Effect of High Dose Insulin on Infectious Complications Following Major Surgery

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

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).

Study Overview

• Status: Recruiting
• Conditions: Surgical Site Infection After Major Surgery
• Intervention / Treatment: Other: Standard glucose management; Other: Hyperinsulinemic normoglycemic clamp

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ralph Lattermann, MD PhD; Phone Number: 37023 514-934-1934; Email: ralph.lattermann@gmail.com
• Study Contact Backup: Name: Thomas Schricker, MD PhD; Phone Number: 36057 514-934-1934; Email: thomas.schricker@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Recruiting
      • Royal Victoria Hospital, McGill University Health Centre
      • Contact: Thomas Schricker, MD PhD; Phone Number: 36057 514-934-1934; Email: thomas.schricker@mcgill.ca
      • Contact: Ralph Lattermann, MD PhD; Phone Number: 35802 514-934-1934; Email: ralph.lattermann@muhc.mcgill.ca
      • Principal Investigator: Ralph Lattermann, MD PhD
      • Sub-Investigator: Thomas Schricker, MD PhD
      • Sub-Investigator: George Carvalho, MD MSc
      • Sub-Investigator: Peter Metrakos, MD
      • Sub-Investigator: Linda Wykes, PhD
      • Sub-Investigator: Mazen Hassanain, MD
    • Montreal, Quebec, Canada, H3A1A1
      • Not yet recruiting
      • Royal Victoria Hospital
      • Contact: Ralph Lattermann, MD PhD; Phone Number: 37023 514-934-1934; Email: ralph.lattermann@gmail.com
      • Sub-Investigator: Roupen Hatzakorzian, MD
      • Sub-Investigator: Prosanto Chaudhury, MD MSc
      • Sub-Investigator: Charles Frenette, MD
      • Contact: Thomas Schricker, MD PhD; Phone Number: 36057 514-934-1934; Email: thomas.schricker@mcgill.ca
      • Sub-Investigator: Peter Metrakos, MD
• Chile
  • Santiago
    • Independencia, Santiago, Chile, 8380456
      • Not yet recruiting
      • Hospital Clinico Universidad de Chile
      • Contact: Daniela B Advis, M.D.; Phone Number: +5629788211; Email: dbravoadvis@uchile.cl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• > 18 years old
• elective liver, pancreatic or colorectal surgery
• ability to give informed consent

Exclusion Criteria:

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard glucose management; 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; Blood glucose levels will be treated by a standard insulin sliding scale.
Active Comparator: Hyperinsulinemic normoglycemic clamp; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Ralph Lattermann, MD PhD, Department of Anaesthesia, McGill University Health Center

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 3, 2012
• First Submitted That Met QC Criteria: February 6, 2012
• First Posted (Estimated): February 7, 2012

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Insulin, surgery, infection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wound Infection; Surgical Wound Infection
• Other Study ID Numbers: 2012-01 (AP HM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No