fluids

Grand Rounds March 20, 2026: FLUID: A Cross-Over Trial of Hospital Wide Ringer’s Lactate vs Normal Saline (Lauralyn McIntyre, MD, FRCPC, MSc; Monica Taljaard, PhD)

Posted on by Sophia Ramirez

Speakers

Lauralyn McIntyre, MD, FRCPC, MSc
Senior Scientist, Acute Care Research Program
Ottawa Hospital Research Institute
Professor, University of Ottawa

Monica Taljaard, PhD
Senior Scientist
Methodological and Implementation Research
Ottawa Hospital Research Institute
Full Professor, School of Epidemiology and Public Health
University of Ottawa

Keywords

Fluids; Crystalloid fluids; Mortality; Hospital Readmission; Health Systems; Hospitals; Ringer’s Lactate; Saline

Key Points

  • Crystalloid fluids are among the most common interventions administered to patients; they touch nearly every person admitted to the hospital. However, the evidence base to inform their use is limited. Few trials were done until this past decade, and recent trials tend to focus on the critically ill. Though those studies found very small clinical outcome differences between fluids, even a 0.5% reduction in death and hospital readmission translates to 2,500 lives and $5 million saved in Ottawa alone.
  • The study team sought to address this study question at the hospital/health system level by comparing the effects of two usual care fluids, normal saline and Ringer’s Lactate, on the death or readmission of all hospitalized patients. After a pilot trial indicated feasibility, they launched FLUID: a cluster-randomized, cross-over trial across four Ontario hospitals.
  • The FLUID trial found a 0.5% reduction in death in the patients that received Ringer’s Lactate. This is a small but clinically meaningful reduction, with major implications for mortality at the hospital and health care system level. The findings are limited by the study’s early termination due to the COVID-19 pandemic.

Discussion Themes

While there are theoretical benefits to multiple crossovers, including the mitigation of period effects, the logistical burden of restocking an entire hospital’s fluid supply more than once was insurmountable.

The study team used a composite endpoint that gave hospital readmission the same weight as death. McIntyre attributed this decision to the significance of readmission for their patient partners and to its status as an indicator of resource use and subsequent mortality risk.

Trials disrupted by crises such as a pandemic or supply chain issues may be salvaged by Bayesian sequential testing, which allows researchers to assess data continuously without alpha penalties.

FLUID exemplifies the importance of asking simple, high-impact research questions. It was also incredibly cost-effective, costing less than $400,000 (in Canadian dollars) to conduct.

March 18, 2026: A Cross-Over Trial of Ringer’s Lactate vs Normal Saline, in This Week’s Rethinking Clinical Trials Grand Rounds

Posted on by Sophia Ramirez

In this Friday’s Rethinking Clinical Trials Grand Rounds, Lauralyn McIntyre and Monica Taljaard of the University of Ottawa will present “FLUID: A Cross-Over Trial of Hospital Wide Ringer’s Lactate vs Normal Saline.”

The Grand Rounds session will be held on Friday, March 20, 2026, at 1:00 pm eastern.

McIntyre is a senior scientist in the Acute Care Research Program at the Ottawa Hospital Research Institute and a professor at the University of Ottawa. Taljaard is a senior scientist in methodological and implementation research at the Ottawa Hospital Research Institute and a full professor at the University of Ottawa.

Join the online meeting

Add to your calendar:
Google
iCal
Outlook

Or join the Grand Rounds mailing list to receive calendar invitations.

Grand Rounds May 2, 2025: Fluid REStriction in Heart failure versus liberal fluid UPtake: The FRESH-UP Study (Roland RJ van Kimmenade, MD, PhD)

Posted on by Sophia Ramirez

Speaker

Roland RJ van Kimmenade, MD, PhD
Cardiologist, Radboud University Medical Center
Nijmegen, the Netherlands

Keywords

Heart Failure; Fluids; Cardiology

Key Points

  • We are facing a pandemic of heart failure (HF), with an incidence of 1 – 20 cases of heart failure per 1,000 people. The incidence of HF is stable – if not declining – but mortality remains high, at about 15 – 30% after one year. Attributable health care costs are up, and the prevalence of HF in the general population is increasing.
  • Orthopnea and edema are symptoms of heart failure caused by congestion, or “fluid retention.” This has led to an intuitive assumption that patients should monitor their fluid intake to 1.5 – 2L per day (including beverages, ice cream, soup, and some fruit). Patients are advised to do things like chew gum or suck on frozen grapes to relieve dry mouth and thirst.
  • The literature supporting fluid restriction is limited; as of 2018, the studies supporting it had small sample sizes and heterogeneous populations. They found no differences in mortality and hospitalization. Sets of clinical practice guidelines from 2021 and 2022 also noted that more evidence was needed for fluid restriction, and that existing evidence was low quality.
  • To address this gap in the evidence, the research team used crowdfunding to conduct the Fluid REStriction in Heart failure versus liberal fluid Uptake (FRESH-UP) Study. The randomized, open-label, multicenter clinical trial study took place between May 17, 2021 and June 13, 2024.
  • The primary outcome was health status at 3 months, as assessed by the Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS). The key secondary outcome was thirst distress at 3 months, as assessed by the Thirst Distress Scale for patients with HF (TDS-HF).
  • Participants were randomized to one of two arms: liberal fluid intake (no restriction) or fluid restriction, with a maximum of 1500 mL of fluid per day.
  • After three months, the research team found that the difference in KCCQ-OSS (adjusted for baseline scores) was 2.17, with a p value of 0.06. These findings favor liberal fluid intake, but the primary outcome was not met.
  • Thirst distress was higher in the fluid restriction group. No differences were observed for safety events between groups.
  • The FRESH-UP study questions the benefit of fluid restriction in chronic HF.

Discussion Themes

Patient-centered research is key in pragmatic trials; this trial came about because a patient voiced their discomfort and questioned the validity of fluid restriction. The researchers took this as a cue to question a key assumption in their field.

The Dutch Heart Foundation facilitated the crowdfunding, from the legal requirements to the website. The money raised from crowdfunding got them far enough to apply for a second grant.

As in clinical practice, the pragmatic nature of the trial made it difficult to guarantee participant fidelity throughout the entire experiment (though they did monitor intake at week six). The research team conducted a survey of participants afterwards to assess adherence. 93% of the patients reported that they adhered well to their regimes.

“Gaps in Evidence” in clinical guidelines is not a summary of failure, but a source of inspiration!