• Diabetic Ketoacidosis (DKA) is a medical emergency requiring immediate treatment

• Use this guideline for adults and those aged 16-18 admitted to adult wards.

• Patients with DKA should be admitted to MADU or ITU

• Regular review of clinical status is crucial

• Refer all patients to Diabetes Inpatient Team on admission via Epic

• Euglycaemic DKA (where glucose is less than 11mmol/L) can occur with severe vomiting, in pregnancy or in those treated with SGLT-inhibitor and should be treated like a hyperglycaemic DKA, following this guideline

• Although less common, DKA can still occur in patients with type 2 diabetes

• DKA diagnosed >24 hours after admission is an SI and should be reported on InPhase (previously called RL)

This is a controlled document. If you are using a printed copy, check it against the guidelines site to ensure you are using the latest edition. Print copies must be destroyed after use.

Abbreviations

Diagnostic criteria: all three of the following must be present to make the diagnosis

• capillary blood glucose above 11 mmol/L or known to have diabetes mellitus

• capillary or blood ketones above 3 mmol/L or urine ketones ++ or more

• venous pH less than 7.3 and/or bicarbonate less than 15 mmol/L

Criteria of Severity:

ketones > 6mmol/L, bicarbonate < 5mmol/L, Ph< 7.0, K+< 3.5 mmol/L on admission, GCS < 12, Systolic BP < 90mmHg, O2<92%, pulse >100/ <60/bpm, Anion gap above 16 – Involve ITU early if any of parameters exist.

Immediate management: time 0 to 60 minutes

If intravenous access cannot be obtained request critical care support immediately

1: Commence 0.9% sodium chloride solution (use a large bore cannula) via an infusion pump

If Systolic BP below 90 mmHg

Likely due to low circulating volume, but consider heart failure, sepsis, etc. Give 500 mls 0.9%

sodium chloride solution over 10-15 minutes.

If SBP remains <90 mmHg repeat whilst awaiting senior input and involve the ITU / critical care team if the SBP remains <90mmHg or after 2 IV fluid boluses

If Systolic BP is >90 mmHg, give 1 L 0.9% sodium chloride over next 60 minutes.

The addition of potassium is likely to be required in the second litre of fluid

2: Commence a fixed rate intravenous insulin infusion (FRIII).

0.1unit/kg/hr based on estimate of weight

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

If patient normally takes long-acting insulin analogue prescribe at usual dose and time and give alongside IV insulin infusion. e.g. glargine (Abasaglar®, Lantus®, Semglee®, Toujeo®), detemir (Levemir®), degludec (Tresiba®), insulatard (Humulin I®)

3: Assess patient

- Respiratory rate; temperature; blood pressure; pulse; oxygen saturation

- Glasgow Coma Scale

- Full clinical examination

4: Further investigations

• U&E and FBC

• Blood cultures, MSU

• ECG, CXR, Pregnancy test in women of childbearing age

• Venous BG

5: Establish monitoring regimen

• Hourly capillary blood glucose and ketone measurement

• Venous bicarbonate and potassium at 60 minutes, 2 hours and 2 hourly thereafter

• 4 hourly serum electrolytes

• Consider cardiac monitoring and pulse oximetry

6: Identify and manage precipitating causes

Aims of treatment

Ketones rate of fall 0.5mmol/L/hr

Glucose rate of fall at least 3mmol/L/hr

Potassium in normal range

Avoid hypoglycaemia (glucose <4mmol/L)

1. Reassess patient – vital signs and glucose and ketones (both hourly), pH (VBG at 60 minutes then 2 hourly)

2. Continue fluid replacement (bags as follows)

0.9% sodium chloride 1 L with potassium chloride over 2 hours

0.9% sodium chloride 1 L with potassium chloride over 2 hours

0.9% sodium chloride 1 L with potassium chloride over 4 hours

Add 10% glucose 125ml/hr if blood glucose <14mmol/l

Consider reducing IV insulin to 0.05units/kg/hr when glucose less than 14mmol/L, if ketones and pH are improving

More cautious fluid replacement may be needed in 18-25 years, elderly, pregnant, heart or renal failure (ITU and/or central line)

3. Assess response to treatment every 2 hours

If ketones and glucose are not falling as expected (see above for targets), always first check the insulin infusion pump is working and connected and that the correct insulin residual volume is present (to check for pump malfunction or cannula patency).

If, after the above has been confirmed, response to treatment inadequate, increase the insulin infusion rate by 1 unit per hour and review until targets achieved.

4. Additional measures:

Regular observations and Early Warning Score (NEWS2)

Accurate fluid balance chart, minimum urine output 0.5 ml/kg/hr

Consider urinary catheter if anuric (not passed urine >1 hour)

Consider NG tube with airway protection, if obtunded or persistent vomiting

Measure arterial blood gases if oxygen saturation < 92%

Thromboprophylaxis with dalteparin as per VTE prophylaxis guidelines

ECG monitoring if potassium low or cardiac status concerns

Ensure long-acting basal insulin has been given to those already on it; patients with newly diagnosed type 1 diabetes should be given long-acting basal insulin (e.g. glargine or degludec) at a dose of 0.25 units/Kg subcutaneously daily.

Aims of treatment

• Ensure clinical and biochemical parameters improving and avoid hypoglycaemia

• Continue IV fluid replacement

• Assess for complications of treatment e.g. fluid overload, cerebral oedema

• Treat precipitating factors as necessary

Action 1: Re-assess patient, monitor vital signs

• If patient not improving at this stage, seek senior advice

• Continue IV fluid via infusion pump at reduced rate

• 0.9% sodium chloride 1 L with KCl over 4 hours

• 0.9% sodium chloride with KCl over 6 hours

• Add 10% dextrose 125 mls/hr if the glucose falls below 14 mmol/L

• Consider reducing the rate of intravenous insulin infusion to 0.05 units/ kg/hour when glucose falls below 14 mmol/L

Reassess cardiovascular status at 12 hours and fluid status (and check for fluid overload)

Ensure long acting subcutaneous insulin has been given

Action 2 – Review biochemical and metabolic

parameters

• At 6 hours check venous pH, bicarbonate, potassium, capillary ketones and glucose

• Resolution of DKA is defined at ketones <0.6 mmol/l AND venous pH >7.3 (do not use bicarbonate as a marker at this stage)

• Ensure a referral has been made to the inpatient diabetes team (see below)

Once ketones are < 0.6mmol/l, patients should have ketones checked at6 hours AND at any stage if blood glucose > 15mmol/l as per JBDS/ trust guidelines.

By 24 hours the ketonaemia and acidosis should have resolved. Request senior review if not improving

Once ketones < 0.6 mmol/L and venous pH>7.3 if long acting subcutaneous insulin already administered and the person is eating and drinking normally, transfer to subcutaneous rapid acting insulin with meals.

Do NOT discontinue intravenous insulin infusion until 30 minutes after subcutaneous rapid acting insulin has been given.

However, if not eating and drinking, switch to variable rate IV insulin infusion (VRIII), alongside IV fluid replacement.

Reassess for complications of treatment, e.g. fluid overload, cerebral oedema

Refer to diabetes inpatient team (DIT) if not already done

WPH Please refer via Epic type in (inpatient consult to diabetes specialist nurse)

- Diabetes Specialist Nurses 07776225313

FPH Please refer via Epic type in (inpatient consult to diabetes specialist nurse)

- Diabetes Specialist Nurses FPH- 07393 250 876

Diabetic ketoacidosis can be diagnosed if all 3 criteria are met

Capillary blood glucose >11 mmol/L

Capillary ketones equal or > 3mmol/L or urine ketones ++ or more

Venous pH < 7.3 and or bicarbonate ≤ 15 mmol/L

It is important to remember:

• Euglycaemic DKA where glucose is less than 11mmol/L can occur with severe vomiting, in pregnancy or in those treated with SGLT inhibitor (with Type 1 or Type 2 diabetes). This condition is treated in the same was as DKA but initiate with glucose 10% at 125ml/hr (because the glucose is <14mmol/l) and 0.1units/kg/hr insulin (reducing this to 0.05 units/kg/hr if glucose falling)).
  Please note that if DKA occurs in those treated with SGLT-2 inhibitors, a ‘Yellow Card’ should be completed. The drug should not be restarted before discussion with the diabetes team.

• DKA can occur in patients with Type 2 diabetes. This most often occurs in people of Hispanic or Afro-Caribbean descent. Treatment is the same, but they may not need long term insulin.

• Consider other causes of ketosis such as alcohol or starvation ketosis if glucose is normal. Ketones can be as high as 6mmol/L, but acidosis rarely occurs if renal function is normal. Ensure a careful history is taken, to differentiate between these forms of ketosis and euglycaemic DKA.

Purpose

This guideline is for the management of diabetic ketoacidosis in adults (aged 16 years or older) with diabetes mellitus admitted to all adult wards within the trust. It has been designed to support doctors, nurses in the safe and effective management of adult patients in hospital.

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.

Table: Typical deficits in DKA in adults

Water - 100 ml/kg

Sodium - 7-10 mmol/kg

Chloride - 3-5 mmol/kg

Potassium - 3-5 mmol/kg

A fixed rate intravenous insulin infusion (FRIII) calculated on 0.1 units/per kilogram body

weight is recommended (see table below to assist). It may be necessary to estimate the

weight of the individual. Insulin has several effects, but the following are the most important

when treating DKA:

• Suppression of ketogenesis

• Reduction of blood glucose

• Correction of electrolyte disturbance

The insulin infusion is made up of 50 units of soluble human insulin in 49.5 ml 0.9% sodium

chloride solution (producing a concentration of 1 unit/ml).

A table has been introduced to assist in the calculation of the insulin dose for weight:

Once the glucose drops to <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 if ketones and pH are improving.

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 FRIII rate should be increased

To ensure that ketones are cleared, an FRIII should be continued as well as an infusion of

0.9% sodium chloride solution to maintain fluid replacement. But once the blood glucose

falls below 14.0 mmol/L, a 10% dextrose infusion should be added to act as the substrate

for the insulin, to prevent hypoglycaemia. It is quite often necessary to infuse 0.9% sodium

chloride solution and 10% dextrose concurrently. There are no bags which contain both fluids, so two bags will need to be run concurrently. The intravenous insulin and dextrose should not be discontinued until the person with diabetes is eating and drinking normally.

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.

The following groups need specialist input as soon as possible and special attention needs to

be paid to their fluid balance:

• Elderly

• Pregnant

• Young people 18 to 25 years of age (see section on cerebral oedema)

• Heart or kidney failure

• Other serious co-morbidities

In line with several aspects of the Best Practice Tariff, people with diabetes who are admitted

with DKA should be referred to the diabetes specialist team within one working day. Every

opportunity should be taken to educate the person with diabetes. They should

be counselled about the precipitating causes and early warning symptoms. Things to

consider are:

• Identification of precipitating factor(s) e.g. intercurrent illness or omission of insulin Injections

• Review of their usual glycaemic control

• Review of their injection technique / blood glucose monitoring / equipment / injection sites

• For those on insulin pumps, review of their use of the device and provision of further education in the use of such technology, as necessary.

• Insulin pumps should be disconnected and stored safely when not in use.

• Prevention of recurrence e.g. provision of written sick day rules

• Insulin effectiveness e.g. their own insulin may be expired or denatured. This should be checked prior to reuse

• Assess the need for, and where necessary, provision of handheld ketone meters for use at home – this should be the default position

• Provision of a contact number on how to contact the diabetes specialist team

• Education of health care professionals on the management of ketonaemia

• Provision of a written care plan – allowing the person with diabetes to have an active role in their own diabetes management, with a copy of this going to their GP

• For those with recurrent admissions, there is often a psychological element (e.g. eating disorders, other undiagnosed mental health disorders), that is likely to benefit from formal mental health team involvement.

People who present with recurrent episodes of DKA comprise a significant proportion of all

DKA admissions – in the UK accounting for 66% of those with type 1 diabetes and 35% of

those with type 2. Many of these individuals have fragmented care, social, behavioural

or psychological considerations that need to be accounted for. Other risk factors for

recurrent episodes include female sex, adolescence, low socioeconomic status, and previous

DKA admissions. Recurrent episodes of DKA re associated with increased risk of long term

cognitive decline and premature mortality. Strategies to help individuals may include

frequent telephone contacts, formal referral to psychology, supervised insulin administration

– e.g. using ultra long-acting insulin analogues.

Cerebral Oedema

Cerebral oedema causing symptoms is relatively uncommon in adults, although may occur in those who are physically slight or in younger adults. Asymptomatic cerebral oedema may be a common occurrence, and may exist prior to treatment starting. The exact cause of this phenomenon is unknown. It is thus possibly an idiosyncratic response to the metabolic injury and subsequent treatment. However, any deterioration in Glasgow Coma Scale score should prompt urgent treatment and imaging. If cerebral oedema is suspected, urgent treatment with mannitol or hypertonic saline to induce osmotic fluid shifts should be started and not be delayed whilst awaiting imaging.

1. Consider reducing rate of insulin infusion to 0.05 units/kg/hr when glucose drops to <14 mmol/L to reduce the risk of hypoglycaemia and / or hypokalaemia

2. Crystalloid rather than colloid solutions are recommended for fluid resuscitation

3. 0.9% sodium chloride solution (‘normal saline’) is the fluid resuscitation of choice

4. Cautious fluid replacement in young adults

5. Bicarbonate administration is not recommended routinely

6. Phosphate should not be supplemented routinely

7. The rate of glucose lowering should be least 3.0 mmol/L/hr

Fortunately, this is a relatively rare occurrence. There are limited data on the management

of DKA in this circumstance. The lack of renal insulin clearance means that DKA

is much less likely to occur. It may also be difficult to determine because of the chronic

metabolic acidosis associated with advanced chronic kidney disease (stages 4 and 5).

Recent data suggest that those presenting in DKA with end stage renal disease have lower ß-hydroxybutyrate concentrations, and higher glucose and anion gap than those with preserved renal function. Bicarbonate and pH were not significantly different.

When DKA does occur in end stage renal disease, several issues need to be considered.

Fluid replacement

The inability to develop an osmotic diuresis means that dialysis associated hyperglycaemia

and ketosis can occur without much dehydration. A mixed picture of DKA and HHS may

also occur because of the high serum tonicity. In addition, the circulating intravascular

volume may increase at the expense of intracellular volume that resolves as the glucose and

ketosis normalises. Therefore, there may be no need for fluid replacement in those with end

stage renal failure or those on dialysis. However, for those who are deemed hypovolaemic,

aliquots of 250 ml (0.9% sodium chloride or 10% dextrose) may be given with frequent

clinical assessments.

Insulin treatment

For people with end stage renal failure or those on dialysis, insulin replacement is the

mainstay of treatment. This should be given as a FRIII at an initial rate of 0.1 units/kg/hr, but

may need to increase if the required rate of glucose fall is not achieved. However, the failure

to renally clear insulin increases the risk of hypoglycaemia. However, the rate of glucose

reduction is the same as for people with preserved renal function – i.e. 3.0 mmol/L/hour. If

the rate of fall is faster, or the glucose falls to <14.0 mmol/L strongly consider reducing the

rate of intravenous insulin infusion to 0.05 units/kg/hr.

Potassium

Potassium supplementation is not usually required because the lack of the osmotic diuresis

means that there is significantly less potassium loss that for those with preserved renal

function. However, the acidosis may lead to significant hyperkalaemia, and this is more

common in those with renal failure. In this circumstance, continuous cardiac monitoring

is essential and critical care or the specialist renal team should be involved to consider urgent

haemodialysis / hemofiltration.

DKA is a medical emergency with a significant morbidity and mortality. It should be

diagnosed promptly and managed intensively. The specialist diabetes team should

always be involved as soon as possible and ideally within 24 hours because this has been

demonstrated to be associated with a better experience for the person with diabetes and

reduced length of stay.

Where young people aged 16-18 years are managed by adult medical teams because of

local arrangements, it is considered appropriate for them to be managed using local adult

guidelines that the teams are familiar with rather than using potentially unfamiliar paediatric

guidelines.

Where individuals aged 16-18 years are managed by paediatric teams the paediatric

guidelines should be followed. https://www.bsped.org.uk/clinical-resources/guidelines/

The presence of one or more of the following may indicate severe DKA:

• Blood ketones over 6.0 mmol/L

• Bicarbonate level below 5.0 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 below 92% on air (assuming normal baseline respiratory function)

• Systolic BP below 90 mmHg

• Pulse over 100 or below 60 bpm

• Anion gap above 16 [Anion Gap = (Na+ + K+) – (Cl- + HCO3-)]

If the individual exhibits any of these signs, resuscitation and treatment should be started

without delay, and an intensive monitoring regimen put in place. Depending on local

circumstances individuals who fulfil the criteria for severity or who require intensive

monitoring should be reviewed by a consultant physician and considered for swift referral

to a Level 2/HDU (High Dependency Unit) environment, or if the individual has failed to

improve after initial resuscitation measures. It may also be necessary to consider a

surgical cause for the deterioration. If surgery is required there will need to be urgent

senior multidisciplinary discussion on the optimum time to operate.

In those using an insulin pump, if transfer to a Level 2 / HDU or ITU is necessary, then the

pump should be stopped, removed, and stored safely.

Early data on the use of continuous glucose monitoring (e.g. Freestyle Libre®, Dexcom G6®, etc) in critical illness suggest it may be safe to use, but these are preliminary. As such, current guidelines do not support their use.

Diabetic ketoacidosis (DKA) is a complex disordered metabolic state characterised by hyperglycaemia, ketonaemia, and acidosis. 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, catecholamines). 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 the blood is 3-beta-hydroxybutyrate.

There are several mechanisms responsible for fluid depletion in DKA. These include osmotic diuresis due to hyperglycaemia, vomiting - commonly associated with DKA - and eventually, inability to take in fluid due to a diminished level of consciousness. Electrolyte shifts and depletion are in part related to the osmotic diuresis. Hyperkalaemia and hypokalaemia need particular attention.

Restarting SC insulin for those already established on insulin

The person’s previous regimen should generally be re-started if their most recent HbA1c suggests acceptable level of control i.e. HbA1c 64 mmol/mmol (<8.0%) With all regimens the intravenous insulin infusion should not be discontinued for at least 30 to 60 minutes after the administration of the subcutaneous dose given in association with a meal.

If they were on basal bolus insulin

• There should be an overlap between the insulin infusion and first injection of fast acting insulin. The fast-acting insulin should be injected with the meal and the intravenous insulin and fluids discontinued 30 to 60 minutes later.

• If the person was previously on a long-acting insulin such as glargine, degludec, detemir or isophane, this should have been continued and thus the only action should be to restart their normal rapid acting insulin at the next meal.

• If the basal insulin had been stopped in error, the insulin infusion should not be stopped until some form of background insulin has been given. If the basal insulin was normally taken once daily in the evening and the intention is to convert to subcutaneous insulin in the morning, give half the usual daily dose of basal insulin as isophane (Insulatard®, Humulin I®) in the morning. This will provide essential background insulin until the long-acting analogue can be recommenced. Check the blood ketone and glucose levels regularly. A long or intermediate acting insulin should be given at least 2 hours before VRIII discontinuation.

If they were on twice daily fixed-mix insulin.

• Re-introduce the subcutaneous insulin before breakfast or before the evening meal. Do not change at any other time. Maintain the insulin infusion for 30 to 60 minutes after the subcutaneous insulin was given.

If they were on CSII (insulin pump)

• Ensure the availability of necessary supplies/ and or consumables

• Ensure that the individual has been assessed as being able to use the CSII (see Self-administration of Insulin guidelines)

• If they are deemed as able to use the pump (Level 2 self-administration), recommence the CSII at the normal Basal rate. Continue intravenous insulin infusion until the meal bolus has been given. Do not recommence CSII at bedtime

Estimate Total Daily Dose (TDD) of insulin

This estimate is based on several factors, including the person with diabetes’ sensitivity to

insulin, degree of glycaemic control, insulin resistance, weight, and age. The TDD can be

calculated by multiplying the individual’s weight (in kg) by 0.5 to 0.75 units.

Use 0.75 units/kg for those thought to be more insulin resistant i.e. teenagers, obese patients.

Example: a 72 kg person would require approximately 72 x 0.5 units or 36 units in 24

Hours

Calculating a Basal Bolus (QDS)

Regimen:

Give 50% of total dose with the evening meal in the form of once daily long-acting insulin (degludec or glargine) and divide remaining dose equally between pre-breakfast, pre-lunch and pre-evening meal.

Administer the first dose of fast acting subcutaneous insulin preferably prior to breakfast or

lunch. Only administer the first dose before the evening meal if appropriate monitoring can

be guaranteed. Do not convert to a subcutaneous regimen at bedtime.

In those new to insulin therapy, dose requirements may decrease within a few days because

the insulin resistance associated with DKA resolves. Close supervision from the diabetes

specialist team is required.