Hyponatraemia: confident diagnosis, effective treatment and avoiding disasters. Dr James Ahlquist Endocrinologist Southend Hospital

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1 Hyponatraemia: confident diagnosis, effective treatment and avoiding disasters Dr James Ahlquist Endocrinologist Southend Hospital

2 Hyponatraemia: a common electrolyte disorder Electrolyte disorder Prevalence Hyponatraemia Mild (Serum [Na + ] < 135 mmol/l) 15 22% of hospitalised patients 1 Approximately 7% of ambulatory patients 1 Moderate 1 (Serum [Na + ] < 130 mmol/l) Up to 7% of hospitalised patients 1 Severe 2 (Serum [Na + ] 125 mmol/l) Around 3% of patients 2 Hyperkalaemia 2 5% of patients 3 Hypercalcaemia < 1%; 15 cases per 100,000 person-year 4 1. Ellison DH, Berl T. N Engl J Med. 2007;356(20): Hoorn EJ, et al. Nephrol Dial Transplant. 2006;21(1): Weir MR, Rolfe M. Clin J Am Soc Nephrol. 2010;5(3): Lumachi F, et al. Curr Med Chem. 2008;15(4):

3 Hyponatraemia: caused by different underlying conditions Aetiology of hyponatraemia (serum Na + <130 mmol/l) 7% 2% 4% (n=121) 35% 20% Primary polydipsia Hypervolaemia Hypovolaemia SIADH Diuretic-induced Adrenal insufficiency 32% 1. Fenske W, et al. Am J Med. 2010;123(7):

4 Sequence of assessment Confirm hyponatraemia, additional tests Likely causes from history: wet or dry? Hypervolaemic: heart failure, liver failure, renal failure Euvolaemic: SIADH, glucocorticoid deficiency Hypovolaemic: Diarrhoea, vomiting, burns, Addison s disease

5 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 polyuria (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)

6 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.

7 Clinical assessment of volume status is important in the differential diagnosis of hyponatraemia Hypovolaemia Dry tongue, CVP, urea, pulse, BP Euvolaemia Hypervolaemia Oedema, ascites, LVF, JVP, CVP Urine [Na + ] < 20 mmol/l Vomiting, diarrhoea, skin losses, burns Hypothyroidism Any cause + hypotonic fluids CCF, Cirrhosis, Nephrotic syndrome Urine [Na + ] > 40 mmol/l Diuretics, Addison s, CSW, Na + losing nephropathy SIADH Glucocorticoid deficiency Renal failure, any cause + diuretics 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

8 Hypotonic hyponatraemia Excess water intake Urine osmolality Impaired renal dilution < 100 mosm/kg > 100 mosm/kg Frequent causes: Primary polydipsia Low solute intake < 30 mosm/kg Urine sodium > 30 mosm/kg Clinical status ECF volume ECF volume Decision making Hypovolaemia [Total body water ] [Total body sodium ] Hypervolaemia [Total body water ] [Total body sodium ] Hypovolaemia [Total body water ] [Total body sodium ] Euvolaemia [Total body water ] [Total body sodium ] Action required Extrarenal solute loss: Gastrointestinal loss (diarrhoea, vomiting) Third space burns Pancreatitis Traumatised muscle Oedematous disorders: Heart failure Liver cirrhosis Nephrotic syndrome Renal solute loss: Diuretic excess Salt losing nephritis Osmotic diuresis (mannitol, glucose) Glucocorticoid deficiency Glucocorticoid deficiency Hypothyroidism Pain Nausea SIADH Adapted from Fenske W, et al. Am J Med. 2010;123(7): Schrier R.W. J Curr Opin Crit Care. 2008;14(6): Verbalis J. Best Pract Res Clin Endocrinol Metab. 2003;17(4):

9 Diagnosis of SIADH Decreased serum osmolality: serum osmolality <275 mosmol/kg Inappropriate urinary concentration: High urine osmolality >100 mosmol/kg Clinically euvolemic High urinary sodium excretion >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.

10 SIADH is associated with several different causes 1,2 Cancers Pulmonary diseases Central nervous system disorders Medications Other causes (e.g. idiopathic, hereditary) 1. Ellison DH, et al. N Engl J Med. 2007;356(20): Verbalis JG, et al. Am J Med. 2013;126(10 Suppl 1):S1-S42.

11 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

12 Medical therapy for SIADH Demeclocycline Loop diuretics (+ salt) Tolvaptan tablets (Samsca) 15 mg or 30 mg NHS cost 74.68/tablet

13 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 (5% dextrose, desmopressin)

14 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.

15 Summary Hyponatraemia: challenge, worth getting right Correct diagnosis: clinical, tests and good understanding SIADH: treatment options Acute hyponatraemia: rare, serious, important

16 Am J Med 2013; 126 S1-S42 Eur J Endocrinol 170 (3) G1-G47

17 UK consensus advice Eur J Clin Invest 2015; 45 (8):

18 Eur J Clin Invest 2015; 45 (8):