Philips Medizin Systeme Böblingen GmbH (Böblingen,
Germany); and he has received honoraria for consulting, institu-
tional restricted research grants, and refunds of travel expenses
from Tensys Medical (San Diego, CA). Dr. Vincent has disclosed
that he does not have any potential conflicts of interest.
For information regarding this article, E-mail: jlvincent@intensive.org
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