Paediatric Diabetic Ketoacidosis

Diabetic ketoacidosis in a child, defined by hyperglycaemia with ketosis and metabolic acidosis. It is the commonest cause of death in children with type 1 diabetes, and the great majority of that mortality is from cerebral oedema rather than from the metabolic derangement itself. Every element of the fluid and insulin regimen is designed around that single risk.

Diagnostic criteria

• Blood glucose above 11.1 mmol/L, or known diabetes. Euglycaemic ketoacidosis occurs in the fasting child, in pregnancy, on sodium glucose cotransporter 2 inhibitors and where insulin has been given before arrival, and a normal glucose does not exclude the diagnosis.

• pH below 7.3 or bicarbonate below 15 mmol/L.

• Ketones in urine at 2 plus or greater, or serum ketones at 3 mmol/L or greater.

Severity classification, which determines the intensity of monitoring and the location of care

• Mild: pH 7.2 to below 7.3, bicarbonate 10 to below 15 mmol/L.

• Moderate: pH 7.1 to below 7.2, bicarbonate 5 to below 10 mmol/L.

• Severe: pH below 7.1, bicarbonate below 5 mmol/L.

Severe ketoacidosis, and any child under 2 years or newly diagnosed, carries a substantially higher risk of cerebral oedema and warrants high dependency or intensive care level monitoring.

Why children differ from adults

• Cerebral oedema occurs in 0.5 to 1 percent of paediatric episodes with a mortality of 20 to 25 percent and permanent neurological morbidity in a further 10 to 25 percent of survivors. It is essentially confined to children and is the reason paediatric protocols correct deficits more slowly, avoid fluid boluses in the non shocked child, delay insulin, and use lower insulin infusion rates than adult protocols.

• Children present in ketoacidosis at first diagnosis far more often than adults, particularly the very young in whom polyuria is mistaken for a urinary infection and enuresis for behavioural regression, and in whom Kussmaul breathing is diagnosed as pneumonia or asthma. Delayed diagnosis is the single commonest reason a child arrives severely acidotic.

• Fluid deficits are proportionally larger and are less well tolerated in either direction.

Pathophysiology of cerebral oedema

Not fully established. The traditional explanation of osmotic shift with rapid fluid correction is incomplete, since oedema occurs before treatment starts in some children.

Current understanding implicates cerebral hypoperfusion and reperfusion injury with vasogenic oedema, driven by dehydration and acidosis, together with an osmotic component. Recognised risk factors are young age, new diagnosis, a long duration of symptoms, severe acidosis, a high urea, marked hypocapnia, bicarbonate administration and a failure of the sodium to rise as the glucose falls.

Fluid deficits

Assess and classify dehydration, recognising that clinical assessment is unreliable and tends to overestimate. Use 5 percent for mild, 7 percent for moderate and 10 percent for severe as working figures, and cap the assumed deficit at 10 percent regardless of appearance, since assuming more leads to over infusion.

History

Polyuria, polydipsia, enuresis in a previously dry child, weight loss, nausea, vomiting, abdominal pain and reduced level of consciousness. Abdominal pain is common and correlates with the severity of acidosis, but it also occurs with a surgical precipitant, so pain that persists after the acidosis resolves requires surgical assessment.

Clinical signs

Dehydration, deep sighing Kussmaul respiration, a fruity smelling breath from acetone, and lethargy or drowsiness.

Assessment of shock, which changes the fluid approach entirely

• AVPU below A, that is not alert.
• Weak or absent peripheral pulses.
• Prolonged capillary refill time.
• Cold extremities.

True shock is uncommon in paediatric ketoacidosis and its presence should also prompt a search for sepsis or another cause, since children in ketoacidosis are usually dehydrated but perfused.

Assessment of dehydration

Reduced skin turgor, dry mucous membranes, sunken eyes, absent tears, tachycardia, delayed capillary refill, reduced urine output and weight loss against a recent recorded weight, which is the most objective measure available.

Precipitants to identify in every child

New diagnosis; insulin omission, which in adolescents is frequently deliberate and is associated with eating disorder, needle phobia, family conflict and depression; pump failure or set occlusion, which produces ketoacidosis rapidly since there is no long acting insulin depot; intercurrent infection; and gastroenteritis.

• Capillary blood glucose and blood ketones at the bedside.
• Venous blood gas for pH, bicarbonate, potassium, sodium and lactate. Venous sampling is adequate and avoids repeated arterial puncture in a child.
• Urea, electrolytes, creatinine, calculated osmolality and corrected sodium.
• Full blood count, recognising that leucocytosis occurs with ketoacidosis alone and does not by itself indicate infection.
• Blood cultures, urinalysis and culture, and chest radiography where infection is suspected.
• Electrocardiogram, both for the effects of potassium derangement and for continuous monitoring of T wave changes, which give a real time indication of potassium status when the laboratory is slow.
• Weight, measured rather than estimated where possible, since all fluid and insulin calculations depend on it.
• HbA1c, which distinguishes a new diagnosis from established poorly controlled disease.
• Coeliac and thyroid screening at diagnosis or once stable.
• Do not delay treatment for investigations.

Senior review is a required element. No child with ketoacidosis should be managed without discussion with a senior paediatrician, and severe cases require early involvement of intensive care.

The order is fixed: assess for shock, give fluid, then insulin after the first hour, with potassium in the fluid from the outset.

Pathway by presentation

Shock

• Airway, with a nasogastric tube in the child with reduced consciousness or persistent vomiting, given gastric stasis and aspiration risk.

• Breathing: give oxygen by non rebreathing mask.

• Circulation: 0.9 percent sodium chloride 10 mL/kg over 30 minutes.

• Repeat the bolus if shock persists, but do not give more than 40 mL/kg within 4 hours. Exceeding this is associated with cerebral oedema, and a child requiring more than this has another problem, usually sepsis or haemorrhage, which must be identified.

• Once shock is corrected, move to the deficit replacement calculation.

Dehydration above 5 percent, not in shock, with acidotic breathing or vomiting

• Resuscitation fluid of 0.9 percent sodium chloride 10 mL/kg over 1 hour. Note the slower rate than in shock: this is deficit replacement, not resuscitation, and giving it as a rapid bolus in a child who is not shocked is a recognised contributor to cerebral oedema.

• Keep nil by mouth.

• Calculate the remaining fluid requirement to be given over 48 hours.

Minimal dehydration, tolerating oral fluids

• Start subcutaneous regular insulin at 0.2 units/kg per dose every 4 hours.

• Oral rehydration.

• Reassess at 6 hours. If there is no improvement, move to the intravenous pathway with fluid calculated over 48 hours and an insulin infusion.

Fluid calculation

• Calculate maintenance plus the estimated deficit, and deliver the total evenly over 48 hours rather than over 24. Slow, even correction is the central principle of paediatric ketoacidosis management.

• Cap the assumed deficit at 10 percent.

• Do not subtract the resuscitation fluid given for shock from the deficit calculation, but do subtract any fluid given for rehydration in the non shocked child.

• Use 0.9 percent sodium chloride with added potassium as the initial fluid.

• Keep the child nil by mouth initially. Oral fluids are introduced only when there is clear clinical improvement, and any oral intake is subtracted from the intravenous rate.

• Include ongoing losses only where they are substantial.

• Do not give additional boluses once shock is corrected.

After the first hour of fluids

Insulin

• Start regular insulin by continuous intravenous infusion, 1 hour after fluids have been started. Delaying insulin for the first hour allows fluid alone to lower the glucose and reduces the rate of osmolar change, which reduces cerebral oedema risk. Under 5 years: 0.03 to 0.05 units/kg/hour. Over 5 years: 0.05 to 0.1 units/kg/hour.

• These rates are lower than the adult 0.1 units/kg/hour, deliberately, since a faster fall in glucose and osmolality is associated with cerebral oedema in children.

• Do not give an insulin bolus. Bolus insulin at the start increases the risk of cerebral oedema and of hypokalaemia and confers no benefit.

• Where an infusion pump is unavailable, dilute 50 units of regular insulin in 50 mL of normal saline so that 1 unit equals 1 mL, and deliver by a controlled method with meticulous rate checking.

• Prime the giving set with the insulin solution before connecting, since insulin adsorbs to plastic and the first millilitres deliver less than intended.

• Continue the child's usual long acting basal insulin where they are already established on it, which smooths the eventual transition.

Potassium

• Check potassium and add 20 mmol of potassium per 500 mL of fluid, which is equivalent to 40 mmol per litre, unless the child is anuric or has acute kidney injury.

• Total body potassium is profoundly depleted despite a normal or raised serum value at presentation, because acidosis and insulin deficiency shift potassium out of cells. Insulin and fluid drive it back in and the serum level falls sharply. Hypokalaemia is a preventable cause of death in this condition.

• If the potassium is below 3.0 mmol/L, hold or delay insulin and replace potassium first, with continuous cardiac monitoring.

• If the child is anuric, withhold potassium until urine is passed and recheck frequently.

• Monitor the electrocardiogram for T wave changes as a continuous surrogate.

Ongoing management and critical observations

• Hourly fluid input and output. Weigh nappies in infants.

• Hourly blood glucose.

• Neurological status at least hourly, and more frequently in the high risk child. This is the observation that detects cerebral oedema and it must be performed by someone who will recognise a change.

• Electrocardiographic monitoring for T wave changes.

• Electrolytes and blood gas every 2 to 4 hours after starting intravenous fluid therapy.

• Hourly ketones where available.

• Monitor the corrected sodium, which should rise as the glucose falls. A sodium that falls or fails to rise during treatment indicates excess free water and is a warning sign for cerebral oedema.

Acidosis improving

• If the blood glucose falls to 14 to 17 mmol/L, or if the blood glucose falls by more than 5 mmol/L per hour, change to 5 percent dextrose in 0.9 percent sodium chloride.

• To make 5 percent dextrose in 0.9 percent saline, add 50 mL of 50 percent dextrose to 450 mL of 0.9 percent saline.

• Do not reduce or stop the insulin at this point except at the lower end of the dosing range. Insulin is required to clear ketones and stopping it causes the ketoacidosis to persist or rebound. Add dextrose to allow the insulin to continue rather than reducing insulin to allow the glucose to rise.

• Where the glucose continues to fall despite 5 percent dextrose, increase to 10 percent dextrose rather than stopping the insulin.

Resolution of ketoacidosis

Defined by all of:

• Clinically well, drinking well and tolerating food.

• pH above 7.3.

• Serum ketones below 1.0 mmol/L.

Transition to subcutaneous insulin

• Calculate the total daily dose of insulin: Prepubertal: 0.5 to 1 unit/kg/day. Pubertal: 1 to 2 units/kg/day.

• Give 30 percent of the total daily dose as long acting insulin such as glargine 24 hourly, or as intermediate acting insulin 12 hourly.

• Give 70 percent as regular or short acting insulin divided into 3 equal doses before breakfast, lunch and dinner.

• If transitioning using regular or short acting insulin, give the calculated dose 30 minutes before a meal and stop the intravenous insulin infusion 30 minutes afterwards.

• If transitioning using long acting or intermediate acting insulin, give the calculated dose and stop the intravenous insulin infusion 2 hours afterwards.

• Monitor and record glucose 30 minutes before and 2 hours after breakfast, lunch and dinner.

The overlap is essential in every case. Intravenous insulin has a half life of a few minutes, so stopping it before the subcutaneous dose is absorbed produces immediate rebound ketosis. This overlap is the single most frequently omitted step in the transition and is a common cause of a second episode within the same admission.

The dose is adjusted according to blood glucose readings over subsequent days.

No improvement after 6 hours

Re evaluate systematically rather than simply increasing the insulin:

• Recheck the intravenous fluid calculation, since arithmetic errors are common and consequential.

• Check ketones, since a falling glucose with persisting ketones means the insulin rate is too low.

• Check the insulin delivery system, dose and storage. Confirm the infusion is actually running, that the line is connected and not disconnected or occluded, that the concentration is correct, and that the insulin has not been stored improperly and lost potency.

• Assess the need for additional resuscitation.

• Consider sepsis, which both precipitates and perpetuates ketoacidosis. If febrile, start antibiotics.

Neurological deterioration

Warning signs, which must be known by everyone caring for the child:

• Headache, which is often the first symptom and which is easily dismissed.

• Irritability.

• Incontinence in a previously continent child.

• Slowing heart rate, which is a particularly important sign since bradycardia in a dehydrated child is not expected and indicates rising intracranial pressure.

• Reduced consciousness level.

• Specific neurological signs including cranial nerve palsies, abnormal pupillary responses, papilloedema, posturing and abnormal respiratory pattern.

Cerebral oedema typically develops 4 to 12 hours after treatment begins, which is precisely when the child appears to be improving biochemically and when vigilance falls.

On recognising deterioration:

• Exclude hypoglycaemia by checking the blood glucose, since a glucose below 4 mmol/L produces identical symptoms and is instantly correctable.

• If not hypoglycaemia, assume cerebral oedema and treat immediately.

Management of cerebral oedema

• Call senior staff immediately.

• Prop the head of the bed to 30 degrees.

• Give oxygen.

• Give mannitol 0.5 to 1 g/kg, to a maximum of 200 g, intravenously over 15 minutes; or 3 percent hypertonic saline 2.5 to 5 mL/kg over 15 minutes.

• Restrict intravenous fluids to 70 percent of the total daily fluid requirement.

• Move to intensive care or paediatric intensive care.

• Obtain cranial imaging only once the child is stabilised. Treatment precedes imaging, and delaying mannitol for a scan is a serious error.

• Repeat mannitol after 2 hours if there is no response.

• Intubate and ventilate if the conscious level does not permit airway protection, avoiding aggressive hyperventilation, which worsens cerebral ischaemia.

Additional points

• Do not correct the acidosis with bicarbonate. It produces paradoxical central nervous system acidosis, worsens hypokalaemia, delays ketone clearance and is independently associated with cerebral oedema in children. There is no clinical situation in paediatric ketoacidosis in which it is required.

• If febrile, start antibiotics after cultures.

• Thromboprophylaxis is considered in adolescents and in children with central venous access, since ketoacidosis is prothrombotic.

• Nasogastric decompression in the obtunded or vomiting child.

• Involve the diabetes specialist nurse and the paediatric diabetes team from admission, not at discharge.

Before discharge

• Establish the precipitant. In an established patient this is most often insulin omission, and the reason for the omission must be explored honestly and without blame, since fear, cost, needle phobia, eating disorder, family conflict and depression are all common and none of them is solved by repeating the education alone.

• Structured education or re education, including sick day rules, ketone testing and when to seek help.

• Provide ketone testing strips to every child with type 1 diabetes and teach their use. A child who tests ketones at home when unwell and acts on the result usually does not arrive in ketoacidosis.

• Written sick day rules: never stop insulin, test glucose and ketones more frequently, maintain fluid and carbohydrate intake, give additional rapid acting insulin according to ketone level, and seek help for persistent vomiting, ketones that do not clear, drowsiness or abdominal pain.

• Psychological assessment for recurrent presenters, in whom the underlying issue is almost never a knowledge deficit.

• Screen for coeliac disease and thyroid disease.

• Diabetes team follow up within days, with school liaison and a written care plan.