What is the best fluid management strategy for a patient with type 2 diabetes on canagliflozin, presenting with worsening metabolic acidosis, a low bicarbonate level, an elevated anion gap, and a rising chloride level?

Fluid Management for SGLT2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis

Stop canagliflozin immediately and initiate balanced crystalloid resuscitation with lactated Ringer's solution or Plasma-Lyte at 15-20 mL/kg/hour (1-1.5 liters in the first hour), avoiding normal saline which will worsen the existing hyperchloremic component of the acidosis. 1, 2

Immediate Diagnostic Confirmation

Your patient's laboratory pattern—bicarbonate 13 mEq/L, anion gap 15 mmol/L, and rising chloride (103→108 mEq/L)—suggests euglycemic diabetic ketoacidosis (EDKA) from canagliflozin with a superimposed hyperchloremic component. 3, 4, 5

• Immediately obtain serum beta-hydroxybutyrate and urine ketones to confirm ketoacidosis, as these will be markedly elevated despite normal glucose levels. 1, 3, 6
• Check arterial blood gas to assess pH severity—if pH <7.2, this represents severe acidosis requiring intensive monitoring. 1
• Measure serum lactate to exclude concurrent lactic acidosis from tissue hypoperfusion. 1, 2
• Obtain comprehensive metabolic panel including potassium, as acidosis correction will shift potassium intracellularly and may unmask hypokalemia. 1, 2

Fluid Selection: Critical Decision Point

Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) exclusively—do NOT use normal saline (0.9% NaCl). 7, 2

The rising chloride (103→108 mEq/L) indicates your patient is developing hyperchloremic metabolic acidosis, likely from prior normal saline administration. Normal saline contains 154 mEq/L of chloride, which causes:

• Renal vasoconstriction and increased risk of acute kidney injury 7
• Worsening metabolic acidosis through chloride accumulation 7
• Increased inflammatory cytokine secretion 7

The Surviving Sepsis Campaign and Mayo Clinic guidelines explicitly recommend balanced crystalloids over normal saline for metabolic acidosis. 7, 2

Insulin and Dextrose Protocol

Start continuous intravenous insulin infusion (0.1 units/kg/hour of regular insulin) with concurrent dextrose 5% or 10% infusion to suppress ketogenesis while preventing hypoglycemia. 3, 4, 5

• This differs from hyperglycemic DKA—you must provide exogenous glucose because the patient is already euglycemic. 3, 5
• Continue insulin infusion until anion gap closes to <12 mmol/L and bicarbonate rises to >18 mEq/L. 1
• Monitor glucose hourly and adjust dextrose concentration (5% vs 10%) to maintain glucose 150-200 mg/dL during treatment. 3, 4

Electrolyte Management

Aggressively monitor and replace potassium, as insulin therapy will drive potassium intracellularly and precipitate life-threatening hypokalemia. 1, 2

• Check potassium every 2 hours initially. 1, 2
• Add potassium chloride 20-40 mEq/L to IV fluids if potassium <5.0 mEq/L. 3
• Hold insulin if potassium falls below 3.3 mEq/L until repleted. 7

Bicarbonate: When NOT to Use It

Do NOT administer sodium bicarbonate at this time. 7, 1, 2

• Bicarbonate is only indicated if pH <7.0-7.15 with severe hemodynamic instability despite adequate resuscitation. 1, 2
• Multiple studies show bicarbonate makes no difference in resolution of organic acidosis (DKA, lactic acidosis) and may worsen outcomes. 7, 2
• Your patient's bicarbonate of 13 mEq/L with anion gap 15 will correct with insulin, dextrose, and balanced crystalloid resuscitation. 1, 3

Monitoring Requirements

Serial laboratory monitoring every 1-2 hours initially is mandatory. 1, 2

• Arterial blood gas and pH 1, 2
• Serum electrolytes with calculated anion gap 1, 2
• Glucose and beta-hydroxybutyrate 1, 3
• Potassium (most critical—can shift rapidly) 1, 2

Critical Pitfall: Premature Insulin Discontinuation

Do not stop the insulin infusion until BOTH the anion gap normalizes (<12 mmol/L) AND bicarbonate rises above 18 mEq/L. 1, 3

• Case reports document recurrent acidosis when insulin is stopped prematurely, even after initial improvement. 3, 8
• When transitioning to subcutaneous insulin, administer basal insulin 2-4 hours BEFORE stopping the IV infusion to prevent rebound ketoacidosis. 7, 3

Duration of SGLT2 Inhibitor Effect

SGLT2 inhibitors can cause EDKA for 5-7 days or longer after discontinuation due to prolonged renal effects. 8

• Canagliflozin has a half-life of 10-13 hours, but its pharmacodynamic effects on renal glucose excretion persist much longer. 8
• One case report documented EDKA occurring 5 days after stopping an SGLT2 inhibitor before cardiac surgery. 8
• Permanently discontinue canagliflozin—do not restart this medication. 3, 4, 5, 6

Expected Timeline for Resolution

With appropriate treatment (balanced crystalloids, insulin, dextrose), expect:

• Anion gap closure within 12-24 hours 3, 4
• Bicarbonate normalization within 24-36 hours 3, 5
• Transition to subcutaneous insulin by 24-48 hours 3