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Diabetic Ketoacidosis
Melanie J. Lippmann, MD
image BASICS
DESCRIPTION
  • A life-threatening medical emergency in diabetics secondary to severe insulin deficiency and characterized by hyperglycemia, ketosis, and metabolic acidosis
  • System(s) affected: endocrine/metabolic
EPIDEMIOLOGY
Incidence
  • In the United States: 46 episodes/10,000 diabetics; 2/100 patient-years of type 1 diabetes mellitus (DM) (1)
  • Predominant age: 19 to 44 years (56%) and 45 to 65 years (24%); only 18% are <20 years.
ETIOLOGY AND PATHOPHYSIOLOGY
A deficiency of insulin, exacerbated by an increase in counterregulatory hormones (e.g., catecholamines, cortisol, glucagon, and growth hormone) leading to a hyperglycemic crisis, osmotic diuresis, ketosis with metabolic acidosis, and frequently accompanied by electrolyte disturbances
  • Noncompliance/insufficient insulin: 25%
  • Infection: 30-40%
  • First presentation of DM: 10-25%
  • Myocardial infarction (MI): 5-7%
  • No cause identified: 10-30%
  • Cerebrovascular accident (CVA)
  • Medications (corticosteroids, sympathomimetics, atypical antipsychotics)
  • Illicit drugs (cocaine)
  • Trauma
  • Surgery
  • Emotional stress
  • Pregnancy
RISK FACTORS
  • Type 1 > type 2 DM
  • Younger patients at higher risk
GENERAL PREVENTION
  • Close monitoring of glucose during periods of stress, infection, and trauma
  • Careful insulin control and regular monitoring of blood glucose levels
  • “Sick day” management instructions
COMMONLY ASSOCIATED CONDITIONS
Complications of chronic (and poorly controlled) DM such as nephropathy, neuropathy, and retinopathy
image DIAGNOSIS
PHYSICAL EXAM
  • Hypotension
  • Tachycardia
  • Hypothermia or fever
  • Tachypnea, Kussmaul respirations
  • Fruity odor of ketotic breath (acetone smell)
  • Decreased reflexes
  • Abdominal tenderness, decreased bowel sounds
  • Dry mucous membranes, poor skin turgor
  • Decreased perspiration
  • Altered mental status
  • Coma
DIFFERENTIAL DIAGNOSIS
  • Hyperosmolar hyperglycemic crisis
  • Alcoholic ketoacidosis
  • Starvation ketosis
  • Toxic ingestions (e.g., salicylates, methanol)
  • Lactic acidosis
  • Uremia/chronic renal failure
  • Sepsis
  • Acute pancreatitis
DIAGNOSTIC TESTS & INTERPRETATION
  • ECG
    • Usually shows sinus tachycardia
    • Changes consistent with electrolyte abnormalities
    • Ischemia/MI as a precipitating factor
  • Urine and blood cultures
  • Consider lumbar puncture (meningitis).
  • Chest x-ray to rule out possible infectious etiology
Initial Tests (lab, imaging)
Diagnostic Procedures/Other
Only if surgical problem is the underlying precipitant (e.g., appendicitis, cholecystitis)
image TREATMENT
  • Oxygen and airway management, as needed
  • Establish IV access.
  • Cardiac monitoring
  • Start isotonic crystalloid solution (0.9% saline).
  • Fingerstick glucose testing
GENERAL MEASURES
  • All but mild cases require inpatient management.
  • Severe DKA requires an ICU setting.
  • Goals
    • Fluid resuscitation
    • Insulin therapy to normalize serum glucose
    • Resolution of anion gap acidosis
    • Correction of electrolytes
  • Identify and treat the precipitating cause (e.g., infection, MI)
  • Laboratory testing during management:
    • Serum glucose q1-2h until stable
    • Electrolytes, phosphorus, and venous pH q2-6h as needed
MEDICATION
First Line
  • Insulin (1)[C]
    • Bolus 0.1 U/kg IV then continuous infusion at 0.1 U/kg/hr (do not use initial insulin bolus in children)
    • If without bolus, 0.14 U/kg/hr continuous infusion (4)
    • Aim for rate of serum glucose decline of 100 mg/dL/hr
    • When glucose 200 mg/dL, reduce infusion to 0.02 to 0.05 U/kg/hr IV or give rapid-acting insulin at 0.1 U/kg SC q2h; goal glucose is 150 to 200 mg/dL.
    • Overlap and continue IV insulin infusion for 1 to 2 hours after SC insulin is initiated.
  • IV fluids to correct dehydration: Start with 0.9% NaCl bolus, calculate corrected sodium; if serum Na+ is high, consider 0.45% NaCl to replace free fluid loss or when adding potassium replacement.
    • When glucose is 200 mg/dL, change to 5% dextrose with 0.45% NaCl at 150 to 250 mL/hr.
  • Potassium: falsely elevated due to acidosis; when K+ ≤5.2 mg/dL and if urine output is adequate, start replacement with 20 to 30 mEq/L of K+ in 1 L IV fluids (1).
    • Hold insulin if K+ ≤3.3 mg/dL; give IV potassium 20 to 30 mEq/hr with fluids until >3.3 mg/dL to prevent cardiac arrhythmia (class III).
    • For each 0.1 unit of pH, serum K+ will change by ˜0.6 mEq in opposite direction.
  • P.297

  • Phosphorus: Routine replacement may lead to hypocalcemia; if very low (<1.0), give 20 to 30 mEq/L of K-Phos in fluids.
  • Sodium bicarbonate: no demonstrable benefit with a pH >7.0 (2,5)[B]; rehydration usually leads to resolution of acidosis. Guidelines recommend its use with pH <6.9 or in patients with life-threatening hyperkalemia; however, there is evidence that it may increase cerebral edema, especially in children (6)[A].
  • Magnesium: If Mg ≤1.8 mg/dL and the patient is symptomatic, consider replacement.
  • Precautions
    • If the patient is on an insulin pump, it should be stopped.
    • If glucose does not fall by 10% in 1st hour, give regular insulin 0.14 U/kg IV bolus, then continuous infusion at previous rate.
    • If using bicarbonate, add 100 mmol or 2 ampules of sodium bicarbonate to 400 mL isotonic solution with 20 mEq KCL over 200 mL/hr for 2 hours until venous pH is >7.0, then stop infusion (1).
Second Line
Insulin, SC or IM: Load with 0.3 U/kg SC, followed by 0.1 U/kg/hr; space dosing to q2h once glucose <250 mg/dL; in uncomplicated DKA, may be safe and cost effective (7)[B]
Pediatric Considerations
  • Children with moderate to severe DKA should be transferred to the nearest pediatric critical care hospital.
  • Cerebral edema is a rare complication (˜1%) but has a mortality of 20-50%:
    • Diagnostic criteria exist for diagnosis; CT may rule out alternative diagnoses (8).
    • Treat with IV bolus of mannitol 1 g/kg in 20% solution, reduce IV fluid rate, and consider hypertonic 3% saline (9).
Geriatric Considerations
Must be careful with impaired renal function or congestive heart failure when correcting fluid and electrolyte abnormalities
Pregnancy Considerations
  • Pregnancy itself is diabetogenic and also results in a compensated respiratory alkalosis (HCO319 to 20 mEq/L) with theoretically reduced buffering capacity
  • Pregnant women are more susceptible to DKA.
  • Euglycemic DKA
  • Increased risk of preeclampsia and fetal death
  • &bgr;-Tocolytics and corticosteroids can trigger DKA.
  • Perinatal death: 9-35%
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
ADA admission guidelines: blood glucose >250 mg/dL; pH <7.3; HCO3 ≤15 mEq/L; ketones in urine; ICU setting for severe DKA (10)
IV Fluids
  • 1 to 1.5 L over the 1st hour, then, if serum corrected Na is high or normal, give 0.45% NaCl at 250 to 500 mL/hr depending on hydration state.
  • Switch to 5% dextrose in 0.45% saline at maintenance rate when serum glucose <200 mg/dL; maintain blood glucose between 150 and 250 mg/dL.
  • Overly rapid correction of fluid balance may precipitate cerebral edema (2)[C]; if the blood glucose level is falling too rapidly, consider using a 10% dextrose solution instead.
Pediatric Considerations
Bolus 10 to 20 mL/kg initially; 4-hour fluid total should be <50 mL/kg to reduce chance of cerebral edema.
Discharge Criteria
  • Discharge when DKA has resolved: anion gap <12, glucose <200 mg/dL; pH >7.3; bicarbonate >18 mEq/L; additionally, patients must be tolerating PO intake and able to resume home medication regimen.
  • Underlying precipitant (e.g., infection) must be identified and treated.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Monitor mental status, vital signs, and urine output q30-60min until improved, then q2-4h.
  • Monitor blood sugar q1h until <200 mg/dL, then q2-6h.
  • Monitor electrolytes, BUN, venous pH, and creatinine q2-4h.
DIET
  • NPO initially
  • Advance to preketotic diet when nausea and vomiting are controlled.
  • Avoid foods with high glycemic index (e.g., soft drinks, fruit juice, white bread, etc.).
PROGNOSIS
  • 16% of all diabetes-related fatalities
  • Overall DKA mortality of 0.5-2%.
  • In children <10 years of age, DKA causes 70% of diabetes-related fatalities.
REFERENCES
1. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343.
2. Agus MS, Wolfsdorf JI. Diabetic ketoacidosis in children. Pediatr Clin North Am. 2005;52(4):1147-1163.
3. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005;71(9):1705-1714.
4. Kitabchi AE, Murphy MB, Spencer J, et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care. 2008;31(11):2081-2085.
5. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in diabetes. Diabetes Care. 2004;27(Suppl 1):S94-S102.
6. Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis—a systematic review. Ann Intensive Care. 2011;1(1):23.
7. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117(5):291-296.
8. Watts W, Edge JA. How can cerebral edema during treatment of diabetic ketoacidosis be avoided? Pediatr Diabetes. 2014;15(4):271-276.
9. Brown TB. Cerebral oedema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J. 2004;21(2):141-144.
10. American Diabetes Association. Hospital admission guidelines for diabetes. Diabetes Care. 2004;27(Suppl 1):S103.
Additional Reading
&NA;
  • American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(Suppl 1):S11-S66.
  • Sheikh-Ali M, Karon BS, Basu A, et al. Can serum beta-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care. 2008;31(4):643-647.
See Also
&NA;
Diabetes Mellitus, Type 1
Codes
&NA;
ICD10
  • E10.10 Type 1 diabetes mellitus with ketoacidosis without coma
  • E13.10 Oth diabetes mellitus with ketoacidosis without coma
  • E10.11 Type 1 diabetes mellitus with ketoacidosis with coma
Clinical Pearls
&NA;
  • Admit if blood glucose >250 mg/dL, pH <7.3, HCO3 ≤15 mEq/L, and ketones in urine.
  • Potassium is falsely elevated due to acidosis; start replacement when K+ ≤5.2 mg/dL and urine output is adequate.