Endothelial Function After Cardiac Surgery

NCT ID: NCT02882074

Last Updated: 2024-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-02-20

Brief 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.

Conditions

Endothelial Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Human albumin

Human albumin 5% during surgery.

Group Type: OTHER

Human albumin

Intervention Type: DRUG

human albumin 5% during surgery

Hydroxyethyl starch

Hydroxyethyl starch 6% (130/0.4) solution during surgery

Group Type: OTHER

Hydroxyethyl starch

Intervention Type: DRUG

6% Hydroxyethyl starch 130/0.4 during surgery

Interventions

Human albumin

human albumin 5% during surgery

Intervention Type: DRUG

Hydroxyethyl starch

6% Hydroxyethyl starch 130/0.4 during surgery

Intervention Type: DRUG

Other Intervention Names

albumin; HES

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Sessler, M.D.

Role: STUDY_CHAIR

Department Chair

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

16-342

Identifier Type: -

Identifier Source: org_study_id