Saline Against Lactated Ringers or Plasmalyte in the Emergency Department

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Critical Illness, Acute Kidney Injury

Intervention / Treatment
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* Other: 0.9% Saline
* Other: Physiologically-balanced isotonic crystalloid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient in the Vanderbilt Adult Emergency Department Felt by treating clinician to require intravenous isotonic crystalloid Felt by treating clinician to require inpatient hospital admission Exclusion Criteria: 1. Age < 18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.9% Saline<br>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<br>* 0.9% Saline will be used whenever an isotonic crystalloid is ordered<br>* Other names: 0.9% sodium chloride;|
| Active Comparator: Physiologically-balanced<br>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<br>* Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered<br>* Other names: Plasma-Lyte© A;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crystalloid, acute kidney injury