Ulinastatin's Anti-inflammatory Reaction in Cardiac Surgery (ulistin)

Effect of Ulinastatin on Postoperative Systemic Inflammatory Response in Cardiac Surgery

The purpose of the present study is to determine whether ulinastatin, urinary anti-trypsin inhibitor, attenuates cardiopulmonary bypass (CPB)-activated systemic inflammatory response in cardiac surgery with CPB.

Serial measurements and analysis of several inflammatory cytokines (bactericidal permeability increasing protein, interleukin-6, tumor necrosis factor-α)as well as markers of cardiac injury, renal impairment and oxygenation profile will be performed to determine ulinastatin's efficacy.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: placebo; Drug: ulinastatin

Detailed Description

Applying aortic cross-clamp (ACC) and cardiopulmonary bypass (CPB) for cardiac surgery produces variable systemic inflammatory reactions. As a common complication of those reactions, pulmonary dysfunction, which usually indicated by postoperative hypoxemia, is frequently associated with cardiac surgery employing CPB and has been used as a major predictor of morbidity and mortality.

Circulating humoral and cellular factors are involved in the development of the systemic inflammatory reactions including organ dysfunction. So far, many studies analyzed the concentration of inflammatory marker (cytokine) to determine the degree of systemic inflammatory responses in various conditions.

Ulinastatin has anti-inflammatory activity and suppresses the infiltration of neutrophils. Previous studies suggested ulinastatin's cytoprotective effect against ischemia-reperfusion injury in major organs and its inhibition of inflammatory marker production.

The purpose of the present study is to determine ulinastatin's possible protective efficacy of in attenuating CPB-activated systemic inflammatory response regarding postoperative cardiac, renal and pulmonary dysfunction in cardiac surgery with CPB. Serial measurements and analysis of several inflammatory cytokines, such as bactericidal permeability increasing protein (BPI), interleukin (IL)-6, tumor necrosis factor (TNF)-α, as well as markers of cardiac injury, renal impairment and oxygenation profile, such as creatine kinase-MB (CK-MB), troponin I (TnI), C-reactive protein (CRP), arterial O2 tension /inspired O2 fraction (PaO2/FiO2 ratio), will be performed to this purpose.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 143-729
    • Konkuk University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• elective cardiac surgery employing CPB

Exclusion Criteria:

• urgent/emergency surgery,
• previous heart surgery,
• combined CABG and valve surgery,
• age > 75 yrs,
• left ventricular ejection fraction < 0.45,
• diabetes treated with insulin,
• active gastropathic disorder,
• treatment for chronic obstructive pulmonary disease,
• preoperative use of steroids
• postoperative re-operation due to bleeding control
• pre and postoperative renal replacement therapy
• left ventricular assist device implantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; normal saline, same amount, iv	Drug: placebo; placebo (the same amount of normal saline) iv before the initiation of CPB; Other Names: normall saline
Active Comparator: ulinastatin; 5000 unit/kg iv	Drug: ulinastatin; ulinastatin 5000 unit/kg iv before the initiation of CPB; Other Names: ulistin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
bactericidal permeability increasing protein	5-30 min before the end of anesthesia
interleukin-6	5-30 min before the end of anesthesia
tumor necrosis factorTNF-α	5-30 min before the end of anesthesia

Secondary Outcome Measures

Outcome Measure	Time Frame
Creatine kinase-MB	before anesthesia, 24 hour after the end of anesthesia
troponin I	before anesthesia, 24 hour after the end of anesthesia
C-reactive protein	before anesthesia, 24 hour after the end of anesthesia
serum creatinine	before anesthesia, 24 hour after the end of anesthesia
PaO2/FiO2 ratio	before anesthesia, 24 hour after the end of anesthesia

Collaborators and Investigators

• Sponsor: Konkuk University Medical Center

Publications and helpful links

General Publications

• Nakanishi K, Takeda S, Sakamoto A, Kitamura A. Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction. Crit Care Med. 2006 May;34(5):1351-7. doi: 10.1097/01.CCM.0000215110.55899.AE.
• Hill GE. Cardiopulmonary bypass-induced inflammation: is it important? J Cardiothorac Vasc Anesth. 1998 Apr;12(2 Suppl 1):21-5.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: January 25, 2012
• First Posted (Estimate): January 26, 2012

Study Record Updates

• Last Update Posted (Estimate): January 26, 2012
• Last Update Submitted That Met QC Criteria: January 25, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: cardiac surgery; cardiopulmonary bypass; systemic inflammation; ulinastatin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Urinastatin
• Other Study ID Numbers: KUH1160040