Hyperosmolar Hyperglycaemic State (HHS) Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is a life-threatening diabetic emergency, especially common in our elderly population with poorly controlled Type 2 Diabetes Mellitus, often triggered by an infection.
High-Yield Definition: As per the Malaysian CPG for Management of T2DM (6th Edition, 2020), HHS is characterised by a triad of:
Severe hyperglycemia (plasma glucose >33.3 mmol/L)
High effective serum osmolality (>320 mOsm/kg)
Absence of significant ketoacidosis (venous pH >7.3, bicarbonate >18 mmol/L)
Clinical One-Liner: Basically, it's dangerously high sugar causing profound dehydration in an elderly diabetic, without the severe acidosis you see in DKA.
II. Etiology & Risk Factors
Etiology: Caused by a state of relative insulin deficiency combined with a major physiologic stressor. There is enough insulin to prevent ketosis, but not enough to control glucose.
Risk Factors (Common Triggers in our setting):
Infection (~60% of cases): Pneumonia and Urinary Tract Infections (UTIs) are the most common precipitants.
Non-compliance: Stopping insulin or oral hypoglycemic agents.
Acute Illness: Myocardial infarction, stroke, pancreatitis, acute kidney injury.
Medications: Glucocorticoids, thiazide diuretics, atypical antipsychotics.
Situational: Poor access to water, especially in dependent or institutionalised elderly patients.
III. Quick Pathophysiology
Severe hyperglycemia overwhelms the kidneys' ability to reabsorb glucose, leading to massive osmotic diuresis. This causes a huge loss of water and electrolytes, leading to profound intracellular and extracellular dehydration and a state of hyperosmolarity. This hyperosmolarity is what causes the characteristic neurological dysfunction, from confusion to coma. The relative insulin sufficiency suppresses lipolysis and ketogenesis, which is why significant acidosis is absent.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Altered Mental Status (GCS <15): Alert senior, protect airway if GCS ≤8.
Hypotension (SBP <100 mmHg): Alert senior, secure two large-bore IV cannulas, start fluid resuscitation STAT.
Oliguria/Anuria: Insert urinary catheter to monitor output, signifies severe volume depletion or AKI.
History:
Common (>50%): Insidious onset (days to weeks) of polyuria, polydipsia, profound weakness, lethargy, progressive confusion.
Less Common (10-50%): Nausea, vomiting, weight loss, focal neurological signs (e.g., hemiparesis, seizures) that mimic a stroke.
Pertinent Negatives: Ask about fever, cough, or dysuria (to find the trigger). Note the absence of abdominal pain and Kussmaul breathing (points against DKA).
Physical Examination:
General: Look for profound signs of dehydration (dry mucous membranes, reduced skin turgor, sunken eyes).
Vitals: Tachycardia, hypotension, tachypnea (shallow, not Kussmaul). May have a low-grade fever from infection or be hypothermic.
Neurology: This is key. Assess GCS. Patient can be anywhere from confused to drowsy to comatose. Check for focal deficits.
Clinical Pearl: Always, always check a capillary blood glucose on any elderly patient who presents with confusion or stroke-like symptoms. You will diagnose HHS this way.
V. Diagnostic Workflow
Differential Diagnosis:
Diabetic Ketoacidosis (DKA):
Points For: Hyperglycemia, dehydration.
Points Against: Absence of significant acidosis (pH >7.3), minimal urine/serum ketones.
How to Differentiate: Venous Blood Gas (VBG) is the fastest way.
Cerebrovascular Accident (Stroke):
Points For: Altered mental status, focal neurological deficits.
Points Against: Profound hyperglycemia and dehydration. Neurological signs should improve with fluid resuscitation.
How to Differentiate: Urgent CT Brain.
Sepsis with Encephalopathy:
Points For: Altered mental status, fever, signs of infection. Sepsis is often the trigger for HHS.
Points Against: The extreme level of hyperglycemia is more suggestive of HHS as the primary process.
How to Differentiate: Full septic workup (FBC, CRP, blood cultures, lactate) and source investigation (CXR, UFEME).
Investigations Plan:
Bedside / Initial (First 15 Mins):
Capillary Blood Glucose (CBG): Will often read "HIGH" or ">33.3".
ECG: Look for MI as a trigger or signs of electrolyte disturbance (e.g., peaked T-waves from hyperkalemia).
VBG with electrolytes: The single most important initial blood test. Gives you pH, bicarb, K+, Na+, and lactate immediately.
First-Line Labs & Imaging:
Plasma Glucose: To confirm the CBG reading.
Renal Profile (Urea, Creatinine): Expect pre-renal AKI. Urea is disproportionately high.
Serum Osmolality: Calculated Effective Osmolality = 2 * (Na+) + Glucose. (All in mmol/L). A value >320 mOsm/kg is diagnostic.
Full Blood Count (FBC): Look for leukocytosis indicating infection. High hematocrit suggests hemoconcentration.
CXR, UFEME, Blood C&S: To find the infectious trigger.
Confirmatory / Gold Standard: The diagnosis is clinical and biochemical, based on the triad mentioned above. There is no single "gold standard" imaging test.
VI. Severity Assessment
Severity is a continuum based on the level of consciousness (GCS), degree of hyperosmolality, and hemodynamic stability. The key calculation you must make is the water deficit.
Estimated Water Deficit (Litres) = 0.6 x (Body Weight in kg) x [1 - (140 / Measured Na+)]
A typical 70kg patient may have a fluid deficit of 9-12 litres. This informs the volume and rate of your resuscitation.
VII. Management Plan
Management has three main goals: 1) Restore volume, 2) Gradually correct osmolarity and hyperglycemia, 3) Treat the underlying cause. Fluids are the absolute priority.
Immediate Stabilisation (The ABCDE Plan):
A (Airway) & B (Breathing): Ensure patent airway. Give supplemental oxygen to maintain SpO2 >94%.
C (Circulation) - FLUIDS:
Start with 0.9% NaCl (Normal Saline). Give 1 Litre STAT over the first hour.
After the first litre, the choice of fluid depends on the corrected sodium.
Corrected Na+ = Measured Na+ + [2.4 x ((Glucose - 5.6) / 5.6)]
If corrected Na+ is high (>145), switch to 0.45% NaCl.
If corrected Na+ is normal/low, continue 0.9% NaCl.
The goal is to replace half the deficit in the first 24 hours, and the rest over the next 24 hours.
D (Disability) - INSULIN:
ONLY start insulin AFTER the first litre of fluid is given.
DO NOT give an IV insulin bolus. This can cause a rapid drop in osmolality and lead to cerebral edema.
Start a fixed-rate IV insulin infusion at 0.05 units/kg/hour.
Aim for a gradual fall in blood glucose of 3-5 mmol/L per hour.
E (Exposure/Electrolytes) - POTASSIUM:
Despite a normal or high initial reading, total body potassium is depleted.
Insulin will drive potassium into cells, causing rapid hypokalemia.
Start IV potassium replacement once serum K+ is <5.5 mmol/L. Add 20-40 mmol of KCl to each litre of fluid.
Definitive Treatment (The Ward Round Plan):
Find and treat the underlying cause: Start empirical antibiotics if sepsis is suspected.
Thromboprophylaxis: HHS is a highly prothrombotic state. Start prophylactic LMWH (e.g., Clexane) once the patient is rehydrated, unless contraindicated.
Monitoring: Hourly CBG, 2-4 hourly electrolytes. Close monitoring of GCS and fluid balance.
Transition: Once plasma glucose is ~14 mmol/L, change IV fluids to 5% Dextrose + 0.45% NaCl to prevent hypoglycemia, and reduce the insulin infusion rate.
Long-Term & Discharge Plan:
Once stable, eating, and drinking, convert from IV insulin to a subcutaneous regimen.
Crucial diabetes education for patient and family.
Ensure follow-up in the medical or diabetes clinic.
VIII. Complications
Immediate (From Treatment):
Cerebral Edema: From too-rapid correction of glucose/osmolality. Management: Alert senior, IV Mannitol. This is why gradual correction is key.
Hypokalemia & Hypoglycemia: From aggressive insulin therapy. Management: Proactive replacement and close monitoring.
Short-Term (From Disease):
Thromboembolism (DVT, PE, MI, Stroke): Management: Prophylactic LMWH.
Rhabdomyolysis: Management: Aggressive fluid resuscitation.
Long-Term:
Persistent cognitive dysfunction: Management: Supportive care, rehabilitation.
IX. Prognosis
Prognosis is much worse than DKA, with mortality rates of 10-20% in most series.
Key Poor Prognostic Factors: Advanced age, presence of coma on admission, and high serum osmolality.
X. How to Present to Your Senior
Use a clear, structured format.
"Dr, for review please. This is Puan Siti in Resuscitation Bay 2, a 72-year-old lady with a background of T2DM on metformin, brought in by her son for increasing confusion over the last few days.
On assessment, her GCS is 11/15, she is tachycardic at 120 and hypotensive at 90/50. She looks clinically dehydrated.
Her CBG is 'HIGH', and the initial VBG shows a pH of 7.35, bicarb of 20, and K+ of 5.2.
My main differential is Hyperosmolar Hyperglycemic State, likely precipitated by a UTI.
I have already secured two large-bore IV lines, started the first litre of Normal Saline, sent off the full panel of bloods, and inserted a urinary catheter.
I would like your guidance on starting a low-dose insulin infusion once this first bag of fluid is in."
XI. Summary & Further Reading
Top 3 Takeaways:
Fluids First, Fluids Fast: The cornerstone of management is aggressive rehydration.
Go Slow with Insulin: Start insulin only after fluids. No bolus. Lower glucose gradually.
Find and Treat the Trigger: HHS doesn't happen in a vacuum. Find the underlying cause.
Key Resources:
