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Intranasal insulin is reported to improves memory performance in patients suffering from cognitive impairment. The investigators have previously shown that intraoperative insulin administration preserves both short and long-term memory function after cardiac surgery. Applying intranasal insulin bypasses blood-brain barrier and cause elevation of insulin concentrations in the cerebrospinal fluid without major effects on peripheral insulin level. Patients undergoing major surgery are exposed to carbohydrate and insulin metabolism alteration. The goal of the study is to study the effect of intranasal insulin on blood glucose, plasma and cerebrospinal insulin concentration in patients undergoing cardiac surgery or endovascular thoracic aneurysm repair.
Clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from Alzheimer's disease or cognitive impairment. A single dose of intranasal insulin acutely improved memory in memory-impaired older adults. Cognitive impairment in post-operative period is an increasing problem as more elderly patients undergo major surgery. The investigators have previously shown that intraoperative insulin administration while maintaining normoglycaemia preserves both short and long-term memory function after open heart surgery.
Applying insulin as a nasal spray bypasses blood-brain barrier and cause significant and sustained elevation of insulin concentrations in the cerebrospinal fluid (CSF) without major effects on peripheral insulin levels. The administration of 40 IU of intranasal insulin(INI) rapidly increases CSF insulin concentration within seven minutes, peaking after 30 minutes and remaining elevated for more than 80 minutes.
Presently it is not clear if CNS insulin plays a relevant role in controlling blood glucose in humans.
Patients undergoing major surgery are exposed to metabolic and endocrine alterations in carbohydrate, protein, and insulin metabolism, often summarized as the catabolic stress response. While the effect of intravenous insulin on glucose metabolism during surgery has been extensively studied the influence of intranasal insulin administration on intraoperative plasma insulin and blood glucose concentrations is unknown.
Goal and Objectives The goal of the present study is to study the effect of intranasal insulin on
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intranasal 40 | Experimental | Patients will receive 40 IU of intranasal insulin (Humulin R) via a metered nasal dispenser |
|
| Intranasal 80 | Experimental | Patients will receive 80 IU of intranasal insulin (Humulin R) via a metered nasal dispenser |
|
| Placebo | Placebo Comparator | Patients will receive intranasal normal saline via a metered nasal dispenser |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Humulin R | Drug | Study subjects will receive intranasal insulin (Humulin R) via a metered nasal dispenser. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Blood Glucose | Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Circulating concentrations of glucose will be measured. | During Surgery |
| Plasma Insulin | Arterial blood samples will be collected every 10 to 30 minutes during the surgery. Plasma insulin will be measured. | During Surgery |
| Cerebrospinal Fluid Insulin | Cerebrospinal Fluid will be taken every 10 to 30 minutes during the endovascular thoracic aneurysm repair surgery. Insuring concentration of Cerebrospinal fluid will be measured. | During Surgery |
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Inclusion Criteria:
All patients (>18 years) undergoing elective open heart surgery requiring CPB or elective endovascular thoracic aortic aneurysm repair at the RVH.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hiroaki Sato, MD., PhD. | Contact | +15149341934 | 36717 | hiroaki.sato2@mcgill.ca |
| Thomas Schricker, MD., PhD. | Contact | +15149341934 | 34883 | thomas.schricker@mcgill.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Victoria Hospital McGill University Health Centre | Recruiting | Montreal | Quebec | H4A 3J1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33721199 | Derived | Roque P, Nakadate Y, Sato H, Sato T, Wykes L, Kawakami A, Yokomichi H, Matsukawa T, Schricker T. Intranasal administration of 40 and 80 units of insulin does not cause hypoglycemia during cardiac surgery: a randomized controlled trial. Can J Anaesth. 2021 Jul;68(7):991-999. doi: 10.1007/s12630-021-01969-5. Epub 2021 Mar 15. | |
| 30895515 |
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| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D001014 | Aortic Aneurysm |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D000783 | Aneurysm |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Normal Saline | Drug | Study subjects will receive intranasal placebo (normal saline) via a metered nasal dispenser. |
|
| Nakadate Y, Sato H, Roque P, Sato T, Matsukawa T, Wykes L, Kawakami A, Schricker T. Accuracy of blood glucose measurements using the NOVA StatStrip(R) glucometer during cardiac surgery: a prospective observational study. Can J Anaesth. 2019 Aug;66(8):943-952. doi: 10.1007/s12630-019-01350-7. Epub 2019 Mar 20. |
| D001018 |
| Aortic Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |