01OverviewDefinition, clinical context and the essential points that orientate the chapter.
HHS usually develops over days from relative insulin deficiency sufficient to limit major ketogenesis but insufficient to control glucose. Extreme hyperglycaemia drives osmotic diuresis, causing profound water loss, electrolyte depletion, renal impairment and hypertonicity. Older age, impaired thirst or access to water, infection, vascular events, glucocorticoids, diuretics and previously unrecognised type 2 diabetes are common contexts.
Neurological change relates more closely to rising osmolality and its rate of change than to glucose alone. Lethargy, confusion, focal deficits, seizure and coma can occur, but clinicians must still assess stroke, sepsis, medication toxicity and other cerebral causes. Thrombosis, rhabdomyolysis, acute kidney injury and pressure injury are important complications of dehydration and immobility.
HHS treatment differs fundamentally from rapid glucose correction. The priorities are controlled restoration of circulation, serial osmolality, cautious electrolyte management and delayed low-dose insulin when fluid no longer produces an adequate glucose fall. The current JBDS chart and local critical-care thresholds govern practice; frailty, end-stage organ disease and mixed emergencies need individual senior decisions.
Key points
- Typical HHS combines marked hypovolaemia with glucose at least 30 mmol/L, calculated osmolality at least 320 mOsm/kg, minimal ketonaemia and no substantial ketoacidosis, but the whole syndrome matters more than one threshold.
- Calculate osmolality using the JBDS expression 2 × sodium + glucose + urea, with all components in mmol/L, and plot it against glucose, sodium and fluid balance.
- Correct gradually: the usual osmolality target is a fall of 3–8 mOsm/kg/hour and glucose should not fall faster than 5 mmol/L/hour.
- Use 0.9% sodium chloride as the principal initial fluid, tailoring rate to haemodynamics, age, renal function and heart failure rather than copying a DKA timetable.
- Do not start insulin immediately in uncomplicated HHS; fluid alone lowers glucose and restores circulation, whereas premature insulin can shift water intracellularly and precipitate cardiovascular collapse.
- When glucose stops falling after adequate fluid, commence fixed-rate intravenous insulin at 0.05 units/kg/hour under the HHS protocol; earlier insulin is reserved for specified ketonaemic or mixed presentations.
- A rising measured sodium is expected as glucose falls and does not by itself justify hypotonic fluid if osmolality is declining at the safe target rate.
- Search actively for infection, infarction, stroke, medicines, dehydration, care dependency and new diabetes, then plan rehabilitation because recovery may take several days.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Relative insulin deficiency
Insulin action is insufficient to control glucose but often adequate to limit major ketogenesis, commonly in established or previously unrecognised type 2 diabetes.
Acute precipitating illness
Infection, stroke, myocardial injury or another physiological stress raises counter-regulatory hormones and worsens hyperglycaemia over several days.
Reduced water access
Older age, impaired thirst, cognitive or physical dependence and inadequate care support prevent replacement of the large osmotic urine loss.
Medicine-related worsening
Glucocorticoids, diuretics and other treatment changes can increase glucose or fluid loss in a susceptible person.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Glucose rises progressively
Relative insulin deficiency and stress hormones increase hepatic glucose production while peripheral use remains inadequate as the process continues.
- 2Osmotic diuresis develops
Filtered glucose exceeds renal reabsorptive capacity, drawing water and electrolytes into urine and producing profound cumulative losses.
- 3Hypertonicity intensifies
Water loss exceeds sodium loss, increasing effective osmolality and drawing water from brain cells while the condition remains active.
- 4Renal clearance deteriorates
Volume depletion reduces filtration and glucose excretion, further raising glucose and osmolality in a self-amplifying cycle.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Several days of thirst, polyuria, weakness, weight loss and declining intake may progress to severe dehydration, tachycardia, hypotension and oliguria.
Confusion, drowsiness, visual change, focal signs, seizure or coma becomes more likely with severe or rapidly changing osmolality and requires parallel neurological assessment.
Classical HHS has blood ketones no higher than 3.0 mmol/L with pH at least 7.3 and bicarbonate at least 15 mmol/L despite profound hyperglycaemia.
Marked hyperosmolality can coexist with ketones above 3.0 mmol/L and acidosis; this overlap uses the DKA insulin rate with HHS-informed fluid caution and specialist oversight.
Fever, cough, dysuria, acute ischaemic symptoms, medication change, reduced care support or inability to reach water can reveal the driver and alter immediate management.
Unilateral swelling, hypoxia, chest pain, limb ischaemia or new focal neurology demands urgent investigation because severe dehydration and immobility create a prothrombotic state.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Paired glucose, sodium and urea with calculated osmolalityFirst step - Why
- Confirm the hyperosmolar syndrome and quantify the hourly rate of physiological correction.
- Interpretation and limitations
- An osmolality of 320 mOsm/kg or above supports HHS; plot serial results, aiming for a 3–8 mOsm/kg/hour decline rather than chasing glucose in isolation.
- 02
Blood ketones and venous blood gas - Why
- Distinguish uncomplicated HHS from DKA overlap or another acid–base disorder.
- Interpretation and limitations
- Ketones up to 3.0 mmol/L with pH at least 7.3 and bicarbonate at least 15 mmol/L fits typical HHS; greater ketonaemia plus acidosis invokes the mixed DKA/HHS pathway.
- 03
Potassium, creatinine and serial renal profile - Why
- Identify acute kidney injury and guide safe potassium and fluid prescriptions during changing insulin action.
- Interpretation and limitations
- Whole-body potassium is depleted despite a possible high first result; abnormal renal clearance or oliguria makes standard replacement hazardous and needs senior chart-led management.
- 04
Neurological and functional assessment - Why
- Track hypertonic cerebral effects while identifying stroke, delirium triggers and rehabilitation needs.
- Interpretation and limitations
- Consciousness should improve gradually as osmolality normalises; focal signs, seizures or deterioration require urgent imaging and specialist evaluation rather than faster metabolic correction.
- 05
Precipitant investigations - Why
- Find infection, myocardial injury, stroke, pancreatitis, medication effect or inadequate support.
- Interpretation and limitations
- Direct cultures, imaging, ECG, troponin and other tests from the clinical picture; stress leucocytosis alone is not proof of bacterial infection.
- 06
Strict fluid balance and body weight - Why
- Estimate deficit, document renal response and guard against pulmonary or peripheral fluid overload.
- Interpretation and limitations
- Large deficits are replaced over many hours, not as an automatic bolus sequence; interpret urine output and cumulative balance with repeat examination and cardiorenal reserve.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Diabetic ketoacidosis
Substantial ketonaemia and metabolic acidosis indicate DKA; marked hyperosmolality can coexist and creates a mixed presentation requiring both principles.
Stroke
Focal deficits or altered consciousness may reflect cerebral ischaemia rather than hypertonicity alone, and stroke can also precipitate HHS.
Sepsis
Infection can independently cause delirium, hypotension and kidney injury while driving hyperglycaemic decompensation, so active source assessment is essential.
Medication or toxic encephalopathy
Sedatives, anticholinergics or other substances can explain mental-state change, but do not remove the physiological significance of severe hyperosmolality.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01DiagnoseConfirm HHS and identify overlapFirst stepAn adult has extreme hyperglycaemia, dehydration, cognitive change or a prolonged osmotic prodrome.+
- 1Perform ABCDE and obtain bedside glucose, blood ketones, venous gas, sodium, potassium, urea and creatinine, then calculate and record osmolality immediately.
- 2Assess volume, consciousness, oxygenation, urine output, comorbidity and thrombosis while searching for infection, vascular events and medicines that precipitated deterioration.
- 3Classify typical HHS, mild ketonaemia without acidosis or mixed DKA/HHS because insulin timing and dose differ, and involve senior diabetes and critical-care clinicians accordingly.
02RehydrateRestore volume at a controlled rateThe diagnosis is HHS without shock requiring a separate immediate resuscitation decision.+
- 1Begin 0.9% sodium chloride through the current HHS schedule, using repeated haemodynamic and respiratory examination to reduce rates for heart, kidney or frailty constraints.
- 2Measure or calculate osmolality hourly initially, ensuring the fall remains 3–8 mOsm/kg/hour and the glucose decline does not exceed 5 mmol/L/hour.
- 3Continue 0.9% sodium chloride while osmolality falls appropriately even if sodium rises; consider 0.45% sodium chloride only under the protocol when adequate positive balance fails to reduce osmolality.
03InsulinIntroduce fixed rate at the right momentGlucose has stopped falling despite adequate fluid replacement, or clinically significant ketonaemia changes the timing.+
- 1In uncomplicated HHS, defer insulin until fluid response is assessed; premature intracellular glucose shift can reduce circulating volume and accelerate dangerous osmotic change.
- 2Start fixed-rate intravenous insulin at 0.05 units/kg/hour when indicated by the HHS chart, adding glucose substrate once the protocol glucose threshold is reached.
- 3If ketones exceed 3.0 mmol/L with acidosis, use the mixed DKA/HHS pathway and 0.1 units/kg/hour DKA insulin rate with cautious HHS fluid principles and senior supervision.
04RecoverComplete resolution and rehabilitationOsmolality, glucose, cognition and hydration are improving after active replacement.+
- 1Continue treatment until osmolality is below the protocol threshold, hypovolaemia is corrected, urine output is adequate, cognition approaches baseline and glucose is controlled.
- 2Transition to a specialist-agreed subcutaneous regimen only when clinically stable and eating, using timed overlap so insulin delivery remains continuous where required.
- 3Address the precipitant, mobility, pressure care, thrombosis risk, hydration access, cognition and community support; discharge may appropriately lag behind biochemical improvement.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Intravenous 0.9% sodium chloride
Use the staged volumes and rates on the current adult JBDS HHS chart, modified after each clinical and osmolality review for shock, age, heart failure, renal impairment and the measured fluid response.Do not copy a one-size fluid schedule or change to hypotonic fluid for sodium rise alone. Monitor pulmonary status, urine output, sodium and osmolality; shock, oliguria or overload needs immediate senior and critical-care reassessment.
Fixed-rate intravenous insulin for HHS
When glucose has ceased falling after adequate fluid, use 0.05 units/kg/hour under the JBDS HHS protocol; use 0.1 units/kg/hour only for specified mixed DKA/HHS with significant ketonaemia and acidosis.Early use can cause precipitous osmotic change and circulatory collapse. Verify weight, pump, glucose substrate and potassium, and do not improvise between rates when overlap classification or renal handling is uncertain; obtain specialist direction.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Thrombosis
Profound dehydration, hyperviscosity and immobility create a prothrombotic state, increasing both venous and arterial thrombotic events during HHS.
Neurological injury
Hypertonicity can cause lethargy, focal signs, seizure or coma, while overly rapid treatment-related shifts may worsen cerebral function.
Acute kidney injury
Severe water loss and poor perfusion reduce filtration, complicate electrolyte management and slow clearance of glucose and medicines.
Rhabdomyolysis and pressure injury
Hypertonicity, electrolyte depletion, immobility and reduced consciousness can damage muscle and skin during a prolonged illness.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Calculate osmolality hourly for the first six hours and then at the interval set by the HHS chart, plotting the trajectory rather than interpreting isolated results.
- Measure glucose hourly during insulin treatment and sufficiently frequently during fluid-only correction to ensure its decline remains no faster than 5 mmol/L/hour.
- Track sodium and potassium against changing glucose, prescribing potassium solely from the current chart and measured renal function rather than estimated total deficit.
- Repeat pulse, pressure, respiratory rate, oxygen saturation, temperature, consciousness, capillary refill, urine output and chest examination throughout the high-risk phase.
- Assess venous thromboembolism risk and provide prophylaxis under the live HHS and local policy unless contraindicated, while investigating any clinical thrombosis therapeutically.
- Continue daily cognitive, mobility, nutrition, skin and rehabilitation assessment because full recovery commonly extends beyond normalisation of the laboratory values.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Osmolality is the compass
Glucose, sodium and urea move together during treatment; their combined osmolality trajectory best shows whether cerebral tonicity is changing safely.
Sodium rise can be appropriate
As extracellular glucose falls, water shifts back into cells and measured sodium rises; concern depends on the concurrent osmolality trend and rate.
Fluid lowers glucose first
Restored renal perfusion and dilution can produce a substantial glucose fall without insulin, explaining why the initial therapeutic sequence differs from DKA.
Neurology recovers slowly
Cognition may lag behind circulation and biochemical improvement, but new focal signs or deterioration still demand an independent neurological diagnosis.
Overlap is not rare noise
Significant ketonaemia and acidosis changes the insulin rate; explicitly classify mixed disease rather than averaging two protocols informally.
Discharge requires infrastructure
Water access, mobility, cognition, carers, medicines support and sick-day recognition are central recurrence interventions in the often frail HHS population.
11Common pitfallsFrequent interpretation and management errors.
- 01
Starting a high-dose insulin infusion before restoring circulation in uncomplicated HHS and provoking a rapid intravascular-to-intracellular water shift.
- 02
Reacting to a rising sodium by changing fluid without first calculating whether overall osmolality is falling at the intended rate.
- 03
Using glucose alone as the treatment target while failing to plot osmolality, consciousness, perfusion and total fluid balance.
- 04
Treating mixed DKA/HHS as uncomplicated HHS despite ketones above 3.0 mmol/L with clear metabolic acidosis.
- 05
Replacing a large estimated water deficit rapidly in an older adult with heart or kidney disease without repeated respiratory and haemodynamic examination.
- 06
Ending care when glucose normalises even though hyperosmolality, cognitive impairment, immobility, thrombosis risk or the precipitating illness persists.