Protection of Modified Glucose - Insulin - Potassium on the Heart Surgery Patient

• Liver/Kidney dysfunction [ Time Frame: within the first 30 days after surgery ] [ Designated as safety issue: Yes ]

  Liver dysfunction including jaundice,transaminase elevation 1.5 times more than normal,et al.

  Kidney dysfunction including oliguria,anuria,Cretinine/BUN elevation 1.5 times more than normal,et al.

• Heart dysfunction [ Time Frame: within the first 30 days after surgery ] [ Designated as safety issue: Yes ]
  Heart dysfunction including lower cardiac output(CI<2.2L/m2), lower left ventriculus ejection fraction (LVEF<45%) et al.
• Arrhythmia [ Time Frame: within the first 3 days after surgery ] [ Designated as safety issue: Yes ]
  Arrhythmia including atrial fibrillation, tachycardia, bradycardia,et al.
• Cumulative cerebrovascular events [ Time Frame: within the first 30 days after surgery ] [ Designated as safety issue: Yes ]
  Cerebrovascular events as bleeding, thrombosis, paraplegia, transient unconsciousness, et al.

The purpose of this study is to evaluate the protective effects of modified glucose - insulin - potassium (MGIK) liquid in patients undergoing cardiopulmonary bypass (CPB).

Cardiopulmonary bypass (CPB) is a necessary technique to maintain the circulation during cardiac surgery. But CPB itself is associated with a series of problems of organs, such as hyperglycemia induced by neuroendocrine stress. The research showed that hyperglycemia induced by stress would cause a worsened hospital outcome for patients undergoing cardiac surgery. Intraoperative and postoperative glucose control is beneficial for patients.

It has been for more than 40 year since the first application of Glucose - insulin - potassium (GIK) in cardiac surgery. GIK was considered as a cardiac energy additive. Opie pointed out that GIK is a drug that cost only a few dollars but gets unexpected result. But the clinical application of GIK shows neutral or negative results too. The beginning time of application, and the ratio of glucose and insulin may be the key cause for the difference.

Harold L. Lazar revealed that modified GIK (high ratio of glucose, 3:1) could promote recovery in patients with coronary artery bypass surgery. Howell NJ and other multicenter clinical study revealed that GIK with high ratio insulin had a greater effect than predicted on the treatment of aortic valve replacement patients.

In our pilot test of 40 valve replacement cases, the investigators also found that GIK with high insulin ratio could reduce stress response and prevent organ damage during heart surgery.

Therefore, the investigators are planning to continue to use the GIK with high insulin ratio for more heart surgery patients and estimate whether GIK could protect the organs in patients undergoing heart surgery.

• Insulin Resistance
• Disorder by Body System or Organ Function
• Ischemia-reperfusion Injury
• Complication of Extracorporeal Circulation

• Drug: Modified glucose - insulin - potassium
  MGIK group： CPB+MGIK（N=500），receives a MGIK infusion run at 60 ml.h-1 during operation.
  Other Name: MGIK
• Drug: Balanced salt solution
  CPB+ BSS（N=500）,receives BSS run at 60ml.h-1 during operation
  Other Name: BSS

• Active Comparator: Modified glucose - insulin - potassium
  Intervention: Drug: Modified glucose - insulin - potassium
• Placebo Comparator: Balanced salt solution
  Interventions:

  • Drug: Modified glucose - insulin - potassium
  • Drug: Balanced salt solution

Inclusion Criteria:

• Elective CPB surgery
• Left ventricular ejection fraction(LVEF) ≥ 45%，left ventricular diastolic end diameter(LVDED) ≤ 70mm，Cardiothoracic Ratio(CTR) ≤ 0.70；
• Informed agreement signed

Exclusion Criteria:

• History of heart surgery
• ASA classification = V
• Severe renal insufficiency defined as SVS risk renal status = 3
• Severe respiratory insufficiency defined as SVS risk pulmonary status = 3
• Presence of connective tissue disease
• Active infection
• Pregnant woman or positive pregnancy test
• Myocardial infarction or cerebrovascular accident within 6 weeks prior to study enrollment
• Subject has had a cerebral vascular accident (CVA) within 2 months
• History of drug abuse
• Subject has a history of bleeding diathesis, coagulopathy, or refuses blood transfusion
• Enrollment in another clinical study
• Unwillingness to cooperate with study procedures or follow-up visits