ArticleAmerican journal of respiratory and critical care medicine2018
Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 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
- 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
- Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients.Scientific reports · 2024Trial
- Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial.Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 2022Trial
- Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock.The western journal of emergency medicine · 2021Trial
- Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis.Critical care (London, England) · 2020Trial
- Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial.The Lancet. Respiratory medicine · 2019Trial
- Gastroenteritis aggressive versus slow treatment for rehydration (GASTRO): a phase II rehydration trial for severe dehydration: WHO plan C versus slow rehydration.BMC medicine · 2019Trial
- Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial.Intensive care medicine · 2018Trial
- Advancing Microcirculatory Therapies in Pediatric Sepsis: Current Opportunities and Future Directions.Journal of intensive care medicine · 2026Review
- Fluids in sepsis.BJA education · 2026Review
- Article
- Animal models of critical illness in the Asia-Pacific region: current practices, shared challenges, and future directions.Intensive care medicine experimental · 2026Review
- Optimal time and volume of fluid resuscitation in patients with sepsis: a nationwide multicenter cohort study.Scientific reports · 2025Article
- Storage duration of packed red blood cells transfused during veno-venous extracorporeal membrane oxygenation is associated with elevated pulmonary artery pressure and lung injury in a sheep model.Critical care (London, England) · 2025Article
- Impact of Venous CONgestion on Organ Function and Outcomes in Sepsis (ICON-Sepsis): a prospective observational cohort study protocol.BMJ open · 2025Article
- Serum hyaluronic acid in critically ill dogs and influence of intravenous fluid therapy.PloS one · 2025Article
- An ovine septic shock model of live bacterial infusion.Intensive care medicine experimental · 2024Article
- Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines.Annals of intensive care · 2024Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
rationaleFluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.
objectivesIn this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.
methodsEndotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. MEASUREMENTS AND MAIN
resultsAfter resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02).
conclusionsFluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.
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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.