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More than Diamond Crystal: Approaches and Management Strategies for Hyponatremia

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Participants 196

  • April
  • Alyssa
  • Ashley
  • Amber
  • Sherif
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  • D-amino D-arginine vasopressin (DDAVP)
  • 2000:1 ADH:vasopressor activity
  • Highly selective for V2 receptor in collecting duct
  • Maintains AVP response when volume resuscitation is complete but sodium is not increased to a safe level yet



AVP response maintained after volume resuscitation

Desmopressin Clamp

  • Can use DDAVP as overcorrection prophylaxis, reaction, or rescue in patients at high risk of overcorrection

Cerebral Salt Wasting

  • Clinical syndrome frequently encountered in patients with cerebral disease
    • Most frequently aSAH
  • Pathophysiology believed to be linked to excess ANP and BNP production
  • Laboratory evaluation nearly identical to SIADH
    • Volume assessment essential
  • Often present in patients in whom hypovolemia may cause significant clinical consequence (vasospasm in patients with aSAH)

Solute Replacement

  • 1:1 replacement of urine output with normal saline
    • May require hypertonic infusions as well for persistent sodium decline
  • Daily urine output can be remarkable (10-12 L/day)
  • CSW will generally resolve within 10-14 days of original CNS insult


  • Mineralocorticoid which can stimulate sodium retention through simulated RAAS activity
  • Little consistent data but some supporting trend towards even sodium balance
    • Dosing ranges from 0.1-0.2mg QD-TID
  • Major side effect is potassium wasting, which can exacerbate hyponatremia
    • Aggressive potassium repletion


  • Excessive endogenous AVP production

SCLC: Small cell lung cancer

PJP: Pneumocystis jirovecii pneumonia

GBS: Guillain Barre Syndrome

SSRI: Selective serotonin reuptake inhibitor

Effect of Saline

Hypertonic Saline

  • 3% hypertonic saline has an osmolality of 1026 mOsm/L
    • Hypertonic to urine in most (but not all) cases of SIADH

Loop Diuretics

Hypertonic Saline and Loop Diuretics

  • Loop diuretics dilute the urine, reducing water resorption in the collecting ducts
  • This lowers urine osmolality, improving effectiveness of hypertonic saline in SIADH


  • Direct antagonism of V2 receptor which is responsible for upregulation of aquaporins and water retention
  • Effective in SIADH… with a catch

SALT Trial

  • Patients with euvolemic or hypervolemic hyponatremia randomized to tolvaptan 15mg QD or placebo
  • Significantly more patients reached goal of eunatremia by day 30

Risk of Overcorrection

  • Reports of significant overcorrection appeared after publication of SALT
  • While not universal, caution must be exhibited when using V2 antagonist for SIADH
  • Several risk factors have been identified
    • Younger age
    • Lower baseline sodium
  • 7.5 mg daily effective with lower risk of overcorrection

Salt Tablets

  • Often added when fluid restriction not possible or is clinically inappropriate (aSAH, ischemic stroke)
  • Used as initial therapy in 31% of neurocritically ill patients
    • Median sodium response of 3.5 mEq
  • 250 mL 3% sodium chloride equivalent to 7.5g of oral sodium chloride

Cohort of 1,116 patients with non-cancer SIADH

Sodium Change Percent of Patients
> -2 mEq/L 9.6%
±2 mEq/L 33.7%
2-5 mEq/L 18.5%
≥ 5 mEq/L 38.2%



  • Ineffective osmol
  • Can increase water excretion in collecting ducts leading to water diuresis and increased plasma osmolality
  • Dosing starts at 30 g/day, increase to effect
  • Potential ICP lowering effect