Increased Risk of Perioperative Ketoacidosis Linked to Diabetes Medication

Recent research indicates that the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i), commonly prescribed for managing type 2 diabetes mellitus (T2DM), may elevate the risk of developing perioperative euglycemic ketoacidosis (eKA). These medications, known as gliflozins, function by inhibiting sodium-glucose transport protein 2, effectively lowering elevated blood sugar levels associated with T2DM. Additionally, SGLT2i have demonstrated beneficial effects for patients suffering from chronic kidney disease, heart failure, and coronary artery disease.

While these drugs contribute positively to glycemic control, they are also linked to instances of euglycemic ketoacidosis, a condition characterized by elevated ketone levels in the blood. Under normal circumstances, ketones serve as a vital energy source by converting fat cells. However, when produced in excess, they can lead to acidosis, rendering the blood dangerously acidic.

The association between SGLT2i and ketoacidosis is partly due to their impact on insulin secretion. The risk of eKA can become pronounced during the perioperative phase, where reduced carbohydrate intake and the physiological stress of surgery can heighten insulin demands and metabolic rates. An increasing number of case reports highlight postoperative eKA occurrences among SGLT2i users, underscoring the severity of the condition if not promptly treated.

Intriguingly, clinical studies have noted that eKA incidents associated with SGLT2i often present with only mildly elevated glucose levels, which complicates the diagnosis. Researchers at the University of California, San Francisco (UCSF) undertook a multicenter, retrospective cohort study to assess the risk of postoperative eKA and related clinical outcomes--including acute kidney injury (AKI) and mortality--when comparing SGLT2i users to non-users.

The findings, published in JAMA Surgery, revealed that patients utilizing SGLT2i before surgery exhibited a small yet statistically significant increase in the risk of postoperative eKA. Conversely, these patients showed a lower risk of developing AKI and mortality within 30 days following surgical procedures.

According to the study's senior author, the elevated risk of perioperative eKA warrants careful monitoring and may require intensified interventions, such as insulin administration or continuous dextrose infusion. These measures could potentially lead to longer hospital stays or unexpected admissions to intensive care units.

The study analyzed data from the Veterans Affairs Healthcare System (VAHCS) National Registry, focusing on adult patients who were on SGLT2i prior to undergoing inpatient surgical procedures. These individuals were matched with a control group of non-users, considering factors such as demographics, comorbidities, and surgical characteristics.

Ultimately, 7,439 SGLT2i users were compared to 33,489 controls. Results indicated that the likelihood of experiencing perioperative eKA was 11% higher among SGLT2i users compared to their counterparts, increasing to 18% in cases of emergency surgery. However, they also demonstrated a 31% reduction in postoperative AKI and a 30% decrease in mortality rates within the same 30-day frame.

While the risk of eKA was found to be modest, it was evident in both emergency and elective surgical contexts. Although SGLT2i are typically withheld before elective surgeries, this practice does not seem to mitigate the risk of eKA effectively.

As the medical community continues to navigate the complexities of diabetes management, understanding the implications of SGLT2i use during surgery remains crucial for patient safety and optimal postoperative outcomes.