EUGLYCEMIC DIABETIC KETOACIDOSIS A RARE CAUSE FOR DELAYED EXTUBATION

Euglycemic diabetic ketoacidosis a rare cause for delayed extubation: A case report

Marutheesh M

Gayathri krishna Reddy, Murali jayaraman, Harish Mallapura Maheshwarappa

consultant anesthetist, Kauvery Hospital, Hosur

Consultant Surgical Gastroenterology, Kauvery Hospital, Hosur

Director Critical Care, Kauvery Hospital, Banglore

Consultant anesthetist and Intensivist, Kauvery Hospital, Hosur

Abstract

Euglycemic diabetic ketoacidosis is ketoacidosis in individuals with near-normal blood sugar levels, making it difficult to diagnose. This can result in overlooked cases.

Background

Case description: A 46-year-old male with diabetes and hypertension presented with abdominal pain and fever. Gallstones and bile duct dilation were found. Elevated glucose levels and sugar in urine were detected. Gangrenous changes in the gallbladder were discovered during surgery. Severe metabolic acidosis required a ventilator and ICU transfer.

Summary

Euglycemic diabetic ketoacidosis was considered due to SGLT-2 inhibitor use. Treatment included fluids, insulin, and dextrose infusion. Extubation was successful the next day.

Conclusion

Euglycemic DKA should be considered in critically ill patients with diabetes, even with low blood sugar or no ketones in the urine. Diagnosis involves assessing metabolic acidosis, measuring serum ketones, and ruling out other causes.

Clinical significance:

Euglycemic diabetic ketoacidosis (DKA) is a metabolic emergency that poses a serious risk to life. Anaesthesiologists, emergency medicine and intensive care units struggle with the absence of hyperglycemia because it might delay diagnosis and treatment, which harms patient outcomes and its incidence has risen with the use of sodium/glucose cotransporter-2 inhibitors.

Keywords:

Euglycemic; DKA; SGLT-2 Inhibitors; Case Report

Definition

Diabetic ketoacidosis (DKA) is a severe complication of diabetes that can be life-threatening. It can occur in both type 1 and type 2 diabetes patients, often triggered by acute illnesses. DKA is diagnosed based on high blood sugar levels, metabolic acidosis, and the presence of ketones in the blood. However, there is a subtype called euglycemic DKA, which refers to ketoacidosis with near-normal or slightly elevated blood sugar levels. This can make it challenging to diagnose in emergencies. Euglycemic DKA is characterized by moderate dehydration and symptoms such as fatigue and decreased appetite. Prompt testing for metabolic acidosis and blood ketone levels can help detect it early. Although relatively rare, the use of sodium/glucose cotransporter-2 (SGLT-2) inhibitors in diabetes management has led to an increase in reported cases of euglycemic DKA [1, 2, 3].

Pathophysiology

The main cause of euglycemic diabetic ketoacidosis (DKA) is a lack of carbohydrates, while insulin deficiency or resistance plays a smaller role. Counter regulatory hormones are unaffected, leading to a higher ratio of glucagon to insulin and the start of ketogenesis. Fasting or prolonged physical activity can trigger euglycemic DKA by depleting liver glycogen stores. This leads to increased levels of glucagon, promoting lipid oxidation and the production of ketone bodies. The presence of ketonemia and glycosuria (common with SGLT-2 inhibitors) contributes to the development of euglycemic DKA as shown in Fig.1 [4].

Fig (1): Pathophysiology of Euglycemic diabetic ketoacidosis (DKA)

Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are responsible for metabolic acidosis, while hyperglycemia through glycosuria and osmotic diuresis causes dehydration and hypovolemia. A: Pathophysiology of diabetic ketoacidosis; B: Pathophysiology of euglycemic diabetic ketoacidosis. FFA: Free fatty acids; â†‘: Increase; â†“: Decrease; ~: No change.

The three most common causes of euglycemic DKA are SGLT-2 inhibitors, pregnancy, and prolonged fasting. The three most common causes of euglycemic DKA are SGLT-2 inhibitors, pregnancy, and prolonged fasting. Euglycemic DKA is rare in cases like bariatric surgery, acute pancreatitis, sepsis, cocaine intoxication, insulin pump malfunction, chronic liver disease, glycogen storage disease, and gastroparesis. Bariatric surgery patients are especially at risk due to low-carb diets and fasting. Type 1 diabetics, SGLT-2 inhibitor users, and those fasting during surgery are at even higher risk. Giving insulin during transport may lower blood glucose levels upon admission (4).

Table.1: Precipitating factors for EDKA in patients on SGLT-2 inhibitors

Risk factors	Pathophysiology
Infection	Insulin resistance due to counter regulatory hormones (adrenaline, glucagon, etc.), increased peripheral glucose utilization, decreased intake.
Surgery	Perioperative fasting, gastrointestinal surgery has increased incidence as fasting is prolonged and/or gut absorption is slow
Fasting	Decreased glycogen stores, increased risk with SGLT-2 inhibitors and type 1 DM
Alcohol intake	Decreased carbohydrate intake, osmotic diuresis, increased ketogenesis due to altered NADH/NAD ratio
Acute vascular events	Increased counter regulatory hormones, decreased oral intake
Trauma	Decreased oral intake, increased counterregulatory hormone, blood glucose dilution by large ï¬‚uid shifts during resuscitation

*ACS – Acute coronary syndrome; DM – Diabetes mellitus; NAD – Nicotinamide adenine dinucleotide; NADH – Nicotinamide adenine dinucleotide hydrogen; SGLT2 – Sodium/ glucose cotransporter-2.

Case Presentation

A 46-year-old male patient with a history of diabetes and hypertension presented to the emergency department with persistent right upper abdominal pain and fever. An ultrasound revealed acute cholecystitis with cholelithiasis and bile duct dilation. Upon arrival, the patient had a fever, elevated heart rate, and normal blood pressure.

Physical examination and neurologic exam were normal. Laboratory testing showed elevated glucose levels and sugar in the urine.

Management

The patient underwent laparoscopic cholecystectomy and intraoperative findings revealed gangrenous changes in the gallbladder. The patient remained stable throughout the procedure, due to an abnormal breathing pattern patient was not extubated, and an arterial blood gas (ABG) analysis at the end of surgery showed severe metabolic acidosis, as indicated in Table 2.

Upon arrival at the ICU, the patient had a high GRBS of 200mg/dl. They were paralyzed and put on mechanical ventilation. The medical team ruled out sepsis, respiratory acidosis, Myocardial Infarction and considered the possibility of Euglycemic DKA due to the patient’s use of SGLT-2 inhibitors.

Urine ketones confirmed this, and the patient received a 100meq bolus of Inj Sodabicarb. After an initial 1L bolus of IV normal saline, the medical team started a continuous IV infusion of insulin and a 5% dextrose infusion to prevent hypoglycemia. If the GRBS went above 250mg/dl, IV normal saline was given. These interventions successfully resolved the patient’s ketosis and acidosis.

The next morning, the patient was extubated after overnight ventilation. Upon discharge, they were prescribed Glimeperide, metformin, and sitagliptin to manage their glucose levels in the future.

Table 2: ABG Analysis of the patient

Time	2 pm	5 pm	7.30 pm	12 am
PH	6.9	7.09	7.25	7.38
Pco2	52	32	26	30
Hco3	10.9	9.7	11.4	17.7
Lactate	1.9	1.8	1.2	1.1
Po2	259	129	148	100
So2	100	99	99	98
BE	22	19	14	6.5

Discussion

HDKA and EDKA have similar symptoms and signs, making it difficult to distinguish between them. The main difference is in serum glucose concentrations. In EDKA, serum glucose concentrations are normal or near-normal, making diagnosis challenging. Hypovolemia during the perioperative period can hide the typical polyuria caused by hyperglycemia, a common sign of DKA. SGLT2i-associated DKA leads to greater loss of bicarbonate, possibly due to renal wasting. This results in severe mixed or normal AG metabolic acidosis.

In EDKA presentations, average blood glucose levels are about half of those seen in HDKA, typically ranging from 180-200mg/dl. This difference may be due to physiological changes during the perioperative period, such as fasting and the surgical stress response [6, 7]. There is no specific association between the cessation of SGLT2i and the occurrence of DKA.

The American College of Endocrinology recommends discontinuing SGLT2i at least 24 hours before elective surgery or invasive procedures, and immediate cessation for emergency procedures[8] Recent editorials suggest a 48-hour or longer interruption based on the terminal half-life of SGLT2i [9]

However, there is no consensus guideline regarding the duration of withholding SGLT2i before surgery, with some sources suggesting a 5-7 day withholding period before major surgery(10) and up to 2 weeks for bariatric procedures when a very low-calorie diet is introduced 1-2 weeks before the operation.

SGLT2 inhibitors are often stopped before surgery and resumed 24-48 hr after, but for minor procedures, they may not need to be stopped or only on the day of the surgery. However, for patients with delayed oral intake, like those undergoing cardiac or abdominal surgery, stopping SGLT2 inhibitors for a longer period may be necessary. This requires coordination among specialists and managing perioperative hyperglycemia is important to prevent complications. When SGLT2 inhibitors are used with other glucose-lowering agents, appropriate strategies should be in place. It is best to start SGLT2 inhibitors after the patient can eat normally again.

Conclusion

Sodium-glucose co-transporter-2 inhibitor-associated diabetic ketoacidosis (DKA) can occur with normal or near-normal blood glucose levels, and euglycemic DKA (EDKA) may be more common during the perioperative period. It is important to identify the causes and understand the presentation and management of DKA, especially EDKA, to improve perioperative outcomes. The bariatric surgical population requires special attention due to additional risk factors for DKA, such as preoperative use of a very low-calorie diet (VLCD) and reduced postoperative intake. Guidelines are needed to assess risk, manage the use of SGLT2 inhibitors and insulin, and monitor and treat DKA in this patient population. Large-scale studies can help identify risk factors and develop universally applicable strategies for perioperative management of SGLT2 inhibitor therapy.

Clinical significance

It is important to consider the possibility of ketosis in patients with diabetic ketoacidosis (DKA), even if their serum glucose levels appear normal. The presence of normal blood sugar levels can mask the underlying DKA, leading to a diagnostic and therapeutic challenge. Therefore, a high level of clinical suspicion is necessary to diagnose euglycemic DKA (EDKA). In ill patients with diabetes, regardless of their blood glucose levels, it is crucial to assess blood pH and check for the presence of blood or urine ketones.

List of abbreviations

EDKA – Euglycemic diabetic ketoacidosis DKA- Diabetic ketoacidosis

HDKA – Hyperglycaemic diabetic ketoacidosis SGLT2i- Sodium Glucose cotransport 2 Inhibitor

ABG – Arterial blood gas

GRBS – General random blood sugar

VLCD – Very low-calorie diet

ICU – Intensive care unit

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Dr. Marutheesh. M

Consultant anesthetist and Intensivist

Dr. Gayathri Krishna Reddy

Senior Consultant – Anaesthesia

Dr. Murali Jayaraman

Consultant-Surgical Gastroenterologist

Dr. Harish M. M

Director- Institute of Critical Care Medicine

EUGLYCEMIC DIABETIC KETOACIDOSIS A RARE CAUSE FOR DELAYED EXTUBATION