Hyperosmotic Hyperketotic State (HHS)
A life-threatening diabetes complication characterized by severe dehydration, extremely high blood sugar, and altered consciousness
Quick Facts
- Type: Diabetic Emergency
- ICD-10: E11.00
- Mortality: 10-20%
- Age Group: Usually >65 years
Overview
Hyperosmotic Hyperketotic State (HHS), also known as Hyperosmolar Hyperglycemic State, is a serious and potentially life-threatening complication of diabetes mellitus. This condition is characterized by extremely high blood glucose levels (typically over 600 mg/dL), severe dehydration, and altered mental status without significant ketoacidosis.
HHS develops more gradually than diabetic ketoacidosis (DKA), often over days to weeks, making it sometimes overlooked until it becomes severe. The condition primarily affects people with type 2 diabetes, particularly older adults, and carries a mortality rate of 10-20% even with appropriate treatment. The high death rate is often due to the underlying precipitating illness and the patient's advanced age.
The pathophysiology involves severe insulin deficiency or resistance, leading to uncontrolled glucose production by the liver and decreased glucose uptake by tissues. This results in profound hyperglycemia and osmotic diuresis, causing massive fluid and electrolyte losses. Unlike DKA, patients with HHS typically retain enough insulin activity to prevent significant ketone production, but not enough to control blood glucose levels.
Early recognition and prompt treatment are crucial for survival. The condition requires immediate hospitalization and intensive medical management to correct fluid deficits, reduce blood glucose levels, and address any underlying precipitating factors. With timely intervention, many patients can recover completely, though some may experience residual neurological deficits.
Symptoms
HHS symptoms develop gradually over days to weeks, often making early detection challenging. The condition primarily affects older adults with type 2 diabetes and can progress from mild symptoms to life-threatening complications.
Early Symptoms
Progressive Symptoms
- Extreme thirst (polydipsia)
- Increased hunger (polyphagia)
- Blurred vision
- Headache
- Nausea and vomiting
- Abdominal pain
- Weight loss
- Dry mouth and sticky saliva
Severe Symptoms (Medical Emergency)
- Altered mental status or confusion
- Drowsiness or lethargy
- Seizures
- Hallucinations
- Focal neurological deficits
- Coma
- Severe dehydration signs (dry skin, sunken eyes)
- Rapid, weak pulse
- Low blood pressure
- Cool, clammy skin
Signs of Dehydration
- Decreased skin elasticity (skin tenting)
- Dry mucous membranes
- Absence of sweating
- Decreased urine output
- Sunken appearance of eyes and cheeks
Warning Signs in Elderly Patients
Elderly patients may present with atypical symptoms:
- Falls or difficulty walking
- Incontinence
- Sudden behavioral changes
- Increased confusion
- Social withdrawal
- Poor oral intake
Causes
HHS results from severe insulin deficiency combined with various precipitating factors that increase glucose production or decrease glucose utilization. Understanding these causes is essential for prevention and treatment.
Primary Underlying Cause
Insulin Deficiency or Resistance
- Inadequate insulin production by pancreatic beta cells
- Severe insulin resistance in target tissues
- Insufficient insulin therapy in diagnosed diabetics
- New-onset diabetes that has gone undiagnosed
Common Precipitating Factors
Infections
- Pneumonia (most common)
- Urinary tract infections
- Sepsis
- Skin and soft tissue infections
- Gastrointestinal infections
- Meningitis or encephalitis
Cardiovascular Events
- Myocardial infarction (heart attack)
- Stroke
- Pulmonary embolism
- Acute heart failure
Medications
- Corticosteroids
- Thiazide diuretics
- Beta-blockers
- Phenytoin
- Immunosuppressive agents
- Atypical antipsychotics
Other Contributing Factors
- Inadequate fluid intake: Common in elderly or disabled patients
- Medication non-compliance: Stopping diabetes medications
- Alcohol or drug abuse: Particularly cocaine use
- Trauma or burns: Physical stress increases glucose levels
- Surgery: Surgical stress can precipitate HHS
- Kidney disease: Impaired glucose clearance
- Endocrine disorders: Hyperthyroidism, Cushing's syndrome
- Pancreatitis: Destroys insulin-producing cells
Environmental and Social Factors
- Heat exposure leading to dehydration
- Limited access to healthcare
- Social isolation preventing recognition of symptoms
- Cognitive impairment affecting self-care
- Economic barriers to medication access
Risk Factors
Several factors increase the likelihood of developing HHS. Understanding these risk factors helps identify high-risk individuals who need closer monitoring and preventive measures.
Non-Modifiable Risk Factors
- Age: Most common in adults over 65 years
- Type 2 diabetes: Especially long-standing diabetes
- Gender: Slightly more common in women
- Ethnicity: Higher rates in African Americans and Hispanics
- Previous episodes: History of HHS or DKA
- Cognitive impairment: Dementia or intellectual disability
Medical Risk Factors
- Poor diabetes control: Consistently high HbA1c levels
- Kidney disease: Impaired glucose and fluid regulation
- Heart disease: Increases stress response
- Chronic infections: Recurring urinary tract infections
- Malnutrition: Impairs immune function
- Dehydration tendency: Limited mobility or water access
- Multiple medications: Polypharmacy increasing drug interactions
Lifestyle and Social Risk Factors
- Medication non-adherence: Inconsistent diabetes medication use
- Poor self-monitoring: Infrequent blood glucose checking
- Social isolation: Living alone without support
- Limited healthcare access: Lack of regular medical care
- Substance abuse: Alcohol or drug use
- Inadequate diabetes education: Poor understanding of condition
Situational Risk Factors
- Acute illness: Any infection or medical emergency
- Surgery or trauma: Physical stress responses
- Hot weather: Increased dehydration risk
- Travel: Disrupted medication schedules
- Nursing home residence: Potential for delayed recognition
High-Risk Populations
- Elderly diabetics with multiple comorbidities
- Patients with undiagnosed diabetes
- Individuals with mental health conditions
- Those with limited English proficiency
- Homeless or unstably housed individuals
- Patients with frequent hospitalizations
Diagnosis
Diagnosing HHS requires a combination of clinical presentation, laboratory findings, and exclusion of other conditions. Rapid diagnosis is crucial given the condition's high mortality rate.
Diagnostic Criteria
The diagnosis of HHS is established when all of the following criteria are met:
- Plasma glucose: >600 mg/dL (33.3 mmol/L)
- Serum osmolality: >320 mOsm/kg
- Absence of ketoacidosis: Serum ketones <3 mmol/L
- Altered mental status: Ranging from confusion to coma
Initial Assessment
Clinical Evaluation
- Vital signs: Blood pressure, heart rate, temperature, respiratory rate
- Mental status: Glasgow Coma Scale assessment
- Hydration status: Skin turgor, mucous membranes, urine output
- Neurological exam: Focal deficits, reflexes, pupil response
- Cardiovascular assessment: Heart sounds, peripheral pulses
Laboratory Tests
Essential Tests
- Blood glucose: Typically >600 mg/dL
- Serum osmolality: Calculated or measured (>320 mOsm/kg)
- Arterial blood gas: To assess acid-base status
- Serum ketones: Beta-hydroxybutyrate or acetoacetate
- Basic metabolic panel: Electrolytes, BUN, creatinine
- Complete blood count: Looking for infection markers
Additional Tests
- Hemoglobin A1c: Indicates long-term glucose control
- Urinalysis: Glucose, ketones, protein, infection signs
- Blood cultures: If infection suspected
- Liver function tests: May be elevated
- Lipase/amylase: To rule out pancreatitis
- Troponin: If cardiac event suspected
Imaging Studies
- Chest X-ray: To identify pneumonia
- CT head: If focal neurological signs present
- Urinary tract imaging: If UTI suspected
- Echocardiogram: If heart failure suspected
Severity Assessment
Glasgow Coma Scale
- 15: Normal consciousness
- 13-14: Mild alteration
- 9-12: Moderate alteration
- 3-8: Severe alteration/coma
Osmolality Calculation
Osmolality = 2(Na + K) + Glucose/18 + BUN/2.8
Normal: 285-295 mOsm/kg; HHS: >320 mOsm/kg
Differential Diagnosis
- Diabetic ketoacidosis (DKA)
- Stroke or cerebrovascular accident
- Meningitis or encephalitis
- Uremia
- Drug intoxication or poisoning
- Hyperosmolar states from other causes
Treatment Options
HHS treatment requires immediate intensive care with focus on fluid replacement, insulin therapy, and electrolyte correction. Treatment must address both the metabolic crisis and any precipitating factors.
Emergency Management
Initial Stabilization
- Airway, breathing, circulation: Ensure adequate ventilation
- IV access: Large-bore IV lines for fluid resuscitation
- Continuous monitoring: Cardiac, oxygen saturation, blood pressure
- Neurological assessment: Frequent mental status checks
Fluid Replacement Therapy
Phase 1: Initial Fluid Resuscitation
- Normal saline (0.9%): 1-2 L in first hour if hypotensive
- Rate adjustment: Based on cardiac status and age
- Goal: Restore intravascular volume quickly
- Monitor: Blood pressure, urine output, heart rate
Phase 2: Maintenance Fluid Therapy
- Hypotonic saline (0.45%): If sodium >155 mEq/L
- Normal saline: If sodium 135-155 mEq/L
- Rate: 250-500 mL/hour depending on losses
- Total deficit: Usually 8-12 L over 24-48 hours
Insulin Therapy
Regular Insulin Protocol
- Initial dose: 0.1 units/kg/hour IV continuous infusion
- No bolus: Unlike DKA, bolus insulin not recommended
- Target glucose reduction: 50-75 mg/dL per hour
- Goal glucose: Reduce to 250-300 mg/dL initially
Insulin Adjustment
- If glucose not decreasing: Double insulin rate
- When glucose <300 mg/dL: Add dextrose to IV fluids
- Continue insulin until osmolality <315 mOsm/kg
- Transition to subcutaneous insulin when stable
Electrolyte Management
Potassium Replacement
- If K+ >5.2 mEq/L: No replacement initially
- If K+ 3.3-5.2 mEq/L: Add 20-30 mEq/L to IV fluids
- If K+ <3.3 mEq/L: Delay insulin until K+ corrected
- Target range: 4-5 mEq/L
Phosphorus and Magnesium
- Replace if severely deficient
- Monitor for refeeding syndrome
- Gradual replacement over days
Treatment of Precipitating Factors
- Infections: Appropriate antibiotics
- Myocardial infarction: Cardiology consultation
- Medications: Discontinue precipitating drugs
- Other medical conditions: Condition-specific treatment
Supportive Care
- DVT prophylaxis: Given high thrombotic risk
- Gastric protection: Proton pump inhibitors if indicated
- Pressure ulcer prevention: Frequent turning, padding
- Nutrition support: When stable and conscious
Monitoring During Treatment
- Glucose: Every 1-2 hours initially
- Electrolytes: Every 2-4 hours
- Osmolality: Every 4-6 hours
- Mental status: Continuously
- Fluid balance: Strict intake/output monitoring
Prevention
Preventing HHS involves good diabetes management, recognizing early warning signs, and addressing risk factors before they lead to crisis. Prevention strategies are particularly important for high-risk populations.
Diabetes Management
Blood Glucose Control
- Regular monitoring: Check blood glucose as prescribed
- Medication adherence: Take diabetes medications consistently
- HbA1c targets: Generally <7% for most adults (individualized)
- Insulin adjustment: Work with healthcare provider for dose optimization
Diet and Lifestyle
- Consistent meal timing: Regular eating schedule
- Carbohydrate counting: Match insulin to carbohydrate intake
- Hydration: Adequate fluid intake, especially during illness
- Regular exercise: As approved by healthcare provider
- Weight management: Maintain healthy weight
Sick Day Management
When Ill
- Continue medications: Never stop diabetes medications
- Increase monitoring: Check glucose every 2-4 hours
- Stay hydrated: Drink fluids regularly
- Monitor for ketones: Check urine or blood ketones
- Contact healthcare provider: If glucose consistently >300 mg/dL
Medication Adjustments
- Have sick day medication plan
- Know when to increase insulin doses
- Understand when to seek medical attention
- Keep emergency medications available
High-Risk Population Strategies
Elderly Patients
- Simplified regimens: Easy-to-follow medication schedules
- Caregiver involvement: Family or professional support
- Regular check-ins: Frequent healthcare contact
- Environmental modifications: Easy access to water and food
Cognitive Impairment
- Supervised medication administration
- Simple glucose monitoring devices
- Emergency contact information readily available
- Medical alert bracelets or necklaces
Healthcare System Prevention
- Regular follow-up: Scheduled diabetes appointments
- Patient education: Ongoing diabetes self-management training
- Risk stratification: Identify high-risk patients
- Care coordination: Team-based diabetes care
- Community resources: Support groups and programs
Environmental Prevention
- Heat exposure: Air conditioning during hot weather
- Travel preparation: Extra medications and supplies
- Emergency planning: Natural disaster preparedness
- Medication storage: Proper insulin storage conditions
Early Warning System
- Know personal glucose patterns
- Recognize early symptoms of dehydration
- Establish clear guidelines for seeking help
- Maintain emergency contact information
- Have transportation plan for medical emergencies
When to Seek Emergency Care
HHS is a life-threatening emergency requiring immediate medical attention. Recognizing warning signs early can be life-saving, as delayed treatment significantly increases mortality risk.
Call 911 Immediately If You Experience:
- Altered mental status: Confusion, disorientation, or difficulty thinking clearly
- Severe dehydration: Extreme thirst that cannot be satisfied
- Blood glucose >400 mg/dL: That doesn't respond to usual treatment
- Persistent vomiting: Unable to keep fluids down
- Signs of shock: Rapid pulse, low blood pressure, cold skin
- Seizures or loss of consciousness: Any neurological emergency
- Severe weakness: Unable to stand or walk
Urgent Medical Attention Needed For:
- Blood glucose consistently >300 mg/dL despite treatment
- Increased urination and thirst lasting more than 24 hours
- Progressive weakness or fatigue
- Nausea and vomiting preventing medication intake
- Signs of infection with elevated glucose
- Any concerning change in mental status
- Inability to maintain adequate fluid intake
High-Risk Situations
During Illness
- Any infection, especially pneumonia or UTI
- Fever >101°F (38.3°C)
- Chest pain or shortness of breath
- Severe diarrhea or vomiting
- Signs of heart attack or stroke
Medication Issues
- Ran out of diabetes medications
- Started new medications that may affect glucose
- Steroid use for other conditions
- Unable to take oral medications
What NOT to Do
- Don't wait: Symptoms will not improve on their own
- Don't drive yourself: Altered mental status makes driving dangerous
- Don't stop medications: Continue diabetes medications unless advised otherwise
- Don't ignore mild symptoms: Early treatment is more effective
- Don't assume it's something else: High glucose symptoms need medical evaluation
Emergency Preparation
Information to Have Ready
- Complete list of medications and doses
- Recent blood glucose readings
- Medical history and allergies
- Emergency contact information
- Insurance information
- Healthcare provider contact details
What to Bring to Hospital
- All medications in original containers
- Blood glucose meter and supplies
- Medical identification bracelet or card
- Recent medical records if available
- Comfortable clothing and personal items
For Caregivers and Family
- Learn warning signs: Know what to watch for
- Have emergency plan: Know when and how to get help
- Medication management: Help ensure medications are taken
- Monitor glucose levels: Assist with blood glucose checking
- Stay calm: Provide reassurance while seeking help
Frequently Asked Questions
HHS typically occurs in type 2 diabetes with less insulin deficiency, resulting in extremely high glucose (>600 mg/dL) without significant ketone production. DKA usually occurs in type 1 diabetes with severe insulin deficiency, causing moderate glucose elevation (300-500 mg/dL) but significant ketoacidosis. HHS develops more slowly over days to weeks, while DKA develops rapidly over hours to days.
HHS rarely occurs in people without known diabetes, but it can be the presenting feature of undiagnosed type 2 diabetes, especially in elderly individuals. Some people may have had diabetes for years without knowing it, and HHS becomes their first major symptom that leads to diagnosis.
Initial stabilization typically takes 24-48 hours in the hospital, but complete recovery may take several days to weeks. Mental status usually improves within 24 hours of treatment, though some patients may have residual cognitive effects. Most patients require 3-7 days of hospitalization, followed by ongoing diabetes management optimization.
Most patients recover completely with prompt treatment. However, some may experience persistent neurological deficits, especially if treatment was delayed. The underlying diabetes typically requires more intensive management afterward. Some patients may need ongoing cognitive assessment and rehabilitation.
Yes, HHS can recur, especially if diabetes remains poorly controlled or if precipitating factors aren't addressed. The recurrence rate is about 15-20%. Prevention through good diabetes management, regular medical care, and early treatment of illnesses is crucial to prevent repeat episodes.
Most cases of HHS are preventable through good diabetes management, including consistent medication use, regular blood glucose monitoring, adequate hydration, and prompt treatment of illnesses. Early recognition of warning signs and seeking medical attention when glucose levels are persistently elevated can prevent progression to HHS.
References
- Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care. 2014;37(11):3124-31.
- Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.
- Stoner GD. Hyperosmolar Hyperglycemic State. Am Fam Physician. 2017;96(11):729-736.
- Joint British Diabetes Societies. The Management of the Hyperosmolar Hyperglycaemic State (HHS) in Adults with Diabetes. 2012.
- American Diabetes Association. Standards of Medical Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1).
- Nyenwe EA, Kitabchi AE. The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management. Metabolism. 2016;65(4):507-21.