Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral medications initially developed and FDA-approved as antidiabetic drugs to lower blood sugar in adults with type 2 diabetes. Subsequent clinical trials revealed significant benefits for kidney health in individuals with chronic kidney disease and heart failure, reducing the risk of heart attack, stroke, and exacerbations of heart failure. Patients taking SGLT2 inhibitors are associated with a different risk profile and clinical context for anesthesia and surgery.
SGLT2 is expressed in the proximal tubule of the kidney and is responsible for about 90% of filtered glucose reabsorption, making it an ideal target for diabetes treatment. Mechanistically, SGLT2 inhibitors block glucose reabsorption, leading to its excretion from the kidneys and ultimately reducing blood glucose levels in patients with type 2 diabetes. Common SGLT2 inhibitors, such as Canagliflozin, Dapagliflozin, Empagliflozin, and Ertugliflozin, have half-lives ranging from 12 to 16 hours.
The prevalence of type 2 diabetes among patients undergoing surgical procedures is increasing globally. A review conducted in the United States in 2004 estimated that 15 to 20% of surgical patients have diabetes. Additionally, about a quarter of individuals with type 2 diabetes will require surgery at some point in their lives, often due to chronic complications affecting the cardiovascular, ophthalmologic, renal, or orthopedic systems. Compared to nondiabetic patients, those with type 2 diabetes are at a higher risk of postoperative complications, including gastroparesis, cardiovascular events, and postoperative infections. Surgical stress can lead to insulin resistance and increased endogenous glucose production, resulting in stress hyperglycemia, characterized by blood glucose levels exceeding 180 mg/dl (10 mM). Prolonged elevation of glucose levels can have deleterious effects, such as immune dysfunction, increased susceptibility to infections, endothelial dysfunction, thrombosis, stroke, acute myocardial infarction, and oxidative stress due to enhanced production of reactive oxygen species. In addition, diabetic patients may take medications, such as SGLT2 inhibitors, that affect preoperative preparation and/or their physiological response to anesthesia and surgery.
Several medical societies have issued guidelines regarding the perioperative use of SGLT2 inhibitors in diabetic patients undergoing anesthesia surgery. A recent 2020 article by Peisner and colleagues reviewed guidelines from various organizations, including the Association of Anesthetists of Great Britain and Ireland, French Society of Anesthesia and Intensive Care Medicine, French Society for the Study of Diabetes, German Society for Anesthesiology and Intensive Care Medicine, German Society for Internal Medicine, German Society for Surgery, American Diabetes Association, and European Medicines Agency. Peisner et al. concluded that for patients undergoing ambulatory surgery, SGLT2 inhibitors should be discontinued on the morning of surgery and resumed once the patient is able to tolerate oral food intake. In cases of emergency surgery, SGLT2 inhibitors should be stopped altogether.
Discontinuing SGLT2 inhibitors in patients undergoing anesthesia surgery offers several advantages, including a reduced likelihood of urinary tract infections and dehydration. Furthermore, continuing SGLT2 inhibitors during the perioperative period increases the risk of euglycemic diabetic ketoacidosis, a condition that is often overlooked, wherein organic acids accumulate in the blood despite normal glucose levels in postoperative patients. While rare, euglycemic ketoacidosis is a serious complication associated with perioperative SGLT2 therapy.
In summary, SGLT2 inhibitors represent a significant advancement in the management of type 2 diabetes, offering benefits beyond glycemic control, particularly in kidney health and cardiovascular risk reduction. However, their use in the perioperative setting requires careful consideration due to potential risks such as urinary tract infections and euglycemic diabetic ketoacidosis. Guidelines from medical societies provide valuable recommendations for managing SGLT2 inhibitors during anesthesia surgery, emphasizing the need for individualized care to optimize outcomes and minimize complications in diabetic patients undergoing surgical procedures.
References
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