Anestesia
Anestesia
Anestesia
Abstract
Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed
therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in
the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clini‑
cians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major
determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below
65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations,
the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients
undergoing non-cardiac surgery, pending the implementation of a “validity criteria checklist” before applying volume
expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output
monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid vol‑
ume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow
and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors
and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data
strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital
lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algo‑
rithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative
morbidity and duration of hospital stay in high-risk surgical patients.
Keywords: Hemodynamic optimization, Blood pressure, Fluid responsiveness, Vasopressors, Perioperative morbidity,
High-risk surgery, Health costs
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Fellahi et al. Ann. Intensive Care (2021) 11:58 Page 2 of 10
GDT are on the one hand not explicit enough to allow a To date, there is no universal definition for arterial
reproducible decision-making process, and on the other hypotension during anesthesia. However, evidence from
hand not suited to manage uncertainty [8]. Management several large observational studies suggest that intraoper-
of uncertainty refers to situations where there is no evi- ative mean arterial pressure (MAP) below 60–70 mmHg
dence reported in the guidelines or situations where the may be associated with postoperative acute kidney injury,
clinical reasoning tools (analysis of “abnormality”, criti- myocardial injury, and death [11–14]. Although injury is
cal analysis of the information gathered from the clinical magnified with increasing hypotension magnitude, avail-
situations/monitors, positive and differential diagnoses, able evidence suggests that MAP below 60 mmHg sus-
treatment plan, evaluation of the effectiveness of the tained for 5 min or more may be associated with organ
treatment plan) are not explicit [9]. dysfunction and increased mortality [15, 16]. Elevated
To facilitate/accelerate implementation of guidelines risks or organ injury were also reported with prolonged
on perioperative GDT, a national panel of experts in the exposure (< 10 min) to MAP below 70 mmHg [17]. To
field, representative of the whole French territory and specifically prevent acute kidney injury, French Guide-
who have previously collaborated on guidelines of the lines suggest to maintain MAP between 60 and 70 mmHg
French Society of Anesthesiology and Critical Care is intraoperatively [18]. In patients with chronic arterial
proposing an approach based on questions/answers on hypertension undergoing elective non-cardiac surgery,
issues that are frequently mentioned by clinicians. These targeting MAP values higher than 70 mmHg may be rea-
six relevant questions are: sonable, ideally adapted to the clinical and surgery condi-
tions [19]. Even if systolic, pulse pressure (the difference
1. Which blood pressure goals should be targeted dur- between systolic and diastolic pressures) and MAP were
ing anesthesia and the perioperative period? recently found to have comparable discriminative abil-
2. Intraoperative fluids management: restrictive, stand- ity in evaluating the risk of organ injury [20], MAP is
ard, liberal and beyond? the major determinant of organ perfusion. Moreover,
3. Are dynamic indices and maneuvers useful to predict systolic and diastolic pressures are indirectly calculated
and manage volume expansion? from MAP and may be less reliable when the oscillo-
4. When should we measure stroke volume (SV) and metric method is used. For this reason, MAP should be
cardiac output (CO)? the main monitoring variable on which interventions to
5. Fluids or vasoconstrictors: how to decide? prevent/correct arterial hypotension should be based
6. What is the economic impact of hemodynamic mon- on. Whether or not relative changes in MAP for a given
itoring for GDT? patient rather than absolute values should be preferred
is still a matter of debate. In a simpler approach, anes-
The members of the panel first identified the questions thetic management of arterial hypotension could be
and subsequently organized the answers by summariz- based on absolute values without considering percentage
ing elements of guidelines, knowledge, and explicit clini- changes from (difficult to document) preoperative arte-
cal reasoning tools followed by decision algorithms when rial pressure values [21]. In a more complex approach, a
appropriate. The decision algorithms were adopted fol- multicenter randomized controlled trial performed in
lowing a modified Delphi process and the RAND/UCLA high-risk surgical patients undergoing major abdomi-
Appropriateness Method [10]. We consider that explicit nal surgery (all received SV-guided intraoperative fluid)
clinical reasoning tools will improve the decision-making compared an individualized strategy using low-dose
process and facilitate management of uncertainty. norepinephrine to maintain intraoperative systolic arte-
rial pressure within 10% of the preoperative reference
Q1. Which blood pressure goals should be targeted value to a strategy of standard management. The study
during anesthesia and the perioperative period? revealed a significant reduction in postoperative organ
Monitoring blood pressure is a prerequisite during anes- dysfunction in the individualized strategy group [22]. Of
thesia. The main objective is to prevent postoperative note, the use of intraoperative continuous low-dose nor-
complications resulting from either arterial hypo- or epinephrine on a devoted peripheral intravenous line was
hypertension. The arterial pressure can be monitored at safe and can be recommended for routine practice.
different anatomical sites, using various techniques, non- Finally, because even short cumulative durations of
invasively or invasively, and in a continuous or intermit- arterial hypotension are associated with poor outcome
tent manner. Although all excessive excursions of arterial and because continuous (versus intermittent) measure-
pressure may be detrimental, the association between ment of arterial pressure was associated with higher
intraoperative arterial hypotension and postoperative sensitivity to diagnose arterial hypotension during anes-
complications is the most thoroughly documented. thesia, continuous measurement of arterial pressure
Fellahi et al. Ann. Intensive Care (2021) 11:58 Page 3 of 10
should be preferred. Non-invasive continuous monitor- similar for all individuals. This “one size fits all” strategy
ing of arterial pressure is not yet considered interchange- is bound to result in inadequate volume management in
able with invasive monitoring and there is insufficient the vast majority of patients [25]. Low-risk patients will
evidence to recommend its use in high-risk surgical usually tolerate the deviation from their adequate volume
patients and/or high-risk surgery. Future efforts should requirements, but high-risk patients will be exposed to
concentrate on trying to verify whether treating hypoten- the above-mentioned complications. The available lit-
sive episodes as detected by those new techniques results erature do not provide evidence-based recommendations
in improvement in patient outcome rather that repeat- regarding continuous fluid infusion. The basal fluid losses
ing validation studies that are bound to provide the same via insensible perspiration are approximately 0.5 ml/kg/h,
results over and over. extending to 1 ml/kg/h during major abdominal surgery
[26]. When continuous fluid infusion is used, it should
Experts’ opinion:
We propose to prefer continuous be limited to less than 2 ml/kg/h, including drug infusion
invasive arterial pressure moni- [25].
toring in moderate to high-risk Therefore, optimizing tissue perfusion in high-risk
surgical patients, ideally using patients relies on an individualized approach. The MAP
an algorithm-based approach will be maintained above a level close to the usual value
which aims at preventing/manag- of the patient, as suggested above. Minimal value for
ing arterial hypotension. We also hemoglobin concentration and transfusion thresholds
propose to maintain MAP above will vary according to the comorbidities of each patient.
And since the ideal values of organ flow for a given
65 mmHg or within 10–20% of
patient are unknown, it is recommended to titrate flu-
preoperative reference resting
ids using small iterative boluses (100 to 250 ml crystal-
values (agreement 100%).
loids over 5 to 10 min) guided by measurements of SV
variation [27] (Fig. 1). A SV increase > 10–12% (to avoid
Q2. Intraoperative fluids management: restrictive, being confounded by measurement variability) assessed
standard, liberal and beyond? one minute after the end of fluid infusion indicates that
Intravenous fluid administration is the most frequent the patient is able to increase flow and tissue perfusion
therapeutic intervention to maintain or restore tissue in response to fluids. A lack of increase of SV after fluid
perfusion during surgical procedures. However, it is well bolus is the most reliable indication that additional vol-
established that inadequate volume therapy can result in ume therapy may generate congestion and edema and
deleterious effects, especially in frail or high-risk patients. thus become deleterious. The smaller the volume admin-
Insufficient fluid administration will lead to reduced flow istered, the minimal the congestion resulting from the
and potentially inadequate perfusion in some territories unnecessary volume overload. The number of studies
where the conductive vessels are more resistive. These that have demonstrated the reduction in complications
territories may differ from one patient to another and can associated with a SV-guided fluid titration in high-risk
involve every organ. The reduced local blood flow can
induce cellular hypoxia and subsequent organ dysfunc-
tion or failure. On the other hand, if fluid is administered
in excess, venous congestion and edema will ensue. The
consequences of fluids in excess are probably as deleteri-
ous as the consequences of hypovolemia, and many stud-
ies have established a clear relation between positive fluid
balance and postoperative complications [23, 24]. Thus,
targeting the right amount of volume expander required
by each surgical patient during the procedure is a daily
challenge for practitioners. Recommendations are often
blurry with statements indicating to maintain “adequate
volemia” or “optimal volume”, which do not translate into
Fig. 1 Typical intraoperative goal-directed therapy algorithm based
quantitative meaningful information. Even worse, some on an individualized approach. MAP mean arterial pressure, PPV pulse
protocols suggest to administer an identical predefined pressure variation, SVV stroke volume variation. Values for PPV/SVV,
amount of fluids to everyone, taking into account the MAP and cardiac index are indicative and must be adapted on an
body weight and the duration of the surgical procedure, individual basis. The use of vasopressors could also be considered
when diastolic arterial pressure < 40 mmHg
assuming that the requirements and the tolerance are
Fellahi et al. Ann. Intensive Care (2021) 11:58 Page 4 of 10
surgical patients provides compelling evidence to sup- a transient rise in tidal volume from 6 to 8 ml/kg IBW
port that simple approach to minimize the deleterious could be useful to predict fluid responsiveness with sen-
side effects of intraoperative fluids [28, 29]. sitivity and specificity values > 90% [42]. As well, an abso-
lute decrease in PPV > 2% during a mini-fluid challenge
Experts’ opinion:
We propose to routinely use a could help to predict fluid responsiveness [43]. Limita-
personalized approach of intra- tions to the interpretation of PPV also include cardiac
operative fluid infusion/volume arrhythmias, right and left ventricular failure, decreased
expansion based on the indi- lung compliance, and spontaneous breathing activity [32,
vidual hemodynamic response 40]. Importantly, the coelioscopic surgery-induced pneu-
to volume titration to reduce the moperitoneum is a frequent situation which decreases
deleterious side effects of fluids thoracic compliance, leading to changes in the interpre-
and improve patients’ outcome tation of PPV (a situation defined as false positive but this
requires a commentary: the patient is preload-dependent
(agreement 100%).
due to decreased venous return secondary to increased
abdominal pressure meaning that volume expansion will
Q3. Are dynamic indices and maneuvers useful
unfrequently correct fluid responsiveness) [44, 45]. Fur-
to predict and manage volume expansion?
ther studies are needed to determine the impact of an
Fluid responsiveness is defined as a significant increase
increased abdominal pressure between 10 and 15 mmHg
in blood flow in response to a fluid bolus [30]. Predict-
on PPV threshold values that should be considered to
ing fluid responsiveness is useful to identify patients who
identify intraoperative fluid responsiveness. Meanwhile,
may benefit from volume expansion and, more impor-
PPV must be interpreted with caution in that specific
tantly, to prevent fluid administration in non-responders
surgical setting or in patients in prone position. Finally,
[31]. Cardiac preload indices, such as central venous pres-
dynamic indices seem to predict fluid responsiveness
sure, have repeatedly been shown to be unreliable predic-
with insufficient accuracy in an open-chest condition
tors of fluid responsiveness. On the contrary, the arterial
during cardiac and/or thoracic surgery [46].
pulse pressure variation (PPV) induced by mechanical
Subsequently, it could be reasonable for routine prac-
ventilation is known as a sensitive and specific marker of
tice to implement a “validity criteria checklist” before
fluid responsiveness [32]. In patients receiving controlled
using PPV or similar approaches to estimate fluid
mechanical ventilation with a tidal volume ≥ 7–8 ml/
responsiveness (Table 2) [47]. When PPV cannot be used,
kg of ideal body weight (IBW), fluid responsiveness is
it remains possible to assess fluid responsiveness in sur-
very likely when PPV is > 13%, very unlikely when PPV
gical patients undergoing general anesthesia by measur-
is < 9% and uncertain when PPV ranges between 9 and
ing changes in SV during an end-expiratory occlusion
13% (grey zone of uncertainty) [33]. Importantly, tidal
test, a lung recruitment maneuver or during a mini-fluid
volumes of 7–8 ml/kg of IBW are consistent with recent
challenge [48, 49]. Out of the operating room, the most
recommendations for perioperative lung-protective ven-
validated maneuver is the passive leg raising test [50].
tilation [34]. Since the sentinel study by Lopes et al. [35],
The main limiting factor to the clinical adoption of those
numerous clinical studies using either PPV or the pulse
methods is the availability of a cardiac output monitor
contour-derived stroke volume variation (SVV) to indi-
to quantify SV changes (Table 1). The pleth variability
vidualize fluid therapy showed a decrease in postopera-
index (PVI), a non-invasive surrogate for PPV, may also
tive complications and hospital lengths of stay [36]. The
be useful to predict fluid responsiveness during sur-
estimation of PPV requires either invasive or non-inva-
gery [51]. Recently, the quantification of changes in the
sive recording of a continuous arterial pressure wave-
peripheral perfusion index (PI), a variable used as a sig-
form [37–39]. There are several limitations to the use of
nal quality indicator by most pulse oximeters, has been
PPV/SVV which have been described in detail elsewhere
proposed in an exploratory study to predict fluid respon-
[40]. For instance, protective mechanical ventilation is a
siveness with acceptable sensitivity and specificity [52].
potential obstacle to the use of PPV when very low tidal
However, monitors using finger cuff technologies have in
volumes are used (e.g. 6 ml/kg IBW or less) [41]. During
common the risk of poor reliability in cases of peripheral
very low tidal volume ventilation, a high PPV still sug-
hypoperfusion.
gests fluid responsiveness whereas a low PPV cannot rule
out fluid responsiveness. Therefore, alternative meth-
ods have been proposed to predict fluid responsiveness. Experts’ opinion:
We propose to implement a
They include the assessment of PPV changes during a “validity criteria checklist” before
tidal volume challenge or during a mini-fluid challenge using PPV (or similar methods)
(Table 1). Thus, a 3.5% absolute increase in PPV during to estimate fluid responsiveness,
Fellahi et al. Ann. Intensive Care (2021) 11:58 Page 5 of 10
Table 1 Main advantages and limitations of dynamic indices and maneuvers developed to predict fluid responsiveness (chronologic
order from top to bottom)
Methods (year of first validation) Main advantages Main limitations
PPV (2000) Automatically calculated by most bedside Need for general anesthesia, an arterial line and a
monitors tidal volume > 7 ml/kg
SVV (2001) Automatically calculated by most CO monitors Need for a CO monitor, general anesthesia, an
arterial line and a tidal volume > 7 ml/kg
Changes in CO during a PLR maneuver (2006) Useful when Vt < 7 ml/kg IBW Need for a CO monitor, PLR maneuver difficult to
perform during surgery
PVI (2008) Non-invasive from a pulse ox Need for general anesthesia and a tidal vol‑
ume > 7 ml/kg, influenced by peripheral
perfusion
Changes in SV during an EEO test (2009) Useful when Vt < 7 ml/kg IBW Need for a CO monitor, prone to error measure‑
ments (small magnitude of changes in SV)
Changes in SV during a mini-fluid challenge Useful when Vt < 7 ml/kg IBW Need for a CO monitor, prone to error measure‑
(2011) ments (small magnitude of changes in SV)
Changes in PPV during a mini-fluid challenge Useful when Vt < 7 ml/kg IBW Prone to error measurements (small magnitude of
(2015) changes in PPV)
Changes in PPV during a Vt challenge (2017) Useful when Vt < 7 ml/kg IBW Prone to error measurements (small magnitude of
changes in PPV)
Changes in SV during a LRM (2017) Useful when Vt < 7 ml/kg IBW Need for a CO monitor
Changes in PI during a PLR maneuver (2019) Useful when Vt < 7 ml/kg IBW, non-invasive Influenced by peripheral perfusion, PLR maneuver
(pulse ox) difficult to perform during surgery
Low level of scientific validation
Changes in PI during a LRM (2020) Useful when Vt < 7 ml/kg IBW, non-invasive Influenced by peripheral perfusion
(pulse ox) Low level of scientific validation
CO cardiac output, EEO end-expiratory occlusion, IBW ideal body weight, LRM lung recruitment maneuver, PI perfusion index, PLR passive leg raising, PPV pulse
pressure variation, Pulse ox pulse oximetry, PVI pleth variability index, SV stroke volume, SVV stroke volume variation, Vt tidal volume
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