Diabetic Ketoacidosis (DKA): Pathophysiology, Management, and Perioperative Anaesthetic Management

MD Anaesthesia Examination Long Answer

PART 1 - DEFINITION AND DIAGNOSTIC CRITERIA

1. Hyperglycaemia - blood glucose > 250 mg/dL (though euglycaemic DKA is recognised, especially with SGLT2 inhibitors)
2. Ketosis - urine ketones 2+ or more, or serum beta-hydroxybutyrate > 3.0 mmol/L
3. Metabolic acidosis - arterial/venous pH < 7.3, serum bicarbonate < 18 mmol/L

PART 2 - PATHOPHYSIOLOGY

Central Mechanism: Insulin Deficiency + Counter-Regulatory Hormone Excess

INSULIN DEFICIENCY + GLUCAGON EXCESS
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    _____|______________________________
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LIVER                           ADIPOSE/MUSCLE
    |                                  |
Gluconeogenesis ↑             FFA release ↑ (hormone-sensitive lipase activated)
Glycogenolysis ↑              Amino acid release ↑ (proteolysis)
Ketogenesis ↑                 (amino acids --> liver --> gluconeogenic substrate)
(acetoacetate, β-hydroxybutyrate, acetone)
    |
HYPERGLYCAEMIA + KETONAEMIA

1. Hyperglycaemia and Osmotic Diuresis

• Glucose cannot enter insulin-dependent peripheral cells
• Hepatic glucose output unchecked (gluconeogenesis + glycogenolysis)
• Once renal threshold (~180 mg/dL) is exceeded, glycosuria occurs
• Osmotic diuresis pulls water, Na+, K+, Mg2+, Ca2+, PO4 into urine
• This leads to profound dehydration - average fluid deficit 3-5 L in adults (up to 100-120 mL/kg in children)

2. Ketogenesis

• Insulin deficiency activates hormone-sensitive lipase in adipose tissue
• Massive release of free fatty acids (FFAs) into circulation
• In the liver: FFAs undergo incomplete beta-oxidation → acetoacetate and β-hydroxybutyrate (strong acids)
• Acetone (from spontaneous decarboxylation of acetoacetate) produces the classic fruity breath
• In DKA, β-hydroxybutyrate dominates; the beta-hydroxybutyrate: acetoacetate ratio rises to 3:1 or higher (note: nitroprusside-based urine ketone strips detect only acetoacetate, so ketosis may be UNDER-estimated)
• Cellular starvation state also decreases peripheral ketone utilisation, worsening ketonaemia

3. Metabolic Acidosis and Respiratory Compensation

• Accumulation of ketoacids generates a high anion gap metabolic acidosis
• Anion Gap = Na - (Cl + HCO3); normal 8-12 mEq/L; elevated in DKA
• Respiratory compensation: Kussmaul breathing (deep, sighing respirations) - the body eliminates CO2 to buffer the acidosis
• Bicarbonate is consumed as a buffer
• With large volumes of normal saline (0.9% NaCl) resuscitation, a hyperchloraemic normal anion gap acidosis may supervene

4. Electrolyte Disturbances

5. Precipitating Factors (The "I's")

• Infection (most common - UTI, pneumonia, cellulitis)
• Insulin omission or inadequate insulin (non-adherence, pump failure)
• Infarction (myocardial, cerebral, mesenteric)
• Iatrogenic/Drugs - corticosteroids, SGLT2 inhibitors (euglycaemic DKA), atypical antipsychotics (clozapine, olanzapine), thiazides, sympathomimetics
• Illness - pancreatitis, trauma, surgery, burns
• Illicit drugs - cocaine
• Initial presentation of type 1 diabetes
• Endocrinopathies - Cushing's, thyrotoxicosis, acromegaly

PART 3 - CLINICAL FEATURES

History

• Polyuria, polydipsia, polyphagia (or anorexia), weight loss
• Nausea, vomiting, abdominal pain (can mimic acute abdomen - due to ileus or splanchnic vasoconstriction from acidosis; rarely pancreatitis)
• Weakness, lethargy, confusion
• Preceding illness, missed insulin doses

Physical Examination

• Dehydration: dry mucous membranes, sunken eyes, reduced skin turgor, decreased JVP
• Tachycardia and orthostatic hypotension (hypovolaemia)
• Kussmaul breathing: deep, rapid respirations
• Fruity/acetone breath
• Altered mental status, stupor, or coma (reflects hyperosmolality)
• Low-grade fever (infection may be masked or absent; hypothermia is a serious sign)
• Abdominal tenderness

Investigations

• Bedside: Blood glucose, urine dipstick (glucose 4+, ketones 2-4+)
• Blood gas: pH, pCO2, HCO3 (venous acceptable for monitoring)
• Serum electrolytes: Na, K, Cl, HCO3, urea, creatinine
• Anion gap calculation
• Serum/capillary ketones: beta-hydroxybutyrate >3 mmol/L diagnostic
• Full blood count: WBC elevated (metabolic acidosis per se, not always infection)
• Blood cultures, urine culture (identify precipitant)
• HbA1c (baseline glycaemic control)
• ECG: hyperkalemia/hypokalemia changes, exclude MI as precipitant
• Serum amylase/lipase: often elevated from non-pancreatic sources; misleading
• Chest X-ray: exclude pneumonia as precipitant
• Phosphate, magnesium, calcium

PART 4 - MANAGEMENT OF DKA

Principles: The "FRIED" Approach

• F - Fluids (rehydration)
• R - Replace electrolytes (K, PO4, Mg)
• I - Insulin infusion
• E - Eliminate precipitating cause
• D - Dextrose when glucose approaches 250 mg/dL

A. FLUID RESUSCITATION

1. Haemodynamic shock (SBP < 90 mmHg, HR > 120): Give isotonic crystalloid (0.9% NaCl or Balanced salt solution like Plasmalyte/Ringer's lactate) as rapidly as possible - boluses of 500 mL-1 L until haemodynamically stable
2. Marked dehydration without shock: 1 L of 0.9% NaCl in first hour, then reassess
3. General adult protocol: 2-3 L 0.9% NaCl over first 2-3 hours, then switch to 0.45% NaCl (half-normal saline) at 250-500 mL/h, guided by corrected Na, urine output

B. POTASSIUM REPLACEMENT

• ECG monitoring for signs of hypo/hyperkalaemia
• Once patient is eating and IV fluids are discontinued, switch to oral K+ supplementation

C. INSULIN THERAPY

1. Bolus: 0.1 unit/kg IV regular insulin bolus (optional - some protocols omit this)
2. Infusion: Regular insulin 0.1 unit/kg/hour IV infusion
3. Target: Decrease blood glucose by 50-75 mg/dL/hour
4. If glucose falls > 100 mg/dL/hour, halve the infusion rate
5. When blood glucose reaches 200-250 mg/dL: reduce infusion to 0.05 unit/kg/h AND add dextrose to IV fluids
6. Continue insulin infusion until:
   • pH > 7.30
   • HCO3 > 18 mEq/L
   • Anion gap < 12 mEq/L
   • Serum/urine ketones clearing

• When patient is eating, pH normalised, anion gap closed
• Administer first dose of subcutaneous basal insulin 2 hours before stopping the IV infusion (overlap) to prevent rebound ketoacidosis

D. BICARBONATE THERAPY

• May worsen hypokalaemia
• Paradoxical CSF acidosis (CO2 crosses blood-brain barrier more freely than bicarbonate)
• May delay closure of anion gap
• Consider only if: pH < 6.9, life-threatening hyperkalaemia, severe haemodynamic compromise

E. PHOSPHATE REPLACEMENT

• Routine phosphate replacement is NOT recommended
• Indicated if: serum phosphate < 1.0 mEq/L, or if severe symptomatic hypophosphataemia (respiratory muscle weakness, haemolysis, rhabdomyolysis)
• Replace as potassium phosphate

F. MONITORING

G. TREATMENT OF PRECIPITATING CAUSE

• Blood and urine cultures
• Broad-spectrum antibiotics if infection suspected
• ECG, troponin, echo if MI suspected
• Hold SGLT2 inhibitors
• Correct all causative factors

PART 5 - PERIOPERATIVE ANAESTHETIC MANAGEMENT OF A PATIENT WITH DKA POSTED FOR SURGERY

A. GENERAL PRINCIPLES

B. PREOPERATIVE ASSESSMENT AND OPTIMISATION

• Determine type and duration of diabetes (T1DM vs T2DM; risk of DKA recurrence in T1DM)
• Assess degree of DKA severity (mild/moderate/severe per criteria above)
• Assess for precipitating cause and surgical urgency
• Assess volume status: skin turgor, capillary refill, HR, BP, orthostatic changes
• Airway assessment: Critical in diabetics

• Diabetic autonomic neuropathy can cause:
  • Cardiovascular instability: hypotension on induction, reduced heart rate variability
  • Gastroparesis: increased aspiration risk (delayed gastric emptying - always treat as full stomach)
  • Impaired hypoglycaemia awareness: silent hypoglycaemia under anaesthesia
• Test for postural hypotension, resting tachycardia, HR response to Valsalva

• ABG (pH, pCO2, pO2, HCO3, lactate, SaO2)
• Blood glucose (hourly)
• Serum electrolytes (Na, K, Cl, HCO3, phosphate, magnesium)
• Anion gap
• Serum ketones/beta-hydroxybutyrate
• Full blood count, CRP (infection screen)
• Renal function (urea, creatinine) - prerenal AKI common
• HbA1c
• 12-lead ECG (silent MI as precipitant; hyperkalaemia/hypokalaemia changes)
• Chest X-ray (precipitating pneumonia; pulmonary oedema from aggressive resuscitation)
• Coagulation profile
• Group and crossmatch (if major surgery)
• Echocardiogram if cardiac dysfunction suspected

• Postpone until DKA fully resolved:
  • pH > 7.30, HCO3 > 18 mEq/L, anion gap closed
  • Blood glucose < 200 mg/dL
  • Serum K+ 3.5-5.0 mEq/L
  • Adequate rehydration (urine output, normal BUN:creatinine)
• Optimise HbA1c (ideally < 8%) - if > 8%, refer to endocrinologist for optimisation (though this may not always be feasible)
• Hold SGLT2 inhibitors 3-7 days before surgery (risk of euglycaemic DKA)
• Hold metformin (risk of lactic acidosis with contrast/renal impairment)
• Schedule as first case of the day to minimise fasting stress

• Start DKA resuscitation IMMEDIATELY - surgery should proceed alongside resuscitation, not after
• Liaise with surgical team and endocrinologist/intensivist
• Minimum targets before theatre if time permits:
  • K+ corrected to > 3.3 mEq/L (mandatory before insulin and before induction)
  • Volume resuscitation initiated, HR < 120, SBP > 90 mmHg
  • Blood glucose trending down with insulin infusion
  • Acid-base correction underway
• Anaesthesia should not be indefinitely delayed for emergency (life-threatening) surgical pathology

C. INTRAOPERATIVE MANAGEMENT

• Standard ASA/ACC monitoring: ECG, SpO2, NIBP, EtCO2, temperature
• Invasive arterial line (A-line): Essential for:
  • Continuous BP monitoring (haemodynamic instability expected)
  • Frequent ABG sampling (pH, pCO2, glucose, K+, lactate)
• Central venous line (CVP): For major surgery, guiding fluid resuscitation, vasopressor infusion
• Urinary catheter: Urine output monitoring - target 0.5-1 mL/kg/h
• Temperature probe: Hypothermia worsens acidosis and insulin resistance
• Blood glucose every 30-60 minutes intraoperatively

• Rapid sequence induction (RSI) is mandatory in ALL DKA patients:
  • Gastroparesis (even without obvious symptoms) delays gastric emptying
  • Vomiting + aspiration risk is high in obtunded/acidotic patient
  • Precautionary use of sodium citrate (30 mL PO) and metoclopramide if time permits
• Consider pre-oxygenation with head-up position
• Difficult airway preparedness: Have video laryngoscope, bougie, supraglottic airway, and surgical airway kit readily available (stiff joint syndrome, limited neck mobility)
• Avoid nasogastric/nasotracheal routes if coagulopathy or basal skull concerns

• Prefer haemodynamically stable agents given cardiovascular instability:
  • Ketamine (1-2 mg/kg IV): Cardiovascular stimulant, bronchodilator; caution in tachycardia
  • Etomidate (0.3 mg/kg IV): Minimal cardiovascular depression; note adrenal suppression
  • Propofol with caution: Causes vasodilation and myocardial depression; reduce dose in hypovolaemic patients
• Suxamethonium for RSI: Use only if K+ is within acceptable range (< 5.5 mEq/L). Suxamethonium raises serum K+ by ~0.5-1.0 mEq/L - potentially catastrophic in hyperkalaemic DKA. If K+ is high or unknown, use rocuronium 1.2 mg/kg with sugammadex immediately available
• Pre-treat with atropine if autonomic neuropathy causes bradycardia

• Either volatile (sevoflurane/isoflurane) or TIVA (propofol infusion)
• Avoid nitrous oxide (N2O) - potential for gut distension in ileus; increases PONV
• Opioid choice: titrate carefully; DKA patients may have altered opioid pharmacokinetics
• Mechanical ventilation strategy: Critical
  • If patient had Kussmaul breathing pre-operatively (compensatory respiratory alkalosis), the ventilator must replicate the pre-operative respiratory effort
  • Target EtCO2 at the pre-operative pCO2 (typically low, e.g. 20-25 mmHg in severe DKA)
  • If you allow pCO2 to rise to "normal" values (35-40 mmHg) with controlled ventilation, the respiratory compensation is abolished, and pH will DROP dramatically - this can precipitate cardiovascular collapse
  • Formula guidance: If pH 7.2 and pCO2 20, do not allow pCO2 > 25 mmHg
• Tidal volumes: 6-8 mL/kg IBW; avoid volutrauma/barotrauma

• Continue the pre-operative DKA resuscitation protocol:
  • IV regular insulin infusion at 0.1 units/kg/h (continue pre-operative rate)
  • IV fluid (0.9% NaCl or Plasmalyte) as the primary resuscitation fluid
  • Separate dextrose-containing fluid (5% dextrose or 10% dextrose) infused concurrently when glucose < 250 mg/dL - titrate independently of the insulin line
  • Potassium in fluids as per protocol
• Blood glucose targets intraoperatively: 140-180 mg/dL (ADA; most societies agree this range is safe)
• Tight glycaemic control (80-110 mg/dL) is NOT recommended intraoperatively - risk of iatrogenic hypoglycaemia is too high
• Avoid glucose-containing fluids (Ringer's lactate with dextrose, 5% dextrose as primary resuscitation) until glucose is controlled
• Use colloids (albumin) cautiously in massive haemorrhage
• Avoid excessive 0.9% NaCl - hyperchloraemic acidosis will worsen underlying DKA acidosis and confuse interpretation of ABG

• Warming blankets, warmed IV fluids, warm environment
• Hypothermia worsens acidosis and reduces insulin effectiveness

D. POSTOPERATIVE MANAGEMENT

• All DKA patients undergoing surgery require ICU-level care postoperatively
• Continue DKA protocol monitoring (hourly glucose, 2-4 hourly electrolytes, ABG)
• Continue insulin infusion until DKA criteria for resolution are met

• Full reversal of neuromuscular blockade (TOF ratio > 0.9)
• pH > 7.30 (patient must be able to maintain respiratory compensation post-extubation)
• Alert, following commands, airway reflexes intact
• Haemodynamically stable
• Adequate analgesia (PONV will interrupt oral intake and insulin resumption)

• Regional/neuraxial analgesia preferred when feasible (reduces opioid need, attenuates surgical stress response, reduces hyperglycaemia)
• Epidural analgesia attenuates the neuroendocrine stress response and may reduce the degree of perioperative hyperglycaemia
• NSAIDs with caution (renal impairment is common in DKA)
• Multimodal analgesia

• Critical - vomiting will prevent oral intake, perpetuate dehydration, and delay transition to subcutaneous insulin
• Use ondansetron, dexamethasone (note: dexamethasone raises glucose, monitor closely), scopolamine patch, droperidol
• Avoid neostigmine (increases secretions, nausea)

• When: Patient eating well, pH > 7.30, anion gap closed, ketones cleared
• Method: Administer first dose of long-acting subcutaneous insulin (e.g. glargine) 2 hours before stopping IV insulin infusion to prevent rebound ketoacidosis
• Resume pre-admission antidiabetic regimen or endocrinology-guided new regimen
• Continue monitoring glucose 4-hourly

• Hypoglycaemia (most dangerous under sedation)
• Rebound ketoacidosis (if insulin stopped prematurely)
• Cerebral oedema (especially in children - rapid osmotic shifts)
• Pulmonary oedema (overly aggressive fluid resuscitation in elderly/cardiac patients)
• Hypokalaemia leading to arrhythmia
• Aspiration pneumonitis
• Acute kidney injury (from dehydration + contrast + NSAIDs)
• Thromboembolism (hypercoagulable state in DKA)

PART 6 - SPECIAL CONSIDERATIONS

SGLT2 Inhibitor-Associated Euglycaemic DKA

• Increasingly recognised perioperatively
• Blood glucose may be NORMAL or mildly elevated (< 250 mg/dL) despite full DKA
• High index of suspicion in patients on dapagliflozin, empagliflozin, canagliflozin
• Hold SGLT2 inhibitors 3-7 days before elective surgery (FDA recommendation 2020)

Insulin Pumps (CSII - Continuous Subcutaneous Insulin Infusion)

• For short operations: may continue pump at basal rate if accessible and glucose > 110 mg/dL
• For major/long surgery: convert to IV insulin infusion
• Know the basal rate settings; correctional dosing set at glucose > 180 mg/dL
• Hourly glucose monitoring mandatory

DKA in Children

• Extra caution: risk of cerebral oedema (leading cause of DKA mortality in paediatrics)
• Slower rehydration (48 hours), careful sodium correction
• Avoid rapid falls in osmolality
• Perform head CT if GCS deteriorates during treatment

DKA in Pregnancy

• Higher risk, can occur at lower glucose levels (near-euglycaemic DKA)
• Fetal mortality 10-30% if untreated
• Maternal respiratory compensation (pCO2 baseline is already ~30 mmHg in pregnancy)
• Aggressive insulin and fluid therapy; fetal monitoring; involve obstetrics

SUMMARY TABLE: DKA Perioperative Anaesthetic Checklist

REFERENCES (Textbook Sources)

• Rosen's Emergency Medicine: Concepts and Clinical Practice, p. 2542-2548
• Goldman-Cecil Medicine (International Edition), p. 2483-2486
• Barash, Cullen and Stoelting's Clinical Anesthesia, 9e, p. 1779-1783
• Current Surgical Therapy, 14e, p. 1510-1512
• Szabó GV et al. Balanced electrolyte solutions vs 0.9% saline in DKA. [Diabetes Metab Res Rev, 2024 - PMID 38925619]
• Alnuaimi A et al. Subcutaneous vs continuous insulin infusion in DKA. [BMC Endocr Disord, 2024 - PMID 39090718]
• Thammakosol K et al. Early subcutaneous basal insulin with IV insulin in DKA. [Diabetes Obes Metab, 2026 - PMID 41208563]