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Cited by 45Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyHyperglycemia and glycemic control in critically ill and hospitalized patients

Lower vs Higher Fluid Volumes in Adult Patients With Sepsis

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Sivapalan, Praleene, Ellekjaer, Karen L., Jessen, Marie K., Meyhoff, Tine S., Cronhjort, Maria, Hjortrup, Peter B., Wetterslev, Jørn, Granholm, Anders +2 more·2023·CHEST
DOI 10.1016/j.chest.2023.04.036PMC PMC10567931
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Abstract

BACKGROUND: IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists. RESEARCH QUESTION: Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis? STUDY DESIGN AND METHODS: We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available. RESULTS: We included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of serious adverse events showed a relative risk of 0.95 (97% CI, 0.83-1.07; low certainty evidence). Health-related quality of life was not reported. INTERPRETATION: Among adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on health-related quality of life. TRIAL REGISTRATION: PROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.

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  • Systematic reviews and meta-analyses found no evidence that fluid restriction or fluid de-resuscitation is superior to higher fluid volumes for mortality in septic shock.

    “Systematic reviews and meta-analyses additionally found no evidence that fluid restriction or fluid de-resuscitation is superior to higher fluid volumes for mortality in septic shock, underscoring uncertainty about optimal cumulative fluid balance strategies [24,25,26].”

    From Artificial Intelligence to Facilitate SEP-1 Measure Compliance and Fluid Management in Sepsis (2026) · cites this paper as [25]

    The Results > Primary Outcomes (page not specified) report no significant mortality advantage for lower versus higher IV fluid volumes, and the Discussion > Strengths and Limitations says the septic-shock subgroup was consistent with the primary analysis. However, the review covers adults with sepsis as well as septic shock and does not establish a separate mortality finding for fluid de-resuscitation in septic shock. (LLM, conf=0.84)

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Authors
Sivapalan, P., Ellekjaer, K. L., Jessen, M. K., Meyhoff, T. S., Cronhjort, M., Hjortrup, P. B., Wetterslev, J., Granholm, A., Møller, M. H., & Perner, A.
Affiliations
  • Copenhagen University Hospital (DK)
  • Aarhus University (DK)
  • Karolinska Institutet (SE)
  • University of Copenhagen (DK)
Corresponding author
Sivapalan, Praleene
ORCID
Venue
CHEST
Publisher
Elsevier BV
Published
2023-10
Volume
164
Issue
4
Pages
892-912
ISSN
0012-3692 (ISSN-L)
DOI
10.1016/j.chest.2023.04.036
PMC
PMC10567931
OpenAlex
W4367693613
Cited by
45
References
7
Citations by year
2026: 5 · 2025: 13 · 2024: 20 · 2023: 7
FWCI
1.76
Type
journal article
Language
en
Open access
Licence
Locations
  • CHEST Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
Funders
  • Pfizer
  • Aarhus Universitet
  • Aarhus Universitetshospital
  • Karolinska Institutet
  • Novo Nordisk
  • Rigshospitalet
  • Novo Nordisk Fonden (NNF17OC0028608)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
sepsis, intravenous fluid volume, fluid management, all-cause mortality, serious adverse events, health-related quality of life, adults, trial sequential analysis
MeSH terms
Adult, Fluid Therapy, Humans, Quality of Life, Sepsis

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