Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial

Abstract

BackgroundPrior studies in critically ill patients suggest the supra-physiologic chloride concentration of 0.9% (“normal”) saline may be associated with higher risk of renal failure and death compared to physiologically balanced crystalloids. However, the comparative effects of 0.9% saline and balanced fluids are largely unexamined among patients outside the intensive care unit, who represent the vast majority of patients treated with intravenous fluids.Methods/designThis study, entitled Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department (SALT-ED), is a pragmatic, cluster, multiple-crossover trial at a single institution evaluating clinical outcomes of adults treated with 0.9% saline versus balanced crystalloids for intravenous fluid resuscitation in the emergency department. All adults treated in the study emergency department receiving at least 500 mL of isotonic crystalloid solution during usual clinical care and subsequently hospitalized outside the intensive care unit are included. Treatment allocation of 0.9% saline versus balanced crystalloids is assigned by calendar month, with study patients treated during the same month assigned to the same fluid type. The first month (January 2016) was randomly assigned to balanced crystalloids, with each subsequent month alternating between 0.9% saline and balanced crystalloids. For balanced crystalloid treatment, clinicians can choose either Lactated Ringer’s or Plasma-Lyte A©. The study period is set at 16 months, which will result in an anticipated estimated sample size of 15,000 patients. The primary outcome is hospital-free days to day 28, defined as the number of days alive and out of the hospital from the index emergency department visit until 28 days later. Major secondary outcomes include proportion of patients who develop acute kidney injury by creatinine measurements; major adverse kidney events by hospital discharge or day 30 (MAKE30), which is a composite outcome of death, new renal replacement therapy, and persistent creatinine elevation >200% of baseline; and in-hospital mortality.DiscussionThis ongoing pragmatic trial will provide the most comprehensive evaluation to date of clinical outcomes associated with 0.9% saline compared to physiologically balanced fluids in patients outside the intensive care unit.Trial registrationClinicalTrials.gov, NCT02614040. Registered on 18 November 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1923-6) contains supplementary material, which is available to authorized users.

Balanced Crystalloids versus Saline in Critically Ill Adults

“…15 The need for access to an intravenous crystalloid at all times precluded the use of washout periods, and patients who remained in the ICU from the end of one calendar month to the start of another may have been exposed to both types of crystalloid. The effect of dual exposure was evaluated in prespecified sensitivity analyses.…”

Balanced Crystalloids versus Saline in Noncritically Ill Adults

“…The rationale, design, and statistical analysis plan were prespecified and have been published. 20 The protocol is also available with the full text of this article at NEJM.org. The institutional review board at Vanderbilt University approved the trial with waiver of informed consent.…”

“…The trial was monitored by an independent data and safety monitoring board. 20 The first and fourth authors vouch for the completeness and accuracy of the data and analyses.…”

“…20 In brief, the type of isotonic crystalloid was assigned according to calendar month, with all patients in the trial emergency department during the same month assigned to the same fluid, either balanced crystalloids or saline. During balanced-crystalloids months, clinicians had the option of choosing either lactated Ringer’s solution or Plasma-Lyte A. Clinicians and patients were aware of the treatment assignments.…”

“…20 Relative contraindications to the use of balanced crystalloids included hyperkalemia and brain injury; the severity of hyperkalemia and brain injury at which saline was used instead of balanced crystalloids was determined by the treating provider. There were no relative contraindications listed for saline in the electronic advisor.…”