High Dose Insulin for Surgical Site Infections

Recruiting at 2 trial locations

Overseen By Thomas Schricker, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Disqualifiers: Diabetes, Hypertension, Bipolar, others

Compensation: Varies

Number of Visits: 1

Duration: Perioperative period

460 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage blood sugar levels during and after major abdominal surgeries, such as those involving the liver, pancreas, or colon, to determine if it reduces the risk of surgical site infections. The study compares standard glucose management with the hyperinsulinemic normoglycemic clamp method, a high-dose insulin therapy that uses insulin and dextrose to stabilize blood sugar. The goal is to determine if this new approach can better prevent post-surgery infections. Eligible participants are adults scheduled for liver, pancreatic, or colorectal surgery who can provide consent. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve surgical outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the hyperinsulinemic normoglycemic clamp technique is safe for managing glucose during surgery?

Research has shown that the hyperinsulinemic normoglycemic clamp technique is generally well-tolerated. Studies have found that maintaining stable blood sugar levels with a steady insulin infusion can reduce infections at surgical sites. For instance, one study found that this method lowered infection rates during surgeries, suggesting it as a safe option.

While no treatment is without risks, evidence indicates that this approach is safe with close blood sugar monitoring. Any side effects, such as low blood sugar, are usually managed by adjusting sugar intake. This method's use in other medical situations further supports its safety record.

Overall, available data supports the hyperinsulinemic normoglycemic clamp as a safe treatment when carefully supervised. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the hyperinsulinemic normoglycemic clamp technique for preventing surgical site infections because it offers a precise way to maintain blood sugar levels during surgery. Unlike standard glucose management that reacts to high blood sugar with insulin adjustments, this method proactively keeps blood sugar within a tight range through a controlled infusion of insulin and dextrose. This approach could lead to fewer infections by optimizing blood sugar control, potentially improving recovery outcomes for surgical patients.

What evidence suggests that the hyperinsulinemic normoglycemic clamp technique is effective for reducing surgical site infections?

This trial will compare two approaches to glucose management during surgery. Research has shown that a special technique called the hyperinsulinemic-normoglycemic clamp, which participants in one arm of this trial may receive, can effectively control blood sugar levels. In patients undergoing heart surgery, this method reduced infections by nearly 50% and lowered the risk of postoperative complications, such as liver issues. The technique maintains steady blood sugar levels during and after surgery, improving recovery and reducing infection risk. Studies have found that it reduces cell damage and supports energy storage, leading to better outcomes after surgery. ^{1 2 6 7 8}

Who Is on the Research Team?

Ralph Lattermann, MD PhD

Principal Investigator

Department of Anaesthesia, McGill University Health Center

Are You a Good Fit for This Trial?

This trial is for adults who are scheduled for elective liver, pancreatic, or colorectal surgery and can give informed consent. It aims to see if managing blood sugar with high-dose insulin during and after surgery can reduce infections at the surgical site.

Inclusion Criteria

I understand the details of the clinical trial and can consent to participate.

I am scheduled for surgery on my liver, pancreas, or colon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants undergo major abdominal surgery with either standard glucose management or hyperinsulinemic normoglycemic clamp technique

Perioperative period

In-hospital stay

Follow-up

Participants are monitored for surgical site infections and surgical morbidity for 30 days post-surgery

30 days

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Hyperinsulinemic normoglycemic clamp
• Standard glucose management

Trial Overview The study compares standard glucose management to a technique called hyperinsulinemic normoglycemic clamp, which involves giving insulin and dextrose to maintain normal blood sugar levels during major abdominal surgery.

How Is the Trial Designed?

Group I: Hyperinsulinemic normoglycemic clamp Active Control 1 Intervention

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.

Group II: Standard glucose management Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Insulin remains the preferred treatment for managing diabetes in hospitalized patients, as it provides better glycemic control compared to non-insulin therapies, which have shown inconsistent results.

Recent studies indicate that non-insulin treatments, like oral hypoglycemic agents and GLP-1 receptor agonists, are not effective in the inpatient setting due to high blood sugar levels and side effects, highlighting insulin's superior safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Insulin in the Inpatient Setting: Need for Continued Use. Kumar, S., Molitch, ME.[2020]

Stress hyperglycemia is linked to a higher risk of surgical site infections (SSIs), but the evidence supporting strict glycemic control to prevent these infections is weak and associated with a risk of hypoglycemia.

Current guidelines for managing blood sugar in surgical patients are based on studies of critically ill patients, highlighting the need for more research to find the best glycemic targets for non-critically ill patients and to explore alternative treatments for stress hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and prevention of surgical site infection. Kao, LS., Phatak, UR.[2013]

Intensive insulin therapy to maintain blood glucose levels between 80-110 mg/dL in critically ill surgical ICU patients significantly reduced the risk of mortality by 43% and hospital mortality by 34%, based on a study of 1548 patients.

This therapy also led to a 46% reduction in severe infections and a 35% decrease in the need for prolonged antibiotic treatment, suggesting that controlling blood glucose levels is crucial for improving outcomes in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin therapy for the critically ill patient. Van den Berghe, G.[2019]

Stringent control of hyperglycemia in critically ill patients with diabetes has been shown to significantly reduce morbidity and mortality, highlighting the importance of effective glycemic management in hospital settings.

The development of insulin analogs and improved delivery systems has enhanced the safety and convenience of insulin therapy, making it easier to manage blood sugar levels both in inpatient and outpatient settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin strategies for managing inpatient and outpatient hyperglycemia and diabetes. Moghissi, ES.[2011]

The study involving 110 patients (70 non-diabetic and 40 diabetic) demonstrated that using a hyperinsulinemic-normoglycemic clamp technique effectively maintained blood glucose levels within the target range during and after cardiac surgery, achieving normoglycemia in 92.8% of non-diabetic and 87.4% of diabetic patients intraoperatively.

The incidence of severe hypoglycemia was very low, at only 2.7% overall, with non-diabetic patients experiencing just 0.2% during surgery, indicating that this method is both effective and safe for managing glucose levels in surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative tight glucose control with hyperinsulinemic-normoglycemic clamp technique in cardiac surgery. Sato, H., Carvalho, G., Sato, T., et al.[2010]

The hyperinsulinemic normoglycemic clamp technique effectively maintained normal blood glucose levels during elective cardiac surgery in both nondiabetic and diabetic patients, achieving significantly better glucose control compared to conventional insulin infusion methods.

In the clamp group, blood glucose levels remained within the target range (4.0-6.0 mmol/L) throughout the surgery, while control group patients experienced hyperglycemia, highlighting the technique's efficacy in preventing perioperative hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of normoglycemia during cardiac surgery. Carvalho, G., Moore, A., Qizilbash, B., et al.[2022]

In a study of 82 intubated, injured patients, those with pneumonia showed a significant increase in insulin requirements after bronchoalveolar lavage (BAL), suggesting a link between infection and hyperglycemia.

The increase in insulin needs (26.2 units in pneumonia patients compared to 7.6 units in non-pneumonia patients) could serve as an early indicator of pneumonia, with high predictive value for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased insulin requirements are associated with pneumonia after severe injury. Martin, RS., Smith, JS., Hoth, JJ., et al.[2015]

In a study of 36 non-diabetic patients undergoing elective cardiac surgery, the computer-guided GIN therapy achieved excellent glycemic control, maintaining blood glucose levels within the target range more effectively than manual control.

The GIN Computer Software (GINCS) resulted in a higher percentage of blood glucose measurements within the target range during surgery, with no instances of hypoglycemia, demonstrating its safety and efficacy in managing glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose and insulin administration while maintaining normoglycemia during cardiac surgery using a computer-assisted algorithm. Sato, T., Carvalho, G., Sato, H., et al.[2013]

Infusing insulin at doses of 0.20 and 0.15 mU.kg(-1).min(-1) in healthy individuals significantly suppressed glucose production and lowered plasma glucose levels to subphysiological levels, indicating these doses may be excessive for insulin replacement.

The study suggests that the commonly used doses of insulin in the pancreatic clamp technique may need to be reassessed, as lower doses (0.10 mU.kg(-1).min(-1)) did not produce the same effects, highlighting the importance of selecting appropriate hormone doses for accurate biological assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basal insulin, glucagon, and growth hormone replacement. Breckenridge, SM., Raju, B., Arbelaez, AM., et al.[2016]

The euglycemic glucose clamp technique is essential for accurately measuring the pharmacokinetic (how the body processes insulin) and pharmacodynamic (how insulin affects blood sugar levels) properties of different insulin preparations.

Initial studies on new insulin formulations should be conducted in healthy subjects to ensure controlled conditions, followed by verification in diabetes patients, as previous methods lacked the reliability needed for valid results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of insulin absorption and insulin action. Heinemann, L., Anderson, JH.[2011]

In a study of pediatric burn patients, those who did not receive insulin had a lower incidence of mortality and shorter hospital stays compared to those who received sliding scale insulin, indicating potential risks associated with insulin treatment in this population.

While insulin administration improved muscle strength and bone mineral content, it also led to increased resting energy expenditure and hypoglycemic episodes, suggesting that alternative glucose management strategies may be necessary for severely burned children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of stress-induced diabetes on outcomes in severely burned children. Finnerty, CC., Ali, A., McLean, J., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-surgical-wound-infection-1-2012-3c57e

High Dose Insulin for Surgical Site Infections Studies using the hyperinsulinemic-normoglycemic clamp technique in cardiac surgery patients have shown that while it can effectively control blood sugar levels ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6509049/

Hyperinsulinemic Normoglycemia during Cardiac Surgery ... Others similarly reported a nearly 50% reduction in blood stream and sternal wound infections in cardiac surgical and critically ill patients who received ...

3. academic.oup.com academic.oup.com/jcem/article/97/1/217/2833409

High-Dose Insulin Therapy Reduces Postoperative Liver ... Results: The hyperinsulinemic-normoglycemic clamp technique reduced postoperative liver dysfunction, infections, and complications. Markers of energy stores ...

4. researchgate.net researchgate.net/publication/369276948_Randomized_controlled_trial_of_the_effect_of_hyperinsulinemic_normoglycemia_during_liver_resection_on_postoperative_hepatic_function_and_surgical_site_infection?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJzY2llbnRpZmljQ29udHJpYnV0aW9ucyIsInByZXZpb3VzUGFnZSI6bnVsbCwic3ViUGFnZSI6bnVsbH19

(PDF) Randomized controlled trial of the effect ... Background: While avoidance of preoperative fasting followed by hyperinsulinemic-normoglycemic clamp (HNC) reduced postoperative hepatic ...

5. researchgate.net researchgate.net/publication/300366159_Effect_of_Insulin_Therapy_using_Hyper-insulinemic_Normoglycemic_Clamp_on_Inflammatory_Response_in_Brain_Dead_Organ_Donors

Effect of Insulin Therapy using Hyper-insulinemic ... The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears ...

6. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2022.855409/full

Glycemic Control Regimens in the Prevention of Surgical ... Subgroup analyses showed that intensive insulin regimens decreased the risk of SSIs in patients with diabetes, in cardiac and abdominal surgical ...

7. apsf.org apsf.org/article/perioperative-hyperglycemia-raises-risks/

Perioperative Hyperglycemia Raises Risks Continuous insulin infusion resulted in lower glucose levels and was associated with significantly lower incidence of sternal wound infection (0.8 vs. 2%) and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00524472

Outcomes Study of Hyperinsulinemic Glucose Control in ... Our secondary hypothesis is that hyperinsulinemic normoglycemic therapy will reduce length of stay in intensive care unit, atrial dysrhythmias, creatinine ...