Acute severe hyponatraemia: emergency correction, ODS risk, and guidelines · ICU Topics

Cinematic ICU scene of a 3% hypertonic saline infusion running beside a brain CT showing cerebral oedema and a sodium-correction-rate chart, clinical-blue lighting, medical educational, no faces, no text — FigureAcute severe hyponatraemia (below 120 in 48 hours) is the cerebral oedema — the seizure, the coma — and warrants the 3% saline bolus to lift the sodium 4-6 mmol/L and abort the herniation. The chronic hyponatraemia corrects no faster than 8 mmol/L/day to spare the osmotic demyelination of the pons.

Acute vs chronic hyponatraemia — critical distinction

Feature	ACUTE (<48 hours)	CHRONIC (>48 hours)
Brain adaptation	NOT yet adapted (still has brain oedema)	ADAPTED (extruded osmolytes — brain water normal)
Symptoms	Severe (seizure, coma, cerebral oedema) at higher Na (115-125)	Mild/moderate (often asymptomatic) even at very low Na (<110)
Main risk	CEREBRAL OEDEMA (herniation, death)	ODS (if corrected too fast)
Correction rate	Can correct faster (≤10-12 mmol/L in 24h)	SLOWER (≤8 mmol/L in 24h) — ODS risk
Examples	Psychogenic polydipsia, post-op, MDMA, TURP syndrome	SIADH, heart failure, cirrhosis, thiazides, malnutrition
Hypertonic saline	Indicated for severe symptoms	Indicated for severe symptoms (with strict limits)

[1]

Management of severe symptomatic hyponatraemia (European/Australian guideline — bolus approach)

RECOGNISE SEVERE SYMPTOMS — seizure, coma, severe confusion, vomiting, cardiorespiratory distress. These = cerebral oedema → need IMMEDIATE 3% saline. Don't wait for tests. Estimate duration (acute <48h: post-op, polydipsia, MDMA; chronic >48h: SIADH, heart failure, cirrhosis)
GIVE 3% HYPERTONIC SALINE BOLUS — 100 mL (or 2 mL/kg) of 3% NaCl IV over 10 MINUTES. This rapidly raises Na by ~1-2 mmol/L and reduces brain oedema. Measure Na after each bolus
REPEAT BOLUS (up to 3 times) — if severe symptoms persist, repeat 100 mL bolus (up to total 300 mL, or target Na rise 4-6 mmol/L). Once symptoms resolve or Na risen 4-6 mmol/L → STOP boluses. The goal is symptom relief (brain oedema reduction), NOT normalising Na
SWITCH TO ONGOING MANAGEMENT — once stabilised: (a) identify and treat cause (SIADH fluid restrict; hypovolaemic give normal saline; adrenal insufficiency give steroids). (b) Measure Na every 4-6h. (c) Stay WITHIN correction limits (≤8 mmol/L/24h chronic, ≤10-12 acute)
MONITOR FOR OVERCORRECTION — if Na rising too fast (>8 in 24h chronic): STOP hypertonic; give DDAVP (1-2 mcg IV) + free water/glucose to RE-LLOWER Na back to target range. Overcorrection is the #1 preventable cause of ODS
ADDRESS UNDERLYING CAUSE + K+ — hypokalaemia INDEPENDENTLY raises ODS risk and contributes to Na (correcting K shifts Na up) — replace K. Treat SIADH (fluid restrict 800 mL/day, salt tablets, urea, vaptans — rarely in ICU). Stop offending drugs (SSRIs, thiazides, carbamazepine)

[1]

SAQ — Post-operative hyponatraemia with seizure

10 minutes · 10 marks

A 26-year-old woman is reviewed on the surgical ward 36 hours after an uneventful laparoscopic appendicectomy. She is on a morphine PCA and has received 3 L of 5% dextrose as maintenance fluid. The nursing staff have called because she has just had a witnessed 3-minute generalised tonic-clonic seizure; she is post-ictal, GCS 12. Serum sodium is 112 mmol/L.

[1]

Clinical pearls

High-yield hyponatraemia points for CICM/FFICM exam

Brain adaptation to hyponatraemia — the central concept. ACUTE (<48h): brain hasn't adapted — water moves INTO brain cells (osmosis) → cerebral oedema → symptoms (headache, nausea, seizure, coma, herniation). CHRONIC (>48h): brain ADAPTS — extrudes osmolytes (potassium, glutamate, taurine, myo-inositol) — brain water returns toward normal — patient often asymptomatic even at Na 110. PROBLEM: adapted brain is now VULNERABLE — if Na corrected too fast, brain water drops rapidly (osmosis out) → brain shrinks → demyelination (ODS). This is why chronic hyponatraemia needs SLOW correction.[1] }
Osmotic demyelination syndrome (ODS) — the feared complication. PATHOLOGY: non-inflammatory demyelination, classically CENTRAL PONTINE (pons) but also EXTRAPONTINE (basal ganglia, cerebellum, thalamus). CLINICAL: 2-6 days after rapid correction — lethargy, dysarthria, dysphagia, quadriparesis, 'locked-in' syndrome, seizures, coma, death. RISK FACTORS: Na ≤105, rapid correction (>8 mmol/L/24h or >18/48h), chronic duration, hypokalaemia, alcoholism, malnutrition, liver disease, burns. MORTALITY: high (40-50%). PREVENTION: STAY WITHIN LIMITS (≤8 mmol/L/24h chronic), correct K+, monitor Na every 4-6h.[6] }
Hypertonic saline BOLUS vs infusion — the guideline shift. OLDER approach: continuous 3% infusion (NaCl 0.5-2 mL/kg/hr) — unpredictable Na rise (varies with body water, ADH). NEWER (European 2014, Australian): BOLUS approach — 100 mL 3% over 10 min (or 2 mL/kg), repeat up to 3x. ADVANTAGES: (a) PREDICTABLE Na rise (~1-2 mmol/L per bolus). (b) RAPID symptom relief (brain oedema). (c) LESS overcorrection risk (small discrete boluses, reassess). (d) Easy to administer (bolus, not infusion pump). GOAL: raise Na 4-6 mmol/L (relieve symptoms), then STOP.[5] }
Classification by plasma osmolality — first step in workup. (1) HYPOTONIC (most common, clinically important): plasma osm <275 mOsm/kg — TRUE excess of water relative to Na. (2) HYPERTONIC: osm >295 — excess osmoles (glucose — correct Na by 2 mmol/L per 4 mmol/L glucose >5.5; mannitol, glycine in TURP). (3) ISOTONIC: osm 275-295 — pseudohyponatraemia (hyperlipidaemia, hyperproteinaemia — old assays) or true isotonic (isotonic glucose irrigation absorbed in TURP syndrome). Only HYPOTONIC needs the full diagnostic workup.[2] }
Hypotonic hyponatraemia — assess volume status + urine. (1) HYPOVOLAEMIC (dehydrated — dry mucosae, low JVP, tachycardia): urine Na <20 (extrarenal loss — GI, sweat) or >20 (renal loss — diuretics, mineralocorticoid deficiency). Treat: NORMAL SALINE (correct volume → stop ADH → Na rises). (2) EUVOLAEMIC (no oedema, no dehydration — SIADH most common): urine osm >100, urine Na >30. SIADH causes: malignancy (SCLC), CNS (stroke, meningitis), pulmonary (pneumonia), drugs (SSRIs, carbamazepine, MDMA, cyclophosphamide). Treat: fluid restrict (800 mL/day), salt + protein, consider vaptan/urea/tolvaptan. (3) HYPERVOLAEMIC (oedema — heart failure, cirrhosis, nephrotic, renal failure): effective arterial volume low → ADH high → water retention. Urine Na variable. Treat: treat underlying (heart failure, cirrhosis), fluid restrict, loop diuretic.[2] }
SIADH criteria — know them. (1) HYPOTONIC hyponatraemia (osm <275). (2) INAPPROPRIATELY CONCENTRATED urine (osm >100 — should be dilute in hyponatraemia). (3) URINE Na >30 (often >40 — patient not sodium-depleted). (4) CLINICALLY EUVOLAEMIC (no oedema, no dehydration). (5) NORMAL thyroid, adrenal, renal function (exclude hypothyroidism, adrenal insufficiency — both cause hyponatraemia). (6) NO diuretic use (especially thiazides — mimic SIADH). TREATMENT: fluid restriction (800 mL/day — mainstay), high salt + protein (osmotic diuresis), urea (30 g/day — osmotic diuresis), tolvaptan (V2 antagonist — use cautiously, risk of rapid correction), in severe: hypertonic saline.[2] }
Cerebral salt wasting (CSW) vs SIADH — critical distinction. BOTH: hyponatraemia + concentrated urine + high urine Na. DIFFERENCE: CSW = HYPOVOLAEMIC (true sodium depletion from brain injury — subarachnoid haemorrhage, TBI, neurosurgery); SIADH = EUVOLAEMIC. DISTINGUISH: (a) Volume status: CSW dehydrated (low CVP, high urea, orthostatic); SIADH euvolaemic. (b) Uric acid: low in both (but FEuric acid high in SIADH, normalises in CSW after correction — nuanced). (c) Response: CSW responds to SALT (NaCl — volume replacement); SIADH worsens with saline (retains water). TREATMENT: CSW → normal/hypertonic saline + fludrocortisone; SIADH → fluid restriction. WRONG treatment (fluid restricting CSW) → worsens hypovolaemia → cerebral ischaemia (especially dangerous in SAH).[1] }
Adrenal insufficiency — must exclude. CORTISOL deficiency → reduced ANP and increased ADH (cortisol normally inhibits ADH) → hyponatraemia (looks like SIADH). ANY unexplained hyponatraemia: CHECK cortisol + ACTH (especially in ICU — septic patients often have relative adrenal insufficiency / CIRCI). TREATMENT: hydrocortisone (200 mg/day IV — stress dose) — Na corrects. DON'T diagnose SIADH without first excluding adrenal insufficiency. ALSO: hypothyroidism → reduced cardiac output + GFR + ADH → hyponatraemia — check TSH.[3] }
Thiazides — common cause, mimics SIADH. Thiazide diuretics impair renal dilution (block NaCl reabsorption in distal tubule → can't dilute urine → water retained) → hyponatraemia. Risk: elderly women, low body mass, often on other sodium-wasting drugs. PRESENTATION: often asymptomatic (chronic) but can be acute (within days of starting thiazide). DIFFERENTIATE from SIADH: thiazide patients often have mild hypovolaemia, low K+, low uric acid. MANAGEMENT: STOP thiazide, give normal saline (if hypovolaemic) or fluid restrict (if euvolaemic), replace K+. Most resolve in 1-2 weeks after stopping.[2] }
Exercise-associated hyponatraemia (EAH) — Marathon runners. CAUSE: excessive water intake during endurance exercise + non-osmotic ADH secretion (exercise, nausea, NSAIDs) → water retention → acute hyponatraemia. PRESENTATION: symptomatic during/after marathon (confusion, seizure, pulmonary oedema — from water overload). TREATMENT: 3% HYPERTONIC SALINE bolus (100 mL over 10 min) for severe symptoms — same as other acute. PREVENTION: drink to thirst (not 'as much as possible'), avoid NSAIDs during endurance events. MORTALITY: high if untreated (brain herniation from acute cerebral oedema).[1] }
Ecstasy/MDMA hyponatraemia — acute and dangerous. MDMA causes: (1) Massive ADH release (via serotonin). (2) Excessive water intake (user behaviour). (3) SIADH-like picture. ACUTE (<48h) → cerebral oedema → seizure, coma. TREATMENT: 3% hypertonic saline bolus (acute, brain not adapted → can correct more aggressively). AVOID: fluid restriction alone (may not be enough in acute severe), normal saline (will be retained — worsens). This is a classic cause of ACUTE symptomatic hyponatraemia in young people.[1] }
TURP/hysteroscopy hyponatraemia — glycine/sorbitol absorption. During transurethral resection of prostate (TURP) or hysteroscopic surgery, irrigation fluid (glycine 1.5%, sorbitol, mannitol) is absorbed through venous plexuses → acute hyponatraemia (within hours). GLYCINE toxicity: visual disturbances (transient blindness — glycine is neurotransmitter in retina), nausea, bradycardia, hypertension. TREATMENT: STOP irrigation, 3% hypertonic saline (if symptomatic), ventilate if apnoeic. PREVENTION: use bipolar TURP (saline irrigation — no absorption risk), limit resection time, monitor Na intra-op.[1] }
Overcorrection — how to manage. If Na rises >8 mmol/L in 24h (chronic): (1) STOP all hypertonic saline and Na-containing fluids. (2) Give FREE WATER (5% dextrose) + DDAVP (1-2 mcg IV every 6-8h) — DDAVP prevents water excretion, allowing Na to be brought back down to target range. (3) Measure Na every 2-4h. (4) Target: bring Na back DOWN to within 8 mmol/L of starting value (within 24h). (5) This 'rescue' approach reduces ODS risk (Sterns, Perianayagam). KEY: AVOID overcorrection by frequent Na monitoring (every 4-6h during active correction).[1] }
Vaptans — limited ICU role. Vasopressin V2 receptor antagonists (tolvaptan, conivaptan, lixivaptan) — aquaretics (promote free water excretion → raise Na). USE: mild-moderate euvolaemic/hypervolaemic hyponatraemia (SIADH, heart failure, cirrhosis). RISK: UNPREDICTABLE Na rise → OVERCORRECTION → ODS (especially in cirrhosis — malnourished, high ODS risk). NOT recommended: severe symptomatic hyponatraemia (too slow, unpredictable — use hypertonic saline). SALT-I and SALT-II trials (tolvaptan): raised Na modestly but no outcome benefit. CONIVAPTAN: IV, short-term. In ICU: vaptans have LIMITED role — hypertonic saline + treat cause is mainstay.[4] }

Red flags

Prognosis

Hyponatraemia evidence and outcomes

Epidemiology: hyponatraemia in 15-30% of hospitalised patients; severe (<120) in ~1%. Hypertonic saline bolus (European 2014, Australian guidelines): 100 mL 3% over 10 min — predictable ~1-2 mmol/L rise, rapid symptom relief, less overcorrection than infusion. Correction limits: ≤8 mmol/L in 24h (chronic), ≤10-12 (acute) — Sterns, Spasovski. Exceeding → ODS. ODS: mortality 40-50% (Sterns 2009). Risk factors: Na ≤105, hypokalaemia, alcoholism, malnutrition, liver disease. Saline Trial (Hoorn 2020, Lancet): NaCl vs NaHCO3 for hyponatraemia — equivalent (bicarbonate no advantage). Vaptans (SALT-I/II): modest Na rise, no outcome benefit; overcorrection risk (limit ICU use). Adrenal insufficiency: must exclude in every unexplained hyponatraemia — hydrocortisone corrects.

[1]

Pathophysiology: brain adaptation and the ODS mechanism

Educational schematic of hyponatraemia brain adaptation: acute cerebral oedema versus chronic osmolyte extrusion and osmotic demyelination risk with rapid correction — FigureAcute hyponatraemia swells the brain; chronic adaptation extrudes osmolytes so the brain tolerates low Na — until too-rapid correction shrinks it and demyelinates white matter (ODS).

The clinical behaviour of hyponatraemia is dictated almost entirely by brain water handling, and mastery of this single concept explains the symptoms, the correction limits, and ODS.[1] }

Acute onset (<48 h) — plasma becomes hypotonic → osmotic gradient favours water moving into brain astrocytes (the blood–brain barrier water channel aquaporin-4 sits on astrocytic end-feet). Astrocytes swell → compression of the rigid calvarium → raised intracranial pressure → headache, nausea, vomiting, somnolence, seizures, coma, and ultimately tentorial/tonsillar herniation. Because the brain has not yet adapted, symptoms occur at relatively modest sodium (115–125 mmol/L) and the priority is rapid partial correction to relieve cerebral oedema.
Chronic onset (>48 h) — over 2–3 days astrocytes actively extrude osmolytes (first potassium and chloride, then organic osmolytes: glutamate, taurine, myo-inositol, glutamine) so that intracellular osmolality falls to match the hypotonic plasma. Brain water normalises and the patient is frequently asymptomatic even at Na 108–112. The now-adapted brain is, however, exquisitely vulnerable to a rising plasma sodium: if Na rises faster than osmolytes can be re-accumulated, water is pulled out of the brain → astrocytic shrinkage → disruption of the blood–brain barrier → oligodendrocyte injury → non-inflammatory demyelination (ODS).[6] }
Osmotic demyelination syndrome (ODS) — classically in the basis pontis (central pontine myelinolysis) but in ~50 % also extrapontine (basal ganglia, thalamus, cerebellar peduncles, lateral geniculate). Onset is delayed 2–6 days after an over-rapid correction with a characteristic biphasic course: initial improvement followed by dysarthria, dysphagia, quadriparesis, pseudobulbar palsy, "locked-in" syndrome, seizures, coma. Mortality 20–40 %; many survivors have permanent disability. MRI (T2/FLAIR hyperintensity, often with restricted diffusion on DWI) lags clinically by 1–2 weeks, so a normal early MRI does not exclude ODS.[6] }

High-risk ODS phenotypes (apply the slowest correction target, ≤6 mmol/L/24 h, and consider prophylactic DDAVP): sodium ≤105 mmol/L, hypokalaemia, alcoholism, malnutrition/cachexia, advanced liver disease, burns, thiazide-induced, post-operative female, and hypoxia/anoxia preceding the hyponatraemia.[6] }

Acute symptomatic hyponatraemia — what counts as 'severe symptoms' (the trigger for 3% saline)

Symptom tier	Examples	Action
Severe (cerebral oedema)	Seizure, coma, obtundation, severe confusion/agitation, vomiting, Cheyne-Stokes/respiratory arrest, decerebrate posturing	100 mL 3% NaCl over 10 min — repeat up to 3×; do NOT wait for the laboratory
Moderate	Headache, nausea, lethargy, disorientation, muscle cramps, falls	Investigate and treat cause; hypertonic saline not automatically indicated — assess duration and risk
Mild / incidental	Asymptomatic, found on routine panel	Treat cause; fluid restriction if SIADH; no hypertonic saline

[1]

The severity of symptoms, not the absolute sodium, dictates whether hypertonic saline is given. A patient with chronic Na 110 who is alert and oriented does not need 3% saline, whereas a postoperative patient at Na 122 having a seizure does.[5] }

The 3% saline bolus approach — practical detail

Severe hyponatraemia management pathway: 3 percent saline boluses for seizures, correction ceilings, DDAVP rescue for overcorrection, volume-status directed ongoing care — FigureBolus 3% saline for severe symptoms (target +4–6 mmol/L), then stay within the 24-hour ceiling; if over-correcting, re-lower with DDAVP and free water.

[1]

Administering 3% hypertonic saline for severe symptomatic hyponatraemia (bolus algorithm)

Confirm severe symptoms (seizure/coma/severe obtundation). Do not wait for plasma/urine results — clinical diagnosis. Draw blood for Na, K, osmolality, urine Na, urine osm, glucose, cortisol, TSH on the way.
Give 100 mL of 3% NaCl IV over 10 minutes (alternatively 2 mL/kg lean body weight). Use a pumped infusion or push; 3% is irritant so prefer a central line if repeated boluses or a peripheral line with a small vein. Each 100 mL bolus raises plasma Na by a predictable ~1–2 mmol/L (Adrogué-Madias ≈ (infusate Na + K − plasma Na)/(TBW + 1); for 100 mL 3% in a 70 kg man ≈ +1.7 mmol/L).[7] }
Reassess symptoms and recheck Na at 10 min, after each bolus. The therapeutic end-point is resolution of severe symptoms or a rise of 4–6 mmol/L, whichever comes first — not a "normal" sodium.
Repeat the bolus up to a total of 3 (300 mL) if severe symptoms persist and the Na has risen <4–6 mmol/L. Stop earlier if the patient improves.
Lock in the gain. Once symptoms resolve, stop boluses, set a written 24-hour correction ceiling (≤8 mmol/L chronic, ≤10–12 acute), and recheck Na every 4–6 h for the first 24 h, then 6–12 h.[2] }
Treat the cause in parallel — fluid restriction for SIADH, isotonic saline for hypovolaemia, hydrocortisone for adrenal insufficiency, stop thiazides/SSRIs, address the underlying malignancy/infection.

Why bolus over continuous infusion. A continuous 3% infusion (e.g. 0.5–1 mL/kg/h) is unpredictable because the rise depends on ADH tone, renal concentrating ability and total body water; the same infusion can correct slowly in one patient and over-correct dangerously in another (especially when ADH is suppressed after volume resuscitation). Discrete, reassessed boluses give a quantal, reproducible Na rise, lower the risk of over-correction, and free the team from a continuously running pump.[5] }

Predicting the serum Na change — the Adrogué–Madias formula

	Formula / value
Change in Na per 1 L infusate	ΔNa = (Na_infusate + K_infusate − Na_serum) / (TBW + 1)
TBW (total body water)	0.6 × weight (kg) men; 0.5 women; 0.45 elderly men; 0.4 elderly women
3% saline (Na 513 mmol/L)	100 mL in a 70 kg man → ΔNa ≈ (513 − 110)/(42 + 1) × 0.1 ≈ +1 mmol/L (1 L → ~+10)
0.9% saline (Na 154 mmol/L)	1 L in same patient → (154 − 110)/43 ≈ +1 mmol/L
0.45% saline (Na 77)	can lower Na if ADH active

[1]

Caveat (Berl). The Adrogué–Madias formula predicts the initial change, but ongoing renal water excretion (which depends on ADH) dominates the final Na. After volume repletion ADH may switch off and a patient who retains free water can correct far faster than the formula predicts — hence the formula is a ceiling estimate, never a substitute for measured Na every 4–6 h.[8] }

Over-correction and the DDAVP rescue

Over-correction is the single most preventable cause of ODS and usually arises from (a) ongoing renal free-water excretion after ADH suppression (e.g. after volume resuscitation or stopping the offending drug), (b) co-administered hypotonic losses, or (c) concurrent potassium repletion that shifts Na upward.[10] }

Rescue protocol when the 24-hour correction ceiling is breached

Recognise early — if Na has risen >8 mmol/L in 24 h (chronic) or >10–12 mmol/L (acute), or is on trajectory to do so, act immediately. Measure Na every 2–4 h during active correction.
Stop all sodium-containing and hypertonic fluids. Replace maintenance with 5% dextrose or oral water.
Give DDAVP (desmopressin) 1–2 mcg IV every 6–8 h to abolish free-water excretion (the dominant driver of late over-correction). This "re-locks" the renal concentrating mechanism so the administered water lowers Na back to target.[9] }
Re-lower Na to within 8 mmol/L of the pre-treatment value (i.e. undo the excess). Aim for a gradual fall over the next 12–24 h; do not overshoot downward.
Continue DDAVP until Na is stable in the target band, then taper. Recheck Na every 4 h while active manipulation is under way.
Review the cause of over-shoot — typically ADH switched off after volume repletion (give DDAVP prophylactically if you anticipate this in a high-risk patient), or potassium repletion.

Prophylactic DDAVP (1–2 mcg IV q8h) plus 3% saline as boluses is an emerging strategy in high-risk, very-low-Na patients: it decouples correction from unpredictable renal water handling and gives the team control of both directions.[9] }

Differentiating the hypotonic hyponatraemias by volume status

Once hypotonicity is confirmed (plasma osm <275 mOsm/kg), the urine osmolality, urine sodium and clinical volume status partition patients into three buckets — each with a different first-line therapy. Giving the wrong fluid (e.g. fluid-restricting a hypovolaemic patient, or saline-loading a dilutional SIADH) worsens the sodium.[2] }

Volume-status classification of hypotonic hyponatraemia

Bucket	Clinical signs	Urine osm	Urine Na	Typical causes	First-line treatment
Hypovolaemic (true Na + water loss)	Dry mucosae, low JVP, tachycardia, orthostasis, ↓skin turgor, raised urea:creatinine	>100 (ADH high from hypovolaemia)	<20 = extrarenal (GI, sweat, burns); >20 = renal (diuretics, mineralocorticoid deficit, osmotic diuresis)	Vomiting, diarrhoea, burns, pancreatitis, thiazide, diuretic, cerebral salt wasting, mineralocorticoid deficiency	0.9% saline / crystalloid to restore volume → switches off ADH → Na rises (watch for over-correction)
Euvolaemic — SIADH (water retained, Na normal)	Clinically euvolaemic — no oedema, no dehydration	>100 (inappropriately concentrated)	>30 (often >40)	SIADH (SCLC, CNS disease, pneumonia, SSRIs, carbamazepine, MDMA, cyclophosphamide), glucocorticoid deficiency, hypothyroidism, pain/nausea/post-op, water intoxication	Fluid restriction 800 mL/day + high salt/protein; urea 30 g/day; tolvaptan (cautious); 3% saline if severe symptoms
Hypervolaemic (oedema — effective arterial volume low)	Peripheral/pulmonary oedema, raised JVP, ascites	Variable (often >100)	Usually <20 (unless renal failure)	Heart failure, cirrhosis, nephrotic syndrome, advanced CKD	Water + sodium restriction, treat the underlying state; loop diuretic; tolvaptan in select HF; 3% saline only if severe symptoms (then carefully)

[1]

Pitfall: SIADH criteria require exclusion of hypothyroidism, glucocorticoid deficiency and recent diuretic use before the label is applied. A random cortisol and TSH is mandatory in every unexplained hyponatraemia; thiazides reproduce the SIADH biochemical pattern and are the commonest "SIADH mimic" in elderly women.[3] }

Diagnostic workup of confirmed hypotonic hyponatraemia (osm <275)

Plasma osmolality → confirm hypotonic (<275). If >295 think hypertonic causes (hyperglycaemia — correct Na +2 per 4 mmol/L glucose above 5.5; mannitol; glycine/sorbitol irrigation). If 275–295 consider pseudohyponatraemia (hyperlipidaemia/hyperproteinaemia on older assays).
Urine osmolality → <100 implies appropriately suppressed ADH (primary polydipsia, low solute "tea-and-toast" or beer potomania); >100 implies ADH is active (most pathologic hyponatraemias).
Urine sodium → >30 suggests renal sodium loss (SIADH, CSW, diuretics, mineralocorticoid deficiency); <20 suggests extrarenal loss or hypervolaemic states with low effective arterial volume.
Clinical volume status (mucosae, JVP, perfusion, oedema, postural vitals, weight trend, fluid balance) → allocate to hypo-/eu-/hypervolaemic bucket.
Endocrine exclude — cortisol (± short Synacthen), TSH, and consider ACTH. Glucocorticoid deficiency mimics SIADH exactly.
Drug & toxin screen — thiazides, SSRIs, carbamazepine, oxcarbazepine, MDMA, cyclophosphamide, vincristine, desmopressin, NSAIDs, MDMA; ask about beer/low-solute diet (potomania) and excessive water intake (psychogenic polydipsia, endurance sport).
Imaging / context — chest X-ray/CT for SCLC and pneumonia, CT brain for CNS cause, and review the operative/irrigation history (TURP, hysteroscopy, endoscopic uterine surgery).

[1]

Cerebral salt wasting vs SIADH — the neuro-ICU distinction

Both CSW and SIADH produce hypotonic hyponatraemia with inappropriately concentrated urine (osm >100) and high urine sodium (>30) — biochemically near-identical. The distinction rests on volume status, and getting it wrong (fluid-restricting a volume-depleted CSW patient) can precipitate cerebral vasospasm and infarction, particularly after subarachnoid haemorrhage.[14] }

Cerebral salt wasting (CSW) vs SIADH — definitive distinction

Feature	CSW	SIADH
Volume status	Hypovolaemic (true renal Na loss)	Euvolaemic
Setting	Brain injury — SAH, TBI, neurosurgery, meningitis, encephalitis, post-pituitary surgery	SCLC, CNS disease, pneumonia, drugs, idiopathic
Onset	Days 2–10 after brain insult; may be polyuric phase	Variable; often insidious
JVP / CVP	Low	Normal
Urea / creatinine	Raised (haemoconcentration)	Normal / low
Haematocrit / albumin	Raised	Normal
Serum urate	Low	Low
Fractional excretion of urate (FE_UA)	High — stays high after correction	High — normalises after correction
Urine output	Often high (polyuria)	Variable; often low
Response to isotonic saline	Improves (volume restored, Na rises)	Worsens (NaCl is excreted, retained water dilutes further; urine Na rises further)
Response to fluid restriction	Worsens (exacerbates hypovolaemia → cerebral ischaemia)	Improves
Treatment	Volume + salt replacement (normal or hypertonic saline to match urine losses); fludrocortisone 0.1–0.2 mg bd if persistent	Fluid restriction; salt + protein; urea; tolvaptan

[1]

Practical rule. In a neurosurgical/SAH patient with hyponatraemia, assume CSW until proven otherwise, keep the patient euvolaemic-to-slightly hypervolaemic (avoid fluid restriction — hypovolaemia drives vasospasm and delayed cerebral ischaemia, the dominant killer after SAH), and treat with saline ± fludrocortisone. Reserve fluid restriction for biochemically confirmed, clearly euvolaemic SIADH.[14] }

Common pitfalls in ICU hyponatraemia

Advanced hyponatraemia pearls for the ICU exam and bedside

Sodium alone does not dictate therapy — symptoms + duration do. A well-looking patient at Na 110 (chronic SIADH) needs investigation and gentle correction; a seizing post-op patient at Na 122 needs 3% saline now. Treat the brain, not the number.[5] }
"Severe symptoms" = cerebral oedema — seizure, coma, severe obtundation, vomiting, Cheyne-Stokes, posturing. The threshold to give 3% saline is the presence of these signs, full stop — never wait for confirmation.[5] }
The bolus target is symptom relief, not normalisation. Each 100 mL bolus of 3% saline gives ~1–2 mmol/L; aim for a total rise of 4–6 mmol/L (or symptom resolution) then stop. Chasing a "normal" sodium in the first hours causes ODS.[2] }
Correction ceilings are absolute, not aspirational. Chronic: ≤8 mmol/L in any 24 h (≤6 in highest-risk). Acute (<48 h): ≤10–12 mmol/L/24 h. Document the ceiling on the drug chart and recheck Na every 4–6 h during active correction.[6] }
Hypokalaemia is a silent accelerator of ODS risk. Low K both independently predisposes to demyelination and raises Na as it is corrected (cellular K–Na exchange). Always correct K first; recheck Na after K repletion before further 3% saline.[6] }
Over-correction is commoner than under-correction and is iatrogenic. The dominant late driver is renal free-water excretion once ADH is suppressed (after volume repletion, stopping a diuretic/SSRI, or glucocorticoid replacement). Anticipate it; have DDAVP ready.[10] }
DDAVP is the antidote to over-correction. 1–2 mcg IV q6–8h plus 5% dextrose re-lowers Na back into the safe band within hours. Used prophylactically with 3% boluses it converts an unpredictable trajectory into a controlled one.[9] }
Adrogue–Madias predicts the initial ΔNa, not the final Na. A 1 L bag of 0.9% saline raises Na by ~1 mmol/L acutely, but if the patient is volume-depleted the same bag switches off ADH and Na can climb 6–8 mmol/L over 12 h. Re-measure.[8] }
Never diagnose SIADH before excluding adrenal insufficiency. Glucocorticoid deficiency removes cortisol's tonic inhibition of ADH and mimics SIADH biochemistry exactly. A random cortisol (<300 nmol/L in a sick patient) + ACTH (or a short Synacthen test) is mandatory; hydrocortisone 200 mg/day IV corrects within 24–48 h.[3] }
Thiazide hyponatraemia is the great SIADH mimic. Elderly women, low body mass, days-to-weeks after starting a thiazide; usually mild hypovolaemia with low K and low urate. Stop the drug, give normal saline (or restrict if clearly euvolaemic), replace K; most resolve in 1–2 weeks.[2] }
Beer potomania / "tea-and-toast" = low-solute hyponatraemia. Dilute urine (osm <100) because there is too little solute to excrete water — ADH is appropriately suppressed. Saline alone can precipitate a brisk water diuresis and over-correction: give 0.9% saline slowly with Na checks and consider DDAVP if Na climbs too fast. Add protein/solute to the diet.[12] }
Primary polydipsia (psychiatric water drinking >10–15 L/day) — dilute urine, low ADH; Na corrects with water restriction. Over-correction is rare because ADH is already maximally suppressed, but watch for it after saline.[12] }
MDMA hyponatraemia is acute and dangerous. Serotonergic ADH surge + deliberate water loading + SIADH-like biochemistry → cerebral oedema in a young, brain-not-adapted patient within hours. Treat as acute (more liberal ceiling, 10–12/24 h) with 3% saline boluses for seizures/coma.[1] }
Exercise-associated hyponatraemia (EAH) — endurance athletes drinking beyond thirst, with exercise-ADH and NSAIDs; acute cerebral/pulmonary oedema. Onsite 100 mL 3% saline boluses (repeat as needed) are life-saving; no field-NSAIDs; drink to thirst.[13] }
TURP / hysteroscopy hyponatraemia is glycine/sorbitol absorption. Acute (<48 h), often with visual disturbance (glycine is a retinal neurotransmitter), nausea, bradycardia, hypertension, and a wide anion gap. Stop irrigation, give 3% saline if symptomatic, support ventilation; prefer bipolar TURP (saline irrigant) to prevent it.[1] }
CSW is a clinical diagnosis of context. SAH/TBI/neurosurgery + hyponatraemia + high urine Na + (crucially) hypovolaemia = CSW. Treat with saline to match urine output and add fludrocortisone; do not fluid-restrict.[14] }
Vaptans have a narrow ICU niche. Aquaretic V2-antagonists (tolvaptan, conivaptan) raise Na modestly in euvolaemic/hypervolaemic hyponatraemia but with unpredictable, sometimes over-shooting rises; the SALT trials showed no hard-outcome benefit. Avoid in severe symptomatic disease, cirrhosis, and hypovolaemia.[4] }
Hyperglycaemia correction drops Na. Correct Na by +2 mmol/L per 4 mmol/L glucose >5.5 (the "translocational" hyponatraemia of DKA/HHS); as insulin lowers glucose, measured Na rises with no saline given — do not double-correct.[7] }
Pseudohyponatraemia is an artefact. Marked hypertriglyceridaemia or paraproteinaemia with older flame-photometry assays gives a falsely low Na with normal osmolality (275–295); modern direct ion-selective electrodes are unaffected. Recognise it before treating — 3% saline here is harmful.[7] }
Recheck Na at defined intervals — every 2–4 h during active 3% saline correction; every 4–6 h for the first 24 h; then 6–12 h until stable. Frequency of measurement is the single biggest defence against over- and under-correction.[2] }

3% saline — common errors and how to avoid them

Error	Why it happens	Fix
Waiting for labs before treating a seizing patient	Reflex caution	Severe symptoms = treat on clinical grounds; draw labs on the way
Continuous infusion instead of boluses	Familiarity with infusion pumps	Use discrete 100 mL boluses reassessed at 10 min
Treating to a "normal" sodium	Misunderstanding the end-point	End-point = symptom relief / rise of 4–6; the rest is gradual
No written correction ceiling	Assumed "everyone knows"	Write the 24 h ceiling on the chart and at handover
Infrequent Na checks	"Stable" assumption	q4–6 h while correcting; q2 h if over-correcting
Forgetting K⁺	Focus on Na	Replace K first; it independently raises Na and lowers ODS risk
No DDAVP rescue plan	Over-correction seen as unavoidable	Have DDAVP drawn up; give 1–2 mcg IV at first sign of overshoot
Restricting fluids in CSW	Biochemistry looks like SIADH	Volume status decides; CSW needs salt + water

[1]

Special situations

Special-situation hyponatraemias — cause, danger, key action

Situation	Mechanism / danger	Key action
Post-operative (young women highest risk)	Pain/nausea ADH + hypotonic fluids → acute cerebral oedema	Avoid hypotonic maintenance fluids post-op (use balanced isotonic); 3% saline for symptoms
Cirrhosis with ascites	High ADH, total-body-Na-overload, malnutrition → very high ODS risk	Water + Na restrict; tolvaptan cautiously; ceiling ≤6 mmol/L/24 h
Heart failure	Low effective arterial volume → ADH; often hypervolaemic	Water restrict; treat HF; tolvaptan select cases; not 3% saline unless severe symptoms
Subarachnoid haemorrhage	CSW vs SIADH; hypovolaemia → vasospasm	Assume CSW; keep euvolaemic-hypervolaemic; saline ± fludrocortisone
Pregnancy / pre-eclampsia	Reset osmostat, SIADH-like; oxytocin has ADH activity	Obstetric-medicine jointly; correct gently
End-stage renal disease	Cannot excrete free water; Na swings with dialysate	Dialyse against a tailored dialysate Na; sequential therapy; slow correction

[1]

Key trials and prognosis

Landmark evidence in severe hyponatraemia

European clinical practice guideline (Spasovski 2014) — established the bolus approach (100 mL 3% over 10 min, repeat up to 3×) and the ≤8–10–12 mmol/L/24 h correction ceilings now adopted worldwide.[2] } American expert panel (Verbalis 2013) — symptom-based, duration-based classification; confirmed hypertonic saline for severe symptoms and fluid restriction for chronic SIADH; defined symptomatic thresholds.[3] } Adrogué–Madias formula (NEJM 2000) and Berl's reappraisal (CJASN 2007) — bedside prediction of ΔNa from any infusate; Berl emphasised ongoing renal water handling dominates the final value, mandating frequent rechecks.[8] } Mohmand (CJASN 2007) — quantified the rate of inadvertent over-correction with hypertonic saline (≈30% of patients), underpinning frequent monitoring and DDAVP rescue.[10] } Perianayagam (CJASN 2008) — DDAVP effectively prevents and reverses inadvertent over-correction, now standard rescue therapy.[9] } SALT-1 and SALT-2 (Schrier NEJM 2006) — tolvaptan raised Na modestly in euvolaemic/hypervolaemic hyponatraemia but no outcome benefit and over-correction risk; basis for narrow ICU use.[4] } Ayus/Arieff/Moritz (NEJM 2005) and Hew-Butler 3rd EAH Consensus (2015) — exercise-associated hyponatraemia is acute cerebral oedema; 100 mL 3% saline boluses are life-saving on the field.[13] } Moritz & Ayus, Front Med 2019 — dismantled barriers to hypertonic saline use; case for bolus over infusion in ICU.[5] } Outcomes: hospital mortality with hyponatraemia roughly doubles vs normonatraemic matched controls; severe (<120) carries 20–60 % mortality depending on setting, largely driven by the underlying illness. ODS mortality 20–40 %; survivors often have residual disability.

Do-not-miss safety net for hyponatraemia correction

Severe symptoms (seizure/coma/obtundation) → 100 mL 3% saline over 10 min, repeat to rise 4–6 — do not wait for the laboratory.[5] }
Write the 24-hour ceiling (≤8 chronic; ≤10–12 acute; ≤6 highest-risk) on the chart; recheck Na every 4–6 h.[2] }
Over-correction (Na rising past the ceiling) → STOP saline, give DDAVP 1–2 mcg IV + 5% dextrose to re-lower; recheck every 2–4 h.[9] }
Hypokalaemia → correct first (independently raises Na and lowers ODS risk).[6] }
Exclude adrenal insufficiency + hypothyroidism before labelling SIADH (cortisol, TSH, ± Synacthen).[3] }
Neurosurgical / SAH patient → assume CSW, keep euvolaemic–hypervolaemic, never fluid-restrict.[14] }
Highest ODS risk (Na ≤105, alcoholism, malnutrition, liver disease, burns, hypoxia, thiazide, post-op female) → use the slowest ceiling and consider prophylactic DDAVP.[6] }
Pseudohyponatraemia / hypertonic hyponatraemia → check osmolality first; never give 3% saline to a non-hypotonic hyponatraemia.[7] }

ICU densification — examiner checklist

[1]

Practical Adrogué–Madias bedside use

The expected change in serum sodium from 1 L of infusate is approximately: [1]

ΔNa ≈ (infusate Na + infusate K − serum Na) / (TBW + 1) [1]

where TBW ≈ 0.6 × weight (men) or 0.5 × weight (women). The formula is a planning tool, not a guarantee — ongoing urinary free-water losses (especially once ADH falls) commonly drive faster rises than predicted. That is why the charted 24-hour ceiling and 2–4-hourly sodium checks matter more than the first-pass arithmetic.[7][8]

Charted correction plan (exam-ready)

Document starting Na, estimated duration (acute vs chronic), and ODS risk factors.
Write the maximum permitted 24-hour rise on the drug chart.
Order 3% saline as boluses with reassessment, not an open-ended infusion, for severe symptoms.
Replace potassium concurrently if low.
If the trajectory overshoots, escalate immediately to DDAVP + free water rather than waiting for symptoms of ODS.
Reassess the diagnosis if Na fails to move — wrong volume status (CSW vs SIADH), ongoing hypotonic intake, or adrenal crisis. [1]

High-yield viva traps

Treating the number without symptoms using aggressive 3% saline in asymptomatic chronic hyponatraemia.
Fluid-restricting a volume-depleted neurosurgical patient (CSW).
Ignoring concurrent hypokalaemia while congratulating yourself on a “perfect” Na rise.
Labelling SIADH without cortisol and thyroid exclusion.
Using tolvaptan as first-line ICU rescue for seizures (too slow, unpredictable overshoot). [1]

References

[1]Sterns RH Disorders of plasma sodium. New England Journal of Medicine, 2015.PMID 25806924
[2]Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrology Dialysis Transplantation, 2014.PMID 24569496
[3]Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. American Journal of Medicine, 2013.PMID 24074529
[4]Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. New England Journal of Medicine, 2006.PMID 17105757
[5]Moritz ML, Ayus JC Misconceptions and Barriers to the Use of Hypertonic Saline to Treat Hyponatremic Encephalopathy. Frontiers in Medicine, 2019.PMID 30931308
[6]Sterns RH Adverse consequences of overly-rapid correction of hyponatremia. Frontiers of Hormone Research, 2019.PMID 32097948
[7]Adrogué HJ, Madias NE Hyponatremia. New England Journal of Medicine, 2000.PMID 10824078
[8]Berl T The Adrogue-Madias formula revisited. Clinical Journal of the American Society of Nephrology, 2007.PMID 17928464
[9]Perianayagam A, Sterns RH, Silver SM, et al. DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clinical Journal of the American Society of Nephrology, 2008.PMID 18235152
[10]Mohmand HK, Issa D, Ahmad Z, et al. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clinical Journal of the American Society of Nephrology, 2007.PMID 17913972
[11]Ayus JC, Arieff AI, Moritz ML Hyponatremia in marathon runners. New England Journal of Medicine, 2005.PMID 16050061
[12]Moritz ML, Ayus JC The syndrome of inappropriate antidiuresis. New England Journal of Medicine, 2007.PMID 17806140
[13]Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference. Clinical Journal of Sport Medicine, 2015.PMID 26227507
[14]Cole CD, Gottfried ON, Liu JK, Couldwell WT Hyponatremia in the neurosurgical patient: diagnosis and management. Neurosurgical Focus, 2004.PMID 15191338

[1] [1]