Crystalloid FLUID Choices for Resuscitation of Hospital Patients
Condition: Fluid Therapy
Study type: Interventional

Summary: 
      Salt fluids are used extensively for acutely ill patients who are admitted to hospital. Two
      salt fluids commonly used are Normal Saline and Ringer's Lactate. Both are used to rehydrate
      patients, restore fluid volume and help stabilize blood pressure and failing organs. Both
      salt fluids have been used for several decades. Until recently, it was thought the fluids are
      essentially equivalent other than some minor differences related to the concentration of salt
      components (sodium and chloride) and buffers (Ringer's Lactate has lactate as a buffer).
      Recent data suggest that salt fluids containing less chloride like the Ringer's Lactate,
      cause less acid in the blood, less kidney failure, and less death. However, the studies to
      date are small and weak in their design and it is possible that there are no important
      differences that affect patients. Hence, the research team will conduct a robust pragmatic
      clinical trial where several academic and community hospitals will be randomized to use
      either Ringer's Lactate only or Normal Saline only for a period of three months. The trial
      will yield high quality and robust data to determine if Ringers Lactate reduces death and
      re-admissions to hospital. Before embarking on this large-scale trial, it is important to
      conduct a smaller (pilot) trial to evaluate if the larger trial will be feasible and not too
      costly. In this small trial involving no less than 4 hospitals, the investigators will
      determine how well the fluid interventions are adhered to in each hospital, record how long
      it takes to receive approval from research ethics boards and be ready to start the study. The
      investigators will also record challenges and develop solutions related to the operations of
      the trial, and describe important clinical and outcome data essential for the design and
      planning of the large trial.
    

Detailed description: 
      Other than the administration of oxygen, crystalloid resuscitation fluids are the most common
      intervention administered to the majority of hospitalized patients. These fluids may be used
      as a life saving measure to re-establish hemodynamic stability, for rehydration, and to
      replace losses and maintain intravascular volume in the surgical setting. In the province of
      Ontario alone, approximately 1 million patients per year will receive one or both of these
      resuscitation fluids during their hospital admission. The two most common usual care
      resuscitation crystalloid fluids are Normal Saline and Ringer's Lactate and until recently
      there was no evidence to suggest that one crystalloid fluid was clinically superior to the
      other. However, the safety of Normal Saline is now being questioned due to its high chloride
      content and its association with the development of hyperchloremic metabolic acidosis.
      Studies in healthy volunteers and observational studies in the critically ill and surgical
      patient populations have associated saline with an increased risk of acute renal injury and
      requirement for dialysis, post-operative infections, death and increased resource and blood
      transfusion use. The evidence base is currently weak given that the majority of studies are
      observational and suffer from methodological weaknesses including confounding by indication,
      selection bias, and inability to disentangle the effects of a specific fluid due to
      interaction of co-interventions administered. As such, several authors and editorials have
      called for adequately powered randomized controlled trials with clinically relevant outcomes
      to determine if Ringer's Lactate is indeed superior to Normal Saline for resuscitation.

      Given their widespread use, small differences in clinical outcomes between crystalloid
      resuscitation fluids are highly relevant. Furthermore, small absolute differences in
      important clinical outcomes translate into significant savings to hospitals and the health
      care system. To illustrate, if death and hospital re-admissions were each reduced by an
      absolute 0.5%, this would translate to approximately 2500 lives saved and savings of 10
      million dollars to the Ontario health care system. Hence, in collaboration with the Canadian
      Critical Care Trials Group, the Crystalloid FLUID Choices for Hospitalized Patients (FLUID)
      trial will examine whether Ringer's Lactate as compared to Normal Saline reduces clinically
      important outcomes such as death, and hospital re-admissions - outcomes that are particularly
      relevant to hospitals and the health care system. This proposal is a large pragmatic cluster
      cross-over comparative effectiveness trial that will be conducted in both academic and
      community centres in Ontario. It will involve waivers of consent and a novel design making
      use of provincially available health administrative data through the Institute of Clinical
      Evaluative Sciences (ICES) to facilitate all data collected in the trial. The trial will
      answer this fundamental fluid resuscitation question with much less cost in comparison to an
      individual patient randomized controlled trial. It will help build expertise and capacity for
      future trials of similar design in the province of Ontario and throughout Canada. However,
      prior to embarking on a large-scale trial, it is imperative to conduct a pilot trial to
      determine feasibility and optimize the trial design.
    

Intervention name(s): Ringer's Lactate; Normal Saline
Intervention type(s): Other; Other
Intervention description(s): After a 1 week run in half of participating hospitals will be crossed over to using Ringer's Lactate as 500 or 1000 ml boluses or infusions as specified by the treating physicians for the second 90-day test period.; After a 1 week run in half of participating hospitals will be crossed over to using Normal Saline as 500 or 1000 ml boluses or infusions as specified by the treating physicians for the final 90-day test period.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Ringer's Lactate; Normal Saline; resuscitation fluids; hypovolemia