Preoperative Cessation of SGLT2i

Oct 07, 2022   |  Saloni Kumar, MD; Sanjeev P. Bhavnani, MD, FACC; Parag Goyal, MD, FACC; Michael W. Rich, MD, FACC; Ashok Krishnaswami, MBBS, FACC

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Quick Takes

  • Sodium-glucose co-transporter 2 (SGLT2)-inhibitors are increasingly being prescribed by cardiovascular clinical teams for patients with heart failure with and without diabetes mellitus.
  • The cardiovascular teams should be aware of recent Food and Drug Administration (FDA) advisory warnings for increased incidence of euglycemic diabetic ketoacidosis when SGLT2-inhibitors medications are continued prior to non-cardiac surgeries.
  • These warnings have stated that continuing SLGT2-inhibitors preoperatively can lead to poor patient outcomes and increased hospital length of stay.
  • When caring for patients being referred for surgery it is important to advise patients to stop their SGLT2-inhibitors 3-4 days prior to surgery to minimize the risk of postoperative ketoacidosis and urinary tract infections.

Euglycemic diabetic ketoacidosis (EDKA) is an uncommon but life-threatening diagnosis and must be considered in postoperative patients who have been on SGLT2-inhibitors. EDKA in this setting has been reported to occur any time during the course of medication use.

It should be considered when a patient has:

  • An anion gap metabolic acidosis and pH <7.3
  • Elevated ketones in the blood or urine
  • A blood glucose <200

Given the clinical overlap with starvation ketoacidosis, it is a difficult diagnosis to make. The mechanism of both is similar, except that in EDKA, the patient has diabetes mellitus and has been taking a SLGT2-inhibitor.

The mechanism (Figure 1) by which this phenomenon is thought to occur is through an increased glucagon:insulin ratio. SGLT2-inhibitors can cause:1-3

  • Increasing urinary excretion of glucose by blocking reabsorption of glucose at the proximal convoluted tubule
  • Lower insulin levels needed to maintain fasting glucose levels which can lead to ketosis
  • Increased glucagon
  • Hypovolemia due to glucosuria
  • An increase in counter-regulatory hormones which lead to lipolysis and ketosis
  • Suppressed removal of beta-hydroxybutyrate and acetoacetate by the kidneys

Figure 1: Proposed Mechanisms of EDKA

Figure 1
Figure 1: Proposed Mechanisms of EDKA.1-3 Courtesy of Kumar S, Bhavnani SP, Goyal P, Rich MW, Krishnaswami A.

The symptoms of EDKA include anorexia, nausea, vomiting, and dyspnea. The treatment is similar to that of DKA except patients oftentimes need a dextrose drip to allow for high enough doses of insulin to suppress ketone formation and close the anion gap. The patient should be discharged without their SGLT2-inhibitor.1

The FDA released multiple warnings4 related to the elevated risk of DKA. The recommendation is for canagliflozin, dapagliflozin, and empagliflozin to be discontinued 3 days before scheduled surgery and ertugliflozin should be stopped at least 4 days prior to surgery. This differs from other diabetic medications which are typically held the day of surgery. With the increase in SLGT2-inhibitors being prescribed for both diabetes and heart failure, it is crucial that providers are aware of this preoperative hold parameter and recognize patients at risk for EDKA.

References

  1. Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis (StatPearls [Internet]). 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK554570/. Accessed 09/01/2022.
  2. Lam DWH. Euglycemic Diabetic Ketoacidosis in the Modern Era (youtube.com) 2018. Available at: https://www.youtube.com/watch?v=-UNimRawMHg. Accessed 09/01/2022.
  3. Wang KM, Isom RT. SGLT2-inhibitor induced euglycemic diabetic ketoacidosis: a case report." Kidney Med 2020;2:218-221.
  4. FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections (fda.gov). 2022. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious. Accessed 09/01/2022.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure, Geriatric Cardiology

Keywords: Sodium-Glucose Transporter 2, Diabetic Ketoacidosis, Canagliflozin, Blood Glucose, 3-Hydroxybutyric Acid, Acetoacetates, Glucagon, Acid-Base Equilibrium, Hypovolemia, Lipolysis, Patient Discharge, Nausea, Vomiting, Dyspnea, Heart Failure, Insulins, Kidney, Sodium-Glucose Transporter 2 Inhibitors


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