Hyponatraemia

Meet the patient

A 72-year-old woman is admitted after a fall with a fractured neck of femur. She takes a thiazide for blood pressure and an SSRI for low mood, both started in the last two months. She is dry, mildly confused, and her sodium comes back at 118 mmol/L.[8][10]

The orthopaedic team want her "sorted for theatre" and are eyeing a bag of saline. Before you touch a drip, two exam questions are live and you must answer both: what is her volume status? and is this acute and severe enough to need 3% saline now? Everything on this page exists to answer those two questions at consultant depth — and to stop you killing her in either direction.[1][3]

What hyponatraemia actually is — a water problem, not a sodium problem

Hyponatraemia is serum sodium under 135 mmol/L, and it is the commonest electrolyte disorder you will meet on the wards — present in 15 to 20 percent of emergency admissions, up to 20 percent of critically ill patients, and roughly 35 percent of hospitalised patients.[1][3]

Sodium is the master extracellular osmole, so a fall in sodium is — almost always — a fall in tonicity, and water moves into cells. The organ that cannot tolerate that swelling is the brain, caged in a rigid skull. Clinically, then, hyponatraemia is a disease of the central nervous system: cerebral oedema when it is acute, subtle cognitive and gait failure when it is chronic.[3]

The dogma to be stamped on you: hyponatraemia is a relative excess of water to sodium, and ADH is almost always the culprit. With the sole exceptions of primary polydipsia and a handful of salt-wasting states, arginine vasopressin acting on the V2 receptor is making the kidney hold water it should be excreting. Even the dehydrated patient — who has lost both salt and water — becomes hyponatraemic, because the body prizes volume over osmolality and refuses to switch ADH off.[1]

The whole job collapses into two questions, and answering them correctly is the difference between a good outcome and a coroner's case:[2]

1. What is the volume status? — hypovolaemic, euvolaemic or hypervolaemic. This localises the cause and the definitive therapy.
2. What is the onset and severity? — acute or chronic; mild, moderate or severe. This sets the speed of correction and which danger you are trying to avoid.[1]

The two ways these patients die are the mirror image of those two questions. Under-treat an acute case and the brain herniates; over-treat a chronic case and the pons demyelinates. Hold both dangers in your head at once — that is the entire job.[2][6]

The three axes — classify on three independent dials

Classify on three independent axes, and hold all three at once. Call them the three dials — osmolality, volume, onset — and turn each one before you treat. Miss a dial and you treat the wrong patient.[1]

Dial 1 — serum osmolality (turn this first, always)

[1]

Dial 2 — volume status (only once hypo-osmolar is confirmed)

[1]

Dial 3 — onset and severity (sets the speed and the danger)

[1]

Severity bands by absolute sodium — a guide only, because the symptoms and the rate of fall matter more than the number:[1]

• Mild — 130 to 134 mmol/L: usually asymptomatic, or subtle poor concentration and fatigue.
• Moderate — 125 to 129 mmol/L: headache, nausea, confusion, gait instability.
• Severe or profound — under 125 mmol/L: vomiting, seizures, coma; under 120 carries significant mortality, and profound (under 105 to 110) carries the highest risk of ODS if you over-correct.[6]

How common, how lethal

Hyponatraemia is the commonest inpatient electrolyte derangement, and it is not benign. Even "asymptomatic" cases carry a signal you ignore at your peril.[1][12]

[1]

Risk factors and the subtype they favour — a high-yield map for the viva:[1]

The mortality signal matters: even mild, "asymptomatic" hyponatraemia is independently associated with a roughly 2.5-fold rise in in-hospital mortality, longer stays, more falls, more fractures and osteoporosis. That is why it is never just a laboratory curiosity to chart and ignore.[12]

Why it happens — the osmostat, ADH and the brain's dilemma

The osmostat and ADH — a tight negative-feedback loop

Body water is held within a narrow osmolality (275 to 295 mOsm/kg) by a negative-feedback loop, and hyponatraemia means that loop has been defeated.[1]

1. Osmoreceptors in the organum vasculosum of the lamina terminalis (OVLT) sense a 1 to 2 percent rise in plasma osmolality and fire magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus.
2. Those neurons release arginine vasopressin (ADH) from the posterior pituitary into the circulation.
3. ADH binds V2 receptors on the basolateral membrane of collecting-duct principal cells, triggering a Gs-cAMP cascade.
4. cAMP drives aquaporin-2 (AQP2) channels into the apical (luminal) membrane, making the collecting duct water-permeable.
5. Water is reabsorbed down the cortico-medullary gradient built by the countercurrent multiplier and urea recycling, producing concentrated urine (up to 1000 to 1200 mOsm/kg) and dilute plasma.
6. Reverse it — water intake lowering osmolality — and ADH is suppressed, AQP2 is internalised, and the kidney makes maximally dilute urine (50 to 80 mOsm/kg). A normal adult can excrete up to 15 to 20 L of free water a day when ADH is fully off.[1]

So a healthy kidney protects you from hyponatraemia by excreting free water — which means hyponatraemia cannot develop unless the kidney cannot excrete the water it is given (ADH is on, or the diluting capacity is overwhelmed).[1][3]

Two prerequisites for true hypo-osmolar hyponatraemia

True hypo-osmolar hyponatraemia needs both of these:[4]

1. A source of free water — oral intake, IV D5W, irrigation fluid, or water released in catabolism.
2. An impaired ability to excrete it — almost always because ADH is present and acting on the collecting duct. The only real exceptions are primary polydipsia (intake that overwhelms even a maximally diluting kidney) and advanced renal failure (diluting capacity lost).[1]

This is why ADH sits at the centre of every form. In hypovolaemia ADH is high from volume depletion; in SIADH it is high for no good reason; in heart failure and cirrhosis the effective arterial volume is low despite total-body sodium overload, so the baroreceptors drive ADH anyway. Even the oedematous patient behaves, from the kidney's point of view, as if dry.[1]

The brain's dilemma — adapt now, risk demyelinating later

The brain is caged in bone and cannot swell, so astrocytes mount a volume-regulatory response. A fall in extracellular tonicity pushes water into astrocytes; to avoid exploding they shed osmolytes:[2]

1. Within minutes to hours — astrocytes extrude inorganic osmolytes (potassium, chloride) through ion channels and the AQP4 channel; loss of AQP4 itself protects against cerebral oedema.
2. Within 24 to 48 hours — they extrude organic osmolytes (the old "idiogenic osmoles": myo-inositol, glutamate, glutamine, taurine, betaine). This is the adaptation that lets the chronic hyponatraemic brain survive.[2]

That adaptation is the key to everything that follows:[2]

• Acute (under 48 h) — no time to shed osmolytes, so the brain swells: cerebral oedema, raised intracranial pressure, seizures, herniation. It can be fatal if untreated.
• Chronic (over 48 h) — the brain has shrunk by losing osmolytes, so symptoms are mild; but correct the sodium fast and the now-hypo-osmolar brain loses water faster than it can re-recruit osmolytes, and you cause osmotic demyelination syndrome (ODS) — demyelination of the basis pontis (central pontine myelinolysis, CPM) often with extrapontine sites.[6]

ODS amplifiers (lower your safe-correction threshold when these are present): hypokalaemia, alcohol use disorder, diuretic use, gastrointestinal losses, female sex, profound hyponatraemia (under 105 to 110), malnutrition and hepatic failure.[1][6]

Viva gold: osmotic demyelination was first described by Adams, Victor and Mancall in 1959 and named central pontine myelinolysis. The brain stem told them where; the corrected sodium told them why.[6]

What you see at the bedside — symptoms track the rate of fall

Severity tracks the rate of fall, not the absolute number. A patient whose sodium has crashed to 120 over twelve hours is gravely ill; one who has lived at 120 for weeks may be walking and talking. The symptoms split by tempo: cerebral oedema and raised intracranial pressure when acute, subtle neuro-cognitive and gait failure when chronic.[3]

Symptom severity bands (the European guideline grading):[1]

• Moderately severe or severe — vomiting, cardiovascular collapse, abnormal or somnolent, seizure, coma (GCS under 8). Treat as an emergency.
• Mildly symptomatic — nausea without vomiting, confusion, headache.
• Asymptomatic — no symptoms attributable to hyponatraemia.[1]

Acute severe hyponatraemia — the brain is herniating (under 48 h)

The picture is acute raised intracranial pressure, and it is an emergency:[5]

• Headache, nausea, vomiting — vomiting in a hyponatraemic patient is a red flag, full stop.
• Confusion, disorientation, agitation, lethargy, progressing to obtundation.
• Generalised tonic-clonic seizure, often self-limiting.
• Coma, decorticate or decerebrate posturing, fixed dilated pupils, respiratory arrest — signs of tentorial herniation, often fatal.
• Signs of the precipitant — a fresh surgical wound, recent MDMA, a marathon bib, a newly started diuretic.[10]

The feared exam scenario: a premenopausal woman, 24 to 48 hours after elective gynaecological or pelvic surgery, develops headache, nausea and seizure. That is acute post-operative hyponatraemia from SIADH, with high mortality from cerebral oedema — young women after gynaecological surgery are the highest-risk group.[2]

Chronic hyponatraemia — the patient who is "just a bit off"

Chronic disease is subtle and easy to miss. The patient, often elderly, is written off as "off legs":[9]

• Fatigue, lethargy, apathy, poor concentration.
• Cognitive impairment, forgetfulness, a depression-like picture.
• Gait instability and falls — a 3-fold increased fall risk even at Na 130 to 134, from mild cerebral oedema disrupting cerebellar-vestibular function, and a major cause of hip fracture in the elderly.
• Anorexia, nausea, muscle cramps.
• Osteoporosis — chronic hyponatraemia directly drives osteoclastogenesis (ADH acts on bone) and carries an increased fracture risk (23.3 vs 17.3 percent over 7.4 years in a prospective cohort).[3]

Symptoms of the cause — do not miss these

Hunt for the cause while you classify the sodium:[1]

• SIADH — small-cell lung cancer (cough, haemoptysis, weight loss, smoker), CNS disease (headache, focal signs, meningism), pneumonia (cough, fever).
• Hypovolaemia — thirst, oliguria, orthostatic dizziness, dry mucosae; dig for diuretics, vomiting or diarrhoea.
• Hypervolaemia — dyspnoea (heart failure), jaundice and ascites (cirrhosis), periorbital and dependent oedema (nephrotic).
• Adrenal insufficiency — fatigue, weight loss, hyperpigmentation, abdominal pain, hypotension; it is effortlessly mislabelled as SIADH because cortisol deficiency unmasks ADH action.
• Hypothyroidism — cold intolerance, bradycardia, constipation, dry skin.[2]

Atypical presentations

The sodium is often found after the fall, not before:[3]

• Elderly — fall, delirium or hip fracture as the presenting complaint, with sodium 128 found incidentally. The "off-legs" elderly patient needs sodium on the panel.
• Premenopausal women — acute post-operative hyponatraemia with high mortality; vomiting in this group is a red flag.
• Pregnant — gestational hyponatraemia (Na falls about 5 mmol/L physiologically from relaxin and an ADH-like effect), and oxytocin in labour (structurally close to ADH) causes iatrogenic hyponatraemia — restrict free water in labour.
• Endurance athlete — collapse, seizure or pulmonary oedema at the finish line; weight gained during the race from over-drinking is the clue.
• Beer potomania — a chronic drinker on a near-zero-solute diet, suddenly confused; this one corrects dangerously fast.
• Diabetic on a thiazide — the commonest outpatient drug cause; check within 14 days of starting.[8]

The differential — structured by volume status

The differential is the volume status — full stop. Within each box, the specific cause is nailed by urine sodium, urine osmolality and the clinical context.[1][3]

Hypovolaemic hyponatraemia (clinical dehydration)

Euvolaemic hyponatraemia (no oedema, no dehydration)

Hypervolaemic hyponatraemia (oedema)

The trap that costs marks — SIADH versus cerebral salt wasting. Both turn up in CNS disease with a high urine sodium, but CSW is hypovolaemic (negative fluid balance, falling weight, raised haematocrit and urea, responds to saline) while SIADH is euvolaemic. CSW gets saline plus fludrocortisone; SIADH gets fluid restriction. Restricting fluid in CSW because you called it SIADH is a dangerous, classic error.[11]

The bedside assessment — volume status decides everything

Begin with ABCDE, vital signs, and a deliberate volume-status examination — because the volume status decides everything.[3]

Volume-status assessment — what to look for:[1]

• Hypovolaemia — dry axillae and mucosae, reduced skin turgor (over 2 s tenting), cool peripheries, orthostatic drop (systolic fall over 20 or diastolic over 10 mmHg on standing), resting tachycardia, low JVP, oliguria.
• Hypervolaemia — raised JVP (over 3 cm above the sternal angle), pulmonary crackles, S3 gallop, dependent oedema (sacral in the bed-bound, ankle in the ambulant), ascites, hepatomegaly.
• Euvolaemia (SIADH) — none of the above: normal JVP, no oedema, no dryness. The absence of findings is the finding.[1]

Named signs and manoeuvres worth performing:[1]

• Orthostatic vital signs — lying and standing BP and HR; a postural drop means at least 10 to 15 percent volume depletion.
• Jugular venous pressure — under 3 cm in hypovolaemia, raised in hypervolaemia.
• Capillary refill — over 2 s in hypovolaemia.
• Skin turgor — tenting in hypovolaemia (unreliable in the elderly).
• Tendon reflexes — slowed in hypothyroidism and in hyponatraemia itself.
• Cerebellar gait — impaired tandem gait is an early sign of even mild chronic hyponatraemia and predicts falls.[3]

The drug chart audit is not optional. Every hyponatraemia assessment must comb the chart for: thiazides (the commonest cause), SSRIs (especially in the elderly), carbamazepine or oxcarbazepine (common, dose-dependent), NSAIDs (potentiate ADH), vincristine, cyclophosphamide, desmopressin (nocturia, haemophilia, von Willebrand), MDMA, oxytocin, antipsychotics, TCAs and opiates.[10]

Recognise the patient who needs escalation now — these warrant HDU or ICU and 3% saline: seizure, coma (GCS under 8), respiratory arrest, signs of herniation, severe symptoms with acute onset, or a rapidly falling sodium. At the bedside, always assess and correct hypoxia (it worsens cerebral oedema) and hypokalaemia (it worsens ODS risk).[3][5]

Investigations — osmolality first, then the urine, then the cause

The strategy is stepwise — never give 3% saline or treat empirically before you have confirmed the type.[1][3]

Step 1 — confirm true hypo-osmolar hyponatraemia

Serum osmolality is the gating test:[3]

• Under 275 mOsm/kg — true (hypo-osmolar) hyponatraemia — proceed to step 2.
• 275 to 295 — pseudohyponatraemia — check triglycerides and total protein or IgM (Waldenstrom). Treat the hyperlipidaemia or hyperproteinaemia; do not touch the sodium.
• Over 295 — translocational hyponatraemia — check glucose. measured Na falls about 2.4 mmol/L for every 5.5 mmol/L (100 mg/dL) glucose rise (classic factor 1.6; above 400 mg/dL, use 4.0). Also consider mannitol (osmolar gap, a patient on mannitol for raised ICP).[1][17]

Step 2 — determine volume status clinically

Classify the patient at the bedside into hypo-, eu- or hypervolaemic, then use the urine indices to localise within the box.[1]

Step 3 — urine osmolality and urine sodium

Urine osmolality (Uosm) splits the world in two:[1]

• Under 100 mOsm/kg — ADH is fully suppressed and the urine is appropriately dilute. Causes: primary polydipsia, low solute intake (beer potomania, tea-and-toast), or a recent water load. The kidney is doing the right thing; the patient has simply overwhelmed it.
• Over 100 mOsm/kg — ADH is acting (inappropriately), which covers every other cause (SIADH, hypovolaemia, hypervolaemia). A Uosm over 100 essentially rules out primary polydipsia.[1]

Urine sodium (UNa) — interpret with the volume status, never in isolation:[1]

• Hypovolaemic with UNa under 20 — extrarenal loss (GI, burns, third-space).
• Hypovolaemic with UNa over 30 — renal loss (diuretics, Addison's, salt-losing nephropathy, CSW).
• Euvolaemic (SIADH) with UNa over 30 — euvolaemia maintains natriuresis (the patient eats salt and excretes it).
• Hypervolaemic with UNa under 20 — heart failure, cirrhosis (avid sodium retention from low effective arterial volume).
• Hypervolaemic with UNa over 30 — advanced CKD or AKI, or the patient is on diuretics.[1]

Step 4 — confirmatory and cause-finding tests

The essential panel:[1]

• Serum osmolality, urine osmolality, urine sodium (the diagnostic triad).
• Serum potassium — hypokalaemia amplifies ODS risk; correct before sodium.
• Glucose — for translocational correction.
• Renal function (urea, creatinine) — to exclude renal failure; high urea suggests hypovolaemia, low urea supports SIADH.
• Liver function and albumin — cirrhosis; also corrects anion gap interpretation.
• Thyroid function (TSH, free T4) — exclude hypothyroidism.
• 9 am cortisol / short Synacthen test — exclude adrenal insufficiency; mandatory in every unexplained case, as cortisol deficiency mimics SIADH.
• Serum uric acid — under 0.30 mmol/L supports SIADH (also low in SIADH with low fractional excretion of urate); raised in hypovolaemia and hypervolaemia.
• Lipid profile and total protein / immunoglobulins — if pseudohyponatraemia suspected.
• ECG — to detect arrhythmia and assess for hyperkalaemia (in adrenal insufficiency).
• Chest X-ray / CT — small-cell lung cancer, pneumonia, heart failure.
• CT/MRI brain — if CNS cause of SIADH suspected; MRI changes of ODS may not appear for 1 to 2 weeks after over-correction.
• Fractional excretion of urate — under 4 percent is highly supportive of SIADH (and differentiates from cerebral salt wasting where it is normal).
• Cosyntropin (Synacthen) stimulation test — for primary adrenal insufficiency.[1]

Distinguishing the difficult cases

Hypovolaemic versus euvolaemic with a urine Na over 30 — the confounder is diuretics. A thiazide makes a genuinely hypovolaemic patient look like SIADH (high urine Na). Stop diuretics for 2 to 3 days and re-evaluate; the fractional excretion of uric acid (over 9 percent in SIADH) and the response to 0.9% saline (Na rises in hypovolaemia, no change or worse in SIADH) settle it.[1][11]

SIADH versus cerebral salt wasting (CSW):[11]

The emergency — 3% saline for the brain that is herniating

Time-critical hyponatraemia is severe symptomatic or acute (under 48 h), and the single goal of resuscitation is to raise Na 4 to 6 mmol/L within the first 1 to 2 hours to relieve cerebral oedema. That small rise is enough to reverse impending herniation. Do not aim to normalise — ever.[3][5]

The resuscitation bundle (the European and Sterns-Adrogue consensus):[1][2]

1. ABCDE — secure the airway, give oxygen (hypoxia worsens cerebral oedema and ODS risk); IV access; cardiac monitor for seizure and arrhythmia.
2. Treat seizures — IV benzodiazepine per local protocol if needed — but know that the definitive anticonvulsant is 3% saline, not the benzodiazepine; the seizures stop as the sodium rises.[18]
3. 3% hypertonic saline — 100 mL IV bolus, with boluses of 100 to 150 mL repeated in rapid succession until symptoms resolve or Na has risen 4 to 6 mmol/L — this can be given through a peripheral line outside the ICU.[5][3]
4. Check serum sodium every 2 to 4 hours during active correction, and hourly after each bolus in ICU.
5. Stop the offending agent — diuretics, SSRIs, desmopressin, opiates — and treat the precipitant (pneumonia, pain, nausea).
6. Correct hypokalaemia and hypoxia aggressively — both are independent ODS risk factors, and potassium repletion itself raises sodium via the cellular Na-K exchange.
7. Reassess — once symptoms resolve and Na has risen 4 to 6 mmol/L in the first few hours, switch to slow correction (under 10 mmol/L in 24 h) and definitive cause-specific therapy.

Do not exceed 10 mmol/L in any 24 h (in high-ODS-risk patients target 4 to 6 mmol/L/day and do not exceed 8). If you overshoot, relower with desmopressin plus free water (D5W) to drag it back into the safe band — this is the modern approach to over-correction.[3][4][6]

Cardinal rules of resuscitation:[2]

1. Symptoms and onset decide the urgency, not the number. A sodium of 120 with a seizure is an emergency; a sodium of 120 found on a routine outpatient panel is not.
2. 4 to 6 mmol/L within the first 1 to 2 hours is the target for severe symptomatic disease — not normalisation. A small rise reverses cerebral oedema.
3. Cap correction at 8 to 10 mmol/L in 24 h in chronic or unknown-onset disease, and assume chronic if you do not know.[3][6]

Definitive therapy — match the treatment to the volume box

Once the patient is stable, definitive therapy is cause-specific and the speed of correction is onset-specific.[1][3]

The correction corridor (reproduced verbatim)

The Adrogue-Madias formula estimates the rise in Na per litre of infusate:[15]

Change in Na = (Na-infusate − Na-serum) / (TBW + 1), where TBW is total body water — 0.6 × weight in men, 0.5 in women, 0.7 in children. It is exact only for the addition of 1 litre of infusate; scaling the answer down to smaller volumes is not linear, so treat it as a rough guide — measure the actual sodium and do not trust the formula to run your patient.[15]

Hypovolaemic hyponatraemia — give saline

0.9% saline (Na 154 mmol/L) is the treatment. Give isotonic saline boluses in hypovolaemia or shock, then reassess with sodium every 2 to 4 h. Restoring volume switches off non-osmotic ADH, the sodium usually rises briskly, and the dilute water is excreted as dilute urine. Beware auto-correction: once ADH is suppressed in chronic severe hypovolaemia the kidney can correct on its own — check Na often and be ready to add D5W and desmopressin if the rise tops 10 mmol/L in 24 h. Add potassium chloride if hypokalaemic.[1][3]

• Addison's disease — stress-dose hydrocortisone, 0.9% saline resuscitation, and find and treat the precipitant (infection, Addisonian crisis). Mineralocorticoid (fludrocortisone) is not needed acutely — hydrocortisone has mineralocorticoid activity at stress doses.
• Cerebral salt wasting — 0.9% saline or balanced crystalloid to hold euvolaemia, fludrocortisone, and treat the underlying CNS insult.
• Diuretic-induced — stop the diuretic, replete volume and potassium, and pick a different antihypertensive.[1][2][11]

Euvolaemic hyponatraemia — SIADH, stepped

SIADH is managed stepwise — escalate only when fluid restriction fails.[1][2]

1. Fluid restriction — first-line. Intake must fall below urine output; if output beats intake, the sodium will rise. Bedside test: a urine-to-plasma electrolyte ratio (UNa + UK) / PNa over 1 means restriction will fail — the kidney is dumping more electrolyte than is in plasma. Restrict every source — oral, IV and hidden (medications, ice chips).
2. Enhance solute intake — oral urea in divided doses (poor palatability is its main drawback); the European guideline's preferred second-line, it provides an osmotic load that drives free-water excretion. Alternative: a high-protein, high-salt diet.
3. Loop diuretic plus normal saline — a loop diuretic orally, with 0.9% saline to match the urine output and prevent hypovolaemia. Use it when restriction fails or is intolerable.
4. Vasopressin receptor antagonists (vaptans) — tolvaptan 15 mg orally daily (titrate to 60 mg), or demeclocycline (historical; slow and potentially nephrotoxic). Vaptans block V2 and drive aquaresis — free-water excretion without sodium loss. Use cautiously: monitor Na every 6 h for the first 24 h (over-correction risk), restrict fluid after the first dose, and never combine with hypertonic saline. The SALT-1 and SALT-2 trials showed tolvaptan raises Na in euvolaemic and hypervolaemic hyponatraemia.[7]
5. Treat or remove the cause — resect the small-cell tumour, swap the SSRI, treat the pneumonia, stop the offending drug.

The other euvolaemic causes have their own fix. Glucocorticoid deficiency — hydrocortisone at stress doses restores ADH suppression and the sodium corrects. Hypothyroidism — levothyroxine; sodium corrects over days. Primary polydipsia — water restriction and treatment of the psychiatric driver. Beer potomania — modest solute re-feeding and slow correction (very high ODS risk from rapid spontaneous correction); do not fluid-restrict severely, give small amounts of isotonic saline, and monitor closely.[2][16]

Hypervolaemic hyponatraemia — restrict, loop, treat the cause

Fluid restriction plus a loop diuretic plus treatment of the underlying cause. Sodium correction is slow and partial — the priority is haemodynamic.[1][3]

• Heart failure — optimise GDMT (ACE inhibitor or ARB, beta-blocker, mineralocorticoid antagonist, SGLT2 inhibitor, loop diuretic); tolvaptan is licensed in some countries for short-term HF-related hyponatraemia.
• Cirrhosis — albumin, treat ascites with diuretics, avoid NSAIDs, consider transplant; use vaptans with great caution in cirrhosis (over-rapid correction risk).
• Nephrotic syndrome — treat the cause, protein repletion, loop diuretic with or without albumin.
• Advanced CKD or AKI — dialysis if severe; correct sodium slowly via the dialysate sodium.[1]

The scenarios you will actually meet

SIADH in detail — the four cause-boxes

Acute severe scenarios

Post-operative hyponatraemia — young women, 24 to 48 h after gynaecological or genitourinary surgery, with SIADH from pain, nausea, opiates and hypotonic fluids. Stop hypotonic fluids, treat pain and nausea, and give 3% saline if symptomatic. Mortality is high and the case is medico-legally notorious.[2]

TURP or hysteroscopy syndrome — absorption of glycine 1.5% or sorbitol irrigation through open venous sinuses causes acute dilutional hyponatraemia with transient blindness (glycine is a retinal neurotransmitter), bradycardia and QT prolongation. Stop the procedure, drain the bladder, supportive care; 3% saline if seizures.[1][10]

Exercise-associated hyponatraemia (EAH) — endurance athletes who over-drink, with non-osmotic ADH plus excessive hypotonic intake. It is acute and can be fatal — cerebral and pulmonary oedema at the finish line. Weight gain during the race is the clue. Treat with 3% saline 100 mL bolus on site if symptomatic, avoid NSAIDs, and prevent it by drinking to thirst, not to a schedule.[13][19]

MDMA or ecstasy — acute SIADH plus polydipsia; severe, rapid fall in Na with seizures. Treat with 3% saline.[14]

Beer potomania — a chronic drinker on a near-zero-solute diet who cannot excrete free water (you need solute to excrete water). It is dangerous because re-feeding solute triggers rapid spontaneous correction (the urine suddenly turns dilute, Na climbs fast) with high ODS risk. Treat with cautious solute repletion, modest saline, Na every 2 to 4 h, and pre-empt with desmopressin plus D5W if it rises too fast.[16]

Diuretic-induced — thiazide is the commonest drug cause; female, elderly, low body mass, hyponatraemia within 14 days of initiation. Stop the diuretic, replete potassium, and monitor for over-correction.[8][9]

Osmotic demyelination syndrome (ODS / CPM)

This is the feared complication of over-rapid correction of chronic hyponatraemia, and it is largely iatrogenic.[6]

• Mechanism — when Na is corrected faster than the brain can re-recruit organic osmolytes (myo-inositol, glutamate, taurine), astrocytes shrink, the blood-brain barrier breaks down, and oligodendrocytes undergo apoptosis, producing demyelination concentrated in the basis pontis (CPM) and often extrapontine sites (basal ganglia, thalamus, cerebellum, external capsule).
• Risk factors — chronic Na under 105 to 110 mmol/L, hypokalaemia, hypoxia or anoxia, hepatic failure, alcohol use disorder, malnutrition or anorexia, advanced age, female, premenopausal, burns.
• Clinical course — the patient improves as Na rises, then 2 to 7 days later develops dysarthria, dysphagia, flaccid then spastic quadriparesis, a "locked-in" syndrome (paralysed but conscious), seizures, coma, and often death or permanent disability. Mortality is 20 to 40 percent, with major residual morbidity in survivors.
• Diagnosis — MRI brain (T2 or FLAIR hyperintensity in the central pons), but changes lag the clinical picture by 1 to 2 weeks; treat on clinical grounds if the correction was too fast.
• Management — prevent it by correcting slowly; if you have over-corrected, relower Na immediately with D5W plus desmopressin back into the safe band — there is evidence this reduces ODS incidence.[6]

How patients come to harm — the preventable list

Complications of the disease:[9]

• Cerebral oedema and herniation — acute severe disease; can be fatal untreated.
• Seizures — acute disease; resolve as the sodium rises.
• Falls, fractures, osteoporosis — chronic disease; ADH directly stimulates osteoclasts.
• Cognitive impairment and gait instability — chronic disease; reversible with correction.
• Increased mortality — increased even with mild hyponatraemia (risk ratio 2.60 overall, 2.48 in hospitalised patients).[1]

Complications of treatment:[7]

• Osmotic demyelination syndrome — over-rapid correction of chronic disease.
• Volume overload and pulmonary oedema — hypertonic saline in heart failure; monitor.
• Hypokalaemia and metabolic acidosis — large-volume saline.
• Hypernatraemia — over-correction or vaptans; monitor every 2 to 4 h.
• Over-rapid correction and increased thirst — vaptans; monitor sodium closely.[3][7]

The classic pitfalls — do not ship these:[1][2]

• Treating a normal-osmolality or translocational hyponatraemia with 3% saline — always check osmolality and glucose first.
• Restricting fluid in cerebral salt wasting mislabelled as SIADH — CSW needs saline.
• Missing Addison's disease — every unexplained SIADH needs a cortisol; secondary adrenal insufficiency looks identical to SIADH.
• Not measuring Na during correction — auto-correction in hypovolaemia and beer potomania is unpredictable.
• Over-correcting — the single most preventable cause of ODS.
• Under-treating acute symptomatic disease for fear of ODS — acute disease has low ODS risk and high herniation risk; give 3% saline.
• Combining vaptans with hypertonic saline — dangerous synergy and over-correction.
• Giving D5W or 0.45% saline to a hyponatraemic patient — both are hypotonic and worsen Na.[1]

Prognosis and disposition

Prognosis tracks the cause, the onset and the absolute sodium.[1][12]

• Mild chronic hyponatraemia — usually resolves with cause management; the falls and fracture risk persists until corrected.
• Acute severe (under 120, seizure or coma) — high mortality without treatment, much better with prompt 3% saline.
• Hypervolaemic hyponatraemia in heart failure or cirrhosis — a marker of advanced disease carrying high mortality at 1 year (the sodium is a prognostic marker, not the cause of death).
• Profound chronic (under 105) — high ODS risk; correction is a tightrope; involve nephrology or endocrinology.
• Drug-induced — excellent with drug cessation and repletion.
• Post-operative acute — high mortality even with treatment; a medico-legal minefield.[2]

Disposition:[2]

• ICU — severe symptomatic (seizure, coma), 3% saline infusion, Na under 120 with high ODS risk, or need for frequent monitoring.
• HDU or step-down — moderate symptoms, active correction, frequent Na monitoring.
• Ward — mild-to-moderate chronic, asymptomatic, fluid-restriction management.
• Outpatient — chronic stable SIADH on long-term fluid restriction or vaptan, with endocrine or oncology follow-up for the cause.[1]

Special populations

Pregnancy — sodium falls modestly and physiologically (the osmostat resets downwards), and oxytocin — structurally close to vasopressin and able to mimic its renal water-retaining effect — given in prolonged labour with hypotonic fluids causes iatrogenic acute hyponatraemia — restrict free water in women receiving oxytocin. Severe symptomatic hyponatraemia in pregnancy is treated with 3% saline as in the non-pregnant (the fetus benefits from maternal stabilisation).[14][3]

Elderly — high prevalence (polypharmacy, falling diluting capacity, SSRIs and thiazides), atypical presentation (delirium, falls, hip fracture), a lower threshold to admit and monitor, and slow correction (high ODS risk from malnutrition and comorbidity).[3][8]

Children — sodium dosing is weight-based and cerebral-oedema risk is higher (larger brain-to-skull ratio). Common causes: gastroenteritis with dehydration (hypovolaemic), meningitis, diuretics, cystic fibrosis (salt loss in sweat), posterior pituitary tumours, and neonatal (mother's oxytocin, dilute formula). Use 0.9% saline for hypovolaemia and 3% saline 4 to 6 mL/kg boluses for severe symptomatic disease (a rapid 3 to 5 mmol/L rise), and correct at under 8 mmol/L in 24 h.[18][6]

Cirrhosis — hyponatraemia marks advanced disease and carries a poor prognosis. Restrict fluid, treat ascites with diuretics and albumin; use vaptans only with great caution in cirrhosis (over-rapid correction risk); consider transplant.[7][3]

Heart failure — hyponatraemia marks advanced HF and a poor prognosis; optimise GDMT (ACE inhibitor, beta-blocker, MRA, SGLT2 inhibitor); tolvaptan raises sodium short-term (SALT trials); long-term outcome benefit is unproven.[7][3]

Endurance athletes — prevent EAH by drinking to thirst, not to schedule; a symptomatic athlete at the finish line gets 3% saline 100 mL bolus (oral or IV); NSAIDs potentiate EAH.[13][19]

Chronic stable or outpatient SIADH — long-term fluid restriction is the mainstay; oral urea is effective; tolvaptan for selected cases with hepatic monitoring.[1][3]

Evidence, guidelines and regional differences

The landmark trials and what they changed:[1]

• SALT-1 and SALT-2 (Schrier et al., NEJM 2006) — tolvaptan (15 mg titrated up to 60 mg daily) raised Na in euvolaemic and hypervolaemic hyponatraemia at day 4 and day 30, establishing vaptans as therapy; sodium fell again after the drug was stopped.[7]
• European Clinical Practice Guideline (Spasovski et al., Intensive Care Med 2014) — the international consensus; it introduced the 100 mL 3% saline bolus for severe symptomatic disease, the 10 mmol/L in 24 h limit, and the classification by symptom severity.[1]
• Verbalis et al. Expert Panel Guidelines (Am J Med 2013) — the American counterpart; symptom-based rather than absolute-Na-based management, with fluid restriction first-line.[2]
• Adrogué, Tucker and Madias (JAMA 2022) — the modern synthesis: volume-status classification, 4 to 6 mEq/L within 1 to 2 hours for severe symptoms, the 10 mEq/L/24 h cap, and urea and vaptans for SIAD.[3][4]

The reference framework is the European 2014 guideline and the American expert panel 2013 together; recent work refining the Adrogue-Madias formula (Chen et al., Kidney360 2021) sharpens its bedside use.[1][15]

[1]

Controversies — whether tolvaptan has any role outside short-term inpatient care (no mortality benefit, cost, over-correction risk); whether profound chronic hyponatraemia (under 110) should ever be aggressively corrected or only symptomatically; whether bolus versus continuous hypertonic saline is safer — SALSA found both effective and safe, with fewer relowering treatments needed after boluses; and whether permissive over-correction in low-ODS-risk acute disease is safe. The conservative consensus — symptom-based therapy, a 10 mmol/L in 24 h cap, and relowering if over-corrected — is stable.[3][4]

The mantra, and the mnemonics

The mantra: water, not sodium — volume first, then onset. Three percent for the seizing brain, creep for the chronic one, and relower the moment you overshoot.[1][2][3]

The high-yield lines that decide a viva answer:[1]

• Hyponatraemia is a water problem, not a sodium problem — ADH is almost always the culprit.
• First test: serum osmolality — excludes pseudohyponatraemia and translocational (corrected Na = measured Na + 2 × (glucose − 5.5) / 5.5).
• Urine Osm over 100 = ADH acting; under 100 = polydipsia or low solute.
• Urine Na with volume status localises the cause — UNa over 30 plus euvolaemic = SIADH; UNa under 20 plus hypervolaemic = HF or cirrhosis; UNa under 20 plus hypovolaemic = GI loss.
• Severe symptomatic (seizure or coma) = 3% saline 100 mL IV bolus, repeat as required, target Na rise 4 to 6 mmol/L within the first 1 to 2 hours.
• Correction cap: 10 mmol/L in 24 h, 18 in 48 h; use 8 in high-ODS-risk (hypokalaemia, hypoxia, alcohol, malnutrition, Na under 105).
• Assume chronic if the onset is unknown — the safe default.
• ODS (CPM) presents 2 to 7 days after over-correction — dysarthria, dysphagia, locked-in; MRI lags by 1 to 2 weeks.
• Over-corrected? D5W plus desmopressin to relower.
• Every unexplained SIADH needs a cortisol — secondary adrenal insufficiency looks identical.
• Beer potomania corrects dangerously fast — the trickiest; pre-empt with desmopressin plus D5W if rising too fast.
• Premenopausal woman after gynaecological surgery — acute SIADH, high mortality, medico-legal.
• Restricting fluid in cerebral salt wasting is dangerous — CSW is hypovolaemic and needs saline.
• Never combine vaptans with hypertonic saline — over-correction.
• Use vaptans with great caution in cirrhosis — over-rapid correction risk.[7]

Ward-round test — four stems, thirty seconds each

Stem 1 — the post-operative seizure (answer)

A 34-year-old woman, 36 hours after an elective laparoscopic hysterectomy, becomes confused and then has a generalised seizure. She has received 3 L of 5% dextrose as maintenance. Sodium is 116 mmol/L. What is the diagnosis, and what do you do in the next ten minutes? Model: Acute (under 48 h) severe symptomatic hyponatraemia from post-operative SIADH, compounded by hypotonic maintenance fluid — a high-mortality, medico-legally dangerous scenario, especially in a premenopausal woman. Stop the dextrose immediately, secure the airway, give oxygen, treat the seizure with lorazepam, and give 3% hypertonic saline 100 mL IV bolus, repeating as required to raise Na 4 to 6 mmol/L within the first 1 to 2 hours — that rise alone reverses the cerebral oedema. Do not aim to normalise. Check Na after each bolus, then switch to slow correction (under 10 mmol/L in 24 h), and treat the pain and nausea driving the ADH.[3][5]

Stem 2 — the elderly woman on the SSRI and thiazide (answer)

The 72-year-old from the vignette: dry, confused, Na 118, on a thiazide and an SSRI, found after a fall. Is she hypovolaemic or euvolaemic, and does she get 3% saline? Model: Two questions before one bag. First, volume status: she is dry with an orthostatic drop — this is hypovolaemic until proven otherwise, so the thiazide is the lead diagnosis, not SIADH. Give 0.9% saline boluses, recheck Na every 2 to 4 h, and watch for auto-correction (be ready to add D5W and desmopressin if she climbs past 10 mmol/L in 24 h). Second, onset and severity: she has no seizure or coma, and this is almost certainly chronic, so she does not need 3% saline — assume chronic and creep. And before you label any residual "SIADH", send a 9 am cortisol — Addison's and secondary adrenal insufficiency masquerade as SIADH and are the classic missed diagnosis. Stop both the thiazide and the SSRI.[8][1][2]

Stem 3 — the beer-drinker who is correcting himself (answer)

A 58-year-old chronic drinker on a tea-and-toast diet presents confused; Na is 104 mmol/L, urine osmolality 80. You give a little solute and recheck at 4 hours: Na is now 116. What just happened, and what do you do? Model: Beer potomania — very low solute intake means the kidney cannot excrete free water (you need solute to excrete water), and the urine is appropriately dilute (Uosm under 100). The trap is that re-feeding solute flips the kidney into a sudden water diuresis and the Na rockets up — he has climbed 12 mmol/L in 4 hours, far past the 8 to 10 mmol/L in 24 h safe corridor, straight into ODS territory. Stop everything, give D5W, and give desmopressin to relower him back into the safe band, checking Na every 2 to 4 h. He is the classic patient who demyelinates from correction, not from the disease.[16][6]

Stem 4 — SAH, high urine sodium, and the wrong bag (answer)

A 60-year-old, day 3 after a subarachnoid haemorrhage, has Na 122 with a high urine sodium and high urine output. The team has started fluid restriction for "SIADH" and the patient is getting drier. What is the likely diagnosis and the error? Model: This is more likely cerebral salt wasting (CSW) than SIADH — both occur in CNS disease with a high urine sodium, but CSW is hypovolaemic (negative fluid balance, falling weight, raised haematocrit and urea, polyuria) while SIADH is euvolaemic. Fluid restriction is the error: CSW needs 0.9% saline to maintain euvolaemia and fludrocortisone, not restriction. Restricting fluid in CSW worsens hypovolaemia, sustains ADH, and can precipitate vasospasm and infarction in the SAH patient. The discriminator is volume status — check weight, fluid balance, haematocrit and urea, and treat CSW as hypovolaemic.[11][1]

References

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2. [2]Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations Am J Med, 2013.PMID 24074529
3. [3]Adrogué HJ, Tucker BM, Madias NE Diagnosis and Management of Hyponatremia: A Review JAMA, 2022.PMID 35852524
4. [4]Baek SH, Jo YH, Ahn S, et al. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial JAMA Intern Med, 2021.PMID 33104189
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