Acute Kidney Injury
Conditions
Keywords
Pilot Projects, Plasmalyte A, Ringer's lactate, Sodium Chloride, Critical Care, Resuscitation
Brief summary
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.
Interventions
OTHER0.9% sodium chloride
OTHERPhysiologically balanced fluid
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to the adult medical intensive care unit (MICU) at Vanderbilt University Medical Center
Exclusion criteria
* Age\<18 years old
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Isotonic Crystalloid Which is 0.9% Saline | 30 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Isotonic Crystalloid Which is Physiologically Balanced | 30 days | 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. |
| Total Intravenous Input | 30 days | Total volume of intravenous fluid administration during admission to the intensive care unit, censored at 30 days |
| Total Isotonic Crystalloid Input | 30 days | Total volume of intravenous isotonic crystalloid administration during admission to the intensive care unit, censored at 30 days |
| Total Intravenous Colloid Input | 30 days | Total volume of intravenous colloid administration (excluding blood products) during admission to the intensive care unit, censored at 30 days |
| Total Intravenous Blood Product Administration | 30 days | Total volume of packed red blood cells, platelets, and fresh frozen plasma administered during admission to the intensive care unit, censored at 30 days |
| Highest Serum Chloride Between Enrollment and Day 30 | 30 days | highest serum chloride (mmol/L) during admission to the intensive care unit, censored at 30 days |
| Highest Serum Sodium Between Enrollment and Day 30 | 30 days | Highest serum sodium concentration (mmol/L) during admission to the intensive care unit, censored at 30 days |
| Lowest Bicarbonate Concentration Between Enrollment and Day 30 | 30 days | Lowest serum bicarbonate concentration (mmol/L) during admission to the intensive care unit, censored at 30 days |
| Incidence of Acute Kidney Injury | 30 days | Incidence of stage II or III acute kidney injury by Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury criteria, censored at 30 days |
| Number of Patients With MAKE30 | 30 days | 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) |
| Increase in Serum Creatinine | 30 days | Increase in serum creatinine during hospitalization, censored at 30 days Change from baseline to highest value, median (IQR), mg/dl |
| New Use of Renal Replacement Therapy | 30 days | Receipt of new renal replacement therapy after the first study day, censored at 30 days |
| Persistent Renal Dysfunction | 30 days | Persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline) |
| Number of Contraindications | 30 days | Number of contraindications to assigned study fluid identified by providers, censored at 30 days |
| Incidence of Hyperchloremia | 30 days | Incidence of hyperchloremia defined as a serum chloride greater than or equal to 110 mmol/L |
| Incidence of Severe Hypochloremia | 30 days | Incidence of severe hypochloremia defined as a serum chloride less than 90mmol/L |
| Intensive Care Unit Free Days to Day 28 | 28 days | 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. |
| Ventilator-free Days (VFD) to Day 28 | 28 days | 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. |
| Dialysis-free Survival to Day 28 | 28 days | 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. |
| Peak Creatinine in the First 30 Days | 30 days | Highest creatinine value in the first 30 days |
| In-hospital Mortality | 30 days | Death prior to the earlier of hospital discharge or day 30 |
Countries
United States
Participant flow
Recruitment details
This cluster-randomized, multiple-crossover trial enrolled 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015.
Participants by arm
| Arm | Count |
|---|---|
| 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.
0.9% sodium chloride | 454 |
| 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.
Physiologically balanced fluid | 520 |
| Total | 974 |
Baseline characteristics
| Characteristic | Total | Physiologically Balanced Fluid | 0.9% Sodium Chloride |
|---|---|---|---|
| Acute kidney injury, stage II or greater | 183 Participants | 96 Participants | 87 Participants |
| Age, Continuous | 58 years | 57 years | 58 years |
| Body mass index | 26.6 kg/m^2 | 26.7 kg/m^2 | 26.4 kg/m^2 |
| Chronic kidney disease, stage III or greater | 223 Participants | 119 Participants | 104 Participants |
| Mechanical ventilation | 329 Participants | 174 Participants | 155 Participants |
| Previous renal replacement therapy | 86 Participants | 42 Participants | 44 Participants |
| Region of Enrollment United States | 974 participants | 520 participants | 454 participants |
| Sex: Female, Male Female | 460 Participants | 252 Participants | 208 Participants |
| Sex: Female, Male Male | 514 Participants | 268 Participants | 246 Participants |
| Source of ICU Admission Another ICU within the hospital | 29 Participants | 14 Participants | 15 Participants |
| Source of ICU Admission Emergency Department | 566 Participants | 310 Participants | 256 Participants |
| Source of ICU Admission Hospital ward | 159 Participants | 79 Participants | 80 Participants |
| Source of ICU Admission Operating room | 10 Participants | 4 Participants | 6 Participants |
| Source of ICU Admission Outpatient | 11 Participants | 7 Participants | 4 Participants |
| Source of ICU Admission Transfer from another hospital | 199 Participants | 106 Participants | 93 Participants |
| Vasopressors | 225 Participants | 114 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 68 / 454 | 72 / 520 |
| other Total, other adverse events | 0 / 454 | 0 / 520 |
| serious Total, serious adverse events | 0 / 454 | 0 / 520 |
Outcome results
Primary
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).
Time frame: 30 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 0.9% Sodium Chloride | Proportion of Isotonic Crystalloid Which is 0.9% Saline | 91.2 Percentage of fluid that was saline |
| Physiologically Balanced Fluid | Proportion of Isotonic Crystalloid Which is 0.9% Saline | 21.0 Percentage of fluid that was saline |
p-value: 0.00195% CI: [0.66, 0.74]Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Dialysis-free Survival to Day 28 | 28.0 days |
| Physiologically Balanced Fluid | Dialysis-free Survival to Day 28 | 28.0 days |
Secondary
Highest Serum Chloride Between Enrollment and Day 30
highest serum chloride (mmol/L) during admission to the intensive care unit, censored at 30 days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Highest Serum Chloride Between Enrollment and Day 30 | 109 mmol/L |
| Physiologically Balanced Fluid | Highest Serum Chloride Between Enrollment and Day 30 | 108 mmol/L |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Highest Serum Sodium Between Enrollment and Day 30 | 141 mmol/L |
| Physiologically Balanced Fluid | Highest Serum Sodium Between Enrollment and Day 30 | 141 mmol/L |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Incidence of Acute Kidney Injury | 129 Participants |
| Physiologically Balanced Fluid | Incidence of Acute Kidney Injury | 135 Participants |
Secondary
Incidence of Hyperchloremia
Incidence of hyperchloremia defined as a serum chloride greater than or equal to 110 mmol/L
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Incidence of Hyperchloremia | 171 Participants |
| Physiologically Balanced Fluid | Incidence of Hyperchloremia | 171 Participants |
Secondary
Incidence of Severe Hypochloremia
Incidence of severe hypochloremia defined as a serum chloride less than 90mmol/L
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Incidence of Severe Hypochloremia | 34 Participants |
| Physiologically Balanced Fluid | Incidence of Severe Hypochloremia | 32 Participants |
Secondary
Increase in Serum Creatinine
Increase in serum creatinine during hospitalization, censored at 30 days Change from baseline to highest value, median (IQR), mg/dl
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Increase in Serum Creatinine | 0.07 mg/dL |
| Physiologically Balanced Fluid | Increase in Serum Creatinine | 0.07 mg/dL |
Secondary
In-hospital Mortality
Death prior to the earlier of hospital discharge or day 30
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | In-hospital Mortality | 68 Participants |
| Physiologically Balanced Fluid | In-hospital Mortality | 72 Participants |
Secondary
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.
Time frame: 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Intensive Care Unit Free Days to Day 28 | 25.1 days |
| Physiologically Balanced Fluid | Intensive Care Unit Free Days to Day 28 | 25.2 days |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Lowest Bicarbonate Concentration Between Enrollment and Day 30 | 19 mmol/L |
| Physiologically Balanced Fluid | Lowest Bicarbonate Concentration Between Enrollment and Day 30 | 19 mmol/L |
Secondary
New Use of Renal Replacement Therapy
Receipt of new renal replacement therapy after the first study day, censored at 30 days
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | New Use of Renal Replacement Therapy | 14 Participants |
| Physiologically Balanced Fluid | New Use of Renal Replacement Therapy | 24 Participants |
Secondary
Number of Contraindications
Number of contraindications to assigned study fluid identified by providers, censored at 30 days
Time frame: 30 days
Population: Order for intravenous crystalloid is the unit analyzed; each patient could have multiple orders for intravenous crystalloid
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| 0.9% Sodium Chloride | Number of Contraindications | 28 Orders for intravenous crystalloid |
| Physiologically Balanced Fluid | Number of Contraindications | 66 Orders for intravenous crystalloid |
Secondary
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)
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Number of Patients With MAKE30 | 112 Participants |
| Physiologically Balanced Fluid | Number of Patients With MAKE30 | 128 Participants |
Secondary
Peak Creatinine in the First 30 Days
Highest creatinine value in the first 30 days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Peak Creatinine in the First 30 Days | 1.19 mg/dL |
| Physiologically Balanced Fluid | Peak Creatinine in the First 30 Days | 1.19 mg/dL |
Secondary
Persistent Renal Dysfunction
Persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline)
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Persistent Renal Dysfunction | 59 Participants |
| Physiologically Balanced Fluid | Persistent Renal Dysfunction | 76 Participants |
Secondary
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.
Time frame: 30 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 0.9% Sodium Chloride | Proportion of Isotonic Crystalloid Which is Physiologically Balanced | 8.8 Percentage of fluid that was balanced |
| Physiologically Balanced Fluid | Proportion of Isotonic Crystalloid Which is Physiologically Balanced | 78.8 Percentage of fluid that was balanced |
Secondary
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
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Total Intravenous Blood Product Administration | 0 milliliters |
| Physiologically Balanced Fluid | Total Intravenous Blood Product Administration | 0 milliliters |
Secondary
Total Intravenous Colloid Input
Total volume of intravenous colloid administration (excluding blood products) during admission to the intensive care unit, censored at 30 days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Total Intravenous Colloid Input | 0 milliliters |
| Physiologically Balanced Fluid | Total Intravenous Colloid Input | 0 milliliters |
Secondary
Total Intravenous Input
Total volume of intravenous fluid administration during admission to the intensive care unit, censored at 30 days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Total Intravenous Input | 2000 milliliters |
| Physiologically Balanced Fluid | Total Intravenous Input | 2125 milliliters |
Secondary
Total Isotonic Crystalloid Input
Total volume of intravenous isotonic crystalloid administration during admission to the intensive care unit, censored at 30 days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Total Isotonic Crystalloid Input | 1424 mL |
| Physiologically Balanced Fluid | Total Isotonic Crystalloid Input | 1617 mL |
Secondary
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.
Time frame: 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.9% Sodium Chloride | Ventilator-free Days (VFD) to Day 28 | 28.0 days |
| Physiologically Balanced Fluid | Ventilator-free Days (VFD) to Day 28 | 28.0 days |