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Sodium and Water
    Lecture for Fellows
     Joel M. Topf, M.D.
• 77 yo female
• increased intraocular pres-
  sure following cataract surgery

• admitted for mannitol infusion
  to redu...
• over 3 days she received
 • 2.5 liters of 20% mannitol
   •   how much mannitol is that?




 • ibuprofen for musculoske...
• over 3 days she received
 • 2.5 liters of 20% mannitol
   •   how much mannitol is that?
       20% means 20 g per 100 m...
112        38
                            180
                        3.2



• multiple seizures
• no measured osmolality
...
112        38
                            180
                        3.2



• multiple seizures
• no measured osmolality
...
119         38
                               180



• continues to have seizures
• developed anuria
• measured osmolality...
119         38
                               180



• continues to have seizures
• developed anuria
• measured osmolality...
119         38
                               180



• continues to have seizures
• developed anuria
• measured osmolality...
119         38
                               180



• continues to have seizures
• developed anuria
• measured osmolality...
MW 182    MW 180
C6H14O6   C6H12O6
• Gap is 64 mmol. How much mannitol is
  that?

• molecular weight of mannitol is 182
• 64 x 18.2 = 1,164 mg/dL
• use Katz...
• Gap is 64 mmol. How much mannitol is
  that?

• molecular weight of mannitol is 182
• 64 x 18.2 = 1,164 mg/dL
• use Katz...
• Gap is 64 mmol. How much mannitol is
  that?

• molecular weight of mannitol is 182
• 64 x 18.2 = 1,164 mg/dL
• use Katz...
Acute oliguric renal failure in mannitol
poisoning may be due to a combination of
mannitol-induced renal
vasoconstriction ...
summary

     Na 112 and seizing patient

  3% was worst possible therapy

If you are treating altered osmolality,
     ch...
Serum sodium falls from
133 to 99 in 2 hours
This patient:

 a. is doomed
 b. is lucky this is a lab
    error
 c. is asym...
TURP
TURP   • Before the development of
         bipolar electrocautery
         allowed use of isotonic
         electrolyte b...
• increased absorption with longer
  procedures

• higher infusion pressure
 • essentially no absorption at 15 cm
 • > 40 ...
• all the solutions (except distilled water) are
  isotonic or nearly isotonic

• lowers the serum sodium but the serum
  ...
• Desmond et al., in a study of 72 TURPS
• sodium fell 10-54 mmol/L in 19
• Osmolality fell in only 2
• Those 2 developed ...
• massive extracellular fluid gain
 • 200 mL/min
 • pulmonary edema
 • reflex bradycardia
 • hypertension
• use of distilled water can cause
 • hemolysis
 • hyponatremia
 • hemoglobinuria and acute renal failure
glycine
• metabolized to ammonia
• major inhibitory neurotransmitter (GABA
  activity).
 • likely cause of blindness
• pot...
...   glycine      after TURP has been
reported at a level greater than   14,300
pmol/L. This concentration is         17
...
• do not treat isolated hyponatremia
• caution in use of diuretics to treat volume
  overload, patients are in sodium bala...
esrd and hyponatremia
• does urea protect patients from CPM?
 • is the rapid rise in Na balanced by a
    simultaneous dec...
• scientific data supports the theory that
  uremia is protective against CPM

  • uremia is associated with rapid uptake o...
Soupart et al. Rapid reaccumulation of brain organic osmolytes in azotemic rats after
         correction of chronic hypon...
• one study found reversibility of MRI
  diagnosed CPM.

• in 6 of 9 patients with follow-up MRI
  showed improvement or r...
• 52 y.o. admitted with nausea and vomitting
• CKD for 1 year, HTN 2 years
 100        102
             17

• Dialysis was...
• 52 y.o. admitted with nausea and vomitting
• CKD for 1 year, HTN 2 years
 100        102                121
            ...
day after hemodialysis
•   bilateral limb tremors        •    action tremor

•   progressive facial diplegia   •    mask f...
Sanguida. Central pontine and extrapontine myelinolysis after rapid correction
 of hyponatremia by hemodialysis in a uremi...
Sanguida. Central pontine and extrapontine myelinolysis after rapid correction
 of hyponatremia by hemodialysis in a uremi...
• Strategies to consider when dialyzing a
  patient with hyponatremia
  • lower the dialysate sodium
  • lower the blood a...
• Strategies to consider when dialyzing a
  patient with hyponatremia
  • lower the dialysate sodium
  • lower the blood a...
exercise induced
      hyponatremia

• 87% of marathon runners drop their
  sodium
• 12-20% become hyponatremic
• almost n...
risk factors
•   female

•   slow

•   more water intake

•   small body size

•   NSAIDs

•   decreased urination
weight loss   weight gain
• weight gain argues against volume
  deficiency as the cause

• near uniform finding in the literature for
  measurable ADH...
Rx: 3% saline
dose: 1 mL/kg/hr or

100 mL bolus which can be repeated twice
at 10 minute intervals based on clinical
impro...
is it siadh or volume
       deficiency?
• this should be easy but in a study of 35
  non-edematous patients, clinical prediction
  of hypovolemia:

  • correctly ...
• A second study by Shrier et al. of 58
  hyponatremic patients without edema.
• A second study by Shrier et al. of 58
  hyponatremic patients without edema.
• A second study by Shrier et al. of 58
  hyponatremic patients without edema.
• clinical distinguishing siadh from volume
  depletion difficult and is missed in roughly
  half of cases

• gold standard...
• urine Na < 30 mmol/L
• urine Na runs higher in elderly patients
  (50-60 mmol/L)
• SIADH
                                               ° Salt depletion




Musch and Decaux.. International urology and n...
• SIADH
                                               ° Salt depletion
                                UNa < 30 is pretty...
• SIADH
                                               ° Salt depletion
                                UNa < 30 is pretty...
• SIADH
                                                ° Salt depletion




Musch W, Hedeshi A, Decaux G: Low sodium excr...
• seless
                                   a < 1% is u
                                               SIADH
             ...
• seless
                                   a < 1% is u
                                               SIADH
             ...
• seless
                                   a < 1% is u
                                               SIADH
             ...
• seless
                                        a < 1% is u
                                                    SIADH
   ...
• SIADH ° Salt depletion




Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low
               ...
• SIADH ° Salt depletion




FENa <0.5%


       Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%


       Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIA...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%


       Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIA...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%


       Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIA...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%                    FENa <0.15%


       Musch W, Hedeshi A, Decaux...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%                    FENa <0.15% and FEurea <45%


       Musch W, H...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%                    FENa <0.15% and FEurea <45%


       Musch W, H...
• SIADH ° Salt depletion




FENa <0.5% and FEurea <55%                    FENa <0.15% and FEurea <45%


       Musch W, H...
criteria for salt
          depletion
• Urine Cr / Plasma Cr < 140
 • FENa < 0.5% and
 • FE Urea < 55%
• Urine Cr / Plasma...
Saline infusions
• Gold standard for diagnosis
• necessary in patients with combined salt
  depletion and SIADH
• Caution ...
Saline responsive SIADH?
• 2 liter isotonic saline infusion in 17 SIADH
  patients
  • Na 126
  • Urine Na + Urine K = 128...
538
uric acid and SIADH
• uric acid falls 50% in SIADH
 • drop due to dilution should only be 10%
 • due to increase in uric a...
Fenske et al. Value of fractional uric acid excretion in differential diagnosis of
hyponatremic patients on diuretics. J C...
done...
now go fix some numbers
Hyponatremia
Hyponatremia
Hyponatremia
Hyponatremia
Hyponatremia
Hyponatremia
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Hyponatremia

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Talk on sodium aimed at nephrology fellows, only for the hard core fluid and electrolyte geeks

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  • Transcript of "Hyponatremia"

    1. 1. Sodium and Water Lecture for Fellows Joel M. Topf, M.D.
    2. 2. • 77 yo female • increased intraocular pres- sure following cataract surgery • admitted for mannitol infusion to reduce intraocular pressure • PMHx: CHF, Htn, CKD (bl Cr 1.5 mg/dL) • Meds: captopril, furosemide
    3. 3. • over 3 days she received • 2.5 liters of 20% mannitol • how much mannitol is that? • ibuprofen for musculoskeletal pain • day 4 • confuision, dyspnea, anuria
    4. 4. • over 3 days she received • 2.5 liters of 20% mannitol • how much mannitol is that? 20% means 20 g per 100 mL 2.5 L is 25 x 100 mL 25 x 20 = 500 g of mannitol • ibuprofen for musculoskeletal pain • day 4 • confuision, dyspnea, anuria
    5. 5. 112 38 180 3.2 • multiple seizures • no measured osmolality calculate the serum osmolality: • given 3% saline and lasix
    6. 6. 112 38 180 3.2 • multiple seizures • no measured osmolality calculate the serum osmolality: 247 • given 3% saline and lasix
    7. 7. 119 38 180 • continues to have seizures • developed anuria • measured osmolality 326 Calculate the osmolality
    8. 8. 119 38 180 • continues to have seizures • developed anuria • measured osmolality 326 Calculate the osmolality 262
    9. 9. 119 38 180 • continues to have seizures • developed anuria • measured osmolality 326 Calculate the osmolality and the gap 262
    10. 10. 119 38 180 • continues to have seizures • developed anuria • measured osmolality 326 Calculate the osmolality and the gap 262 64
    11. 11. MW 182 MW 180 C6H14O6 C6H12O6
    12. 12. • Gap is 64 mmol. How much mannitol is that? • molecular weight of mannitol is 182 • 64 x 18.2 = 1,164 mg/dL • use Katz’s and Hillier’s conversion to quantify the pseudohyponatremia
    13. 13. • Gap is 64 mmol. How much mannitol is that? • molecular weight of mannitol is 182 • 64 x 18.2 = 1,164 mg/dL • use Katz’s and Hillier’s conversion to quantify the pseudohyponatremia Katz: (1.6 x 11) + 119 = 136
    14. 14. • Gap is 64 mmol. How much mannitol is that? • molecular weight of mannitol is 182 • 64 x 18.2 = 1,164 mg/dL • use Katz’s and Hillier’s conversion to quantify the pseudohyponatremia Katz: (1.6 x 11) + 119 = 136 Hillier: (2.4 x 11) + 119 = 145
    15. 15. Acute oliguric renal failure in mannitol poisoning may be due to a combination of mannitol-induced renal vasoconstriction and direct tubular toxicity. As mannitol is excreted exclusively by the kidney, its accumulation in renal failure will further worsen renal function, thus making prompt hemodialysis the most appropriate treatment in such a circumstance.
    16. 16. summary Na 112 and seizing patient 3% was worst possible therapy If you are treating altered osmolality, check the serum osmolality
    17. 17. Serum sodium falls from 133 to 99 in 2 hours This patient: a. is doomed b. is lucky this is a lab error c. is asymptomatic d. requires 3% saline +/– loop diuretics
    18. 18. TURP
    19. 19. TURP • Before the development of bipolar electrocautery allowed use of isotonic electrolyte based irrigants... ...used non-conducting: • distilled water • glycine • sucrose • manitol
    20. 20. • increased absorption with longer procedures • higher infusion pressure • essentially no absorption at 15 cm • > 40 cm greatly increases absorption
    21. 21. • all the solutions (except distilled water) are isotonic or nearly isotonic • lowers the serum sodium but the serum osmolality remains normal • no cellular water shift
    22. 22. • Desmond et al., in a study of 72 TURPS • sodium fell 10-54 mmol/L in 19 • Osmolality fell in only 2 • Those 2 developed pulmonary edema and encephalopathy • the 5 largest changes in sodium (34-54 mmol/L) had no signs of TURP syndrome
    23. 23. • massive extracellular fluid gain • 200 mL/min • pulmonary edema • reflex bradycardia • hypertension
    24. 24. • use of distilled water can cause • hemolysis • hyponatremia • hemoglobinuria and acute renal failure
    25. 25. glycine • metabolized to ammonia • major inhibitory neurotransmitter (GABA activity). • likely cause of blindness • potentiates NMDA activity • anti-PCP, anti-ketamine • don’t be fooled, neurologic symptoms may not be symptomatic hyponatremia
    26. 26. ... glycine after TURP has been reported at a level greater than 14,300 pmol/L. This concentration is 17 times greater than that in children dying from glycine encephalopathy and over 65 times that in adults. Normal adult level, 219 pmol/L.
    27. 27. • do not treat isolated hyponatremia • caution in use of diuretics to treat volume overload, patients are in sodium balance, and loop diuretics may cause salt wasting and worsen the hyponatremia. • experts recommend saline and loop diuretics to correct the volume overload while preserving sodium balance
    28. 28. esrd and hyponatremia • does urea protect patients from CPM? • is the rapid rise in Na balanced by a simultaneous decline in urea? • are other factors protective? • how do you dialyze as patient with severe hyponaremia?
    29. 29. • scientific data supports the theory that uremia is protective against CPM • uremia is associated with rapid uptake of the osmolyte myoinositol
    30. 30. Soupart et al. Rapid reaccumulation of brain organic osmolytes in azotemic rats after correction of chronic hyponatremia. J Am Soc Nephrol (2002) 13: 1433-41.
    31. 31. • one study found reversibility of MRI diagnosed CPM. • in 6 of 9 patients with follow-up MRI showed improvement or resolution. Found within one month of onset. • Frequent findings in their cases of CPM • Sodium < 136 in 10/17 • BUN:Cr <13.5:1 in 11/17 Tarhan et al. Osmotic demyelination syndrome in end-stage renal disease after recent hemodialysis: MRI of the brain. Am j roentgenology (2004) 182; 809-16.
    32. 32. • 52 y.o. admitted with nausea and vomitting • CKD for 1 year, HTN 2 years 100 102 17 • Dialysis was initiated • 2.5 hours Sanguida. Central pontine and extrapontine • qB 150 mL/min myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.
    33. 33. • 52 y.o. admitted with nausea and vomitting • CKD for 1 year, HTN 2 years 100 102 121 17 • Dialysis was initiated • 2.5 hours Sanguida. Central pontine and extrapontine • qB 150 mL/min myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.
    34. 34. day after hemodialysis • bilateral limb tremors • action tremor • progressive facial diplegia • mask facies • dysarthria • cogwheel rigidity • dysphagia • bradykinesia • four limbs weakness Sanguida. Central pontine and extrapontine myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.
    35. 35. Sanguida. Central pontine and extrapontine myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.
    36. 36. Sanguida. Central pontine and extrapontine myelinolysis after rapid correction of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.
    37. 37. • Strategies to consider when dialyzing a patient with hyponatremia • lower the dialysate sodium • lower the blood and dialysate flow • shorten the treatment
    38. 38. • Strategies to consider when dialyzing a patient with hyponatremia • lower the dialysate sodium • lower the blood and dialysate flow • shorten the treatment
    39. 39. exercise induced hyponatremia • 87% of marathon runners drop their sodium • 12-20% become hyponatremic • almost none are symptomatic
    40. 40. risk factors • female • slow • more water intake • small body size • NSAIDs • decreased urination
    41. 41. weight loss weight gain
    42. 42. • weight gain argues against volume deficiency as the cause • near uniform finding in the literature for measurable ADH in patients with exercise induced hyponatremia • ADH secretion normally stops at osmolality < 275 mOsm/Kg
    43. 43. Rx: 3% saline dose: 1 mL/kg/hr or 100 mL bolus which can be repeated twice at 10 minute intervals based on clinical improvement
    44. 44. is it siadh or volume deficiency?
    45. 45. • this should be easy but in a study of 35 non-edematous patients, clinical prediction of hypovolemia: • correctly found only 41% of cases (sensitivity) • Specificity was 80% Musch W, Thimpont J,Vandervelde D et. al. Am J Med. 1995; 99:348-55.
    46. 46. • A second study by Shrier et al. of 58 hyponatremic patients without edema.
    47. 47. • A second study by Shrier et al. of 58 hyponatremic patients without edema.
    48. 48. • A second study by Shrier et al. of 58 hyponatremic patients without edema.
    49. 49. • clinical distinguishing siadh from volume depletion difficult and is missed in roughly half of cases • gold standard for diagnosis is sodium response to fluid challenge • prospective use of the lab can help make the diagnosis
    50. 50. • urine Na < 30 mmol/L • urine Na runs higher in elderly patients (50-60 mmol/L)
    51. 51. • SIADH ° Salt depletion Musch and Decaux.. International urology and nephrology (2001) vol. 32: 475-93
    52. 52. • SIADH ° Salt depletion UNa < 30 is pretty good misses salt depletion in the elderly Musch and Decaux.. International urology and nephrology (2001) vol. 32: 475-93
    53. 53. • SIADH ° Salt depletion UNa < 30 is pretty good misses salt depletion in the elderly Musch and Decaux.. International urology and nephrology (2001) vol. 32: 475-93
    54. 54. • SIADH ° Salt depletion Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    55. 55. • seless a < 1% is u SIADH • FEN • FEN a < 0.5% identifies all of the ° Salt depletion SD patients but misclassifies nearly half the SIADH Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    56. 56. • seless a < 1% is u SIADH • FEN • FEN a < 0.5% identifies all of the ° Salt depletion SD patients but misclassifies nearly half the SIADH Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    57. 57. • seless a < 1% is u SIADH • FEN • FEN a < 0.5% identifies all of the ° Salt depletion SD patients but misclassifies nearly half the SIADH Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    58. 58. • seless a < 1% is u SIADH • FEN • FEN a < 0.5% identifies all of the ° Salt depletion SD patients but misclassifies nearly half the SIADH U/P is a measure of daily urine production Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    59. 59. • SIADH ° Salt depletion Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    60. 60. • SIADH ° Salt depletion FENa <0.5% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    61. 61. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    62. 62. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    63. 63. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    64. 64. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% FENa <0.15% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    65. 65. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% FENa <0.15% and FEurea <45% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    66. 66. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% FENa <0.15% and FEurea <45% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    67. 67. • SIADH ° Salt depletion FENa <0.5% and FEurea <55% FENa <0.15% and FEurea <45% Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol96 :11 –18,2004
    68. 68. criteria for salt depletion • Urine Cr / Plasma Cr < 140 • FENa < 0.5% and • FE Urea < 55% • Urine Cr / Plasma Cr > 140 • FENa < 0.15% and • FE Urea < 45%
    69. 69. Saline infusions • Gold standard for diagnosis • necessary in patients with combined salt depletion and SIADH • Caution in the interpretation of the saline infusion challenge • increase of 5 mmol/L has been proposed • Sensitivity 71% and Specificity 70% Musch and Decaux.. International urology and nephrology (2001) vol. 32: 475-93
    70. 70. Saline responsive SIADH? • 2 liter isotonic saline infusion in 17 SIADH patients • Na 126 • Urine Na + Urine K = 128 • Urine Osm = 502 • All patients had fixed urine osmolality despite fluid restriction
    71. 71. 538
    72. 72. uric acid and SIADH • uric acid falls 50% in SIADH • drop due to dilution should only be 10% • due to increase in uric acid clearance or FE Uric Acid • less uric reabsorption • stable uric acid secretion • FE Uric Acid >12% (16% in the elderly)
    73. 73. Fenske et al. Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. J Clin Endocrinol Metab (2008) 93: 2991-7
    74. 74. done... now go fix some numbers
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