CASE

A 5 yo boy is brought to the Emergency Department by his mother. She tells you that he is sleepy and doesn't look well. He has been drinking a lot of water and passing a lot of urine over the past two days.
He has no past history. Immunisations are up to date.
Vitals are: GCS 14-15, T 37.3, PR 117, RR 25, Sats 98% RA, BP 85/52
A bedside BSL is 27mmol/L

Your working diagnosis is newly diagnosed diabetes and potential Diabetic Ketoacidosis (DKA)

In terms of DKA, which of the following is true?
(a) Although a serious disease, it is not associated with mortality in children > 3yo
(b) The mainstay of treatment is rapid intravenous fluid delivery, usually 20mL/kg of Normal Saline and repeat
(c) The most important part of the treatment is insulin delivery, in the form of a bolus and then an immediate infusion
(d) Cerebral oedema is a feared complication, although there is evidence that subclinical oedema is present in some, at presentation
(e) Potassium supplementation is not required in children

answer

The answer is (d)
Mortality in DKA approaches 1% and is due to cerebral oedema. 

What Predisposes patients to Cerebral Oedema?

1. < 5yo
2. New Onset Diabetes
3. Late presentation
4. Severe dehydration
5. Severe Disease pH <7.1
6. Large fluid load given
7. Early initiation of insulin, or insulin bolus
8. Low HCO3
9. Reduced levels of consciousness

Most of the studies are small or retrospective or both. However the rate of development of cerebral oedema has not changed, so we need to potentially change the way we approach patients.
In a case-controlled UK study, those children receiving insulin in the first hour and large volumes of fluid in the first four hours, had an increased risk of cerebral oedema. 
Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006;49:2002-9. 

When does Cerebral Oedema occur and how does it present?

There is a rapid onset of progressive neurological deterioration.
The most common period is 4-12 hours post commencement of treatment.
The symptoms and signs include:

answer

• fluctuating level of consciousness
• headache
• vomiting
• bradycardia
• hypertension
• cranial nerve palsy
• abnormal posturing

How to Diagnose DKA: ​How do we classify DKA?

In order to diagnose DKA there must be:
BSL > 11mmol/L  PLUS
Venous pH <7.3  AND/OR HCO3 < 15mmol/L
​There must also be ketonuria/ketonaemia

We can use the pH or the HCO3 to classify the severity of DKA
HOW DO WE CLASSIFY MILD DKA?

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pH < 7.3 OR HCO3 < 15 mmol/L

HOW DO WE CLASSIFY MODERATE DKA?

ANSWER

PH < 7.2 OR HCO3 < 10MMOL/L

HOW DO WE CLASSIFY SEVERE DKA?

ANSWER

pH < 7.1 or HCO3 < 5mmol/L

Initial Resuscitation

One of our greatest concerns in the unwell child is the presence of shock. This is recognised in an unwell child, with very poor perfusion i.e.., increased capillary refill time, mottled extremities and thready rapid pulse. You can tolerate a systolic blood pressure of (70 + 2 x age)mmHg
Early, rapid and appropriate resuscitation is the key.
Haemodynamic compromise is not that common in children with DKA.
FLUID RESUSCITATION: WHAT AND HOW MUCH?

ANSWER

In a resuscitation situation give normal saline. My recommendation is 5-10ml/kg of normal saline. You can repeat this. i.e. start a little slower and then increase. Do not give more than 20mL/kg. If you are needing large volumes, think of sepsis as a potential. The two can occur together. In a child with early diabetes, sepsis can result in DKA.
​If larger volumes needed, speak to your consultant.

How much fluid to give?

In DKA in children we can take two approaches:
(i)  Estimate the fluid losses by calculating the weight loss.
​(ii) Estimate clinically the level of dehydration

There are potential issues with both of these. Firstly there may not be a previous and recent weight on the child and you will have to estimate. There may also be a greater weight loss due to insulin deficiency driven catabolism, resulting in an overestimate of fluid loss.
​BEWARE: OVERSTIMATION OF FLUID DEFICIT AND REPID FLUID RESUSCITATION PREDISPOSE TO CEREBRAL OEDEMA.

If you were to clinically assess dehydration, what would be the features of mild, moderate and severe dehydration and what percentage would you ascribe to each?

• MILD
• MODERATE
• SEVERE

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The child is normally well and there may be features that are just clinically detectable: MAX 3%

There will be dry mucous membranes, and reduced skin turgor MAX 5%

Dry mucous membranes, reduced skin turgor, poor capillary refill, sunken eyes, cold peripheries MAX 8%

How should the fluid be given?

Patients with mild disease may tolerate oral fluids. If a child is vomiting, IV fluids must be considered, however a single dose of Ondansetron, may facilitate oral rehydration.

In Moderate to Severe Disease the DEFICIT should be replaced over 48 hours.

In this patient you have assumed  5%, what is the deficit?
(a) 750mL
(b) 1000mL
(c) 1250mL
(d) 1500mL
​(e) 2000mL

answer

The answer is (b).
Calculate as follows. The weight is expected to be 20kg. 5% deficit is 5/100 x 20000(mL) = 1000mL
​Give this over 48 hours.

We can't just give the deficit over 48 hours, we must also give the maintenance over that 48 hours.
The maintenance dose per 24 hours for this 5 yo boy is:
(a)  1200mL
(b)  1500mL
(c)  1750mL
(d) 2000mL
(e) 3000mL

answer

The answer is (b)
Up to 10 kg:  100ml/day x weight up to 10kg i.e., 100x 10 = 1000ml
10-20kg:          50ml/day x weight above 10kg and below 20kg = 50 x 10  = 500ml
>20kg                20ml /day x weight above 20 kg   = 0

Total is 1500ml/day or 3000ml over 48 hours.

The total required by this child will be the deficit (1500ml) + the maintenance (3000ml) i.e. 4500ml over 48 hours.

But Wait! Two More things will determine how fast to give the fluid!

The Sodium and the Osmolality
Correct the Na for hyperglycaemia
Na = measured Na + [ 2x (glucose -5.5)]/5.5
This child's glucose was 27mmol/L
His Na was 132mmol/L
Corrected Na is 132 + (2 x (27-5.5))/5.5 = 140mmol/L

If the Na >150mmol/L regardless of osmolality, dehydration correction should occur over 72 hours

Calculating Osmolality = 2 x (Na + K) + Gluc. If > 310 = Hyperosmolality

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PLEASE NOTE: Be sure to discuss with the Endocrine/Paediatric Team and your Emergency Specialist if any of the following exist:

• Neonatal DKA
• Hypernatraemia
• Hyperosmolality
• Hyperkalaemia
• Anuria

In all others proceed as below.

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What type of Fluid?

answer

0.9% Sodium Chloride is the fluid to give, as hypotonic fluids may be associated with raised intracranial pressure.

What about Potassium?

We know that potassium levels at presentation are not an accurate guide to the total body potassium stores. Once insulin commences and acidosis is corrected, the potassium levels will drop.
​0.9% NaCl + 40mmol of KCL is an appropriate fluid to start with. Do not add K if the patient is hyperkalaemic or anuric.
Maximum potassium replacement should be 0.3 mmol/kg/hr.

What about INSULIN?

Insulin decreases the blood sugar level and suppresses lipolysis and ketogenesis. It is required in moderate and severe DKA. Fluid alone may be enough in mild cases.

​In mild cases:short acting subcutaneous insulin (Actrapid) 0.1-0.2 U/kg every 4-6 hours In very young children i.e. < 5yo give 0.05U/kg

When to start insulin and how much to give in moderate to severe cases.

answer

NEVER GIVE A BOLUS DOSE!
Start the infusion one- two hours after fluid therapy.
Use an infusion of INSULIN at 0.1Units/kg/hr
Use ideal body weight.
​If the patient were known to have diabetes and had an insulin pump. This should be stopped.

Working out when to add glucose

Insulin should be continued until there is resolution of ketoacidosis. This is determined by:

1. Resolution of a raised anion gap. ie., the anion gap [Na -(Cl+HCO3)] should equal 12
2. pH >7.3 and HCO3 >15mmol/L

At this time go to subcutaneous insulin- start this one hour before stopping infusion.

When the Blood Sugar Level fall to <15mmol/L: ADD GLUCOSE and continue INSULIN at the same rate.
0.9%NaCl + 5% glucose + 40mmol KCL

What would you do if hypoglycaemia (BSL < 4mmol/L)? 2 correct answers:
(a) Stop the insulin infusion completely
(b) Stop the insulin infusion for up to an hour
(c) Give 2mL/kg of 10% Dextrose over 3 minutes
​(d) Give 5mL/kg of 10% Dextrose over 10 minutes

answer

Replace some of the glucose with 2ml/kg of 10% Dextrose over 3 minutes and temporarily stop the insulin infusion for about an hour.

What about Sodium Bicarbonate?

(a) NaHCO3 is a safe drug to use in acidosis, especially if pH < 7.3
(b) Use 50ml of NaHCO3 in all acidotic DKA with pH < 7.3
(c) Use NaHCO3 when monitoring potassium levels in DKA
(d) NaHCO3 is contraindicated when the BSL is > 15mmol/l
​(e) NaHCO3 is contraindicated in DKA

answer

The answer is (e). There is an association between bicarbonate and the increased risk of cerebral oedema.

What would you do if you recognised Cerebral Oedema?

answer

Get help from senior specialist early.
Nurse, head up at 20-30 degrees
Reduce Fluid administration
Give high flow oxygen
Give mannitol 0.5-1g/kg over 20 minutes OR
Hypertonic Saline 3% 3-5ml/kg over 15 minutes
​If intubated do not hyperventilate. Aim for Co2 of 35-40mmHg. Hyperventilated has been associated with cerebral oedema.