Diabetic ketoacidosis (DKA)

Contents

Diagnostic Criteria

The Joint British Diabetes Societies (JBDS) 2023 criteria for DKA:

Feature Threshold
Blood glucose >11 mmol/L or known diabetes mellitus
Blood ketones ≥3 mmol/L or urine ketones ≥2+
Bicarbonate <15 mmol/L or venous pH <7.3

All three criteria should be met. If bicarbonate is low but ketones are at the threshold, reconsider: alcoholic ketoacidosis and starvation ketosis must be excluded.

Severity stratification (JBDS):

Severity pH Bicarbonate Ketones
Mild 7.25–7.29 15–18 ≥3
Moderate 7.00–7.24 10–14 ≥3
Severe <7.00 <10 ≥3

Severe DKA warrants ICU/HDU admission.

Pathophysiology

DKA results from absolute or relative insulin deficiency combined with excess counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone).

Hyperglycaemia

  • ↓ Insulin → ↓ glucose uptake by muscle and fat
  • ↑ Glucagon → ↑ hepatic glycogenolysis and gluconeogenesis (from amino acids, lactate, glycerol)
  • Result: hyperglycaemia → osmotic diuresis → dehydration and electrolyte losses

Ketosis

  • ↓ Insulin → ↑ lipolysis → ↑ free fatty acids (FFAs) delivered to liver
  • ↑ Glucagon:insulin ratio → ↑ hepatic fatty acid oxidation (carnitine transport activated)
  • Excess acetyl-CoA → ketone body synthesis: β-hydroxybutyrate (β-OHB) and acetoacetate (AcAc), and acetone
  • β-OHB:AcAc ratio normally ~3:1; rises further in co-existing lactic acidosis (↑ NADH shifts equilibrium toward β-OHB)
  • Point-of-care ketone meters measure β-OHB directly — more sensitive and specific than urine dipstick (which measures AcAc)

Anion Gap Metabolic Acidosis

  • Ketones (as ketoacids) accumulate → H⁺ liberated when ketoacids dissociate at physiological pH
  • Anion gap = Na − (Cl + HCO₃); normal <12 mmol/L; elevated in DKA (typically 16–30)

Electrolyte Depletion

  • Total body potassium deficit despite normal or elevated serum K at presentation
    • Acidosis drives H⁺ intracellularly in exchange for K⁺ (transcellular shift)
    • Serum K appears falsely normal or elevated
    • Insulin treatment drives K back into cells → hypokalaemia risk
  • Sodium: true depletion from osmotic diuresis; may appear low (pseudohyponatraemia from hyperglycaemia — correct: add 1.6 mmol/L Na per 5.5 mmol/L glucose above normal)
  • Phosphate and magnesium: total body depletion from osmotic diuresis; usually managed by monitoring without routine replacement

Clinical Features and Precipitants

Symptoms

Polyuria, polydipsia, nausea, vomiting, abdominal pain (can mimic surgical abdomen), fatigue, Kussmaul breathing (deep sighing respirations — respiratory compensation for metabolic acidosis), acetone breath (pear-drop smell)

Signs

Dehydration (dry mucous membranes, reduced skin turgor), tachycardia, hypotension (if severe), Kussmaul respirations, altered consciousness (in severe DKA)

Precipitants

Category Examples
Infection Most common (30–40%): UTI, pneumonia, cellulitis
Insulin omission Deliberate or inadvertent; pump failure
New diagnosis T1DM 20–25% of DKA episodes
Drugs SGLT-2 inhibitors (euglycaemic DKA — glucose may be <11!); steroids; antipsychotics
Other MI, stroke, pancreatitis, surgery, alcohol

SGLT-2 inhibitor-associated DKA: blood glucose may be near-normal (euglycaemic DKA) — do not rely on hyperglycaemia to trigger investigation; check ketones in unwell patients on SGLT-2 inhibitors.

Management — JBDS Guidelines

1. Fluid Resuscitation

Estimated fluid deficit: 5–8 litres (average adult). Use 0.9% sodium chloride (JBDS guideline — the standard regimen):

Timeframe Volume
0–1h 1000 mL 0.9% NaCl
1–2h 1000 mL 0.9% NaCl
2–4h 1000 mL 0.9% NaCl
4–8h 1000 mL 0.9% NaCl with KCl
8–12h 1000 mL 0.9% NaCl with KCl

Note: some evidence suggests balanced crystalloids (Hartmann's) may reduce hyperchloraemic acidosis and resolve ketoacidosis faster, but JBDS 2023 still recommends 0.9% NaCl as the standard, with balanced crystalloid as an acceptable alternative.

If haemodynamically compromised (SBP <90 mmHg): 500 mL 0.9% NaCl bolus stat before commencing protocol.

2. Fixed-Rate Insulin Infusion (FRII)

  • Rate: 0.1 units/kg/hour of actrapid (soluble insulin) in 0.9% NaCl
  • Do not adjust the insulin rate in response to glucose (it is fixed at 0.1 units/kg/hr to clear ketones)
  • Continue long-acting insulin at the usual dose throughout DKA treatment

3. Potassium Replacement

Serum potassium Action
<3.5 mmol/L Do NOT start insulin until K repleted; senior review
3.5–5.5 mmol/L Add 40 mmol KCl per litre of fluid
>5.5 mmol/L No potassium added; monitor hourly

Never give insulin until K ≥3.5 mmol/L — the insulin-driven K shift can cause dangerous hypokalaemia.

4. When to Add Dextrose

  • When blood glucose falls to <14 mmol/L: commence 10% glucose at 125 mL/hour alongside 0.9% NaCl
  • Continue insulin infusion until ketones <0.6 mmol/L AND pH >7.3 AND bicarbonate >18 mmol/L — do not stop insulin solely because glucose is normal
  • Glucose monitoring: hourly; ketone monitoring: hourly

5. Resolution Criteria (to switch to subcutaneous insulin)

  • Ketones <0.6 mmol/L
  • Venous pH >7.3
  • Bicarbonate >18 mmol/L
  • Patient eating and drinking

Overlap subcutaneous insulin for ≥30 minutes before stopping the infusion.

6. Bicarbonate

  • Not recommended in DKA management
  • Rapid correction of systemic pH paradoxically worsens intracellular and CSF acidosis (CO₂ crosses freely; bicarbonate does not)
  • Potential harms: hypokalaemia, worsening intracellular acidosis, cerebral oedema risk
  • May be considered in severe life-threatening hyperkalaemia (K >6.5 with ECG changes) — specialist decision

Complications

Cerebral Oedema

  • Uncommon in adults; most feared in children (<16 years)
  • Presents as sudden deterioration in GCS, headache, Cushing's triad 4–12h into treatment
  • Mechanism: rapid osmolar shifts from overly aggressive fluid administration or rapid glucose correction; cellular swelling from insulin-driven glucose uptake
  • Treatment: mannitol 0.5–1 g/kg IV or hypertonic saline; urgent CT; neurosurgical input

Hypokalaemia

  • Most common and dangerous complication of DKA treatment
  • Insulin drives K into cells; failure to replace causes cardiac arrhythmia
  • Monitor serum K and ECG closely throughout

Hyperchloraemic Acidosis

  • After ketoacidosis resolves, a non-anion gap metabolic acidosis persists from chloride load (0.9% NaCl) and bicarbonate loss
  • Self-limiting; resolves with continued treatment and renal correction
  • Do not confuse with persistent ketosis — check ketones and anion gap

Aspiration

  • Nausea, vomiting, and reduced consciousness are common → aspiration risk
  • Insert NG tube and consider prokinetics in obtunded patients

Thromboembolism

  • Dehydration + hyperosmolality + sepsis → high VTE risk
  • LMWH thromboprophylaxis from admission

DKA vs HHS vs Mixed

Feature DKA HHS
Glucose >11 (often 15–30) >30 mmol/L
Osmolality Mildly elevated Very high (>320 mOsm/kg)
Ketones ≥3 mmol/L <3 mmol/L (or absent)
pH <7.3 Normal or mildly reduced
Typical patient T1DM, younger T2DM, elderly
Deficit Moderate (~5–8L) Severe (~8–10L+)
Fluid 0.9% NaCl Cautious replacement (see HHS page)

Mixed DKA/HHS exists and is increasingly recognised, particularly with SGLT-2 inhibitor use.

Viva Questions

1. Describe the pathophysiology of DKA and explain why potassium management is so critical.

DKA results from insulin deficiency combined with counter-regulatory hormone excess. Glucagon stimulates hepatic glycogenolysis and gluconeogenesis, causing hyperglycaemia and osmotic diuresis (with total body depletion of sodium, potassium, phosphate). Reduced insulin:glucagon ratio activates hepatic fatty acid oxidation, producing excess acetyl-CoA which is shunted into ketone body synthesis (β-hydroxybutyrate and acetoacetate). These ketoacids dissociate at physiological pH, generating H⁺ and an elevated anion gap metabolic acidosis. Potassium management is critical because of a characteristic transcellular shift: in DKA, acidosis drives H⁺ into cells in exchange for K⁺ coming out, raising serum potassium despite total body depletion of 3–5 mmol/kg. When insulin is given, this shift reverses rapidly — K moves back into cells, and if not replaced, fatal hypokalaemia with cardiac arrhythmia can occur. Therefore: check serum K before starting insulin; never give insulin if K <3.5 mmol/L; add potassium to IV fluids when K is 3.5–5.5 mmol/L; monitor hourly throughout.

2. Why is bicarbonate not given in DKA?

Bicarbonate administration is not recommended in DKA despite the severe metabolic acidosis, because there is no clinical evidence of benefit and several reasons to expect harm. Bicarbonate does not freely cross the blood-brain barrier, whereas the CO₂ produced when bicarbonate neutralises H⁺ does (CO₂ + H₂O → H₂CO₃). This can paradoxically worsen intracellular and cerebrospinal fluid acidosis, potentially contributing to cerebral oedema. Bicarbonate also drives K into cells (worsening hypokalaemia), may suppress the respiratory drive, and shifts the oxyhaemoglobin dissociation curve leftward (reducing O₂ delivery). The treatment of DKA acidosis is insulin (which stops ketogenesis) and fluids (which restore renal function and allow excretion of H⁺ and ketoanions) — not exogenous bicarbonate. The acidosis resolves as the underlying biochemical abnormality is corrected.

3. A patient with DKA has a blood glucose of 8 mmol/L after 10 hours but still has ketones of 2.4 mmol/L. What do you do?

This is a common scenario — glucose normalises faster than ketones because glucose is cleared by renal excretion and cellular uptake, while ketone clearance depends on insulin-mediated hepatic suppression of ketogenesis. The treatment target for DKA is ketone resolution (<0.6 mmol/L), not glucose normalisation. Do not stop the insulin infusion simply because glucose has reached normal range. Instead: if glucose is <14 mmol/L and insulin is running at the fixed rate, start 10% glucose at 125 mL/hour to prevent hypoglycaemia while maintaining the insulin at 0.1 units/kg/hour. Continue monitoring ketones hourly and check pH/bicarbonate. Continue insulin until ketones <0.6 mmol/L, pH >7.3, and bicarbonate >18 mmol/L — all three criteria must be met before switching to subcutaneous insulin. Also look for a reason for slow resolution: inadequate insulin dose, ongoing precipitant (infection, missed insulin, occult source).

4. What is euglycaemic DKA and why does it matter?

Euglycaemic DKA is a variant in which ketoacidosis occurs without marked hyperglycaemia (blood glucose <11 mmol/L or near-normal). It is most commonly associated with SGLT-2 inhibitor use (gliflozins: empagliflozin, dapagliflozin, canagliflozin). SGLT-2 inhibitors increase renal glucose excretion, masking the hyperglycaemia that would normally accompany ketosis. They also increase glucagon secretion and shift metabolism toward fat oxidation, increasing ketone production. Patients present with features of DKA — nausea, vomiting, acidosis — but a blood glucose that may trigger false reassurance. SGLT-2 inhibitor-associated DKA should be considered in any unwell patient on these drugs with unexplained metabolic acidosis. The diagnostic clue is a high anion gap metabolic acidosis with elevated ketones but near-normal glucose. Management principles are the same as standard DKA, but glucose targets are different — additional glucose may be needed earlier to prevent hypoglycaemia during insulin therapy; some protocols reduce the insulin infusion rate once glucose falls to a safe range. The SGLT-2 inhibitor should be withheld during illness ("sick day rules").