Isotonic Solution Administration Logistical Testing (SALT)

Isotonic Solution Administration Logistical Testing: Pilot Study for the Isotonic Solutions and Major Adverse Renal Events Trial

The administration of intravenous crystalloids is ubiquitous in the care of the critically ill. Commonly available crystalloid solutions contain a broad spectrum of electrolyte compositions including a range of chloride concentrations. Recent studies of associated higher fluid chloride content with acute kidney injury and mortality but no large, randomized trials have been conducted. In preparation for a large, cluster-randomized, multiple-crossover trial comparing 0.9% sodium chloride to physiologically-balanced isotonic crystalloids (Lactated Ringers or Plasmalyte-A) in intensive care unit patients, this pilot study will enroll all patients admitted to the medical intensive care unit at a single tertiary center for a sixth month period. The primary objective will be to test the ability of an electronic order entry tool to ensure administration of assigned study fluid or record contraindications to assigned study fluid. The pilot study will also demonstrate the feasibility of collecting demographic, severity of illness, fluid management, vital sign, laboratory, acute kidney injury and renal replacement therapy, and outcome data in an automated, electronic fashion.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Other: 0.9% sodium chloride; Other: Physiologically balanced fluid

• Study Type: Interventional
• Enrollment (Actual): 974
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Vanderbilt University Medical Center

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:

• Admitted to the adult medical intensive care unit (MICU) at Vanderbilt University Medical Center

Exclusion Criteria:

• Age<18 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.9% sodium chloride; Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission.	Other: 0.9% sodium chloride
Active Comparator: Physiologically balanced fluid; Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission.	Other: Physiologically balanced fluid; Other Names: Lactated ringers or Plasmalyte-A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Isotonic Crystalloid Which is 0.9% Saline	Proportion of total intravenous isotonic crystalloid administered during admission to the intensive care unit that is 0.9% sodium chloride, censored at 30 days. The primary outcome was the proportion of intravenous isotonic crystalloid administered in the ICU that was saline. This was a continuous variable calculated for each patient as the volume of saline received divided by volume of saline received plus volume of balanced crystalloids received with a range from 0.0 (no saline received) to 1.0 (only saline received).	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Isotonic Crystalloid Which is Physiologically Balanced	Proportion of total intravenous isotonic crystalloid administered during admission to the intensive care unit that is either Lactated ringers or Plasmalyte-A, censored at 30 days.	30 days
Total Intravenous Input	Total volume of intravenous fluid administration during admission to the intensive care unit, censored at 30 days	30 days
Total Isotonic Crystalloid Input	Total volume of intravenous isotonic crystalloid administration during admission to the intensive care unit, censored at 30 days	30 days
Total Intravenous Colloid Input	Total volume of intravenous colloid administration (excluding blood products) during admission to the intensive care unit, censored at 30 days	30 days
Total Intravenous Blood Product Administration	Total volume of packed red blood cells, platelets, and fresh frozen plasma administered during admission to the intensive care unit, censored at 30 days	30 days
Highest Serum Chloride Between Enrollment and Day 30	highest serum chloride (mmol/L) during admission to the intensive care unit, censored at 30 days	30 days
Highest Serum Sodium Between Enrollment and Day 30	Highest serum sodium concentration (mmol/L) during admission to the intensive care unit, censored at 30 days	30 days
Lowest Bicarbonate Concentration Between Enrollment and Day 30	Lowest serum bicarbonate concentration (mmol/L) during admission to the intensive care unit, censored at 30 days	30 days
Number of Patients With MAKE30	Incidence of Major Adverse Kidney Events by 30 days -- a composite outcome defined as one or more of the following: death, new use of renal replacement therapy, or persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline)	30 days
In-hospital Mortality	Death prior to the earlier of hospital discharge or day 30	30 days
New Use of Renal Replacement Therapy	Receipt of new renal replacement therapy after the first study day, censored at 30 days	30 days
Persistent Renal Dysfunction	Persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline)	30 days
Number of Contraindications	Number of contraindications to assigned study fluid identified by providers, censored at 30 days	30 days
Incidence of Hyperchloremia	Incidence of hyperchloremia defined as a serum chloride greater than or equal to 110 mmol/L	30 days
Incidence of Severe Hypochloremia	Incidence of severe hypochloremia defined as a serum chloride less than 90mmol/L	30 days
Increase in Serum Creatinine	Increase in serum creatinine during hospitalization, censored at 30 days Change from baseline to highest value, median (IQR), mg/dl	30 days
Incidence of Acute Kidney Injury	Incidence of stage II or III acute kidney injury by Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury criteria, censored at 30 days	30 days
Intensive Care Unit Free Days to Day 28	ICU-free days to 28 days after enrollment will be defined as the number of days alive and not admitted to an intensive care unit service after the patient's final discharge from the intensive care unit before 28 days. If the patient is admitted to an intensive care unit service at day 28 or dies prior to day 28, ICU-free days will be 0.	28 days
Ventilator-free Days (VFD) to Day 28	Ventilator-free days to day 28 will be defined as the number of days alive and with unassisted breathing to day 28 after enrollment, assuming a patient survives for at least two consecutive calendar days after initiating unassisted breathing and remains free of assisted breathing. If a patient returns to assisted breathing and subsequently achieves unassisted breathing prior to day 28, VFD will be counted from the end of the last period of assisted breathing to day 28. If the patient is receiving assisted ventilation at day 28 or dies prior to day 28, VFD will be 0.	28 days
Dialysis-free Survival to Day 28	Dialysis free survival to day 28 will be defined as the number of days alive and without dialysis receipt to day 28 after enrollment, assuming a patient survives for at least two consecutive calendar days after last receipt of dialysis and remains free of dialysis. If the patient is receiving dialysis at day 28 or dies prior to day 28, VFD will be 0.	28 days
Peak Creatinine in the First 30 Days	Highest creatinine value in the first 30 days	30 days

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Todd W Rice, M.D., M.Sc., Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK. The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med. 2011 Nov;39(11):2419-24. doi: 10.1097/CCM.0b013e31822571e5.
• 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.
• Raghunathan K, Shaw A, Nathanson B, Sturmer T, Brookhart A, Stefan MS, Setoguchi S, Beadles C, Lindenauer PK. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med. 2014 Jul;42(7):1585-91. doi: 10.1097/CCM.0000000000000305.
• Semler MW, Wanderer JP, Ehrenfeld JM, Stollings JL, Self WH, Siew ED, Wang L, Byrne DW, Shaw AD, Bernard GR, Rice TW; SALT Investigators * and the Pragmatic Critical Care Research Group; SALT Investigators. Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial. Am J Respir Crit Care Med. 2017 May 15;195(10):1362-1372. doi: 10.1164/rccm.201607-1345OC.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Critical Care; Pilot Projects; Ringer's lactate; Sodium Chloride; Plasmalyte A; Resuscitation"
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: 141349