Management

Desmopressin

• 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

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DDAVP Clamp

 

AVP response maintained after volume resuscitation

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Desmopressin Clamp

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

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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)

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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

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Fludrocortisone

• 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

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SIADH

• Excessive endogenous AVP production

SCLC: Small cell lung cancer

PJP: Pneumocystis jirovecii pneumonia

GBS: Guillain Barre Syndrome

SSRI: Selective serotonin reuptake inhibitor

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Effect of Saline

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Hypertonic Saline

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

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Loop Diuretics

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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

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Vaptans

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

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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

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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

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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%

 

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Urea

• 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