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Pearl 1: Key Principles

• Hyponatremia is a problem of excess of free water relative to solute in the body
  • One end of the spectrum: not enough solute intake
    • e.g. tea and toast
  • Other end of the spectrum: too much water in the body
    • Absolute excess of free water:
      • E.g primary polydipsia
    • Relative excess of free water: ADH release from
      • Hypovolemia
      • Decreased effective circulation (e.g. CHF, cirrhosis, nephrotic syndrome)
      • Inappropriate release (SIADH)
• Therefore, a detailed solutes/fluids history is needed to manage hyponatremia
  • Account for all fluids that the patient is getting, including water, coffee, Diet Coke, Gatorade, etc.
  • How much solute is the patient taking in? (e.g. big or small meals?)
• Most of the time, hyponatremia is multifactorial.
  • You can’t rely on algorithmic cutoffs because there may be multiple contributors to the direction the urine Osm may be in
    • In particularly, common issues like pain, nausea and certain medications (more in pearl 5) can increase ADH (inappropriately), reabsorb more free water and increase urine Osm
• For more information, see

Pearl 2: Fluids in hyponatremia management

• Giving fluids
  • hypovolemic hyponatremia
    • fluid choice does not matter; any fluid will turn off hypovolemic baroreceptor stimulus for ADH release
    • expert opinion: for patients with cirrhosis and some component of hypovolemia, can use albumin as fluid
  • SIADH:
    • if giving fluids, fluid choice does not matter as long as it’s hypertonic to the urine
      • lactated ringers has an osmolality of 272 mOsm/L
      • normal saline (0.9%) has an osmolality of 308 mOsm/L
• Withholding fluids: fluid restriction
  • used mainly in SIADH
  • restricting to amount less than what patient is drinking should work
    • protip: physically put their allowed amount in front of them
  • predictors of success: generally if patient is excreting free water
    • urine-to-plasma electrolyte ratio (UNa + UK)/SNa
      • if <1 (actively excreting free water), will likely respond to fluid restriction
    • urine osmolality
      • if high (e.g. >500), actively excreting free water and will likely respond

Pearl 3: Solutes in hyponatremia management

• Basis: the body needs solute to excrete free water
  • UOsm ranges from 50-1200 mOsm/L; can never excrete urine that is UOsm 0
• Types of solute:
  • Salt tabs: not very effective
    • doses commonly prescribed are not high enough, and if we increase dosing, can often lead to medical side effects (e.g. HTN)
    • makes patients thirsty and they will just drink more water
    • retrospective cohort shows modest (5.2 mEq/L) improvement in serum sodium in euvolemic hyponatremia after 48 hr tx
  • Protein supplements - solute without thirst response
    • theoretical mechanism same as urea (), never prospectively studied
    • benefits: cheaper, good for patients with low muscle mass, doesn’t taste bad like urea or prompt thirst response like salt tabs
  • Urea powder -  used in Europe and some US institutions
    • works by osmotic and aquaretic mechanisms ()
    • however, not FDA approved (is a medical food), costs money since regulated like an OTC supplement, tastes like urine
    • BUN levels may increase during treatment, which does not represent renal impairment ()

Pearl 4: Lasix (furosemide) in hyponatremia management

• Mechanism: inhibits the Na-K-2Cl channel in the thick ascending limb of the Loop of Henle, disrupting the medullary gradient in the interstitium which is the impetus for water to flow
  • Reabsorption of water requires both (1) aquaporins and (2) gradient for water flow
• Dosing: because mechanism relies on disrupting gradient, need to dose frequently to prevent gradient from reconstituting
• Adjuncts: often given with salt tabs, since as mentioned earlier, still need solute to excrete free water, so need to replenish solute that is depleted by Lasix
• Evidence: which looked at FR vs FR + loop vs FR + loop + NaCl, there was an initial improvement in Na at day 7 for FR+loop+NaCl, but this wasn’t durable over 28d of observation
  • Experts say since small study, this needs to be followed up with larger study before it is expected to change current management, which often includes Lasix+NaCl

Pearl 5: Etiologies of hyponatremia

• Diagnosis of the cause of hyponatremia is an important part of management
• Specific etiologies:
  • thyroid disorders (specifically myxedema coma) rarely cause hyponatremia, specifically in isolation, so send TSH only if high enough pre-test probability with other signs
  • adrenal insufficiency can be a bit more vague so not unreasonable to evaluate
    • protip: on urine studies, adrenal insufficiency can cause an SIADH-like picture due to CRH stimulating ADH release directly, but in severe adrenal insufficiency, there can also be a hypovolemic component due to circulatory collapse
  • medications: antiepileptics and antipsychotic medications are common culprits
    • however, any drug can do it and almost all drugs have been associated with it
  • other stimuli: pain, nausea
• When should imaging be obtained? (expert opinions)
  • Chest pathology is common, so review old chest x-rays or CTs, or if there are none, not unreasonable to obtain
  • Brain imaging is a bit more costly and invasive, so really depends on if there are abnormal neurologic findings on exam

Contributors

Timothy Rowe, MD – Host/ editor

Shreya Trivedi, MD, ACP Member – Host/ editor

Clement Lee, MD – Host, editor

Jeffrey William, MD - Guest

Marcus Foo – Editor

John Hwang, MD - Guest

Helbert Rondon, MD, FACP - Guest

Reviewers

Richard Sterns, MD

Tomas Guerrero, MD

Sheldon Chen, MD

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date:  August 3, 2022

Expiration Date: August 3, 2025

CME Credit

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The ¹Ü¼ÒÆÅÐÄË®ÂÛ̳ designates this enduring material (podcast) for 0.75 AMA PRA Category 1 Creditâ„¢.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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