Fluid Therapy, Hypotension, Septic Shock
Conditions
Brief summary
The purpose of the study is to determine if a protocol that assesses patients' daily fluid intake and output can decrease the overall amount of fluid patients receive during the first five days in the ICU. The study will also determine if decreasing overall fluids can decrease adverse events associated with mechanical ventilation, such as ventilator-associated pneumonias. The protocol will include daily ultrasounds and blood draws to evaluate fluid balance. Ultrasound will be used to measure changes in the diameter of the inferior vena cava with respiration.
Interventions
OTHERFluid minimization protocol
Fluid nonresponsive patients will have continuous infusions concentrated, maintenance fluids discontinued, and carrier fluids minimized. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance in patients demonstrating fluid non-responsiveness.
DEVICEUltrasound
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patient with septic shock as the primary cause of hypotension 2. Requiring vasopressors for 12 hours after adequate fluid resuscitation and at the time of enrollment
Exclusion criteria
1. Patients with a history of end-stage renal disease requiring outpatient dialysis 2. Patients whose goals of care are consistent with comfort measures only 3. Pregnant patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Fluid Administered | Day 3 | Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 3 |
| Net Fluid Balance | Day 3 | Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator Days | Hospital stay, median of 16 days | Number of days requiring mechanical ventilation support, including continuous noninvasive positive pressure ventilation |
| Rate of Renal Replacement Therapy | ICU stay, median of 10 days | Percentage of patients requiring renal replacement therapy |
| Mortality | Hospital stay, median of 16 days | Percentage of patients who died during their hospitalization |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluid Minimization Group Patients in the fluid minimization arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Intubated patients will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ. Fluid challenge as a leg raise or infusion of 250 mL of crystalloid over 5 minutes will be performed and parameters repeated. Fluid responsiveness based on the changes in the parameters. Fluid nonresponsive patients will undergo the fluid minimization protocol.
Fluid minimization protocol: Fluid nonresponsive patients will have continuous infusions concentrated, maintenance fluids discontinued, and carrier fluids minimized. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance. | 41 |
| Usual Care Group Patients in the usual care arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Patients who are intubated will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ. | 41 |
| Total | 82 |
Baseline characteristics
| Characteristic | Fluid Minimization Group | Usual Care Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 31 Participants | 62 Participants |
| Age, Continuous | 58 years | 60 years | 58 years |
| APACHE II score | 25 units on a scale | 26 units on a scale | 25 units on a scale |
| BMI | 32.62 kg/m^2 | 31.13 kg/m^2 | 32.33 kg/m^2 |
| Intubation status | 28 Participants | 31 Participants | 59 Participants |
| Presence of active malignancy | 16 Participants | 10 Participants | 26 Participants |
| Presence of ARDS | 26 Participants | 25 Participants | 51 Participants |
| Presence of chronic kidney disease | 6 Participants | 3 Participants | 9 Participants |
| Presence of COPD | 5 Participants | 7 Participants | 12 Participants |
| Presence of diabetes mellitus | 12 Participants | 10 Participants | 22 Participants |
| Presence of diastolic heart failure | 4 Participants | 4 Participants | 8 Participants |
| Presence of end-stage liver disease | 13 Participants | 7 Participants | 20 Participants |
| Presence of hyperlipidemia | 10 Participants | 10 Participants | 20 Participants |
| Presence of hypertension | 14 Participants | 19 Participants | 33 Participants |
| Presence of systolic heart failure | 4 Participants | 5 Participants | 9 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 41 Participants | 41 Participants | 82 Participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
| SOFA score | 13 units on a scale | 12 units on a scale | 13 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 23 / 41 | 20 / 41 |
| other Total, other adverse events | 0 / 41 | 0 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 |
Outcome results
Primary
Cumulative Fluid Administered
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 3
Time frame: Day 3
Population: Five patients in the fluid minimization group and two patients in the usual care group died prior to the first time point analysis at day three. One patient in the usual care group was transferred out of the ICU prior to the first time point analysis at day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluid Minimization Group | Cumulative Fluid Administered | 4417 mL of study fluid |
| Usual Care Group | Cumulative Fluid Administered | 4110 mL of study fluid |
Primary
Cumulative Fluid Administered
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 5
Time frame: Day 5
Population: Five patients in the fluid minimization group and four patients in the usual care group died prior to analysis at day 5. Five patients in the fluid minimization group and six patients in the usual care group were transferred out of the ICU prior to analysis at day 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluid Minimization Group | Cumulative Fluid Administered | 6244 mL of study fluid |
| Usual Care Group | Cumulative Fluid Administered | 8690 mL of study fluid |
Primary
Net Fluid Balance
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 3
Time frame: Day 3
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluid Minimization Group | Net Fluid Balance | 1952 mL |
| Usual Care Group | Net Fluid Balance | 3124 mL |
Primary
Net Fluid Balance
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 5
Time frame: Day 5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluid Minimization Group | Net Fluid Balance | 2641 mL |
| Usual Care Group | Net Fluid Balance | 3616 mL |
Secondary
Mortality
Percentage of patients who died during their ICU stay
Time frame: ICU stay, median of 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluid Minimization Group | Mortality | 23 Participants |
| Usual Care Group | Mortality | 20 Participants |
Secondary
Mortality
Percentage of patients who died during their hospitalization
Time frame: Hospital stay, median of 16 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluid Minimization Group | Mortality | 23 Participants |
| Usual Care Group | Mortality | 20 Participants |
Secondary
Rate of Renal Replacement Therapy
Percentage of patients requiring renal replacement therapy
Time frame: ICU stay, median of 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluid Minimization Group | Rate of Renal Replacement Therapy | 17 Participants |
| Usual Care Group | Rate of Renal Replacement Therapy | 16 Participants |
Secondary
Ventilator Days
Number of days requiring mechanical ventilation support, including continuous noninvasive positive pressure ventilation
Time frame: Hospital stay, median of 16 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluid Minimization Group | Ventilator Days | 8 days |
| Usual Care Group | Ventilator Days | 5 days |