Clinician Article

Lower vs Higher Fluid Volumes During Initial Management of Sepsis: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.

  • Meyhoff TS
  • Moller MH
  • Hjortrup PB
  • Cronhjort M
  • Perner A
  • Wetterslev J
Chest. 2020 Jun;157(6):1478-1496. doi: 10.1016/j.chest.2019.11.050. Epub 2020 Jan 23. (Review)
PMID: 31982391
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  • Emergency Medicine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Infectious Disease
    Relevance - 6/7
    Newsworthiness - 6/7
  • Intensivist/Critical Care
    Relevance - 6/7
    Newsworthiness - 6/7
  • Hospital Doctor/Hospitalists
    Relevance - 5/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 5/7


OBJECTIVE: IV fluids are recommended during the initial management of sepsis, but the quality of evidence is low, and clinical equipoise exists. We aimed to assess patient-important benefits and harms of lower vs higher fluid volumes in adult patients with sepsis.

METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized clinical trials of IV fluid volume separation in adult patients with sepsis. We adhered to our published protocol; the Cochrane handbook; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and the Grading of Recommendations Assessment, Development and Evaluation statements. The primary outcomes were all-cause mortality, serious adverse events (SAEs), and quality of life.

RESULTS: We included nine trials (n = 637); all were published after 2015 and had an overall high risk of bias. We found no statistically significant difference between lower vs higher fluid volumes in all-cause mortality (relative risk [RR], 0.87; 95% CI, 0.69-1.10; I2 = 0%; TSA-adjusted CI, 0.34-2.22) or SAEs (RR, 0.91; 95% CI, 0.78-1.05; I2 = 0%; TSA-adjusted CI, 0.68-1.21). No trials reported on quality of life. We did not find differences in the secondary or exploratory outcomes. The quality of evidence was very low across all outcomes.

CONCLUSIONS: In this systematic review, we found very low quantity and quality of evidence supporting the decision on the volumes of IV fluid therapy in adults with sepsis.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03668236; URL: www.clinicaltrials.gov.

Clinical Comments

Emergency Medicine

Unfortunately, this systematic review does little to answer the question of how we should manage fluid resuscitation in septic patients. The review is well done, but the existing evidence is not sufficient to guide these decisions.

Emergency Medicine

There is interesting information regarding fluids in sepsis, in order to avoid overload.

Infectious Disease

Though with high bias and lower quality level of evidence, the current meta analysis explores if there is any difference in high vs low volume early resuscitation in sepsis. Low vs high classification is variable across the studies and hence further weakens the overall conclusions. Regardless, the results can be used in a limited way to not force excessive volume in patients with sepsis.

Infectious Disease

This mta-analysis of this database of RCTs examining total IV crystalloid resuscitation volume in septic shock was inadequate to address the question because both treatment groups appear to have received a similar early (1st 24 h) volume and total volume separation was not achieved or only achieved after 24 h. However, Meyhof and investigators of the RCTs may have missed the point: Rivers (N Engl J Med 2001) and a meta-analysis of Rivers' and 8 additional similar RCTs (Jones, Crit Care Med 2008) examining early hemodynamically-driven (first 24 h) IV fluid resuscitation of septic shock found a robust survival advantage with larger (delta ~1 L) early resuscitation volume (OR 0.50, 0.37-0.69), with similar 3-day total volume. Meyhof's et al result reaffirms that the early resuscitation is critical and if achieved, fluid support beyond the first 24 h has little impact unless the patient receives excessive fluid and becomes overloaded, which will increase mortality (Boyd, Crit Care Med 2011).

Infectious Disease

Methods employed were very well done.

Intensivist/Critical Care

Interesting! I thought fluid resuscitation was relatively certain, it's in our guidelines.....

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