Diabetic Ketoacidosis

Author:  Adrian Robert Marsh / Editor: Lou Mitchell / Reviewer: Nicholas Blundell, Mehdi Teeli / Codes: C3AP4, EnC2, EnP2, SLO1Published: 08/11/2021

DKA is a common presentation to the emergency department.

The presentation can mimic many other disease processes. The ED physician must be able to diagnose, appropriately investigate, initiate treatment and manage complications.

There is a new nationally agreed guideline on the management of DKA, published by the Joint British Diabetes Societies Inpatient Care Group [1].

DKA is defined by this guideline as [1]:

  • Ketonaemia > 3.0 mmol/L or significant ketonuria (more than 2+ on standard urine sticks)
  • Blood glucose > 11.0 mmol/L or known diabetes mellitus
  • Serum venous bicarbonate of < 15.0 mmol/L and/or
  • venous pH < 7.3


The pancreatic islets of Langerhans secrete insulin from the B cells. Insulin is secreted initially as a pro-hormone from which C-peptide is cleaved leaving the active insulin hormone.

Insulin actions

Insulin has many actions as shown in the table below. The most well known is the stimulation of glucose and amino-acid uptake from the blood to various tissues. This is coupled with the stimulation of anabolic processes including glycogen, protein and lipid synthesis.

A deficiency in insulin causes an increase in glucagon, catecholamines, cortisol and growth hormone. These hormones stimulate hepatic glucose production via glycogenolysis and gluconeogenesis.

In addition, there is a decreased intake of glucose by the cells. This leads to hyperglycaemia, resulting in glycosuria which causes an osmotic diuresis and dehydration.

Table: Actions of Insulin




Glucose uptake




Glycogen synthesis


Protein synthesis


Uptake of ions, especially potassium


Fatty Acids and Ketone Bodies

Insulin deficiency results in lipolysis increasing free fatty acid production. The fatty acids are then degraded through eight stages within the mitochondria. Each stage releases one molecule of acetyl-co-enzyme A. In the absence of insulin more of this is formed than can enter the citric acid cycle and the acetyl-co-enzyme is reduced to beta hydroxy-butyric acid or decarboxylated to acetoacetic acid and subsequently to acetone. The acetoacetic acid also reduces the glucose uptake by cells. Beta hydroxy-butyric acid, acetoacetic acid and acetone are acids causing in part the acidosis.

Beta hydroxy-butyric acid also causes nausea and vomiting, increasing the dehydration.

The increase in cortisol, catecholamines and growth hormone activates hormone-sensitive lipase which leads to lipolysis causing the release of free-fatty acids which are taken up by the liver.

Osmotic Diuresis

When the concentration of glucose exceeds the maximum re-absorption capacity of the kidney, glucose remains in the filtrate. This causes an increase in osmotic pressure causing water and potassium to move out and into the urine. Fluid and electrolyte losses in typical DKA

Table: Fluid and electrolyte losses in typical DKA

Water ml/Kg 100
Sodium mmol/Kg 7-10
Potassium mmol/Kg 3-5
Chloride mmol/Kg


Phosphate mmol/Kg 1-1.5
Magnesium mmol/Kg 1-2
Calcium mmol/Kg 1-2

Below are some of the main osmotic diuresis changes with severe fluid and electrolyte loss:

Sodium changes

Hyperglycaemia is restricted to the extra-cellular space, this leads to a shift in water from the intra-cellular to the extra-cellular space, initially diluting plasma sodium. The osmotic diuresis causes the water to be lost in excess of the sodium in the initial stages. This leads to an artificially lowered plasma sodium concentration that can be corrected by the following formula displayed [16].

Potassium changes

Potassium depletion is due to excessive urinary potassium loss secondary to the osmotic diuresis. The diuresis leads to an increased delivery of fluid and potassium to potassium secretory sites in the distal nephron. The plasma potassium levels are usually within the normal range or high despite the loss, as hyperglycaemia and acidosis causes the potassium ions to shift from the intra-cellular to the extra-cellular compartment [2,3,7,8].

In the UK and other developed nations, whilst the mortality from DKA remains <1% it is the leading cause of death amongst people under 58 years old with T1DM.[13] Unsurprisingly perhaps, mortality increases with age and with the presence of pre-existing comorbidities The mortality rate is still high at over 40% in some low- and middle-income countries. This high mortality rate illustrates the necessity of early diagnosis and the implementation of effective prevention programmes. Cerebral oedema remains the most common cause of mortality, particularly in young children and adolescents. The main causes of mortality in the adult population include severe hypokalaemia, adult respiratory distress syndrome, and co-morbid states which may have precipitated the DKA such as pneumonia, acute myocardial infarction and sepsis.

Patients who present in DKA may complain of polyuria, polydipsia, weakness, nausea, vomiting (50-80%), coffee-ground haematemesis (25% of vomiting patients) and abdominal pain (30%) [15]. Physical findings are, dry mucous membranes, tachycardia, hypotension, alteration in mental state, sweet smell to the breath and Kussmaul’s respirations.

Fig 1: History and examination may also reveal the underlying cause [7,8,16-18]

Learning bite

In a patient who presents with abdominal pain and vomiting the diagnosis of DKA can easily be missed.

Initial bedside tests include:

  • Capillary blood glucose
  • Blood gases to determine pH, bicarbonate and potassium
  • Urine dipstick for ketones and urinalysis
  • ECG to investigate the possibility of a myocardial infarction, which may be silent

Learning bite

There is no need to take arterial blood routinely in suspected DKA. Venous blood can be used, as the mean difference between arterial and venous pH is 0.03. Arterial sampling should only be undertaken if there is a concern that there is respiratory failure [19-21].

As with any critically unwell patient management starts with ensuring that there is a patent airway, and ensure adequate oxygenation and ventilation. If the GCS is reduced or ventilation is impaired, this may well necessitate intubation via a rapid sequence induction. In the initial phase of resuscitation high flow oxygen through a non-rebreathing mask should be administered. Patients should be on continuous 3-lead cardiac monitoring. If there is hypotension this needs to be treated in the first instance with IV fluid resuscitation. Inotropes may be needed in septic or cardiac shock following adequate fluid resuscitation.

An adequate history must be taken and examination performed searching for the underlying cause that precipitated DKA.

General Management

Management revolves around IV fluid rehydration, insulin administration, correction of electrolyte abnormalities and treatment of the underlying cause.


There is universal agreement that the most important initial therapeutic intervention in DKA is appropriate fluid replacement followed by insulin administration.

The main aims for fluid replacement are:

  • Restoration of circulatory volume
  • Clearance of ketones
  • Correction of electrolyte imbalance

The typical fluid and electrolyte deficits are shown in the table below. For example, an adult weighing 70 kg presenting with DKA may be up to 7 litres in deficit. This should be replaced as crystalloid. In people with kidney failure or heart failure, as well as the elderly and adolescents, the rate and volume of fluid replacement may need to be modified. The aim of the first few litres of fluid is to correct any hypotension, replenish the intravascular deficit, and counteract the effects of the osmotic diuresis with correction of the electrolyte disturbance.

Courtesy of Mehdi Teeli


Low dose insulin therapy is effective regardless of the route of administration. Intravenous administration is the preferred route because of the delayed onset of action with subcutaneous insulin.

Intravenous insulin causes a more rapid fall in glucose and ketones than subcutaneous insulin. However, there is no difference in the length of stay, total amount of insulin or hypoglycaemic events in either route of administration.

Current practice is to commence a fixed rate intravenous insulin infusion at 0.1 UNITS/kg. In addition to this if the patients normally uses exogenous basal insulin (i.e. Lantus) this should also be administered as normal.


Despite a total body potassium deficit, commonly there is initially hyperkalaemia that will resolve with insulin and volume expansion and the subsequent correction of the acidosis.

In the presence of an adequate urine output (0.5ml/kg/hr) potassium replacement needs to be initiated when the potassium level is below 5.5mmol/L. Expert guidance recommends the following potassium replacement;

Add potassium using pre-prepared bags only as follows:


  • >5.5 mmol/l – none
  • 3.5-5.5 mmol /l – 20 mmol/500 ml bag (i.e. 40 mmol/l)
  • <3.5 mmol/l – senior advice is required, and pharmacy involvement may be needed. The patient MUST be looked after in a high dependency area

Anticipate a fall in potassium and replace, once the first plasma potassium result is known. Measure plasma potassium level (and also pH and bicarbonate) at 60 minutes, 2 hours, and 2 hourly thereafter [1].

Intravenous Insulin Regime

A fixed rate intravenous insulin infusion calculated on 0.1 units/per kilogram body weight is recommended.

The insulin infusion is made up of 50 units of soluble human insulin in 49.5 ml 0.9% sodium chloride solution (i.e. 1 unit /ml).

Recommendation (JBDS)

Once the glucose drops to less than 14 mmol/L then in addition to adding a 10% dextrose infusion consider reducing the rate of intravenous insulin infusion to 0.05 units/kg/hr to avoid the risk of developing hypoglycaemia and hypokalaemia.

Metabolic treatment targets

The recommended targets are

  • Reduction of the blood ketone concentration by 0.5 mmol/L/hour
  • Increase the venous bicarbonate by 3.0 mmol/L/hour
  • Reduce capillary blood glucose by 3.0 mmol/L/hour
  • Maintain potassium between 4.0 and 5.5 mmol/L

If these targets are not achieved, then the fixed rate insulin should be increased by 1 unit/hr increments hourly until targets achieved.

In addition to this if the patients normally use exogenous basal insulin (i.e. Lantus) this should also be administered as normal.

Euglycemic DKA

This is the development of DKA in people known to have diabetes but where the glucose is normal, or not particularly raised. Improved education for those with diabetes with increased home capillary glucose and ketone monitoring has led to partial treatment of DKA prior to admission with consequent lower blood glucose levels at presentation. This condition is treated in exactly the same way as hyperglycaemic DKA.

  1. Initiate glucose 10% straight away at 125 ml/hr because the glucose is < 14 mmol/L
  2. Begin with 0.1units/kg/hr insulin rate
  3. If glucose falling despite 10% glucose reduce to 0.05 units/kg/hr to avoid hypoglycaemia

Ketosis prone type 2 diabetes DKA does not exclusively occur in people with type 1 diabetes, and people with type 2 diabetes may also develop DKA – so called ‘ketosis prone type 2 diabetes. This most often occurs in people of Afro-Caribbean or Hispanic descent. The treatment for this condition is the same as for others with DKA, but they often come off insulin quickly after the resolution of the DKA and underlying precipitating condition.

Specific Management

In DKA there are a number of specific biochemical and haematological considerations that need to be monitored and managed.


Phosphate levels are affected in DKA in a similar way as potassium. However phosphate supplementation does not change the correction of glucose, bicarbonate or pH. Phosphate should not be routinely given [3,4,7].


There is also a magnesium deficiency in DKA. The symptoms are difficult to recognise and overlap with calcium, potassium and sodium deficiencies.

They are paresthesia, tremor, carpopedal spasm, agitation, seizures and cardiac arrhythmias. Correction of magnesium should be considered in symptomatic patients or those with hypokalaemia.

In magnesium deficiency treatment of hypokalaemia with potassium is often refractory to treatment. The mechanism still remains unexplained.


Adequate fluid and insulin therapy will resolve the acidosis in DKA and the use of bicarbonate is not indicated (R). The acidosis may be an adaptive response as it improves oxygen delivery to the tissues by causing a right shift of the oxygen dissociation curve. Excessive bicarbonate may cause a rise in the CO2 partial pressure in the cerebrospinal fluid (CSF) and may lead to a paradoxical increase in CSF acidosis [42]. In addition, the use of bicarbonate in DKA may delay the fall in blood lactate: pyruvate ratio and ketones when compared to intravenous 0.9% sodium chloride infusion [43]. Intensive care teams may occasionally use intravenous bicarbonate if the pH remains low and inotropes are required.

Level 2 care


Anti-thrombo-embolic therapy

The risk of DVT and PE is high in DKA. Patients should receive low weight molecular heparin as per the hospital protocol.


Blood sugar monitoring should be undertaken hourly, as should ketone measurement. A common complication of treatment of DKA is hypoglycaemia. In the patient with poor tissue perfusion there can be a significant difference between capillary and venous glucose, which is why bedside ketone monitoring is now advised. In patients with adequate tissue perfusion, the difference between venous and capillary glucose is less than 1 mmol/L and is adequate for monitoring.

Serum potassium level should be measured on arrival, at 60 minutes, 2 hours, and 2 hourly after that. The most rapid changes occur early in treatment. Bicarbonate should be measured every two hours for the first 6 hours [1]. Urine output should be recorded. Those with a poor urine output, cardiovascular disease or multiple co-morbidities may benefit from catheterisation and further invasive monitoring. These patients and those with a decreased GCS should be referred to HDU/ITU, otherwise refer to the on-call medical team.

Learning bite

A raised white cell count does not always indicate the presence of an infection, as the white cell count is proportional to the blood ketone body concentration.

There are potential complications of the treatment of the patient with DKA:


This is caused by the administration of insulin, hourly monitoring of blood sugar concentration is needed to avoid this complication [2,3,7,15].


Hypokalaemia is a common complication, exacerbated by starting insulin in the face of hypokalaemia, inadequate potassium replacement or by the use of sodium bicarbonate. Hypokalaemia can lead to muscle cramping or weakness, nausea or vomiting, polyuria, polydipsia, psychosis, delirium, hallucinations and importantly cardiac arrhythmias and cardiac arrest.

Cerebral oedema

Fortunately cerebral oedema is very rare in adults. Multiple factors in the treatment may contribute to cerebral oedema, these include osmotically active particles in the intra-cellular space driven by the insulin and rapid changes in sodium concentrations. This risk can be minimised by slow correction of hyperglycaemia and avoiding overzealous fluid replacement [2,7].

Acute respiratory distress syndrome

The partial pressure of oxygen steadily decreases during treatment to low levels. This is believed to be due to interstitial oedema and reduced lung compliance. The mechanism is similar to that causing cerebral oedema [7].

Hyperchloraemic metabolic acidosis

This is common, due to the loss of substrates in the urine that are necessary for bicarbonate regeneration, the large concentration of chloride infused in intravenous fluids and the shift of fluids if sodium bicarbonate is used. The acidosis normally corrects in the subsequent 24 to 48 hours through increased renal excretion. However the persistent base deficit can catch out the unwary.

If the blood sugar and ketones are not measured then the diagnosis of DKA will not be made; it is especially important in patients with the following symptoms:

  • Nausea
  • Vomiting
  • Abdominal pain
  • Altered mental state or GCS

If the potassium is below 3.5 mmol/L this needs to be corrected prior to starting insulin.

The acidosis of DKA is treated with fluid and insulin therapy.  The use of bicarbonate is not indicated and may cause harm.

The underlying precipitating cause for DKA needs to be sought and treated.

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  2. Savage WM, Kivlert A. ABCD guidelines for the management of hyperglycaemic emergencies in adults. Practical diabetes int, 2006, 23(5), pp. 227-231.
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  4. Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am. 1995 Jan;79(1):9-37.
  5. Foster DW, McGarry JD. The metabolic derangements and treatment of diabetic ketoacidosis. N Engl J Med. 1983 Jul 21;309(3):159-69.
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  7. Abbas E, Kitabchi AE, Guillermo E, et al. Hyperglycemic crises in adult patients with diabetes. A consensus statement from the diabetes association. Diabetes Car; 2006, 29: pp.2739-2748.
  8. Umpierrez GE, Murphy MB and Kitabchi AE. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrom. Diabetes Spectrum 2002 Jan; 15(1): 28-36.
  9. Gerich JE, Lorenzi M, Bier DM, et al. Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. J Clin Invest. 1976 Apr;57(4):875-84.
  10. McGarry JD, Woeltje KF, Kuwajima M, Foster DW. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab Rev. 1989 May;5(3):271-84.
  11. Felig P, Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest. 1971;50(8):1702-1711.
  12. Edwards CRW, Bouchier IAD, Haslett C, Chilvers ER. (1995) Davidson’s Principles and Practice of Medicine. 17th Edition. Churchill Livingstone.; pp.728-732.
  13. Diabetes UK. (1994). Diabetes in the UK 2004.
  14. Research and statistics. gov.uk
  15. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005 May 1;71(9):1705-14. PMID: 15887449.
  16. English P, Williams G. Hyperglycaemic crises and lactic acidosis in diabetes mellitus. Postgrad Med J. 2004 May;80(943):253-61.
  17. Umpierrez GE, Khajavi M, Kitabchi AE. Review: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Am J Med Sci. 1996 May;311(5):225-33.
  18. Hennis ED, Stahl E and Kreisberg RA. (1994) The hyperosmolar hyperglycaemic syndrome. Diabetes Rev; 2: pp.115.
  19. Brandenburg MA, Dire DJ. Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis. Ann Emerg Med. 1998 Apr;31(4):459-65.
  20. Ma OJ, Rush MD, Godfrey MM, Gaddis G. Arterial blood gas results rarely influence emergency physician management of patients with suspected diabetic ketoacidosis. Acad Emerg Med. 2003 Aug;10(8):836-41.
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  1. Terrianne Carpenter says:

    very clear review of topic and treatment priorities

  2. Dr Tahseen Ansari says:

    Precise and to the point.

  3. Dr. Rangani Kamanitha Handagala says:


  4. Dr Punithan Samana Annamalai says:


  5. Dr Ibrahim Abdo Mohammed Hussein says:

    This module collect all data need for treating DKA

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