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

Surgery Clinical Trial

Official title:

Risk Factors, Hepatic Dysfunction, and Open-heart Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04271098
• Other study ID #: 2011.3/05
• Status: Completed
• Start date: January 1, 2012
• Est. completion date: September 1, 2012

Study information

• Verified date: February 2020
• Source: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 340
• Est. completion date: September 1, 2012
• Est. primary completion date: July 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Disease
• Heart Diseases
• Hepatic Impairment
• Hyperbilirubinemia
• Surgery

Intervention

Procedure:
• Open-Heart Surgery for nine months duration
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:
• Relation between possible risk factors and hyperbilirubinemia
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.
• Follow-up period
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

References & Publications (11)

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. — View Citation

Chu CM, Chang CH, Liaw YF, Hsieh MJ. Jaundice after open heart surgery: a prospective study. Thorax. 1984 Jan;39(1):52-6. — View Citation

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. — View Citation

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. — View Citation

Lockey E, McIntyre N, Ross DN, Brookes E, Sturridge MF. Early jaundice after open-heart surgery. Thorax. 1967 Mar;22(2):165-9. — View Citation

McSweeney ME, Garwood S, Levin J, Marino MR, Wang SX, Kardatzke D, Mangano DT, Wolman RL; Investigators of the Ischemia Research and Education Foundation; Multicenter Study of Perioperative Ischemia Research Group. Adverse gastrointestinal complications a — View Citation

Michalopoulos A, Alivizatos P, Geroulanos S. Hepatic dysfunction following cardiac surgery: determinants and consequences. Hepatogastroenterology. 1997 May-Jun;44(15):779-83. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	Use of aortic cross-clamp time; as a risk factor	Use of aortic cross-clamp time	During intraoperative time
Secondary	Use of cardiopulmonary bypass time; as a risk factor	Use of cardiopulmonary bypass time	During intraoperative time
Secondary	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
Secondary	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
Secondary	Use of prolonged mechanical ventilation; as a risk factor	Duration of prolonged mechanical ventilation	During the first 30 days of postoperative period
Secondary	Development of pneumonia; as a risk factor	Presence of development of pneumonia	During the first 10 days of postoperative period
Secondary	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
Secondary	Cerebrovascular event; a risk factor	Development of cerebrovascular event (stroke, transient ischemic attack), seizure	During the first 10 days of postoperative period
Secondary	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
Secondary	Need of renal replacement therapy; a risk factor	Need for renal replacement therapy (RRT)	During the first 10 days of postoperative period
Secondary	Need of reoperation; a risk factor	Need of reoperation secondary to bleeding	During the first 10 days of postoperative period
Secondary	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
Secondary	Duration of intensive care unit stay; a risk factor	Duration of intensive care unit stay	During the first 10 days of postoperative period
Secondary	Duration of in-hospital stay; a risk factor	Duration of in-hospital stay	During the first 30 days of postoperative period