Diabetic Ketoacidosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ifrah Fatima, M.B.B.S[2]

Overview

Diabetic ketoacidosis is diagnosed in the presence of symptoms like lethargy, fruity breath, thirst, weight loss, abdominal pain, and Kussmaul breathing and laboratory findings of hyperglycemia (Plasma glucose > 250 mg/dL), anion gap metabolic acidosis (pH < 7.3) and Serum bicarbonate < 15 mEq/L) and ketonemia/ ketonuria. The mainstay of treatment involves aggressive hydration with normal saline, glucose correction with insulin, potassium repletion and correction of acidosis and ketosis.

Causes

The following are the causes of diabetic ketoacidosis (DKA):

Common Causes

• Lack of insulin
  • New diagnosis of Type 1 diabetes mellitus
  • Non compliance with insulin in a known diabetic patient
  • Insufficient insulin dose in hospitalized patients
• Drugs:
  • Antipsychotic agents (clozapine, olanzapine, risperidone)
  • Illicit drugs (cocaine and alcohol)
  • Corticosteroids
  • Glucagon
  • Interferon
  • Pentamidine
  • Sympathomimetic agents (albuterol, dopamine, dobutamine, terbutaline, ritodrine, thiazide diuretics)

• Infections:
  • Pneumonia
  • Sepsis
  • Urinary tract infection

Less common causes

Nonadherence to insulin treatment plans:

• Body image issues
• Financial problems
• Psychological factors

Physiological stressors:

• Acromegaly
• Thrombosis
• Cerebrovascular accident
• Cushing's disease
• Hemochromatosis
• Myocardial infarction
• Pancreatitis
• Pregnancy
• Psychological stress
• Shock/hypovolemia
• Trauma

Diagnosis

• The diagnosis of diabetic ketoacidosis is made in the presence of:
  • Hyperglycemia- Plasma glucose > 250 mg/dL
  • Anion gap metabolic acidosis- pH < 7.3; Serum bicarbonate < 15 mEq/L
  • Ketonemia/ Ketonuria
• Shown below is a table summarizing the diagnosis of Diabetic ketoacidosis according the the American Diabetes Association (ADA) guidelines.

VARIABLE	DIABETIC KETOACIDOSIS
	MILD (Plasma Glucose > 250mg/dL or 13.88 mmol/L)	MODERATE (Plasma Glucose > 250mg/dL or 13.88 mmol/L)	SEVERE (Plasma Glucose > 250mg/dL or 13.88 mmol/L)
Arterial pH	7.25 to 7.30	7.00 to < 7.24	< 7.00
Serum bicarbonate	15 to 18 mEq/L	10 to < 15 mEq/L	< 10 mEq/L
Urine ketone (Nitroprusside reaction method)	Positive	Positive	Positive
Serum ketone (Nitroprusside reaction method)	Positive	Positive	Positive
Effective serum osmolality	Variable	Variable	Variable
Anion gap	> 10 mEq/L (10 mmol/L)	> 12 mEq/L (12 mmol/L)	> 12 mEq/L (12 mmol/L)
Mental status	Alert	Alert/drowsy	Stupor/coma

Criteria for resolution

• According to American Diabetes Association, the following criteria must be met for labeling resolution of DKA:
  • Blood glucose <200mg/dl

PLUS

• Any two of the following:
  • Bicarbonate greater than or equal to 15 mEq/L
  • Venous pH > 7.3
  • Anion gap less than equal to 12 mEq/L
• Bicarbonate level should not be relied upon to assess the resolution of DKA. This is because high volumes of 0.9 % saline (NaCl) may lead to hyperchloremia in patients. The hyperchloremic acidosis will lower the bicarbonate and thus lead to difficulty is assessing whether the ketosis has resolved. The hyperchloremic acidosis may cause renal vasoconstriction and be a cause of oliguria.
• DKA usually resolves in 24 hours with appropriate treatment.

Treatment

Shown below is an algorithm summarizing the treatment of Diabetic ketoacidosis according the American Association of Clinical Endocrinologists (AACE) guidelines and American Diabetes Association guidelines.

Step-wise approach to management of diabetic ketoacidosis

DKA treatment protocol according to ADA guidelines

Fluids

Bicarbonate

Insulin

Potassium

Hydration status

pH greater than equal to 6.9

pH less than 6.9

0.1 u/kg/B.WT. as IV bolus

0.14 u/kg/B.WT/hr as continous IV infusion

K < 3.3 mEq/L

K = 3.3 - 5.2 mEq/L

K > 5.2 mEq/L

Severe hypovolemia

Mild dehydration

Cardiogenic shock

0.1 u/kg/B.WT. as IV continous infusion

Hold insulin and give 20-30mEq/L of potassium until K+ > 3.3mEq/L

Give 20-30mEq/L in each liter of IV fluids to maintain serum K 4-5mEq/L

Do not give potassium but check serum potassium every 2 hours

0.9% Nacl (1L/hr) as IV infusion

Check corrected serum sodium

Hemodynamic monitoring and add pressors accordingly

If serum glucose does not fall by 10 % within one hour of therapy then give 0.14 U/Kg as IV bolus and continue previous regimen

High serum Na (>145 mEq/L)

Normal serum Na (135-145 mEq/L)

Low serum Na (< 135 mEq/L)

When serum glucose drops to 200 mg/dl, reduce regular insulin to 0.02-0.05 U/Kg/hour, or give rapid-acting insulin at 0.1 U/kg SC every 2 hours, maintain serum glucose between 150 mg/dl to,200 mg/dl until resolution

0.45% NaCl (250-500 ml per hour depending on hydration status

0.9% NaCl (200-500 ml per hour) depending on hydration status

When serum glucose decreases to 200 mg/dl, switch to 5% dextrose with 0.45% NaCl at 150-250 ml/hour

Do's

• Correct hypovolemia and dehydration aggressively.
• In patients with potassium(K) < 3.3 mEq/L, fluids and potassium replacement must be done before initiating insulin therapy, to prevent further hypokalemia.
• Monitor plasma glucose levels every hourly.
• Monitor serum electrolytes and pH levels every 2-3 hourly.

Don'ts

• Avoid rapid correction of plasma osmolality and serum sodium, to prevent fatal cerebral edema.
• Maximum reduction in plasma osmolality should be 3 mOsmol/kg per hour.

References

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