Saline Against Lactated Ringers or Plasmalyte in the Emergency Department (SaLt-ED)

Saline Against Lactated Ringers or Plasmalyte in the Emergency Department (SaLt-ED)

This study will be a cluster-randomized, single-center trial comparing 0.9% saline (normal saline) vs physiologically-balanced crystalloid fluids (Lactated Ringers or Plasmalyte A) for intravenous fluid administration in the emergency department.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Acute Kidney Injury
• Intervention / Treatment: Other: 0.9% Saline; Other: Physiologically-balanced isotonic crystalloid

Detailed Description

The administration of intravenous fluids is ubiquitous in the care of the acutely ill. Commonly available isotonic crystalloid solutions contain a broad spectrum of electrolyte compositions including a range chloride concentrations. Recent studies have associated solutions with supraphysiologic chloride content with hyperchloremia, metabolic acidosis and renal vasoconstriction, acute kidney injury and renal replacement therapy, and increased mortality but no large, randomized-controlled trials have been conducted. SaLt-ED will be a large, cluster-randomized trial enrolling adults requiring intravenous isotonic crystalloid administration and hospital admission from the Vanderbilt University Emergency Department from January 1st 2016 until April 30 2017. The primary endpoint will be hospital-free days to day 28.

• Study Type: Interventional
• Enrollment (Actual): 14000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center Adult Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient in the Vanderbilt Adult Emergency Department
2. Felt by treating clinician to require intravenous isotonic crystalloid
3. Felt by treating clinician to require inpatient hospital admission

Exclusion Criteria:

1. Age < 18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.9% Saline; Patients in a month randomized to physiologically-balanced isotonic fluid will receive 0.9% Saline whenever isotonic intravenous fluid administration is ordered by the treating provider.	Other: 0.9% Saline; 0.9% Saline will be used whenever an isotonic crystalloid is ordered; Other Names: Normal saline; 0.9% sodium chloride
Active Comparator: Physiologically-balanced; Patients in a month randomized to physiologically-balanced isotonic fluid will receive physiologically-balanced isotonic crystalloid (Plasma-Lyte© A or Lactated Ringer's) whenever isotonic intravenous fluid administration is ordered by the treating provider.	Other: Physiologically-balanced isotonic crystalloid; Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered; Other Names: Lactated Ringers; Ringer's Lactate; Plasma-Lyte© A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital-free days to day 28	The number of days alive and free of hospitalization in the first 28 days after study enrollment. Patients alive at the time of discharge will be presumed to be alive at 28 days. A patient who dies before hospital discharge will receive zero hospital-free days. A patient who remains in the hospital 28 days after enrollment will receive zero hospital-free days.	28 days after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage II or greater KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES (KDIGO) Acute Kidney Injury	Proportion of patients with Stage II or greater acute kidney injury by KDIGO creatinine criteria (defined as rise in serum creatinine level of at least 2-fold, a serum creatinine level greater than or equal to 4.0 mg/dL with an acute increase of at least 0.5 mg/dL, or initiation of new renal replacement therapy).	30 days after enrollment censored at hospital discharge
Major adverse kidney event by hospital discharge or day 30 (MAKE30)	At least one of: death, new renal replacement therapy, or persistent renal dysfunction at the time of hospital discharge (serum creatinine level ≥ 200% of baseline). Patients discharged prior to day 30 will be assumed not to develop this outcome between hospital discharge and day 30.	30 days after enrollment
In-Hospital Mortality	Death before hospital discharge	30 days or hospital discharge, whichever occurs first
Hospital length of stay	Duration of hospitalization	Hospital length of stay assessed 90 days after enrollment
ICU-free days to day 28	Days alive and free of the intensive care unit in the first 28 days. Patients discharged prior to day 28 will be assumed to not have ICU days between discharge and day 28.	28 days
Ventilator-free days to day 28	Days alive and free of mechanical ventilation in the first 28 days. Patients discharged prior to day 28 will be assumed to not have any ventilator days between discharge and day 28.	28 days
Vasopressor-free days	Days alive and free of vasopressor receipt in the first 28 days. Patients discharged prior to day 28 will be assumed to not have vasopressor days between discharge and day 28.	28 days
Receipt of new renal replacement therapy	Receipt of any form of renal replacement therapy in the first 30 days after enrollment in a patient who had not received renal replacement therapy prior to enrollment	30 days after enrollment or hospital discharge, whichever occurs first
Duration of new renal replacement therapy	Duration of renal replacement therapy in the first 30 days after enrollment in a patient who had not received renal replacement therapy prior to enrollment	30 days after enrollment
Peak creatinine	Highest creatinine in the 28 days after enrollment or hospital discharge, whichever occurs first	28 days after enrollment or hospital discharge, whichever occurs first
Change from baseline to peak creatinine	Change from baseline creatinine at enrollment to the highest creatinine before death or hospital discharge in the first 28 days	28 days after enrollment or hospital discharge, whichever occurs first
Incidence of metabolic acidosis and alkalosis	Incidence of metabolic acidosis and alkalosis in the first 30 days after enrollment as defined by bicarbonate values outside of the laboratory normal range.	30 days after enrollment or hospital discharge, whichever occurs first
Incidence of hyperchloremia and hypochloremia	Incidence of hyperchloremia and hypochloremia in the first 30 days after enrollment as defined by serum chloride values outside of the laboratory normal range.	30 days after enrollment or hospital discharge, whichever occurs first

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Wesley Self, MD MPH, Vanderbilt University

Publications and helpful links

General Publications

• Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J; SAFE TRIPS Investigators. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care. 2010;14(5):R185. doi: 10.1186/cc9293. Epub 2010 Oct 15.
• Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17;308(15):1566-72. doi: 10.1001/jama.2012.13356.
• Young P, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, McGuinness S, Mehrtens J, Myburgh J, Psirides A, Reddy S, Bellomo R; SPLIT Investigators; ANZICS CTG. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA. 2015 Oct 27;314(16):1701-10. doi: 10.1001/jama.2015.12334. Erratum In: JAMA. 2015 Dec 15;314(23):2570.
• Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, Coston TD, Felbinger M, Flemmons LN, Hellervik SM, Lindsell CJ, Liu D, McCoin NS, Niswender KD, Slovis CM, Stollings JL, Wang L, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open. 2020 Nov 2;3(11):e2024596. doi: 10.1001/jamanetworkopen.2020.24596.
• Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586. Epub 2018 Feb 27.
• Self WH, Semler MW, Wanderer JP, Ehrenfeld JM, Byrne DW, Wang L, Atchison L, Felbinger M, Jones ID, Russ S, Shaw AD, Bernard GR, Rice TW. Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017 Apr 13;18(1):178. doi: 10.1186/s13063-017-1923-6.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: November 18, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 15, 2017
• Last Update Submitted That Met QC Criteria: September 14, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: acute kidney injury; crystalloid
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Emergencies; Critical Illness; Acute Kidney Injury; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: 151769