It is difficult to clinically distinguish SIADH from volume depletion in hyponatremic patients without edema, with correct prediction occurring in only around 40% of cases. The gold standard for diagnosis is the sodium response to fluid challenge. A urine sodium less than 30 mmol/L favors SIADH, but this can miss salt depletion in elderly patients. A fractional excretion of sodium less than 0.5% identifies patients with salt depletion but misclassifies around half of SIADH cases. Combined fractional excretion of sodium less than 0.5% and urea less than 55% may best differentiate SIADH from salt depletion.

1. Sodium and Water
Lecture for Fellows
Joel M. Topf, M.D.

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. • 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. • 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. 112 38
180
3.2
• multiple seizures
• no measured osmolality
calculate the serum osmolality:
• given 3% saline and lasix

6. 112 38
180
3.2
• multiple seizures
• no measured osmolality
calculate the serum osmolality: 247
• given 3% saline and lasix

7. 119 38
180
• continues to have seizures
• developed anuria
• measured osmolality 326
Calculate the osmolality

8. 119 38
180
• continues to have seizures
• developed anuria
• measured osmolality 326
Calculate the osmolality
262

9. 119 38
180
• continues to have seizures
• developed anuria
• measured osmolality 326
Calculate the osmolality and the gap
262

10. 119 38
180
• continues to have seizures
• developed anuria
• measured osmolality 326
Calculate the osmolality and the gap
262 64

11. MW 182 MW 180
C6H14O6 C6H12O6

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. • 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. • 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. 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. summary
Na 112 and seizing patient
3% was worst possible therapy
If you are treating altered osmolality,
check the serum osmolality

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

19. TURP

20. TURP • Before the development of
bipolar electrocautery
allowed use of isotonic
electrolyte based irrigants...
...used non-conducting:
• distilled water
• glycine
• sucrose
• manitol

21. • increased absorption with longer
procedures
• higher infusion pressure
• essentially no absorption at 15 cm
• > 40 cm greatly increases absorption

22. • 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

23. • 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

24. • massive extracellular fluid gain
• 200 mL/min
• pulmonary edema
• reflex bradycardia
• hypertension

25. • use of distilled water can cause
• hemolysis
• hyponatremia
• hemoglobinuria and acute renal failure

26. 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

27. ... 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.

28. • 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

29. 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?

30. • scientific data supports the theory that
uremia is protective against CPM
• uremia is associated with rapid uptake of
the osmolyte myoinositol

31. 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.

32. • 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.

33. • 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.

34. • 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.

35. 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.

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. Sanguida. Central pontine and extrapontine myelinolysis after rapid correction
of hyponatremia by hemodialysis in a uremic patient. Ren Fail 2007: 29 635-8.

38. • Strategies to consider when dialyzing a
patient with hyponatremia
• lower the dialysate sodium
• lower the blood and dialysate flow
• shorten the treatment

39. • Strategies to consider when dialyzing a
patient with hyponatremia
• lower the dialysate sodium
• lower the blood and dialysate flow
• shorten the treatment

43. exercise induced
hyponatremia
• 87% of marathon runners drop their
sodium
• 12-20% become hyponatremic
• almost none are symptomatic

44. risk factors
• female
• slow
• more water intake
• small body size
• NSAIDs
• decreased urination

45. weight loss weight gain

46. • 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

47. 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

48. is it siadh or volume
deficiency?

49. • 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.

50. • A second study by Shrier et al. of 58
hyponatremic patients without edema.

51. • A second study by Shrier et al. of 58
hyponatremic patients without edema.

52. • A second study by Shrier et al. of 58
hyponatremic patients without edema.

54. • 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

55. • urine Na < 30 mmol/L
• urine Na runs higher in elderly patients
(50-60 mmol/L)

56. • SIADH
° Salt depletion
Musch and Decaux.. International urology and nephrology (2001) vol. 32: 475-93

57. • 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

58. • 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

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. • 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

61. • 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

62. • 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

63. • 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

64. • SIADH ° Salt depletion
Musch W, Hedeshi A, Decaux G: Low sodium excretion in SIADH patients with low
diuresis. Nephron Physiol96 :11 –18,2004

65. • 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

66. • 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

67. • 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

68. • 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

69. • 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

70. • 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

71. • 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

72. • 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

73. 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%

74. 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

75. 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

77. 538

78. 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)

79. 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

80. done...
now go fix some numbers