Isotonic Solution Administration Logistical Testing

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Other: 0.9% sodium chloride
* Other: Physiologically balanced fluid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to the adult medical intensive care unit (MICU) at Vanderbilt University Medical Center Exclusion Criteria: Age<18 years old

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.9% sodium chloride<br>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<br> <br> |
| Active Comparator: Physiologically balanced fluid<br>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<br> <br> * Other names: Lactated ringers or Plasmalyte-A;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pilot Projects, Plasmalyte A, Ringer's lactate, Sodium Chloride, Critical Care, Resuscitation