Effect of High Dose Insulin on Infectious Complications Following Major Surgery

Study Overview
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Brief Summary
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Despite improvements in surgical techniques and perioperative care, the high incidence of postoperative surgical site infections remains a major problem in patients undergoing major abdominal surgery (liver, pancreatic and colorectal surgery). Using the hyperinsulinemic-normoglycemic clamp technique, i.e. continuous infusion of insulin combined with dextrose titrated to clamp blood glucose between 4 and 6 mmol/L, we successfully established and preserved normoglycemia during the perioperative period. Our objective of this study is to determine if the maintenance of perioperative normoglycemia by a hyperinsulinemic normoglycemic clamp reduces the rates of incisional and space/ surgical site infections following abdominal surgery (liver, pancreatic and colorectal surgery).

Detailed Description
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This randomized, open-label, controlled trial will be performed in adult (>18 years old) patients scheduled for elective open abdominal aortic aneurysm repairs and open hepatobiliary procedures including liver resections, pancreatectomies, duodenectomies, gastrojejunostomies, choledochojejunostomies and hepaticojejunostomies) at the Royal Victoria Hospital (RVH), McGill University Health Centre (MUHC), Montreal, QC, Canada. Inclusion criteria: above 18 years old, scheduled for elective open abdominal aortic aneurysm repairs and open hepatobiliary procedures. Exclusion criteria: inability to give consent, current wound infection, previous surgery at the same site within the preceding 30 days, allergy to insulin. RECRUITMENT Initial contact prior to surgery will be made by a research team member not involved in the care of the patient who will explain the research project and obtain written consent. Consenting patients will then be randomized with the assistance of a computerized randomization system.

Official Title
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Effect of Hyperinsulinemic Normoglycemic Clamp (HINC) on Infectious Complications Following Major Abdominal Surgery. A Randomized Controlled Trial.

Conditions
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Surgical Site Infection After Major Surgery

Intervention / Treatment
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* Other: Hyperinsulinemic normoglycemic clamp
* Other: Standard glucose management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years old elective liver, pancreatic or colorectal surgery ability to give informed consent Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard glucose management<br>Arterial-blood glucose levels will be checked at induction of anesthesia and every 30 - 60 min thereafter with an StatStrip Xpress® (Nova Biomedical, MA, USA) ( A blood glucose level above 10 mmol/l will be treated with a 2U bolus of IV insulin (Humulin® R regular insulin, Eli Lilly and Company, Indianapolis, IN) followed by a 1 U/hour drip infusion adjusted according to a standard sliding scale | Other: Standard glucose management<br>* Blood glucose levels will be treated by a standard insulin sliding scale.<br>|
| Active Comparator: Hyperinsulinemic normoglycemic clamp<br>The blood glucose level will be checked prior to intubation. A 2U bolus of IV insulin will be given if blood glucose level is higher than 6 mmol/l, followed by an IV infusion of 2 U/kg/min (0.12 U/kg/hour). Dextrose 20% (D20W®) will be titrated to maintain blood glucose between 4 and 6 mmol/l. Blood glucose levels will be measured at 5-30 min intervals with a to ensure normoglycemia. At the end of surgery, the insulin infusion will be stopped, and the dextrose infusion weaned off in the post anesthesia care unit. | Other: Hyperinsulinemic normoglycemic clamp<br>* Patients will receive an IV infusion of 2 mU/kg/min (0.12 U/kg/hour) starting in the operating room. Dextrose 20% will be titrated to maintain blood glucose between 4 and 6 mmol/l. At the end of surgery, the insulin infusion will be stopped and the dextrose infusion weaned off in the postanesthesia care unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical site infection | Surgical site infections will be defined according to the CDC's NNIS system. | for 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical morbidity | Surgical morbidity in the 30 days following the operation will be assessed as per Clavien score. | 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, surgery, infection