DKA resolution criteria and misleading urine ketones

Electrolyte Disordersmedium

A 35-year-old woman presents to the hospital with 2 days of worsening nausea, vomiting, and abdominal pain. Her past medical history is significant for type 1 diabetes and hypothyroidism. She reports running out of her home insulin several days ago, and a review of systems is positive for polyuria and increased thirst. On arrival, BP is 94/52 mm Hg, heart rate is 134/min, and respiratory rate is 24/min. On physical examination, she appears somewhat lethargic, with dry mucus membranes and a 2/6 systolic murmur best heard over the left upper sternal border. The rest of her physical examination is unremarkable. Based on her initial laboratory results, she is initiated on an IV insulin drip and potassium-containing IV fluids for management of diabetic ketoacidosis (DKA). Several hours later, she reports improving nausea and abdominal pain, and she is able to eat crackers. Laboratory data (initial; five hours later; reference range): Serum: sodium 132 mEq/L; 138 (136–145); potassium 4.8 mEq/L; 4.5 (3.5–5.0); chloride 98 mEq/L; 106 (98–106); total CO₂ 14 mEq/L; 22 (23–28); creatinine 1.4 mg/dL; 1.1 (0.5–1.1); glucose 384 mg/dL; 235 (70–99, fasting); albumin 3.6 g/dL; 3.3 (3.5–5.5); β-hydroxybutyrate 6.2 mmol/L; 0.4 (<0.5); lactate 2.0 mmol/L; 1.8 (0.7-2.1). Venous blood gas: pH 7.22; 7.30 (7.32–7.41); pCO₂ 32 mm Hg; 42 (42–53); pO₂ 42 mm Hg; 44 (35–42). Urinalysis: pH 6.0; 5.5 (4.5–8.0); specific gravity 1.023; 1.012 (1.005–1.025); glucose 4+; 2+ (negative); ketones small; large (negative); protein 2+; 1+ (negative). Which ONE of the following is the MOST appropriate next step in management?

  1. A.Transition insulin from IV to subcutaneous dosingCorrect
  2. B.Continue insulin IV until urinary ketones are decreasing
  3. C.Continue insulin IV and transition to dextrose-containing IV fluids
  4. D.Continue insulin IV until urinary ketones are undetectable

Explanation

The next best step is to transition the patient from IV insulin to subcutaneous insulin. Expert opinion recommends transitioning to subcutaneous insulin once DKA has resolved. Resolution of DKA is evidenced by normalization of both the anion gap (AG) and levels of serum ketoacids, specifically β-hydroxybutyrate (BHB). In this patient, the AG has normalized from 20 to 10, and BHB is now normal at 0.4 mmol/L, indicating that a switch to subcutaneous insulin is appropriate. Urinary ketones are not a reliable indicator of resolution of DKA, especially during treatment. Unlike direct measurements of serum BHB, urinary measurements of ketones are based on the use of a nitroprusside reaction that provides a semiquantitative measure of the ketoacid acetoacetate and does not register the presence of BHB. As ketoacidosis resolves with treatment, BHB is oxidized to acetoacetate and nitroprusside testing of ketones (in urine or serum) may give the misleading impression that ketosis is not improving or even worsening, as seen in this patient, in whom urinary ketones are increasing, whereas other measures of DKA are improving. Thus, treatment decisions should not be made based on urine ketone values. As this patient’s DKA has resolved, it is inappropriate to continue IV insulin therapy with or without the addition of dextrose-containing fluids. Dextrose-containing fluids may be added once serum glucose decreases below 200 mg/dL and thus are not needed here, particularly in the setting of planned transition of insulin therapy from IV to subcutaneous.

Why each option

A.
Correct. The anion gap normalized from 20 to 10 and beta-hydroxybutyrate fell to 0.4 mmol/L, so DKA has resolved and subcutaneous insulin is appropriate.
B.
Urine nitroprusside detects acetoacetate, not beta-hydroxybutyrate, so ketonuria rises during recovery and should not guide continued IV insulin.
C.
Dextrose-containing fluids are added when glucose falls below about 200 to 250 mg/dL during ongoing ketoacidosis, which has already resolved here.
D.
Waiting for undetectable urine ketones prolongs IV insulin unnecessarily because acetoacetate persists in urine after ketoacidosis has resolved.

Reference: Kitabchi AE, Diabetes Care 2009 (Hyperglycemic crises in adult patients with diabetes); Umpierrez GE, Diabetes Care 2024 (Hyperglycemic crises in adults with diabetes: a consensus report)

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