Diabetic emergencies and glucose control

Definition / Overview

Diabetic Ketoacidosis (DKA)

DKA is a life-threatening metabolic emergency defined by the biochemical triad of:

• Hyperglycaemia: blood glucose $> 11\,\text{mmol/L}$
• Ketonaemia/ketonuria: blood ketones $\geq 3\,\text{mmol/L}$ or urine ketones $\geq 2+$
• Acidosis: venous $\text{pH} < 7.3$ or bicarbonate $< 15\,\text{mmol/L}$

Severity classification:

In children, DKA accounts for approximately 30-40% of new Type 1 diabetes mellitus (T1DM) presentations. Mortality is low at experienced centres but cerebral oedema remains the dominant cause of DKA-related death and disability in paediatric patients, particularly those under 5 years.

Hyperglycaemia without DKA

Clinically significant hyperglycaemia in the PICU also arises in the context of critical illness stress response, parenteral nutrition, corticosteroid therapy, sepsis, and post-cardiac surgery. Targets and management differ from DKA.

Hypoglycaemia

Clinically significant hypoglycaemia is defined as blood glucose $< 3.0\,\text{mmol/L}$. Severe hypoglycaemia implies cognitive impairment or seizure requiring intervention. Neonates and infants are at greatest risk due to limited glycogen stores, high glucose utilisation rates, and immature counter-regulatory responses.

Pathophysiology

DKA

Absolute or relative insulin deficiency triggers:

1. Uncontrolled hepatic glucose output via gluconeogenesis and glycogenolysis, causing hyperglycaemia
2. Reduced peripheral glucose uptake in muscle and adipose tissue
3. Unopposed lipolysis generating free fatty acids, which undergo hepatic beta-oxidation to ketone bodies ($\beta$-hydroxybutyrate, acetoacetate)
4. Osmotic diuresis from glycosuria leading to dehydration, sodium, potassium, phosphate, and magnesium losses
5. High anion gap metabolic acidosis from ketoacid accumulation

Total body potassium is depleted despite serum $\text{K}^+$ that may appear normal or elevated on presentation (due to transcellular shift driven by acidosis and hyperosmolality). This has critical implications for insulin administration.

Cerebral Oedema in DKA

The precise mechanism remains incompletely understood. Contributing factors include:

• Rapid shifts in osmolality with rehydration
• Disruption of the blood-brain barrier
• Neuroinflammation from the underlying acidosis and hypoperfusion
• Vasogenic and cytotoxic components

Children under 5 years and those with severe biochemical derangement on presentation carry the highest cerebral oedema risk. Overly rapid fluid administration and excessive free water delivery are associated risk factors in the literature.

Hypoglycaemia Counter-Regulation

Normal glucose defence involves sequenced release of glucagon, adrenaline, cortisol, and growth hormone. Children with recurrent hypoglycaemia (particularly those with T1DM) may develop hypoglycaemic unawareness from impaired adrenergic response. Neonates have immature glucagon responses and reduced hepatic glycogen stores, exacerbating vulnerability.

Clinical Features and Diagnosis

DKA

Early/Classic:

• Polyuria, polydipsia, weight loss (days to weeks pre-presentation in new-onset T1DM)
• Nausea, vomiting, and abdominal pain
• Kussmaul breathing (deep, rapid, sighing respirations compensating for metabolic acidosis)
• Ketotic (fruity/acetone) breath
• Dehydration: tachycardia, prolonged capillary refill, dry mucous membranes

Severe/Impending Cerebral Oedema:

• Headache, irritability, drowsiness
• Bradycardia and rising blood pressure (Cushing's triad)
• Pupillary changes, focal neurology
• Glasgow Coma Scale (GCS) $\leq 13$ or falling

PICU admission indications:

• Severe DKA (pH $< 7.1$, bicarbonate $< 5\,\text{mmol/L}$)
• Depressed or declining conscious state
• Age $< 2$ years
• Haemodynamic instability
• Dysrhythmia
• Failure of initial management

Hyperglycaemia (Critical Illness)

• Blood glucose $> 10\,\text{mmol/L}$ on two consecutive measurements in the PICU setting
• May be asymptomatic; detected on routine monitoring
• Associated with increased infection risk, impaired wound healing, and worse outcomes in PICU

Hypoglycaemia

• Autonomic symptoms (sweating, pallor, tachycardia, tremor) in older children
• Neuroglycopenic symptoms (confusion, seizures, coma) at lower glucose levels
• Neonates may present only with jitteriness, apnoea, poor feeding, or seizure
• Measure whole-blood glucose with point-of-care testing; confirm laboratory glucose if in doubt

Investigation and Monitoring

DKA

At presentation:

Ongoing monitoring (PICU):

• Hourly BGL and 2-hourly blood ketones until resolution
• 2-hourly electrolytes initially, then 4-hourly once stable
• Continuous cardiac monitoring for dysrhythmia
• Strict fluid balance including hourly urine output
• Neurological observations hourly; GCS documented

Management

Step 1: Resuscitation

Haemodynamically compromised child (shock, impaired perfusion): give isotonic saline (0.9% NaCl) $10\,\text{mL/kg}$ IV bolus over 10-15 minutes; repeat up to $20\,\text{mL/kg}$ total if poor perfusion persists, then reassess. Avoid excessive fluid resuscitation beyond that required to restore perfusion.

Airway: if GCS $\leq 8$ or deteriorating, secure airway with a cuffed endotracheal tube (size $= \text{age}/4 + 3.5$ for cuffed ETT). Maintain $\text{pCO}_2$ at a level appropriate to the degree of acidosis: do not allow inadvertent hypercarbia in an intubated child with DKA, as this worsens acidosis.

Nil by mouth until conscious and clinically improving.

Step 2: Rehydration

Rehydration should be gradual over 24-48 hours. The standard approach uses:

$$\text{Total fluid} = \text{Deficit} + \text{Maintenance (Holliday-Segar)}$$

• Estimate dehydration: mild DKA $\approx 5\%$; severe DKA $\approx 8-10\%$
• Deficit (mL) $= \%\,\text{dehydration} \times \text{weight (kg)} \times 10$
• Subtract resuscitation fluid already given from calculated deficit
• Spread remaining deficit + maintenance evenly over 48 hours for moderate/severe DKA (or 24 hours for mild DKA at some centres)

Fluid choice: 0.9% NaCl is the standard first-line rehydration fluid. Switch to 0.45% NaCl with glucose once BGL falls to $\approx 14\,\text{mmol/L}$ and add glucose to the infusion to prevent hypoglycaemia while insulin continues.

Potassium: add KCl to fluids once urine output is confirmed and serum $\text{K}^+ < 5.5\,\text{mmol/L}$. Typical starting rate: $\text{K}^+ 40\,\text{mmol/L}$ in IV fluid. Do not start insulin if $\text{K}^+ < 3.5\,\text{mmol/L}$ without first correcting hypokalaemia.

Sodium bicarbonate: not recommended routinely. Use only in life-threatening hyperkalaemia with ECG changes or in pH $< 6.9$ with cardiovascular compromise, with extreme caution.

Phosphate: routine replacement is not supported. Replace only if symptomatic (e.g. respiratory muscle weakness, haemolytic anaemia).

Step 3: Insulin

• Do not start insulin for at least 1-2 hours after commencing rehydration (reduces cerebral oedema risk, allows time for initial volume and potassium management)
• Standard rate: regular (short-acting) insulin $0.05-0.1\,\text{units/kg/hour}$ IV infusion
• Lower rate ($0.05\,\text{units/kg/hr}$) is preferred in young children and those with severe DKA
• Target BGL fall of $2-5\,\text{mmol/L/hour}$; if falling faster, increase glucose concentration in IV fluid rather than reducing insulin rate until ketosis resolves
• Continue insulin infusion until ketones cleared (blood ketones $< 0.6\,\text{mmol/L}$, pH $> 7.3$, bicarbonate $> 15\,\text{mmol/L}$)
• Transition to subcutaneous insulin when eating and biochemically resolved; overlap by 30-60 minutes with long-acting insulin before stopping infusion

Step 4: Monitoring and Treatment of Cerebral Oedema

Risk factors for cerebral oedema:

• Age $< 5$ years
• New-onset T1DM
• Prolonged or severe acidosis at presentation
• Rapid fall in serum osmolality during treatment
• Elevated urea at presentation (marker of severe dehydration)
• Administration of bicarbonate

Early warning signs:

• Headache, behavioural change, GCS deterioration
• Bradycardia, hypertension, irregular respirations

Management of confirmed or suspected cerebral oedema:

1. Immediately reduce IV fluid rate by 30-50%
2. Give hypertonic saline 3% $2.5-5\,\text{mL/kg}$ IV over 10-15 minutes; or mannitol $0.5-1\,\text{g/kg}$ IV over 20 minutes if hypertonic saline unavailable
3. Elevate head of bed 30°
4. Prepare for intubation if GCS is falling or airway is at risk; target normocapnia (not hyperventilation as a sustained strategy)
5. Urgent CT brain once stabilised to exclude other causes (haemorrhage, thrombosis)
6. Notify PICU consultant and neurosurgery early

Management of Hyperglycaemia in the PICU (Non-DKA)

• Avoid tight glycaemic control in critically ill children; evidence from the SPECS and CHiP trials demonstrated harm from intensive insulin therapy targeting normoglycaemia
• Current practice: target BGL $6-10\,\text{mmol/L}$ in most PICU patients; accept $\leq 12\,\text{mmol/L}$ in the initial resuscitation phase
• Insulin infusion when BGL persistently $> 10\,\text{mmol/L}$ on two readings; begin at $0.02-0.05\,\text{units/kg/hour}$ and titrate with hourly BGLs
• Ensure adequate glucose delivery is not interrupted while on insulin infusion; hypoglycaemia is the primary harm of treatment
• Neonates and infants: higher risk of hypoglycaemia; use lower infusion rates and more frequent monitoring; consider reducing dextrose concentration of feeds/TPN first before starting insulin

Management of Hypoglycaemia

Conscious child able to take orally

• Fast-acting glucose $0.3\,\text{g/kg}$ orally (e.g. glucose gel, juice, glucose tablets)
• Recheck BGL in 15 minutes; repeat if still $< 3.5\,\text{mmol/L}$
• Follow with complex carbohydrate once BGL normalised

Impaired consciousness or unable to swallow

1. IV access available: $10\%$ dextrose $2\,\text{mL/kg}$ (= $0.2\,\text{g/kg}$) IV bolus over 3-5 minutes; recheck in 15 minutes; commence $10\%$ dextrose infusion at maintenance rate
2. No IV access: glucagon IM/SC $0.5\,\text{mg}$ if $<25\,\text{kg}$; $1\,\text{mg}$ if $\geq 25\,\text{kg}$; ineffective in hepatic failure or glycogen-depleted states
3. Neonates: $10\%$ dextrose $2\,\text{mL/kg}$ IV; avoid 50% dextrose (hyperosmolar, risk of central pontine myelinolysis and venous injury)
4. Once conscious and tolerating orals, transition to oral feeds/nasogastric glucose supplementation
5. Investigate and treat the underlying cause (hyperinsulinism, metabolic disorder, adrenal insufficiency, sepsis)

Recurrent or persistent hypoglycaemia: consider inborn errors of metabolism, congenital hyperinsulinism, growth hormone or cortisol deficiency. Critical sample (insulin, C-peptide, cortisol, growth hormone, fatty acid profile, organic acids, amino acids) must be taken during or immediately after a hypoglycaemic episode.

Complications and Special Considerations

Hypokalaemia During DKA Treatment

Total body potassium is always depleted in DKA. As insulin drives glucose and potassium intracellularly, uncorrected hypokalaemia can cause fatal dysrhythmia. Potassium $\text{K}^+$ should be checked before and 2-hourly during insulin infusion. Replace aggressively if $< 3.5\,\text{mmol/L}$.

Hyperosmolar Hyperglycaemic State (HHS) in Children

Increasingly recognised in adolescents with Type 2 DM or atypical diabetes. Characterised by extreme hyperglycaemia (often $> 33\,\text{mmol/L}$), hyperosmolality ($> 320\,\text{mOsm/kg}$), and severe dehydration without significant ketonaemia. Rehydration must occur more slowly than DKA (over 48-72 hours) to avoid osmotic demyelination and cerebral oedema. Venous thromboembolism risk is substantial; anticoagulation with low-molecular-weight heparin should be considered.

Concurrent Infection

Infection is the most common precipitant of DKA in children with established T1DM. Leukocytosis is non-specific in DKA. Targeted investigation and empiric antimicrobials guided by clinical findings.

New-Onset T1DM

DKA may be the first presentation. Coordinate early with the paediatric diabetes team. Education for the family regarding sick-day management, insulin administration, and hypoglycaemia recognition should begin during the admission.

Transition to Ward and Outpatient Care

• Structured transition to subcutaneous insulin must be supervised by the diabetes team before PICU discharge
• Document peak neurological status and any concerns regarding cerebral oedema risk
• Arrange diabetes educator, dietitian, and psychology input before discharge
• Australian tertiary centres use standardised DKA order sets aligned with national consensus guidance; local protocols should be followed where they exist

PICU Viva Framing: Key Points

• Cerebral oedema is the leading cause of DKA-related death in children; early recognition and immediate treatment with hypertonic saline are life-saving
• Potassium management is a higher priority than insulin initiation; never start insulin in a hypokalaemic child without correction
• Fluid rate, not content, is the dominant modifiable cerebral oedema risk factor; restrict to calculated deficit + maintenance over 48 hours
• Tight glycaemic control harms critically ill children (unlike adults); target a moderate range and prioritise prevention of hypoglycaemia
• Hypoglycaemia investigation requires a critical sample taken contemporaneously with the low glucose; do not delay or miss this opportunity
• HHS in the adolescent with T2DM or atypical diabetes requires very slow rehydration and VTE prophylaxis