Evidence map›Paper›PMID 41321198›Full record

Trial reportActa anaesthesiologica Scandinavica2026

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.

Jens Christensen, Praleene Sivapalan, Tine Sylvest Meyhoff, Hans Järnbert-Pettersson, Anders Perner, Morten Hylander Møller, Theis Lange, Peter Buhl Hjortrup, Eva Joelsson-Alm, Sandra Jonmarker and 4 more

Registry-linked trialAbstract readRandomized Controlled TrialComparative Study
In one paragraph

Trial report in Acta anaesthesiologica Scandinavica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04282252 (The Effect of Restrictive Fluid Management on Cardiac Function and Glycocalyx Degradation, a Preplanned Substudy of the CLASSIC Trial), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT04282252 phase4completednot on this map

The Effect of Restrictive Fluid Management on Cardiac Function and Glycocalyx Degradation, a Preplanned Substudy of the CLASSIC Trial

TypeinterventionalSponsorKarolinska InstitutetRan2020 to 2022Enrolled54ConditionsSeptic ShockArmsI.V. SOLUTIONS
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jens ChristensenDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-4459-8011
Praleene SivapalanCopenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-0442-0032
Tine Sylvest MeyhoffCopenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-1840-1596
Hans Järnbert-PetterssonDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Anders PernerCopenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Morten Hylander MøllerCopenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-6378-9673
Theis LangeUniversity of Copenhagen, Section of Biostatistics, Copenhagen, Denmark.ORCID 0000-0001-6807-8347
Peter Buhl HjortrupCopenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Eva Joelsson-AlmDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-9041-2468
Sandra JonmarkerDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5836-8594
Fredric SjöbergDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Johan MårtenssonDepartment of Physiology and Pharmacology, Section of Anaesthesia and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
Anna Håkansson GladhDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Maria CronhjortDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-0444-8553

Funding

Region Stockholm RS 2021-0933Svenska Läkaresällskapet SLS-934824
6 · The paper itself

Abstract

Shedding of the endothelial glycocalyx may be a pathophysiological mechanism in septic shock, to which intravenous (IV) fluid therapy may contribute. We aimed to investigate the effects of restrictive versus standard IV fluid therapy on glycocalyx shedding in adult intensive care unit (ICU) patients with septic shock. In this preplanned sub-study of the CLASSIC trial, ICU patients with septic shock were randomized to restrictive or standard IV fluid therapy at one Danish and one Swedish ICU between February 2020 and October 2021. Plasma markers of glycocalyx shedding were measured at four timepoints: within the first hour after randomization (T0), the following morning (T1), the morning after (T2), at ICU discharge or up to 90 days after randomization (T3). The primary outcome was the change in plasma hyaluronan levels from T0 to T1. A total of 54 patients were included, below the planned sample size of 200, leading to important differences between groups. Mean hyaluronan levels decreased by 11 ng/mL (95% CI 35-41) more in the restrictive group compared to the standard group from T0 to T1. The interaction effect between group and time was non-significant (p value: 0.872). In this underpowered sub-study we found no statistically significant difference in endothelial glycocalyx shedding between adult ICU patients with septic shock randomized to restrictive versus standard IV fluid therapy. We consider these findings hypothesis-generating; further research is needed to confirm these results. EDITORIAL COMMENT: In this substudy of the CLASSIC trial, glycocalyx degredation products and related substances were measured serially in sepsic study participants randomized to restrictive or usual fluid treatment protocols. No differences between treatment glycocalyx degredation product and related substance levels were observed. Trial Registration: ClinicalTrials.gov identifier: NCT04282252.

Indexed as

Fluid TherapyGlycocalyxShock, SepticAgedFemaleHumansHyaluronic AcidIntensive Care UnitsMaleMiddle AgedHyaluronic Acid

Identifiers

PMID41321198
PMCPMC12666609

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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.