Recommendations

Urgent

Consider DKA in: 

  • Patients with known diabetes who are unwell[2][17]

    • DKA is most common in people with type 1 diabetes but can also present in those with type 2 diabetes.[42][46][47]

  • Any patient with increased thirst, polyuria, recent unexplained weight loss, or excessive tiredness, AND any of the following:[17][48]

    • Nausea and vomiting

    • Abdominal pain[2][49]

    • Hyperventilation (Kussmaul's respiration)[50]

    • Dehydration

    • Reduced consciousness.

Urgently order a venous blood gas, blood ketones, and capillary blood glucose.[42]

  • These tests should be done at the bedside.

Diagnose DKA if:[51][17][47][52]

  • Blood ketones are ≥3.0 mmol/L OR there is ketonuria (more than 2+ on standard urine sticks)

    AND

  • Blood glucose is >11.1 mmol/L OR known diabetes 

    • This blood glucose cut-off is recommended in the 2020 Joint British Diabetes Societies (JBDS) guideline "Diabetes at the front door" and supersedes the 11.0 mmol/L cut-off recommended in the 2013 JBDS guideline "The management of diabetic ketoacidosis in adults".[42][52]

    AND

  • Bicarbonate (HCO3-) is <15.0 mmol/L, AND/OR venous pH is <7.3. 

Ensure continuous cardiac monitoring and involve senior or critical care support if:[42][17]

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

  • Glasgow Coma Scale <12 [ Glasgow Coma Scale ] 

  • Blood ketones >6 mmol/L

  • Venous bicarbonate <5 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 ]

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

Involve the specialist diabetes team as soon as possible and definitely within 24 hours.[42]

Key Recommendations

Clinical presentation

Other features of DKA are:

  • Acetone smell on breath[17]

    • Smells like pear drops or nail varnish remover

  • Hypothermia[53]

    • Suspect sepsis as a precipitant if there is fever as this is not a feature of DKA. Sepsis may also cause hypothermia, however. 

History

Ask about causes of DKA. These are:

  • Infection[17][47]

    • The most common causes are pneumonia and urinary tract infection.

    • Suspect sepsis as a cause of DKA if there is fever or hypothermia, hypotension, refractory acidosis, or lactic acidosis.[51]

  • Discontinuation of insulin (either unintentional or deliberate)[17][47]

  • Inadequate insulin

    • Due to:

      • Malfunctioning insulin pen or pump[54]

      • Degradation of insulin due to storage at incorrect temperature.[55]

  • New onset of diabetes[17] 

  • Acute illness

    • Common causes include myocardial infarction, sepsis, and pancreatitis.[47][15][30]

  • Physiological stress 

    • This includes:

      • Pregnancy[17] 

      • Trauma[56]

      • Surgery.[56]

  • Drugs[17]

    • Corticosteroids[57]

    • Thiazides

    • Sympathomimetics[26]

    • Second-generation antipsychotics[58]

    • Immune checkpoint inhibitors[59]

    • Cocaine, cannabis, and acute intoxication with alcohol[56][60]

    • Sodium-glucose co-transporter 2 (SGLT2) inhibitors.[21][22]

Examination

Examine the chest:

  • Look for hyperventilation (Kussmaul's respiration).[17]

  • Auscultate for crepitations or reduced air entry.

    • This may indicate pneumonia as a cause of DKA or pulmonary oedema.

  • Monitor for pulmonary oedema. This typically occurs several hours after treatment is started and can occur even in patients with normal cardiac function.[42][17]

Assess for signs of dehydration:[17] 

  • Dry mucous membranes

  • Decreased skin turgor or skin wrinkling

  • Slow capillary refill

  • Tachycardia with a weak pulse

  • Hypotension.

Assess conscious level hourly using the Glasgow Coma Scale to monitor for cerebral oedema.[42][ Glasgow Coma Scale ]

  • Signs include headache, irritability, slowing pulse, rising blood pressure, reducing conscious level. These may occur several hours after starting treatment.[51][61]

  • Involve immediate critical care input and give mannitol.[62] 

Examine the abdomen

  • Look for an intra-abdominal cause of DKA such as pancreatitis.[47][15][30]

  • However, DKA commonly causes abdominal pain and may be mistaken for an acute abdomen.[63]

Check the patient’s feet to look for new ulceration or infection.[64]

Check the patient’s skin for rashes, signs of cellulitis, or open wounds that may have precipitated DKA.

Investigations

Always order:

  • Venous blood gas

    • This will show a metabolic acidosis with a raised anion gap. Involve senior or critical care support if pH is <7.0.[42] [ Anion Gap ]

    • Check the potassium level. Involve senior or critical care support if it is <3.5 mmol/L.[42]

    • Calculate plasma osmolality. This is high (>320 mmol/kg) in patients with DKA.[53][61] [ Osmolality Estimator (serum) ]

  • Blood ketones

    • This will show ketonaemia (ketones ≥3.0 mmol/L).[42]

    • Use urinary ketones if near-patient blood ketone testing is unavailable. This will show ketonuria (more than 2+ on standard urine sticks).[42]

  • Blood glucose

    • Hyperglycaemia (blood glucose >11.1 mmol/L) is common.[52]

      • This blood glucose cut-off is recommended in the 2020 Joint British Diabetes Societies (JBDS) guideline "Diabetes at the front door" and supersedes the 11.0 mmol/L cut-off recommended in the 2013 JBDS guideline "The management of diabetic ketoacidosis in adults".[42][52]

    • Be aware that some patients can present with euglycaemic DKA and have a normal blood glucose.[65]

  • Urea and electrolytes

    • This commonly shows hyponatraemia and hyperkalaemia, but hypokalaemia may also be present and indicates severe DKA.[42][46]

    • It may also show hypomagnesaemia and hypophosphataemia.[42][66]

  • Full blood count[46]

    • Leukocytosis is common.

    • Suspect infection if there is a leukocytosis of more than 25 × 10⁹/L (25,000/microlitre).[46]

Full recommendations

Consider DKA in:

  • Patients with known diabetes who are unwell[2][17]

    • DKA is most common in people with type 1 diabetes but can also present in those with type 2 diabetes.[46]

  • Any patient with increased thirst, polyuria, recent unexplained weight loss, or excessive tiredness AND any of the following:[17][48]

    • Nausea and vomiting

    • Abdominal pain[49][2]

    • Hyperventilation (Kussmaul's respiration)[50]

    • Dehydration

    • Reduced consciousness.

      • This is strongly associated with more severe DKA and a worse prognosis.[67]

Practical tip

Patients with type 2 diabetes who have increased risk of DKA are those with newly diagnosed diabetes or obesity.[61]

Practical tip

DKA is the initial presentation in up to 25% of patients with newly diagnosed diabetes.[46]

DKA is easily missed, especially when it is the initial presentation of diabetes in infants or older patients, or when patients present with other acute medical illnesses such as stroke or myocardial infarction.[61]

Other features of DKA are:

  • Acetone smell on breath[17]

    • The patient’s breath smells like pear drops or nail varnish remover. This is due to high ketone levels.

    • A significant proportion of people are unable to smell acetone even if it is present.

  • Hypothermia

    • Severe hypothermia is associated with a mortality rate of 30% to 60%.[68]

    • Mild hypothermia may be seen in some patients with DKA due to peripheral vasodilation.[46]

Practical tip

Fever is not a feature of DKA but DKA may be caused by sepsis. Suspect sepsis as a cause of DKA if there is fever or hypothermia, hypotension, refractory acidosis, or lactic acidosis.[51]

Ensure continuous cardiac monitoring and involve senior or critical care support if:[42][42]

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

  • Glasgow Coma Scale <12 [ Glasgow Coma Scale ]

  • Blood ketones >6 mmol/L

  • Venous bicarbonate <5 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 ]

  • 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.[69]

Prognostic factors for survival in patients with DKA are unclear.

There is limited evidence from a case series of patients with DKA in India for several favourable prognostic indicators, including being male, having lower APACHE scores, and having lower serum phosphate levels on presentation.

  • A case series assessed 270 patients hospitalised with DKA in India over 2 years.[70]

    • It found that survival was more likely among males than females (odds ratio [OR] 7.93, 95% CI 3.99 to 13.51).[70]

    • Other favourable prognostic factors in multivariate analysis (adjusting for type of diabetes, blood pressure, total leukocyte count, urea, serum creatinine, serum magnesium, serum osmolality, serum glutamic oxaloacetic transaminases, serum glutamic pyruvic transaminases, and serum albumin) were lower APACHE scores (OR 2.86, 95% CI 1.72 to 7.03) and lower serum phosphate (OR 2.71, 95% CI 1.51 to 6.99) at presentation.[70]

    • However, this study reported a high overall mortality rate and may not represent the UK or European context.[70]

Involve the specialist diabetes team as soon as possible and definitely within 24 hours.[42] 

  • The specialist diabetes team should also be involved in the assessment of the cause of DKA.

  • It is unsafe to manage DKA without the specialist diabetes team and could compromise patient care.[42] 

Ask about possible causes of DKA. These include:[46][42][53][26][33][71][35][36]

  • Infection (most common cause of DKA)[17][53][26]

    • The most common causes are pneumonia and urinary tract infection.

    • Suspect sepsis as a cause of DKA if there is fever or hypothermia, hypotension, refractory acidosis, or lactic acidosis.[51]

  • Discontinuation of insulin (unintentional or deliberate; second most common cause of DKA)[17][53][26]

    • Ask sensitively about reasons for deliberate discontinuation of insulin, which may include fear of weight gain or hypoglycaemia, financial barriers, and psychological factors such as needle phobia and stress.[2][17]

    • Younger patients with type 1 diabetes may omit insulin due to fear of hypoglycemia, weight gain, eating disorders, or the stress of having a chronic disease. These factors may account for 20% of recurrent DKA.[72]

  • Inadequate insulin

    • Common reasons are:

      • Malfunctioning insulin pen or pump[54][55]

      • Degradation of insulin due to storage at incorrect temperature.[55]

  • New onset of diabetes[17]

  • Acute illness

    • Common causes include myocardial infarction, sepsis, and pancreatitis[15][30]

      • Maintain a high level of suspicion for myocardial infarction as patients with diabetes often present with atypical symptoms.

  • Physiological stress

    • This includes pregnancy, trauma, and surgery.

    • Some women may develop DKA during menstruation.[73][74]

  • Past medical history

    • History of diabetes:

      • DKA is most common in people with type 1 diabetes but can occur in those with type 2 diabetes.[46]

  • Drug history[17]

    • Drugs that may cause DKA include:

      • Corticosteroids (increase insulin resistance)[57]

      • Thiazides (unclear cause but may increase insulin resistance, inhibit glucose uptake, and decrease insulin release)

      • Sympathomimetics (alter glucose metabolism)[26]

      • Second-generation antipsychotics (alter glucose metabolism)[58]

      • Immune checkpoint inhibitors (cause insulin deficiency)[59]

      • Cocaine, cannabis, and acute intoxication with alcohol (DKA is associated with cocaine use but the mechanism is unclear)[56][60]

      • SGLT2 inhibitors (prevent reabsorption of glucose and facilitate its excretion in urine).[21][22]

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.[75][76]

Practical tip

Diagnosis of DKA in pregnancy is often delayed because it can occur at lower blood glucose levels and faster than in non-pregnant patients.[77]

DKA usually occurs in the second and third trimesters due to increased insulin resistance.[77]

Examine the chest.

  • Look for hyperventilation (Kussmaul's respiration).[17][50]

    • This is a late sign of DKA and occurs with more severe acidosis.

    • Characterised by deep sighing respirations at a slow or normal rate.

    Auscultate for crepitations or reduced air entry.[78]

    • This may be due to pneumonia, which can be caused by aspiration from gastroparesis in DKA or a primary infection.[51][79][80][81]

    • Basal crepitations are also a sign of pulmonary oedema or acute respiratory distress syndrome (ARDS) secondary to fluid overload. This is an uncommon complication of treatment for DKA.[42][82]

Check for signs of dehydration. These are:[17]

  • Dry mucous membranes

  • Decreased skin turgor or skin wrinkling

  • Slow capillary refill

  • Tachycardia with a weak pulse

  • Hypotension.

Assess conscious level hourly using the Glasgow Coma Scale to monitor for cerebral oedema.[42][ Glasgow Coma Scale ]

  • Mental status can range from alert in mild DKA to coma in severe DKA.[53]

  • Cerebral oedema can develop during treatment of DKA due to rapid correction of hyperglycaemia.[42]

    • Signs include headache, irritability, slowing pulse, rising blood pressure, reducing conscious level. These may occur several hours after starting treatment.[51][61]

      • Papilloedema is a late sign of cerebral oedema.[51]

    • Involve immediate critical care input and give mannitol.[62]

    • Cerebral oedema has a mortality rate of 70%. It is most common in children and adolescents but can occur in adults.[2]

Examine the abdomen for a possible cause of DKA, such as pancreatitis.[47][15][30] DKA can both cause and mimic an acute abdomen.[49] 

  • Look for abdominal distension, which may indicate bowel obstruction.[83]

  • Palpate the abdomen to check for rebound tenderness and guarding caused by irritation of the peritoneum.[83]

  • Auscultate for bowel sounds.[84]

    • Hyperactive ‘tinkling’ bowel sounds may be present in early bowel obstruction.

    • Reduced or absent bowel sounds may be present in late bowel obstruction, perforated viscus, haemoperitoneum, or any cause of peritoneal inflammation.

  • Perform a rectal examination.[83]

    • Ensure you take a chaperone with you.

    • Assess for occult or frank blood, pain, or a mass.

Practical tip

The severity of abdominal pain caused directly by DKA correlates strongly with the severity of the metabolic acidosis.[49]

Check the patient’s feet to look for new ulceration or infection.[64]

Practical tip

Check the feet for loss of protective sensation in any patient with diabetes.

  • Follow your local guidelines, but a quick simple test is the Ipswich Touch Test©️, which involves lightly touching/resting the tip of the index finger for 1 to 2 seconds on the tips of the first, third, and fifth toes and the dorsum of the hallux.[85]

  • If your patient has reduced sensation, they are at high risk of pressure ulceration. Inform the nursing staff and provide pressure-relieving devices. 

A daily heel check for signs of pressure trauma should be done by nursing or healthcare assistant staff.

  • There is a debate about whether compression stockings should or should not be used in people with diabetes - do not use them if there is vascular disease.

Check the patient’s skin for rashes and signs of cellulitis or open wounds.

  • Infections such as meningitis or cellulitis may precipitate DKA.[86][87]

  • Periumbilical discolouration (Cullen's sign) or bruising of the flanks (Grey Turner's sign) indicates haemorrhagic pancreatitis.[88]

Diagnose DKA if:[51][17][47][52]

  • Blood ketones are ≥3.0 mmol/L OR there is ketonuria (more than 2+ on standard urine sticks)

    AND

  • Blood glucose is >11.1 mmol/L OR known diabetes 

    • This blood glucose cut-off is recommended in the 2020 Joint British Diabetes Societies (JBDS) guideline "Diabetes at the front door" and supersedes the 11.0 mmol/L cut-off recommended in the 2013 JBDS guideline "The management of diabetic ketoacidosis in adults".[42][52]

    AND

  • Bicarbonate (HCO3-) is <15.0 mmol/L AND/OR venous pH is <7.3.

Practical tip

Assessment of glucose, ketones, and electrolytes, including bicarbonate and venous pH, should be done at or near the bedside.[42] 

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

Practical tip

Rarely, patients present with euglycaemic DKA (EDKA) and have a normal blood glucose level.[17][89]

  • Exclude other causes of an anion gap metabolic acidosis before confirming EDKA.

  • The mechanism of EDKA is unclear but may be due to decreased insulin secretion with increased counter-regulatory hormone secretion (cortisol, glucagon, catecholamines, and growth hormone).[19]

  • Possible precipitants of EDKA are pregnancy, starvation, alcohol use, insulin pumps, and SGLT2 inhibitors.[89][19] 

  • Patients with EDKA secondary to treatment with an SGLT2 inhibitor may have less polyuria and polydipsia due to a lower glucose level. They may instead present with malaise, anorexia, tachycardia, or tachypnoea with or without fever.[17]

Always order the following investigations

Venous blood gas[42]

  • This will show a metabolic acidosis with a raised anion gap[ Anion Gap ]

    • Anion gap >16 indicates severe DKA.

  • 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.

  • Use the potassium level on venous blood gas to replace potassium if ≤5.5 mmol/L. Discuss with a senior or critical care if potassium is <3.5 mmol/L.

  • Calculate the plasma osmolality. [ Osmolality Estimator (serum) ]

    • Plasma osmolality is high (>320 mmol/kg) in DKA and is an indication of dehydration.[53][61]

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?”[90]

  • 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).[91]

  • Bicarbonate values also show close agreement between venous and arterial samples (8 studies; 1211 patients).[91]

  • 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).[91]

  • Agreement on lactate is close enough to categorise as high or normal (3 studies; 338 patients).[92] 

  • Evidence regarding arteriovenous agreement for base excess is unclear (2 studies; 429 patients; only 1 study reporting close agreement).[93][94]

  • If data from the venous blood gas does not appear to match the patient’s clinical condition, an arterial blood gas should be performed.[90]


Venepuncture and phlebotomy animated demonstrationVenepuncture and phlebotomy animated demonstration

Blood ketones[42]

  • This will show ketonaemia (ketones ≥3.0 mmol/L) in DKA.[42]

  • Use urinary ketones if near patient blood ketone testing is unavailable. This will show ketonuria (more than 2+ on standard urine sticks).[42]

Practical tip

Bear in mind that a patient’s medications can cause errors in detecting ketone bodies.[46]

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. Therefore, use clinical judgement and other biochemical tests in patients who are taking these medications.

Blood glucose

  • Hyperglycaemia (blood glucose >11.1 mmol/L) is common.[52]

    • This blood glucose cut-off is recommended in the 2020 Joint British Diabetes Societies (JBDS) guideline "Diabetes at the front door" and supersedes the 11.0 mmol/L cut-off recommended in the 2013 JBDS guideline "The management of diabetic ketoacidosis in adults".[42][52]

  • Be aware that some patients can present with euglycaemic DKA and have a normal blood glucose.[65]

Urea and electrolytes

  • Hyponatraemia is common in DKA.[42]

    • Hypernatraemia with hyperglycaemia indicates severe dehydration, however.[46]

  • Hyperkalaemia is common but hypokalaemia is an indicator of severe DKA.[42][46]

    • Hypokalaemia on arrival indicates severe total-body potassium deficit and is an indicator of severe DKA.[46] 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. 

  • Hypomagnesaemia and hypophosphataemia may also be present.[42][66]

Full blood count

  • Leukocytosis is common in DKA and correlates with blood ketone levels.[46]

  • However, leukocytosis more than 25 × 10⁹/L (25,000/microlitre) may indicate infection and requires further investigation.[46]

Consider ordering the following investigations

Urinalysis

  • Order if near-patient testing for ketones is unavailable or you suspect a urinary tract infection.[42][51]

  • Shows ketonuria (more than 2+ on standard urine sticks) in patients with DKA.[42]

  • May be positive for glucose.[95]

  • Other findings include leukocytes and nitrites in the presence of infection, and myoglobinuria and/or haemoglobinuria in rhabdomyolysis.[95][96][97]

ECG

  • Use to look for cardiac precipitants of DKA such as myocardial infarction.[42]

    • Findings may include abnormal T or Q waves or ST segment changes.[98]

  • Look for cardiac effects of electrolyte abnormalities.

    • Evidence of hypokalaemia (U waves) or hyperkalaemia (tall ‘peaked’ T waves) may be present.[99][100]


How to perform an ECG animated demonstrationHow to perform an ECG animated demonstration

Pregnancy test

  • Order in all women of childbearing age.[42]

Amylase and lipase

  • Amylase is elevated in most patients with DKA.[46]

  • Serum lipase is usually normal in patients with DKA.[46]

    • This may differentiate DKA from pancreatitis (lipase level will be elevated in patients with pancreatitis). However, mildly elevated serum lipase level in the absence of pancreatitis has also been reported in patients with DKA.

Cardiac enzymes

  • Order troponin T or I if you suspect myocardial infarction as a precipitant.[101]

Creatinine kinase

  • Elevated if rhabdomyolysis is present. This is common in DKA and present in around 10% of patients.[96]

Chest x-ray

  • Order if there are reduced oxygen saturations.[42]

  • Signs of pulmonary oedema are pleural effusions, interstitial and alveolar oedema, prominent superior vena cava, Kerley B lines, and dilated upper lobe blood vessels.[102]

  • Consolidation occurs in pneumonia.

Liver function tests (LFTs)

  • Use to screen for an underlying hepatic precipitant of DKA. Abnormal LFTs indicate underlying liver disease (e.g., non-alcoholic fatty liver disease or congestive heart failure).[103][104]

Blood, urine, and sputum cultures

  • Order these if there are signs of infection.

  • The most common infections are pneumonia and urinary tract infections.[56]

  • Patients with DKA who have an infection are usually normothermic or hypothermic due to peripheral vasoconstriction, so fever may not be seen.[53]

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