The Investigation of the Causes of Hepatic Dysfunction in the Postoperative Period During Open-heart Surgeries

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Risk Factors, Hepatic Dysfunction, and Open-heart Surgery

Conditions
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Hyperbilirubinemia, Hepatic Impairment, Surgery, Cardiac Disease

Intervention / Treatment
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* Procedure: Open-Heart Surgery for nine months duration
* Other: Relation between possible risk factors and hyperbilirubinemia
* Other: Follow-up period


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Open-heart surgery<br>Patients undergoing open-heart surgery with cardiopulmonary bypass | Procedure: Open-Heart Surgery for nine months duration<br>* 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.<br>* Other names: Hepatic function related tests;Other: Relation between possible risk factors and hyperbilirubinemia<br>* 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.<br>Other: Follow-up period<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of serum total bilirubin values on 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | Use of aortic cross-clamp time | During intraoperative time | 
| Use of cardiopulmonary bypass time; as a risk factor | Use of cardiopulmonary bypass time | During intraoperative time | 
| Use of inotropic support; as a risk factor | 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 | 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 | Duration of prolonged mechanical ventilation | During the first 30 days of postoperative period | 
| Development of pneumonia; as a risk factor | Presence of development of pneumonia | During the first 10 days of postoperative period | 
| Development of perioperative heart attack; a rsik factor | Presence of perioperative myocardial infarction | During intraoperative time and in the first 10 days of postoperative period | 
| Cerebrovascular event; a risk factor | Development of cerebrovascular event (stroke, transient ischemic attack), seizure | During the first 10 days of postoperative period | 
| Presence of rhythm disturbance; a risk factor | 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 | Need for renal replacement therapy (RRT) | During the first 10 days of postoperative period | 
| Need of reoperation; a risk factor | Need of reoperation secondary to bleeding | During the first 10 days of postoperative period | 
| Presence of other adverse events; a risk factor | 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 | Duration of intensive care unit stay | During the first 10 days of postoperative period | 
| Duration of in-hospital stay; a risk factor | Duration of in-hospital stay | During the first 30 days of postoperative period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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open-heart surgery, postoperative, complications, hyperbilirubinemia, hepatic impairment