Anesthesia Patient Safety Podcast
The official podcast of the Anesthesia Patient Safety Foundation (APSF) is hosted by Alli Bechtel, MD, featuring the latest information and news in perioperative and anesthesia patient safety. The APSF podcast is intended for anesthesiologists, anesthetists, clinicians and other professionals with an interest in anesthesiology, and patient safety advocates around the world.
The Anesthesia Patient Safety Podcast delivers the best of the APSF Newsletter and website directly to you, so you can listen on the go! This includes some of the most important COVID-19 information on airway management, ventilators, personal protective equipment (PPE), drug information, and elective surgery recommendations.
Don't forget to check out APSF.org for the show notes that accompany each episode, and email us at podcast@APSF.org with your suggestions for future episodes. Visit us at APSF.org/podcast and at @APSForg on Twitter, Facebook, and Instagram.
Anesthesia Patient Safety Podcast
#257 Sweet Trouble: Perioperative Management of SGLT2 Inhibitors
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized treatment for type 2 diabetes, heart failure, and chronic kidney disease—but they're creating new challenges for anesthesia professionals. With more patients on these medications heading to surgery, understanding their unique perioperative risks has never been more critical.
At the heart of this issue lies euglycemic ketoacidosis—a potentially life-threatening complication that's particularly insidious because it lacks the classic hyperglycemia that would normally trigger suspicion. We dive deep into the latest evidence, revealing that patients on SGLT2 inhibitors have an increased risk of developing postoperative ketoacidosis compared to those not taking these medications, with significantly worse outcomes when complications occur.
We present a practical algorithm for risk stratification, considering factors like procedure duration, anesthesia type, diabetes control, and comorbidities. You'll learn which patients should hold their medication, which can proceed with caution, and what monitoring strategies to implement when patients haven't properly discontinued their medication before surgery. This guidance is especially valuable for emergency cases where postponement isn't an option.
Whether you're developing institutional protocols or making decisions for individual patients, this episode equips you with the knowledge to navigate the complexities of SGLT2 inhibitor management in the perioperative period. Subscribe to stay informed about the latest in anesthesia patient safety and join our mission to ensure no one is harmed by anesthesia care.
For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/257-sweet-trouble-perioperative-management-of-sglt2-inhibitors/
© 2025, The Anesthesia Patient Safety Foundation
You're listening to the Anesthesia Patient Safety Podcast, the official podcast of the Anesthesia Patient Safety Foundation. We're bringing you the very best from the APSF newsletter and website, as well as the latest information in perioperative patient safety. Thanks for joining us.
Speaker 2:Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Allie Bechtel and I'm your host. Thank you for joining us for another show. It is almost time for the release of the June 2025 APSF newsletter, but there is still time for us to return to the February 2025 newsletter. We are checking out the editorial article today.
Speaker 2:Sodium glucose co-transporter 2 inhibitors, or SGLT2 inhibitors, are used for treatment of type 2 diabetes. There are additional benefits for these medications for patients with heart failure and chronic kidney disease, as demonstrated by the Emperor and theOR and the CANVAS randomized controlled trials. This means that patients taking SGLT2 inhibitors are coming to an operating theater near you and you need to be prepared to provide safe anesthesia care. Before we dive further into the episode today, we'd like to recognize Merck, a major corporate supporter of APSF. Merck has generously provided unrestricted support to further our vision that no one shall be harmed by anesthesia care. Thank you, merck. We wouldn't be able to do all that we do without you.
Speaker 2:We are returning to the February 2025 APSF newsletter. Today, our featured article is the editorial Euglycemic Ketoacidosis Concerns in Perioperative Use of SGLT2 Inhibitors Re-Examining Current Recommendations by Huang and colleagues. To follow along with us, head over to apsforg and click on the newsletter heading First. One down is the current issue. Then scroll down until you get to our featured article today. I will include the link in the show notes as well. This is an important topic for anesthesia professionals since there are concerns about patients developing euglycemic ketoacidosis, which is an uncommon but life-threatening side effect associated with SGLT2 inhibitor use. Sglt2 inhibitor medications inhibit glucose reabsorption in the proximal convoluted tubule, leading to glycosuria and reductions in serum glucose levels, without an increase in insulin levels. Glucagon production may also be increased, leading to lipolysis ketoacid production increased, leading to lipolysis ketoacid production and, rarely, anion gap metabolic acidosis. There is an increased risk during the perioperative time period due to fasting and increased stress hormones, so anesthesia professionals need to be aware and be prepared.
Speaker 2:Let's get started with a review of the current recommendations and challenges. Here we go. At this time, there are no consensus recommendations for the perioperative management of SGLT2 inhibitors. Plus, many of the published recommendations are outdated or based on limited data. Based on limited data Check out table 1 in the article for a summary of current notable recommendations on perioperative SGLT2 inhibitor use.
Speaker 2:The 2020 anesthesiology article recommended continuing SGLT2 inhibitors for ambulatory surgery, but holding this medication on the morning of surgery, based on expert opinion. Also in 2020, the United States Food and Drug Administration published recommendations to hold SGLT2 inhibitors for at least three to four days before all scheduled surgery. These recommendations were based on limited case reports and the elimination half-life of SGLT2 inhibitors. The American Association of Clinical Endocrinologists and American College of Endocrinology recommendations were first published in 2016 and then updated in 2020, and included immediate cessation prior to emergency surgery and holding for 24 to 48 hours before elective surgery. Based on case reports and expert opinion. Fast forward to 2023 and the FDA recommendations were evaluated by reviewing 99 reported cases of SGLT2 inhibitor-associated diabetic ketoacidosis. None of these cases were in patients who held their medication for longer than three days. For these reviewed cases, only about 58% discontinued their SGLT2 inhibitors preoperatively, continued their SGLT2 inhibitors preoperatively, and none of the reviewed cases stopped their medication for more than two days preoperatively. Following this, the FDA recommendations were adopted by several organizations.
Speaker 2:So what is happening here? Why is there a lack of evidence when it comes to the perioperative management of SGLT2 inhibitors? There are several factors. First, and most concerning, is that the presentation of the associated euglycemic ketoacidosis is atypical, so it is likely underreported, which leads to challenges with understanding the prevalence and impact on perioperative outcomes. If we look at the literature outside of the perioperative space, there are two large meta-analyses that assessed AD2 randomized controlled trials, which revealed that SGLT2 inhibitors are not significantly associated with a higher risk of diabetic ketoacidosis compared to other hypoglycemic medications. To other hypoglycemic medications, the American Association of Clinical Endocrinologists and the American College of Endocrinology have stated that the risk of diabetic ketoacidosis associated with SGLT2 inhibitors is no greater than the low levels that occur in patients with diabetes. Keep in mind that these studies and physician statements make no mention of the risk of euglycemic ketoacidosis, which has a different clinical presentation, different diagnostic criteria and different occurrence rate. So why does perioperative SGLT2 inhibitor administration increase the risk for euglycemic ketoacidosis compared to other hypoglycemic medications? What is so special about these medications, and are there other perioperative factors that affect the risk of developing this complication? We might not have all the answers, but it's time to dive into the literature for a review of the recent updates on perioperative SGLT2 inhibitor use. Here we go In 2022, the first and largest population-based study examining the incidence of SGLT2 inhibitor-associated postoperative diabetic ketoacidosis was published and included almost 150,000 patients with type 2 diabetes over a five-year time period, the incidence of postoperative diabetic ketoacidosis within 30 days was six times higher in patients taking SGLT2 inhibitors compared to those not taking this medication.
Speaker 2:In addition, patients taking SGLT2 inhibitors who developed diabetic ketoacidosis had higher rates of complications, including need for mechanical ventilation, infection and hospital length of stay, and an overall increased mortality. The big takeaway is that this is the first study to establish SGLT2 inhibitor use as an independent risk factor for developing postoperative diabetic ketoacidosis. There are some limitations to this study no uniform diagnostic criteria for diabetic ketoacidosis and no confirmation of euglycemic presentation. It is important to keep in mind that SGLT2 inhibitors can cause prolonged glycosuria and ketonemia for up to 9-10 days after stopping the medication, so this can be a confounding factor. Let's fast forward to 2023 and a single institution retrospective analysis published in the British Journal of Anesthesia. This study included 463 patients on SGLT2 inhibitors and found that all patients on these medications, after holding for 1.5 days, developed some degree of ketoacidosis, with a mean increase in anion gap from 12.6 millimoles per liter pre-op to 13.4 millimoles per liter post-op. The authors concluded the following an anion gap acidosis likely from keto acids developed in all patients who do not hold their SGLT2 medications preoperatively, if the medication is not stopped, then post-operative monitoring of the anion gap and serum ketones can help identify patients with euglycemic diabetic ketoacidosis, and this is particularly important for patients undergoing emergency surgery. I will include the citation in the show notes so that you can check out the article in more detail. The authors of the APSF article highlight that without clear diagnostic criteria to differentiate the types of ketoacidosis, it remains difficult to understand the incidence and impact of this complication and thus develop evidence-based perioperative guidelines for patients taking SGLT2 inhibitors.
Speaker 2:With that literature review, it's time to discuss practical practice considerations and recommendations. Let's check out table 2 in the article for risk factors for the development of perioperative SGLT2 inhibitor-associated euglycemic ketoacidosis. These include the following Underlying comorbidities, such as female sex, advanced or poorly controlled type 2 diabetes Recently a hemoglobin A1c greater than 8% was reported to cause a 3.1 fold increased risk. Liver disease. Insulin use, which was reported to cause a 2.8-fold increased risk. And obesity. The surgical type, including emergency bariatric and cardiac Emergency surgery, has been reported to increase the risk by almost 25%. And other perioperative considerations, such as pre and post-operative hypovolemia.
Speaker 2:Post-operative nutrition, since inadequate nutrition can worsen post-operative catabolic state and worsen the metabolic complications. Infection or sepsis due to impaired, adequate glycemic control and physiologic stress, and glucocorticoid use, which can promote hyperglycemia and insulin resistance. Let's take a look at the guidelines that were developed by the University of Pennsylvania to incorporate the following factors Anticipated procedure duration, anesthesia type, preoperative hemoglobin A1c, glucose and basic metabolic panel and underlying patient comorbidities. The guideline continues to use the FDA recommendation for preoperative SGLT2 inhibitor cessation and needs further optimization, but it is the first published approach to develop an algorithm to guide the management of high-risk euglycemic ketoacidosis cases that anesthesia professionals can use to provide safe anesthesia care for patients taking these medications. We also need to consider that for some patients, the risks of holding their SGLT2 inhibitor outweighs the benefits. The EMPEROR trial revealed a cardioprotective benefit for taking empagliflozin, and the patients that were prospectively withdrawn from treatment had an increased risk of cardiovascular death and hospitalization for heart failure within 30 days of discontinuation back to their pre-treatment baseline.
Speaker 2:Since there is a rapid reversal of the cardioprotective benefits of SGLT2 inhibitors, some advocate for early detection and treatment of ketoacidosis with intraoperative lab monitoring for acidosis and insulin infusion use instead of perioperative discontinuation of SGLT2 inhibitors in patients with heart failure. For patients taking SGLT2 inhibitors for cardiorenal indications who do not have type 2 diabetes, they should continue to take their medication perioperatively, since there is no increased risk for euglycemic ketoacidosis in these patients. The authors recommend using a perioperative algorithm for patients taking SGLT2 inhibitors, and we are going to check out figure one in the article, which I will include in the show notes. Keep in mind that this is an area that is lacking evidence in the current literature and this algorithm may not apply in every case. The first step is to hold SGLT2 inhibitors for three days prior to elective surgery, except for patients with significant history of heart failure or patients without type 2 diabetes taking SGLT2 inhibitors for cardiorenal protection, and four days for patients taking ertugliflozin. Okay, so what do we do if patients do not hold their medication appropriately?
Speaker 2:If it is an elective procedure, the next step is to assess for risk factors for DKA. Remember these risk factors include advanced or poorly controlled type 2 diabetes with hemoglobin A1c greater than 8%. Liver disease, obesity. Type of surgery, including bariatric or cardiac. Poor nutritional status. Significant preoperative hypovolemia. Underlying infection or sepsis and glucocorticoid use. For patients without risk factors, the patient is low risk for DKA and can proceed with surgery in the following cases the use of MAC.
Speaker 2:Local or regional anesthesia. Duration of anesthetic less than one hour. Anticipated return to baseline nutritional intake post op and no other significant comorbidities For patients at high risk for the development of DKA if you can reschedule the surgery with appropriate outpatient follow-up and proper instruction on SGLT2 inhibitor hold time. If you can't reschedule the surgery, head over to the emergent urgent surgery pathway For patients who did not hold their SGLT2 inhibitor appropriately, who need to undergo emergent or urgent surgery that cannot be rescheduled. Recommend proceeding with surgery but consider the following Preoperative basic metabolic panel to check glucose and anion gap.
Speaker 2:Continue close interoperative monitoring for glucose and acidosis. An interoperative insulin infusion use and close postoperative monitoring for DKA at advanced level of care until return to adequate nutritional intake. Remember, for non-diabetic patients taking SGLT2 inhibitors for heart failure or cardiorenal protection, this algorithm likely does not apply and, based on the current available data, they should continue their SGLT2 inhibitor and are considered low risk for the development of diabetic ketoacidosis. These patients may require close perioperative monitoring for acidosis depending on other risk factors. The authors leave us with the following call to action that I'm going to read now.
Speaker 2:We believe that SGLT2 inhibitors pose an increased risk for diabetic ketoacidosis and other comorbidities in the perioperative setting. However, the optimal preoperative hold time for these medications and how cases should be handled if the hold time is not met remains controversial. Anesthesia professionals must remain vigilant since many patients do not adhere to a universal hold time or may not follow preoperative instructions. While further research is needed, we encourage clinicians to consider the currently reported risk factors. We encourage clinicians to consider the currently reported risk factors along with other patient and surgical factors to risk stratify and individualize the management of patients taking SGLT2 inhibitors, from case cancellation consideration to enhanced postoperative monitoring.
Speaker 2:Do you have a protocol that you follow at your institution for patients taking SGLT2 inhibitors? If not, you may consider using this algorithm, which you can find in the show notes. This is an important way that anesthesia professionals can help to keep patients taking SGLT2 inhibitors safe during and after anesthesia care. If you have any questions or comments from today's show, please email us at podcast at apsforg. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit apsforg for detailed information and check out the show notes for links to all the topics we discussed today. Thanks for listening. If you enjoy listening to the Anesthesia Patient Safety Podcast and we hope that you do. Please take a minute to give us a five-star rating. Subscribe and share this podcast with your colleagues and anyone you know who is interested in anesthesia. Patient safety Until next time, stay vigilant so that no one shall be harmed by anesthesia care.