LTHT Guidelines for the Management of Diabetic Ketoacidosis in Adults
Where Individuals Aged 16-18 Are Managed by Paediatric Teams, the Paediatric Guidelines Should Be Followed

• Summary Guideline
• Background
• Epidemiology
• Morbidity and mortality
• Diagnosis
• Symptoms and signs
• Investigations
• Principles of management
• Fluid therapy
• Intravenous glucose infusion
• Insulin therapy
• Potassium Therapy
• Other treatments
• Monitoring
• Metabolic targets
• Resolution of DKA
• Complications
• Hypoglycaemia in DKA
• Other considerations
• Special patient groups
• The diabetes specialist team
• Abbreviations

Summary Guideline

The guidelines which follow are designed to be used in conjunction with the DKA treatment chart (LTHT Adult Diabetic Ketoacidosis IV insulin treatment chart)

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Background

Diabetic ketoacidosis (DKA) is a complex disordered metabolic state characterised by hyperglycaemia, acidosis, and ketonaemia. DKA usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter regulatory hormones (i.e., glucagon, cortisol, growth hormone, and epinephrine). This type of hormonal imbalance enhances hepatic gluconeogenesis and glycogenolysis resulting in severe hyperglycaemia.

Enhanced lipolysis increases serum free fatty acids that are then metabolised as an alternative energy source in the process of ketogenesis. This results in accumulation of large quantities of ketone bodies and subsequent metabolic acidosis. Ketones include acetone, 3-beta-hydroxybutyrate, and acetoacetate. The predominant ketone in DKA is 3-beta-hydroxybutyrate.

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Epidemiology

DKA remains a significant clinical problem in spite of improvements in diabetes care. In the UK, the incidence of DKA is between 8.0 - 51.3 cases per 1000 T1DM patients, and the prevalence is highest in patients aged 18-24².

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Morbidity and mortality

Mortality rates have fallen significantly in the last 20 years through early diagnosis and implementation of effective prevention programs, and better understanding of the pathophysiology DKA with close monitoring and correction of electrolytes³. The main causes of mortality are severe hypokalaemia, adult respiratory distress syndrome, and other comorbidities such as pneumonia, myocardial infarction and sepsis³. In children and young adolescents cerebral oedema remains the most common cause of mortality³.

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Diagnosis

DKA consists of the biochemical triad of acidaemia, ketonaemia and hyperglycaemia. The following three mandatory features must be documented clearly.

Acidaemia
This is defined as a low blood bicarbonate level (<15 mmol/L) or pH<7.3 on venous blood gas testing. Venous blood gas testing should be performed with a heparinised blood sample.

Ketonaemia or ketonuria

Ketonaemia
If blood ketone meters are available:
Blood ketones >3mmol/L suggest significant ketonaemia.
Blood ketone meters measure 3-beta-hydroxybutyrate, the most abundant ketone in DKA.
Refer to LHP guideline (Measuring capillary blood ketones (leedsth.nhs.uk) if criteria for DKA are not met.

Ketonuria
2+ or greater ketones in the urine.
Urinalysis detects ketoacetate, which is produced in lower quantities than 3-beta-hydroxybutyrate in DKA.
Urine ketones typically lag blood ketones.

Hyperglycaemia
Venous blood glucose >11mmol/L.

Diabetic ketoacidosis is possible with normal or only mildly elevated blood glucose values, especially in pregnancy, SGLT-2 inhibitor use. This is also known as euglycaemic DKA

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Symptoms and signs

Symptoms: Polyuria, polydipsia, blurred vision, vomiting, abdominal pain, infective symptoms

Signs: Fast heart rate, low blood pressure, fast respiratory rate, acetone smell on breath, signs of dehydration, tender abdomen, reduced conscious level.

Alternative hyperglycaemic Diagnoses

• Hyperglycaemia without acidosis or ketones. In the absence of dehydration and intercurrent illness. This is not a medical emergency.
• Hyperglycaemia with ketosis but not acidosis. This is not a medical emergency but may indicate the need for hydration along with subcutaneous insulin. Refer to LHP guideline (Measuring capillary blood ketones (leedsth.nhs.uk)
• Hyperosmolar hyperglycaemic state. This is a medical emergency. This is differentiated from DKA by its gradual onset, occurrence in older patient group, reduced conscious level or mental obtundation. Criteria for HHS include: high osmolality (≥ 320 mosmol/kg), hyperglycaemia (≥ 30 mmol/L) without significant ketosis (<3mmol/L) or acidosis (pH >7.3, bicarbonate >15mmol/L) and hypovolaemia.
• LHP guideline:  Hyperosmolar hyperglycaemic state (HHS) in adults with diabetes (leedsth.nhs.uk).

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Investigations

Always, at presentation:

• Venous U&E, bicarbonate, lab venous glucose, venous blood gas
• Capillary blood glucose (CBG)
• Full blood count
• Urine analysis, and send for microscopy and culture
• Blood ketones (if available)

Often indicated (depending on clinical suspicion):

• 12 lead ECG
• Chest radiograph
• Blood cultures
• Amylase (if suspicion of pancreatitis. However DKA may mimic acute abdomen, and cause moderate elevation of serum amylase in the absence of pancreatitis)
• Pregnancy test: If woman of child-bearing age, as pregnancy may trigger DKA. In this situation diabetologists and obstetricians must be contacted urgently. DKA in pregnancy carries a high risk of foetal death.

Sometimes indicated

• Arterial blood gas analysis (if oxygen saturations  <95% on air, or atypical venous blood gas result)
• Liver function tests, calcium, phosphate

Assessment of severity

One or more of the following criteria may indicate severe DKA. Early senior review is essential, and admission to HDU or ICU environment may be appropriate:

• Blood ketones over 6 mmol/L
• Bicarbonate level below 5 mmol/L
• Venous/arterial pH below 7.0
• Hypokalaemia on admission (under 3.5 mmol/L)
• GCS less than 12 or abnormal AVPU scale
• Oxygen saturation is below 92% on air (do ABG in this situation)
• Systolic blood pressure below 90 mmHg after initial fluid resuscitation
• Pregnancy and DKA
• Anion gap above 16 [Anion Gap = (Na+ + K+) – (Cl- + HCO3- )
• Pulse over 100 or below 60 bpm

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Principles of management

Fluid therapy

The most important initial therapeutic intervention DKA is appropriate fluid replacement, subsequently followed by insulin administration.

If IV access cannot be obtained, critical care support should be requested immediately.

The main aims of fluid replacement are:

• restoration of circulatory volume
• clearance of ketones
• correction of electrolyte imbalance

Typical deficits in DKA:

Restoration of circulatory volume

Systolic BP (SBP) below 90mmHg

• Likely to be due to low circulating volume, but consider other causes such as heart failure, sepsis, etc.
• Give 500mls 0.9% sodium chloride solution over 10-15 minutes. If SBP remains 90mmHg, give 1L 0.9% sodium chloride over the next 60 minutes. The addition of potassium is likely to be required in this second litre of fluid

Systolic BP on admission 90 mmHg and over

• Give 1L 0.9% sodium chloride over the first 60 minutes

Fluid replacement should be with crystalloid.

Even in the hypotensive DKA patient initial fluid resuscitation should be with crystalloid, as the hypotension results from a loss of electrolyte solution and therefore it is physiological to replace with crystalloid.

Sodium chloride 0.9% solution should be the fluid of choice for resuscitation in all clinical areas as it supports safe practice and is available ready to use with adequate ready mixed potassium.

Adult guidelines suggest rapid initial fluid replacement in the first few hours.

For a previously well 70kg adult, without significant co-morbidity, we would suggest:

In patients of different weight, or those with kidney failure, heart failure, as well as in the elderly or adolescents, the rate of volume of fluid replacement will need to be modified.

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Intravenous glucose infusion

When the blood glucose is less than 14 mmol/L, introduce intravenous glucose 10% infusion.

• Reduce insulin to 0.05units/kg/hour as per table in “insulin therapy” section.
• Continue sodium chloride 0.9% solution to correct circulating volume.
• If the patient has a hypoglycaemia episode please refer to the LHP hypoglycaemia guideline
• If hypoglycaemia persists please seek specialist advice, especially if still in DKA.

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Insulin therapy

Insulin infusion should be given intravenously.

Insulin acts:

• to suppress ketone production
• to reduce blood glucose
• to correct electrolyte imbalance

A fixed rate IV insulin infusion should be calculated based on 0.1 units of insulin per kilogram body weight per hour. Sometimes it may be necessary to estimate the weight of the patient.

Fixed dose per kilogram bodyweight dosing of insulin has been shown to enable rapid blood ketone clearance. This can be monitored with bedside ketone measurement. The fixed rate may need to be adjusted in cases of insulin resistance, hypoglycaemia or if metabolic targets (ketone and bicarbonate levels) are not met.

Once blood glucose drops below <14mmol/L, reducing the rate of insulin to 0.05units/kg/hr should be considered to avoid risk of developing hypoglycaemia. This is in addition to prescribing glucose 10% IV infusion. Monitoring blood glucose levels every 1-2 hours can prevent hypoglycaemia as patients may not experience symptoms of hypoglycaemia.

Fixed rate insulin 0.05units/kg/hr

Long-acting  basal insulins should be continued when the patient is admitted with DKA.

These are: Lantus® (insulin glargine), Levemir® (insulin detemir) Abasaglar® (insulin glargine) or Tresiba® (insulin degludec), Humulin I®, Insulatard® , Insuman Basal.

Continuation of long-acting insulin analogues during the initial management of DKA provides background insulin when the IV insulin is discontinued. This helps to avoid rebound hyperglycaemia when IV insulin is stopped and also helps to reduce excess length of stay.

Short-acting insulin should be discontinued whilst the patients is on intravenous insulin infusion. This must be restarted shortly before discontinuing the intravenous insulin infusion, once the patient is eating and drinking.

In those already on long acting basal insulin, it should continue to be prescribed at their usual dose. In those newly diagnosed, then a long acting basal insulin should be commenced, at a dose of 0.25 units/Kg subcutaneously once daily.

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Potassium Therapy

• Hypokalaemia and hyperkalaemia can be complications of DKA or its treatment. Both these conditions are potentially life-threatening.
• It is recommended that no potassium is prescribed with the initial rapid fluid resuscitation or if the serum potassium level remains above 5.5 mmol/L.
• Potassium levels will almost always fall as DKA is treated with insulin. Therefore potassium replacement should be in accordance with the table below as long as the patient is passing urine.
• It is recommended that ready mixed sodium chloride 0.9% solution with potassium is used.
• If the serum potassium levels fall below 3.5 mmol/L the potassium regimen needs review.
• If using peripheral IV access, potassium replacement should be at no more than 20 mmol/L/hour, with ECG monitoring.
• If more rapid potassium replacement is required, central IV access should be considered and LTHT potassium replacement protocols should be followed.
• This will involve transfer of the patient to the high dependency unit or equivalent facility for monitoring.

Potassium replacement table

Electrolyte measurements can be obtained from most blood gas analysers. These can be used to monitor potassium and bicarbonate levels. These should be corroborated with lab values at presentation and after six hours of treatment.

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Other treatments

Thromboprophylaxis
DKA predisposes to venous thromboembolism. Unless contraindicated patients with DKA should be initiated on appropriate thromboprophylaxis. This should be based on LTHT guidelines VTE prophylaxis for General Medical patients.

Bicarbonate
Adequate fluid and insulin therapy will resolve the acidosis in DKA and the use of bicarbonate is not indicated. There is some evidence that the use of bicarbonate in DKA is detrimental.

Phosphate
Phosphate deficits in DKA may average one mmol per kilogram of body weight. There is no evidence of benefit of phosphate replacement in DKA. However in cases of severe or symptomatic hypophosphataemia, phosphate replacement should occur in line with LTHT guideline Hypophosphataemia in Adults.

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Monitoring

Venous blood gas measurements

• Recent evidence shows that there is no significant difference between venous and arterial pH, and minimal difference between arterial and venous bicarbonate. Therefore it is not necessary to use arterial blood gas to measure acid-base status unless there is concern about hypoxia.
• Arterial line insertion should only be performed if its use will influence management, i.e. for frequent arterial oxygen level measurements or for monitoring blood pressure in the critically unwell patient.
• Venous blood gas samples should be used to monitor bicarbonate, pH and potassium levels, and should be corroborated with laboratory venous bicarbonate and potassium at admission, 6 hours and 24 hours.

Ketonaemia

• Ketonaemia is the hallmark of DKA. The resolution of DKA is dependent upon the suppression of ketonaemia and measurement of blood ketones now represents best practice in monitoring the response to treatment.
• Currently the assessment of the ketone status of the patient is performed by measuring urine ketones. It is envisaged that, bedside measurement of blood ketones (3-beta-hydroxybutyrate) will become available in the key clinical areas where patients with DKA are treated.

CLINICAL
Re-assess the patient hourly for the first 4 - 6 hours and frequently thereafter dependent on patient’s condition

• Check vital signs at least hourly (blood pressure, pulse, urine output, oxygen saturations), and escalate in line with NEWS guidance.
• Consider CVP / urinary catheter if clinical evidence of poor LV or renal function.
• Consider NG tube if drowsy or vomiting.

LABORATORY
Monitor capillary glucose and ketones hourly.
Regular clinical and biochemical reviews are needed during first 24 hours

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Metabolic treatment targets

• Increase venous bicarbonate by 3 mmol/L per hour until >15mmol/L
• Reduce capillary blood glucose by 3 mmol/L per hour until <14mmol/L.
• Reduce blood ketone concentration by 0.5 mmol/L per hour until <0.6mmol/L.
• Maintain potassium between 4.0 and 5.5 mmol/L

If these rates are not achieved the fixed rate IV insulin infusion rate should be increased by 1 unit per hour and response monitored.

NOT IMPROVING?   CHECK: 

• IV pump operation, insulin addition, patency of cannula, patient weight.
• Re-assess for concomitant illness.  Consider other causes of acidosis.
• If CBG not falling CONSIDER increase rate of insulin infusion by 1 unit / hour, every hour. Re-assess regularly.

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Resolution of DKA

• By 24 hours the ketonaemia and acidosis should have resolved.
• Resolution is defined as ketones <0.6mmol/L (or urine ketones <2) and pH>7.3.
• If patient is not eating and drinking and there is no ketonaemia move to a variable rate IV insulin infusion.
• If patient is eating and drinking normally and no ketonaemia switch to usual subcutaneous insulin.
• Ensure basal subcutaneous insulin has been given within the last 12 hours before IV insulin is discontinued. Ideally, also give fast-acting subcutaneous insulin and a meal and discontinue IV insulin 30 minutes later.
• For new diagnosis diabetes, conversion to subcutaneous insulin is best managed by the diabetes specialist team.
• The patient with DKA must be reviewed by the local diabetes team within 24 hours of admission.
• Arrange outpatient follow-up with diabetes team.

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Complications

Cerebral oedema
Cerebral oedema is relatively uncommon in adults during DKA. The symptoms to be aware of include headache, irritability, drowsiness or decreasing levels of consciousness Care must be taken when treating adolescents and young adults in particular. Cerebral oedema in DKA is much more common in children. Avoidance of overzealous fluid resuscitation in these patient groups is important.

Pulmonary oedema
Elderly patients and those with impaired cardiac function are at particular risk of pulmonary oedema, particularly in the first few hours of initiation of treatment. Care must be taken in these patient groups and monitoring of central venous pressure should be considered.

Expectation and outcome
Patients with diabetic ketoacidosis usually respond well and promptly to treatment. Failure to improve is important to recognise as it may well indicate an underlying illness or complication.
If the patients symptoms, overall clinical status, or serum bicarbonate do not improve or new adverse clinical features develop, an underlying illness or complication should be sought. In these circumstances consider seeking early advice from ITU/critical care reach.

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Hypoglycaemia in DKA

Please refer to hypoglycaemia guideline on LHP

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Other considerations

In any patient admitted with DKA it is important to consider:

• Identification of precipitating factors. For example, infection or omission of insulin injections.
• Prevention of recurrence through provision of sick day rules.
• Ineffective insulin, because of either expiration denaturation.
• Provision of handheld ketone meters and educational management of ketonaemia.

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Special patient groups

The following groups of patients need specialist input as soon as possible and special attention with regards to fluid balance.
Elderly
Pregnant women (call diabetes team immediately)
Heart or kidney failure

End stage renal disease and dialysis
Patients with end-stage renal failure can present with hyperglycaemia and ketosis. These patients are unable to develop an osmotic diuresis therefore fluid replacement may not be required.

Insulin is the primary treatment and should be started at 0.1units/kg/hour. It is advised to reduce to 0.05units/kg/hour when glucose is <14mmol/L. Potassium is unlikely to be needed in a patient with renal failure due to the lack of osmotic diuresis, however hyperkalaemia is more common. Increased cardiac monitoring is advised due to this potential complication.

Euglycaemic DKA
Euglycaemic DKA occurs in people living with diabetes where the glucose is normal or not raised to the extent that it is in DKA. This condition is treated in the same way as hyperglycaemic DKA.

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

The use of SGLT-2 inhibitors has highlighted the importance of using pH and ketones to guide the diagnosis and management due to the risk of developing euglycaemic DKA with these agents.

IF DKA occurs with SGLT-2 inhibitor use, they should be stopped. A “Yellow Card” should also be completed. Whether the drugs should be restarted once the individual has recovered should be discussed with the diabetes team.

Alcoholic ketoacidosis (AKA)
In alcoholic ketoacidosis, the normal glucose concentration glucose is the key difference with DKA – however, a careful history needs to be taken to differentiate it also from euglycaemic DKA. Ketoacidosis without a raised glucose in a person with alcoholism is virtually diagnostic of alcoholic ketoacidosis4. If alcoholic ketoacidosis is suspected, then ß-hydroxybutyrate (capillary ketone) should be measured and not urine ketones, because acetoacetate production can be supressed in alcoholic ketoacidosis⁵.

For patients with elevated blood glucose fulfilling criteria for DKA, follow the DKA protocol.

For patients with normal blood glucose or low blood glucose level, start treatment with 5% dextrose6 rather than insulin infusion to aid in correction of acidosis and ketosis7. Concurrent normal saline can be given based on clinical need and indication. This condition can usually be managed without insulin.

Please ensure patient received thiamine in the form of Pabrinex and ensure all other electrolytes imbalances are corrected.

Please also refer:

1. The management of alcohol withdrawal symptoms
2. The Management of Alcohol Withdrawal in Older People

The early involvement of diabetes specialist teams in these patient groups is crucial.

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The diabetes specialist team

Diabetes specialist teams must always be involved in the care of those admitted to hospital DKA, ideally at presentation and definitely within 24 hours.. This has been shown to improve safety and shorten patient stay.

Diabetes specialists should also be involved in the assessment of the precipitating cause of DKA, management, discharge and follow-up. This will enable safer and more efficient patient care. This should also ensure rigorous implementation of DKA guidelines.

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