What is the appropriate management for an adult patient with a history of diabetes, currently presenting with early appendicitis and metabolic acidosis, who was previously on Invokana (canagliflozin)?

Management of Early Appendicitis with Metabolic Acidosis in a Diabetic Patient on Canagliflozin

This patient requires immediate discontinuation of canagliflozin, urgent appendectomy without delay, aggressive fluid resuscitation with balanced crystalloids, insulin therapy, and close monitoring for euglycemic diabetic ketoacidosis (euDKA)—a life-threatening complication of SGLT2 inhibitors that can occur even with normal glucose levels. 1, 2, 3

Immediate Preoperative Actions

Recognize Euglycemic DKA from Canagliflozin

• Check serum ketones (beta-hydroxybutyrate) immediately, as this patient's metabolic acidosis (pH 7.24, anion gap 15, BE -9) in the setting of recent canagliflozin use strongly suggests euDKA, which can present with glucose levels as low as 168 mg/dL or even normal glucose 2, 4, 3
• The combination of surgical stress, fasting state, and SGLT2 inhibitor use creates a perfect storm for euDKA through increased glucagon secretion, volume depletion (up to 10% plasma volume loss from glucosuria), and enhanced ketogenesis 5, 3
• Do not be falsely reassured by normal or mildly elevated glucose—euDKA is the hallmark complication of SGLT2 inhibitors in surgical patients 2, 4, 3

Fluid Resuscitation Strategy

• Initiate aggressive IV fluid resuscitation with balanced crystalloids (lactated Ringer's or Plasma-Lyte) immediately, targeting mean arterial pressure ≥65 mmHg, as normal saline will worsen the metabolic acidosis through hyperchloremia 6, 7, 8
• The European Society of Anesthesiology specifically recommends balanced crystalloids over normal saline to prevent hyperchloremic acidosis, which would compound this patient's existing metabolic derangement 6, 7

Insulin Therapy

• Start continuous IV insulin infusion immediately if ketones are elevated, even with normal glucose, as this is the definitive treatment for euDKA 2, 3
• Add dextrose-containing fluids (D5 or D10) to the resuscitation if glucose falls below 200 mg/dL while continuing insulin to clear ketones 2, 3

Metformin Considerations

• Verify that metformin was appropriately discontinued, as metformin-associated lactic acidosis (MALA) could be contributing to the acidosis, particularly given the surgical stress, potential dehydration, and acute illness 1, 8
• The mortality rate of MALA is 30-50%, and risk factors include renal impairment, dehydration, and concurrent use of ACE inhibitors, ARBs, or NSAIDs—all common in diabetic patients 1, 8

Surgical Timing and Approach

Proceed to Surgery Without Delay

• Do not delay appendectomy to "optimize" the acidosis medically—surgical source control is paramount, and the 2020 WSES Jerusalem Guidelines support early appendectomy for early appendicitis 1, 6
• Brief resuscitation (few hours maximum) is acceptable to prevent hemodynamic instability on induction, but prolonged delay worsens outcomes, particularly in diabetic patients who present with more complicated disease 6, 9
• Diabetic patients with appendicitis are significantly more likely to present with perforation (38.9% vs 18.5% in non-diabetics) and have longer hospital stays, making early intervention even more critical 9

Intraoperative Management

• Use laparoscopic approach if expertise is available, as current evidence shows superior outcomes with lower complication rates in complicated appendicitis when laparoscopic expertise exists 1
• Remove the appendix even if it appears grossly normal, as surgeon's macroscopic judgment of early appendicitis is highly inaccurate and variable 1
• Monitor for the "lethal triad" (acidosis, hypothermia, coagulopathy) which would necessitate abbreviated surgery and ICU resuscitation 6, 7

Anesthetic Considerations

• Assess for diabetic gastroparesis preoperatively by questioning about abdominal bloating, early satiety, and vomiting, as this increases aspiration risk and may require rapid sequence intubation 1
• Evaluate for cardiac autonomic neuropathy (CAN) by checking for resting tachycardia, orthostatic hypotension (drop in BP from lying to standing), or QTc >440 ms on ECG, as CAN increases risk of perioperative hemodynamic instability and requires high-dependency unit monitoring 1
• Neither general anesthesia nor regional anesthesia shows superiority in diabetic patients, so choose based on standard surgical considerations 1

Monitoring and Endpoints

Serial Laboratory Assessment

• Obtain arterial blood gases, lactate, beta-hydroxybutyrate, and basic metabolic panel every 2-4 hours until acidosis resolves and ketones clear 6, 2, 3
• Target lactate clearance as a key endpoint—persistent or rising lactate despite resuscitation suggests ongoing tissue hypoperfusion or unrecognized pathology 6
• Monitor for hyperkalemia, which can accompany acidosis in surgical patients and requires immediate correction 6

Hemodynamic Targets

• Mean arterial pressure ≥65 mmHg 6
• Central venous pressure 8-12 mmHg if central access obtained 6
• Adequate urine output (≥0.5 mL/kg/hr) 6

Postoperative Management

Continue Aggressive Treatment

• Maintain IV insulin infusion until anion gap closes and ketones normalize, which typically takes 24-48 hours in euDKA cases 2, 3
• One reported case of canagliflozin-associated euDKA in a bariatric surgery patient required insulin drip until POD 4, prolonging hospital stay by 2 days 2

Medication Restart Criteria

• Do not restart canagliflozin—permanently discontinue this medication given the life-threatening complication 1, 2, 5
• Do not restart metformin until 48 hours postoperatively and only after confirming eGFR ≥60 mL/min/1.73m², patient eating/drinking normally, and no ongoing hemodynamic instability 1, 8
• Transition to alternative diabetes management (basal-bolus insulin regimen or other oral agents without DKA risk) in consultation with endocrinology 1

High-Dependency Monitoring

• Admit to ICU or high-dependency unit given the combination of severe metabolic acidosis, euDKA, and diabetic comorbidities that increase perioperative risk 1, 6
• Diabetic patients with appendicitis have significantly higher complication rates (19.4% vs 8.6%) and longer length of stay (3.0 vs 1.0 days), necessitating closer monitoring 9

Critical Pitfalls to Avoid

• Do not assume normal glucose excludes DKA—this is the defining feature of SGLT2 inhibitor-associated ketoacidosis and the most dangerous misconception 2, 4, 3
• Do not use normal saline for resuscitation—it will worsen the acidosis through hyperchloremic mechanisms 6, 7
• Do not delay surgery to "correct" the acidosis first—source control is the priority, and brief resuscitation followed by prompt surgery yields better outcomes 6
• Do not restart canagliflozin postoperatively—the ADA/EASD consensus warns that SGLT2 inhibitors should be used with extreme caution in insulin-deficient states and surgical stress, and this patient has demonstrated life-threatening susceptibility 1
• Do not overlook cardiac autonomic neuropathy—diabetic patients may have silent ischemia and dysautonomia requiring specialized monitoring 1