Washington Manual Summary — DKA vs HHS
"Diabetic ketoacidosis and hyperosmolar hyperglycaemic state represent the two extreme ends of the spectrum of hyperglycaemic crises. Both are medical emergencies associated with significant morbidity and mortality if not recognised and treated promptly. The cornerstone of management in both is aggressive intravenous fluid resuscitation, insulin therapy, and electrolyte replacement, with particular attention to potassium — which must be corrected before insulin is started."
Washington Manual of Critical Care, 4th Ed. Wolters Kluwer 2023. Chapter: Hyperglycaemic Emergencies.DKA vs HHS — Comparison at a Glance
🔴 DKA (Diabetic Ketoacidosis)
- Glucose: Usually 14–33 mmol/L (250–600 mg/dL)
- pH: <7.30 (acidosis — defining feature)
- Anion gap: >12 mEq/L (elevated)
- Serum ketones: ≥3 mmol/L (βOHB) or large
- Bicarbonate: <18 mEq/L
- Osmolality: Variable, usually <320 mOsm/kg
- Consciousness: Usually alert to drowsy
- T1DM: More common; also T2DM (SGLT2i DKA)
- Onset: Hours to 1–2 days
- Mortality: ~1–5%
🔵 HHS (Hyperosmolar Hyperglycaemic State)
- Glucose: Usually >33 mmol/L (600 mg/dL), often 55–110
- pH: ≥7.30 (no significant acidosis)
- Anion gap: Normal or mildly elevated
- Serum ketones: Absent or mild
- Bicarbonate: ≥18 mEq/L
- Osmolality: >320 mOsm/kg (often 340–380)
- Consciousness: Often obtunded or comatose
- T2DM: Almost exclusively; elderly
- Onset: Days to weeks
- Mortality: ~15–20% (higher — older patients, comorbidities)
ICU Admission Criteria
- DKA with: pH <7.0, GCS <13, potassium <3.0 or >6.0 mEq/L, suspected precipitant (ACS, sepsis), inability to protect airway
- HHS: all patients (high mortality, need close monitoring)
- Any hyperglycaemic crisis with haemodynamic instability
Common Precipitants (6 Is)
- Infection — most common (50–60%); UTI, pneumonia, foot infection
- Insulin omission/dose error — common in T1DM
- Ischaemia — ACS, stroke, mesenteric ischaemia
- Intoxication — alcohol, cocaine
- Inflammation — acute pancreatitis (also caused by DKA)
- Iatrogenic — steroids, SGLT2 inhibitors (euglycaemic DKA — BG may be normal!), thiazides
Marino Physiology — Osmolarity, Anion Gap & Ketone Chemistry
"The fundamental pathophysiology of DKA is absolute or relative insulin deficiency combined with excess of counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone). This drives three simultaneous metabolic disasters: uncontrolled gluconeogenesis and glycogenolysis, impaired peripheral glucose uptake, and accelerated lipolysis with ketone production. The resulting metabolic acidosis is a high anion gap acidosis from ketoacids (betahydroxybutyrate and acetoacetate)."
Marino PL. The ICU Book, 5th Ed. Metabolic & Endocrine Crises. Wolters Kluwer; 2025.Anion Gap (AG) = Na⁺ − (Cl⁻ + HCO₃⁻)
Normal AG = 8–12 mEq/L (if albumin normal). In DKA: AG typically 20–30 mEq/L.
βOHB vs acetoacetate: βOHB is the predominant ketone in DKA (3:1 ratio) but is NOT detected by urine dipstick (which only detects acetoacetate). Serum βOHB (point-of-care) ≥3 mmol/L confirms DKA and is superior for monitoring resolution.
Paradox during treatment: As DKA resolves, βOHB is converted to acetoacetate — urine ketones can appear to WORSEN even as the patient improves. Do not judge resolution by urine ketones alone.
Effective Osmolarity = 2 × Na⁺ + Glucose (mmol/L)
Normal: 275–295 mOsm/kg. HHS defined by eff.osm >320 mOsm/kg.
Corrected Sodium in Hyperglycaemia: For every 5.6 mmol/L (100 mg/dL) rise in glucose above normal, actual Na⁺ is 1.6 mEq/L lower than measured. As glucose falls with treatment, Na⁺ will rise — this is expected and normal. Watch for hypernatraemia as glucose normalises (switch from NS to ½NS at that point).
Why is HHS more lethal? The extreme hyperosmolarity (340–380 mOsm/kg) causes dehydration of brain cells → coma, thrombosis, rhabdomyolysis. These patients are often elderly with multiple comorbidities and present days late.
Total body potassium is always DEPLETED in DKA (average deficit 3–5 mEq/kg). However, serum K⁺ may be normal, high, or low at presentation because:
- Acidosis drives K⁺ out of cells into plasma (every 0.1 unit fall in pH → 0.5–1 mEq/L rise in serum K⁺)
- Insulin deficiency prevents cellular K⁺ uptake
Clinical implication: When insulin is given and acidosis corrects, K⁺ will shift back into cells → serum K⁺ can fall precipitously → life-threatening hypokalaemia → cardiac arrest.
Rule: NEVER start insulin until serum K⁺ ≥3.5 mEq/L. If K⁺ is 3.0–3.5, replace and re-check before insulin. If K⁺ <3.0, do NOT start insulin — replace aggressively first.
Most feared complication, primarily in children (<21 years), but can occur in adults. Pathophysiology debated: possibly related to rapid osmolarity shifts from aggressive hypotonic fluid or excessively rapid glucose correction.
Signs: Headache, altered consciousness, Cushing triad during treatment — NOT at presentation.
ADA 2024 prevention: Use isotonic fluids (NS) not hypotonic saline initially; avoid bicarbonate (causes CSF paradoxical acidosis); correct glucose no faster than 2–4 mmol/L/h once target glucose 10–14 mmol/L is reached.
Treatment: IV mannitol 0.5–1 g/kg over 15 min (first line) or 3% NaCl 5–10 mL/kg.
Evidence-Based Management Protocol
2nd–4th Hour: 250–500 mL/h NS or 0.45% NaCl (if corrected Na⁺ normal or high)
When BG <13.9 mmol/L (250 mg/dL): Switch to 5% Dextrose + 0.45% NaCl at 150–250 mL/h — this allows insulin to continue without causing hypoglycaemia
Total 24h fluid: Typically 4–6 litres in adults. Avoid fluid overload (pulmonary oedema risk, especially in elderly).
1st Hour: 1000 mL NS over 1h
Hour 2 onwards: Switch to 0.45% NaCl once corrected Na⁺ is normal — at 200–500 mL/h
Target: Reduce osmolality by 3–8 mOsm/kg/h (do NOT correct too fast — brain oedema risk)
Glucose target: 13–15 mmol/L for HHS (slower correction than DKA); add dextrose when BG <16 mmol/L
Do NOT give IV insulin bolus — Joint British 2023 removed the loading bolus; it increases hypokalaemia risk without clinical benefit
Prerequisite: K⁺ must be ≥3.5 mEq/L before starting insulin
Target: Reduce BG by 2–4 mmol/L/h; reduce ketones by ≥0.5 mmol/L/h or bicarbonate rise of 3 mEq/L/h
Switch to subcutaneous insulin: When ketones <0.3 mmol/L, bicarbonate ≥15, pH ≥7.3, patient eating — overlap SC insulin with IV by 30–60 min before stopping infusion
Dose: 100 mEq NaHCO₃ in 400 mL sterile water over 2h; repeat until pH ≥7.0
Do NOT give bicarb routinely — no benefit shown in multiple RCTs; risks: paradoxical CSF acidosis, hypokalaemia (bicarb drives K⁺ into cells), delay in ketone clearance
Joint British 2023: bicarb contraindicated in DKA unless pH <6.9 with haemodynamic compromise.
1. BG <11.1 mmol/L (200 mg/dL)
2. Serum βOHB <0.3 mmol/L (or urine ketones trace/negative)
3. Venous pH >7.30 and bicarbonate ≥15 mEq/L
Check every 2–4h during treatment; do NOT stop insulin infusion until all three met AND patient eating.
βOHB point-of-care testing: Available in most major centres now; strongly preferred over urine ketones for monitoring DKA resolution.
SGLT2 inhibitor DKA (Euglycaemic DKA): Increasingly seen with empagliflozin/dapagliflozin use. BG may be normal (7–12 mmol/L). Classic insulin protocol still applies; hold SGLT2i. High clinical suspicion needed — a patient on an SGLT2i with high AG acidosis + normal BG has DKA until proven otherwise.
Phosphate replacement: Not routinely given in Indian centres due to limited availability; consider in severe hypophosphataemia (<0.3 mmol/L) with weakness or haemolysis.
Drug Reference — DKA & HHS
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Normal Saline 0.9% | Initial fluid — DKA & HHS | 1000 mL over 1h; then 250–500 mL/h | Switch to 0.45% NaCl when corrected Na⁺ normal or high |
| Actrapid (Regular Insulin) IV | DKA insulin infusion | 0.1 U/kg/h fixed rate (e.g. 70 kg → 7 U/h) | Only start when K⁺ ≥3.5 mEq/L; no IV bolus |
| Dextrose 5% + 0.45% NaCl | DKA when BG <13.9 mmol/L | 150–250 mL/h (allows insulin continuation) | Run alongside saline if needed; check BG 1–2 hourly |
| Sodium Bicarbonate 8.4% | DKA with pH <6.9 only | 100 mEq in 400 mL sterile water over 2h | Repeat until pH ≥7.0; do NOT use routinely |
| Phosphate (Potassium phosphate) | Severe hypophosphataemia (<0.3 mmol/L) | 0.2–0.4 mmol/kg over 6h IV | Rare indication; monitor Ca²⁺ (hypocalcaemia risk) |
Potassium Replacement Protocol
| Serum K⁺ | Insulin | K⁺ Replacement Rate |
|---|---|---|
| <3.0 mEq/L | HOLD INSULIN | 40 mEq/h IV (via central line) until K⁺ ≥3.5 |
| 3.0–3.5 mEq/L | HOLD INSULIN | 20–40 mEq/h IV; recheck in 1h before starting insulin |
| 3.5–5.0 mEq/L | ✅ Start/continue insulin | 20–30 mEq/h IV in fluids (mix in saline bag) |
| >5.0 mEq/L | ✅ Start/continue insulin | Monitor — no replacement; recheck every 2h |
NEVER start insulin with K⁺ <3.5 mEq/L. Insulin drives K⁺ into cells — if starting from a low baseline, serum K⁺ can fall to 2.5–3.0 mEq/L within 1–2h → VT/VF cardiac arrest. This is the leading cause of preventable death in DKA.
Step-by-Step Management Algorithm
Hour 0–1: Resuscitation & Diagnosis
- IV access × 2; bloods: BG, βOHB, VBG/ABG, U&E, Mg²⁺, PO₄, FBC, LFT, CRP, blood cultures
- 12-lead ECG (look for hyperkalaemia changes: peaked T waves, wide QRS), chest X-ray, urinalysis
- Calculate AG: Na⁺ − (Cl⁻ + HCO₃⁻); calculate effective osmolarity
- 1000 mL NS over 1h — start immediately
- Check K⁺: if <3.5, replace before insulin
Hour 1–2: Insulin & Electrolytes
- Start insulin infusion 0.1 U/kg/h ONLY if K⁺ ≥3.5
- Add KCl 20–40 mEq to each litre of saline if K⁺ 3.5–5.0
- Fluid rate: 250–500 mL/h saline (depending on dehydration severity)
- Monitoring: BG hourly, K⁺ every 2h, VBG every 2–4h
- Identify and treat precipitant (antibiotics for infection, ACS workup)
BG Reaches 13.9 mmol/L (250 mg/dL)
- Add 5% Dextrose to fluids (D5W + 0.45% NaCl 150–250 mL/h)
- Continue insulin infusion (do NOT stop — acidosis may still be present)
- Reduce insulin rate if BG falling fast or <10 mmol/L (target 8–12 mmol/L)
- Continue K⁺ monitoring and replacement
DKA Resolution: Transition to SC Insulin
- Resolution criteria met: pH >7.30 + HCO₃⁻ ≥15 + βOHB <0.3 mmol/L + patient eating
- Give SC long-acting insulin (e.g. glargine) at least 30–60 min BEFORE stopping IV infusion
- Do NOT abruptly stop IV insulin without SC cover — rebound ketosis
- If patient's usual insulin unknown — start at 0.2–0.3 U/kg SC BD (basal-bolus)
- Diabetes team review, patient education on sick-day rules
Thyroid Storm & Adrenal Crisis
Thyroid Storm (Thyrotoxic Crisis)
Life-threatening exacerbation of thyrotoxicosis — mortality 10–25% even with treatment. Precipitants: surgery, infection, trauma, iodine load, radioiodine, abrupt antithyroid drug withdrawal.
Score ≥45: Thyroid storm (treat immediately) | 25–44: Impending storm (treat aggressively) | <25: Unlikely storm
1. Beta-blocker FIRST: Propranolol 60–80 mg PO/NGT every 4–6h (or esmolol IV if unstable) — controls heart rate, blocks T4→T3 conversion
2. Antithyroid drug (ATD): PTU 500–1000 mg loading dose → 250 mg every 4h PO/NGT (preferred over methimazole — also blocks T4→T3 conversion) OR Methimazole 20–30 mg QDS
3. Iodine (give AFTER ATD — ≥1h gap): Lugol's iodine 8 drops QDS or potassium iodide (SSKI) 5 drops every 6h PO — blocks new thyroid hormone release. MUST give ATD first — iodine alone provides substrate for more hormone synthesis (Jod-Basedow).
4. Hydrocortisone: 100 mg IV every 8h — reduces T4→T3 conversion; treats possible co-existent relative adrenal insufficiency; anti-inflammatory
5. Supportive: Cooling blankets (avoid salicylates — displace T4 from TBG), IV fluids, treat AF (digoxin or amiodarone if beta-blocker insufficient), treat precipitant
Adrenal Crisis (Acute Adrenal Insufficiency)
Adrenal crisis should be suspected in any patient with unexplained hypotension or cardiovascular collapse that does not respond appropriately to fluids and vasopressors — particularly in those with known adrenal disease, on chronic steroids, with pituitary disease, or after abrupt steroid withdrawal. It is a life-threatening emergency where treatment must precede laboratory confirmation.
Washington Manual of Critical Care, 4th Ed. Chapter: Adrenal Disorders.Hydrocortisone: 100 mg IV bolus IMMEDIATELY → 50–100 mg IV every 6h (or continuous infusion 200 mg/24h) STRONG
Glucose: Add dextrose — these patients commonly have hypoglycaemia (cortisol is a counter-regulatory hormone)
Electrolytes: Hyponatraemia + hyperkalaemia = classic pattern (aldosterone deficiency). Correct Na⁺ with saline; K⁺ usually resolves with cortisol replacement.
Do NOT use dexamethasone for adrenal crisis — it has no mineralocorticoid activity. Use hydrocortisone (which has both gluco- and mineralocorticoid effects).
Taper: Once stable and oral intake resumed → taper to physiological replacement: hydrocortisone 10–20 mg/day PO (or prednisolone 5–7.5 mg/day) + fludrocortisone 0.1 mg daily.
Major illness/surgery: Hydrocortisone 100 mg IV 8-hourly (stress dose) until stable
Patients on chronic steroids (>5 mg prednisolone/day for >4 weeks) — always assume HPA axis suppression and give stress doses perioperatively
Common Mistakes in Endocrine Emergencies
The single most dangerous error in DKA management. Insulin causes K⁺ to shift intracellularly — if serum K⁺ is 3.3 mEq/L at baseline, it can fall to 2.6 mEq/L within 2h of insulin, precipitating fatal arrhythmia. Check K⁺ first, replace to ≥3.5 mEq/L, then start insulin.
Bicarb does not improve DKA outcomes and causes harm: it drives K⁺ into cells (worsening hypokalaemia), creates paradoxical CSF acidosis (worsening cerebral oedema risk), and delays ketone clearance. ADA 2024 restricts bicarb to pH <6.9 only.
Stopping IV insulin without giving SC basal insulin first leads to rebound ketoacidosis within hours (particularly in T1DM). Always give long-acting SC insulin (glargine) 30–60 min before stopping the infusion, when the patient is eating and meeting resolution criteria.
Blood glucose may be 7–12 mmol/L in SGLT2i-associated DKA — the elevated glucose threshold for diagnosis is absent. A patient on an SGLT2 inhibitor with high AG acidosis + ketones has DKA regardless of glucose level. These drugs increase urinary glucose excretion, masking the expected hyperglycaemia.
Iodine must be given AFTER antithyroid drugs (≥1h gap). Giving iodine first provides substrate for additional thyroid hormone synthesis (Jod-Basedow phenomenon), worsening thyrotoxicosis. The ATD must first block the organification pathway before iodine can be used to block hormone release.
Dexamethasone has no mineralocorticoid activity — it corrects the cortisol deficit but not the aldosterone deficit, so salt wasting and hyperkalaemia continue. Use hydrocortisone 100 mg IV (which has significant mineralocorticoid action) for adrenal crisis. Dexamethasone may be used short-term only if hydrocortisone unavailable and serum cortisol sample must be drawn first.
References
- American Diabetes Association. Standards of Care in Diabetes — 2024. Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State. Diabetes Care 2024;47(Suppl 1):S282–S292.
- Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults, 4th Ed. 2023. Available at JBDS-IP website.
- Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients with Diabetes. Diabetes Care 2009;32:1335–1343. (foundational ADA guidelines)
- Burch HB, Wartofsky L. Life-threatening Thyrotoxicosis: Thyroid Storm. Endocrinol Metab Clin North Am 1993;22:263–277. (Burch-Wartofsky Score)
- Bartalena L, Bogazzi F, Chiovato L et al. 2018 European Thyroid Association (ETA) Guidelines for the Management of Amiodarone-Associated Thyroid Dysfunction. Eur Thyroid J 2018;7:55–66.
- Bornstein SR, Allolio B, Arlt W et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016;101:364–389.
- Marino PL. The ICU Book, 5th Ed. Metabolic & Endocrine Emergencies. Wolters Kluwer; 2025.
- Washington Manual of Critical Care, 4th Ed. Chapters: Hyperglycaemic Emergencies; Thyroid Disorders; Adrenal Disorders. Wolters Kluwer 2023.