3.5 ESICM Guidelines on Fluid De-resuscitation

Fluid resuscitation is the cornerstone of shock management, widely accepted and applied by intensivists as the initial resuscitation strategy. However, inappropriate fluid resuscitation leads to intravascular fluid accumulation, closely associated with adverse outcomes such as pulmonary edema, prolonged mechanical ventilation, acute kidney injury (AKI), intra-abdominal hypertension, and delayed wound healing. Therefore, after patients survive the acute resuscitation phase, how to safely and effectively clear excess fluid becomes a key clinical management focus and challenge. In 2025, the European Society of Intensive Care Medicine (ESICM) published clinical practice guidelines for fluid therapy in adult critically ill patients, with Part III focusing on fluid clearance therapy during the resuscitation de-escalation phase (“fluid de-resuscitation”). Together with Parts I (“Resuscitation Fluid Selection”) and II (“Resuscitation Fluid Volume”), it forms a complete adult critically ill patient fluid management framework, filling the evidence gap from “active resuscitation” to “proactive clearance,” holding significant clinical guidance value. This section interprets the recommendations covered in Part III of the guidelines, outlining opinions, evidence-based data, and clinical applicability, aiming to discuss the concepts and clinical value of fluid de-escalation therapy post-resuscitation.

1. Significance of Fluid De-resuscitation Therapy

Fluid resuscitation in shock patients is not a single, static intervention but requires continuous, dynamic adjustment according to the evolving pathophysiological characteristics of critically ill patients. While rapid volume expansion improves cardiac output, it inevitably carries the risk of intravascular fluid accumulation and tissue edema. This risk is further elevated in patients with oliguria/anuria or severe capillary leakage, potentially outweighing the benefits of resuscitation. Therefore, defining the timing of fluid resuscitation is crucial for volume management.

Fluid accumulation causes fatal damage to tissues and organs: (1) interstitial fluid accumulation increases the diffusion distance between cells and capillaries, impairing oxygen and nutrient exchange, leading to cellular hypoxia and metabolic waste accumulation; (2) in closed anatomical compartments (e.g., cranial, pericardial), fluid accumulation directly compresses parenchymal tissue—cerebral edema can elevate intracranial pressure and precipitate brain herniation, while pericardial effusion can restrict cardiac diastolic function; (3) prolonged edema activates fibroblasts, promotes collagen deposition, and causes tissue fibrosis—hepatocyte ischemia/hypoxia leads to degeneration, atrophy, or necrosis; renal interstitial edema compresses renal tubules, impairing filtration and reabsorption, hindering renal function recovery, and potentially leading to congestion-induced cirrhosis; and (4) pulmonary edema causes hypoxemia and prolongs respiratory support needs.

Malbrain et al. proposed a four-phase fluid therapy model (Resuscitation, Optimization, Stabilization, and Evacuation—the ROSE concept), emphasizing that each phase should have clear goals, monitoring tools, and treatment strategies. The evacuation phase specifically points to fluid de-resuscitation, which differs from traditional reliance on the patient’s autonomous clearance of accumulated fluid. Instead, it employs active intervention strategies to reduce volume load to an optimal state in the shortest time.

Although theoretical analysis suggests that aggressive fluid clearance may improve outcomes in critically ill patients, clinical trials have shown only limited benefits. A pooled analysis of 13 randomized controlled trials (RCTs) indicated that, compared to usual care, fluid de-resuscitation therapy reduces average ICU length of stay and mechanical ventilation time in critically ill patients. Although the evidence level is low, it demonstrates the positive significance of de-resuscitation. Regarding other prognostic indicators (mortality, renal replacement therapy [RRT] requirement, AKI incidence), de-resuscitation showed no significant difference from usual care. Notably, some studies failed to achieve preset negative fluid balance targets, and overlapping fluid management between groups (e.g., control groups also using diuretics) weakened the statistical significance of intergroup differences.

Additionally, the ESICM expert panel considered other factors influencing de-resuscitation, such as high accessibility and low cost of diuretics versus the limited availability of ultrafiltration/RRT in resource-constrained settings. Synthesizing evidence and implementation feasibility, the ESICM guidelines recommend implementing fluid de-resuscitation in adult critically ill patients post-acute resuscitation (conditional recommendation, low evidence). While the guidelines positively evaluate de-resuscitation, they emphasize strict indication control: it is only applicable to hemodynamically stable patients not requiring continuous resuscitation, with individualized monitoring to avoid hypovolemia or kidney injury from over-clearance.

2. Measures for Fluid De-resuscitation

Currently, clinical attempts to achieve negative fluid balance often rely on empiric pharmacological selection, including loop diuretics, carbonic anhydrase inhibitors, thiazides, thiazide-like drugs, and mineralocorticoid receptor antagonists (MRAs). These can be used singly or in combination. Due to low cost and wide accessibility, diuretics suit most clinical scenarios. However, diuretic response varies significantly among individuals and is unpredictable, potentially prolonging fluid accumulation. Diuretic use is a “double-edged sword”: while improving organ congestion and tissue edema, it may cause inadequate cardiac preload, leading to decreased cardiac output and prerenal injury. A multicenter prospective observational study found that diuretics account for 22.2% of all drug-induced AKI, second only to antibiotics.

Beyond pharmacotherapy, ultrafiltration/RRT is a common de-escalation tool. Pure ultrafiltration removes only fluid, while RRT clears water, electrolytes, solutes, and exogenous waste. Although ultrafiltration/RRT allows precise clearance rate control, it requires invasive procedures, is costly, and demands high resources. Regarding internal environment impact, ultrafiltrate electrolyte concentration resembles plasma; diuretics have lower sodium excretion efficiency, potentially causing sodium retention. For anuric renal failure, diuretic resistance, or life-threatening volume overload, ultrafiltration/RRT remains irreplaceable. Like diuretics, inappropriate ultrafiltration/RRT can cause intravascular volume depletion and AKI. Previous studies show variable renal impacts, influenced by patient heterogeneity, mismatch between clearance rate and vascular refilling time, and quality control differences.

A pooled analysis of 10 RCTs showed that compared to usual care, diuretic-based fluid clearance significantly reduced RRT requirement (RR = 0.72, 95%CI 0.55–0.96), with reduced ICU stay and mechanical ventilation time. Mortality (RR = 0.90, 95%CI 0.79–1.02) and AKI incidence (RR = 0.78, 95%CI 0.40–1.53) showed no significant difference. Subgroup analyses (fluid accumulation, respiratory failure, sepsis, AKI) also showed no mortality difference. Considering health economics, pros/cons, and research results, the ESICM guideline panel recommends using diuretics for fluid clearance in critically ill patients post-acute resuscitation, though the optimal regimen remains unknown.

A pooled analysis of 4 RCTs showed no significant mortality difference between ultrafiltration/RRT and usual care (RR = 1.13, 95%CI 0.83–1.53), with no differences in mechanical ventilation time, quality of life, cognitive dysfunction risk, or PTSD. Subgroup analyses showed no benefit. Considering high costs and limited accessibility, the guidelines oppose routine use of ultrafiltration or extracorporeal fluid removal in adult critically ill patients post-acute resuscitation without other RRT indications, except for renal failure or diuretic resistance.

3. Issues in the De-escalation Guidelines and Future Research Directions

(1) Individualization and Dynamic Assessment of Fluid Clearance

The ESICM guidelines repeatedly emphasize that fluid clearance must be performed under hemodynamic stability without continuous resuscitation needs. This requires clinicians to comprehensively assess volume status, organ function, diuretic response, and complication risks, implementing “titrated” clearance. Currently, no standard volume assessment protocol exists. Common tools include clinical indicators (fluid balance, skin edema, pulmonary crackles), hemodynamic monitoring (CVP, PCWP, IVC diameter/variability, cardiac output, EVLW), and biomarkers (BNP, NGAL). Accurate judgment relies on thorough understanding and clinical experience, requiring continuous dynamic assessment and timely strategy adjustment. This easily leads to inter-physician variability. Future research should explore rational indicator combinations to standardize treatment across practitioners.

(2) Terminological Confusion and Practice Inconsistency

Previous literature has used multiple terms for high volume load—“volume excess,” “fluid overload,” “fluid excess,” “fluid accumulation”—lacking clear definitions and unified standards. In the initial resuscitation phase, some patients with heart failure or RV dilation do not require expansion but rather volume down-regulation via diuretics (“reverse fluid resuscitation”). Dehydration during resuscitation is also an important measure to improve hemodynamics and tissue perfusion, fundamentally different in timing from evacuation-phase de-resuscitation, and requires careful distinction. Clinical fluid clearance strategies also vary significantly; for example, some studies mix “fluid restriction” with “active clearance,” making intervention effects difficult to isolate. Future efforts must standardize concepts and terminology to align clinical practice and research.

(3) Urgent Issues and Research Directions

The ESICM guidelines explicitly identify several areas requiring further research: (1) optimal clearance strategies (diuretic type, dose, administration route, combination regimens); (2) target populations and clearance rates for ultrafiltration/RRT; (3) long-term outcomes (impact on quality of life, cognitive function, physical function); (4) cost-effectiveness analysis, especially mechanical vs pharmacological clearance; and (5) special populations (heart failure, liver failure, trauma, postoperative patients) lacking targeted evidence. Additionally, no consensus exists on stopping criteria or management of hemodynamic fluctuations during clearance. Answering these questions through multidisciplinary collaboration to develop individualized treatment plans may truly reveal the advantages of fluid de-resuscitation.

In summary, the ESICM guidelines provide important evidence-based guidance for fluid de-resuscitation in critically ill patients. The guidelines highlight the complexity and individualized needs of fluid management, emphasizing balance between “resuscitation” and “de-resuscitation.” Future high-quality research, especially in special populations, long-term outcomes, and cost-effectiveness, is needed to further refine clinical practice.

(Tang Bo; Peking Union Medical College Hospital)

References

  1. Ostermann M, Alshamsi F, Raventos AA, et al. European Society of Intensive Care Medicine Clinical Practice Guideline on fluid therapy in adult critically ill patients: Part 3—fluid removal at deescalation phase. Intensive Care Med. 2025;51(10):1749-1763.

  2. Mekontso Dessap A, Cecconi M. Stepwise fluid management in critical illness. Intensive Care Med. 2025. doi:10.1007/s00134-025-08263-8.

  3. Messina A, Bakker J, Chew M, et al. Pathophysiology of fluid administration in critically ill patients. Intensive Care Med Exp. 2022;10(1):46.

  4. Malbrain MLNG, Van Regenmortel N, Saugel B, et al. 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. Ann Intensive Care. 2018;8(1):66.

  5. Ostermann M, Liu K, Kashani K. Fluid management in acute kidney injury. Chest. 2019;152(1):181-189.

  6. Zhang J, Crichton S, Dixon A, et al. Cumulative fluid accumulation is associated with the development of acute kidney injury and non-recovery of renal function: a retrospective analysis. Crit Care. 2019;23(1):392.

  7. Silversides JA, McMullan R, Emerson LM, et al. Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the role of active deresuscitation after resuscitation-2 (RADAR-2) randomised clinical trial. Intensive Care Med. 2022;48(2):190-200.

  8. Ostermann M, Awdishu L, Legrand M. Using diuretic therapy in the critically ill patient. Intensive Care Med. 2024;50(8):1331-1334.

  9. Che ML, Yan YC, Zhang Y, et al. Analysis of drug-induced acute renal failure in Shanghai. Zhonghua Yi Xue Za Zhi. 2009;89(11):744-749.

  10. Rosner MH, Ostermann M, Murugan R, et al. Indications and management of mechanical fluid removal in critical illness. Br J Anaesth. 2014;113(5):764-771.

  11. Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3-4):132-143.

  12. Sansom B, Tonkin-Hill G, Kalfas S, et al. The relationship between commencement of continuous renal replacement therapy and urine output, fluid balance, mean arterial pressure and vasopressor dose. Crit Care Resusc. 2022;24(3):259-267.

  13. Bisht H, Tripathi A, Arya A, et al. Ultrafiltration in heart failure: a review. Cureus. 2023;15(6):e39933.

  14. Malbrain M, Martin G, Ostermann M. Everything you need to know about deresuscitation. Intensive Care Med. 2022;48(12):1781-1786.

  15. White KC, Laupland KB, Ostermann M, et al. Current fluid management practice in critically ill adults on continuous renal replacement therapy: a binational, observational study. Blood Purif. 2024;53(8):624-633.

  16. De Backer D, Ostermann M, Monnet X. The nuts and bolts of fluid de-escalation. Intensive Care Med. 2023;49(9):1120-1122.