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Mortality benefit of crystalloids administered in 1–6 hours in septic adults in the ED: systematic review with narrative synthesis
  1. Gabor Zoltan Xantus1,
  2. Penny Allen2,
  3. Sharon Norman1,
  4. Peter Laszlo Kanizsai3
  1. 1 School of Medicine, Cardiff University, Cardiff, UK
  2. 2 School of Medicine, Rural Clinical School University Tasmania, Launceston, Tasmania, Australia
  3. 3 Department of Emergency Medicine, University of Pecs, Pécs, Baranya, Hungary
  1. Correspondence to Gabor Zoltan Xantus, Cardiff University, Cardiff CF10 3AT, UK; gabor.xantus{at}


Background Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the ‘Sepsis-6 bundle’ within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings.

Method A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1–6 hours.

Results Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23–43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects.

Conclusion This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.

  • clincial management
  • acute care
  • death/mortality

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Handling editor Simon Carley

  • Contributors GZX incepted the idea, registered the study at PROSPERO, searched the relevant databases and wrote the first drafts and submitted the article. GZX and PA assessed the final articles using the relevant Critical Appraisal Skills Program tool and assessed for risk of bias with the Newcastle-Ottawa Tool for cohort studies and the Cochrane Bias Assessment for RCTs. PLK resolved dispute between GX and PA during critical appraisal and reviewed edited the final draft. SN reviewed the search and keyword selection, appraised the evidence and edited/reviewed the work in progress submission.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.