SGLT-2 Inhibitors-a Culprit of Diabetic Ketoacidosis Postbariatric Surgery. Case Rep Crit Care

Design

Case presentation

Case 1: A 56-year-old male presented to the emergency department 4 days after gastic bypass surgery for conversion from lap band to Roux-en-Y. The patient had a medical history significant for type 2 diabetes mellitus, gastroesophageal reflux disease (GERD), and morbid obesity. A few months prior to admission, the patient was started on canagliflozin 300 mg daily due to insufficient blood sugar control with metformin 500 mg twice daily. Upon arrival, he was experiencing weakness, malaise, polyuria, polydipsia, and shortness of breath. He was tachycardic and tachypneic. His lab values upon presentation to the emergency room (ER) were the following: sodium 127 mmol/L, potassium 4 mmol/L, bicarbonate 4 mmol/L, creatinine 1.7 mg/dL, blood glucose 208 mg/dL, anion gap 32, beta-hydroxybutyrate >4.5 mmol/L, pH 6.91, and lactate 2.4 mmol/L. The patient was negative for any infections. He was started on intravenous insulin infusion, dextrose, and fluids for the next 72 hours, until the gap was closed, then discontinued on canagliflozin and switched to Levemir 38 units. 

Case 2: A 59-year-old female presented with decreased appetite and inability to take anything by mouth. Her past medical history was pertinent for type 2 diabetes mellitus, hypertension, dyslipidemia, GERD, and morbid obesity, with a laparoscopic sleeve gastrectomy performed 5 weeks prior. Oral intake had begun to create an uncomfortable sensation, leading to an aversion of food, as well as nausea, flatus, and watery bowel movements. The patient's home medications included dapagliflozin 10 mg daily, which was resumed after surgery, while her daily home insulin (Lantus 65 units twice daily) was withheld. Her lab values upon presentation to the emergency room were the following: sodium 136 mmol/L, potassium 3.6 mmol/L, bicarbonte 10 mmol/L, creatinine 1.0 mg/dL, blood glucose 173 mg/dL, anion gap 32, beta-hydroxybutyrate >9 mmol/L, pH 7.28, and lactate 0.8. Urinalysis showed glucose levels greater than 1,000 mg/dL with a large number of ketones. No suspicions were found in the computerized tomography (CT) scan, gastrointestinal series, or gastric emptying. The patient was treated in the intensive care unit (ICU) for 6 days, receiving intravenous insulin infusion, dextrose, and fluids. Dapagliflozin was discontinued; the patient was discharged and to be followed up by an endocrinologist.

Case 3: A 52-year-old female presented to the emergency room with complaints of fatigue over the previous few days. She had a past medical history of type 2 diabetes mellitus, hypertension, dyslipidemia, and morbid obesity, having received gastric sleeve bypass surgery 2 weeks prior to presentation. Additionally, she was experiencing shortness of breath, chills, weakness, decreased appetite, and polyuria. The patient stated that some symptoms, such as decreased appetite and generalized weakness, began about 2 years ago when canagliflozin 300 mg daily was initiated. Her lab values upon presentation were the following: sodium 142 mmol/L, potassium 3.2 mmol/L, bicarbonate 8 mmol/L, creatinine 1.1 mg/dL, blood glucose 196 mg/dL, anion gap 35, beta-hydroxybutyrate >9 mmol/L, pH 7.2, and lactate 1.6. Urinalysis revealed a glucose level >1000 mg/dL, with a large number of ketones. No suspicions were found in CT angiography, electrocardiogram, and blood culture. The patient received intravenous insulin, dextrose, and fluids in the ICU, ultimately resulting in an improved appetite. Upon discharge, the patient was switched to basal-bolus insulin and both metformin and canagliflozin were discontinued.  

Study Author Conclusions

A Case of SGLT2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis Following Coronary Artery Bypass Surgery

Design

Case presentation

A 60-year-old male was admitted for coronary artery bypass graft (CABG) surgery after receiving cardiac catheterization from a referring hospital. The patient had a medical history of coronary artery disease, hypercholesterolemia, and type 2 diabetes mellitus. Current medications included glimepiride, metformin, subcutaneous semaglutide, and empagliflozin. Notably, semaglutide and empagliflozin were not reported by the patient upon admission.  Upon arrival, the patient was asymptomatic, with normal vitals. Laboratory testing revealed a white blood cell count of 7.6 K/μL, hemoglobin of 14.6 g/dL, serum glucose of 157 mg/dL, bicarbonate of 24 mmol/L , anion gap of 12 mmol/L, troponin of 0.09 ng/mL, and glycated hemoglobin of 9.6% (81 mmol/mol). Urinalysis revealed glucosuria of > 1,000 mg/dL and ketonuria of 15 mg/dL.

The patient's oral antihyperglycemic medications were replaced with a subcutaneous insulin regimen; CABG surgery was performed on the third day of admission. However, a few hours following the procedure, the patient developed an elevated anion gap metabolic acidosis with an arterial pH of 7.275, as well as a reduced bicarbonate level (15 mmol/L) and increased anion gap (25 mmol/L). While his glucose level was within normal range, β-hydroxybutyric acid level was elevated. The patient was diagnosed with euglycemic diabetic ketoacidosis (DKA) and was given an intravenous insulin drip with 5% dextrose in water as well as 24-hour intravenous norepinephrine for hypotension. Ketoacidosis resolved over the following 2 days, after which the patient was transitioned to basal and premeal subcutaneous insulin. 

The cause of this patient's DKA was not readily determined, but further investigation revealed that the patient had been switched from long-term canagliflozin therapy to empagliflozin about 1 year before he was admitted to the hospital. The most recent empagliflozin dose had been taken on the morning of admission, about 48 hours before the CABG surgery. The patient was educated on the importance of discontinuing empagliflozin at least 3 days before any procedure that requires long-term fasting. 

Study Author Conclusions

Euglycemic DKA can occur postoperatively in patients with a history of sodium-glucose cotransporter-2 (SGLT2) inhibitor use, even 48 hours after discontinuing therapy. With the rapidly expanding use of SGLT2 inhibitors to include, in addition to diabetes, cardiac and renal indications, both providers and patients should be aware of this complication and should consider discontinuing SGLT2 inhibitors at least 48 to 72 hours prior to major surgery. Persistent glycosuria, despite discontinuation of the medication, should warrant closer monitoring for metabolic acidosis following procedures. Detailed medication history and testing for ketones in the blood are imperative to prevent a delay in insulin therapy. Preventive perioperative therapy with both glucose and insulin in patients recently treated with SGLT2 inhibitors might be an effective strategy.

Early detection of euglycemic ketoacidosis during thoracic surgery associated with empagliflozin in a patient with type 2 diabetes: A case report

Design

Case presentation

A 59‐year‐old man who had a 12‐year history of type 2 diabetes mellitus on 25 mg empagliflozin with intensive insulin therapy was recently diagnosed with left bacterial empyema and treated with antibiotics for 4 days without symptomatic improvements. Upon transferring to the study institution for surgical treatment, he was treated with empagliflozin and insulin for diabetes at the former hospital (day 0). Empagliflozin was taken for the last time 28 h before surgery, and he was treated with insulin glargine 13 h before surgery. 

The patient then underwent thoracoscopic debridement and intrathoracic lavage with the infusion of 1% glucose drip without insulin. Unfortunately, approximately 2 h after the initiation of surgery, he was found to be acidotic on arterial blood gas with 162 mg/dL of blood glucose level. Urine test was positive for ketone, and further tests showed elevated levels of total ketone bodies, acetoacetic acid, and 3‐hydroxybutyric acid in serum. Insulin infusion with drip infusion of 5% glucose was initiated immediately, and he awoke from anesthesia normally without digestive symptoms. After the continuous insulin infusion, his acidosis and ketosis gradually resolved over the next 24 h. During the 2-week follow-up, his bacterial empyema had almost resolved and he was treated with insulin alone for diabetes and did not present ketosis or acidosis. 

Study Author Conclusions

In summary, the case report presented a patient with type 2 diabetes and bacterial empyema, who developed intraoperative euglycemic diabetic ketoacidosis (eDKA) associated with empagliflozin. This is the first case of eDKA associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors during thoracic surgery, which could be rapidly resolved by emergent intervention. When patients are taking SGLT2is, especially those with precipitating factors, it is clinically important to be aware of the potential risk of eDKA and to increase monitoring for the immediate initiation of treatment.

Normoglycemic Ketoacidosis in a Postoperative Gastric Bypass Patient Taking Canagliflozin

Design

Case presentation

A 52-year-old female with a body mass index of 42 kg/m² and a past medical history of type 2 diabetes mellitus (T2DM), gastroesophageal reflux disease, hepatosteatosis, and hypercholesterolemia elected to undergo laparoscopic gastric bypass surgery. Her diabetes medications included metformin 1000 mg daily and canagliflozin 300 mg daily which were both continued until the day of surgery, at which time they were held. She was placed on a low-carbohydrate diet the week before the procedure, and was kept nil per os (NPO) beginning the night prior to the operation. Throughout the procedure she received 3.5 L of crystalloid fluid intravenously over 2.5 hours, with a blood loss of 80 mL and a urine output of 600 mL. After surgery she was placed on 0.45% normal saline as maintenance fluids.

During postoperative day one, she was found to have significant facial and upper chest flushing and a faint fruity odor on her breath alongside a urine output of 4 L. At this point her lab values were: serum glucose 112 mg/dL, serum potassium 5.2 mEq/L, serum sodium 137 mEq/L, serum chloride 114 mEq/L, carbon dioxide 5 mEq/L, and an anion gap of 18. An arterial blood gas revealed pH 7.06, pCO2 19.9 mmHg, and bicarbonate 5.5 mmol/L. While searching for an underlying etiology for the patient's acidosis, additional lab values revealed lactic acid 0.6 mEq/L, a "large amount" of serum acetone, urine glucose 500 mg/dL, and urine ketones 80. Imaging was then carried out, which yielded a normal gastrointestinal swallow series, chest radiograph, and computerized tomographic scans of the chest, abdomen, and pelvis. The patient was then transferred to the surgical intensive care unit, rehydrated with dextrose-containing fluids, started on insulin and bicarbonate drips, and placed on a continuous positive airway pressure device. Her pH was corrected within 12 hours, and her acetone levels & urine output normalized over the following 3 days. Her preoperative serum glucose level trended between 112-140 mg/dL prior to initiation of the insulin drip, and between 89-115 mg/dL postoperative and throughout the remainder of her hospital stay. She was eventually discharged home on postoperative day 5. 

Study Author Conclusions

In our patient, several factors may have contributed to her likelihood of developing normoglycemic ketoacidosis. First, she had been on metformin, which suppresses hepatic gluconeogenesis but also lessens the normal suppression of fatty acid oxidation9 . Secondly, her use of canagliflozin effectively decreased her glucose stores and in turn increased her propensity for fatty acid oxidation while also causing an osmotic diuresis. Additionally, she was placed on a routine preoperative diet that may have added to her fatty acid oxidation and relative hypovolemia. With these risk factors in place in the setting of the physiologic stress of surgery, it is conceivable that ketoacidosis would follow. There is not enough discrete evidence to place weight on which of these risk factors was greater; however, the majority of T2DM patients on metformin with preoperative diets have successfully undergone RYGB surgery without developing this complication. The most striking and suspect difference in this patient was her use of canagliflozin.

Canagliflozin has been shown to be beneficial in the management of T2DM. However, its safety profile needs to be carefully examined so that patients in high risk situations for ketoacidosis, such as this case study, can avoid serious complications. This has been, to date, the first reported T2DM patient on canagliflozin who suffered from ketoacidosis after Roux-en-Y gastric bypass.