Hyperosmolar Hyperglycaemic State / HONK

OVERVIEW

• Hyperosmolar hyperglycaemic state (HHS) = Hyperosmotic Hyperglycaemic Syndrome (HHS)
• three times less frequent than DKA
• deaths often due to co-morbid conditions (MI)
• higher mortality rate than DKA
• part of a continuum with DKA, with insulin resistance predominant over insulin deficiency

PATHOPHYSIOLOGY

• acute stressor/triggers:
  • infection – half of patients (common sources include pneumonia, urinary tract)
  • Pancreatitis, trauma, heat exposure
  • MI
  • Insulin nonadherence or inadequate dosing
  • Surgery
  • Medication changes (glucocorticoid, thiazides, phenytoin, beta-blockers, anti-calcineurin immunosuppressives, HIV protease inhibitors, antipsychotics)
• increases levels of cortisol and catecholamines –>
  • decreased insulin sensitivity
  • decreased insulin
• -> decreased glucose utilisation in skeletal muscle, increased fat and muscle breakdown
• has enough insulin to prevent ketoacidosis/ketone production
• but not enough insulin to control hyperglycemia

• increased hepatic gluconeogenesis
• increase in glucagon, cortisol, catecholamines
• increased BSL
• glycosuria + osmotic diuresis –> loss of water
• Patients fail to compensate adequately for water loss by increasing oral water intake (e.g., due to baseline debility, bed-bound status, or a relatively insensitive central drive to maintain normal tonicity).
• Over a period of several days, uncontrolled water loss leads to a hypertonic state. This may lead to altered mental status (which exacerbates the patient’s inability to drink an adequate amount of water)

Here is a more detailed comparison of Hyperosmolar Hyperglycemic Nonketotic State (HONK) and Diabetic Ketoacidosis (DKA), focusing on etiology, pathology, signs, symptoms, management, and follow-up based on Australian guidelines:

Aspect	HONK (Hyperosmolar Hyperglycemic Nonketotic State)	DKA (Diabetic Ketoacidosis)
Etiology	– Common in type 2 diabetes, elderly patients. – Precipitating factors: infection, dehydration, myocardial infarction, stroke, surgery, medications (e.g., steroids, thiazides, antipsychotics).	– Common in type 1 diabetes; can occur in type 2 diabetes with significant insulin deficiency. – Precipitating factors: infection (most common), missed insulin, stress, acute illness (MI, stroke), medications (e.g., SGLT2 inhibitors).
Pathology	– Marked hyperglycemia (>30 mmol/L), severe dehydration, hyperosmolarity (>320 mOsm/kg). – Relative insulin deficiency prevents lipolysis and ketogenesis, leading to minimal or absent ketonemia. – Hyperosmolar state leads to severe electrolyte imbalance and neurological disturbances.	– Absolute insulin deficiency leads to increased lipolysis, ketosis, and metabolic acidosis. – Hyperglycemia (>13.9 mmol/L) with significant ketosis and acidosis (arterial pH <7.3, bicarbonate <15 mmol/L). – Increased counter-regulatory hormones (glucagon, cortisol, catecholamines) exacerbate hyperglycemia and ketogenesis.
Signs and Symptoms	– Gradual onset over days to weeks. – Severe dehydration, dry mucous membranes, hypotension, tachycardia. – Neurological symptoms: altered mental status, seizures, focal deficits, coma (more common than in DKA). – Minimal or absent ketone breath and Kussmaul respiration.	– Rapid onset within hours to a day. – Symptoms include polyuria, polydipsia, nausea, vomiting, abdominal pain. – Kussmaul respiration (deep, rapid breathing), acetone (fruity) breath odor. – Altered mental status in severe cases, ranging from confusion to coma.
Laboratory Findings	– Blood glucose >30 mmol/L (often >40-50 mmol/L). – Serum osmolality >320 mOsm/kg. – Absence or minimal ketonemia and ketonuria. – pH usually >7.3, bicarbonate >18 mmol/L. – Elevated serum sodium (hypernatremia). – Hypokalemia common after insulin therapy initiation.	– Blood glucose >13.9 mmol/L. – Serum ketones >3 mmol/L or positive urine ketones. – Arterial pH <7.3, serum bicarbonate <15 mmol/L. – Elevated anion gap metabolic acidosis. – Variable potassium levels; often initially normal or elevated but drops rapidly after insulin therapy.
Management	1. Fluid Resuscitation: – Start with IV normal saline (0.9%) bolus; adjust rate based on hydration status and sodium level. – Switch to 0.45% saline if serum sodium is high (>150 mmol/L). – Replace half of the fluid deficit over the first 12 hours, and the rest over the next 12-24 hours. 2. Insulin Therapy: – Start low-dose insulin infusion (0.05 units/kg/hr) after initial fluid resuscitation. – Target glucose reduction of 3-4 mmol/L per hour; avoid rapid drops to prevent cerebral edema. 3. Electrolyte Replacement: – Monitor and correct potassium levels; initiate potassium replacement if <5.0 mmol/L. – Monitor phosphate and magnesium, replace as needed. 4. Address Underlying Cause: – Treat infections, stop precipitating medications, manage comorbid conditions (e.g., MI).	1. Fluid Resuscitation: – IV normal saline 1L in the first hour; adjust based on cardiovascular and renal status. – Switch to 5% dextrose with 0.45% saline when blood glucose drops below 14 mmol/L to prevent hypoglycemia while continuing ketone clearance. 2. Insulin Therapy: – Start with an IV insulin infusion (0.1 units/kg/hr); adjust based on glucose and ketone levels. – Continue insulin until ketosis resolves, pH normalizes, and the patient can tolerate oral intake. 3. Electrolyte Replacement: – Potassium replacement is critical; start if potassium <5.5 mmol/L. Avoid insulin if potassium <3.3 mmol/L until corrected. – Monitor and replace phosphate and magnesium if low. 4. Address Precipitating Factors: – Manage infections, discontinue precipitating medications, provide education on insulin adherence.
Monitoring	– Hourly monitoring of blood glucose and neurological status. – Electrolytes, renal function, osmolality every 2-4 hours initially. – Adjust fluids and insulin based on clinical and laboratory responses. – Cardiac monitoring if at risk of electrolyte-induced arrhythmias.	– Monitor blood glucose and ketones hourly. – Electrolytes, venous blood gases every 2-4 hours initially. – Monitor for complications: cerebral edema, hypokalemia, hypoglycemia. – ECG monitoring for potassium-related arrhythmias if indicated.
Follow-Up	1. Transition to Subcutaneous Insulin: – Transition once patient is clinically stable, osmolality normalizes, and able to eat. – Restart or adjust long-term diabetes medications, considering any new contraindications. 2. Diabetes Education: – Address medication adherence, dietary management, sick-day plans. 3. Outpatient Monitoring: – Regular follow-up to optimize glycemic control and prevent recurrence. 4. Review Comorbid Conditions: – Manage hypertension, hyperlipidemia, renal function, cardiovascular health.	1. Transition to Subcutaneous Insulin: – Continue insulin infusion until ketones are cleared, pH is normalized, and the patient can eat. – Restart basal insulin before stopping infusion and overlap with short-acting insulin as needed. 2. Patient Education: – Address prevention of future DKA episodes through medication adherence, sick-day management, and recognizing early symptoms. 3. Monitoring for Complications: – Assess for complications such as recurrent DKA, cardiovascular issues, and psychological impacts. 4. Adjust Long-term Management: – Optimize insulin regimen and manage other diabetes-related comorbidities.

HISTORY

• polydipsia
• polyuria
• weight loss
• weakness
• slow onset
• progressive dehydration
• coma
• causes: MI, infection, diuretics, CVA, PE

RISK FACTORS

• elderly
• type II DM
• mental obtundation/dementia
• physical impairment limiting access to H2O
• renal dysfunction
• inappropriate diuretic use
• steroids
• beta-blockers
• phenytoin

EXAMINATION

• CVS – tachycardia, decreased skin turgor, sunken eyes, dry mouth
• RESP – tachypnoea
• CNS – drowsy, delirium, coma, focal or generalised seizures, visual changes, hemiparesis

INVESTIGATIONS

• very high osmolarity (> 320mosmol/kg)
• very high glucose
• little or no ketonuria (beta-hydroxybutyrate)
• hyponatraemia (or pseudohyponatraemia -> hyperglycaemia draws water out of cells) or hypernatraemia
• hypokalaemia
• hypomagnesaemia
• ABG:
  • pH normally > 7.3 (metabolic acidosis is not severe)
  • normal anion gap
• Beta-hydroxybutyrate level (most precise way to quantify the presence and severity of ketoacidosis)
• normal level of ketones
• renal dysfunction commonly present

Diagnostic Criteria

• serum osmolarity > 320mosmol/L
• serum glucose > 33mmol/L
• profound dehydration (elevated urea:creatinine ratio)
• no ketoacidosis

Investigations for cause

• CXR: chest infection
• compliance with medication
• ECG + TNT: MI
• FBC
• CRP
• blood cultures
• urine

MANAGEMENT

• HHS is a deranged state which develops gradually over days to weeks.
• However, these patients generally adapt to their new state and often tolerate it relatively well.
• As a general rule of thumb, if an abnormal state develops gradually then it may be treated gradually.
• The primary risk of treating HHS is overly aggressive therapy, which may cause dangerous swings in electrolyte levels and osmolality.
• When in doubt, the safest approach to HHS is generally to correct abnormalities slowly.
• Goals
  • correct dehydration (often 6-9 L of H2O loss)
  • provide insulin
  • replace electrolytes
  • correct metabolic acidosis

Resuscitation

• A – may require intubation if coma and not protecting airway
• B – mechanical ventilation can minimise WOB and manage possible metabolic acidosis
• C – resuscitate with isotonic fluid until patient has a normal heart rate and BP (see below for H2O replacement) or can use colloids.

Treatment

• Calculate corrected Na+
  • if hypernatraemic, the corrected Na+ = measured Na+ + glucose/3
  • monitor this as Na+ changes for glucose
• Calculate H2O deficit
  • H2O deficit = 0.6 x premorbid weight x (1 – 140/corrected Na+)
• Fluid management in first 24 hours
  • maintenance as D5W at standard rate
  • if hypernatraemic: replace half the H2O deficit over 24 hours using ½ normal saline.
• Monitor Na+ closely – should not change more than 10mmol in 24 hours
• Replace other electrolytes as required
  • K+ (often require aggressive replacement – 10-20mmol/hr, make sure not anuric)
  • Mg2+ – Magnesium should be aggressively repleted.magnesium level on the high end will tend to prevent Torsade de Pointes if the potassium level falls.
  • PO4 – Phosphate should be repleted as necessary
  • Ca2+
• Fluid management in second 24 hours
  • when glucose < 15mmol/L -> use D5W @ 100-250mL/hr AND saline
  • keep Na+ between 140-150mmol/L
  • the metabolic acidosis rarely requires specific treatment as responds to volume expansion and insulin therapy.

• General
  • insulin at 0.05 U/kg/h
  • do not allow blood glucose to drop by more than 3 mmol/L/h
  • once glucose <15mmol/L and corrected Na+ 10% dextrose
  • thromboprophylaxis (SCD’s, clexane, TEDS) -> high risk of VTE
  • diagnose cause and treat: infection, compliance, MI, CVA

• Complication Management
  • delirium -> coma
  • cerebral oedema (prevent by resuscitation with isotonic fluid and slow correction of glucose)
  • seizures (focal and generalized)
  • severe dehydration and shock
  • renal failure
  • thrombotic complications: VTE, stroke, AMI
  • intercurrent events: sepsis, MI, aspiration
  • occlusive events: focal CNS signs, chorea, DIC, leg ischaemia, rhabdomyolysis
  • fluid overload and congestive heart failure
  • metabolic derangement: hypokalaemia, hypophosphataemia, hypomagnesaemia, hypoglycaemia, hyperchloraemia with NAGMA