Pfortmueller et al. Annals of Intensive Care (2024) 14:115 Annals of Intensive Care
https://doi.org/10.1186/s13613-024-01336-9
REVIEW Open Access
Fluid accumulation syndrome in sepsis
and septic shock: pathophysiology, relevance
and treatment—a comprehensive review
Carmen Andrea Pfortmueller1* , Wojciech Dabrowski2, Rob Wise3,4,5, Niels van Regenmortel6,7 and
Manu L. N. G. Malbrain2,8,9
Abstract
In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagno-
sis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS)
is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset
organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes.
While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis,
monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock,
including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation
whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics,
or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resus-
citation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, mainte-
nance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.
Trial registration: Not applicable.
Keywords Fluids, Resuscitation, De-resuscitation, Fluid accumulation, Safety, Monitoring
*Correspondence:
Carmen Andrea Pfortmueller
Full list of author information is available at the end of the article
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.
, Pfortmueller et al. Annals of Intensive Care (2024) 14:115 Page 2 of 12
Graphical Abstract
Introduction framework (with the resuscitation—optimization—stabi-
Fluids are widely used in critically ill patients to restore lization and evacuation phases) [14, 15].
hemodynamic stability and tissue perfusion [1]. Fluid
accumulation (FA) is very common in critical illness and What is FAS?
occurs in at least 20% of the ICU population, particu- Fluid accumulation may be defined and calculated by
larly in patients with increased capillary leak due sepsis dividing the cumulative fluid balance by the baseline
and septic shock [2, 3]. Many studies have previously body weight. Please see Fig. 1 for a critical appraisal of
described the negative impact of fluid accumulation syn- this definition. FAS is defined as any degree of fluid accu-
drome (FAS) on clinically relevant outcomes. Several mulation (expressed as a percentage) with new onset
observational trials [4–9], as well as one meta-analysis (of organ failure (which may be described by a sequential
mainly observational trials) [10], suggest that FAS is asso- organ failure assessment (SOFA) organ sub-score equal
ciated with increased mortality in critically ill patients. to or greater than 3) that may be due to FA, [16]. Most
However, current RCTs on the topic have not found a organ systems, including the lungs, heart, and gastroin-
mortality benefit with restrictive fluid management [11, testinal tract, are negatively affected by FAS (see Fig. 2 for
12] and protocolized de-resuscitation [13]. While FAS an overview) [16].
is a well described entity in critical care, with a serious In sepsis and septic shock, a cascade of circulatory
impact on patient outcomes, its monitoring, prevention effects, such as peripheral vasodilatation, myocardial
and treatment is less well described, with much uncer- depression, and increased metabolism, lead to an imbal-
tainty. In this review, we aimed to comprehensively ance between systemic oxygen delivery and oxygen
summarize current literature on pathophysiology, rel- demand, resulting in global tissue hypoxia or shock [18,
evance, diagnosis and treatment of fluid accumulation in 19]. Sepsis and septic shock are not always associated
patients with sepsis/septic shock in line with the ROSE with a volume depleted state, but rather it is the micro-
circulatory alterations together with vasodilatation and
https://doi.org/10.1186/s13613-024-01336-9
REVIEW Open Access
Fluid accumulation syndrome in sepsis
and septic shock: pathophysiology, relevance
and treatment—a comprehensive review
Carmen Andrea Pfortmueller1* , Wojciech Dabrowski2, Rob Wise3,4,5, Niels van Regenmortel6,7 and
Manu L. N. G. Malbrain2,8,9
Abstract
In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagno-
sis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS)
is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset
organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes.
While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis,
monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock,
including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation
whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics,
or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resus-
citation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, mainte-
nance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.
Trial registration: Not applicable.
Keywords Fluids, Resuscitation, De-resuscitation, Fluid accumulation, Safety, Monitoring
*Correspondence:
Carmen Andrea Pfortmueller
Full list of author information is available at the end of the article
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.
, Pfortmueller et al. Annals of Intensive Care (2024) 14:115 Page 2 of 12
Graphical Abstract
Introduction framework (with the resuscitation—optimization—stabi-
Fluids are widely used in critically ill patients to restore lization and evacuation phases) [14, 15].
hemodynamic stability and tissue perfusion [1]. Fluid
accumulation (FA) is very common in critical illness and What is FAS?
occurs in at least 20% of the ICU population, particu- Fluid accumulation may be defined and calculated by
larly in patients with increased capillary leak due sepsis dividing the cumulative fluid balance by the baseline
and septic shock [2, 3]. Many studies have previously body weight. Please see Fig. 1 for a critical appraisal of
described the negative impact of fluid accumulation syn- this definition. FAS is defined as any degree of fluid accu-
drome (FAS) on clinically relevant outcomes. Several mulation (expressed as a percentage) with new onset
observational trials [4–9], as well as one meta-analysis (of organ failure (which may be described by a sequential
mainly observational trials) [10], suggest that FAS is asso- organ failure assessment (SOFA) organ sub-score equal
ciated with increased mortality in critically ill patients. to or greater than 3) that may be due to FA, [16]. Most
However, current RCTs on the topic have not found a organ systems, including the lungs, heart, and gastroin-
mortality benefit with restrictive fluid management [11, testinal tract, are negatively affected by FAS (see Fig. 2 for
12] and protocolized de-resuscitation [13]. While FAS an overview) [16].
is a well described entity in critical care, with a serious In sepsis and septic shock, a cascade of circulatory
impact on patient outcomes, its monitoring, prevention effects, such as peripheral vasodilatation, myocardial
and treatment is less well described, with much uncer- depression, and increased metabolism, lead to an imbal-
tainty. In this review, we aimed to comprehensively ance between systemic oxygen delivery and oxygen
summarize current literature on pathophysiology, rel- demand, resulting in global tissue hypoxia or shock [18,
evance, diagnosis and treatment of fluid accumulation in 19]. Sepsis and septic shock are not always associated
patients with sepsis/septic shock in line with the ROSE with a volume depleted state, but rather it is the micro-
circulatory alterations together with vasodilatation and
