Diabetic Ketoacidosis Definition: Diabetic Ketoacidosis is one of the most serious acute complications of diabetes. It s more common in young patients with type 1 diabetes mellitus. It s usually characterized by hyperglycemia, anion gap metabolic acidosis and ketonemia. Serum glucose concentration is generally below 800 mg/dl and often approximately 350 to 500 mg/dl. Clinical presentation: It usually evolves rapidly over 24 hours. Common signs and symptoms are: Early symptoms of Hyperglycemia: polyuria, polydipsia, weight loss Early signs of Ketoacidosis: Nausea, vomiting, abdominal pain, hyperventilation (Kussmaul respirations), Fruity odor Neurologic symptoms as hyperglycemia worsens: Mental obtundation, lethargy, focal deficits, seizure, coma Signs of volume depletion: decreased skin turgor, dry axillae and oral mucosa, low jugular venous pressure, tachycardia, hypotension
Precipitating factors: Diagnosis: Initial evaluation should include: Airway, breathing, circulation (ABC) Mental status Possible precipitating factors Volume status Initial laboratory evaluation should include: Serum glucose Electrolytes (with calculation of the anion gap) Blood urea nitrogen (BUN) Plasma creatinine Complete blood count (CBC) with differential Urinalysis and urine ketones by dipstick Plasma osmolality Serum ketones (if urine ketones are present) Arterial blood gas (if the serum bicarbonate is substantially reduced or hypoxia is suspected) Electrocardiogram.
Laboratory evaluation and diagnostic criteria: Laboratory findings DKA Mild Moderate Severe Plasma glucose (mg/dl) >250 >250 >250 Plasma glucose (mmol/l) >13.9 >13.9 >13.9 Arterial ph 7.25 to 7.30 7.00 to 7.24 <7.00 Serum bicarbonate (meq/l) 15 to 18 10 to <15 <10 Urine ketones Positive Positive Positive Serum ketones - Nitroprusside reaction Positive Positive Positive Serum ketones - Enzymatic assay of beta hydroxybutyrate (normal 3 to 4 mmol/l 4 to 8 mmol/l >8 mmol/l range <0.6 mmol/l) Effective serum osmolality (mosm/kg) Variable Variable Variable Anion gap (Na+) (Cl + HCO3 ) (meq/l). >10 >12 >12 Alteration in sensoria or mental obtundation Alert Alert/drowsy Stupor/coma The typical total body deficits of water and electrolytes in DKA: Measurement of HbA1c may be useful in determining whether the acute episode is the culmination of an evolutionary process in previously undiagnosed or poorly controlled diabetes or a truly acute episode in an otherwise well-controlled patient.
Treatment: Fluid replacement: The initial goal of treatment is to expand extracellular volume and stabilize cardiovascular status. Fluid repletion is usually initiated with isotonic saline (0.9% NaCl). In hypovolemic patients without shock (and without heart failure), isotonic saline is infused at a rate of 15 to 20 ml/kg lean body weight per hour (approximately 1000 ml/hour in an average-sized person), for the first couple hours, with a maximum of <50 ml/kg in the first four hours. After the second or third hour, optimal fluid replacement depends upon the state of hydration, serum electrolyte levels, and the urine output. The most appropriate IV fluid composition is determined by the sodium concentration "corrected" for the degree of hyperglycemia. Estimated (corrected) plasma sodium = Measured plasma or serum sodium concentration + (2 * (Serum glucose - 100) / 100) If calculated effective serum osmolality < 320 mosm/kg (320 mmol/kg), then consider etiologies other than DKA. Osm (mosm/kg) = (Na * 2) + (Glucose (mg/dl )/ 18) + (BUN (mg/dl) / 2.8) Potassium replacement: Initiated immediately if the serum potassium is <5.3 meq/l. the target goal of serum potassium level is 4-5 meq/l. Potassium replacement is given after ensuring that there is adequate renal function (urine output 50 ml/hour). Phosphate replacement: If the serum phosphate is < 1 mg/dl (0.32 mmol/l), consider adding potassium phosphate 20-30 meq/l to IV fluids. Also consider adding phosphate replacement in patients with cardiac dysfunction, hemolytic anemia, or respiratory distress.
Magnesium replacement: If the serum magnesium is < 1.2 mg/dl (0.5 mmol/l), consider giving magnesium sulfate 8-12 g IV in the first 24 hours, then 4-6 g/day IV for 3-4 days. Bicarbonate and metabolic acidosis: If the ph is < 6.9, consider sodium bicarbonate 100 mmol (100 meq) in 400 ml sterile water plus 20 meq of Potassium Chloride IV at 200 ml/hour for 2 hours and repeat until the PH is 7.00. Monitor ph and bicarbonate concentration every 2 hours. Insulin: The bolus dose of insulin can be omitted if a higher dose of continuous IV regular insulin (0.14 units/kg per hour, equivalent to 10 units/hour in a 70-kg patient) is initiated. Hold insulin if the potassium level is < 3.3 meq/l (3.3 mmol/l) until potassium is replete to avoid complications such as cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness. Volume repletion alone can initially reduce the serum glucose by 35 to 70 mg/dl (1.9-3.9 mmol/l) per hour. When the patient is able to eat and the blood glucose is <200 mg/dl (11.1 mmol/l) and at least two of the following goals are met: Serum anion gap <12 meq/l (or at the upper limit of normal for the local laboratory) Serum bicarbonate 15 meq/l Venous ph >7.30 IV insulin infusion should be tapered and a multiple-dose, subcutaneous insulin schedule should be started while continuing IV insulin for 1-2 hours after starting subcutaneous insulin.
Monitoring: Serum glucose initially every hour until stable. Serum electrolytes, blood urea nitrogen (BUN), creatinine, and venous ph should be measured every two to four hours.
Resolution of DKA: DKA is considered resolved when the following goals are achieved: Serum glucose below 200 mg/dl (11.1 mmol/l) Anion gap <12 meq/l (or less than the upper limit of normal for the local laboratory) Serum bicarbonate 15 meq/l (venous) ph >7.30 The patient is able to eat. References: 1. Hirsch, I., & Emmett,M.(2018). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. In J. E. Mulder (Ed.), UpToDate. Retrieved January 1, 2019 from https://www.uptodate.com/contents/diabetic-ketoacidosis-andhyperosmolar-hyperglycemic-state-in-adults-treatment 2. Hirsch, I., & Emmett,M.(2018). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis. In J. E. Mulder (Ed.), UpToDate. Retrieved January 1, 2019 from https://www.uptodate.com/contents/diabetic-ketoacidosis-andhyperosmolar-hyperglycemic-state-in-adults-clinical-featuresevaluation-and-diagnosis Done by PharmD students: Basma Khalid, Shrouq Amer, Mohammad Alsaeed. Supervised by clinical pharmacist: Eshraq Al-Abweeny.