Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 27-03: Diabetic Ketoacidosis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Hyperglycemia > 250 mg/dL (13.9 mmol/L) Acidosis with blood pH < 7.3 Serum bicarbonate < 15 mEq/L Serum positive for ketones +++ General Considerations ++ May be the initial manifestation of type 1 diabetes Commonly occurs with poor compliance in type 1 diabetics, particularly when episodes are recurrent Develops in type 1 diabetics with increased insulin requirements during infection, trauma, myocardial infarction, or surgery May develop in type 2 diabetics under severe stress such as sepsis or trauma Common serious complication of insulin pump therapy +++ Demographics ++ Incidence is 5 to 8 episodes per 1000 diabetic persons annually Incidence in insulin pump therapy is 1 per 80 patient-months of treatment + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ May begin with a day or more of polyuria, polydipsia, marked fatigue, nausea and vomiting and, finally, mental stupor that can progress to coma Drowsiness is fairly common but frank coma only occurs in about 10% of patients Dehydration, possible stupor Rapid deep breathing and a "fruity" breath odor of acetone Hypotension with tachycardia indicates profound fluid and electrolyte depletion Mild hypothermia usually present; elevated or even a normal temperature may suggest infection Abdominal pain and tenderness in the absence of abdominal disease; conversely, cholecystitis or pancreatitis may occur with minimal symptoms and signs +++ Differential Diagnosis ++ Lactic acidosis in type 1 diabetics, including the use of metformin Alcoholic ketoacidosis Hypoglycemia Hyperglycemic hyperosmolar state Uremia Starvation ketoacidosis Salicylate poisoning + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Plasma glucose of 350–900 mg/dL (19.4–50 mmol/L) Serum ketones at a dilution of 1:8 or greater or beta-hydroxybutyrate more than 4 nmol/L Hyperkalemia (serum potassium level of 5–8 mEq/L) Slight hyponatremia (serum sodium of approximately 130 mEq/L) Hyperphosphatemia (serum phosphate level of 6–7 mg/dL [1.9–2.3 mmol/L]) Elevated blood urea nitrogen and serum creatinine levels Acidosis may be severe (pH ranging from 6.9 to 7.2, and serum bicarbonate ranging from 5 mEq/L to 15 mEq/L) PCO2 is low (15–20 mm Hg) related to hyperventilation Fluid depletion is marked, typically about 100 mL/kg Acetoacetic acid is measured by nitroprusside reagents [Acetest and Ketostix]; the more prevalent beta-hydroxybutyric acid has no ketone group and is therefore not detected by conventional nitroprusside tests Nonspecific elevations of serum amylase and lipase occurs in about 16–25 % of cases of diabetic ketoacidosis; an imaging study may be necessary if the diagnosis of acute pancreatitis is being seriously considered Serum lipase may be useful if the diagnosis of pancreatitis is being seriously considered Leukocytosis up to 25,000/mcL with a left shift may occur with or without associated infection Hyperchloremic metabolic acidosis can develop during initial therapy, as keto acids are lost in the urine and a portion of the bicarbonate deficit is replaced with chloride ions from the saline therapy. This relatively benign condition reverses over a day once intravenous saline is stopped Euglycemic ketoacidosis Occurs in patients in whom diabetic ketoacidosis develops while receiving treatment with SGLT2 inhibitors Patient can have severe acidosis and fluid depletion, but the plasma glucose levels are only modestly elevated, usually < 250 mg/day (13.9 mmol/L) Ketoacidosis with lower glucose levels also occurs in pregnancy and may reflect the expanded plasma volume and the increased glomerular filtration rate + Treatment Download Section PDF Listen +++ +++ Medications +++ Regular insulin ++ Initially in severe ketoacidosis, use only regular insulin Begin with loading dose of 0.1 unit/kg as intravenous bolus, followed by 0.1 unit/kg/h, continuously infused or given hourly as an intramuscular injection "Piggy-back" insulin into the fluid line so the rate of fluid replacement can be changed without altering the insulin delivery rate If plasma glucose level fails to fall at least 10% in the first hour, give repeat loading dose (0.1 or 0.14 unit/kg) Patients who are normally take insulin glargine or insulin detemir can be given usual maintenance doses during initial treatment of diabetic ketoacidosis The continuation of the subcutaneous basal insulins means that lower doses of intravenous insulin will be needed and there will be a smoother transition from intravenous insulin infusion to the subcutaneous regimen +++ Fluids ++ Fluid deficit is usually 4–5 L In the first hour, give at least 1 L of 0.9% saline to reexpand contracted vascular volume After the first 2 L of fluid have been given, the intravenous infusion rate should be 300–400 mL/h Use 0.9 % ("normal") saline unless the serum sodium is > 150 mEq/L, when 0.45% ("half normal") saline solution should be used When blood glucose falls to ~250 mg/dL (13.9 mmol/L), use 5% glucose solutions to maintain blood glucose in 200–300 mg/dL (13.9–16.7 mmol/L) range Failure to give enough volume replacement (at least 3–4 L in 8 h) to restore normal perfusion affects satisfactory recovery Excessive fluid replacement (more than 5 L in 8 h) may contribute to acute respiratory distress syndrome or cerebral edema +++ Electrolytes ++ Administer NaHCO3 if the arterial blood pH is 7.0 or less One or two ampules of NaHCO3 (one ampule contains 44 mEq/50 mL) should be added to 1 L of 0.45% saline with 20 mEq KCl or to 400 mL of sterile water with 20 mEq KCl and infused over 1–2 hours (Note: Addition of NaHCO3 to 0.9% saline produces a markedly hypertonic solution that could aggravate the hyperosmolar state already present.) It can be repeated until the arterial pH reaches 7.1 NaHCO3 should not be given if the pH is 7.1 or greater to avoid increased risk of rebound metabolic alkalosis Total body potassium loss from polyuria and vomiting may be as high as 200 mEq However, initial serum potassium is usually normal or high because of extracellular shifts from acidosis Potassium infusion 10–30 mEq/h should begin 2–3 h after beginning therapy, or sooner if initial serum potassium is low Defer potassium replacement if serum potassium remains above 5 mEq/L, as in chronic kidney disease Phosphate replacement is seldom required. However, if severe hypophosphatemia of < 0.32 mmol/L (< 1 mg/dL) develops during insulin therapy, a small amount of phosphate can be replaced as the potassium salt To minimize the risk of tetany from an overload of phosphate replacement, an average deficit of 40–50 mmol phosphate should be replaced by intravenous infusion at a rate not to exceed 3–4 mmol/h in 60- to 70-kg person A stock solution (Abbott Laboratories) provides a mixture of 1.12 g KH2PO4 and 1.18 g KH2PO4 in a 5-mL single-dose vial representing 22 mmol potassium and 15 mmol phosphate; 5 mL of this stock solution in 2 L of 0.45% saline or 5% dextrose in water, infused at 400 mL/h, will replace the phosphate at the optimal rate of 3 mmol/h and provide 4.4 mEq potassium per hour If serum phosphate remains below 2.5 mg/dL (0.8 mmol/L), a repeat 5-h infusion can be given +++ Subcutaneous insulin regimen ++ Can be initiated once diabetic ketoacidosis is controlled and patient is awake and able to eat The patient should receive subcutaneous basal insulin and rapid-acting insulin analog with the first meal and the insulin infusion discontinued 1 hour later The overlap of the subcutaneous insulin action and insulin infusion is necessary to prevent relapse of the diabetic ketoacidosis A patient with new-onset type 1 diabetes usually still has significant beta cell function and may not need any basal insulin and only very low doses of rapid-acting insulin before meals after recovery from the ketoacidosis Patients with type 2 diabetes and diabetes ketoacidosis due to severe illness may initially require insulin therapy but can often transition back to oral agents during outpatient follow-up +++ Therapeutic Procedures ++ Use a flow sheet listing vital signs, time sequence of laboratory values (arterial pH, plasma glucose, acetone, bicarbonate, serum urea nitrogen, electrolytes, serum osmolality) in relation to therapy Carefully monitor serum potassium during fluid replacement + Outcome Download Section PDF Listen +++ +++ Prognosis ++ Mortality rate has dropped to < 5% due to low-dose insulin infusion, fluid and electrolyte replacement, and careful patient monitoring However, mortality rate is still > 20% in elderly patients and in patients in profound coma in whom treatment has been delayed Acute myocardial infarction and infarction of the bowel following prolonged hypotension worsen the outlook End-stage chronic kidney disease is serious prognostic sign Prior kidney dysfunction worsens the prognosis considerably because the kidney plays a key role in compensating for massive pH and electrolyte abnormalities Symptomatic cerebral edema occurs primarily in the pediatric population +++ Prevention ++ The patient should contact a provider for persistent ketonuria Compliance is particularly important for juvenile-onset diabetics, particularly in the teen years. Intensive family counseling may be needed Urine ketones should be measured with signs of infection or in insulin pump-treated patients when capillary blood glucose is persistently high +++ When to Refer ++ Recurrent diabetic ketoacidosis Poor compliance +++ When to Admit ++ Severe ketosis, hyperosmolality An intensive care unit or step-down unit is preferable for more severe cases + References Download Section PDF Listen +++ + +Fayfman M et al. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 2017 May;101(3):587–606. [PubMed: 28372715] + +Islam T et al. Guidelines and controversies in the management of diabetic ketoacidosis—a mini-review. World J Diabetes. 2018 Dec 15;9(12):226–29. [PubMed: 30588284] + +Karslioglu French E et al. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l114. [PubMed: 31142480] + +Modi A et al. Euglycemic diabetic letoacidosis: a review. Curr Diabetes Rev. 2017;13(3):315–21. [PubMed: 27097605]