ArticleCritical care (London, England)2019
Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation.
Article in Critical care (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07715110 (Biological and Immunomodulatory Effect of Hemoadsorption With Macroporous Resin Cartridges in Septic Shock and Refractory Septic Shock Two Parallel Open-label Randomized Pilot Trials.), which is not on this map. Cited by 117 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Biological and Immunomodulatory Effect of Hemoadsorption With Macroporous Resin Cartridges in Septic Shock and Refractory Septic Shock Two Parallel Open-label Randomized Pilot Trials.
Who cites it
117 citing papers in PubMed, 2 syntheses or guidelines pooled it, 207 citations in OpenAlex.
- Resuscitation-associated endotheliopathy (RAsE): a conceptual framework based on a systematic review and meta-analysis.Systematic reviews · 2023Pooled it
- Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis.Critical care (London, England) · 2020Pooled it
- Impact of intraoperative goal-directed therapy on perioperative outcomes in kidney transplantation: a multicenter randomized controlled trial.Internal and emergency medicine · 2026Trial
- Plasma chondroitin sulfate predicts the effectiveness of fluid resuscitation strategies in patients with sepsis.The Journal of clinical investigation · 2026Trial
- The Effects of Conservative Fluid Management and Active Deresuscitation on Markers of Tissue Perfusion, Kidney Injury, and Vascular Injury in Critically Ill Adults: A Secondary Analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) Trial.Critical care explorations · 2026Trial
- Restrictive Versus Standard Intravenous Fluid Therapy and Endothelial Glycocalyx Shedding in ICU Patients With Septic Shock-A Preplanned Sub-Study of the Randomized CLASSIC Trial.Acta anaesthesiologica Scandinavica · 2026Trial
- Endothelial Glycocalyx Degradation in Sepsis: Analysis of the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) Trial, a Multicenter, Phase 3, Randomized Trial.Annals of the American Thoracic Society · 2025Trial
- Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.Indian journal of pediatrics · 2025Trial
- Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients.Scientific reports · 2024Trial
- Bolus intravenous 0.9% saline leads to interstitial permeability pulmonary edema in healthy volunteers.European journal of applied physiology · 2021Trial
- Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.Acta anaesthesiologica Scandinavica · 2021Trial
- Prophylactic Norepinephrine Infusion Reduces Postoperative Complications and Hospitalization Time in Elderly Patients Undergoing Posterior Lumbar Spinal Fusion.BioMed research international · 2021Trial
- Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery.BMC anesthesiology · 2020Trial
- Prehospital plasma is associated with distinct biomarker expression following injury.JCI insight · 2020Trial
- Comparison of Intraoperative Fluid by Goal-Directed and Conventional Fluid Administration in Patients Undergoing Early Decompressive Craniectomy: A Prospective Randomized Controlled Trial.Asian journal of neurosurgery · 2026Article
- Fluids in sepsis.BJA education · 2026Review
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- From fluid responsiveness to fluid effectiveness: an endothelial perspective on fluid therapy in critical illness.Journal of intensive care · 2026Review
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Speed of intravenous fluid on glycocalyx integrity and central blood volume in a porcine septic shock model.Intensive care medicine experimental · 2026Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundIntravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation.
methodsWe used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate.
resultsConsistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113-341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45-79] ng/ml), as well as in a second cohort of sepsis patients (283 [155-584] ng/ml) at emergency department presentation) compared to controls (177 [144-262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment.
conclusionsGlycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.