Hyperosmolar State

Introduction & Australian Epidemiology

Hyperosmolar hyperglycaemic state (HHS), previously known as hyperosmolar non-ketotic coma (HONK), is a life-threatening diabetic emergency characterised by severe hyperglycaemia, hyperosmolality, and dehydration with minimal or absent ketosis. Unlike diabetic ketoacidosis (DKA), HHS typically develops more gradually over days to weeks, making early recognition challenging but critical for optimal outcomes.

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Critical Emergency: HHS carries a mortality rate of 5-20%, significantly higher than DKA, making prompt recognition and treatment essential.

Australian Epidemiology & Healthcare Context

HHS predominantly affects adults with type 2 diabetes mellitus, with the following Australian epidemiological patterns:

Incidence: Approximately 1-2 cases per 100,000 population annually, representing 5-10% of all diabetic emergencies presenting to Australian emergency departments
Age distribution: Peak incidence in patients aged 60-80 years, with mean age of presentation 65 years
Gender: Slight female predominance (55-60% of cases)
Diabetes type: 85-90% occur in patients with type 2 diabetes; 10-15% represent the initial presentation of previously undiagnosed diabetes
Seasonal variation: Increased incidence during Australian summer months (December-February) due to dehydration risk

High-Risk Australian Populations

Very High Risk

Elderly Patients (>65 years)

Reduced thirst sensation, impaired renal function, polypharmacy, and increased comorbidity burden

Aged care facilities account for 25% of Australian HHS cases

High Risk

Remote & Rural Communities

Limited healthcare access, delayed presentation, higher rates of uncontrolled diabetes

Particular concern in Aboriginal and Torres Strait Islander populations

Elevated Risk

Comorbid Conditions

Renal impairment, heart failure, stroke, dementia, and malignancy

Present in >70% of Australian HHS patients

Common Precipitating Factors in Australia

Infectious Triggers (40-50%)

Pneumonia (most common)
Urinary tract infections
Sepsis from any source
COVID-19 (emerging trigger since 2020)

Non-Infectious Triggers (30-40%)

Medication non-compliance
Acute myocardial infarction
Stroke
Dehydration (heat exposure)
New medications (corticosteroids, diuretics)

ℹ️

Australian Healthcare Impact: HHS accounts for approximately 2,000-3,000 hospitalisations annually across Australia, with average length of stay 8-12 days and total healthcare costs exceeding $50 million per year.

Key Clinical Differences from DKA

Parameter	HHS	DKA
Onset	Days to weeks	Hours to days
Age group	Usually >50 years	Any age
Diabetes type	Type 2 (85-90%)	Type 1 (75-80%)
Glucose level	>30 mmol/L (typically 40-60)	>11 mmol/L (typically 15-30)
Osmolality	>320 mOsm/kg	Usually <320 mOsm/kg
Ketones	Absent or mild	Significantly elevated
pH	>7.30	<7.30
Mortality	5-20%	1-5%

⚠️

Mixed Presentations: Approximately 10-15% of patients present with features of both HHS and DKA ("mixed diabetic emergency"), requiring careful assessment and management of both conditions.

Early recognition and prompt treatment in Australian healthcare settings can significantly reduce morbidity and mortality associated with HHS. This guideline provides evidence-based recommendations aligned with Australian clinical practice standards and available healthcare resources.

Clinical Presentation & Diagnostic Criteria

Clinical Features

⚠️

Recognition Challenge: HHS typically develops insidiously over days to weeks, with less dramatic symptoms than diabetic ketoacidosis (DKA). Altered mental status may be the only presenting feature in elderly patients.

Early Presentation

Progressive polyuria and polydipsia (may be absent in elderly or those with impaired thirst mechanism)
Generalised weakness and fatigue
Nausea and vomiting (less prominent than in DKA)
Weight loss
Blurred vision

Advanced Presentation

Severe dehydration: Poor skin turgor, dry mucous membranes, sunken eyes
Altered mental status: Confusion, lethargy, stupor, coma (correlates with effective osmolality)
Hypotension and tachycardia: Signs of circulatory shock
Neurological signs: Focal deficits, seizures, hemichorea-hemiballismus
Hypothermia or fever (fever suggests underlying infection)

Mild HHS

Conscious & Alert

• Normal mental status
• Glucose 11-22 mmol/L
• Osmolality 300-320 mOsm/kg
• Minimal dehydration

Outpatient/Ward

Moderate HHS

Altered Consciousness

• Confusion, lethargy
• Glucose 22-33 mmol/L
• Osmolality 320-350 mOsm/kg
• Moderate dehydration

Ward/HDU

Severe HHS

Stupor/Coma

• Coma, focal signs
• Glucose >33 mmol/L
• Osmolality >350 mOsm/kg
• Severe dehydration/shock

ICU Required

Diagnostic Criteria

ℹ️

Key Distinction: HHS is characterised by severe hyperglycaemia and hyperosmolality WITHOUT significant ketosis, distinguishing it from DKA.

Primary Diagnostic Criteria (All Must Be Present)

Parameter	HHS Criteria	Notes
Plasma Glucose	≥30 mmol/L (540 mg/dL)	May be >55 mmol/L in severe cases
Effective Osmolality	≥320 mOsm/kg	Calculated: 2[Na⁺] + glucose (mmol/L)
Arterial pH	≥7.30	Absence of significant acidosis
Serum Bicarbonate	≥15 mmol/L	Minimal ketosis
Urine/Serum Ketones	Small or absent	Ketones <3 mmol/L (blood)

Mental Status Classification

Osmolality (mOsm/kg)	Mental Status	Clinical Features
300-320	Alert to drowsy	Normal orientation, mild confusion
320-350	Lethargic	Disoriented, requires stimulation
350-380	Stuporous	Minimal response to stimuli
>380	Comatose	Unresponsive, may have focal signs

Differential Diagnosis

Primary Considerations

Diabetic Ketoacidosis (DKA): pH <7.30, bicarbonate <15 mmol/L, significant ketosis
Mixed HHS/DKA: Features of both conditions (10-15% of hyperglycaemic emergencies)
Euglycaemic DKA: SGLT2 inhibitor-associated, normal glucose with ketosis

Other Hyperosmolar States

Non-ketotic hyperosmolar states: Mannitol, urea, ethylene glycol poisoning
Hypernatraemic dehydration: Water loss exceeding sodium loss
Uremic encephalopathy: Elevated BUN with renal failure

Altered Mental Status Mimics

Cerebrovascular accident: May be precipitating factor or consequence
Septic encephalopathy: Infection-related altered mental status
Drug intoxication/withdrawal: Sedatives, alcohol, illicit substances
Psychiatric emergencies: Severe depression, catatonia

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Critical Recognition: In elderly patients presenting with altered mental status, always check blood glucose and calculate effective osmolality. HHS may present without classic diabetic symptoms.

Risk Factors for Poor Prognosis

Age >70 years
Effective osmolality >350 mOsm/kg
Severe dehydration (>10% body weight loss)
Coma at presentation
Hypotension or shock
Acute kidney injury (creatinine >200 μmol/L)
Concurrent serious illness (MI, stroke, sepsis)
Nursing home residence or limited self-care ability

Investigations

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Emergency Assessment: HHS is a medical emergency requiring immediate biochemical assessment. Do not delay investigations - initiate treatment based on clinical presentation and available rapid tests.

Essential Initial Laboratory Tests

Essential

Point-of-Care Blood Glucose

Immediate bedside testing. Expected >30 mmol/L (>540 mg/dL). Available in all Australian EDs and wards.
Essential

Blood Gas Analysis (VBG/ABG)

pH typically >7.30, bicarbonate usually >18 mmol/L. Assess for mild acidosis. Available in all hospitals.
Essential

Serum/Plasma Osmolality

Diagnostic criterion: effective osmolality >320 mOsm/kg. If not available, calculate using formula. Available in major hospitals.
Essential

Serum Electrolytes (UEC)

Sodium, potassium, chloride, creatinine, urea. Sodium often elevated (>145 mmol/L). Potassium may be normal, high, or low despite total body depletion.
Essential

Ketones (Blood or Urine)

To differentiate from DKA. Beta-hydroxybutyrate <3 mmol/L (blood) or trace to small ketones (urine). Point-of-care meters available.

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Calculated Osmolality Formula: Effective osmolality = 2(Na + K) + glucose + urea. Normal range: 275-295 mOsm/kg. In HHS, calculated osmolality may underestimate measured osmolality due to unmeasured solutes.

Additional Laboratory Investigations

Essential

Full Blood Count

Assess for leukocytosis (infection), haemoconcentration (haematocrit >50%), thrombocytosis. May show pseudoanaemia due to hyperglycaemia.
Available

Liver Function Tests

May be elevated due to dehydration, hepatic steatosis, or medication effects. Available in all laboratories.
Available

Magnesium and Phosphate

Often depleted. Magnesium <0.75 mmol/L suggests deficiency. Phosphate may be low, normal, or high initially.
Available

HbA1c

Reflects glycaemic control over preceding 2-3 months. Helps guide long-term management. May be falsely low in severe illness.
Available

C-Peptide and/or Insulin Level

May help differentiate Type 1 vs Type 2 diabetes in newly diagnosed patients. Not routinely required for acute management.

Precipitant Assessment

Essential

Blood and Urine Cultures

Collect before antibiotics if sepsis suspected. Include aerobic and anaerobic cultures. Urine culture mandatory in all cases.
Essential

Chest X-Ray

Assess for pneumonia, pulmonary oedema, or other respiratory pathology. Portable CXR acceptable if patient unstable.
Available

12-Lead ECG

Assess for myocardial infarction, arrhythmias, or electrolyte-related changes. T-wave changes may reflect hyperkalaemia or hypokalaemia.
Available

Troponin

If myocardial infarction suspected. May be elevated due to dehydration and stress without true coronary event.
Referral

CT Brain

If altered mental state with neurological signs, suspected stroke, or concern for cerebral oedema. Urgent radiology consultation.
Available

Thyroid Function Tests

TSH, T4 if hyperthyroidism suspected as precipitant. Consider in elderly patients or those with unexplained symptoms.

Monitoring Laboratory Tests

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Frequent Monitoring Required: HHS requires intensive biochemical monitoring during treatment to prevent complications such as cerebral oedema, hypokalaemia, and hypoglycaemia.

Every 1-2 hours initially

Blood glucose (point-of-care testing)
Electrolytes (Na, K, Cl, CO2)
Blood gas if acidosis present

Every 4-6 hours

Full UEC including creatinine and urea
Osmolality (calculated or measured)
Magnesium and phosphate

Daily

Full blood count
Liver function tests
Blood cultures if fever persists

Australian Laboratory Availability

Investigation	Rural/Remote	Regional	Metropolitan	Turnaround Time
Point-of-care glucose	✓ Available	✓ Available	✓ Available	Immediate
Blood gas analysis	Limited availability	✓ Available	✓ Available	5-15 minutes
Basic electrolytes	✓ Available	✓ Available	✓ Available	30-60 minutes
Measured osmolality	Send to referral lab	Limited availability	✓ Available	1-4 hours
Ketones (point-of-care)	✓ Available	✓ Available	✓ Available	Immediate
C-peptide/Insulin	Send to referral lab	Send to referral lab	✓ Available	2-24 hours

✅

Key Diagnostic Criteria Summary: HHS diagnosis requires: (1) Blood glucose >30 mmol/L, (2) Effective osmolality >320 mOsm/kg, (3) Absent or mild ketosis (blood ketones <3 mmol/L), and (4) Altered mental state or dehydration. All other investigations support management and identify precipitants.

Special Considerations for Remote Areas

Limited Laboratory Access

Use calculated osmolality if measured osmolality unavailable
Point-of-care testing for glucose, ketones, and basic electrolytes sufficient for diagnosis
Arrange urgent transfer to facility with appropriate monitoring capabilities
Communicate with retrieval services early

Telehealth Support

Utilise telehealth endocrinology consultation if available
Share investigation results with specialist team
Consider phone consultation with metropolitan ICU for complex cases
Document all results clearly for handover during transfer

Treatment

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Emergency Management: HHS is a medical emergency requiring immediate ICU/HDU monitoring and aggressive treatment. Do not delay treatment for confirmatory investigations.

Initial Emergency Management

Airway & Circulation

Assess airway, breathing, circulation. Large-bore IV access (2 x 16G). Consider central access if hypotensive or requiring multiple infusions.

Fluid Resuscitation

Start 0.9% NaCl 1-2L bolus over first 1-2 hours. Adjust based on cardiovascular status and urine output target >0.5mL/kg/hr.

Insulin & Monitoring

Start insulin infusion if glucose >16.7mmol/L. Commence hourly BSL, electrolyte monitoring. Insert urinary catheter.

Fluid Management

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Normal Saline 0.9%

First-line • Initial fluid resuscitation

Initial Phase 1-2L over 1-2 hours

Maintenance 250-500mL/hr based on CVS status

Total Deficit Usually 100-200mL/kg (8-12L)

Target Urine output >0.5mL/kg/hr

Monitoring CVP, fluid balance, clinical assessment

Caution Heart failure, renal impairment

PBS Status ✓ PBS General Benefit

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Half Normal Saline 0.45%

Second phase • When glucose <20mmol/L

Indication When glucose <20mmol/L or Na+ >150mmol/L

Rate 250-500mL/hr

Monitoring Hourly electrolytes initially

Target Gradual correction of hypernatraemia

Caution Avoid rapid Na+ drop >10mmol/L/day

PBS Status ✓ PBS General Benefit

Insulin Therapy

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Insulin (Human/Actrapid)

Actrapid® • IV infusion protocol

Initial Rate 0.05-0.1 units/kg/hr IV

Preparation 50 units in 50mL 0.9% NaCl (1:1)

Target Glucose Decrease 2.8-5.5mmol/L/hr

When to Start If glucose >16.7mmol/L

Adjustment Titrate hourly based on BSL response

Monitoring Hourly BSL, 2-hourly electrolytes

PBS Status ✓ PBS General Benefit

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Insulin Caution: Start insulin only after initial fluid resuscitation has begun. Lower insulin rates than DKA due to greater insulin sensitivity in HHS.

Electrolyte Management

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Potassium Chloride

KCl • Electrolyte replacement

K+ 3.3-5.3mmol/L 20mmol/L in IV fluids

K+ <3.3mmol/L 40mmol/L + delay insulin until K+ >3.3

K+ >5.3mmol/L Withhold K+ supplementation

Maximum Rate 40mmol/hr via central line

Monitoring 2-hourly electrolytes initially

PBS Status ✓ PBS General Benefit

⚡

Magnesium Sulfate

MgSO4 • If Mg2+ <0.75mmol/L

Adult Dose 2g (8mmol) in 100mL 0.9% NaCl

Infusion Rate Over 2-4 hours

Repeat Based on Mg2+ levels

Target Mg2+ 0.75-1.0mmol/L

PBS Status ✓ PBS General Benefit

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Sodium Phosphate

If PO43- <0.32mmol/L • Symptomatic

Adult Dose 20-40mmol in 500mL 0.9% NaCl

Infusion Rate Over 6-12 hours

Indication Severe hypophosphataemia with symptoms

Caution May precipitate hypocalcaemia

PBS Status ✓ PBS General Benefit

Glucose Management During Treatment

🍯

Dextrose 5%

When glucose <14mmol/L

Indication When BSL drops to <14mmol/L

Combination Add to 0.45% NaCl

Rate Continue insulin at reduced rate

Target BSL 8-10mmol/L

Special Populations

🤰 Pregnancy

Insulin Safe in pregnancy. Use human insulin preparations. Continuous insulin infusion preferred for HHS management.

Fluid therapy Monitor for fluid overload. Consider central venous pressure monitoring. Avoid bicarbonate unless severe acidosis.

Monitoring Hourly fetal heart rate monitoring if viable gestation. Obstetric consultation essential. Consider delivery if maternal instability.

👶 Paediatrics

Fluid replacement Calculate deficit based on degree of dehydration (5-15%). Replace over 24-48 hours. Use 0.45% saline initially if serum sodium >150 mmol/L.

Insulin dosing 0.05-0.1 units/kg/hour IV infusion. Lower doses than adults. Avoid bolus doses in children.

Cerebral oedema risk Higher risk than adults. Avoid rapid fluid replacement or insulin boluses. Monitor neurological status closely. Consider mannitol 0.25-0.5 g/kg IV if signs develop.

Electrolytes Potassium 20-40 mmol/L in maintenance fluids once urine output established. Phosphate replacement often required: 0.15-0.3 mmol/kg/dose.

👴 Elderly (≥65 years)

Fluid management Higher risk of fluid overload and heart failure. Consider CVP monitoring. More conservative fluid replacement rates.

Insulin sensitivity May require lower insulin doses. Start at 0.05 units/kg/hour. Monitor glucose closely to avoid hypoglycaemia.

Comorbidities Higher prevalence of cardiovascular, renal, and cognitive impairment. Requires multidisciplinary approach and longer recovery periods.

Medication review Review all medications for precipitating factors (thiazides, steroids, antipsychotics). Assess for polypharmacy interactions.

🫘 Renal Impairment

Insulin Reduced clearance in severe CKD. May need dose reduction and extended monitoring. Half-life prolonged in ESRD.

Fluid balance Careful monitoring required. May need dialysis if fluid overload or severe electrolyte abnormalities. Consider CRRT for haemodynamic instability.

Electrolyte monitoring More frequent monitoring required. Potassium accumulation risk. Phosphate replacement may not be needed if baseline elevated.

Contrast avoidance Avoid contrast-enhanced imaging if possible due to nephrotoxicity risk. Use non-contrast CT for complications assessment.

🫀 Hepatic Impairment

Insulin metabolism Reduced hepatic clearance may prolong insulin action. Monitor glucose levels more frequently. Consider dose reduction in severe cirrhosis.

Lactate monitoring Baseline lactate may be elevated due to impaired hepatic clearance. Serial measurements more important than absolute values.

Synthetic function Monitor albumin, coagulation studies. May affect oncotic pressure and bleeding risk during invasive procedures.

Drug dosing Avoid hepatotoxic medications. Adjust doses of hepatically metabolised drugs according to Child-Pugh class.

🛡️ Immunocompromised

Infection screening Broader infection workup required. Consider atypical organisms, fungal infections, and opportunistic pathogens as precipitants.

Antibiotic therapy Lower threshold for empirical broad-spectrum antibiotics. Consider antifungal coverage if prolonged immunosuppression or recent hospitalisation.

Steroid management Do not abruptly stop chronic steroids. May need stress dose steroids during acute illness. Monitor glucose levels closely as steroids worsen hyperglycaemia.

Recovery monitoring Prolonged recovery expected. Monitor for secondary infections, delayed wound healing, and medication interactions.

⚠️

Critical Care Considerations: All special populations have increased risk of complications and may require ICU/HDU monitoring. Early specialist consultation (endocrinology, nephrology, obstetrics) is recommended.

Dosing Adjustments Summary

Population	Insulin Adjustment	Fluid Rate Modification	Key Monitoring
Pregnancy	Standard dosing, human insulin only	Standard, monitor for overload	Fetal heart rate, obstetric review
Paediatric	0.05-0.1 units/kg/hour (lower doses)	Calculate deficit, replace over 24-48h	Neurological status, cerebral oedema
Elderly	Start 0.05 units/kg/hour	Conservative rates, CVP monitoring	Cardiac status, hypoglycaemia
Renal impairment	Reduce dose in severe CKD	Careful balance, consider RRT	Fluid overload, electrolytes
Hepatic impairment	Consider reduction in severe cirrhosis	Standard, monitor oncotic pressure	Synthetic function, lactate trends
Immunocompromised	Standard dosing	Standard rate	Infection markers, drug interactions

Follow-Up & Prevention

ℹ️

Prevention Focus: HHS is largely preventable through patient education, medication adherence, and early recognition of precipitating factors.

Immediate Post-Discharge Follow-Up

24-48 hours

Emergency contact with diabetes team or GP

Review blood glucose logs and ketones
Assess medication adherence and technique
Ensure adequate fluid intake and electrolyte balance
Screen for ongoing precipitating factors

1 week

Comprehensive diabetes review

HbA1c if not done in past 3 months
Medication review and optimisation
Diabetes self-management education reinforcement
Sick day management plan review

4-6 weeks

Endocrinologist review

Comprehensive diabetes complications assessment
Long-term management optimisation
HbA1c target review and medication adjustment

Long-Term Management & Prevention

Glycaemic Control Optimisation

HbA1c target <53 mmol/mol (7%) if safe and achievable
Individualise targets based on life expectancy, comorbidities
Regular medication adherence counselling
Consider continuous glucose monitoring for high-risk patients

Patient Education

Structured diabetes education program (DESMOND, X-PERT)
Sick day management protocol
Recognition of HHS warning signs
Importance of medication compliance

Risk Factor Management

Blood pressure control (<140/90 mmHg)
Lipid management (statin therapy)
Weight management and lifestyle intervention
Smoking cessation support

Complications Screening

Annual comprehensive diabetic eye examination
Annual foot examination and podiatry referral
Annual ACR and eGFR monitoring
Cardiovascular risk assessment

Sick Day Management Plan

⚠️

Critical Prevention Strategy: All patients must have a written sick day management plan to prevent HHS recurrence.

Essential Sick Day Management Elements

Never stop diabetes medications during illness
Monitor blood glucose every 2-4 hours
Check ketones if glucose >15 mmol/L
Maintain adequate fluid intake (aim 200-250 mL/hour)
Seek immediate medical attention if:
- Persistent vomiting >4 hours
- Blood glucose >20 mmol/L persistently
- Signs of dehydration
- Drowsiness or confusion

Monitoring Schedule

Parameter	Frequency	Target/Action
HbA1c	Every 3-6 months	Individualised target (typically <53 mmol/mol)
Blood pressure	Every visit	<140/90 mmHg (130/80 if high CV risk)
Lipid profile	Annually	LDL <2.0 mmol/L (or <1.8 if high risk)
ACR & eGFR	Annually	ACR <3.5 mg/mmol; eGFR decline <3 mL/min/year
Eye examination	Annually	Diabetic retinopathy screening
Foot examination	Annually	Neuropathy and vascular assessment

High-Risk Patient Management

High Risk

Previous HHS Episode

Diabetes specialist team involvement
3-monthly endocrinologist reviews
Structured diabetes education program
Consider continuous glucose monitoring
Emergency contact details readily available

Specialist diabetes care

Moderate Risk

Risk Factors Present

Poor glycaemic control (HbA1c >64 mmol/mol)
Previous admissions for hyperglycaemia
Medication non-adherence
Limited health literacy
Social disadvantage

Enhanced primary care + specialist input

Prevention Strategies

Primary Prevention

Type 2 diabetes prevention in pre-diabetes
Lifestyle modification programs
Weight management support
Regular health screening in high-risk populations

Secondary Prevention

Optimal diabetes management from diagnosis
Early identification of deteriorating control
Prompt treatment of intercurrent illness
Regular medication review and optimisation

✓

Quality Improvement: Establish diabetes care pathways with clear protocols for sick day management, emergency contact procedures, and regular follow-up to prevent HHS recurrence.

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