Endothelial Function After Cardiac Surgery
Condition: Endothelial Dysfunction
Study type: Interventional

Summary: 
      The purpose of this study is to evaluate whether patients receiving human albumin for plasma
      volume replacement during cardiac surgery have improved postoperative endothelial function
      compared to patients receiving 6% hydroxyethyl starch solutions. The postoperative
      endothelial function, measured with peripheral arterial tonometry as reactive hyperemia index
      (RHI) within 2 hours following surgery, will be compared in cardiac surgical patients
      randomized to receive human albumin or 6% HES solutions for intraoperative volume
      replacement. Within two hours of arrival to the ICU peripheral arterial tonometry using
      EndoPAT will be performed. In a subset of 40 consecutive patients the investigators will
      perform additional EndoPAT measurements to describe the expected changes that occur in
      endothelial function during the perioperative period (baseline, early postoperative and 24
      hours postoperative) using RHI.

      This study will also determine whether human albumin 5% reduces plasma biomarkers of
      endothelial and glycocalyceal damage by measuring plasma concentrations of syndecan 1 and
      endocan at baseline (before surgery), and 1 and 24 hours following surgery. Blood samples
      will be taken on the morning of the surgery, within one hour of arrival to the intensive care
      unit (ICU), and 24 hours after surgery or within 2 hours before discharge from the ICU (three
      times altogether). These samples will be used to measure the plasma concentrations of two
      biomarkers that measure endothelial injury.
    

Detailed description: 
      Cardiac surgical patients enrolled in the SHARP study will be randomized to 5% human albumin
      or 6% HES on entrance to the operating room. Anesthetic and Surgical management will follow
      protocol established by SHARP study including administration of a blinded study solution
      which contains 5% human albumin or 6% HES following separation from cardiopulmonary bypass.
      Blood will collected for measurement of baseline syndecan 1 and endocan following arterial
      line and urinary catheter placement before surgical incision. At 1 and 24 hrs following
      surgery completion, blood will be collected for measurement of syndecan 1 and endocan. Within
      two hours of ICU arrival, assessment of endothelial function will be performed.

      In a subset of patients (patients who consent for multiple measurements), assessment of
      endothelial function will be performed preoperatively (baseline) and 24 hours after surgery.

      Vasoactive substances may influence EndoPAT measurement. Thus the investigators will collect
      data on use of preoperative antihypertensive medications that have direct or indirect effect
      on arterial smooth muscle relaxation. Use of epinephrine, norepinephrine, vasopressin,
      milrinone, nitroglycerine, nitroprusside, and sedatives such as propofol, dexmedetomidine and
      others will be recorded and adjusted for in the analysis. Data on packed red blood cells
      (PRBC) and blood component transfusion will be collected from Anesthesia Record Keeping
      System. Indications for PRBC transfusion include hematocrit (HCT) <22% on cardiopulmonary
      bypass and <24% off cardiopulmonary bypass, and hypovolemia with anemia (HCT<25% with mean
      arterial blood pressure <60 mmHg or heart rate >100 bpm). Blood component transfusion
      (platelets, fresh frozen plasma, cryoprecipitate) may be administered as necessary following
      institutional standard of care. Imbalances in blood product transfusion between study groups
      will be adjusted for in the analysis.
    

Intervention name(s): Human albumin; Hydroxyethyl starch
Intervention type(s): Drug; Drug
Intervention description(s): human albumin 5% during surgery; 6% Hydroxyethyl starch 130/0.4 during surgery
Other intervention name(s): albumin; HES
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other