- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04271098
The Investigation of the Causes of Hepatic Dysfunction in the Postoperative Period During Open-heart Surgeries
February 18, 2020 updated by: Ayse Baysal, Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Risk Factors, Hepatic Dysfunction, and Open-heart Surgery
In a prospective observational study during the six-month duration, coronary artery bypass graft surgery (CABG) and valve repair surgery (mitral, mitral, and aortic valve and/or tricuspid valve) patients were investigated for hepatic dysfunction.
All patients were divided into two groups as with or without hyperbilirubinemia, and this was defined by the occurrence of a plasma total bilirubin concentration of more than 34 µmol/L (2 mg/dL) in any measurement during the postoperative period.
Our goal was to determine the risk factors associated with hepatic dysfunction in patients undergoing open-heart surgery with cardiopulmonary bypass.
The collected parameters include; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and gamma-glutamyl transpeptidase (GGT) and albumin preoperatively and on postoperative days 1, 3 and 7. Possible preoperative, intraoperative, and postoperative risk factors were investigated.
Logistic regression analysis was done to identify the risk factors for postoperative hyperbilirubinemia.
Study Overview
Status
Completed
Detailed Description
There are a series of pathophysiological changes in patients undergoing open-heart surgeries with cardiopulmonary bypass (CPB) that causes liver hypoperfusion, centrilobular sinusoid ischemia, and subsequent reperfusion injuries, hemolysis, or systemic inflammatory response.
These events may eventually lead to various forms of hepatic dysfunction in patients during the postoperative period after open-heart surgeries.
An increased incidence of liver function test abnormalities were reported, and the rates vary between 10 % and 40%.
The occurrence of postoperative hyperbilirubinemia is crucial in increased morbidity and mortality after open-heart surgery with CPB.
There are several reports of the possible risk factors that are associated with hepatic dysfunction.
In previous studies, the incidence of postoperative hyperbilirubinemia was between the range of 20% up to 51% in open-heart surgeries with CPB.
The causes of this higher incidence were related to the presence of various possible risk factors, and these include; valvular heart disease and related low cardiac output states, and low ejection fraction.
Other important risk factors for postoperative hepatic dysfunction after open-heart surgery with CPB were longer operative time and a larger volume of blood transfusion.
However, CPB itself is not a significant constituent in the postoperative development of hyperbilirubinemia.
Splanchnic ischemia before or during operation and in the postoperative period appears to be an essential cause.
Other risk factors that were identified as possible risk factors for postoperative hepatic dysfunction.
We can list these factors as; poor preoperative heart function, hemodynamic instability, emergency surgery, and preoperative liver dysfunction.
Our goal was to determine the possible risk factors associated with hepatic dysfunction in patients undergoing open-heart surgery with CPB.
Study Type
Observational
Enrollment (Actual)
340
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years to 80 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
The study is performed on a patient population undergoing open-heart surgery with cardiopulmonary bypass.
Description
Inclusion Criteria:
- Patients undergoing open-heart surgery with CPB,
- Patients between the ages of 19 to 80,
- American Society of Anesthesiologist (ASA) status of 2 and 3,
- Preoperative ejection fraction (EF) greater than 30%.
- There were five different open-heart surgery group of patients in this study. The groups include; coronary artery bypass grafting (CABG), mitral valvular replacement, aortic valvular replacement, combined mitral and aortic valve replacement, combined mitral, aortic and/or tricuspid valve replacements.
Exclusion Criteria:
- Both CABG and valve replacement,
- Resection of a ventricular or aortic aneurysm,
- Transplantation or another surgical procedure,
- Reoperation of valvular repair surgery, patients with preoperative ejection fraction less than 30%,
- Preoperative hyperbilirubinemia defined as total bilirubin concentration of more than 3 mg/dL,
- Preoperative congestive heart failure, preoperative renal dysfunction (serum creatinine greater than 1.3 mg/dL),
- Chronic oliguria/anuria requiring dialysis,
- Preoperative American Society of Anesthesiologist (ASA) status of 4,
- History of pancreatitis or current corticosteroid treatment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Open-heart surgery
Patients undergoing open-heart surgery with cardiopulmonary bypass
|
In a single group of patients including 340 patients undergoing open-heart surgery during a period of nine months, the collected parameters include; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and gamma-glutamyl transpeptidase (GGT) and albumin preoperatively and on postoperative days of 1, 3 and 7.
All patients were divided into two groups as with or without hyperbilirubinemia, and this was defined by the occurrence of a plasma total bilirubin concentration of more than 34 µmol/L (2 mg/dL) in any measurement during the postoperative period.
For each diagnostic test, a comparison within the group for different time points was statistically evaluated by analysis of variance tests.
Other Names:
Possible preoperative, intraoperative, and postoperative risk factors were investigated.
The relations between hyperbilirubinemia and possible risk factors are sought by the use of the statistical analysis methods including logistic regression analysis.
All patients were investigated for a period of ten days postoperatively.
During this period, intensive care unit (ICU) stay, in-hospital stay, and all adverse events were recorded.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of serum total bilirubin values on postoperative day 1.
Time Frame: Preoperative one day before surgery and postoperative day 1.
|
Change from baseline (preoperative) of serum total bilirubin on postoperative day 1.
|
Preoperative one day before surgery and postoperative day 1.
|
Comparison of serum total bilirubin values on postoperative day 3.
Time Frame: Preoperative one day before surgery and postoperative day 3.
|
Change from baseline (preoperative) of serum total bilirubin on postoperative day 3.
|
Preoperative one day before surgery and postoperative day 3.
|
Comparison of serum total bilirubin values on postoperative day 7.
Time Frame: Preoperative one day before surgery and postoperative day 7.
|
Change from baseline (preoperative) of serum total bilirubin on postoperative day 7.
|
Preoperative one day before surgery and postoperative day 7.
|
Comparison of all serum total bilirubin values at all collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum albumin values on postoperative day 1.
Time Frame: Preoperative one day before surgery and postoperative day 1.
|
Change from baseline (preoperative) of serum albumin on postoperative day 1.
|
Preoperative one day before surgery and postoperative day 1.
|
Comparison of serum albumin values on postoperative day 3.
Time Frame: Preoperative one day before surgery and postoperative day 3.
|
Change from baseline (preoperative) of serum albumin on postoperative day 3.
|
Preoperative one day before surgery and postoperative day 3.
|
Comparison of serum albumin values on postoperative day 7.
Time Frame: Preoperative one day before surgery and postoperative day 7.
|
Change from baseline (preoperative) of serum albumin on postoperative day 7.
|
Preoperative one day before surgery and postoperative day 7.
|
Comparison of all serum albumin values at all collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum alkaline phosphatase (ALP) values on postoperative day 1.
Time Frame: Preoperative one day before surgery and on postoperative day of 1.
|
Change from baseline (preoperative) of serum alkaline phosphatase (ALP) on postoperative day 1.
|
Preoperative one day before surgery and on postoperative day of 1.
|
Comparison of serum alkaline phosphatase (ALP) values on postoperative day 3.
Time Frame: Preoperative one day before surgery and on postoperative day of 3.
|
Change from baseline (preoperative) of serum alkaline phosphatase (ALP) on postoperative day 3.
|
Preoperative one day before surgery and on postoperative day of 3.
|
Comparison of serum alkaline phosphatase (ALP) values on postoperative day 7.
Time Frame: Preoperative one day before surgery and on postoperative day of 7.
|
Change from baseline (preoperative) of serum alkaline phosphatase (ALP) on postoperative day 7.
|
Preoperative one day before surgery and on postoperative day of 7.
|
Comparison of all serum alkaline phosphatase (ALP) values at all collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum alanine transaminase (ALT) values on postoperative day 1.
Time Frame: Preoperatively one day before surgery and on postoperative day of 1.
|
Change from baseline (preoperative) of serum alanine transaminase (ALT) on postoperative day 1.
|
Preoperatively one day before surgery and on postoperative day of 1.
|
Comparison of serum alanine transaminase (ALT) values on postoperative day 3.
Time Frame: Preoperatively one day before surgery and on postoperative day of 3.
|
Change from baseline (preoperative) of serum alanine transaminase (ALT) on postoperative day 3.
|
Preoperatively one day before surgery and on postoperative day of 3.
|
Comparison of serum alanine transaminase (ALT) values on postoperative day 7.
Time Frame: Preoperatively one day before surgery and on postoperative day of 7.
|
Change from baseline (preoperative) of serum alanine transaminase (ALT) on postoperative day 7.
|
Preoperatively one day before surgery and on postoperative day of 7.
|
Comparison of all serum alanine transaminase (ALT) values at all collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum aspartate transaminase (AST) values on postoperative day 1.
Time Frame: Preoperatively one day before surgery and on postoperative day of 1.
|
Change from baseline (preoperative) of serum aspartate transaminase (AST) on postoperative day 1.
|
Preoperatively one day before surgery and on postoperative day of 1.
|
Comparison of serum aspartate transaminase (AST) values on postoperative day 3.
Time Frame: Preoperatively one day before surgery and on postoperative day of 3.
|
Serum aspartate transaminase (AST) values were collected preoperative and postoperative day 3.
|
Preoperatively one day before surgery and on postoperative day of 3.
|
Comparison of serum aspartate transaminase (AST)values on postoperative day 7.
Time Frame: Preoperatively one day before surgery and on postoperative day of 7.
|
Serum aspartate transaminase (AST) values were collected preoperative and postoperative day 7.
|
Preoperatively one day before surgery and on postoperative day of 7.
|
Comparison of all serum aspartate transaminase (AST) values at all collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum lactate dehydrogenase (LDH) values on postoperative day 1.
Time Frame: Preoperatively one day before surgery and on postoperative day of 1.
|
Change from baseline (preoperative) of serum lactate dehydrogenase (LDH) on postoperative day 1.
|
Preoperatively one day before surgery and on postoperative day of 1.
|
Comparison of serum lactate dehydrogenase (LDH) values on postoperative day 3.
Time Frame: Preoperatively one day before surgery and on postoperative day of 3.
|
Change from baseline (preoperative) of serum lactate dehydrogenase (LDH) on postoperative day 3.
|
Preoperatively one day before surgery and on postoperative day of 3.
|
Comparison of serum lactate dehydrogenase (LDH) values on postoperative day 7.
Time Frame: Preoperatively one day before surgery and on postoperative day of 7.
|
Change from baseline (preoperative) of serum lactate dehydrogenase (LDH) on postoperative day 7.
|
Preoperatively one day before surgery and on postoperative day of 7.
|
Comparison of all serum lactate dehydrogenase (LDH) values at collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Comparison of serum glutamyl transpeptidase (GGT) values on postoperative day 1.
Time Frame: Preoperatively one day before surgery and on postoperative day of 1.
|
Change from baseline (preoperative) of serum glutamyl transpeptidase (GGT) on postoperative day 1.
|
Preoperatively one day before surgery and on postoperative day of 1.
|
Comparison of serum glutamyl transpeptidase (GGT) values on postoperative day 3.
Time Frame: Preoperatively one day before surgery and on postoperative day of 3.
|
Change from baseline (preoperative) of serum glutamyl transpeptidase (GGT) on postoperative day 3.
|
Preoperatively one day before surgery and on postoperative day of 3.
|
Comparison of serum glutamyl transpeptidase (GGT) values on postoperative day 7.
Time Frame: Preoperatively one day before surgery and on postoperative day of 7.
|
Change from baseline (preoperative) of serum glutamyl transpeptidase (GGT) on postoperative day 7.
|
Preoperatively one day before surgery and on postoperative day of 7.
|
Comparison of all serum glutamyl transpeptidase (GGT) values at collected times.
Time Frame: Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
A repeated measures statistical analysis using analysis of variance tests was performed.
|
Preoperatively one day before surgery and on postoperative days of 1, 3 and 7.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Use of aortic cross-clamp time; as a risk factor
Time Frame: During intraoperative time
|
Use of aortic cross-clamp time
|
During intraoperative time
|
Use of cardiopulmonary bypass time; as a risk factor
Time Frame: During intraoperative time
|
Use of cardiopulmonary bypass time
|
During intraoperative time
|
Use of inotropic support; as a risk factor
Time Frame: During intraoperative time and in the first 10 days of postoperative period
|
Use of various inotropic support agents
|
During intraoperative time and in the first 10 days of postoperative period
|
Use of intra-aortic balloon pump; as a risk factor
Time Frame: During intraoperative time and in the first 10 days of postoperative period
|
Use of intra-aortic balloon pump
|
During intraoperative time and in the first 10 days of postoperative period
|
Use of prolonged mechanical ventilation; as a risk factor
Time Frame: During the first 30 days of postoperative period
|
Duration of prolonged mechanical ventilation
|
During the first 30 days of postoperative period
|
Development of pneumonia; as a risk factor
Time Frame: During the first 10 days of postoperative period
|
Presence of development of pneumonia
|
During the first 10 days of postoperative period
|
Development of perioperative heart attack; a rsik factor
Time Frame: During intraoperative time and in the first 10 days of postoperative period
|
Presence of perioperative myocardial infarction
|
During intraoperative time and in the first 10 days of postoperative period
|
Cerebrovascular event; a risk factor
Time Frame: During the first 10 days of postoperative period
|
Development of cerebrovascular event (stroke, transient ischemic attack), seizure
|
During the first 10 days of postoperative period
|
Presence of rhythm disturbance; a risk factor
Time Frame: During intraoperative time and in the first 10 days of postoperative period
|
Presence of atrial fibrillation and other rhythm disturbances
|
During intraoperative time and in the first 10 days of postoperative period
|
Need of renal replacement therapy; a risk factor
Time Frame: During the first 10 days of postoperative period
|
Need for renal replacement therapy (RRT)
|
During the first 10 days of postoperative period
|
Need of reoperation; a risk factor
Time Frame: During the first 10 days of postoperative period
|
Need of reoperation secondary to bleeding
|
During the first 10 days of postoperative period
|
Presence of other adverse events; a risk factor
Time Frame: During the first 10 days of postoperative period
|
Presence of other adverse events such as; development of sepsis or need for tracheostomy
|
During the first 10 days of postoperative period
|
Duration of intensive care unit stay; a risk factor
Time Frame: During the first 10 days of postoperative period
|
Duration of intensive care unit stay
|
During the first 10 days of postoperative period
|
Duration of in-hospital stay; a risk factor
Time Frame: During the first 30 days of postoperative period
|
Duration of in-hospital stay
|
During the first 30 days of postoperative period
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Zhou W, Wang G, Liu Y, Tao Y, Du Z, Tang Y, Qiao F, Liu Y, Xu Z. Outcomes and risk factors of postoperative hepatic dysfunction in patients undergoing acute type A aortic dissection surgery. J Thorac Dis. 2019 Aug;11(8):3225-3233. doi: 10.21037/jtd.2019.08.72.
- Wang MJ, Chao A, Huang CH, Tsai CH, Lin FY, Wang SS, Liu CC, Chu SH. Hyperbilirubinemia after cardiac operation. Incidence, risk factors, and clinical significance. J Thorac Cardiovasc Surg. 1994 Sep;108(3):429-36.
- Michalopoulos A, Alivizatos P, Geroulanos S. Hepatic dysfunction following cardiac surgery: determinants and consequences. Hepatogastroenterology. 1997 May-Jun;44(15):779-83.
- Lockey E, McIntyre N, Ross DN, Brookes E, Sturridge MF. Early jaundice after open-heart surgery. Thorax. 1967 Mar;22(2):165-9. doi: 10.1136/thx.22.2.165.
- Collins JD, Bassendine MF, Ferner R, Blesovsky A, Murray A, Pearson DT, James OF. Incidence and prognostic importance of jaundice after cardiopulmonary bypass surgery. Lancet. 1983 May 21;1(8334):1119-23. doi: 10.1016/s0140-6736(83)92863-5.
- Chu CM, Chang CH, Liaw YF, Hsieh MJ. Jaundice after open heart surgery: a prospective study. Thorax. 1984 Jan;39(1):52-6. doi: 10.1136/thx.39.1.52.
- Naschitz JE, Slobodin G, Lewis RJ, Zuckerman E, Yeshurun D. Heart diseases affecting the liver and liver diseases affecting the heart. Am Heart J. 2000 Jul;140(1):111-20. doi: 10.1067/mhj.2000.107177.
- McSweeney ME, Garwood S, Levin J, Marino MR, Wang SX, Kardatzke D, Mangano DT, Wolman RL; Investigators of the Ischemia Research and Education Foundation and the Multicenter Study of Perioperative Ischemia Research Group. Adverse gastrointestinal complications after cardiopulmonary bypass: can outcome be predicted from preoperative risk factors? Anesth Analg. 2004 Jun;98(6):1610-1617. doi: 10.1213/01.ANE.0000113556.40345.2E.
- D'Ancona G, Baillot R, Poirier B, Dagenais F, de Ibarra JI, Bauset R, Mathieu P, Doyle D. Determinants of gastrointestinal complications in cardiac surgery. Tex Heart Inst J. 2003;30(4):280-5.
- Atoui R, Ma F, Langlois Y, Morin JF. Risk factors for prolonged stay in the intensive care unit and on the ward after cardiac surgery. J Card Surg. 2008 Mar-Apr;23(2):99-106. doi: 10.1111/j.1540-8191.2007.00564.x.
- Sharma P, Ananthanarayanan C, Vaidhya N, Malhotra A, Shah K, Sharma R. Hyperbilirubinemia after cardiac surgery: An observational study. Asian Cardiovasc Thorac Ann. 2015 Nov;23(9):1039-43. doi: 10.1177/0218492315607149. Epub 2015 Sep 23.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
January 1, 2012
Primary Completion (ACTUAL)
July 1, 2012
Study Completion (ACTUAL)
September 1, 2012
Study Registration Dates
First Submitted
February 11, 2020
First Submitted That Met QC Criteria
February 13, 2020
First Posted (ACTUAL)
February 17, 2020
Study Record Updates
Last Update Posted (ACTUAL)
February 20, 2020
Last Update Submitted That Met QC Criteria
February 18, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2011.3/05
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
We can share the study protocol, clinical study report, the excel data of our clinical work.
IPD Sharing Time Frame
The data is available upon registration and it will be available on the web site if needed.
IPD Sharing Access Criteria
Accessible to all researchers.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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