There is growing evidence to support the use of sodium-glucose cotransporter-2 (SGLT2)
inhibitors for type 2 diabetes mellitus (T2DM) and the management of heart failure.
As such, more patients undergoing cardiac surgery are on SGLT2-inhibitor therapy.
Despite the numerous benefits of SGLT2 inhibitors on cardiac health, they can be associated
with an increased risk of diabetic ketoacidosis, often with normal glucose levels
(euglycemic diabetic ketoacidosis or EDKA), which potentially can be detrimental in
this vulnerable patient population. In this narrative review, the authors discuss
17 papers that described EDKA in perioperative cardiac surgical patients. The authors
discuss suggested preventative measures and management options, with a particular
emphasis on raising the clinical awareness of the care teams toward this complication.
SGLT2 inhibitor-induced EDKA is a medical emergency that can be difficult to identify
in the postcardiac surgical patient due to the overlap of signs and symptoms with
other frequent scenarios in these patients. A reduction in SGLT2 inhibitor-associated
EDKA can be mitigated by the appropriate perioperative discontinuation of the medication,
clinical awareness, and early investigation to diagnose the condition, with emphasis
on serum β-hydroxybutyrate. Future quality improvement initiatives are needed to assist
in reducing EDKA in patients taking SGLT2 inhibitors in the perioperative surgical
setting.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Cardiothoracic and Vascular AnesthesiaAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- An update on SGLT2 inhibitors for the treatment of diabetes mellitus.Curr Opin Endocrinol Diabetes Obes. 2017; 24: 73-79
- 2019 Update to: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2020; 43: 487-933
- Empagliflozin in heart failure with a preserved ejection fraction.N Engl J Med. 2021; 385: 1451-1461
- Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors.JACC Basic Transl Sci. 2020; 5: 632-644
- Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data.Diabetes Metab Res Rev. 2017; 33https://doi.org/10.1002/dmrr.2924
- Euglycemic diabetic ketoacidosis.StatPearls Publishing, Treasure Island, FL2021
- SGLT2 inhibitors: A systematic review of diabetic ketoacidosis and related risk factors in the primary literature.Pharmacotherapy. 2017; 37: 187-194
- SGLT2 inhibitor–associated diabetic ketoacidosis: Clinical review and recommendations for prevention and diagnosis.Clin Ther. 2016; 38: 2654-2664
- Epinephrine-induced lactic acidosis following cardiopulmonary bypass.Crit Care Med. 1997; 25: 1693-1699
- Perioperative metabolic acidosis: The Bradford Anaesthetic Department Acidosis Study.J Intensive Care Soc. 2019; 20: 11-17
- Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: Pharmacologic glycemic management of type 2 diabetes in adults.Can J Diabetes. 2018; 42: 88-103
U.S. Food and Drug Administration. FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. Available at: https://www.fda.gov/media/94822/download. Accessed May 29, 2022.
- Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.PLoS Med. 2009; 6e1000097
- Perioperative cessation of sodium-glucose cotransporter-2 inhibitors: 72 hours or 7 days?.Anaesth Intensive Care. 2018; 46: 425
- Perioperative implications of sodium-glucose cotransporter-2 inhibitors: A case series of euglycemic diabetic ketoacidosis in 3 patients after cardiac surgery.Can J Anaesth. 2018; 65: 188-193
- A case of SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis following coronary artery bypass surgery.AACE Clin Case Rep. 2021; 7: 20-22
- Diabetic ketoacidosis precipitated by therapy with antidiabetic agents SGLT2 inhibitors: 2 cases.Crit Care Resusc. 2015; 17: 280-282
- Empagliflozin induced euglycemic diabetic ketoacidosis in a patient undergoing coronary artery bypass graft despite discontinuation of the drug 48 hours prior to the surgery.Diabetes Metab Syndr. 2021; 15: 909-911
- Diagnosis and management of SGLT-2 inhibitor-induced euglycemic DKA after cardiac surgery.Crit Care Med. 2021; 49: 211
- A case of empagliflozin-induced euglycaemic diabetic ketoacidosis post-off pump coronary artery bypass surgery [abstract]. In: Clinical care and other categories posters: Case reports.Diabetic Medicine. 2020; 37: 78
- Ketoacidosis related to sodium glucose cotransporter 2 inhibitors after emergency coronary surgery.Interact Cardiovasc Thorac Surg. 2019; 29: 323-324
- Euglycemic diabetic ketoacidosis associated with the use of a sodium–glucose cotransporter-2 inhibitor.CMAJ. 2018; 190: E766-E768
- Perioperative euglycemic diabetic ketoacidosis following use of SGLT-2 inhibitors after cardiac surgery.J Clin Anesth. 2021; 71110201
- Postoperative euglycaemic diabetic ketoacidosis associated with sodium–glucose cotransporter-2 inhibitors (gliflozins): A report of 2 cases and review of the literature.Anaesth Intensive Care. 2018; 46: 215-219
- Just sweet enough? A case of euglycaemic ketoacidosis ‘incidentally’ found in a post surgical patient [abstract]. In: Clinical care and other categories posters: Case reports.Diabetic Medicine. 2018; 35: 105
- The catabolic triad: Case report of fasting, major cardiac surgery and sodium–glucose co-transporter 2 inhibitors leading to perioperative euglycaemic ketoacidosis.Interact Cardiovasc Thorac Surg. 2021; 33: 494-495
- Euglycemic diabetic ketoacidosis post cardiac surgery.Am J Kidney Dis. 2020; 75: 584
- SGLT2 inhibitor–associated euglycemic diabetic ketoacidosis: A South Australian clinical case series and Australian spontaneous adverse event notifications.Diabetes Care. 2018; 41: e47-e49
- Euglycemic diabetic ketoacidosis caused by a sodium-glucose cotransporter 2 inhibitor after coronary artery bypass grafting.J Am Coll Cardiol. 2019; 73: 2423
Hitchen SA, Lan NS, Ali US, et al. Investigating the effect of an education program on diabetes and lipid lowering medication usage following coronary artery bypass graft surgery [e-pub ahead of print]. Intern Med J. https://doi.org/10.1111/imj.15393. Accessed May 29, 2022.
- Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US.JAMA Netw Open. 2021; 4e216139
- Evaluating SGLT2 inhibitors for type 2 diabetes: Pharmacokinetic and toxicological considerations.Expert Opin Drug Metab Toxicol. 2014; 10: 647-663
- Suggested Canadian standards for perioperative/periprocedure glycemic management in patients with type 1 and type 2 diabetes.Can J Diabetes. 2022; 46 (e5): 99-107
- SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials.Lancet. 2019; 393: 31-39
- Drug safety alerts by FDA and CDSCO in 2016: A recent Review & A Study Of Its Implementation In Practice.Int J Adv Pharm Biotech. 2018; 4: 1-9
Centre for Perioperative Care. Guideline for perioperative care for people with diabetes mellitus undergoing elective and emergency surgery. Available at: https://www.cpoc.org.uk/guidelines-resources-guidelines-resources/guideline-diabetes. Accessed May 29, 2022.
- Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium–glucose cotransporter 2 inhibition.Diabetes Care. 2015; 38: 1687-1693
- Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in the perioperative setting.Can J Anaesth. 2017; 65: 143-147
Article info
Publication history
Published online: June 15, 2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
