Cardiopulmonary Bypass Induced Red Blood Cell Lysis

Extra-Cellular Hemoglobin, Organ Injury in Extended Cardiopulmonary Bypass

Studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury, limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Surgery; Cardiopulmonary Bypass; Kidney Injury, Acute
• Intervention / Treatment: Other: Blood and urine collection

Detailed Description

Cost estimates for brain, lung, cardiac, and kidney complications following complex cardiac surgeries that require a medical assist device to by-pass the heart and lungs (cardiopulmonary bypass, CPB) is estimated to cost $80 million per individual states in the US over a ten-year period. These extra costs represent a significant burden on the healthcare system but could be reduced by understanding how medical assist devices lead to organ injury associated with complex cardiac surgeries. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Paul W Buehler, PhD; Phone Number: 14107065171; Email: pbuehler@som.umaryland.edu
• Study Contact Backup: Name: Tobi Rowden, RN; Phone Number: 4107064061; Email: trowden@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Center for Blood Oxygen Transport and Hemostasis
      • Contact: Tobi Rowden, RN; Phone Number: 4107064061; Email: trowden@som.umaryland.edu
      • Contact: Paul W Buehler, PhD; Phone Number: 410-706-5171; Email: pbuehler@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Research Participants will include approximately 90 adult (>/=18 years of age to 75 years of age) medium to high risk patients. Both Male and female subjects who are undergoing complex cardiac surgery requiring, heart valve replacement, or CABG surgery requiring cardiopulmonary bypass >1hr will be eligible for enrollment at the University of Maryland Medical Center (UMMC) in Baltimore, MD. This study is a prospective observational investigation.

Description

Inclusion Criteria:

• Admitted to UMMC for cardiac procedure
• Age: >/=18 y.o TO 75 y.o.
• Undergoing CPB >1hr for the following surgeries (a) complex cardiac surgery (b) heart valve replacement surgery OR (c) CABG surgery.

Exclusion Criteria:

• Pregnant
• Non English speaking
• Unable to consent or have Legally Authorized Representative (LAR) assent to study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cardiac Sugery Patients Requiring Cardiopulmonary >1hour; Patients admitted for a complex cardiac surgery, heart valve replacement and/or CABG surgery requiring CPB >1hour	Other: Blood and urine collection; No intervention - Biological specimen collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 1 during procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 2 during procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 3 during procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline at hour 4 during procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline at hour 4 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline at hour 2 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline at hour 24 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline on day 2 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline on day 3 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline on day 4 post procedure
Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure	Change from baseline on day 5 post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 1 during procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 2 during procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 3 during procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 4 during procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 2 post procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 24 post procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 2 days post procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 3 days post procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 4 days post procedure
Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 5 days post procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 1 during procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 2 during procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 3 during procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 4 during procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 2 post procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 24 post procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at day 2 post procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at day 3 post procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at day 4 post procedure
Blood cell function	CBC and red blood cell deformability	Change from baseline at day 5 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 1 during procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 2 during procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 3 during procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 4 during procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 2 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 24 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 2 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 3 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 4 post procedure
Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 5 post procedure

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Paul Buehler, PhD, University of Maryland

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• 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: HP-00094849; 1R01HL162120-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Deidentified data may be used in a publication

Drug and device information, study documents

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