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Hyponatremia

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by dr Mohammed Abel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt. website: www.nephrotube.blogspot.com

by dr Mohammed Abel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt. website: www.nephrotube.blogspot.com

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  • 1. HYPONATREMIA New Scope of Diagnosis Simple Practical Way of Management Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) - Alexandria drgawad@gmail.com
  • 2. Normal serum sodium 135-145 mEq/L (mmol/L) 2 Hyponatremia serum sodium < 135 mEq/L (mmol/L) the most common disorder of body fluid and electrolyte balance encountered in clinical practice • Beukhof CM, Hoorn EJ, Lindemans J, Zietse R. Clinical Endocrinology 2007 66 367–372 • Upadhyay A, Jaber BL, Madias NE. Seminars in Nephrology 2009 29 227–238
  • 3. Fluid Compartments POTASSIUM SODIUM 3
  • 4. 4 Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Hyponatremia is primarily a disorder of water balance Relative excess of body water compared to total body sodium and potassium content H2O > Na It is usually associated with a disturbance in ADH
  • 5. Hyponatremia Clinical Presentation Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 The presence of these symptoms and their severity depend on both the MAGNITUDE of the hyponatremia and the RATE at which the hyponatremia developed
  • 6. Hyponatremia Pathogenesis of Central Effect M.Gawad www.nephrotubecne.com Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Normally: ICF Osmolality = ECF Osmolality Intracellular Extracellular
  • 7. Hyponatremia Pathogenesis of Central Effect Hyponatremia: ICF Osmolality > ECF Osmolality Intracellular Extracellular M.Gawad www.nephrotubecne.com Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 8. Hyponatremia Pathogenesis of Central Effect Hyponatremia: ICF Osmolality > ECF Osmolality Intracellular Extracellular Intracellular swelling & edema H2O M.Gawad www.nephrotubecne.com Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 9. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Hyponatremia Pathogenesis of Central Effect Hyponatremia: ICF Osmolality > ECF Osmolality
  • 10. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Hyponatremia How brain adapt hyponatremia ?? (especially chronic cases)
  • 11. Hyponatremia How brain adapt hyponatremia ?? (especially chronic cases) Maximal compensation for a decrease in plasma osmolality typically requires up to 48 hours. Adrogue HJ & Madias NE. Hyponatremia. NEJM 2000 342 1581–1589. Avoid rapid correction of hyponatremia
  • 12. Repeat serum Na The level should be repeated to rule out: – Lab error. – blood-drawing error. Precautions of sample taking: – the blood should be drawn through the skin (not from an IV line). – the blood should be drawn from a vein that does not have IV fluids flowing through it.
  • 13. What is the next step? What is the relation between Na and Plasma Osmolality? Normally ranges between 275 and 295 mmol/L
  • 14. True vs Pseudo - Hyponatremia 14Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.699. Translocational
  • 15. True vs Pseudo - Hyponatremia 15Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.699. Exculde Pseudo & Translocational Hyponatremia Translocational
  • 16. 16 Hyperlipidemia & Hyperproteinemia True vs Pseudo - Hyponatremia Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469
  • 17. In which compartment of the following we have to measure sodium concentration ?? Blood 5 liters Plasma 55%, 3 liters Water 90% Lipids, proteins & other inorganic substances Cellular elements 45%, 2 liters RBCs WBCs Platelets Pseudohyponatremia (Normal Plasma Osmolaity) Introduction 17
  • 18. TAKE CARE it is called: Na CONCENTRATION, Not Na LEVEL 18 Pseudohyponatremia (Normal Plasma Osmolaity) Introduction
  • 19. 19 Pseudohyponatremia (Normal Plasma Osmolaity) Hyperlipidemia & Hyperproteinemia Na is here Flame photometry measure Na in relation to all compartments Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469
  • 20. 20 Water + Na Proteins, Lipids Cells Na conc to water = 50% Na conc to all = 25% Water + Na Proteins, Lipids Cells Na conc to water = 50% Na conc to all = 12% The above numbers are not true values, they are only for demonstration Pseudohyponatremia (Normal Plasma Osmolaity) Hyperlipidemia & Hyperproteinemia M.Gawad www.nephrotubecne.com Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469
  • 21. The traditional method of measuring the sodium concentration in plasma flame photometry uses the entire volume of the sample, which includes both the aqueous and nonaqueous phases of plasma. 21 Pseudohyponatremia (Normal Plasma Osmolaity) Hyperlipidemia & Hyperproteinemia Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469
  • 22. Therefore, for patients with marked elevations in plasma lipids or plasma proteins, ask the hospital laboratory to use an ion-specific electrode to measure the plasma sodium concentration. 22 Pseudohyponatremia (Normal Plasma Osmolaity) Hyperlipidemia & Hyperproteinemia Pseudohyponatraemia still occurs despite the use of ion-selective electrodes Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469
  • 23. Serum Na x 93 99 – 1.03 (triglyceride gm/L) – 0.73 (protein gm/L) 23 Corrected Na = Pseudohyponatremia (Normal Plasma Osmolaity) Hyperlipidemia & Hyperproteinemia Stephen Sigworth, MD, MSHA. Sodium Disorders
  • 24. True vs Pseudo - Hyponatremia 24Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.699. Translocational
  • 25. 25 Translocational- Hyponatremia (High Plasma Osmolality) High Serum Glucose or Hypertonic Infusions •Carlotti AP et al. Intensive Care Medicine 2001 27 921–924 •Oster JR et al. Archives of Internal Medicine 1999 159 333–336 •Hillier TA et al. American Journal of Medicine 1999 106 399–403 Translocational
  • 26. Translocational Hyponatremia (High Plasma Osmolaity) Here Na is truly low (i.e. not lab error), but plasma osmolality is high 26 •Carlotti AP et al. Intensive Care Medicine 2001 27 921–924 •Oster JR et al. Archives of Internal Medicine 1999 159 333–336 •Hillier TA et al. American Journal of Medicine 1999 106 399–403 Hypertonic Infusions
  • 27. Translocational Hyponatremia (High Plasma Osmolaity) Here Na is truly low (i.e. not lab error), but plasma osmolality is high 27 •Carlotti AP et al. Intensive Care Medicine 2001 27 921–924 •Oster JR et al. Archives of Internal Medicine 1999 159 333–336 •Hillier TA et al. American Journal of Medicine 1999 106 399–403 Hypertonic Infusions
  • 28. True vs Pseudo - Hyponatremia 28 How to differentiate between 3 types of hyponatremia? Translocational
  • 29. True vs Pseudo - Hyponatremia 29 How to differentiate between 3 types of hyponatremia? Logic = Measure Plasma Osmolality Translocational
  • 30. True vs Pseudo - Hyponatremia 30 Hoorn EJ et al. QJM: Monthly Journal of the Association of Physicians 2005 98 529–540
  • 31. True vs Pseudo - Hyponatremia 34 Cholesterol, TG, Total proteins History, Blood glucose Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Translocational
  • 32. Repeat serum Na Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 33. H2O > Na True Hyponatremia •Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.699. •Adrogue HJ, Madias NE. Clinical Endocrinology 2000 52 667–678
  • 34. True Hyponatremia 37 Hoorn EJ et al. QJM: Monthly Journal of the Association of Physicians 2005 98 529–540
  • 35. True Hyponatremia 38 Clinical assessment of volume status ?! Generally not very accurate Likely to lead to misclassification of hyponatraemia Low sensitivity (0.5–0.8) and specificity (0.3–0.5) Algorithms that start with a clinical assessment of volume status are not accurate •Hoorn EJ et al. QJM: Monthly Journal of the Association of Physicians 2005 98 529–540 •McGee S et al. Journal of the American Medical Association 1999 281 1022–1029 •Musch W et al. American Journal of Medicine 1995 99 348–355
  • 36. Start with urine osmolality and sodium concentration (best determined in the same urine sample) Use the terms: a- Effective circulating volume b- Extracellular fluid volume Instead of hyper, hypo, euo - volumic
  • 37. ` Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 38. ` Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 High sensitivity estimates ranging from 0.87 to 1.0 but variable specificity estimates ranging from 0.52 to 0.83 Musch W et al. International Urology and Nephrology 2001 32 475–493
  • 39. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 40. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 This diagnostic tree is a simplification and does not guarantee completeness in each individual
  • 41. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 42. SIAD is a diagnosis of exclusion Janicic N et al. Endocrinology and Metabolism Clinics of North America 2003 32 459–481
  • 43. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 44. Management - General rules • If possible, stop fluids, medications and other factors that can contribute to or provoke hyponatraemia. • Saline 3% Rate of infusion: depends on onset of hyponatremia and/or severity of symptoms. • Interval of follow up of serum sodium concentration: depends on onset of hyponatremia and/or severity of symptoms. • Technique of serum sodium concentration measurement must be the same. • Maximum correction limit: increase in serum sodium concentration to 10 mmol/l in the first 24 h and 8 mmol/l during every 24 h thereafter, until a serum sodium concentration of 130 mmol/l is reached. • Stop infusion when: above mentioned limit is reached or symptoms improved. • Prompt diagnostic assessment with cause-specific treatment. • Additional diagnostic exploration for other causes of the symptoms if the symptoms do not improve (unresolved hyponatremia) with an increase in serum sodium concentration.
  • 45. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 46. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 There must be sufficient confidence that the symptoms are caused by hyponatraemia
  • 47. ` Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Start: i.v. infusion of 150 ml 3% hypertonic over 20 min (1D) After 20 min: Check serum Na concentration + Repeat an infusion of 150 ml 3% hypertonic saline for the next 20 min Repeating therapeutic recommendations above twice (2D). or until a target of 5 mmol/l increase in serum Na concentration is achieved (2D). Improvement of symptoms No improvement of symptoms Consider using weight-based (2 ml/kg) rather than the fixed 150 ml infusion volumes of 3% hypertonic saline in case of obviously deviant body composition
  • 48. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 49. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 In case of no improvement Continue an i.v. infusion of 3% hypertonic saline → Aiming for an additional 1 mmol/l per h increase in serum sodium concentration (1D). (use Adrogué–Madias Formula) Stopping the infusion of 3% hypertonic saline when (whichever occurs first - 1D). Symptoms improve or Serum Na concentration increases 10 mmol/l in total or The serum Na concentration reaches 130 mmol/l Diagnostic exploration for other causes (1D). Checking the serum Na concentration every 4 h (2D).
  • 50. Adrogué–Madias Formula Adrogue HJ, Madias NE. New England Journal of Medicine 2000 342 1581–1589 Total Body Water Assessment (TBW) men <70 years old 0.6 × body weight men ≥70 years old women <70 years old 0.5 × body weight women ≥70 years old 0.45 × body weight
  • 51. Adrogué–Madias Formula Adrogue HJ, Madias NE. New England Journal of Medicine 2000 342 1581–1589 Total Body Water Assessment (TBW) men <70 years old 0.6 × body weight men ≥70 years old women <70 years old 0.5 × body weight women ≥70 years old 0.45 × body weight Keep in mind that if hypokalaemia is present, correction of the hypokalaemia will contribute to an increase in serum sodium concentration. Kamel KS, Bear RA. Am J Kidney Dis. 1993;21(4):439.
  • 52. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 53. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 There must be sufficient confidence that the symptoms are caused by hyponatraemia
  • 54. i.v. infusion of 150 ml 3% hypertonic over 20 min (2D) Improvement of symptoms No improvement of symptoms Continue an i.v. infusion of 3% hypertonic saline → aiming for a 5 mmol/l per 24-h increase in serum sodium concentration (2D). (use Adrogué–Madias Formula) Stopping the infusion of 3% hypertonic saline when (whichever occurs first): Symptoms improved or Serum Na concentration increases 10 mmol/l in total or The serum Na concentration reaches 130 mmol/l Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Diagnostic exploration for other causes (2D) & cause specific treatment (1D) Checking the serum Na concentration after 1, 6, 12 h (2D).
  • 55. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 56. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 57. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 58. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 59. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 60. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 General rules specific for Chronic hyponatremia Mild hyponatraemia (130 and 135 mmol/l) We suggest against treatment with the sole aim of increasing the serum sodium concentration (2C). Moderate (125 and 129 mmol/l) or Profound (<125mmol/l) hyponatraemia Avoid an increase in serum sodium concentration of >10 mmol/l during the first 24 h and >8 mmol/l during every 24 h thereafter (1D). Check the serum sodium concentration every 6 h until the serum sodium concentration has stabilised under stable treatment (2D).
  • 61. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 62. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 63. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 • Increased number of deaths in those patients treated with vasopressin receptor antagonists in comparison with those treated with placebo. • Vasopressin receptor antagonists may actually worsen outcomes. • Rozen-Zvi B et al. American Journal of Kidney Diseases 2010 56 325–337 • Jaber BL et al. American Journal of Medicine 2011 124 971–979
  • 64. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 The side effects reported for demeclocycline and lithium were such that we recommend not using them for any degree of hyponatraemia.
  • 65. Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
  • 66. Rapid Correction of Hyponatremia Bad Effect Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 How brain adapt hyponatremia ?? (especially chronic cases) Maximal compensation for a decrease in plasma osmolality typically requires up to 48 hours. Avoid rapid correction of hyponatremia
  • 67. Rapid Correction of Hyponatremia Bad Effect Rare but dramatic complication Osmotic demyelination syndrome Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 Occurs with rapid correction of hyponatremia than the recommended limits of correction. Only two cases of osmotic demyelination syndrome have been reported with correction speeds below these limits. Pirzada NA, Ali II.. Mayo Clinic Proceedings 2001 76 559–562 Dellabarca C et al. International Urology and Nephrology 2005 37 171–1730
  • 68. Rapid Correction of Hyponatremia Bad Effect Rare but dramatic complication Osmotic demyelination syndrome Diagnosis: The lesions are detectable by both CT scan and MRI. MRI is more sensitive (because it is better able to visualize the brain stem and is more sensitive to changes in the white matter). Timing is critical in diagnostic studies because lesions do not become apparent for up to four weeks. Because of this delay, an initially negative study does not rule out. Harring TR, Deal NS, Kuo DC. Emerg Med Clin North Am. 2014 May;32(2):379-401.
  • 69. Rapid Correction of Hyponatremia What to do? Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39 If increases >10 mmol/l during the first 24 h or >8 mmol/l in any 24 h thereafter Discontinuing the ongoing active treatment (1D). Consulting an expert to discuss if it is appropriate to start an infusion of 10 ml/kg body weight of electrolyte- free water (e.g. glucose solutions) over 1 h under strict monitoring of urine output and fluid balance (1D). Consulting an expert to discuss if it is appropriate to add i.v. desmopressin 2 μg, with the understanding that this should not be repeated more frequently than every 8h (1D).
  • 70. Hyponatremia in a Patient on Hemodialysis What is the problem? Conventional hemodialysis is necessary to correct blood chemistries and volume overload, yet it may raise serum Na too quickly, potentially resulting in osmotic demyelination syndrome Erik M. Wendland, Andre A. Kaplan. Seminars in Dialysis—Vol 25, No 1 (January-February) 2012
  • 71. Hyponatremia in a Patient on Hemodialysis How to Manage? Among patients with severe chronic hyponatremia (predialysis serum sodium level <130 mEq/L), a cautious strategy is to set the dialysate sodium concentration at a level that is no higher than 15 to 20 mEq/L above the plasma level of the patient Daugirdas, JT, Ross, et al. Acute hemodialysis Prescription. In: Handbook of Dialysis, Philadelphia 2007
  • 72. Hyponatremia in a Patient on Hemodialysis How to Manage? It may be necessary to either cut the dialysis session short or to offset the effect of dialysis by concurrent infusions of 5 percent dextrose (D5W). Every 1L of D5W will becrease serum sodium concentration by 3.5 mEq / L. Hourly measurements of the serum sodium concentration during the course of dialysis are mandatory. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000; 342(20):1493-1499.
  • 73. Erik M. Wendland, Andre A. Kaplan. Seminars in Dialysis—Vol 25, No 1 (January-February) 2012 Female patient with hyponatremia (113 mEq/L) Dialysis for 3 hrs Female patient 50 kg TBW = 25 L Total Na to be transferred to the female = 2 X 25 = 50 mEq/hr = 150 mEq/3hrs Raise Na by 2 mEq/L/hr Female serum Na 113 mEq/L Dialysate Na 130mEq/L a net transfer of 17 mEq/L of Na 150 / 17 = 9 L (9000 ml) of blood would have to equilibrate with the dialysate Blood flow = 9000 ml / 180 min = 50ml/min Hyponatremia in a Patient on Hemodialysis How to Manage?
  • 74. Mohammed Abdel Gawad