Acute Hyponatraemia

Acute hyponatraemia is a serum sodium under 135 mmol/L that has developed in less than 48 hours. Onset may also be unknown in a symptomatic patient with a clear reason for rapid onset. It is dangerous because the brain has not had time to adapt. Water entering cells can cause cerebral oedema, seizures, brain stem herniation and death.

Severity is graded as mild (130 to 134 mmol/L), moderate (125 to 129 mmol/L) and profound (under 125 mmol/L). Symptoms are graded as moderately severe (nausea without vomiting, confusion, headache) or severe (vomiting, seizures, reduced consciousness, cardiorespiratory arrest).

Causes include:

• Water intoxication in primary polydipsia.
• Endurance exercise.
• Ecstasy (MDMA) use.
• Post-operative hyponatraemia, especially hypotonic fluid with non-osmotic antidiuretic hormone release.
• Thiazide diuretics.
• Oxytocin infusion.
• Bowel preparation for colonoscopy.
• Hypotonic intravenous fluids in children.
• Transurethral prostate resection with glycine irrigation.
• Desmopressin.

Premenopausal women and children are at the highest risk of cerebral herniation. Hospital incidence is 15 to 30% among inpatients, with acute severe forms in a small proportion.

Pathophysiology. A rapid fall in plasma osmolality moves water into brain cells. The skull limits expansion, so intracranial pressure rises. Brain cells lose sodium, potassium and organic solutes over 24 to 48 hours. This is why chronic hyponatraemia is safer but vulnerable to overcorrection.

• Mild: nausea, malaise, headache, mild confusion, unsteadiness, falls.
• Moderate to severe: vomiting, drowsiness, agitation, seizures, coma, respiratory arrest, pupil dilatation, decorticate posturing, noncardiogenic pulmonary oedema.
• Setting: marathon runner, ecstasy user at a party, post-operative patient on hypotonic fluids, child on maintenance fluids, patient on a new thiazide, person with psychiatric illness drinking over 10 litres daily.
• Often with signs of the cause: fluid overload, vomiting, diarrhoea, medicines.

Red flags

• Seizure, coma or respiratory failure with sodium under 125 mmol/L.
• Rapid fall (more than 0.5 mmol/L each hour) or sodium under 120 mmol/L with vomiting and headache.
• Premenopausal women or children after surgery.
• Marathon, MDMA or polydipsia presentations.

• Sodium (confirm with laboratory sample, not only blood gas analyser), potassium, chloride, bicarbonate, urea, creatinine, glucose and calcium.
• Serum osmolality: under 275 mosmol/kg confirms hypotonic hyponatraemia. Correct sodium for glucose by adding 2.4 mmol/L for each 5.5 mmol/L over normal glucose.
• Lipids and protein if pseudohyponatraemia is possible.
• Urine osmolality, taken before saline: under 100 mosmol/kg indicates water excess; over 100 mosmol/kg indicates antidiuretic hormone effect.
• Urine sodium, taken before saline: over 30 mmol/L suggests renal sodium loss or inappropriate antidiuretic hormone; under 30 mmol/L suggests hypovolaemia.
• Clinical volume assessment, weight, drug history, intake history, cortisol and thyroid stimulating hormone when no cause is clear.
• CT head if seizure with focal signs or doubt about the diagnosis (but do not delay treatment).
• Pregnancy test in women of childbearing age.

Differential diagnosis

• Seizure from other causes (intracranial haemorrhage, epilepsy, hypoglycaemia).
• Hyperglycaemia with translocational hyponatraemia.
• Pseudohyponatraemia (hyperlipidaemia, paraproteinaemia).
• Adrenal crisis.
• Hypothyroid coma.
• Cerebral salt wasting.
• Alcohol withdrawal.

Severely symptomatic (seizure, coma, vomiting, respiratory arrest): emergency treatment

• Hypertonic saline 3% 150 mL intravenously over 20 minutes (or 2 mL/kg, maximum 100 mL, over 10 to 20 minutes in children). Use a large peripheral vein if no central access. Do not delay treatment.
• Recheck sodium 20 minutes after the bolus. Repeat 3% saline 150 mL over 20 minutes up to two further times (three boluses in total) until sodium rises by 5 mmol/L or symptoms improve. Once symptoms improve, stop hypertonic saline.
• Target a rise of 5 mmol/L in the first hours. Limit the total rise to 10 mmol/L in the first 24 hours and 8 mmol/L in each following 24 hours.
• A lower limit of 8 mmol/L in the first 24 hours applies if the duration is uncertain or risk factors exist: sodium under 105 mmol/L, hypokalaemia, alcoholism, malnutrition, advanced liver disease.
• Seizures: lorazepam 4 mg intravenously (0.1 mg/kg in children, maximum 4 mg), repeated once after 10 minutes if seizures continue. Hypertonic saline remains the key treatment.
• Provide airway protection and oxygen. Use intensive care for respiratory failure or sodium under 120 mmol/L with symptoms.

Moderately symptomatic (nausea, confusion, headache)

• 3% sodium chloride 150 mL intravenously over 20 minutes once, then continued by cause. Target a rise of 5 mmol/L in 24 hours. Recheck sodium after 1, 6 and 12 hours.
• Stop hypotonic fluids, thiazides, desmopressin, oxytocin, selective serotonin reuptake inhibitors and other causes; restrict fluid.

Asymptomatic or mild

• Stop the cause. Restrict fluid to 800 to 1000 mL daily. Check sodium every 4 to 6 hours until it rises.
• Do not give isotonic saline when the urine osmolality is over 100 mosmol/kg and euvolaemia is likely, because it can lower sodium further.

Overcorrection (rise over 10 mmol/L in 24 hours, or over 8 mmol/L in 24 hours for high risk patients)

• Stop active therapy. Give desmopressin 2 microg intravenously every 8 hours (clamping urine output) and 5% glucose 3 mL/kg intravenously over 1 hour. Repeat and adjust to the hourly sodium check.
• Target a return to the 24-hour limit. This is managed in specialist units.

Monitoring. Check sodium every 2 hours for the first 6 hours, then every 4 hours while on therapy. Monitor urine output hourly: more than 100 mL each hour after treatment indicates water diuresis and overcorrection risk. Assess neurological status each hour. Continue sodium checks for at least 48 hours.

Referral and escalation. Use intensive care or high dependency for seizures, coma or hypertonic saline. Refer to endocrinology and nephrology for persistent unexplained hyponatraemia. Referral is urgent for any neurological symptoms.

Special groups

• Children: hypotonic maintenance fluids are a cause. Use isotonic fluids with glucose (0.9% sodium chloride with 5% glucose) and check sodium daily on fluids. Give 3% saline 2 mL/kg for seizures.
• Premenopausal women: high risk of encephalopathy; treat early with hypertonic saline.
• Endurance athletes: give hypertonic saline bolus without waiting for laboratory results.
• Pregnancy: oxytocin infusion with large hypotonic fluids can cause acute hyponatraemia; use isotonic fluids and limit volume.