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EMERGENCY

Hyperosmolar Hyperglycaemic State (HHS)

High EvidenceUpdated: 2025-12-27

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Red Flags

  • Coma or GCS <8 requiring airway protection
  • Severe dehydration with Shock (SBP <90)
  • Serum Osmolality >350 mOsm/kg
  • Mixed DKA/HHS (pH <7.1)
  • Silent Myocardial Infarction
  • Arterial/Venous Thromboembolism
Overview

Hyperosmolar Hyperglycaemic State (HHS)

Hyperosmolar Hyperglycaemic State (HHS), formerly known as HONK (Hyperosmolar Non-Ketotic Coma), is a life-threatening metabolic emergency occurring primarily in patients with Type 2 Diabetes Mellitus. It is defined by the triad of severe hyperglycaemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis.

1. Clinical Overview

Summary

HHS is characterised by a relative insulin deficiency that is sufficient to prevent lipolysis and ketogenesis but insufficient to facilitate glucose utilisation or suppress hepatic gluconeogenesis. This results in extreme hyperglycaemia (>30 mmol/L), which drives a profound osmotic diuresis leading to massive fluid losses (often 9-12 Litres). The mortality rate of HHS (10-20%) is significantly higher than that of Diabetic Ketoacidosis (DKA) (<1%), largely due to the older patient demographic, comorbidities, and the severity of dehydration/electrolyte derangement. Diagnosis requires calculated serum osmolality >320 mOsm/kg. Management prioritizes gradual fluid resuscitation to avoid cerebral oedema, with delayed and cautious insulin therapy.

Key Clinical Facts (Must Know)

  1. Mortality: 10-20% (vs <1% for DKA). It is the most lethal hyperglycaemic emergency.
  2. Definition: Glucose >30 mmol/L, Osmolality >320 mOsm/kg, pH >7.3, Bicarb >15, Ketones <3.0 mmol/L.
  3. Fluid Deficit: Typically 100-220 ml/kg (approx 8-12 Litres in a 70kg adult).
  4. Insulin Timing: Do NOT start insulin immediately. Start fluids first. Insulin (0.05 u/kg/hr) is only started if glucose stops falling with fluids alone.
  5. Sodium: Often pseudohyponatraemia initially, but corrects to hypernatraemia as dehydration worsens. Corrected Sodium is crucial for monitoring.
  6. Complication: Thromboembolism (VTE/Arterial) is a major cause of death. Prophylactic LMWH is mandatory.
  7. Onset: Insidious (days to weeks), unlike DKA (hours/days).
  8. Potassium: Total body deficits are massive (300-1000 mmol) despite normal serum potassium.
  9. Cerebral Oedema: Risk of Pontine Myelinolysis (ODS) if Sodium corrected too fast, or Cerebral Oedema if Osmolality drops too fast (>3 mOsm/kg/hr).
  10. Precipitant: Infection (Pneumonia/UTI) is the cause in 40-60% of cases.

Clinical Pearls

[!TIP] The "Honey" Blood: Patients with HHS are hypercoagulable due to dehydration and viscosity. "Sludging" of blood leads to high risk of MI, Stroke, and DVT. Full mechanical and pharmacological VTE prophylaxis is non-negotiable unless bleeding.

[!TIP] Don't Chase the Glucose: The goal is to normalise Osmolality, not just glucose. A rapid drop in glucose causes a rapid drop in osmolality, shifting water into brain cells -> Cerebral Oedema. Aim for a gentle decline (glucose <5 mmol/L per hour).

[!TIP] The Sodium Trap: As you give fluids (lowering glucose), glucose moves into cells and water follows, concentrating sodium. Sodium should rise as glucose falls. If sodium does NOT rise, you are giving too much free water (risk of oedema).

[!TIP] Mixed Picture: 1 in 3 patients presents with "Mixed DKA/HHS" (Ketosis + Hyperosmolarity). These are high risk. Treat as per HHS algorithm first (priority is fluid/osmolarity), but may need insulin sooner (DKA protocol) if acidosis persists.

[!TIP] Foot Check: The "insidious" onset means a patient may have been lying on the floor for days ("Found down"). Check for pressure ulcers and rhabdomyolysis (CK).

2. Epidemiology

Incidence

  • Rate: <1 per 1,000 person-years in diabetic population.
  • Ratio: Less common than DKA (1 case of HHS for every 6-10 cases of DKA).
  • Trend: Increasing incidence due to aging population and rising T2DM prevalence.

Demographics

  • Age: Primarily adults >60 years (mean age ~70).
  • Gender: No significant gender bias.
  • Diabetes Type: Predominantly Type 2 DM. Rarely in T1DM who take some long-acting insulin (preventing ketosis).
  • Ethnicity: Higher rates in African-American, Hispanic, and Native American populations (paralleling T2DM).

Risk Factors / Precipitants ("The 5 I's")

PrecipitantFrequencyExamples
Infection40-60%Pneumonia (leading cause), UTI/Urosepsis, Cellulitis, Sepsis.
Infarction20%Myocardial Infarction (Silent MI common), Stroke, Mesenteric Ischaemia.
Insulin10%Non-compliance, Dose skipping, Pump failure, Insulin spoilage.
Iatrogenic10%Steroids (Glucocorticoids), Thiazides, Atypical Antipsychotics, SGLT-2 Inhibitors.
Initial10%First presentation of Type 2 Diabetes (undiagnosed).

Other Associations:

  • Social: Poor fluid intake (nursing home residents, dementia, immobility). "Unable to reach the tap".
  • Renal: Chronic Kidney Disease (impairs glucose excretion).
  • Substance: Alcohol abuse, Cocaine.
3. Pathophysiology

HHS results from a "Perfect Storm" of insulin deficiency, massive physiological stress, and impaired renal clearance. Unlike DKA, where insulin causes a "switch must be off" failure (Lipolysis), HHS represents a "dimmer switch is low" failure (Gluconeogenesis).

The Molecular Basis of Hyperglycaemia

The core defect is a Relative Insulin Deficiency.

  1. Receptor Level: Peripheral tissues (Muscle/Adipose) exhibit severe insulin resistance (downregulation of IRS-1 signalling). This prevents Glut-4 translocation, stopping glucose uptake.
  2. Hepatic Level: The liver remains sensitive to Glucagon (which is elevated due to stress).
    • Insulin is insufficient to suppress Glucagon.
    • Result: Unchecked Gluconeogenesis (New glucose creation) and Glycogenolysis (Glycogen breakdown).
  3. Why no Ketones?:
    • Lipolysis (fat breakdown) is highly sensitive to insulin. Only 10% of basal insulin is required to suppress Hormone Sensitive Lipase (HSL).
    • HHS patients have just enough residual beta-cell function to suppress HSL, preventing Free Fatty Acid (FFA) release and subsequent Ketogenesis.

The Role of Counter-Regulatory Hormones

Precipitants (Infection/MI) cause a surge in "Stress Hormones" which antagonise insulin:

  1. Cortisol: Promotes protein catabolism (providing Amino Acid substrates for gluconeogenesis) and increases insulin resistance.
  2. Catecholamines (Adrenaline): Stimulate Glycogenolysis and inhibit insulin secretion.
  3. Growth Hormone: Increases lipolysis and insulin resistance.
  4. Glucagon: The primary driver of hepatic glucose output.

The 5-Step Clinical Mechanism

Step 1: The Initiating Event (Hyperglycaemia)

  • A precipitant (e.g., Pneumonia) causes stress hormone release.
  • Glucose rises.
  • Peripheral uptake fails.
  • Liver pumps out more glucose.
  • Result: Glucose >20 mmol/L.

Step 2: Osmotic Diuresis (The Volume Depletion Phase)

  • Glucose exceeds the Renal Threshold (approx 10 mmol/L).
  • The Sodium-Glucose Co-transporter 2 (SGLT2) in the proximal tubule is saturated.
  • Glucose remains in the tubule, acting as an osmole.
  • Water is retained in the tubule (opposing reabsorption) and excreted.
  • Electrolyte Loss: High flow washes out Sodium (70-150 mmol/L), Potassium (20-70 mmol/L), and Magnesium.
  • Volume: Losses reach 100-200 ml/kg.

Step 3: Dehydration & Renal Failure (The Vicious Cycle)

  • As volume falls, renal perfusion drops (Pre-renal).
  • GFR declines.
  • The kidney can no longer excrete the glucose load.
  • Without the "safety valve" of glucosuria, blood glucose spirals upwards (often >50-100 mmol/L).
  • This creates extreme hypertonicity.

Step 4: Intracellular Dehydration (The Brain)

  • ECF Osmolality rises (>320 mOsm/kg).
  • Water moves from ICF (Cells) to ECF (Blood) to equilibrate.
  • Cerebral Neurons: Shrink.
  • Adaptation: Over days, brain cells generate "Idiogenic Osmoles" (Taurine, Myoinositol) to pull water back in and restore volume.
    • Clinical Correlate: This adaptation protects the brain but makes rapid rehydration dangerous (cell swelling).

Step 5: Hypercoagulability

  • Severe dehydration causes Haemoconcentration (High Hct).
  • High glucose damages endothelium (Glycocalyx dysfunction).
  • Virchow's Triad: Stasis + Hypercoagulability + Endothelial Injury.
  • Result: High risk of DVT, PE, MI, and Stroke.

Classification: HHS vs DKA (Detailed)

Clinical FeatureDiabetic Ketoacidosis (DKA)Hyperosmolar Hyperglycaemic State (HHS)
Primary DefectAbsolute Insulin DeficiencyRelative Insulin Deficiency
Dominant ProcessLipolysis & KetogenesisGluconeogenesis & Osmotic Diuresis
OnsetAcute (<24 hours)Insidious (Days to Weeks)
Glucose>11 mmol/L (often 20-30)>30 mmol/L (often >50-80)
pH<7.3 (Acidosis)>7.3 (Normal/Mild)
Bicarb<15 mmol/L>15 mmol/L
Ketones>3.0 mmol/L (+++)<3.0 mmol/L (+/-)
OsmolalityVariable (<320 typically)>320 mOsm/kg (Diagnostic)
GapHigh Anion GapNormal Anion Gap (usually)
Fluid Deficit3-6 Litres8-12 Litres
Mental StatusAlert (unless severe)Stupor / Coma (correlated with Osm)
4. Clinical Presentation

History

Detailed Presenting Complaints

1. Neurological Manifestations ("The Metabolic Encephalopathy")

HHS is primarily a neurological disease precipitated by metabolic failure.

2. Gastrointestinal Symptoms

3. Constitutional & Musculoskeletal

4. Visual Disturbances

Examination Findings Breakdown

General Appearance

Red Flags (Immediate Threat)

Polyuria/Polydipsia
Gradual onset over weeks.
Systemic
Profound weakness, lethargy, cramps, weight loss.
Neurological
Confusion, hallucinations, focal weakness (mimics stroke), seizures, coma.
Precipitant Symptoms
Cough (Pneumonia), Dysuria (UTI), Chest Pain (MI).
Social
Ask about carers, water access, missed medications.
5. Clinical Examination

General Inspection

  • Mental Status: Drowsy, confused, or comatose. "Metabolic Encephalopathy".
  • Breath: No Ketotic breath (Pear drops) - helps differentiate from DKA.
  • Respiration: No Kussmaul breathing (usually, unless lactic acidosis co-exists).

Assessment of Dehydration

HHS patients are predominantly hyper-tonic dehydrated. Signs may be masked by hypernatraemia (maintains intravascular volume better than hyponatraemia).

SeverityClinical SignsEstimated Deficit
MildDry mucous membranes, Thirst3-5% (2-3 L)
ModerateReduced skin turgor, Sunken eyes, Tachycardia5-10% (3-6 L)
SevereHypotension, Weak pulses, Cool peripheries, Oliguria, Coma>10% (>6-10 L)

Systemic Look

  • Cardiovascular: Tachycardia (often >120), Postural hypotension. Arrhythmias (AF common).
  • Respiratory: Crepitations (Pneumonia/Aspiration).
  • Abdominal: Tenderness? (Check Bowel Ischaemia - high risk in hypovolaemic elderly).
  • Neurological:
    • Psychomotor: Agitated delirium or stupor.
    • Focal: Hemiparesis/Hemisensory loss (can occur solely due to hyperglycaemia - resolves with treatment).
    • Reflexes: Hyperreflexia or extensor planters (metabolic).
6. Investigations

Immediate Bedside / Laboratory Panel

Investigations in HHS are directed at three goals: confirming the diagnosis, assessing severity (degree of dehydration/osmolarity), and identifying the precipitant (The "Why?").

1. Metabolic Profile

  • Serum Glucose: Universally elevated, typically >30 mmol/L, often exceeding 50-60 mmol/L (beyond meter range).
  • Serum Osmolality: The definitive test. Measured osmolality is preferred, but calculated is standard for monitoring.
    • Diagnostic threshold: >320 mOsm/kg.
    • Significance: Every 10 mOsm/kg rise correlates with a drop in GCS.
  • Urea & Electrolytes:
    • Sodium: Can be low (dilutional/pseudohyponatraemia) or high (severe dehydration).
      • Interpretation: A "Normal" sodium (e.g., 140) in the presence of Glucose 50 is actually ABNORMAL (indicates water loss). Corrected Sodium would be ~160.
    • Potassium: Often normal on admission due to insulin deficiency/acidosis shifting K+ out of cells.
      • Warning: Total body potassium is always depleted (300-1000 mmol deficit). It will plummet once insulin starts.
    • Urea/Creatinine: Pre-renal AKI is almost universal. Urea rises disproportionately to Creatinine (Urea:Cr ratio >100) due to dehydration and catabolism.
  • Venous Blood Gas (VBG):
    • pH: Usually >7.3 (Normal or mildly acidotic from Lactate/Uraemia).
    • Bicarbonate: Usually >15 mmol/L.
    • Lactate: Often elevated (Type A from hypoperfusion, Type B from Metformin).

2. Ketone Status

  • Blood Ketones: <3.0 mmol/L.
  • Urine Ketones: Negative or +/++.
  • Why low ketones? The hyperosmolality itself may suppress lipolysis, and residual insulin prevents run-away ketogenesis.

3. Full Blood Count (FBC)

  • Leucocytosis (WBC): Often 15-25 x 10^9/L.
    • Note: This can be a "Stress Leucocytosis" from the metabolic crisis itself, NOT just infection.
    • Action: Do not assume infection solely on WBC. Look for CRP rise or focal signs (CXR/Urine).
  • Haemoglobin/Haematocrit: Elevated due to haemoconcentration (plasma volume loss).

4. Cardiac Enzymes (Troponin)

  • HHS is a massive stress test for the heart.
  • Troponin: Frequently elevated.
  • Differentiating Type 1 vs Type 2 MI: Difficult. If ECG changes -> Treat as STEMI/NSTEMI. If global ST depression -> Rate/Demand related.

Differential Diagnosis

ConditionGlucoseOsmolalityKetonespHSymptoms
HHSHigh (>30)High (>320)Low (<3)>7.3Coma, Dehydration
DKAHigh (>11)Normal/HighHigh (>3)<7.3Kussmaul, Abdo Pain
Alcoholic KetoacidosisLow/N/HighNormalHigh<7.3Vomiting, Alcohol Hx
Lactic AcidosisVariableNormalLow<7.3Shock, Metformin use
StrokeNormal*NormalLowNormalHemiparesis (Sudden)
Uraemic EncephalopathyN (unless DM)HighLow<7.35Renal Failure hx

Note: HHS can mimic Stroke (Hemiparesis), and Stroke can precipitate HHS.

Diagnostic Calculations (CRITICAL)

[!IMPORTANT] 1. Serum Osmolality Formula Osmolality = 2(Na+) + Glucose + Urea Note: Ignore Potassium in this estimation formula (JBDS). Normal range 275-295. HHS >320.

[!IMPORTANT] 2. Corrected Sodium Formula Because hyperglycaemia draws water into vessels, it dilutes Sodium. To know the "true" sodium status: Corrected Na = Measured Na + 2.4 × ((Glucose - 5.5) / 5.5) Simplified: Add ~2.4 mmol/L to Na for every 5.5 mmol/L rise in Glucose above normal.

Etiology Workup ("Why now?")

  • Septic Screen: Blood cultures, Urine culture, CXR.
  • ECG: Silent MI? AF?
  • HbA1c: Undiagnosed diabetes or poor control?
  • CT Head: If focal neurology or persistent coma after rehydration.
  • Abdominal Imaging: If elevated Lactate/Amylase (Mesenteric Ischaemia/Pancreatitis).
7. Management

Principles of Care (JBDS-IP)

The management of HHS differs significantly from DKA. A rapid correction of glucose is dangerous. Goals:

  1. Gradual normalisation of Osmolality (3-8 mOsm/kg/hr).
  2. Restoration of circulatory volume (Fluid Resuscitation).
  3. Electrolyte correction (Potassium/Sodium).
  4. Identification of precipitant (Sepsis/MI).
  5. Prevention of complications (VTE/Oedema).

Acute Management Algorithm

         [HHS DIAGNOSIS]
    Glu >30 | Osm >320 | No Ketosis
                ↓
┌──────────────────────────────────────┐
│  STEP A: IMMEDIATE RESUSCITATION     │
│  - ABCDE Assessment                  │
│  - IV Access x2 (18G)                │
│  - FLUIDS: 0.9% Saline (1L STAT)     │
│    (If SBP &lt;90)                      │
│  - LMWH: Prophylactic dose           │
└──────────────────────────────────────┘
                ↓
┌──────────────────────────────────────┐
│  STEP B: FLUID REPLACEMENT PHASE     │
│  - Aim: Positive balance 3-6L by 12h │
│  - Type: 0.9% NaCl usually           │
│  - Rate: See Protocol below          │
└──────────────────────────────────────┘
                ↓
┌──────────────────────────────────────┐
│  STEP C: INSULIN DECISION (Hour 1-2) │
│  - Is Glucose falling >5mmol/hr?     │
│    YES → NO INSULIN. Continue fluid. │
│    NO  → START INSULIN 0.05 u/kg/hr  │
└──────────────────────────────────────┘
                ↓
┌──────────────────────────────────────┐
│  STEP D: POTASSIUM CONTROL           │
│  - K &lt;3.5: CENTRAL REPLACEMENT (HOLD INSULIN) │
│  - K 3.5-5.5: Add 40mmol/L           │
│  - K >5.5: Nil added                 │
└──────────────────────────────────────┘

Clinical Monitoring & Nursing Standards (The "HHS Pathway")

Nursing care is as critical as the prescription.

1. Observations Frequency

  • 0-6 Hours: Every 30 minutes (GCS, HR, BP, RR, Saturation).
  • 6-12 Hours: Hourly.
  • Fluid Balance: Strict hourly input/outcome (Catheterize always).

2. Neurological Monitoring

  • GCS: Drop in GCS is the first sign of Cerebral Oedema.
  • Pupils: Check for asymmetry (Coning).
  • Confusion: Safety rails, 1:1 nursing if agitated delirium.

3. Skin Integrity

  • HHS patients are elderly and immobile.
  • Waterlow Score: High risk.
  • Action: Pressure relieving mattress (Category 3/4) immediately. Reposition every 2 hours.

4. Mouth Care

  • Severe dehydration causes "crisp" tongue and mucosal cracking.
  • High risk of parotitis.
  • Regular wet swabs/mouth wash.

1. Fluid Resuscitation Protocol

Fluid is the primary treatment. It lowers osmolarity and glucose (via renal excretion) safer than insulin.

Fluid Choice:

  • First Line: 0.9% Sodium Chloride (Normal Saline).
    • Advantage: Isotonic restoration of volume.
    • Disadvantage: Hyperchloraemic acidosis in large volumes (less relevant in HHS than DKA).
  • Alternative: 0.45% Sodium Chloride (Hypotonic Saline).
    • Indication: ONLY if Osmolality is not falling and Sodium is rising steeply despite fluid.
    • Risk: Rapid drop in tonicity -> Cerebral Oedema. Senior decision only.
  • Fluid to Avoid: Hartmann's (Contains Lactate/Potassium - interferes with monitoring initially, though acceptable later).

Rate of Administration (Typical): Adjust for age/renal failure/cardiac failure.

  • 0 - 1 hr: 1 Litre (0.9% NaCl).
  • 1 - 2 hr: 1 Litre (+ KCl).
  • 2 - 4 hr: 1 Litre (+ KCl).
  • 4 - 6 hr: 1 Litre (+ KCl).
  • 6 - 12 hr: 1 Litre (+ KCl).
  • 12 - 24 hr: Based on remaining deficit (approx 100ml/hr).

Monitoring the "Sodium Lag":

  • As glucose falls, water moves back into cells, concentrating Serum Sodium.
  • Expected Na Rise: Sodium should rise by 2.4 mmol/L for every 5.5 mmol/L drop in Glucose.
  • If Na does NOT rise: You are giving too much free water. Risk of Cerebral Oedema. Slow fluids down.
  • If Na rises TOO FAST (>10 in 24h): Risk of Pontine Myelinolysis. Switch to 0.45% Saline (or Dextrose 5% if glucose low).

2. Insulin Therapy Protocol

Fixed Rate Intravenous Insulin Infusion (FRIII)

  • Dose: 0.05 units/kg/hour (e.g., 3-4 units/hr).
  • Timing:
    • Do NOT start at Hour 0 (unless Ketotic/DKA overlap).
    • Start at Hour 1-2 ONLY IF glucose is not falling by >5mmol/L with fluids alone.
  • Titration:
    • If Glucose falls <5 mmol/L/hr -> Increase to 0.1 u/kg/hr.
    • If Glucose falls >10 mmol/L/hr -> STOP insulin (Too fast).
    • If Glucose <14 mmol/L -> Start 10% Dextrose (125ml/hr) and continue insulin (to suppress ketogenesis if present, or switch to SC).

3. Potassium Replacement Protocol

Potassium shifts are dangerous. Insulin drives K+ into cells. Check K+ every hour initially.

Serum K+ Level (mmol/L)ActionReplacement Rate
> 5.5NilNone
3.5 - 5.5Continue/Start K+40 mmol per Litre of fluid
< 3.5HOLD INSULINSenior Review. Central Line required for >20mmol/hr rates. Needs intensive replacement (e.g., 40mmol in 500ml over 2h).

4. VTE Prophylaxis

Mandatory. HHS patients are severely hypercoagulable (Hyperviscosity).

  • LMWH (Enoxaparin/Dalteparin): Prophylactic dose (e.g., Enoxaparin 40mg SC OD).
  • Treatment Dose?: Only if confirmed DVT/PE.
  • Anti-Embolism Stockings: If LMWH contraindicated.

5. Treatment Targets (Hourly Monitoring)

ParameterTarget ChangeAction if Missed
OsmolalityFall 3-8 mOsm/kg/hrIf <3: Increase Insulin. If >8: Stop Insulin/Slow Fluids
GlucoseFall 5-10 mmol/L/hrAs above.
SodiumRise (Calculated)If falling: Slow fluids.
Fluid BalancePositive 3L by 6hrIncrease rate.
Conscious LevelImproveCT Head if deteriorating (Oedema).

Pharmacology of Key Agents

1. Soluble Insulin (Fast Acting)

  • Examples: Actrapid, Humulin S.
  • Mechanism: Binds to Insulin Receptor (Tyr-Kinase), recruiting IRS-1/2, activating PI3K/Akt pathway, translocating GLUT-4 to cell surface.
  • PK:
    • half-life (IV): 5-9 minutes (Why we need continuous infusion).
    • Onset: Immediate.
    • Clearance: Renal (Decrease dose in severe AKI? In HHS, AKI is pre-renal and recovers, usually safely titratable).

2. 0.9% Sodium Chloride

  • Composition: 154 mmol/L Na, 154 mmol/L Cl. (Osmolarity 308).
  • Physiology: Technically slightly hypertonic to plasma (285-295), but isotonic in the bag.
  • Adverse Effects: Hyperchloraemic Metabolic Acidosis (Normal Anion Gap).
  • In HHS: The acidosis risk is outweighed by the need for stable volume expansion.

3. Low Molecular Weight Heparin (Enoxaparin)

  • Mechanism: Potentiates Antithrombin III, inhibiting Factor Xa.
  • Dosing:
    • Prophylactic: 40mg SC OD (eGFR >30).
    • Renal Dose: 20mg SC OD (eGFR <30).
    • Therapeutic: 1.5mg/kg OD or 1mg/kg BD.
  • Monitoring: Anti-Xa levels (in obesity/renal failure).
8. Complications

Complications in HHS are frequently fatal and often iatrogenic (caused by treatment).

1. Cerebral Oedema

Rare in adults (<1%) but high mortality (50%).

  • Mechanism (Theories):
    1. Osmotic Shift: Rapid drop in plasma osmolality causes water to rush into hypertonic brain cells.
    2. Idiogenic Osmoles: Brain cells accumulate organic osmoles (taurine, glutamate) to protect against shrinkage. These take days to clear. If fluids given fast, these osmoles pull water in.
  • Risk Factors: Young age, Rapid rehydration (>50ml/kg in 4h), Rapid fall in Osmolality, Bicarbonate use.
  • Signs: Headache, Bradycardia, Hypertension (Cushing's triad), Declining GCS, Seizures, Papilloedema.
  • Management:
    • Stop Fluids.
    • Hypertonic Therapy: Mannitol (0.5-1g/kg IV) or Hypertonic Saline (3% 5ml/kg).
    • Imaging: CT Head (to confirm/exclude bleed).
    • ICU: Intubation and ventilation maintain pCO2.

2. Osmotic Demyelination Syndrome (ODS)

Formerly "Central Pontine Myelinolysis".

  • Mechanism: Rapid correction of hyponatraemia (or rapid rise in Na during HHS treatment).
  • Target: Limit Sodium rise to <10 mmol/L in 24 hours.
  • Presentation: Delayed (2-6 days). Quadriparesis, Dysarthria, Dysphagia, "Locked-in Syndrome".
  • Prognosis: Often permanent severe disability.

3. Venous Thromboembolism (VTE)

HHS is a highly thrombogenic state.

  • Pathology: Dehydration (Stasis) + Hyperglycaemia (Endothelial damage) + Infection (Hypercoagulable).
  • Incidence: DVT/PE occurs in up to 5-10% even with prophylaxis.
  • Management:
    • Prevention: Enoxaparin 40mg SC daily (adjust for renal).
    • Treatment: If DVT confirmed -> Treatment dose LMWH.

4. Rhabdomyolysis

  • Cause: "Found down" (immobilisation), Statins + Fibrates, Severe hypophosphataemia.
  • Signs: Muscle pain, Dark urine ("Coca-Cola"), AKI.
  • Inv: CK >1000 (often >10,000).
  • Rx: Fluid resuscitation (already doing it). Maintain urine output >1ml/kg/hr.

5. Electrolyte Crises

  • Hypokalaemia: Arrhythmias (VT/VF). Cause: Insulin shifting K+ into cells.
  • Hypophosphataemia: Respiratory depression, muscle weakness. Replace if <0.32 mmol/L.
  • Hypomagnesaemia: Arrhythmias, Seizures.

6. Hypoglycaemia

  • Cause: Insulin continued when glucose <14 mmol/L.
  • Risk: Neuroglycopenia in already confused patient.
  • Prevention: Start 10% Dextrose when Gluc <14. Reduce insulin rate.
9. Prognosis & Outcomes

Mortality statistics

  • HHS: 10-20% (Much higher than DKA).
  • Predictors of Death:
    • Age >75.
    • Sepsis (Pneumonia).
    • Hypotension at presentation.
    • Osmolality >375 mOsm/kg.
    • Sodium >160 mmol/L.

Resolution Criteria (When is HHS "Over"?)

HHS is resolved when:

  1. Osmolality <300 mOsm/kg.
  2. Hypovolaemia corrected (Renal function recovered).
  3. Cognitive status returns to baseline.
  4. Patient is eating and drinking.

Discharge Planning & Prevention

1. Medication Review (The "Safety Check")

Many medications should be held or stopped.

  • SGLT2 Inhibitors (Dapagliflozin/Empagliflozin): STOP. High risk of recurrence/Euglycaemic DKA.
  • Diuretics: Review indication. Reduce dose if possible?
  • Metformin/ACEi: Restart only when renal function (eGFR) is stable.

2. Converting to Subcutaneous Insulin

Most HHS patients are insulin-naive T2DM.

  • Initial Regimen: Basal-Bolus (e.g., Lantus + NovoRapid) is preferred in hospital.
  • Long Term:
    • If HbA1c >10%: Discharge on Insulin (Basal) + Metformin.
    • If HbA1c <9%: May trial Gliclazide + Metformin.
    • Note: Glucotoxicity ("stunned pancreas") implies that insulin is often needed for 4-12 weeks until beta cells recover.

3. Patient Education ("Sick Day Rules")

Every patient must receive a "Sick Day Card". Instructions if feeling unwell (Vomiting/Fever):

  • STOP: SGLT2 Inhibitors, ACE Inhibitors, Diuretics, NSAIDs.
  • CONTINUE: Insulin (never stop, even if not eating).
  • TEST: Check Glucose every 4 hours.
  • HYDRATE: Drink 100ml fluid every hour.

Special Populations & Geriatric Considerations

HHS is predominantly a disease of the elderly (>70 years).

1. Management in Heart Failure

The "Fluid Paradox": The patient needs fluid to survive HHS, but fluid causes Pulmonary Oedema.

  • Strategy:
    • Slower Rate: Maximum 250ml-500ml boluses, or slower infusion (e.g., 500ml over 4 hours).
    • Invasive Monitoring: Arterial Line. CVP (if available).
    • Diuretics?: Furosemide may be needed concurrently if "wet".
    • Endpoint: Aim for "Euvolamia" rather than "Positive Balance". Accept slightly higher Osmolality for longer duration.

2. Management in Dialysis Patients (ESRF)

  • Challenge: Anuric patients cannot have Osmotic Diuresis. They present with Hyperglycaemia + Hyperosmolality but usually Hypervolaemia (Fluid overload from thirst).
  • Action:
    • Fluids: RESTRICT or STOP.
    • Insulin: The primary treatment (Driving glucose into cells lowers Osmolality, but where does the fluid go? It shifts intracellularly).
    • Dialysis: Urgent Haemodialysis is the gold standard for correcting Osmolality and Removal of Glucose generally.

3. Dementia & Delirium

  • Compliance: Patient pulls out IV lines.
  • Capacity: Use Mental Capacity Act (Best Interests).
  • Restraint: Chemical restraint (Haloperidol) may be needed but lowers Seizure threshold. 1:1 Nursing preferred.
  • Aspiration: Keep NBM initially if GCS low. NG Tube if necessary.

4. The "Social Admission"

  • Many HHS patients were living independently but failing.
  • Assessment of function: Was this a gradual decline?
  • Safeguarding: Self-neglect?
10. Evidence & Guidelines

Joint British Diabetes Societies (JBDS) Guidelines (2022)

The JBDS "Management of HHS" is the primary reference for UK practice. Key recommendations include:

1. Diagnostic Criteria

  • Hypovolaemia.
  • Marked Hyperglycaemia (>30 mmol/L).
  • Hyperosmolality (>320 mOsm/kg).
  • Absence of significant ketonaemia (<3.0 mmol/L) or acidosis (pH >7.3).

2. Fluid Therapy Strategy

  • Type: 0.9% Sodium Chloride is the default.
  • Rate: Monitor fluid balance targets rather than fixed excessive rates. Aim for positive balance.
  • Sodium: Monitor corrected sodium. If it falls, fluid is too hypotonic.

3. Insulin Strategy

  • Delay: Do NOT start insulin until fluid resuscitation is established (usually 60-120 mins).
  • Rationale: Insulin causes vascular collapse (sugar moves into cells -> water follows -> hypovolaemia).
  • Dose: Fixed rate 0.05 units/kg/hr.

4. Electrolytes

  • Potassium: Similar replacement to DKA.
  • Magnesium/Phosphate: Check and replace if symptomatic.

American Diabetes Association (ADA) Standards (2024)

  • Consistent with JBDS.
  • Emphasizes the high mortality rate (up to 20%) compared to DKA (<1%).

Key Evidence Summaries

Kitabchi et al. (2001) - "The Hyperglycaemic Crises Consensus"

  • A foundational review defining DKA and HHS (then NKH).
  • Findings: Established the biochemical distinctness. DKA = Lipolysis driven by absolute insulin deficiency. HHS = Gluconeogenesis driven by relative insulin deficiency.
  • Clinical Impact: Formed the basis for modern separate protocols.

Pasquel et al. (2014) - "Mixed DKA/HHS"

  • Study: Retrospective analysis of patients with hyperglycaemic crises.
  • Findings: 30% of patients with HHS also have ketoacidosis (Mixed features).
  • Outcome: The "Mixed" group had higher mortality than DKA alone and higher complication rates.
  • Recommendation: Treat the hyperosmolar/dehydration aspect first (HHS protocol) but be ready to escalate insulin if ketones persist.

Stoner et al (2005) - "Low Dose Insulin"

  • Findings: Confirmed that low dose insulin (0.05-0.1 u/kg/hr) is as effective as high dose, with significantly less hypoglycaemia and hypokalaemia risk.
11. Patient/Layperson Explanation

What is HHS?

"HHS stands for Hyperosmolar Hyperglycaemic State. It is a very serious complication of diabetes, usually Type 2. It happens when blood sugar levels become dangerously high over a period of days or weeks."

How did this happen?

"Normally, insulin helps sugar enter your body's cells. In HHS, although there is a tiny bit of insulin working (enough to stop acid building up, which is why it's not 'Ketoacidosis'), there isn't enough to control the sugar. Because the sugar is so high (often 10x normal), it spills into the urine and pulls huge amounts of water with it. This acts like a strong diuretic, causing you to pee out litres of fluid. You have become severely dehydrated—much more than just 'needing a drink'. Your blood has become thick and salty (concentrated)."

Why is it dangerous?

"Because the blood is thick, it can clot easily, causing heart attacks or strokes. The severe dehydration can also shut down the kidneys. Fluid loss from the brain can cause confusion or coma."

How do we treat it?

"The main treatment is Fluid. We will replace the lost water through a drip very gradually over the next 24-48 hours. We also carefully use insulin to bring the sugar down, but we do this slowly to prevent brain swelling. It takes time to fix safely."

12. References
  1. Joint British Diabetes Societies (JBDS) for Inpatient Care. The management of the hyperosmolar hyperglycaemic state (HHS) in adults with diabetes. JBDS-IP Guidelines. 2022.
  2. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. [PMID: 19564476]
  3. Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care. 2014;37(11):3124-3131. [PMID: 25342831]
  4. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2005;71(9):1723-1730. [PMID: 15887451]
  5. Nugent BW. Hyperosmolar hyperglycemic state. Emerg Med Clin North Am. 2005;23(3):629-648. [PMID: 15982538]
  6. Wachtel TJ, Silliman RA, Lamberton P. Predisposing factors for the diabetic hyperosmolar state. Arch Intern Med. 1987;147(3):499-501. [PMID: 3827427]
  7. MacIsaac RJ, Lee LY, McNeil JJ, Tsalamandris C, Jerums G. Influence of age on the presentation and outcome of acidotic and hyperosmolar diabetic emergencies. Intern Med J. 2002;32(8):379-385. [PMID: 12162395]
  8. Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019;365:l1114. [PMID: 31142480]
  9. Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State. Med Clin North Am. 2017;101(3):587-606. [PMID: 28372715]
  10. Dhatariya K. The management of frank and incipient diabetic ketoacidosis and hyperosmolar hyperglycemic state. Expert Rev Endocrinol Metab. 2022.
  11. Umpierrez G, Korableva I. Hyperglycemic Crises. [Updated 2023]. In: Feingold KR et al. Endotext [Internet].
  12. Scott A. Management of hyperosmolar hyperglycaemic state in adults. Nurs Stand. 2015. [PMID: 25625769]
  13. Wolfsheimer TL. Diabetic ketoacidosis and hyperosmolar hyperglycemic state. Vet Clin North Am Small Anim Pract. 1989. (Comparative physiology).
  14. Ennis ED et al. The hyperosmolar hyperglycemic syndrome. Diabetes Rev. 1994.
  15. Matz R. Management of the hyperosmolar hyperglycemic syndrome. Am Fam Physician. 1999. [PMID: 10524491]
  16. Trence DL et al. Hyperglycemic crises in type 2 diabetes mellitus: lactic acidosis and nonketotic hyperosmolar coma. Endocrinol Metab Clin North Am. 2001. [PMID: 11727403]
  17. Delaney MF et al. Diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Endocrinol Metab Clin North Am. 2000. [PMID: 11149163]
  18. Piniés JA et al. Precipitation of hyperosmolar nonketotic hyperglycemic coma by corticosteroids. Acta Diabetol. 1994. [PMID: 7859560]
  19. Small M et al. Acute metabolic decompensation in diabetes. Gerontology. 1988. [PMID: 3141678]
  20. Levine SN et al. Hyperglycemic hyperosmolar nonketotic coma. Med Clin North Am. 1995. [PMID: 7897557]
13. Examination Focus

Common Exam Questions

1. "Distinguish HHS from DKA." Key Differentiators:

  • Timecourse: HHS weeks, DKA hours.
  • Biochemistry: HHS Glucose >30, Osm >320, No Ketosis. DKA Ketosis dominant.
  • Population: HHS Elderly T2DM. DKA Young T1DM (usually).
  • Insulin: HHS 0.05 u/kg/hr delayed. DKA 0.1 u/kg/hr immediate(ish).

2. "Why specific Sodium correction?" Answer: Measured sodium is artificially lowered by hyperglycaemia (dilutional). Corrected Na gives true tonicity. Formula: Na + 2.4 * ((Gluc-5.5)/5.5). Significance: If Corrected Na Rises during treatment -> Good. If it Falls -> Danger (Excess free water/Cerebral oedema risk).

3. "When do you start insulin in HHS?" Answer: Only after fluid resuscitation has begun AND if glucose is not falling by fluid dilution alone. Usually hour 2-3. Why?: Starting insulin first moves glucose/water into cells, collapsing intravascular volume -> Shock/Death.

4. "Calculate the Osmolality." Formula: 2(Na) + Urea + Glucose. Scenario: Na 150, K 5.0, Gluc 50, Urea 30. Calc: 2(150) + 50 + 30 = 300 + 50 + 30 = 380 mOsm/kg. Normal: 275-295. Interpretation: Severe Hypertonicity (>320 is diagnostic). Coma likely.

5. "What fluid should be used if Sodium rises rapidly (>15 mmol in 24h)?" Answer: Switch to hypotonic fluid (e.g., 0.45% Saline or Dextrose 5% with insulin). Risk: Central Pontine Myelinolysis (ODS).

6. "Why is LMWH mandatory?" Answer: HHS causes extreme hyperviscosity ("treacle blood") due to dehydration. High risk of DVT, PE, and Arterial thrombosis.

Viva Points

Scenario 1: The Junior Doctor Request "The Nurse wants to start the Sliding Scale (VRIII) because the glucose is 45. What do you say?" Response: "Do NOT start it. Start Fluids (1L Normal Saline) first. Explain that in HHS, the priority is volume. Insulin too early causes circulatory collapse. We monitor hourly. If glucose doesn't drop by 5 mmol/L with fluids alone, THEN we start fixed rate insulin at 0.05u/kg."

Scenario 2: The Complication "Patient becomes drowsy 6 hours into treatment. Sats dropping." Differential: Cerebral Oedema (if fluids too fast), Heart Failure (fluid overload), Aspiration Pneumonia. Action: Stop fluids. ABCDE. CT Head. U&Es (check Sodium/Osmolality trajectory).

Scenario 3: The Discharge "Can they go home on Metformin?" Response: "Depends. Initially they need insulin (Basal-Bolus) to clear glucose toxicity. Once stable outpatient, if C-Peptide shows T2DM, can titrate to Metformin/Gliclazide/SGLT2i. Warning: SGLT2i risk of euglycaemic DKA if dehydrated again."

OSCE Station: The "Confused Diabetic"

Scenario: 78M, T2DM. Found confused by neighbours. Task: Assess and initiate management. Steps:

  1. ABCDE: Airway (GCS?). Breathing (No Kussmaul). Circ (Shock?).
  2. Finger Prick: Glucose "Hi" (>27.8). Ketones 0.2.
  3. Diagnosis: Likely HHS.
  4. Action: 1L N.Saline STAT. Catheterise. ECG.
  5. Prescription:
    • Fluids: 1L 0.9% NaCl over 1h, then 1L/2h.
    • Insulin: HOLD. Fluid first.
    • LMWH: Enoxaparin 40mg SC (if renal function ok).
    • Investigations: Lab Glucose, Venous pH, U&Es (for Urea/Na), Osmolality (Calculated).

Common Mistakes

  • Insulin First: The most dangerous error. Risk of cardiac arrest.
  • Wrong Dose: Using DKA dose (0.1 u/kg) instead of HHS prose (0.05 u/kg).
  • Stopping Fluids: Stopping because "Chest is wet" without consulting senior (patient is 10L dehydrated).
  • Ignoring Sodium: Failing to calculate corrected sodium.
  • Discharge: Sending home without VTE prophylaxis (risk remains high for weeks).

MCQ Practice

Q1: A 70M presents with Glucose 45, pH 7.38, Ketones 0.4. BP 90/60. First line? A. Insulin Scale B. Insulin Fixed Rate 0.1 u/kg/hr C. 1L 0.9% Saline STAT D. 500ml 10% Dextrose E. Bicarbonate Answer: C. HHS with Shock. Fluids are priority. Insulin is contraindicated initially.

Q2: Which electrolyte change is most dangerous during HHS treatment? A. Hypernatraemia B. Hypokalaemia C. Hypophosphataemia D. Hypercalcaemia E. Hyponatraemia Answer: B. Hypokalaemia. Insulin drives K+ into cells. Arrhythmia risk is high. Monitor K+ q1-2h.

Q3: Calculated Osmolality formula? A. 2(Na+K) + Glucose + Urea B. 2(Na) + Glucose + Urea C. 2(Na) + Glucose D. Na + Glucose + Urea E. 2(Na+K) + Urea Answer: B. 2(Na) + Glucose + Urea. (JBDS 2022).

Q4: Rate of Osmolality reduction target? A. 1 mOsm/kg/hr B. 3-8 mOsm/kg/hr C. 10-15 mOsm/kg/hr D. >20 mOsm/kg/hr E. As fast as possible Answer: B. 3-8. Too slow = unresolved crisis. Too fast = Cerebral Oedema/Pontine Myelinolysis.

Q5: A patient usually takes Mixed Insulin. They present with HHS. What do you do with their long-acting insulin? A. Stop it completely B. Continue usual dose C. Double the dose D. Give half dose E. Switch to IV only Answer: B. Continue usual long-acting (Basal) insulin if possible, to prevent rebound hyperglycaemia when IV insulin stops. This is "Basal continuation".

Q6: Corrected Sodium calculation reveals a rise from 145 to 160 mmol/L in 12 hours. Best action? A. Continue 0.9% Saline B. Switch to 0.45% Saline C. Give Furosemide D. Give Mannitol E. Start Desmopressin Answer: B. A rapid rise (>10mmol/24h) or failure to fall suggests 0.9% Saline is relatively too hypertonic or insufficient free water. Switch to hypotonic fluid (0.45% NaCl) under supervision to slow the rise and provide free water.

Q7: Which drugs are known precipitants of HHS? A. ACE Inhibitors B. Thiazide Diuretics C. PPIs D. Statins E. Aspirin Answer: B. Thiazides (and Steroids) impair glucose tolerance and can precipitate HHS.

Advanced MCQ Bank (Case Scenarios)

Case 1: The "Mixed" Presentation A 24-year-old female with T1DM presents with vomiting. Glucose 45 mmol/L. pH 7.15. Ketones 4.5. Osmolality 335 mOsm/kg. Q: How do you classify and manage? A. Pure DKA - Standard protocol B. Pure HHS - Fluid only C. Mixed DKA/HHS - Treat as HHS initially (Fluid focus) but start fixed rate insulin earlier (0.05 u/kg) D. Mixed DKA/HHS - Treat as DKA (0.1 u/kg) immediately Answer: C/D. This is "Hyperosmolar DKA". The priority is Fluid (for the Osmolality) BUT the Acidosis is severe. Guidelines suggest using the DKA monitoring chart but perhaps a cautious fluid approach. However, in young T1DM, DKA outcome is dominant. Most would treat as severe DKA with fluid caution. (Discussion point).

Case 2: The Complication 72M treated for HHS. Day 3: develops slurred speech and quadriparesis. MRI shows pontine hyperintensity. Q: What caused this? A. Cerebral Oedema B. Osmotic Demyelination Syndrome (ODS) C. Stroke D. Meningitis Answer: B. ODS. Likely due to rapid correction of sodium.

Case 3: Prevention Which medication should be STOPPED during "Sad/Sick Days" to prevent HHS/DKA? A. Insulin B. Metformin C. Dapagliflozin (SGLT2i) D. Ramipril E. Atorvastatin Answer: C. SGLT2 inhibitors (and B/D: Metformin/Ramipril for AKI risk). SGLT2i specifically cause "Euglycaemic DKA" but in T2DM can contribute to dehydration. Insulin should NEVER be stopped.

Glossary of Terms

  • Anion Gap: The difference between primary measured cations (Na+ and K+) and the primary measured anions (Cl- and HCO3-). Normal = 8-12(16) mEq/L. In HHS, this is typically normal, distinguishing it from DKA. A high anion gap in HHS suggests lactic acidosis or uraemia.
  • Basal Insulin: Long-acting insulin (e.g., Glargine, Detemir, Degludec) that controls glucose production by the liver (gluconeogenesis) during fasting states.
  • Bolus Insulin: Short-acting insulin (e.g., Aspart, Lispro) used to cover mealtime glucose excursions.
  • Cerebral Oedema: A life-threatening complication where fluid shifts into brain cells, causing swelling. Risk factors include rapid rehydration and rapid drops in osmolality.
  • Corrected Sodium: A calculated value that estimates the true serum sodium concentration if the hyperglycaemia were corrected. It accounts for the dilutional effect of glucose drawing water into the intravascular space.
  • Azotaemia: Elevated blood urea and nitrogen, a sign of renal insufficiency common in HHS.
  • Glycosuria: Excretion of glucose in urine.
  • Osmotic Diuresis: Loss of water driven by the osmotic pressure of non-reabsorbed glucose in the renal tubules.
  • Hyperviscosity: Increased thickness of blood due to dehydration, predisposing to thrombosis.
  • Lactic Acidosis: Type A (hypoperfusion) or Type B (Metformin) acidosis.
  • Ketonaemia: Presence of ketones in blood (Beta-hydroxybutyrate).
  • Euglycaemic DKA: DKA with normal blood sugar, often caused by SGLT2 inhibitors.
  • Insulin Resistance: Reduced cellular response to insulin.
  • Gluconeogenesis: Synthesis of glucose from non-carbohydrate precursors (lactate, glycerol, amino acids).
  • Glycogenolysis: Breakdown of glycogen to glucose.
  • Counter-regulatory Hormones: Glucagon, Cortisol, GH, Catecholamines.
  • Waterlow Score: A scale for assessing pressure ulcer risk.
  • Virchow's Triad: Stasis, Hypercoagulability, Endothelial Injury.
  • CVP (Central Venous Pressure): Pressure in the thoracic vena cava, used to estimate preload (volume status).
  • Arterial Line: Intra-arterial catheter for continuous BP monitoring.
  • Sliding Scale (VRIII): Variable Rate Intravenous Insulin Infusion.
  • Basal-Bolus: A regimen of long-acting (Basal) and mealtime (Bolus) insulin mimicking physiological secretion.
  • Hypokalaemia: Low serum potassium (<3.5 mmol/L).
  • Hypernatraemia: High serum sodium (>145 mmol/L).
  • Pontine Myelinolysis: See ODS.
  • Microvascular Complications: Retinopathy, Neuropathy, Nephropathy.
  • Macrovascular Complications: Stroke, MI, Peripheral Vascular Disease.
  • HbA1c: Glycated Haemoglobin, a measure of 3-month average glucose.
  • SGLT2 Inhibitor: Drug class ending in -gliflozin (increases glucose excretion in urine).
  • GLP-1 Agonist: Drug class ending in -tide (increases insulin, decreases glucagon).

Advanced Clinical Reasoning: The "Why" of HHS

Why is the mortality higher than DKA?

  1. Age: HHS patients are older with more comorbidities (Heart Failure, COPD).
  2. Delay: The insidious onset means they present later, with more profound dehydration (10L vs 4L).
  3. Thrombosis: The hyperviscosity is more severe in HHS, leading to fatal PE/Stroke.
  4. Complexity: Managing fluid balance in a 90-year-old with Heart Failure is harder than in a 20-year-old with DKA.

The "Sodium Paradox" Explained

In HHS, Sodium is the most confusing electrolyte.

  • Phase 1 (Presentation): Hyperglycaemia pulls water into vessels -> Dilutes Sodium (Low Measured Na).
  • Phase 2 (Treatment): Glucose falls -> Water goes back to cells -> Sodium "Concentrates" (Measured Na Rises).
  • Phase 3 (Danger): If you give too much free water (0.45%), Sodium drops rapidly -> Brain swelling. If you give too much Salt (0.9%), Sodium rises dangerously -> ODS.
  • Goldilocks Zone: We want Sodium to rise slowly or stay stable as Glucose falls.

Further Advanced Cases

Case 4: The Anuric Patient 80M with ESRF on Haemodialysis. Admitted with HHS (Gluc 50, Osm 330). Q: Management priority? A. 1L Saline STAT B. Insulin 0.1 u/kg C. Urgent Haemodialysis D. 500ml Saline over 4h Answer: C. He cannot excrete the fluid or the glucose (no urine). Dialysis is the only way to fix the Osmolality safely.

Case 5: The Post-Op Challenge 65F post-Cabg (Day 2). Glucose 35. Confusion. Q: Precipitants? A. Infection (Sternal wound/Pneumonia) B. Stress response (Cortisol) C. TPN (Total Parenteral Nutrition) D. Steroids E. All of the above Answer: E. Post-op HHS is common due to "Stress Hyperglycaemia" + Steroids + TPN + Infection.

Case 6: The "Normal" Glucose? Patient has Osmolality 340. Glucose 15. Sodium 170. Q: Is this HHS? A. Yes B. No, it's Hypernatraemic Dehydration C. It's DKA Answer: B. (Strictly). HHS requires Glucose >30. This is Hyperosmolar Hypernatraemia. Management is similar (Fluid!) but insulin is NOT needed (Glucose is nearly normal).

Last updated: 2025-12-27

At a Glance

EvidenceHigh
Last Updated2025-12-27
Emergency Protocol

Red Flags

  • Coma or GCS &lt;8 requiring airway protection
  • Severe dehydration with Shock (SBP &lt;90)
  • Serum Osmolality >350 mOsm/kg
  • Mixed DKA/HHS (pH &lt;7.1)
  • Silent Myocardial Infarction
  • Arterial/Venous Thromboembolism

Clinical Pearls

  • 320 mOsm/kg. Management prioritizes gradual fluid resuscitation to avoid cerebral oedema, with delayed and cautious insulin therapy.
  • 30 mmol/L, Osmolality
  • 15, Ketones &lt;3.0 mmol/L.
  • **Don't Chase the Glucose**: The goal is to normalise **Osmolality**, not just glucose. A rapid drop in glucose causes a rapid drop in osmolality, shifting water into brain cells -
  • Cerebral Oedema. Aim for a gentle decline (glucose &lt;5 mmol/L per hour).

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines