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Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial

Abstract

Purpose

Recent evidence questions a liberal approach to fluid resuscitation in intensive care unit (ICU) patients. Here, we assess whether use of hypertonic saline applied as single infusion at ICU admission after cardiac surgery can reduce cumulative perioperative fluid volume.

Methods

Prospective randomized double-blind single-center clinical trial investigates effects of a single infusion of hypertonic saline (HS) versus normal saline (comparator). Primary endpoint was the cumulative amount of fluid administered in patients in the hypertonic saline versus the 0.9% saline groups (during ICU stay). Upon ICU admission, patients received a single infusion of 5 ml/kg body weight of 7.3% NaCl (or 0.9% NaCl) over 60 min. Patients undergoing cardiac surgery for elective valvular and/or coronary heart disease were included. Patients with advanced organ dysfunction, infection, and/or patients on chronic steroid medication were excluded.

Results

A total of 101 patients were randomized to receive the study intervention (HS n = 53, NS n = 48). Cumulative fluid intake on the ICU (primary endpoint) did not differ between the HS and the NS groups [median 3193 ml (IQR 2052–4333 ml) vs. 3345 ml (IQR 2332–5043 ml)]. Postoperative urinary output until ICU discharge was increased in HS-treated patients [median 2250 ml (IQR 1640–2690 ml) vs. 1545 ml (IQR 1087–1976 ml)], and ICU fluid balance was lower in the HS group when compared to the NS group [296 ml (IQR − 441 to 1412 ml) vs. 1137 ml (IQR 322–2660 ml)].

Conclusion

In a monocentric prospective double-blind randomized clinical trial, we observed that hypertonic saline did not reduce the total fluid volume administered on the ICU in critically ill cardiac surgery patients. Hypertonic saline infusion was associated with timely increase in urinary output. Variations in electrolyte and acid–base homeostasis were transient, but substantial in all patients.

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Acknowledgements

This study was conducted with the assistance of the professional research nurse team of the Department of Intensive Care, Bern University Hospital (responsible trial research nurse: David Zacharias). Further, Drs. M. Luedi, G. Erdoes from the Department of Anaesthesiology, Bern University, and Dr. D. Reineke from the Department of Cardiovascular Surgery, Bern University hospital, supported the conduct of this trial at their respective departments.

Funding

This study was supported by the Swiss Heart Foundation, the Novartis Foundation for Biomedical research, the B.Braun Foundation as well as the Scherbarth Foundation. The money received for this trial by the B. Braun Foundation was awarded as part of a research support program (https://www.bbraun-stiftung.de/de/foerderungen/wissenschaft-und-forschung.html). Money was granted after an independent external peer-review process. B.Braun was neither involved in the study design, conduction, analysis or interpretation of the results. The study medication was purchased from Bichsel pharmacy (Interlaken, Switzerland).

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Authors and Affiliations

Authors

Contributions

CAP designed the trial, conducted the trial, supervised the trial, wrote the first draft, and revised the manuscript; MK performed data assessment, wrote the first draft, and revised the manuscript; NVS performed data clearing and evaluation and revised the manuscript; ASM performed study assessments and revised the manuscript; BH performed study assessments and revised the manuscript; LJ performed study assessments and revised the manuscript; SW performed study assessments and revised the manuscript; JW performed study assessments and revised the manuscript; PZ performed study assessments and revised the manuscript; FS performed study assessments and revised the manuscript; SMJ designed the trial and revised the manuscript; LE designed the trial, supervised the trial, and revised the manuscript; JCS designed the trial, supervised the trial, and revised the manuscript.

Corresponding author

Correspondence to Carmen A. Pfortmueller.

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Conflicts of interest

CAP, MK, NVS, ASM, BH, LJ, SW, JW, PZ, FS, SMJ, and JCS report Grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Dräger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Phagenesis Ltd, and Nycomed outside the submitted work. The money was paid into departmental funds; no personal financial gain applied. Lars Englberger has no conflict of interest to disclose.

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Pfortmueller, C.A., Kindler, M., Schenk, N. et al. Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial. Intensive Care Med 46, 1683–1695 (2020). https://doi.org/10.1007/s00134-020-06132-0

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Keywords

  • Fluid therapy
  • Hypertonic saline
  • Fluid overload
  • Crystalloid solutions
  • Cardiac surgical procedures
  • Hemodynamics
  • Critical illness
  • Perioperative period