Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

Phase 2TerminatedNCT03366220

The University of Texas Health Science Center, Houston16 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Septic Shock

Interventions

PlasmaDRUG

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.

Balanced crystalloidsDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Outcomes

Primary Outcomes

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

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

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

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

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

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 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 High Mobility Group Protein-1 (HMGB-1)

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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

Time Until Lactate Normalization

Time frame: First 24 hours after initiation of fluid resuscitation

Time on Vasopressors