01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Sodium concentration rises when electrolyte-free water loss exceeds replacement or, less commonly, when hypertonic sodium is administered. Cellular dehydration affects the brain, producing irritability, weakness, confusion, neuromuscular hyperreflexia, seizure and coma. Cerebral adaptation to chronic hypertonicity accumulates intracellular osmoles, so overly rapid water replacement can then cause cerebral oedema.
The diagnostic question is why thirst and renal concentration did not prevent the disturbance. Gastrointestinal, skin and respiratory losses usually produce a concentrated low-volume urine. Glycosuria, urea or mannitol causes osmotic diuresis. Central AVP deficiency produces inappropriately dilute polyuria responsive to desmopressin, while renal AVP resistance can follow lithium, hypercalcaemia, hypokalaemia or tubulointerstitial disease.
Fluid type and speed must be individualised. A water-deficit estimate is only a starting point because ongoing urine, stool, drain and insensible losses continue, and formulae assume a stable distribution. Children, pregnancy and acute sodium loading use distinct expert protocols. In adults with central AVP deficiency, Society for Endocrinology inpatient guidance and the patient’s established formulation are central safety controls.
Key points
- Hypernatraemia usually means water deficit relative to body sodium, caused by inadequate access or thirst, extrarenal water loss, osmotic diuresis or arginine vasopressin deficiency or resistance.
- Older, cognitively impaired, intubated, postoperative and care-dependent adults are vulnerable because they cannot obtain water even when renal physiology and thirst would otherwise protect them.
- Assess circulation before calculating free water: shock requires isotonic resuscitation first. In decompensated AVP deficiency with persistent excessive dilute urine, Society guidance advises desmopressin 1–2 micrograms IV or IM and serum sodium every 4 hours during resuscitation.
- Prefer oral or nasogastric water as soon as safe; select intravenous water-equivalent fluid and rate from sodium trajectory, glucose, losses, volume status and local specialist guidance.
- Measure urine volume and osmolality: in hypernatraemia, a kidney that cannot concentrate urine suggests renal water loss from AVP deficiency, AVP resistance or osmotic diuresis.
- Desmopressin is life-sustaining in central AVP deficiency, and omission or delay has caused severe dehydration and death according to the NHS England safety alert.
- Once desmopressin controls a high urine output, ongoing free-water prescription can lower sodium unexpectedly quickly; coordinate the medicine and fluid rather than managing them independently.
- Correction rate depends on duration and symptoms; presumed chronic or unknown-duration disease requires a conservative specialist-agreed trajectory with frequent adjustment, not a one-off deficit calculation.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Inadequate water access or thirst
Frailty, reduced consciousness, dysphagia, dependence on carers or hypothalamic injury prevents drinking enough to match otherwise ordinary losses.
Extrarenal water loss
Fever, sweating, respiratory loss, diarrhoea and drains remove water, usually with a kidney that appropriately produces concentrated low-volume urine.
Renal water loss
Osmotic diuresis, central vasopressin deficiency or renal vasopressin resistance produces excessive urine that may remain inappropriately dilute.
Hypertonic sodium gain
Hypertonic saline, bicarbonate, concentrated feed without water or dialysis error can raise sodium rapidly through iatrogenic solute administration.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Water deficit exceeds sodium loss
Net electrolyte-free water loss, or less commonly sodium gain, increases extracellular tonicity and serum sodium concentration.
- 2Water leaves brain cells
Hypertonic extracellular fluid draws water from neurons and glia, causing cellular dehydration, neurological dysfunction and, in severe acute cases, intracranial bleeding.
- 3Cerebral adaptation develops
With slower onset, brain cells accumulate intracellular osmoles to restore volume, which then creates vulnerability during rapid correction.
- 4Correction can reverse the gradient abruptly
Excessively rapid free-water replacement after adaptation moves water into brain cells and may cause cerebral oedema.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Lethargy, irritability, confusion, hyperreflexia, weakness, seizure or coma suggests clinically important hypertonicity and requires urgent neurological and biochemical assessment.
Tachycardia, hypotension, poor peripheral perfusion, dry mucosa and oliguria indicate priority restoration of intravascular volume before free-water calculation dominates care.
Reduced consciousness, delirium, dysphagia, immobility, absent carers or unavailable drinking water can create hypernatraemia even without unusually large physiological losses.
Large volumes of pale urine, intense thirst, pituitary disease, neurosurgery or missed desmopressin raises central AVP deficiency and must trigger immediate endocrine review.
Hyperglycaemia, high urea generation, mannitol or recovering obstruction can cause high urine volume with substantial solute excretion rather than pure AVP failure.
Hypertonic saline, sodium bicarbonate, concentrated enteral feed without water or dialysis error can raise sodium rapidly and needs immediate source control and specialist correction.
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
Serial serum sodium and measured osmolalityFirst step - Why
- Confirm hypertonicity and quantify the actual response to fluid and desmopressin treatment.
- Interpretation and limitations
- Plot time-stamped results and use the same analytical method where possible; the slope, duration and neurological state determine safety more than a single value.
- 02
Urine volume and osmolality - Why
- Assess whether kidneys concentrate appropriately during a hypertonic stimulus.
- Interpretation and limitations
- A low urine volume with high osmolality supports extrarenal loss or limited intake; persistent dilute polyuria suggests central or renal AVP dysfunction, while osmotic diuresis retains higher solute excretion.
- 03
Glucose, urea, creatinine and electrolytes - Why
- Identify osmotic diuresis, acute kidney injury and potassium or calcium contributors to renal concentrating failure.
- Interpretation and limitations
- Correct glucose interpretation for concurrent sodium movement, and recognise that hypercalcaemia or hypokalaemia may create reversible AVP resistance.
- 04
Strict fluid balance and body weight - Why
- Measure ongoing water loss and the effectiveness and safety of replacement.
- Interpretation and limitations
- Hourly urine during instability, stool and drain losses, intake and daily weight reveal why sodium departs from a predicted formula and guide iterative prescribing.
- 05
Medicine and feed reconciliation - Why
- Find omitted desmopressin, lithium, diuretics, osmotic agents or an inadequate enteral water prescription.
- Interpretation and limitations
- Confirm formulation, route, last dose and usual response; oral, sublingual, nasal and injectable desmopressin are not dose-equivalent.
- 06
Paired endocrine assessment when polyuria persists - Why
- Distinguish central AVP deficiency from renal resistance after acute safety is established.
- Interpretation and limitations
- Formal dynamic testing is specialist-led and unsafe during uncontrolled dehydration; use history, urine response and endocrine imaging or pituitary tests as directed.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Central vasopressin deficiency
Pituitary disease, neurosurgery, intense thirst and large volumes of dilute urine support deficient hormone release, particularly after missed desmopressin.
Nephrogenic diabetes insipidus
Lithium, hypercalcaemia, hypokalaemia or tubulointerstitial disease causes dilute polyuria that responds poorly to desmopressin when combined with the history and other findings.
Osmotic diuresis
Hyperglycaemia, high urea generation or mannitol causes high urine volume containing substantial solute rather than pure free-water diuresis.
Pseudohypernatraemia
Rare analytical effects can produce a discordant result; repeat measurement on an appropriate platform is considered when physiology and sodium do not align.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01ResuscitateRestore effective circulation firstFirst stepThe hypernatraemic adult has shock, hypotension or clinically important hypovolaemia.+
- 1Use ABCDE, obtain urgent serum and urine studies, secure accurate input and output measurement and identify ongoing gastrointestinal, renal, skin or iatrogenic losses.
- 2Give isotonic crystalloid resuscitation according to NICE CG174 and repeated haemodynamic assessment despite the raised sodium, because organ perfusion takes immediate priority.
- 3Once circulation is restored, calculate an initial water plan and move to oral, nasogastric or appropriate intravenous free-water replacement with a documented sodium trajectory.
02ReplaceCorrect water deficit iterativelyHaemodynamics are stable but hypertonicity and a water deficit remain.+
- 1Estimate duration, deficit and ongoing losses, then choose the safest enteral or intravenous route considering swallow, glucose, renal function, heart failure and access.
- 2Set an explicit conservative target for chronic or uncertain-duration hypernatraemia with renal or endocrine advice, prescribing only the next review interval rather than the entire estimated deficit blindly.
- 3Remeasure sodium and fluid balance frequently, increasing, reducing or pausing water according to the observed slope and neurological and respiratory examination.
03AVP-DProtect central AVP deficiencyKnown pituitary disease or persistent dilute polyuria suggests central arginine vasopressin deficiency.+
- 1Verify the established desmopressin preparation, dose, last administration and ward availability immediately, flagging it as life-sustaining and contacting endocrine specialists.
- 2In serious decompensation, restore fluid first and measure serum sodium every 4 hours during resuscitation. If excessive, inappropriately dilute urine persists, give desmopressin 1–2 micrograms IV or IM under Society guidance and reassess before repeating.
- 3Anticipate abrupt reduction in urine output after desmopressin and reduce ongoing free-water delivery if required to avoid an excessive sodium fall and water intoxication.
04PreventMake water and medicine accessibleThe acute sodium disturbance improves and care moves towards ward stability or discharge.+
- 1Address swallowing, cognition, mobility, thirst impairment, staffing and prescribed enteral water so the person can actually receive the planned daily intake.
- 2For AVP deficiency, document dose by formulation and route, ensure uninterrupted stock, provide a patient alert card and establish sick-day and admission instructions.
- 3EscalationAssign repeat sodium, renal and urine-volume review after any medicine or feeding change, with same-day escalation for recurrent polyuria, thirst, confusion or reduced intake.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Desmopressin for central AVP deficiency
Continue the person's verified stable formulation and dose when safe. In decompensated AVP deficiency, restore fluid first; if excessive dilute urine persists, give desmopressin 1–2 micrograms IV or IM, with serum sodium every 4 hours during resuscitation and response review before any repeat dose.Fluid resuscitation takes priority in shock. Monitor sodium, urine output and intake closely because antidiuresis can convert an active water prescription into rapid correction or hyponatraemia; check renal and cardiac cautions and never guess a route conversion.
Enteral water or intravenous glucose 5%
Prescribe the calculated but frequently revised free-water amount over the next monitored interval, preferring oral or nasogastric delivery when safe and using glucose 5% intravenously only within local fluid governance.Account for hyperglycaemia, ongoing losses, heart or renal failure and concurrent desmopressin. Do not use glucose 5% for initial shock resuscitation, and do not deliver a whole estimated deficit without repeat sodium and respiratory reassessment.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Neurological injury
Cerebral dehydration can progress from irritability and weakness to confusion, hyperreflexia, seizure, coma and intracranial bleeding.
Hypovolaemic organ injury
Concurrent water and volume depletion causes hypotension, acute kidney injury, poor perfusion and worsening inability to conserve water.
Cerebral oedema during correction
Over-rapid lowering after chronic adaptation can cause headache, neurological deterioration, seizure or herniation through intracellular water movement.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Measure sodium every four hours during active resuscitation of seriously unwell central AVP deficiency, and use an equivalently close local schedule for unstable severe hypernatraemia.
- Record hourly urine volume and, when useful, urine osmolality until losses and antidiuretic response are predictable; a sudden fall after desmopressin should change the water prescription.
- Repeat neurological observations and glucose with each meaningful sodium change, investigating deterioration for stroke, seizure, infection or cerebral oedema rather than assuming a metabolic cause alone.
- Track pulse, pressure, perfusion, lungs, daily weight and cumulative balance to distinguish correction of intracellular water from intravascular overload.
- Review potassium, calcium, creatinine and urea because renal concentrating ability and fluid tolerance change as companion abnormalities and acute kidney injury resolve.
- After discharge, confirm medicine access, drinking support and a named sodium follow-up; recurrent hypernatraemia often reflects a systems failure as much as physiology.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Shock fluid is still isotonic
A high sodium does not make glucose solution an adequate resuscitation fluid; restore the circulation first, then address the distributed water deficit.
Thirst is a safety organ
Severe hypernatraemia usually requires impaired drinking access or thirst in addition to losses, so social and functional assessment explains many episodes.
Urine behaviour identifies mechanism
The same serum sodium can accompany concentrated oliguria from inaccessible water or dilute polyuria from AVP failure, requiring very different prevention plans.
Desmopressin changes the denominator
Once renal water loss stops, every millilitre of continuing replacement has a larger effect; fluid and hormone prescriptions must be reviewed together.
Formulations cannot be swapped casually
Nasal, oral, sublingual and injectable desmopressin have different bioavailability, making medication reconciliation by microgram number alone unsafe.
Formulae are opening estimates
Total body water fractions and ongoing losses are uncertain in frailty and critical illness, so observed sodium trajectory outranks calculated precision.
11Common pitfallsFrequent interpretation and management errors.
- 01
Starting hypotonic free-water replacement in a shocked patient without first restoring effective circulating volume and reassessing perfusion.
- 02
Writing the entire calculated water deficit as a fixed infusion and failing to respond when urine losses, glucose or renal function changes.
- 03
Omitting or delaying desmopressin because it is treated as an optional home medicine rather than life-sustaining therapy in central AVP deficiency.
- 04
Giving desmopressin without reducing an aggressive water prescription when polyuria stops, causing an avoidably rapid sodium fall.
- 05
Diagnosing AVP deficiency from hypernatraemia alone without documenting urine volume, osmolality, osmotic diuresis and drinking access.
- 06
Discharging a dependent person with advice to drink more but no practical plan for water delivery, swallowing, carers or repeat sodium testing.