diabetic ketoacidosis (DKA)

Etiology

• new onset type 1 diabetes
• inappropriate use of insulin or non-adherence by a type-1 diabetic
• type 1 diabetic with a systemic infection
• type 1 diabetic with an acute myocardial infarction or other vascular event
• type 1 diabetic with trauma or stress
• use of glucocorticoids or adrenergic agonists by type 1 diabetic
• type 1 diabetic with hyperthyroidism or pheochromocytoma
• pancreatitis
• new onset ketosis-prone type 2 diabetes
• pharmaceuticals that increase risk
  • glucocorticoids
  • atypical antipsychotics
  • SGLT2 inhibitors (serum glucose may be normal)

Pathology

• deficiency of insulin
• increase in glucagon
• increase in catecholamines
• increase in cortisol

Clinical manifestations

• nausea/vomiting
• anorexia
• abdominal pain
• fatigue
• weight loss
• shortness of breath
• muscle cramps
• tachycardia
• tachypnea
• orthostatic hypotension
• polyuria
• polydipsia
• hypothermia

Diagnostic criteria

• serum glucose > 250 mg/dL*
• arterial blood gas: pH < 7.30
• serum HCO3- < 18 meq/L
• positive serum or urine ketones
• increased anion gap

* serum glucose may be < 250 mg/dL with euglycemic DKA due to SGLT2 inhibitor

Laboratory

• serum chemistries
  • serum glucose (> 250 mg/dL)*
  • urea nitrogen generally mildy increased
  • serum creatinine
  • electrolytes
    • hyponatremia: expected decrease in Na+ due to glucose (glucose - 100) x 0.016
      • expect serum sodium to increase with insulin administration
    • hyperkalemia (decreased total body K+)
      • expect serum potassium to decrease with insulin administration
    • serum bicarbonate < 15 meq/L
      • generally anion gap metabolic acidosis
  • serum amylase & serum lipase if suspected pancreatitis
    • serum amylase is often elevated in DKA (> 1000 U/L)
      • metabolic decompensation given as the reason
      • not specified if increase is due to pancreatic amylase
      • no explanation why 'metabolic decompensation' should cause a release of amylase
• arterial blood gas, pH < 7.30
• serum ketones positive
  • beta-hydroxybutyrate in blood/plasma/serum
• serum osmolality
• complete blood count with differential
  • non specific leukocytosis often present
    • WBC may be > 20,000/uL
• cultures when indicated: blood, urine, throat, sputum, cerebrospinal fluid
• hemoccult stool for suspected GI blood loss
• urinalysis
  • ketones in urine is less reliable than beta-hydroxybutyrate in blood/plasma/serum
• monitor serum electrolytes & serum glucose during insulin infusion

* serum glucose may be < 250 mg/dL with euglycemic DKA due to SGLT2 inhibitor

Diagnostic procedures

• electrocardiogram
  • monitor significant hyperkalemia or hypokalemia
  • rule out acute myocardial infarction & arrhythmias

Radiology

• chest radiograph
• abdominal CT not needed if abdominal pain resolves with resolution of ketoacidosis

Complications

• infection
  • pyelonephritis
  • pneumonia
• shock
  • hypovolemia
  • aggravation of hypovolemia by acidosis
  • cardiogenic shock from myocardial infarction
• thrombosis
  • increased factor VIII in DKA
  • decreased antithrombin III in DKA
  • hyperosmolar state
  • low cardiac output with acidosis
  • coronary artery disease
• cerebral edema
  • generally observed in children
  • more rapid fall in plasma glucose than in intracerebral glucose
• pancreatitis
• disseminated intravascular coagulation (DIC)

Differential diagnosis

• diabetic ketoacidosis*
  • glucose > 250 mg/dL
  • pH < 7.35 or HCO3- < 15 meq/L
  • positive serum or urine ketones
  • increased anion gap
• alcoholic ketoacidosis*
• starvation ketoacidosis*
• inherited disorders of branched-chain amino acids (uncommon)
• lactic acidosis
• renal failure with GFR < 20 mL/min
• salicylate intoxication
• methanol ingestion
• ethylene glycol ingestion
• paraldehyde ingestion
• formaldehyde ingestion
• toluene ingestion *Criteria for diabetic, alcoholic & starvation ketoacidosis overlap. A higher glucose favors DKA. A very low glucose favors starvation ketoacidosis.

Management

• goals
  • reverse metabolic acidosis
  • replace fluid & electrolytes
• fluid replacement
  • normal saline (1st line)
    • 15 mL/kg/hr for 1 hour
    • 7.5 mL/kg/hr for 2-4 hr
    • 3.75 mL/kg/hr for 24-36 hr until fluid loss is corrected
    • 15-20 mL/kg/hr for 1st few hours
  • if serum Na+ > 145 meq/L, use 1/2 normal saline
  • use of lactated Ringer's solution results in faster resolution of DKA by 3 hours
• insulin therapy
  • do not start insulin therapy until serum K+ > 3.3 meq/L
    • use KCl at 20-30 meq/hour through central line
    • do not start KCl until adequate urine output
  • 0.1 units/kg regular insulin IV bolus (or 10 units)
    • if serum glucose does not decline by 10% in 1st hour, an additional IV bolus of 0.14 units/kg of regular insulin may be given
  • insulin drip
    • 0.1 units/kg/hr of regular insulin
    • once serum glucose drops to 200 mg/dL, change IV fluid to contain dextrose (D5W-1/2NS, D5W-NS) 150-250 mL/hr
    • adjust insulin infusion to maintain serum glucose 150-200 mg/dL
    • ([[[A475260|serum glucose]] (mg/dL)] - 60) x 0.03 units/hr
      • the 60 may be adjusted to the lowest level of acceptable serum glucose
      • the 0.03 may be adjusted for sensitivity of the patient to insulin
    • monitor serum electrolytes & serum glucose during insulin infusion
  • change to subcutaneous insulin (70/30) when ketoacidosis has resolved & the patient is eating
  • stop insulin drip one hour after 1st dose of SQ insulin
  • reducing insulin infusion too early, before clearance of ketones, will cause relapse of DKA
• glucose replacement:
  • IV fluid is switched to D5 normal saline when glucose < 200 mg/dL
  • decrease rate of insulin infusion to diminish risk of hypoglycemia
• K+ replacement
  • if serum K+ < 3 meq/L, add 0.5 meQ/kg/hr in IV fluid
  • if serum K+ 3-4 meq/L, add 0.4 meQ/kg/hr in IV fluid
  • if serum K+ 4-5 meq/L, add 0.3 meQ/kg/hr in IV fluid
  • or add KCl 20-30 meq to each liter of IV fluids
  • K+ replacement if serum K+ < 5.3 meq/L
  • serum K+ should be checked every 2 hours
  • do not start K+ replacement until adequate urine output
• phosphate replacement
  • does not improve recovery or mortality
  • may prevent rhabdomyolysis from hypophosphatemia
• bicarbonate replacement
  • does not improve recovery or mortality
  • do not use unless pH < 6.9
  • 200 mmol of sodium bicarbonate in 100 mL of water + KCl 20 meq infused over 2 hours
• magnesium sulfate 2 g IV for magnesium deficiency
• subcutaneous heparin for patients at risk for DVT
• identify precipitating factors
• diet
  • nothing by mouth until ketoacidosis & nausea/vomiting resolve
  • ADA diet

Diabetes education

More general terms

• ketoacidosis
• diabetes mellitus complication

Additional terms

• diabetes mellitus
• hyperglycemic-hyperosmolar syndrome; hyperglycemic-hyperosmolar nonketotic coma (HHNC)
• hypokalemia
• hypophosphatemia