Crystalloid Fluid Choices for Resuscitation of Hospitalized Patients in Ontario: A Pragmatic Comparative Effectiveness Trial
Quality Improvement & Outcomes
The FLUID pilot trial was an innovative pragmatic cluster randomised cross-over trial, with randomisation done at the hospital level and inclusion of all patients at 4 hospitals in Ontario. The study fluid (normal saline or Ringer’s lactate) was the dominant (at least 80%) fluid stocked throughout the entire hospital to ensure patients received the same study fluid from hospital entry to hospital discharge and the addition of run-outs after study period 1 and 2 served to further reduce the possibility of contamination. ⇒ FLUID relied exclusively on health administrative data for the description of patient baseline characteristics and clinical outcome measures. ⇒ The ability to opt out provided treating physicians with autonomy and ultimately their patient trust and was a key requirement for the use of a waiver of patient informed consent in FLUID. In contrast to trials that have generated evidence in specific populations with fluid interventions limited to geographic locations in the hospital (ICU, ED), the results of FLUID will apply broadly to patients who are admitted throughout the hospital. As such FLUID will provide important evidence-based guidance at the hospital and system level as to what fluid(s) could be predominantly stocked for use throughout the hospital and the associated healthcare resources required for such supply. The pilot trial concluded a larger trial was feasible.The analysis of the large trial data from 7 Ontario hospitals is currently underway.
Background: Normal saline and Ringer’s lactate are the most common fluids administered to hypovolemic and shocked patients. Normal saline may cause hyperchloremic metabolic acidosis and is associated with acute kidney injury and increased death. Ringer’s lactate may cause metabolic alkalosis, hyperkalemia, hyperlactatemia, worse edema, and is more costly. No multi-centre randomized trials comparing the 2 fluids powered for clinically important outcomes have been conducted. Given their extensive use, even small differences in clinical outcomes translate into significant benefits at the population level.
Goals: To conduct a pragmatic, comparative effectiveness randomized controlled trial comparing Ringer’s lactate and normal saline. The primary outcome was a composite of death or re-admission to hospital within 90 days of the index hospitalization. Secondary outcomes include death and re-admission described individually, need for dialysis, re-operation or re-intubation post-operatively, emergency department visits, hospital length of stay, discharge disposition, and a health economic analysis.
Methods: We used an efficient and pragmatic cluster cross-over design at 7 hospitals in Ontario. Hospitals will be randomized to normal saline or Ringers lactate for 3 months, then cross over to the other fluid for the next 3 months after a 1 month washout period. All admitted patients were included under a waiver of informed consent obtained from the research ethics committee; only neonatal patients will be excluded because Ringer’s lactate is not recommended or used in this population. To maximize compliance, the allocated crystalloid study fluid was stocked throughout the hospital (at least 80%) with only small amounts of the other crystalloid fluid made available. Outcome data will be obtained at patient-level through the Institute for Clinical Evaluative Sciences.
Expected Outcomes: Results will have a substantial impact on clinical practice and on the health care system. If one fluid is found to be superior to the other, it will become the dominant fluid stocked in hospitals. In addition to lives saved and hospital admissions avoided, there may be further savings to the health care system through bulk purchasing one type of fluid. We will answer this fundamental fluid therapy question with more efficiency and lower cost compared to an individual patient randomized controlled trial and will build expertise and capacity for future trials of similar design in Ontario and Canada.
Results: Analysis is currently underway
McIntyre L, Taljaard M, McArdle T, etal FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trialBMJ Open 2018;8:e022780. doi: 10.1136/bmjopen-2018-022780 https://bmjopen.bmj.com/content/bmjopen/8/8/e022780.full.pdf
McIntyre LA, Fergusson DA, McArdle T for the Canadian Critical Care Trials Group, et alFLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactateBMJ Open 2023;13:e06