Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Emory University338 enrolled

Overview

High blood glucose levels (hyperglycemia) in cardiac surgery patients with diabetes are associated with increased risk of hospital complications. Blood sugar control with intravenous insulin may prevent such hospital complications. Many patients undergoing cardiac bypass surgery (CABG) develop high blood sugars and require insulin therapy (shortly before or after surgery). It is not clear what the best insulin regimen is or what is the best blood sugar target in these patients. Accordingly, this research study aims to determine optimal blood glucose levels during the in patients undergoing cardiac bypass surgery. Patients will be divided in two groups. The intensive insulin group will be maintained at blood glucose between 100-140 mg/dl and the conventional treatment group at a glucose level between 140-180 mg/dl. The insulins to be used in this trial (lantus, aspart and regular insulin) are approved for use in the treatment of patients with diabetes by the FDA (Food and Drug Administration). A total of 326 patients with high blood glucose after cardiac bypass surgery will be recruited in this study. Patients will be recruited at Emory University Hospital, Emory Midtown Hospital and Grady Memorial Hospital.

Several prospective cohort studies as well as randomized clinical trials (RCT) in cardiac surgery patients have shown that intensified insulin therapy (target BG: 110-140 mg/dl) results in a reduction in short- and long-term mortality compared with conventionally treated patients. The results of recent international trials in critically ill patients; however, have failed to show a significant improvement in mortality or have even shown increased mortality risk as well as increased number of hypoglycemic events with intensive compared to less intensive glycemic control. Based on the results of these ICU trials, new ADA and AACE guidelines recommended a glycemic target between 140 and 180 mg/dl in the ICU including cardiac surgery patients. There is concern that such high BG targets might increase the risk of hospital complications in cardiac surgical patients in whom intensive glucose control has consistently reduced infections, length of hospital stay, resource utilization, and cardiac-related mortality. The overall objective of this proposal is to conduct the first prospective RCT to determine the optimal BG target during the perioperative period in hyperglycemic subjects who undergo CABG in the United States. Subjects will be randomized to undergo intensive insulin therapy adjusted to maintain a BG between 100 mg/dl and 140 mg/dl or to a conventional glucose control with a target BG between 141 mg/dl and 200 mg/dl in the ICU. The central hypothesis of this proposal is that intensive insulin management will reduce perioperative complications compared to a conventional BG control in cardiac surgery patients.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Males or females between the ages of 18 and 80 years undergoing CABG +/- valve surgery. 2. Post surgical hyperglycemia (BG \> 140 mg/dl). 3. Patients with and without a history of type 2 diabetes Exclusion Criteria: 1. Patients requiring combination CABG with additional procedures such aorta replacement. 2. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or GFR \< 30 ml/min) or clinically significant hepatic failure. 3. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state. 4. Moribund patients and those at imminent risk of death (brain death or cardiac standstill). 5. Patients or next-to-kin with mental condition rendering the subject or family member unable to understand the nature, scope, and possible consequences of the study. 6. Female subjects who are pregnant or breast-feeding at time of enrollment into the study.

Outcomes

Primary Outcomes

Number of Subjects That Were Diagnosed for Peri-operative Complications

Number of participants that presented at least 1 complications including sternal wound infection, bacteremia, acute renal failure, respiratory failure, and major cardiovascular events (MACE) during the current hospitalization and up to 6 months after hospitalization

Time frame: Within 6 months of hospitalization

Hospital Mortality

Mortality is defined as death occurring during admission, either during ICU or after transition to non-ICU admission.

Time frame: average 1 month during the hospitalization

Secondary Outcomes

Glycemic Control

1. Hyperglycemic events (BG \> 200 mg/dL) in ICU and non-ICU 2. Hypoglycemic events (BG \< 70 mg/dl; severe hypoglycemia (BG \< 40 mg/dl).

Time frame: average 1 month during the hospitalization

Major Cardiovascular Events

1. Acute myocardial infarction : (1) typical increase and gradual decrease (troponin) or (2) more rapid increase and decrease (creatine kinase MB) of biochemical markers of myocardial necrosis with at least one of the following: (a) ischemic symptoms, (b) development of pathologic Q waves on the electrocardiogram, (c) electrocardiographic changes indicative of ischemia (ST-segment elevation or depression), or (d) coronary artery intervention (e.g., coronary angioplasty). 2. Congestive heart failure 3. Cardiac arrhythmias: malignant arrhythmia

Time frame: average 1 month during the hospitalization

Acute Renal Failure

new-onset abnormal renal function: serum creatinine \> 2.0 mg/dL or an increment level \> 50% from baseline

Time frame: average 1 month during the hospitalization

Respiratory Failure, Defined as PaO2 Value < 60 mm Hg While Breathing Air or a PaCO2 > 50 mm Hg.

Respiratory failure, defined as PaO2 value \< 60 mm Hg while breathing air or a PaCO2 \> 50 mm Hg.

Time frame: average 1 month during the hospitalization

ICU and Hospital Length of Stay, and ICU Readmissions

ICU and hospital length of stay, and ICU readmissions

Time frame: average 1 month during the hospitalization

Surgical Wound Infection

superficial and deep sternal wound infection

Time frame: average 1 month during the hospitalization

Pneumonia (CDC Criteria)

Pneumonia (CDC criteria)

Time frame: average 1 month during the hospitalization

Cerebrovascular Events

permanent stroke and reversible ischemic neurologic deficit.

Time frame: average 1 month during the hospitalization

Duration of Ventilatory Support and ICU Readmission

Duration of ventilatory support and ICU readmission

Time frame: average 1 month during the hospitalization

Thirty Day Mortality

Thirty day mortality

Time frame: within 30 days of discharge

Number of Hospital Readmissions and Emergency Room Visits

Number of hospital readmissions and emergency room visits

Time frame: Within 30 days after discharge

Incidence of Organ Failures Assessed by the Daily SOFA Score

Incidence of organ failures assessed by the daily SOFA score

Time frame: average 1 month during the hospitalization

Measures of Inflammation

Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers

Time frame: average 1 month during the hospitalization

Major Cardiovascular Events

Time frame: within 3 months after discharge

Surgical Wound Infection

Superficial and deep sternal wound infection

Time frame: within 3 months after discharge

Pneumonia (CDC Criteria)

Pneumonia (CDC criteria)

Time frame: Within 3 months after discharge

Cerebrovascular Events

permanent stroke and reversible ischemic neurologic deficit

Time frame: within 3 months after discharge

Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes