Euglycaemic Diabetic Ketoacidosis

Diabetic ketoacidosis with near-normal BSL. Euglycaemic DKA:

• Occurs due to altered balance of glucose production (in the liver) and intake (dietary), and renal glucose clearance
• Typically caused by SGLT2 inhibitors, in the context of physiological stress
  Intercurrent illness, surgery, fasting, reduced carbohydrate intake (such as diet modification for bariatric surgery).
• Is a major adverse event
  ~50% risk of ICU/ admission.

Epidemiology and Risk Factors

Incidence:

• ~2-5/1000 patient-years in a non-operative setting

Key risk factors:

• Use of SGLT2 inhibitors
  May occur even if ceased up to 3 days preoperatively.
• Physiological stress
  • Perioperative patients
    • Fasting
    • Endoscopy
      Additional stress due to use of bowel preparation.
    • Degree of surgical stress
      Counter-regulatory hormone production.
  • Illness
  • Volume depletion
  • Medication changes
    • Insulin withheld/reduced
    • Improper use of SGLT2 inhibitors
  • Renal failure
    Prolonged elimination of SGLT2 inhibitors.

Pathophysiology

SGLT2 inhibitors:

• Reduce BSL by inhibiting renal reabsorption of glucose, promoting glycosuria
  • Fall in plasma glucose reduces insulin secretion from beta cells
  • Fall in insulin ↑ glucagon secretion from alpha cells
    SGLT2 inhibitors also directly stimulate alpha cells.
  • ↑ in glucagon:insulin ratio stimulates:
    • Lipolysis
    • Hepatic fatty acid oxygenation
    • Hepatic ketogenesis
    • Hepatic glycogenolysis & gluconeogenesis
• Reduce renal sodium absorption
• ↑ ketone body reabsorption
  Leads to ketoacidosis without ketonuria

Physiological stress:

• ↑ counter-regulatory hormone production
  • Adrenaline
  • Cortisol
• ↑:
  • Insulin resistance
  • Protein catabolism

Clinical Manifestations

Presentation is similar to DKA, but with a near-normal serum BSL:

• Dominant symptoms
  • Nausea/Vomiting
  • Tachypnoea
• Associated symptoms:
  • Abdominal pain
    Significant.
  • Tachycardia
  • Flushing
  • Altered mental state
  • Polyuria
    May be masked by perioperative hypovolaemia.

Timing:

• May be highly variable
• Hours to 6 weeks in bariatric patients
• Many occur in days postoperatively.

Diagnostic Approach and DDx

Investigations

Bloods:

• BSL <14mmol/L
• Elevated blood ketones
• Low or absent urinary ketones
  Not reliable indicator.
• Elevated urinary glucose
  Urinary glucose does not accurately reflect BSL in patients on SGLT2 inhibitors.

Management

Prevention:

• Insulin
  Cessation or dose reduction will ↑ risk of euglycaemic DKA.
• Avoid glucocorticoids
  ↑ insulin resistance.

Primarily supportive:

• ICU or HDU may be required in up to 50%

Anaesthetic Considerations

• F
  • Assess risk of euglycaemic DKA
    • Factors
      • Duration of fasting
      • Bariatric patients
      • Significance of surgery
      • Time to restarting PO intake
        SGLT2 inhibitors should not be restarted until post-operative catabolic state has been overcome by PO intake.
    • Low risk patients
      • e.g. Healthy, day-case, eating immediately post-operatively.
      • Withhold SGLT2 inhibitor on DOS
        
      • Restart SGLT2 inhibitor 24-48 hours post-operatively, provided PO intake has resumed
    • High risk patients
      • e.g. Major surgery, risk of post-operative ileus, risk of post-operative fast.
      • Cease agent for ⩾3 days, in consultation with endocrinology, surgery, and anaesthesia.

Marginal and Ineffective Therapies

Complications

Prognosis

Key Studies

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References

1. Thiruvenkatarajan V, Meyer EJ, Nanjappa N, Van Wijk RM, Jesudason D. Perioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic review. British Journal of Anaesthesia. 2019 Jul;123(1):27–36.
2. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.