Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy
Open accessAbstract
In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.
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Poor or incomplete source control may additionally lead to a state of ongoing capillary leak and fluid accumulation, referred to as GIPS (global increased permeability syndrome).
“Poor or incomplete source control may additionally lead to a state of ongoing capillary leak and fluid accumulation, referred to as GIPS (global increased permeability syndrome) [8].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [8]
The 'Global increased permeability syndrome' section (page unavailable) describes GIPS as a persistent state with ongoing fluid accumulation, and 'The risk of fluid overload' links capillary leak in sepsis to fluid extravasation. Neither section links GIPS or ongoing capillary leak to poor or incomplete source control. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNutrition may also contribute to fluid accumulation.
“since nutrition may also contribute to fluid accumulation [8].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [8]
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Effective hemodynamic monitoring
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Self-citationSurviving Sepsis campaign: international guidelines for Management of Sepsis and Septic Shock 2026
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Self-citationHow I personalize fluid therapy in septic shock?
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Self-citationIntra-Abdominal Hypertension Is Responsible for False Negatives to the Passive Leg Raising Test
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Self-citationEndothelial glycocalyx: Role in body fluid homeostasis and fluid management
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Individualized sepsis treatment using reinforcement learning
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Parameters of fluid responsiveness
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Self-citationProfile of Fluid Exposure and Recognition of Fluid Overload in Critically Ill Children
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Self-citationOptimal target in septic shock resuscitation
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The Burden of Sepsis and Septic Shock in the Intensive Care Unit
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Bedside hyperspectral imaging indicates a microcirculatory sepsis pattern - an observational study
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Indications for and Timing of Initiation of KRT
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Abdominal Compartment Syndrome in Acute Pancreatitis: A Narrative Review
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Self-citationManagement of peripartum intra‐abdominal hypertension and abdominal compartment syndrome
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Self-citationDeep Learning to Quantify Pulmonary Edema in Chest RadiographsPreprint
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New Insights into the Fluid Management in Patients with Septic Shock
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- Authors
- Malbrain, M. L. N. G., Van Regenmortel, N., Saugel, B., De Tavernier, B., Van Gaal, P.-J., Joannes-Boyau, O., Teboul, J.-L., Rice, T. W., Mythen, M., & Monnet, X.
- Affiliations
- Vrije Universiteit Brussel (BE)
- University Medical Center Hamburg-Eppendorf (DE)
- Université Paris-Sud (FR)
- University College London (GB)
- Vanderbilt University (US)
- Corresponding author
- Malbrain, Manu L. N.G.
- Venue
- Annals of Intensive Care
- Publisher
- Elsevier BV
- Published
- 2018
- Volume
- 8
- Issue
- 1
- Pages
- 66
- ISSN
- 2110-5820 (ISSN-L)
- PMC
- PMC5964054
- OpenAlex
- W2807356795
- Cited by
- 632
- References
- 105
- Citations by year
- 2026: 84 · 2025: 92 · 2024: 76 · 2023: 96 · 2022: 70 · 2021: 84 · 2020: 76 · 2019: 41 · 2018: 13
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Intensive Care (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Abdominal Surgery and Complications
- Keywords
- septic shock, fluid management, goal-directed fluid therapy, fluid resuscitation, intravenous fluid therapy, fluid removal
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