Endothelial Function After Cardiac Surgery

Does Plasma Volume Replacement With 5% Human Albumin Reduce Endothelial Injury and Glycocalyceal Disruption Compared With 6% Hydroxyethylstarch (130/0.4) in Patients Having Cardiac Surgery? A Substudy of the SHARP Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Drug: Human albumin; Drug: Hydroxyethyl starch

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.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 40 - 85 years old
• Scheduled for elective aortic valve replacement with or without coronary artery bypass grafting with or without additional minor surgical procedure.
• Written, informed consent for participation in this investigation.

Exclusion Criteria:

• Patients with Raynaud's disease or other disease associated with upper extremity vascular insufficiency,
• Inability to perform EndoPAT exam (inability to lie still for 15 min, or significant finger deformity),
• Patients with renal failure with oliguria or anuria not related to hypovolemia.
• Patients receiving dialysis.
• Patients with preoperative renal insufficiency (Creatinine > 1.6 mg/dL)
• Anticipated deep hypothermic circulatory arrest
• Known hypersensitivity or allergy to hydroxyethyl starch or the excipients of hydroxyethyl starch
• Clinical conditions with volume overload (e.g., patients in pulmonary edema or congestive heart failure)
• Patients with severe hypernatremia or severe hyperchloremia
• Patients with intracranial bleeding
• Pregnant or breast feeding women
• Critically ill adult patients, including patients with sepsis, due to increased risk of mortality and renal replacement therapy, (e.g. patients who are hospitalized in the intensive care unit prior to surgery)
• Severe liver disease
• Pre-existing coagulation or bleeding disorders
• Any contraindications to proposed interventions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Human albumin; Human albumin 5% during surgery.	Drug: Human albumin; human albumin 5% during surgery; Other Names: albumin
Other: Hydroxyethyl starch; Hydroxyethyl starch 6% (130/0.4) solution during surgery	Drug: Hydroxyethyl starch; 6% Hydroxyethyl starch 130/0.4 during surgery; Other Names: HES

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Hyperemia Index (RHI)	RHI measures endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT) with the EndoPAT device. It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. Increasing score indicates the improvement of coronary endothelial function.	2 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Syndecan	Blood samples will be obtained at specified times	1 hour after surgery, 24 hours after surgery
Plasma Concentrations of Endocan	Blood samples will be obtained at specified times	1 hour after surgery, 24 hours after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Hyperemia Index (RHI)	RHI measures endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT) with the EndoPAT device. It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered a sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. Increasing score indicates the improvement of coronary endothelial function.	24 hours after surgery

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Study Chair: Daniel Sessler, M.D., Department Chair

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: August 17, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimated): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 16-342

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO