Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock
Overview
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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.
Intervention: Plasma (Drug)
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.
Intervention: Balanced crystalloids (Drug)
Outcomes
Primary Outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
Secondary Outcomes
- Number of Intensive Care Unit (ICU)-Free Days(First 30 days after initiation of fluid resuscitation)
- Time Until Lactate Normalization(First 24 hours after initiation of fluid resuscitation)
- Number of Days on Ventilator Support(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))
- 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)
- Time on Vasopressors(First 30 days after initiation of fluid resuscitation)
- Mortality(First 30 days after initiation of fluid resuscitation)
Investigators
Lillian Kao
Professor
The University of Texas Health Science Center, Houston