Ketoacidosis diagnosis

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If your doctor suspects diabetic ketoacidosis, he or she will do a physical exam and various blood tests. In some cases, additional tests may be needed to help determine what triggered the diabetic ketoacidosis.

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http://www.mayoclinic.org/diseases-conditions/diabetic-ketoacidosis/basics/tests-diagnosis/con-20026470

Diagnostic approach

The symptoms of DKA usually develop rapidly over 1 day or less. DKA may be the initial presentation in up to 25% of newly diagnosed diabetic people. Hyperglycaemia is a key diagnostic criterion for DKA; however, a wide range of plasma glucose levels can be present on admission, and approximately 10% of DKA patients present with glucose <13.9 mmol/L (<250 mg/dL) (‘euglycaemic DKA’). Hyperosmolar hyperglycaemic state (HHS) is often discussed as a separate condition. However, DKA and HHS represent 2 points on the spectrum of metabolic derangements in diabetes. In contrast to DKA, HHS may evolve insidiously over days to weeks. Symptoms of hyperglycaemia in both DKA and HHS include polyuria, polydipsia, weakness, and weight loss.

Important factors to consider in the patient’s past or current medical history include infection, MI, pancreatitis, cerebrovascular accidents, acromegaly, hyperthyroidism, and Cushing’s syndrome, as these may be precipitants or risk factors.

It is essential to take a full medication history, in particular looking for corticosteroids, pentamidine, sympathomimetic agents, thiazides, or second-generation antipsychotic agents, as these affect carbohydrate metabolism and may participate in the development of hyperglycaemic crises. Cocaine abuse may be an independent risk factor associated with recurrent DKA. 

Physical examination

Physical signs of volume depletion include dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock. DKA patients may exhibit nausea, vomiting, Kussmaul respiration, acetone breath, and, occasionally, abdominal pain. Abdominal pain may correlate with the degree of acidosis in patients with DKA, and it may be confused with an acute abdominal crisis. Mild hypothermia may be observed in some patients, due to peripheral vasodilation. Hyperthermia is not usual, even in the presence of infection. Mental status may be altered in DKA, varying from alert in mild DKA to stupor and/or coma in severe DKA. In HHS, mental obtundation and coma are more frequent. Focal neurological signs (hemianopia and hemiparesis) and seizures may also be features in HHS. 

Initial laboratory evaluation

Plasma glucose

  • Plasma glucose is typically >13.9 mmol/L (>250 mg/dL) with presence of acidosis and ketonaemia. However, a wide range of plasma glucose levels can be present on admission, and approximately 10% of DKA patients present with glucose <13.9 mmol/L (<250 mg/dL) (‘euglycaemic DKA’).
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Urinalysis

  • Positive for glucose and ketones. Other potential findings include leukocytes and nitrites in the presence of infection, and myoglobinuria and/or haemoglobinuria in rhabdomyolysis.
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Arterial (ABG) and venous blood gases

  • ABG shows a metabolic acidosis, which is essential for the diagnosis of DKA. Arterial pH measurement is necessary for diagnosis of DKA, but venous pH is recommended for monitoring treatment, due to the pain and risk of infection in obtaining frequent arterial samples. A venous pH sample is usually 0.03 units lower than arterial pH, and this difference should be considered.
  • The pH varies from 7.00 to 7.30, and the arterial bicarbonate ranges from <10 mmol/L (<10 mEq/L) in severe DKA to >15 mmol/L (>15 mEq/L) in mild DKA.

Urea and creatinine

  • Typically increased due to volume depletion.

Serum electrolytes

  • Sodium: serum sodium is usually low due to osmotic reflux of water from the intracellular to extracellular space in the presence of hyperglycaemia. Total sodium deficit is 7 to 10 mmol/kg (7 to 10 mEq/kg). Hypernatraemia in the presence of hyperglycaemia indicates profound volume depletion. Alternatively, in the presence of high serum chylomicron concentration, pseudonormoglycaemia and pseudohyponatraemia may occur.
  • Calculation of the corrected sodium: the corrected serum sodium level should be evaluated as this is used to guide appropriate fluid therapy. The equation for SI units is: corrected sodium (mmol/L) = measured sodium (mmol/L) + 0.016 ([glucose {mmol/L} x 18] – 100). The equation for conventional units is: corrected sodium (mEq/L) = measured sodium (mEq/L) + 0.016 (glucose [mg/dL] – 100).
  • Potassium: total potassium deficit is 3 to 5 mmol/kg (3 to 5 mEq/kg). Serum potassium is usually elevated due to extracellular shift of potassium caused by insulin insufficiency, hypertonicity, and acidaemia, but the total body potassium concentration is low due to increased diuresis. Therefore, low potassium level on admission indicates severe total-body potassium deficit.
  • Chloride: usually low. The total chloride deficit is 3 to 5 mmol/kg (3 to 5 mEq/kg).
  • Magnesium: usually low. The total body deficit of magnesium is usually 0.5 to 1 mmol/kg (1 to 2 mEq/kg).
  • Calcium: usually low. Total body calcium deficit is usually about 0.25 to 0.5 mmol/kg (1 to 2 mEq/kg).
  • Phosphate: despite the total body phosphate deficit averaging 1.0 mmol/kg, serum phosphate is often normal or increased at presentation, but decreases with insulin therapy.

Anion gap

  • The calculated serum anion gap in mmol/L (mEq/L) (serum sodium – [serum chloride + bicarbonate]) gives an estimate of the unmeasured anions in plasma, which in DKA are ketoacids. The anion gap is typically more than 10 to 12 mmol/L (10 to 12 mEq/L) in DKA.
  • Normalisation of the anion gap reflects correction of the ketoacidosis as these anions are removed from the blood.

Creatine phosphokinase

  • Rhabdomyolysis is common in cocaine users with concurrent DKA, and creatine phosphokinase levels should be assessed in known or suspected cocaine users who present with DKA.
  • In rhabdomyolysis, pH, and serum osmolality are usually mildly elevated and plasma glucose and ketones are normal. Myoglobinuria and/or haemoglobinuria are detected on urinalysis.

Serum lactate

  • Measured to exclude lactic acidosis. Lactate levels are normal in DKA but elevated in lactic acidosis.

Liver function tests (LFTs)

  • Usually normal and are used to screen for an underlying hepatic precipitant. Abnormal LFTs indicate underlying liver disease such as fatty liver, or other conditions such as CHF.

Serum amylase and lipase

  • Amylase is elevated in the majority of patients with DKA, but this may be due to non-pancreatic sources such as parotid glands.
  • Serum lipase is usually normal and may be beneficial in differentiating pancreatitis in patients with elevated amylase level. However, mildly elevated serum lipase level in the absence of pancreatitis has also been reported in patients with DKA.

Plasma osmolality

  • This is variable in DKA.

FBC with differential

  • Leukocytosis is present in hyperglycaemic crises and correlates with blood ketone levels. However, leukocytosis more than 25 × 10^9/L (25,000/microlitre) may indicate infection and requires further evaluations. 

http://bestpractice.bmj.com/best-practice/monograph/162/diagnosis/step-by-step.html

A Breath Test for Ketoacidosis

In a recent study at Oxford Children’s Hospital,1 researchers tested more than 100 patients with type 1 diabetes between the ages of 7 to 18 years old, measuring gases in their breath and ketone levels in their blood. Researchers found that one gas in particular—acetone— seemed to predict ketone levels well. A new way to monitor patients with Type 1 DM for ketones is down the road.

Typically, doctors find out how much ketone is in the blood by measuring the capillary levels of β hydroxybutyrate (BHB).2 When first diagnosed with Type 1 diabetes, children usually show high BHB levels.3 High BHB levels are associated with diabetic ketoacidosis, which may be lethal.

“Breath acetone on its own does not seem to be a good predictor of blood glucose in this cohort,” said Gus Hancock, PhD, Professor of Chemistry at the University of Oxford, a co-author of the study. “However, the statistically significant relationship that we found between blood ketones and breath acetone is something that we are pursuing.”

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More Research Needed

The researchers expect more studies to be done, especially with children that have diabetic ketoacidosis, so this relationship between acetone in the breath and ketones in the blood can be more fully understood. An exciting new way to monitor for diabetic ketoacidosis may come out of this.

Dr. Hancock and his colleagues are already working on a prototype of a convenient, hand-held device that could monitor breath acetone. Being manufactured by Oxford Medical Diagnostics, the team hopes to start testing the device in 2015, Dr. Hancock said.

“The prototype device works by spectroscopy inside an optical cavity (“Cavity enhanced absorption spectroscopy”) which allows high sensitivity and high selectivity for breath acetone,” Dr. Hancock described. “The aim here is to see if elevated breath acetone would be a good indicator of the onset of diabetic ketoacidosis.”

Diabetes Rates Rising Among Children

Diabetes cases are rising throughout the US; in the last decade alone, a study found there to be 21% more adolescents with Type 1 diabetes.4 Monitoring Type 1 diabetes in children is becoming a prevalent challenge for doctors.

DiabeticLifestyle Editorial Board Member Amy Hess-Fischl commented on how such a device could be useful for patients. “At this point, noninvasive is an attractive option for people with diabetes,” she said, “For small children, it is hard enough to get the information necessary to treat them appropriately (urine ketone testing with toddlers is a nightmare) so an alternate method to make it easy to identify ketones would be welcome.”

Also commenting on the study finding, J. Michael Gonzalez-Campoy, MD, PhD, FACE, noted “The current study offers the promise of real-time testing for the development of ketones in a non-invasive manner.  This will help bring about earlier intervention in diabetic ketoacidosis.” 

Breath tests may not only be convenient, but lifesaving, as well. “Urine ketones tell us about the ketones generated hours ago. Blood ketones tell us what is happening now – the same for exhaled gases,” added Ms Hess Fischl.

However, urine ketone testing is still very popular because it’s cheap, while blood ketone tests typically cost around 10 dollars a strip. Since insurance companies may not cover these tests, it can cause a fiscal problem in families who are trying to monitor their child’s ketone levels.

Monitoring ketone levels is most important when one is sick or has a blood glucose level over 240 mg/dL.

“So, in order for this new test to be used and benefit families and people with type 1 diabetes, it cannot be cost-prohibitive,” she concluded.

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