Investigations

1st investigations to order

venous blood gas

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Result
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Take a venous (rather than arterial) blood gas in all patients with suspected diabetic ketoacidosis (DKA).[2]

  • Use the pH to determine the severity of DKA.

    • pH ≥7.0 indicates mild or moderate DKA.

    • pH <7.0 indicates severe DKA. Discuss these patients with critical care.

  • Hyperkalaemia is common.[1]​​

    • Use the potassium level on venous blood gas to replace potassium if ≤5.0 mmol/L.[1]​ Discuss with critical care if potassium is <3.5 mmol/L.[2]

Practical tip

Exercise caution when interpreting a potassium result obtained from a blood gas analyser.

  • Blood gas analysers are often used as point-of-care tests, providing rapid results (e.g., within minutes) for potassium levels, which is crucial in the initial management of DKA to guide insulin infusion.

  • Studies have shown that measurements from blood gas analysis may underestimate serum potassium levels in DKA.[104][105]

  • Be aware of these potential limitations and interpret results in conjunction with clinical judgement and other laboratory data, especially when making decisions about potassium replacement therapy.

  • Calculate the plasma osmolality.

    • Plasma osmolality is typically elevated in DKA and is an indication of dehydration.​[85]​​

Evidence: Use of a venous versus arterial blood gas

Venous blood gas measurements are widely used instead of arterial blood gas measurements and evidence from case studies suggests there is sufficient agreement between them, when combined with other clinical findings, to use a venous blood gas to guide initial treatment.

A clinical review article aimed to answer the question “can venous blood gas analysis replace arterial blood gas analysis in emergency care?”.[106]

  • Venous blood gas testing may have a lower risk of serious adverse events (e.g., vascular occlusion or infection), is less painful for the patient, and is technically easier to perform than arterial blood gas testing.

  • There is little difference in pH values between venous and arterial samples (based on 13 studies; 2009 participants, with 3 studies [295 patients] in patients with DKA).[107]

  • Bicarbonate values also show close agreement between venous and arterial samples (8 studies; 1211 patients).[107]

  • Agreement for PCO2 is poor and unpredictable (8 studies; 965 patients), but a venous PCO2 ≤45 mmHg (6 kPa) reliably excludes clinically significant hypercarbia (4 studies; 529 patients; 100% sensitivity).[107]

  • Agreement on lactate is close enough to categorise as high or normal (3 studies; 338 patients).[108] 

  • Evidence regarding arteriovenous agreement for base excess is unclear (2 studies; 429 patients; only 1 study reporting close agreement).[109][110]

  • If data from the venous blood gas does not appear to match the patient’s clinical condition, an arterial blood gas should be performed.[106]

Result

metabolic acidosis with a raised anion gap

blood ketones

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Result
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Use urinary ketones if near-patient blood ketone (beta-hydroxybutyrate [BOHB]) testing is unavailable.[2] 

Practical tip

Assessment of ketones should be done at or near the bedside using point-of-care testing.[2] 

  • Order laboratory measurements in certain circumstances, such as when blood ketone meters are ‘out of range’.

Practical tip

Bear in mind that a patient’s medications can cause errors in detecting ketone bodies.[125]​​

Some drugs, such as the ACE inhibitor captopril, contain sulfhydryl groups that can react with the reagent in the nitroprusside test (used to test for ketone bodies) to give a false-positive reaction.[112]​ Therefore, use clinical judgement and other biochemical tests in patients who are taking these medications. 

Result

ketonaemia (ketones [BOHB] ≥3 mmol/L)[2]

blood glucose

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Hyperglycaemia (blood glucose ≥11.1 mmol/L) is common.​[1]​​ 

Be aware that some patients can present with euglycaemic diabetic ketoacidosis (DKA) and have a normal blood glucose.[86] Always use pH and ketones alongside glucose to guide diagnosis and management. Manage euglycaemic DKA in the same way as hyperglycaemic DKA.[2]

Practical tip

Assessment of glucose should be done at or near the bedside using point-of-care testing.[2] 

  • Order laboratory measurements in certain circumstances, such as when blood glucose meters are ‘out of range’.

Result

hyperglycaemia (blood glucose ≥11.1 mmol/L)

urea and electrolytes

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Result
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Hyponatraemia is common in diabetic ketoacidosis (DKA).[2]

  • Hypernatraemia with hyperglycaemia indicates severe dehydration.

Hyperkalaemia is common but hypokalaemia is an indicator of severe DKA.[2]​​

  • Hypokalaemia on arrival indicates severe total-body potassium deficit and is an indicator of severe DKA.[88]​ This is because the total body potassium concentration is low due to increased diuresis.

  • Hyperkalaemia is due to an extracellular shift of potassium caused by insulin insufficiency, hypertonicity, and acidosis.[88]

Hypomagnesaemia, hypophosphataemia, and hypochloridaemia may also be present.[2][87]

Result

  • hyponatraemia and hyperkalaemia are common; hypokalaemia is an indicator of severe DKA​[2]

  • may show hypomagnesaemia, hypophosphataemia, and hypochloridaemia[2][87]

full blood count

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Result
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Leukocytosis is common in DKA and correlates with blood ketone levels.[88]​​

However, leukocytosis more than 25 × 10⁹/L (25,000/microlitre) may indicate infection and requires further investigation.[88]​​

Result

leukocytosis

Investigations to consider

urinalysis

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Result
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Order if near-patient testing for ketones is unavailable or you suspect a urinary tract infection.[2]

Result

ketonuria (2+ or more on standard urine sticks); may be positive for glucose[113]

  • other findings include leukocytes and nitrites in the presence of infection, and myoglobinuria and/or haemoglobinuria in rhabdomyolysis (present in 10% of patients with diabetic ketoacidosis)[113][114][115]

ECG

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Result
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Use to look for cardiac precipitants of diabetic ketoacidosis (DKA) such as myocardial infarction and cardiac effects of electrolyte abnormalities.[2][116]

Ensure continuous cardiac monitoring and involve senior or critical care support if:[2]​​[31]

  • There is persistent hypotension (systolic blood pressure <90 mmHg) or oliguria (urine output <0.5 ml/kg/hour) despite intravenous fluids

  • Stupor and/or coma or Glasgow Coma Scale <12  [ Glasgow Coma Scale Opens in new window ] ​​​ 

  • Blood ketones (beta-hydroxybutyrate) >6 mmol/L

  • Venous bicarbonate <10 mmol/L

  • Venous pH <7.0

  • Potassium <3.5 mmol/L on admission

  • Oxygen saturations <92% on air

  • Pulse >100 bpm or <60 bpm

  • Anion gap >16  [ Anion Gap Opens in new window ]

  • The patient is pregnant or has heart or kidney failure or other serious comorbidities.

    • DKA in pregnancy can result in significant morbidity and mortality for both the mother and the fetus.[2][91]

    • Pregnant women with suspected DKA must be admitted to the delivery suite or the high dependency unit and receive care from both the obstetric and medical (or diabetes) teams.[2]

Result

  • abnormal T or Q waves or ST segment changes in myocardial infarction[116]

  • evidence of hypokalaemia (U waves) or hyperkalaemia (tall ‘peaked’ T waves) may be present[117][118]

pregnancy test

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Order in all women of childbearing age.[2]

Result

positive in pregnancy

amylase and lipase

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Non-specific elevations of amylase can be seen in diabetic ketoacidosis (DKA).[119]

  • In one study, amylase was elevated in 21% of patients with DKA.[42]

Serum lipase is usually normal in DKA.

  • This may differentiate DKA from pancreatitis. However, elevated lipase, traditionally thought to be more specific for pancreatitis, may also accompany DKA and does not necessarily denote concomitant pancreatic inflammation.[42][119]

Result

amylase may be elevated; serum lipase is usually normal

cardiac enzymes

Test
Result
Test

Order troponin T or I if you suspect myocardial infarction as a precipitant.[120]

Practical tip

Some patients with diabetes may present with a ‘silent myocardial infarction’ with no or minimal chest pain. This is thought to be due to cardiac autonomic dysfunction.[96][97]

Result

elevated with myocardial infarction

creatinine kinase

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Result
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Elevated if rhabdomyolysis is present. This is present in around 10% of patients with diabetic ketoacidosis.[114]

Result

elevated with rhabdomyolysis

chest x-ray

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Order if there are reduced oxygen saturations.[2]

Result

  • signs of pulmonary oedema include pleural effusions, interstitial and alveolar oedema, prominent superior vena cava, Kerley B lines, and dilated upper lobe blood vessels[121]

  • consolidation occurs in pneumonia

liver function tests

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Result
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Used to screen for an underlying hepatic precipitant of diabetic ketoacidosis (DKA). Abnormal LFTs may indicate underlying liver disease (e.g., metabolic dysfunction-associated steatotic liver disease or congestive heart failure).[122][123]​ Chronic liver disease is a risk factor for euglycaemic DKA.[124]

Result

elevated with liver disease

blood, urine, and sputum cultures

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Result
Test

Order these if there are signs of infection. The most common are pneumonia and urinary tract infections.[70]

Patients with diabetic ketoacidosis who have an infection are usually normothermic or hypothermic due to peripheral vasoconstriction so fever may not be seen.[67]

Result

positive if infection present

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