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Hyponatraemia John Foote Causes, assessment and management
Hyponatraemia <ul><li>Definitions </li></ul><ul><li>Significance </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Inves...
Acute Hyponatreamia <ul><li>Hyponatraemia which has developed in less than 12-24 hours </li></ul><ul><li>Leads to water mi...
Acute Hyponatraemia and Cerebral Swelling Hyponatreamia Normal
Symptoms of Acute Hyponatraemia <ul><li>Nausea/vomiting </li></ul><ul><li>Headache </li></ul><ul><li>Muscular twitching </...
Chronic Hyponatraemia <ul><li>Hyponatreamia which has developed over more than 24 hours </li></ul><ul><li>ICF solute disca...
Chronic Hyponatraemia <ul><li>Symptoms develop due to neuronal electrolyte depletion with serum [Na + ] at about 115 mmol/...
Central Pontine Myelinolysis <ul><li>Onset occurs 24-48 hours after the over-rapid correction of hyponatraemia </li></ul><...
Water Homeostasis Plasma Osmolality (mOsmol/Kg) Oral water intake Renal water clearance 270 280 290 300
Osmolar Control of ADH Secretion 270 280 290 300 Plasma Osmolality (mOsmol/Kg) Plasma ADH
Non-osmolar Stimulation of ADH Secretion <ul><li>Hypovolaemia </li></ul><ul><li>Systemic hypotension </li></ul><ul><li>Tra...
Response to Vascular Volume Deficit Vascular volume deficit Osmolar ADH control Non-osmolar ADH control Vascular volume ma...
Investigation Pitfall <ul><li>Urine : serum osmolality measurements which are ‘inappropriately raised’ are non-specific, a...
Diagnosis and Assessment <ul><li>Serum sodium concentrations reflect the ratio between water and sodium content of ECF rat...
Diagnosis and Assessment <ul><li>The underlying aetiology will remain unknown in about 50% of cases of hyponatraemia </li>...
Diagnosis and Assessment <ul><li>To correctly classify hyponatraemia it is necessary to: </li></ul><ul><ul><li>Take a hist...
Hyponatreamia? Plasma osmolality     2.[Na + ] + 2.[K + ] + [Urea] + [Glucose] Osmolality can be effective or ineffective...
Pseudohyponatraemia Normo-osmolar Hyponatraemia Normal Pseudohyponatraemia 7% 20% 93% 80% [Na + ] plasma water: 150 mmol/l...
<ul><li>Renal sodium losses </li></ul><ul><li>GI fluid losses </li></ul><ul><li>Skin fluid losses </li></ul><ul><li>Haemor...
Management of Hyponatraemia True Hyponatreamia <ul><li>Correct underlying cause </li></ul><ul><li>Resuscitate with 0.9% sa...
Causes of Dilutional Hyponatraemia <ul><li>Renal insensitivity to ADH suppression </li></ul><ul><ul><li>Renal failure </li...
Criteria for Diagnosis of SIADH <ul><ul><li>Hypo-osmolar hyponatraemia </li></ul></ul><ul><ul><li>Clinical euvolaemia </li...
Management of SIADH <ul><li>Correct underlying cause </li></ul><ul><li>Residual mild hyponatraemia  (Na >125 mmol/l) can b...
Management of Non-SIADH Dilutional Hyponatraemia <ul><li>Renal insensitivity to ADH suppression </li></ul><ul><ul><li>Rena...
Severe Symptomatic Hyponatraemia <ul><li>Patients suffer double jeopardy of a pressure cone on one hand and CPM on the oth...
Is Serum [Na + ] < 125 mmol/l?  Neurological symptoms?  Duration of hyponatraemia?  Yes Chronic hyponatraemia  Yes No Emer...
Hypertonic Saline Therapy <ul><li>Start with 3% saline at 100 ml/hour </li></ul><ul><li>100 ml of 3% saline can be expecte...
Problems <ul><li>Over-reliance on laboratory data </li></ul><ul><li>Misclassification leading to the over-diagnosis of SIA...
Future Treatments <ul><li>Vasopressin (V2) receptor antagonists: </li></ul><ul><li>Highly effective in SIADH and volume ex...
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Hyponatreamia

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Hyponatreamia

  1. 1. Hyponatraemia John Foote Causes, assessment and management
  2. 2. Hyponatraemia <ul><li>Definitions </li></ul><ul><li>Significance </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Investigation and assessment </li></ul><ul><li>Management </li></ul>
  3. 3. Acute Hyponatreamia <ul><li>Hyponatraemia which has developed in less than 12-24 hours </li></ul><ul><li>Leads to water migration from ECF to ICF </li></ul><ul><li>Clinical issue is with cerebral swelling </li></ul><ul><li>Symptomatic at < 125 mmol/l </li></ul>
  4. 4. Acute Hyponatraemia and Cerebral Swelling Hyponatreamia Normal
  5. 5. Symptoms of Acute Hyponatraemia <ul><li>Nausea/vomiting </li></ul><ul><li>Headache </li></ul><ul><li>Muscular twitching </li></ul><ul><li>Cognitive impairment </li></ul><ul><li>Psychosis </li></ul><ul><li>Convulsions </li></ul><ul><li>Coma </li></ul>
  6. 6. Chronic Hyponatraemia <ul><li>Hyponatreamia which has developed over more than 24 hours </li></ul><ul><li>ICF solute discarded to match reduced ECF sodium loss </li></ul><ul><li>Water distribution between ICF and ECF is undisturbed </li></ul>
  7. 7. Chronic Hyponatraemia <ul><li>Symptoms develop due to neuronal electrolyte depletion with serum [Na + ] at about 115 mmol/l </li></ul><ul><li>Rapid correction of hyponatraemia leads to brain shrinkage and risk of central pontine myelinolysis </li></ul>
  8. 8. Central Pontine Myelinolysis <ul><li>Onset occurs 24-48 hours after the over-rapid correction of hyponatraemia </li></ul><ul><li>Devastating neurological deficit </li></ul><ul><ul><li>Quadraparesis </li></ul></ul><ul><ul><li>Psuedobulbar palsy </li></ul></ul><ul><ul><li>Mutism </li></ul></ul><ul><ul><li>Convulsions </li></ul></ul><ul><li>Malnourished or alcohol dependent patients at very high risk </li></ul>
  9. 9. Water Homeostasis Plasma Osmolality (mOsmol/Kg) Oral water intake Renal water clearance 270 280 290 300
  10. 10. Osmolar Control of ADH Secretion 270 280 290 300 Plasma Osmolality (mOsmol/Kg) Plasma ADH
  11. 11. Non-osmolar Stimulation of ADH Secretion <ul><li>Hypovolaemia </li></ul><ul><li>Systemic hypotension </li></ul><ul><li>Trauma </li></ul><ul><li>Highly potent mechanism </li></ul><ul><li>Non-osmolar stimuli are implicated in 95% of cases of severe hyponatraemia </li></ul>
  12. 12. Response to Vascular Volume Deficit Vascular volume deficit Osmolar ADH control Non-osmolar ADH control Vascular volume maintained at the cost of ECF dilution Volume deficit
  13. 13. Investigation Pitfall <ul><li>Urine : serum osmolality measurements which are ‘inappropriately raised’ are non-specific, are often over-reported on laboratory reports, and can be misleading </li></ul>
  14. 14. Diagnosis and Assessment <ul><li>Serum sodium concentrations reflect the ratio between water and sodium content of ECF rather than the absolute amount of either </li></ul><ul><li>In clinical practice hyponatraemia is usefully classified as hypovolaemic, normovolaemic and hypervolaemic types </li></ul>
  15. 15. Diagnosis and Assessment <ul><li>The underlying aetiology will remain unknown in about 50% of cases of hyponatraemia </li></ul><ul><li>Correct management can be instituted if hyponatraemia is correctly classified, whatever the aetiology </li></ul>
  16. 16. Diagnosis and Assessment <ul><li>To correctly classify hyponatraemia it is necessary to: </li></ul><ul><ul><li>Take a history </li></ul></ul><ul><ul><li>Establish if vascular volume is increased, reduced or normal </li></ul></ul><ul><ul><li>Interpret the results of relevant laboratory investigations in the light of the above </li></ul></ul>
  17. 17. Hyponatreamia? Plasma osmolality  2.[Na + ] + 2.[K + ] + [Urea] + [Glucose] Osmolality can be effective or ineffective Serum osmolality? <ul><li>Pseudohyponatraemia </li></ul><ul><li>‘ Drip’ artefact </li></ul>Normal or Raised <ul><li>Hyperglycaemia </li></ul><ul><li>Mannitol therapy </li></ul><ul><li>Radiographic contrast </li></ul>
  18. 18. Pseudohyponatraemia Normo-osmolar Hyponatraemia Normal Pseudohyponatraemia 7% 20% 93% 80% [Na + ] plasma water: 150 mmol/l 150 mmol/l [Na + ] whole plasma: 140 mmol/l 120 mmol/l Non-aqueous phase Aqueous phase
  19. 19. <ul><li>Renal sodium losses </li></ul><ul><li>GI fluid losses </li></ul><ul><li>Skin fluid losses </li></ul><ul><li>Haemorrhage </li></ul><ul><li>Heart failure </li></ul><ul><li>Liver failure </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>SIADH </li></ul><ul><li>Other causes of renal water retention </li></ul>Hyponatreamia? True Hyponatreamia Low Increased Normal Reduced Volume status? Serum osmolality? <ul><li>Pseudohyponatraemia </li></ul><ul><li>‘ Drip’ artefact </li></ul>Normal or Raised <ul><li>Hyperglycaemia </li></ul><ul><li>Mannitol therapy </li></ul><ul><li>Radiographic contrast </li></ul>
  20. 20. Management of Hyponatraemia True Hyponatreamia <ul><li>Correct underlying cause </li></ul><ul><li>Resuscitate with 0.9% saline </li></ul><ul><li>Optimise treatment of underlying disease </li></ul><ul><li>Restrict salt and water </li></ul><ul><li>Diuretics </li></ul><ul><li>Specific treatment for non-SIADH states or for SIADH </li></ul>Increased Normal Reduced Volume status?
  21. 21. Causes of Dilutional Hyponatraemia <ul><li>Renal insensitivity to ADH suppression </li></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>ACTH deficiency </li></ul></ul><ul><ul><li>Thyroid failure </li></ul></ul><ul><li>Reset osmostat - K + deficiency </li></ul><ul><li>Non-osmotic ADH secretion </li></ul><ul><li>SIADH </li></ul>
  22. 22. Criteria for Diagnosis of SIADH <ul><ul><li>Hypo-osmolar hyponatraemia </li></ul></ul><ul><ul><li>Clinical euvolaemia </li></ul></ul><ul><ul><li>Osmolality (urine) > Osmolality (plasma) </li></ul></ul><ul><ul><li>[Na + ] (urine) > 30 mmol/l </li></ul></ul><ul><ul><li>Normal renal function </li></ul></ul><ul><ul><li>No deficiency of cortisol or thyroxine </li></ul></ul><ul><ul><li>No non-osmotic cause for ADH secretion </li></ul></ul>
  23. 23. Management of SIADH <ul><li>Correct underlying cause </li></ul><ul><li>Residual mild hyponatraemia (Na >125 mmol/l) can be left untreated </li></ul><ul><li>Water restriction 500-1000 ml/day </li></ul><ul><li>Demeclocycline 600 mg/day </li></ul>
  24. 24. Management of Non-SIADH Dilutional Hyponatraemia <ul><li>Renal insensitivity to ADH suppression </li></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>ACTH deficiency </li></ul></ul><ul><ul><li>Thyroid failure </li></ul></ul><ul><li>Reset osmostat - K + deficiency </li></ul><ul><li>Non-osmotic ADH secretion </li></ul>
  25. 25. Severe Symptomatic Hyponatraemia <ul><li>Patients suffer double jeopardy of a pressure cone on one hand and CPM on the other </li></ul><ul><li>Rapid correction is indicated with hyponatraemia known to be acute (12-24 hours), or in the presence of neurological symptoms </li></ul><ul><li>Otherwise serum sodium correction should be limited to no more than 0.5 mmol/l/hour in the first 48 hours </li></ul>
  26. 26. Is Serum [Na + ] < 125 mmol/l? Neurological symptoms? Duration of hyponatraemia? Yes Chronic hyponatraemia Yes No Emergency correction with 3% saline 1-2 ml/kg/hour until [Na] > 125 mmol/l Urgent correction with 3% saline 1-2 ml/kg/hour until symptoms resolve, continue at 0.5 mmol/l/hour thereafter <24 h >24 h or unknown Routine assessment and management No Adverse outcome unlikely
  27. 27. Hypertonic Saline Therapy <ul><li>Start with 3% saline at 100 ml/hour </li></ul><ul><li>100 ml of 3% saline can be expected to increase serum [Na + ] by 2 mmol/l </li></ul><ul><li>Formulae to estimate the correction doses of iv saline are unreliable </li></ul><ul><li>Titrate the infusion rate on the basis of hourly serum [Na + ] measurements </li></ul>
  28. 28. Problems <ul><li>Over-reliance on laboratory data </li></ul><ul><li>Misclassification leading to the over-diagnosis of SIADH </li></ul><ul><li>Inappropriate application of therapies </li></ul><ul><li>Inadequate clinical supervision and laboratory monitoring </li></ul>
  29. 29. Future Treatments <ul><li>Vasopressin (V2) receptor antagonists: </li></ul><ul><li>Highly effective in SIADH and volume expanded hyponatraemia </li></ul><ul><li>Standard rules for correction rates apply </li></ul><ul><li>Hyponatraemia relapses on cessation </li></ul><ul><li>Phenomenally expensive </li></ul>

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