Intensive Care Med
https://doi.org/10.1007/s00134-023-07164-y
UNDERSTANDING THE DISEASE
The nuts and bolts of fluid de‑escalation
Daniel De Backer1*  , Marlies Ostermann2 and Xavier Monnet3
© 2023 Springer-Verlag GmbH Germany, part of Springer Nature
Fluids are a key component of the initial resuscitation of
critically ill patients. These are administered to compen-
sate for external losses and relative hypovolemia but also
for internal losses related to capillary leak. The effects of
fluids are often transient, and frequently, their adminis-
tration is to be repeated (see electronic supplementary
material, ESM). Interstitial edema unavoidably results.
When the situation improves, the patient usually elimi-
nates the accumulated fluids spontaneously. In some
conditions, it may appear attractive to actively promote
active fluid withdrawal, for instance, in patients with
severe acute respiratory distress syndrome (ARDS), sta-
bilized sepsis, right ventricular dysfunction, or increased
abdominal pressure. In all these conditions, the indica-
tion and timing of fluid removal varies. Many factors
should be taken into account, including degree of fluid
accumulation, resolution vs. persistence of capillary leak-
age, hemodynamic (in)stability and doses of vasopres-
sors/inotropic agents. Unfortunately, fluid removal may
be associated with hemodynamic compromise, and this
should be prevented. To conduct fluid withdrawal safely,
physicians should address a few questions.
Should I withdraw fluids in this patient?
A positive fluid balance is associated with an increased
risk of death [1]. However, a positive fluid balance may
simply reflect severity of illness and some of these
patients may still benefit from fluid administration. More
than a positive fluid balance per se, signs of fluid intoler-
ance should be considered as triggers for fluid removal.
In addition to clinical signs and context, hemodynamic
*Correspondence: ddebacke@ulb.ac.be
1
Department of Intensive Care, CHIREC Hospitals, Université Libre de
Bruxelles, Boulevard du Triomphe 201, 1160 Brussels, Belgium
Full author information is available at the end of the article
measurements may help, including increased extravas-
cular lung water index, elevated central venous pressure
(CVP) and venous stasis [2]. Among critically ill patients
undergoing fluid withdrawal, those with signs of venous
stasis had a larger response to diuretics [3].
Is it the right time to attempt fluid withdrawal?
There are two prerequisites to be met:
1. Tissue perfusion needs to be adequate. When the
patient still requires resuscitative interventions, fluid
withdrawal may result in tissue hypoperfusion and
should, therefore, be withheld.
2. Patients must not be preload responsive. Presence
of edema or even increased blood volume does not
exclude preload responsiveness [4]. Indeed, if a
patient is on the steep part of the Frank–Starling rela-
tionship, fluid withdrawal can lead to a decrease in
cardiac output. Accordingly, one of the easiest ways
to ensure safe fluid withdrawal is to perform a test of
preload responsiveness. In a trial including 39 criti-
cally ill patients undergoing fluid withdrawal during
dialysis, Monnet et al. [5] observed that intradialytic
hypotension occurred in 13 (33%) patients, who were
identified by a positive passive leg raising test at base-
line.
How to proceed?
When deciding to withdraw fluids, three factors must be
considered: the technique (diuretics vs. ultrafiltration),
the dose, and some safety limits for stopping fluid with-
drawal, especially if a mechanical technique is selected
(Fig. 1). Patients with high vasopressor requirement and
severe organ dysfunction are less likely to tolerate fluid
withdrawal [6].
Diuretics are often suggested first but ultrafiltration is
preferred in patients receiving renal replacement therapy

Fig. 1  Checklist for a safe process of fluid de-escalation. The subse-
quent items (signs of fluid intolerance/absence of preload respon-
siveness) are prerequisites for fluid withdrawal consideration. Once
a decision is made that fluid withdrawal is indicated, method and
dose of fluid withdrawal and then safety limits need to be selected.
The dose of diuretics or ultrafiltration should be adjusted as needed
according to achieved fluid removal/balance as well as tolerance. CVP
central venous pressure, EVLWI extravascular lung water index, PLR
passive leg raising, MAP mean arterial pressure, CRT​ capillary refill time
(RRT) [7]. The pros and cons of diuretics and ultrafiltra-
tion are discussed in ESM. The ultrafiltration rate should
be carefully selected. Usually, ultrafiltration is initiated at
a low rate and progressively increased if tolerated. Con-
tradictory impact of high vs. low ultrafiltration rates on
outcome has been reported in observational trials [8, 9],
suggesting that individual factors may determine toler-
ance to fluid withdrawal. During fluid withdrawal, several
compensatory mechanisms need to occur. First, when
depleting the plasma volume, refilling from the interstit-
ium needs to take place. The plasma capillary refill rate is
highly variable among individuals and may be decreased
in case of vasoplegia and increased capillary permeabil-
ity. Low-dose vasopressors may help to redistribute fluids
from unstressed to stressed blood volume. Maintaining
an adequate plasma oncotic pressure may facilitate refill,
as the addition of albumin to diuretics in hypoproteine-
mic patients with ARDS achieved a more negative fluid
balance and greater hemodynamic stability compared to
diuretics alone [10]. Similarly, albumin administration to
hypoalbuminemic patients undergoing dialysis prevented
intradialytic hypotension [11]. Second, redistribution of
blood from unstressed to stressed volume should also
occur. This may be hampered in patients with vasoplegia;
hence, patients treated with high-dose vasopressors often
tolerate fluid withdrawal poorly. Finally, impaired systolic
or diastolic function may impact patients’ ability to toler-
ate rapid fluid withdrawal.
Of note, while fluid withdrawal is usually feasible, the
amount of fluid that is ultimately withdrawn is often
lower than targeted. For example, Silversides et  al.
effectively achieved a negative fluid balance in patients
submitted to active fluid removal compared to the con-
trol group, but only one-third of the patients in the
intervention group achieved the daily fluid balance tar-
get [7].
When to stop?
The final aspect is to fix safety limits. Often, fluid
removal is stopped when hypotension occurs [5, 12–
14]. However, as hypotension occurs due to a fall in car-
diac output related to a decrease in cardiac preload, and
as peripheral vasoconstriction occurs to redistribute
perfusion to more central organs, signs of hypoperfu-
sion develop prior to hypotension [15]. These warning
signals should be captured at the bedside. However,
invasive hemodynamic monitoring is often not applied
at this stage. Ganter et al. [12] reported that low mixed
venous oxygen saturation ­(SvO2) and impaired periph-
eral perfusion were the signs leading to termination of
fluid removal, beside cardiac output and mean arterial
pressure (MAP). Serial hemodynamic measurements
revealed that the slope of hourly decrease in MAP and
cardiac output were steeper in patients who subse-
quently developed intradialytic hypotension compared
to others [5]. Altered signs of peripheral perfusion,
detected by perfusion index using pulse oximetry, were
associated with development of hypotension [13]. More
recently, Mongkolpun et  al. [15] evaluated the role of
skin blood flow measurements using a laser Doppler in
patients with septic or cardiogenic shock submitted to
fluid withdrawal by RRT. Skin perfusion variables iden-
tified patients with impaired tissue perfusion defined
as a 10% increase in lactate levels, while cardiac out-
put, central S ­ vO2 and MAP remained unaltered. The
SOCRATE score, computed as cardiovascular Sequen-
tial Organ Failure Assessment (SOFA) score ≥ 1, cap-
illary refill time (CRT) ≥ 3  s at the index finger and
lactate level > 2  mmol/l, nicely correlates with the risk
of hypotension (score 0: 10%, score 1: 33%, score 2:
55%, and score 3: 80% risk) [14]. Although these tri-
als allow the identification of patients who are likely
to tolerate fluid removal poorly, they do not inform
clinicians when to stop fluid removal before hypoten-
sion or hyperlactemia occur. Indeed, changes in blood
pressure or cardiac output occurred more rapidly in
patients who developed hypotension, but there is no
information about potential cutoff values regarding
the magnitude of changes prior to the development of
hypotension.
How to react when hemodynamic instability
occurs?
In case of hemodynamic instability, several actions may
be initiated, including stopping fluid removal, increasing
the vasopressor dose, giving albumin and/or administer-
ing a fluid bolus. As this remains supported by minimal
data, a suggestion for management is proposed in ESM.
Take‑home messages
Fluid de-escalation is feasible in many critically ill
patients, provided a structured approach is followed
including careful identification of patients who may
benefit (i.e., signs of fluid intolerance and absence of
preload responsiveness). When a decision is made to
proceed with fluid withdrawal, the technique, rate of
fluid removal, and safety limits need to be carefully
determined.
Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1007/​s00134-​023-​07164-y.
Author details
1 mortality in critically ill patients with fluid overload. Crit Care 22(1):223
 Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles,
Boulevard du Triomphe 201, 1160 Brussels, Belgium. 2 Department of Intensive
Care, King’s College London, Guy’s & St Thomas’ Hospital, London, UK. 3 AP‑HP,
Service de Médecine Intensive‑Réanimation, Hôpital de Bicêtre, DMU 4 COR-
REVE, Inserm UMR S_999, FHU SEPSIS, CARMAS, Université Paris-Saclay, 78 Rue
du Général Leclerc, 94270 Le Kremlin‑Bicêtre, France.
Data availability
Non applicable.
Declarations
Conflicts of interest
DDB: Edwards Lifesciences, Philips, Baxter. MO: Fresenius Medical, Baxter,
Biomerieux, LaJolla Pharma. XM: Getinge, Baxter.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
Received: 21 May 2023 Accepted: 6 July 2023
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