Optimizing Pulsatility During Cardiopulmonary Bypass

Optimizing Pulsatility During Cardiopulmonary Bypass to Reduce Acute Kidney Injury: Prospective Observational Study

Cardiopulmonary bypass during cardiac surgery provides blood flow to the body during surgery but has adverse effects on different organs. Blood flow during cardiopulmonary bypass may be pulsatile or non-pulsatile, which may impact normal organ function after surgery. The study will collect data on the type of cardiopulmonary bypass used during surgery and organ function to determine if there is an association between the type of bypass and organ function.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Endothelial Dysfunction

Detailed Description

Cardiac surgery is a high-risk elective surgical procedure frequently requiring CPB in which a machine pumps blood while the surgeon operates on the heart. CPB contributes to surgical risk by causing endothelial dysfunction and acute kidney injury (AKI). Endothelial dysfunction and AKI happen because heart lung machines typically generate non-pulsatile blood flow, which is abnormal and results in impaired tissue oxygen delivery. Normal blood flow is pulsatile due intermittent contraction and relaxation of the heart during the cardiac cycle, which produces a mechanical signal that induces endothelial cells to produce nitric oxide. Without nitric oxide, blood flow does not penetrate as deeply into organs such as the kidneys which leads to acute kidney injury. AKI increases mortality 10-fold after cardiac surgery placing many people at risk since over 400,000 people have surgery with CPB each year in the United States. Thus, pulsatile CPB may influence endothelial function and renal blood flow after cardiac surgery. This study will observe patients undergoing cardiac surgery with CPB and compare patients who receive pulsatile or non-pulsatile CPB.

• Study Type: Observational
• Enrollment (Estimated): 66

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Contact: Nathan Clendenen, MD MS; Phone Number: 303-724-5000; Email: nathan.clendenen@cuanschutz.edu
      • Principal Investigator: Nathan J Clendenen, MD MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients aged 50 to 70 years scheduled for elective cardiac surgery with cardiopulmonary bypass

Description

Inclusion Criteria:

• Age 50 to 70
• Able to provide informed consent
• Scheduled for elective cardiac surgery with cardiopulmonary bypass

Exclusion Criteria:

• Patients undergoing emergency procedures
• Diagnosed with sepsis
• Experiencing delirium
• Experiencing hemodynamic instability (heart rate > 100 and systolic blood pressure < 90)
• Patients with a mechanical circulatory support device
• Requiring vasoactive medications before surgery
• Patients with a reduced left ventricular ejection fraction (less than 50%)
• Patients with a contraindication to transesophageal echocardiography

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Non-pulsatile cardiopulmonary bypass; Subjects who undergo cardiac surgery with non-pulsatile cardiopulmonary bypass
Pulsatile cardiopulmonary bypass; Subjects who undergo cardiac surgery with pulsatile cardiopulmonary bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function	Percent change in flow mediated dilation of the brachial artery after cardiac surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Acute kidney injury by the KDIGO criteria	From intensive care unit admission after surgery to intensive care unit discharge, up to 7 days
Renal blood flow velocity	Renal blood flow velocity measured by pulse wave doppler	Intra-operative time point: after cardiopulmonary bypass, up to 12 hours
Acute kidney injury risk	Acute kidney injury risk measured by urinary TIMP2*IGFBP7	Measured 4 hours after the end of cardiopulmonary bypass, up to 12 hours
Perioperative death	Death after surgery during the surgical hospital encounter	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Myocardial infarction	Myocardial infarction after surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Stroke	Stroke after surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New renal failure requiring renal replacement therapy	New renal failure requiring renal replacement therapy after surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Re-exploration for bleeding	Need for surgical re-exploration to control hemorrhage	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative sepsis	Post-operative sepsis determined by positive blood culture	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset atrial fibrillation	Post-operative new onset atrial fibrillation	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative blood loss	Post-operative blood loss determined by total surgical drain output	From intensive care unit admission to 24 hours after intensive care unit admission, up to 24 hours
Duration of mechanical ventilation	Duration of mechanical ventilation after surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative delirium	Post-operative delirium determined by the Confusion Assessment Method for the Intensive Care Unit score	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative hospital length of stay	Duration of hospital stay after surgery	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New requirement for mechanical circulatory support	Post-operative initiation of mechanical circulatory support	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Intra-operative red blood cell transfusion	Intra-operative red blood cell transfusion in units	During the intra-operative time period, up to 12 hours
Post-operative red blood cell transfusion	Post-operative red blood cell transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative platelet transfusion	Post-operative platelet transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative plasma transfusion	Post-operative plasma transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative cryoprecipitate transfusion	Post-operative cryoprecipitate transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Intra-operative platelet transfusion	Intra-operative platelet transfusion in units	During the intra-operative time period, up to 12 hours
Intra-operative plasma transfusion	Intra-operative plasma transfusion in units	During the intra-operative time period, up to 12 hours
Intra-operative cryoprecipitate transfusion	Intra-operative cryoprecipitate transfusion in units	During the intra-operative time period, up to 12 hours
Glycocalyx thickness	Glycocalyx thickness determined by sublingual microcirculation microscopy	Start of the intra-operative period to 24 hours after intensive care unit admission
Microvascular circulatory function	Microvascular circulatory function determined by sublingual microcirculation microscopy	Start of the intra-operative period to 24 hours after intensive care unit admission
New onset of acute lung injury	Diagnosis of acute lung injury by PaO2 to FiO2 ratio	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset of left ventricular diastolic dysfunction	Diagnosis new onset diastolic dysfunction by annular e' velocity: septal e' < 7 cm/sec, lateral e' <10 cm/sec, average E/e' ratio > 14, LA volume index > 34 mL/m2, and peak TR velocity > 2.8 m/sec.	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset of left ventricular systolic dysfunction	New onset of left ventricular systolic dysfunction determined by a LV ejection fraction <50%	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset of right ventricular systolic dysfunction	New onset of right ventricular systolic dysfunction determined by a tricuspid annular plane systolic excursion less than 16 mm	From intensive care unit admission after surgery to hospital discharge, up to 30 days

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Nathan J Clendenen, MD, MS, University of Colorado Denver | Anschutz

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Endothelial function; Acute Kidney Injury; Cardiac surgery; Cardiopulmonary bypass
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury
• Other Study ID Numbers: 20-2465; K23HL151882 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No