Septic Shock
Conditions
Brief summary
There is a knowledge gap regarding the optimal initial fluid to achieve effective resuscitation and improved outcomes in septic shock. The purpose of this study is to compare initial resuscitation with plasma to initial resuscitation with balanced crystalloids.
Interventions
DRUGPlasma
Initial resuscitation with plasma will be 10 mL/kg (700 mL in a typical 70 kg adult). Traditional doses of plasma, when used to correct coagulopathy range from 10-15 mL/kg.23 The plasma will be administered at a rate of 2-3 mL/kg/hr (140-210 mL/hr in a typical 70 kg adult). A research physician will be at bedside to follow patient resuscitation. Plasma administration may be terminated before the entire dose is administered if patients show clinical improvement. After the initial dose of plasma has been given, subsequent resuscitation will follow usual care using balanced crystalloids.
DRUGBalanced crystalloids
Usual care using balanced crystalloids (Iso-Lyte or Plasma-Lyte) only will follow Surviving Sepsis Campaign guidelines. Controls will receive 30 mL/kg (2100 mL in a typical 70 kg adult) of crystalloids within the first 3 hours. Subsequent resuscitation with balanced crystalloids will be titrated to the endpoints of resuscitation.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients meeting the following criteria will be enrolled: Have a Sepsis Screening Score (SSS) ≥ 4 with a suspected source of infection (Table 1); and Written informed consent obtained * Patients meeting any of the following criteria will be randomized: Hypotension with MAP \< 65 mmHg; Lactic acid \> 4 mmol/L; Altered mental status; and Decreased urine output of \< 0.5 mL/kg in the past hour.
Exclusion criteria
* Pregnancy * Prisoners * Traumatic brain injury * Evidence of ongoing hemorrhage, history of congenital bleeding disorders, therapeutic anticoagulation * History of myocardial infarction or congestive heart failure * History of acute cerebral vascular event * Major burns (\>20% total body surface area) * History of adverse reactions to blood product transfusion * Contraindications to blood transfusions (eg. Jehovah's Witness) * Contraindications to central venous line and arterial line placement * On intermittent hemodialysis * Do-Not-Resuscitate or Comfort Care status * Participation in another interventional study * Pending transfer to another unit within the hospital that is not STICU or SIMU
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Inflammation as Assessed by Interleukin-1β (IL-1β) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Inflammation as Assessed by Soluble Receptor for Advanced Glycation Endproduct (sRAGE) | 0, 2, end of initial bolus of fluid administration, 12, and 24 hours |
| Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1) | 0, 2, end of initial bolus of fluid administration, 12, and 24 hours |
| Inflammation as Assessed by Interleukin-6 (IL-6) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Inflammation as Assessed by Interleukin-8 (IL-8) | 0, 2, end of initial bolus of fluid administration (about 3 hours) , 12, and 24 hours |
| Inflammation as Assessed by Interleukin-10 (IL-10) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Inflammation as Assessed by Interleukin-1α (IL-1α) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and at 24 hours |
| Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours |
| Endothelial Leakage as Assessed by Soluble FMS-like Tyrosine Kinase-1 (sFLT-1) | 0, 2, end of initial bolus of fluid administration(about 3 hours), 12, and 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Lactate Normalization | First 24 hours after initiation of fluid resuscitation | — |
| Time on Vasopressors | First 30 days after initiation of fluid resuscitation | — |
| Number of Days on Ventilator Support | First 30 days after initiation of fluid resuscitation | — |
| Number of Intensive Care Unit (ICU)-Free Days | First 30 days after initiation of fluid resuscitation | — |
| Number of Hospital Days | From the time of initiation of fluid resuscitation to the time of hospital discharge (up to about 170 days) | — |
| Mortality | First 30 days after initiation of fluid resuscitation | — |
| Number of Participants With Acute Lung Injury | First 30 days after initiation of fluid resuscitation | — |
| Number of Participants With Acute Kidney Injury | First 30 days after initiation of fluid resuscitation | — |
| Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids | First 24 hours after initiation of fluid resuscitation | Data were not collected for 1 participant in the initial resuscitation with plasma arm. |
Countries
United States
Participant flow
Pre-assignment details
Patients with a sepsis screening score \> or equal to 4 (which indicates potential sepsis) and with a suspected source of infection were enrolled, and they were later randomized if septic shock developed, per the protocol. Only 8 enrolled patients progressed to septic shock, and therefore only 8 participants were randomized and started the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Initial Resuscitation With Plasma Initial resuscitation with plasma will be 10 mL/kg (700 mL in a typical 70 kg adult). Traditional doses of plasma, when used to correct coagulopathy range from 10-15 mL/kg.23 The plasma will be administered at a rate of 2-3 mL/kg/hr (140-210 mL/hr in a typical 70 kg adult). A research physician will be at bedside to follow patient resuscitation. Plasma administration may be terminated before the entire dose is administered if patients show clinical improvement. After the initial dose of plasma has been given, subsequent resuscitation will follow usual care using balanced crystalloids.
Plasma: Initial resuscitation with plasma will be 10 mL/kg (700 mL in a typical 70 kg adult). Traditional doses of plasma, when used to correct coagulopathy range from 10-15 mL/kg.23 The plasma will be administered at a rate of 2-3 mL/kg/hr (140-210 mL/hr in a typical 70 kg adult). A research physician will be at bedside to follow patient resuscitation. Plasma administration may be terminated before the entire dose is administered if patients show clinical improvement. After the initial dose of plasma has been given, subsequent resuscitation will follow usual care using balanced crystalloids. | 4 |
| Initial Resuscitation With Balanced Crystalloids Usual care using balanced crystalloids (Iso-Lyte or Plasma-Lyte) only will follow Surviving Sepsis Campaign guidelines. Controls will receive 30 mL/kg (2100 mL in a typical 70 kg adult) of crystalloids within the first 3 hours. Subsequent resuscitation with balanced crystalloids will be titrated to the endpoints of resuscitation.
Balanced crystalloids: Usual care using balanced crystalloids (Iso-Lyte or Plasma-Lyte) only will follow Surviving Sepsis Campaign guidelines. Controls will receive 30 mL/kg (2100 mL in a typical 70 kg adult) of crystalloids within the first 3 hours. Subsequent resuscitation with balanced crystalloids will be titrated to the endpoints of resuscitation. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Initial Resuscitation With Plasma | Initial Resuscitation With Balanced Crystalloids | Total |
|---|---|---|---|
| Age, Continuous | 30.75 years STANDARD_DEVIATION 9.81 | 58 years STANDARD_DEVIATION 9.09 | 44.37 years STANDARD_DEVIATION 9.45 |
| Race/Ethnicity, Customized Black | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 1 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 4 / 4 | 4 / 4 |
Outcome results
Primary
Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: In the plasma arm, sample levels were out of range and thus no value could be obtained for 3 participants at all time points.~In the balanced crystalloids arm, sample levels were out of range and thus no value could be obtained for 3 participants at 0, 2, and 12 hours; for 2 at about 3 hours and at 24 hours; and for all 4 at 12 hours--in addition to those with sample levels out of range, there was 1 other participant for whom no data at all were collected at 3 hours and 24 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 0 hours | 108.35 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Plasma | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 2 hours | 76.63 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Plasma | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | end of initial bolus of fluid administration (about 3 hours) | 48.02 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Plasma | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 12 hours | 171.29 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Plasma | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 24 hours | 97.44 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Balanced Crystalloids | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 0 hours | 61.6 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Balanced Crystalloids | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | end of initial bolus of fluid administration (about 3 hours) | 32.93 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Balanced Crystalloids | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 2 hours | 97.44 pg/mL | Standard Deviation 0 |
| Initial Resuscitation With Balanced Crystalloids | Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF) | 24 hours | 215.23 pg/mL | Standard Deviation 0 |
Primary
Endothelial Leakage as Assessed by Soluble FMS-like Tyrosine Kinase-1 (sFLT-1)
Time frame: 0, 2, end of initial bolus of fluid administration(about 3 hours), 12, and 24 hours
Population: Data was not collected for this outcome measure.
Primary
Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected at end of initial bolus of fluid administration (about 3 hours) and at 24 hours for one participant in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 2 hours | 22.06 ng/mL | Standard Deviation 17.19 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 12 hours | 21.13 ng/mL | Standard Deviation 12.59 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | end of initial bolus of fluid administration (about 3 hours) | 21.87 ng/mL | Standard Deviation 15.88 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 24 hours | 25.69 ng/mL | Standard Deviation 21.02 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 0 hours | 22.44 ng/mL | Standard Deviation 14.94 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 24 hours | 24.43 ng/mL | Standard Deviation 12.78 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 0 hours | 21.29 ng/mL | Standard Deviation 12.22 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 2 hours | 21.50 ng/mL | Standard Deviation 11.66 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | end of initial bolus of fluid administration (about 3 hours) | 23.38 ng/mL | Standard Deviation 14.28 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM) | 12 hours | 22.10 ng/mL | Standard Deviation 11.86 |
Primary
Glycocalyx Breakdown as Assessed by Syndecan-1 Levels
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and at 24 hours
Population: Data was not collected at end of initial bolus of fluid administration (about 3 hours) and 24 hours for one participant in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 2 hours | 294.03 ng/mL | Standard Deviation 499.12 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 12 hours | 291.28 ng/mL | Standard Deviation 496.24 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | end of initial bolus of fluid administration (about 3 hours) | 278.22 ng/mL | Standard Deviation 456.24 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 24 hours | 241.16 ng/mL | Standard Deviation 349.15 |
| Initial Resuscitation With Plasma | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 0 hours | 260.87 ng/mL | Standard Deviation 455.79 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 24 hours | 285.34 ng/mL | Standard Deviation 45.1 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 0 hours | 390.67 ng/mL | Standard Deviation 169.66 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 2 hours | 383.53 ng/mL | Standard Deviation 122.26 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | end of initial bolus of fluid administration (about 3 hours) | 337.37 ng/mL | Standard Deviation 220.03 |
| Initial Resuscitation With Balanced Crystalloids | Glycocalyx Breakdown as Assessed by Syndecan-1 Levels | 12 hours | 350.43 ng/mL | Standard Deviation 196.62 |
Primary
Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1)
Time frame: 0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Population: Data was not collected for this outcome measure.
Primary
Inflammation as Assessed by Interleukin-10 (IL-10)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.~Sample levels were out of range and thus no value could be obtained for one participant at 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours in the initial resuscitation with plasma arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-10 (IL-10) | 2 hours | 216.59 pg/mL | Standard Deviation 349.54 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-10 (IL-10) | 12 hours | 59.79 pg/mL | Standard Deviation 79.01 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-10 (IL-10) | end of initial bolus of fluid administration (about 3 hours) | 257.11 pg/mL | Standard Deviation 422.66 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-10 (IL-10) | 24 hours | 23.51 pg/mL | Standard Deviation 22.55 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-10 (IL-10) | 0 hours | 140.06 pg/mL | Standard Deviation 254.38 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-10 (IL-10) | 24 hours | 6.27 pg/mL | Standard Deviation 1.2 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-10 (IL-10) | 0 hours | 101.88 pg/mL | Standard Deviation 183.79 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-10 (IL-10) | 2 hours | 52.50 pg/mL | Standard Deviation 81.7 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-10 (IL-10) | end of initial bolus of fluid administration (about 3 hours) | 84.52 pg/mL | Standard Deviation 127.6 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-10 (IL-10) | 12 hours | 9.20 pg/mL | Standard Deviation 3.93 |
Primary
Inflammation as Assessed by Interleukin-1α (IL-1α)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1α (IL-1α) | 2 hours | 11724.06 pg/mL | Standard Deviation 8728.74 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1α (IL-1α) | 12 hours | 7998.79 pg/mL | Standard Deviation 7952.26 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1α (IL-1α) | end of initial bolus of fluid administration (about 3 hours) | 12305.08 pg/mL | Standard Deviation 10084.78 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1α (IL-1α) | 24 hours | 5922.11 pg/mL | Standard Deviation 6274.24 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1α (IL-1α) | 0 hours | 15221.21 pg/mL | Standard Deviation 11064.91 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1α (IL-1α) | 24 hours | 1999.86 pg/mL | Standard Deviation 1953.98 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1α (IL-1α) | 0 hours | 7759.09 pg/mL | Standard Deviation 3512.66 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1α (IL-1α) | 2 hours | 7475.72 pg/mL | Standard Deviation 3752.85 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1α (IL-1α) | end of initial bolus of fluid administration (about 3 hours) | 7833.37 pg/mL | Standard Deviation 4661.07 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1α (IL-1α) | 12 hours | 3770.93 pg/mL | Standard Deviation 2453.76 |
Primary
Inflammation as Assessed by Interleukin-1β (IL-1β)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1β (IL-1β) | 2 hours | 7.21 pg/mL | Standard Deviation 10.97 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1β (IL-1β) | 12 hours | 1.95 pg/mL | Standard Deviation 1.35 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1β (IL-1β) | end of initial bolus of fluid administration (about 3 hours) | 8.31 pg/mL | Standard Deviation 13.43 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1β (IL-1β) | 24 hours | 1.56 pg/mL | Standard Deviation 0.66 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-1β (IL-1β) | 0 hours | 17.59 pg/mL | Standard Deviation 29.76 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1β (IL-1β) | 24 hours | 1.61 pg/mL | Standard Deviation 0.26 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1β (IL-1β) | 0 hours | 2.55 pg/mL | Standard Deviation 1.64 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1β (IL-1β) | 2 hours | 1.99 pg/mL | Standard Deviation 0.98 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1β (IL-1β) | end of initial bolus of fluid administration (about 3 hours) | 2.10 pg/mL | Standard Deviation 0.81 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-1β (IL-1β) | 12 hours | 1.48 pg/mL | Standard Deviation 0.44 |
Primary
Inflammation as Assessed by Interleukin-6 (IL-6)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-6 (IL-6) | 2 hours | 1911.7 pg/mL | Standard Deviation 3571.24 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-6 (IL-6) | 12 hours | 1076.74 pg/mL | Standard Deviation 2062.13 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-6 (IL-6) | end of initial bolus of fluid administration (about 3 hours) | 1911.48 pg/mL | Standard Deviation 3587.39 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-6 (IL-6) | 24 hours | 296.94 pg/mL | Standard Deviation 529.58 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-6 (IL-6) | 0 hours | 2455.043 pg/mL | Standard Deviation 4421.03 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-6 (IL-6) | 24 hours | 29.27 pg/mL | Standard Deviation 20.38 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-6 (IL-6) | 0 hours | 782.41 pg/mL | Standard Deviation 977.31 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-6 (IL-6) | 2 hours | 189.41 pg/mL | Standard Deviation 121.41 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-6 (IL-6) | end of initial bolus of fluid administration (about 3 hours) | 109.79 pg/mL | Standard Deviation 9.13 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-6 (IL-6) | 12 hours | 60.02 pg/mL | Standard Deviation 51.39 |
Primary
Inflammation as Assessed by Interleukin-8 (IL-8)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours) , 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-8 (IL-8) | 2 hours | 695.66 pg/mL | Standard Deviation 1276.29 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-8 (IL-8) | 12 hours | 632.78 pg/mL | Standard Deviation 1170.42 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-8 (IL-8) | end of initial bolus of fluid administration (about 3 hours) | 763.04 pg/mL | Standard Deviation 1414.59 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-8 (IL-8) | 24 hours | 158.71 pg/mL | Standard Deviation 242.78 |
| Initial Resuscitation With Plasma | Inflammation as Assessed by Interleukin-8 (IL-8) | 0 hours | 866.78 pg/mL | Standard Deviation 1599.38 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-8 (IL-8) | 24 hours | 43.37 pg/mL | Standard Deviation 10.8 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-8 (IL-8) | 0 hours | 180.46 pg/mL | Standard Deviation 184.81 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-8 (IL-8) | 2 hours | 93.53 pg/mL | Standard Deviation 34.03 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-8 (IL-8) | end of initial bolus of fluid administration (about 3 hours) | 83.13 pg/mL | Standard Deviation 17.28 |
| Initial Resuscitation With Balanced Crystalloids | Inflammation as Assessed by Interleukin-8 (IL-8) | 12 hours | 58.84 pg/mL | Standard Deviation 11.39 |
Primary
Inflammation as Assessed by Soluble Receptor for Advanced Glycation Endproduct (sRAGE)
Time frame: 0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Population: Data was not collected for this outcome measure.
Primary
Sympatho-adrenal Activation as Assessed by Epinephrine (Epi)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.~Sample levels were out of range and thus no value could be obtained for one participant at 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 2 hours | 198 pg/mL | Standard Deviation 145.22 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 12 hours | 143.75 pg/mL | Standard Deviation 113.7 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | end of initial bolus of fluid administration (about 3 hours) | 226.5 pg/mL | Standard Deviation 210.47 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 24 hours | 133 pg/mL | Standard Deviation 77.48 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 0 hours | 239 pg/mL | Standard Deviation 139.9 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 24 hours | 191 pg/mL | Standard Deviation 108.89 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 0 hours | 87.25 pg/mL | Standard Deviation 42.01 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 2 hours | 132 pg/mL | Standard Deviation 34.47 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | end of initial bolus of fluid administration (about 3 hours) | 160.66 pg/mL | Standard Deviation 148.39 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Epinephrine (Epi) | 12 hours | 138.25 pg/mL | Standard Deviation 42.43 |
Primary
Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)
Time frame: 0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Population: Data was not collected for one participant at the end of initial bolus of fluid administration (about 3 hours) and 24 hours in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 2 hours | 5434.25 pg/mL | Standard Deviation 9411.88 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 12 hours | 8360.75 pg/mL | Standard Deviation 15166.41 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | end of initial bolus of fluid administration (about 3 hours) | 5271 pg/mL | Standard Deviation 9131.59 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 24 hours | 6579.25 pg/mL | Standard Deviation 10412.6 |
| Initial Resuscitation With Plasma | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 0 hours | 3539.75 pg/mL | Standard Deviation 3998.06 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 24 hours | 1180.33 pg/mL | Standard Deviation 899.9 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 0 hours | 1757.75 pg/mL | Standard Deviation 718.8 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 2 hours | 2877 pg/mL | Standard Deviation 2349.24 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | end of initial bolus of fluid administration (about 3 hours) | 2398.33 pg/mL | Standard Deviation 1208.69 |
| Initial Resuscitation With Balanced Crystalloids | Sympatho-adrenal Activation as Assessed by Norepinephrine (NE) | 12 hours | 1643.5 pg/mL | Standard Deviation 959.69 |
Secondary
Mortality
Time frame: First 30 days after initiation of fluid resuscitation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Resuscitation With Plasma | Mortality | 1 Participants |
| Initial Resuscitation With Balanced Crystalloids | Mortality | 1 Participants |
Secondary
Number of Days on Ventilator Support
Time frame: First 30 days after initiation of fluid resuscitation
Population: Data were not collected for 1 participant in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Number of Days on Ventilator Support | 13.5 days | Standard Deviation 10.37 |
| Initial Resuscitation With Balanced Crystalloids | Number of Days on Ventilator Support | 9 days | Standard Deviation 15.58 |
Secondary
Number of Hospital Days
Time frame: From the time of initiation of fluid resuscitation to the time of hospital discharge (up to about 170 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Number of Hospital Days | 29 days | Standard Deviation 11.16 |
| Initial Resuscitation With Balanced Crystalloids | Number of Hospital Days | 81.5 days | Standard Deviation 86.54 |
Secondary
Number of Intensive Care Unit (ICU)-Free Days
Time frame: First 30 days after initiation of fluid resuscitation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Number of Intensive Care Unit (ICU)-Free Days | 9.25 days | Standard Deviation 13.2 |
| Initial Resuscitation With Balanced Crystalloids | Number of Intensive Care Unit (ICU)-Free Days | 23.5 days | Standard Deviation 22.53 |
Secondary
Number of Participants With Acute Kidney Injury
Time frame: First 30 days after initiation of fluid resuscitation
Population: Data was not collected for this outcome measure.
Secondary
Number of Participants With Acute Lung Injury
Time frame: First 30 days after initiation of fluid resuscitation
Population: Data was not collected for this outcome measure.
Secondary
Time on Vasopressors
Time frame: First 30 days after initiation of fluid resuscitation
Population: Data were not collected for 2 participants in the initial resuscitation with plasma arm and 2 participants in the initial resuscitation with balanced crystalloids arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Time on Vasopressors | 70.5 hours | Standard Deviation 92.63 |
| Initial Resuscitation With Balanced Crystalloids | Time on Vasopressors | 14.5 hours | Standard Deviation 10.6 |
Secondary
Time Until Lactate Normalization
Time frame: First 24 hours after initiation of fluid resuscitation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Time Until Lactate Normalization | 15.25 hours | Standard Deviation 27.26 |
| Initial Resuscitation With Balanced Crystalloids | Time Until Lactate Normalization | 3.5 hours | Standard Deviation 7 |
Secondary
Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids
Data were not collected for 1 participant in the initial resuscitation with plasma arm.
Time frame: First 24 hours after initiation of fluid resuscitation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Initial Resuscitation With Plasma | Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids | 967.66 mL | Standard Deviation 951.91 |
| Initial Resuscitation With Balanced Crystalloids | Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids | 455 mL | Standard Deviation 530.5 |