Diabetic Ketoacidosis (DKA) in Adults

Background

• Diabetic ketoacidosis (DKA) is a metabolic emergency occurring mainly in patients with type 1 diabetes, characterized by hyperglycemia, metabolic acidosis, and ketonemia.
  • Rarely, DKA occurs in the absence of hyperglycemia in some individuals (such as in patients with type 1 or type 2 diabetes taking sodium-glucose cotransporter-2 [SGLT2] inhibitors).
  • The use of SGLT2 inhibitors in patients with diabetes is reported to be associated with an increased rate of DKA.
• DKA is caused by absolute or relative insulin deficiency along with increased levels of counterregulatory hormones. Precipitating factors for DKA include new-onset diabetes, insulin omission, infection, and other physiologic stressors (such as myocardial infarction).
• Clinical presentation of DKA can vary with severity of DKA and comorbid conditions.
• Complications of untreated DKA may include hyperkalemia, shock, acute renal failure, cardiac complications, and rhabdomyolysis (in patients with severe dehydration). Complications of management of DKA may include cerebral edema, hypokalemia, and hypoglycemia.
• Mortality is reported to be < 1% in adults with DKA, although mortality > 5% is reported in older adults and patients with concomitant life-threatening illnesses or significant comorbidities.

Evaluation

• Initial testing for patients suspected to have DKA should include:
  • glucose
  • ketones (direct measurement of beta-hydroxybutyrate levels is the preferred method for all patients, including patients taking sodium-glucose transporter-2 [SGLT2] inhibitors)
  • electrolytes (including serum bicarbonate)
  • arterial or venous blood gas
  • blood urea nitrogen and creatinine
  • complete blood count with differential
• Initial calculations to perform in patients with DKA should include:
  • Anion Gap Calculator
  • Sodium Correction in Hyperglycemia
• Perform urinalysis to evaluate for urine ketones (dipstick) and glucose and to assess for urinary tract infection.
• Perform electrocardiography (ECG) to assess for abnormalities related to potassium levels.
• Other testing to consider if clinically indicated:
  • blood tests such as HbA1c in patients with diabetes or hyperglycemia (blood glucose > 140 mg/dL [7.8 mmol/L]) admitted to the hospital who have not had HbA1c measured in the past 3 months (Strong recommendation) to differentiate acute decompensation, chronically poorly controlled or previously undiagnosed diabetes
  • urine culture in patients with suspected urinary tract infection
  • chest radiography if pulmonary disease is suspected

Management

• The goals of management of DKA are:
  • to restore intravascular volume
  • to prevent and/or correct electrolyte abnormalities
  • to correct acidosis
  • to correct hyperglycemia
• Fluids and electrolytes
  • IV fluids are first-line treatment.
    • Use 0.9% sodium chloride (normal saline) IV for initial fluid replacement.
    • Subsequent IV fluid choice is based on calculated corrected serum sodium.
      • If corrected serum sodium is high or normal, give 0.45% sodium chloride at 250-500 mL/hour (4-14 mL/kg/hour), depending on hydration state.
      • If corrected serum sodium is low, give 0.9% sodium chloride (normal saline) at 250-500 mL/hour (4-14 mL/kg/hour), depending on hydration state.
  • Bicarbonate therapy in patients with DKA is controversial due to a lack of benefit in randomized trials; however, no prospective randomized studies concerning the use of bicarbonate in DKA with pH values < 6.9 have been reported.
    • Bicarbonate therapy is recommended by the American Diabetes Association in patients with pH < 6.9.
    • Suggested dosing and administration: 100 mEq of sodium bicarbonate in 400 mL of sterile water with 20 mEq of potassium chloride at a rate of 200 mL per hour for 2 hours (repeat every 2 hours until pH ≥ 6.9).
  • Replace potassium after establishing adequate renal function (urine output 50 mL/hour).
  • Consider treatment with magnesium if serum magnesium level is < 1.2 mg/dL (0.5 mmol/L) or if symptoms of hypomagnesemia develop (such as paresthesia, tremor, muscle spasm, seizures, or cardiac arrhythmia).
  • Phosphate supplementation is not routinely recommended but should be considered in patients with any of the following:
    • serum phosphate level < 1 mg/dL (0.3 mmol/L)
    • cardiac dysfunction, anemia, or respiratory distress, to avoid possible skeletal and cardiac weakness and respiratory depression
• Insulin administration
  • IV insulin
    • Indications for IV insulin administration:
      • severe DKA
      • anasarca
      • hypotension
      • associated severe critical illness
    • Do not initiate IV insulin until after beginning fluid resuscitation and hypokalemia correction (insulin can begin promptly after starting fluid resuscitation).
  • Consider subcutaneous insulin instead of IV insulin (using rapid-acting insulin analog) in patients who are alert, tolerate oral fluids (no nausea or vomiting), have a pH > 7, and have bicarbonate ≥ 10 mEq/L (10 mmol/L).
  • Consider basal insulin in patients with newly diagnosed type 1 diabetes and in patients who were previously on basal insulin regimens prior to development of DKA.
• Identify and address the underlying cause of DKA.
• Monitoring during DKA
  • Measure glucose levels every 1 hour after starting IV insulin to ensure at least a 10% drop. When glucose starts to normalize, measure glucose at least every 2-4 hours until stable.
  • Measure serum electrolytes, bicarbonate, blood urea nitrogen, creatinine, and venous pH at least every 2-4 hours during initial resuscitation.
  • Continue cardiac monitoring if needed.
  • Monitor for complications of DKA.
  • Monitor for resolution of DKA.
    • Criteria for resolution of DKA varies by professional organization.
    • American Diabetes Association criteria for resolution of ketoacidosis includes a blood glucose < 200 mg/dL and 2 of the following criteria:
      • serum bicarbonate level ≥ 15 mEq/L
      • venous pH > 7.3
      • calculated anion gap ≤ 12 mEq/L
• Follow-up
  • If the patient cannot eat but is no longer critically ill, it is preferable to continue IV fluids and IV insulin, but subcutaneous insulin can be used.
  • Patients with critical illness should continue IV fluids and IV insulin but change to an insulin protocol with prespecified glycemic targets for critical illness.
  • For a patient managed with IV insulin who is able to eat, convert to subcutaneous insulin after resolution of DKA.
    • If patient has not received long-acting basal insulin in previous 24 hours, give long-acting basal insulin at least 2 hours prior to stopping IV insulin in order to prevent rebound ketoacidosis (long-acting basal insulin is needed due to short half-life of IV insulin [about 10 minutes]).
    • If transition from IV to subcutaneous insulin is timed prior to a meal, prandial dose of short or rapid-acting insulin plus basal insulin might allow discontinuation of IV in 1 hour due to the earlier onset of action of rapid-acting insulin as compared to basal insulin.
    • In patients with known diabetes, restart dose of insulin used before DKA as long as previous glycemic control was adequate.