Hyponatremia

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

• 77 yo female • increased intraocular pressure following cataract surgery • admitted for mannitol infusion to reduce intraocular pressure • PMHx: CHF, Htn, CKD (bl Cr 1.5 mg/dL) • Meds: captopril, furosemide

• 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

• 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

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

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

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

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

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

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

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’s and Hillier’s conversion to quantify the pseudohyponatremia

• 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

• 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

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.

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

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

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

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

• 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

• 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

• 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 • potentiates NMDA activity • anti-PCP, anti-ketamine • don’t be fooled, neurologic symptoms may not be symptomatic hyponatremia

... 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.

• 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

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?

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

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.

• 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.

• 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.

• 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.

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.

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

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

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

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 in patients with exercise induced hyponatremia • ADH secretion normally stops at osmolality < 275 mOsm/Kg

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

is it siadh or volume deﬁciency?

• 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.

• 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 for diagnosis is sodium response to ﬂuid challenge • prospective use of the lab can help make the diagnosis

• 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 nephrology (2001) vol. 32: 475-93

• 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

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

• 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

• 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

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

• 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

• 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

• 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

• 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

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%

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

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

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)

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

done... now go ﬁx some numbers

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Hyponatremia

by Joel Topf on Dec 04, 2009

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Hyponatremia — Presentation Transcript