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Investigation and management of hyponatraemia in patients presenting for urgent medical assessment

Dr James Ahlquist Endocrinologist Southend Hospital Hyponatraemia

common

worrying

badly managed Hyponatraemia

Confident diagnosis Effective treatment

Prevent disasters Hyponatraemia: a common electrolyte disorder

Electrolyte disorder Prevalence

Hyponatraemia

Mild 15–22% of hospitalised patients1 (Serum [Na+] < 135 mmol/L) Approximately 7% of ambulatory patients1 Moderate1 Up to 7% of hospitalised patients1 (Serum [Na+] < 130 mmol/L) Severe2 Around 3% of patients2 (Serum [Na+] ≤ 125 mmol/L) Hyperkalaemia 2–5% of patients3

Hypercalcaemia < 1%; 15 cases per 100,000 person-year4

1. Ellison DH, Berl T. N Engl J Med. 2007;356(20):2064-2072. 2. Hoorn EJ, et al. Nephrol Dial Transplant. 2006;21(1):70-76. 3. Weir MR, Rolfe M. Clin J Am Soc Nephrol. 2010;5(3):531-548. 4. Lumachi F, et al. Curr Med Chem. 2008;15(4):415-421. Hyponatraemia: treatment options

Fix cause

Restrict Normal Give fluids more salt Sequence of assessment

• Confirm hyponatraemia, additional tests • Likely causes from history: wet or dry? • Hypervolaemic: – , liver failure, renal failure • Euvolaemic: – SIADH, glucocorticoid deficiency • Hypovolaemic: – Diarrhoea, vomiting, burns, Addison’s disease Hyponatraemia: caused by different underlying conditions

Aetiology of hyponatraemia (serum Na+ <130 mmol/L)

7% 2% 4% (n=121)

20% Primary Hypervolaemia Hypovolaemia SIADH 35% -induced Adrenal insufficiency

32%

1. Fenske W, et al. Am J Med. 2010;123(7):652-657. A three dimensional approach

• Clinical assessment doesn’t give the diagnosis

• Urine osmolality doesn’t give the diagnosis

• Urine sodium doesn’t give the diagnosis

All three together gives the diagnosis. Lab tests in hyponatraemia

• Serum electrolytes & osmolality • Urine electrolytes & osmolality

• Cortisol (9 am or stressed) to detect adrenal insufficiency • function test to exclude hypothyroidism

Lab tests: interpretation

• Serum electrolytes: for detection • Serum osmolality: to exclude ‘hidden’ osmolality: glucose, urea, triglycerides • Urine osmolality: low (<100) or high (>100) • Low in (excess intake, renal failure) • High (heart failure, SIADH, dehydration) • Urine Na: low (<30) or high (>30) • Low in heart failure, also in dehydration • High in SIADH (also in adrenal insufficiency) Clinical assessment of volume status is important in the differential diagnosis of hyponatraemia

Urine [Na+] Urine [Na+] < 20 mmol/L > 40 mmol/L Hypovolaemia Vomiting, diarrhoea, , Addison’s, Dry tongue, CVP, skin losses, burns CSW, Na+ losing urea, pulse, nephropathy BP

Euvolaemia Hypothyroidism SIADH Any cause + hypotonic Glucocorticoid fluids deficiency

Hypervolaemia CCF, , Renal failure, any Oedema, ascites, cause + diuretics LVF, JVP, CVP

CVP = central venous pressure; BP = blood pressure; CSW = cerebral wasting; LVF = left ventricular failure; JVP = jugular venous pressure; CCF = congestive cardiac failure; SIADH = syndrome of inappropriate secretion of antidiuretic hormone Figure provided by Prof C. Thompson Hypotonic hyponatraemia

Excess water intake Impaired renal dilution Urine osmolality < 100 > 100 mOsm/kg mOsm/kg Urine sodium Frequent causes: • Primary polydipsia < 30 > 30 Clinical status • Low solute intake mOsm/kg mOsm/kg

ECF volume ECF volume Decision making

Hypovolaemia Hypervolaemia Hypovolaemia Euvolaemia [Total body water ] [Total body water ] [Total body water ] [Total body water ] [Total body sodium ] [Total body sodium ] [Total body sodium ] [Total body sodium  ] Action required

Extrarenal solute Oedematous Renal solute loss: • Glucocorticoid loss: disorders: • Diuretic excess deficiency • Gastrointestinal loss • Heart failure (diarrhoea, vomiting) • Liver cirrhosis • Third space burns • Nephrotic syndrome • Salt losing nephritis • Hypothyroidism • Pancreatitis • Osmotic diuresis • Pain • Traumatised muscle (mannitol, glucose) • Nausea • SIADH • Glucocorticoid deficiency

Adapted from Fenske W, et al. Am J Med. 2010;123(7):652-657. Schrier R.W. J Curr Opin Crit Care. 2008;14(6):627-634. Verbalis J. Best Pract Res Clin Endocrinol Metab. 2003;17(4):471-503. … Diagnosis of SIADH

• Decreased serum osmolality: serum osmolality <275 mOsmol/kg • Inappropriate urinary concentration: urine osmolality >100 mOsmol/kg • Clinically euvolemic • Elevated urinary sodium excretion (>20-30 mmol/L) with normal salt and water intake. • Exclude other causes of euvolemic hypo-osmolality: severe hypothyroidism, glucocorticoid insufficiency • Normal renal function, no diuretic use. Treatment of SIADH

• Fix underlying cause • Fluid restrict: realistic? effective? • Modest fluid intake • Urine osmolality >500 mosmol/kg • Check Furst ratio: urine Na+K / serum Na ratio <0.5: fluid restrict to 1000 mL/day ratio 0.5-1: fluid restrict to 500 mL/day ratio >1: fluid restriction not likely to succeed Medical therapy for SIADH

• Loop diuretics (+ salt)

• Tolvaptan tablets (Samsca) 15 mg or 30 mg NHS cost £74.68/tablet Osmotic demyelination syndrome

• Severe hyponatraemia (Na <120 mmol/L) • Chronic: cerebral adaptation has occurred • Correction of low Na by >10 mmol/L per day • High risk: alcohol, malnutrition, liver disease • Neurological changes at day 2-6: • dysarthria, paraparesis, lethargy, confusion • Avoid osmotic demyelination: – cautious correction of hyponatraemia – re-lower Na if necessary Acute symptomatic hyponatraemia

• Post-op or acute severe illness • Acute hyponatraemia (<48 hours) • Headache, nausea, vomiting confusion, seizures, respiratory arrest • Acute cerebral oedema • Level 2 care, IV hypertonic saline: 100 mL 3% saline IV over 10 minutes and repeat until Na rises by 5 mmol/L.

Summary

• Hyponatraemia: challenge, worth getting right

• Correct diagnosis: – clinical, tests and good understanding

• SIADH: treatment options

• Acute hyponatraemia: rare, serious, important Am J Med 2013; 126 S1-S42

Eur J Endocrinol 170 (3) G1-G47 UK consensus advice

Eur J Clin Invest 2015; 45 (8): 888–894