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Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial

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A Correction to this article was published on 12 December 2023

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Abstract

Purpose

Fluid use could modulate the effect of balanced solutions (BS) on outcome of intensive care unit (ICU) patients. It is uncertain whether fluid use practices are driven more by patient features or local practices. It is also unclear whether a “dose–response” for the potential benefits of balanced solutions exists.

Methods

The secondary analysis of the Balanced Solution in Intensive Care Study (BaSICS) compared 0.9% saline versus Plasma-Lyte 148® (BS) for fluid therapy in the ICU. The relative contribution of patient features and enrolling site (the random effect) on the volume of fluid used up to day 3 after admission was assessed using different methods, including a Bayesian regression, a frequentist mixed model, and a random forest, all adjusted for relevant patient confounders. Subsequently, a variety of methods were used to assess whether volume of fluid used modulated the effect of BS on 90-day mortality, including a traditional subgroup analysis for patients that remained alive and in the ICU up to 3 days, a Bayesian network accounting for competing risks, and an analysis based on site practices.

Results

10,505 patients were analyzed. Median fluid use in the BS arm and in the 0.9% saline arm were 2500 mL and 2488 mL, respectively. The random effect in the Bayesian regression explained 0.32 (95% credible intervals (CrI) 0.24–0.41) of all model variance (0.33, 95% credible intervals from 0.32–0.35). Frequentist and random forest models produced similar results. In the analysis including only patients alive and in the ICU at 3 days, there was a strong suggestion of interaction between fluid use and the effect of BS, driven mostly by a lower mortality with BS compared to 0.9% saline as fluid use increased for patients with sepsis. These results were consistent in the Bayesian network analysis and in an analysis based on site practices, where septic patients enrolled to BS at high fluid use sites had a lower mortality (absolute risk reduction of − 0.13 [95% credible interval − 0.27 to − 0.01]; 0.98 probability of benefit).

Conclusion

Baseline patient characteristics collected in the BaSICS trial explain less of the variance of fluid use during the first 3 days than the enrolling site. Volume of fluid used and the effects of BS appear to interact, mostly in the sepsis subgroup where there was a strong association between fluid use after enrollment and the effect of BS on 90-day mortality.

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Data availability

Anonymized data is available upon reasonable request with a simplified statistical plan. Approval from Brazilian regulatory agencies will be necessary.

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Funding

BaSICS was funded by the Brazilian Ministry of Health through the Programa de Desenvolvimento Institucional do SUS – PROADI-SUS. Fluids and logistics were provided by Baxter Hospitalar® (Brazil). This secondary analysis did not receive specific funding.

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Authors and Affiliations

  1. Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, AB, Canada

    Fernando G. Zampieri & Sean M. Bagshaw

  2. HCor Research Institute, São Paulo, Brazil

    Fernando G. Zampieri, Lucas P. Damiani & Alexandre B. Cavalcanti

  3. Intensive Care Department, Hospital São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 04024900, Brazil

    Flavia R. Machado

  4. BP – A Beneficiencia Portuguesa de Sao Paulo, São Paulo, Brazil

    Viviane C. Veiga

  5. Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Luciano C. P. Azevedo

Authors
  1. Fernando G. Zampieri
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  2. Flavia R. Machado
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  3. Viviane C. Veiga
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  4. Luciano C. P. Azevedo
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  5. Sean M. Bagshaw
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  6. Lucas P. Damiani
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  7. Alexandre B. Cavalcanti
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Contributions

Conception and design: FGZ, ABC, VCV, LPD, LCPA, SMB, FRM. Analysis: FGZ, LPD. First manuscript draft: FGZ, ABC, LPD. Review for intellectual relevant content: VCV, LCPA, SMB, FRM. Approval: all authors.

Corresponding author

Correspondence to Fernando G. Zampieri.

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Conflicts of interest

FGZ and FRM received honoraria for board consulting from Baxter®. SMB received consulting fees from Baxter, BioPorto, Novartis, Sea Star Medical, and bioMerieux. LCPA received honoraria for lectures from Baxter®. All the other authors report no conflicts of interest.

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Zampieri, F.G., Machado, F.R., Veiga, V.C. et al. Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial. Intensive Care Med 50, 79–89 (2024). https://doi.org/10.1007/s00134-023-07264-9

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