Hyponatremias

Define hyponatremia

Serum Na < 135 mEq/L

Usually due to impaired water excretion

Excess extracellular water relative to sodium

A WATER ISSUE NOT A SALT ISSUE

What are risk factors for hyponatremia?

Age, increased hypotonic fluid intake

Define chronic hyponatremia

Lasts for longer than 48 hours

Define mild hyponatreamia

Na 125-134 mEq/L

Describe the clinical presentation of chronic, mild hyponatremia

Generally asymptomatic

Associated with impairment of attention, posture, and gait in elderly patients = increased risk of falls

Define moderate hyponatremia

Na 115-124 mEq/L

Describe the clinical presentation of moderate hyponatremia

Headache, lethargy, restlessness, disorientation

Define severe hyponatremia

Na < 115 mEq/L

Describe the clinical presentation of severe hyponatremia

Seizures, coma, respiratory arrest, brainstem herniation, death

What serum lab assessments should be to determine hyponatremia?

Osmolality of Na, Glu, BUN

When is a urine osmolality test helpful in for hyponatremia?

Determine volume status

When is a urine sodium test helpful in hyponatremia?

Determining etiology

What are the goals of hyponatremia treatment?

Resolve symptoms, address underlying causes, restore Na and H2O balance

Why is it important to not correct hyponatremia too quickly?

Correcting hyponatremia too quickly can result in osmotic demyelination syndrome (ODS)

FATAL if it occurs

When may rapid initial correction of hyponatremia be necessary?

In moderate to severe (symptomatic) cases

Just enough to control symptoms

Classify hyponatremias based on serum osmolality

High (> 290 mOsm/L) = hypertonic hyponatremia

Normal (~280 mOsm/L) = isotonic hyponatremia

Low (< 275 mOsm/L) = hypotonic hyponatremia

How can hypotonic hyponatremia be further classified?

Hypovolemic, euvolemic, and hypervolemic

Define isotonic ("pseudo") hyponatremia

Normal measured serum osmolality

What can cause isotonic hyponatremia?

Hyponatremia caused by elevation in lipids or proteins

What could happen if we attempt to correct isotonic hyponatremia?

Could include hypernatremia

Define hypertonic hyponatremia

Excess non-Na effective osmoles

What can cause hypertonic hyponatremia?

Frequently caused by extreme hyperglycemia

Define corrected sodium

Measured serum Na decreases by 1.6 mEq/L for each 100 mg/dL increase in BG over 100 mg/dL

What is the formula for corrected sodium?

Corrected Na = Measured Na + 0.016 (BG - 100)

What is the most common form of hyponatremia?

Hypotonic hyponatremia

Describe hypotonic hyponatremia

Various potential etiologies

Requires assessment of volume status

What can cause hypovolemic hypotonic hyponatremia?

Extrarenal losses = diarrhea, vomiting, excessive sweating

Renal losses = thiazide diuretics, adrenal insufficiency

Describe the steps that can cause hypovolemic hypotonic hyponatremia

Transient hypernatremia causes osmotic AVP release and thirst

If Na and H2O losses continue, it causes hypovolemic and more AVP release

Ultimately, Na loss is greater than H2O loss

What is the result of hypovolemic hypotonic hyponatremia?

Result is concentrated urine

Urine osmolality of > 450 mOsm/kg

What is urine sodium if Na losses are extrarenal vs. renal in hypovolemic hypotonic hyponatremia?

Extrarenal losses = urine sodium < 30 mEq/L (low)

Renal losses = urine sodium > 30 mEq/L (high)

How should hypovolemic hypotonic hyponatremia be treated?

Correct underlying cause, if possible

0.9% NaCl to replete sodium and water deficits

How should acute moderate-severe or severely symptomatic hypovolemic hypotonic hyponatremia be rapidly corrected?

3% NaCl

Limit correction to 4-6 mEq/L in first 1-2 hours

What is the sodium limit for correction of hypovolemic hypotonic hyponatremia if the patient is at high risk for OD?

DO NOT exceed 8 mEq/L in 24 hours

What is the sodium limit for correction of hypovolemic hypotonic hyponatremia if the patient is at low risk for OD?

DO NOT exceed 10 mEq/L in first 24 hours or 18 mEq in first 48 hours

How should severe symptomatic hyponatremia be treated?

3% saline until severe symptoms resolved

Follow with normal saline to correct volume and sodium deficit

Check serum Na q1-4h

What is the target serum Na when treating severe symptomatic hyponatremia?

120-125 mEq/L to avoid overcorrection

What is the formula for Na deficit?

Na deficit = [(Target Na - measured Na) x TBW]

What can cause euvolemic hypotonic hyponatremia?

Polydipsia, low solute intake

SIADH (most common)

Define euvolemic hypotonic hyponatremia

Normal or slightly decreased ECF sodium content

Increased TBW and ECF

Caused by WATER GAIN ONLY! = intake exceeds kidneys' ability to excrete

Define SIADH

Syndrome of Inappropriate AntiDiuretic Hormone

Kidneys ability to excrete water is reduced by increased ADH

What euvolemic hypotonic hyponatremia lab assessment can indicate SIADH?

Uosm > 100 mOsm/kg

UNa 20-30 mEq/L

Serum Osm < 275 mOsm/kg due to volume expansion

What euvolemic hypotonic hyponatremia lab assessment indicates psychogenic polydipsia?

In this case AVP is suppressed

Uosm < 100 mOsm/kg

UNa < 15 mEq/L (due to dilution)

How should euvolemic hypotonic hyponatremia be treated?

Treat underlying cause

How should euvolemic hypotonic hyponatremia as a result of primary polydipsia/low solute intake be treated?

Water restriction

If severe symptoms = 3% saline, loop diuretics

How should euvolemic hypotonic hyponatremia as a result of SIADH be treated?

Correct underlying cause

Water restriction = goal is to maintain serum NaCl ~130 mEq/L

What should not be used to treat euvolemic hypotonic hyponatremia as a result of SIADH and why?

DO NOT use 0.9% NaCl

May worsen hyponatremia

What should be used to treat SEVERE euvolemic hypotonic hyponatremia as a result of SIADH?

3% NaCl

If Uosm > 300 mOsm/kg then add a loop diuretic

What drug class can be used to treat euvolemic hypotonic hyponatremia?

Vasopressin Receptor Antagonists

What drug is a vasopressin receptor antagonist?

Tolvaptan (Samsca)

What is the MOA of tolvaptan?

Selectively inhibits action of V2 receptor, preventing aquaporins transport to cell surface

Causes decreased AVP-dependent water reabsorption

Describe the metabolism of tolvaptan

CYP3A4 substrate

What is the boxed warning of tolvaptan?

Hepatotoxicity

Avoid use > 30 days with chronic liver disease

When is tolvaptan contraindicated?

In patients requiring rapid correction, those unable to sense or respond appropriately to thirst, HYPOVOLEMIC HYPONATREMIA, concomitant strong CYP3A4 inhibitors, anuria patients

What other agent can be used to treat euvolemic hypotonic hyponatremia?

Urea (Ure-Na)

What is the MOA of urea?

Osmotic agent that increases urinary free water excretion and decreases urinary sodium excretion

Low quality of evidence for efficacy

What can cause hypervolemic hypotonic hyponatremia?

HF, cirrhosis

Describe the steps that can cause hypervolemic hypotonic hyponatremia

Decrease in effective circulating volume causes increased renal retention through RAAS, leading to expansion of ECF and edema

Non-osmotic AVP stimulation causes excess H2O retention >> Na retention = hyponatremia

Describe the clinical presentation of hypervolemic hypotonic hyponatremia

Volume overload

SOB, edema, ascites, weight gain (vs "dry weight")

What additional symptoms could be present in moderate-severe or rapidly developing hypervolemic hypotonic hyponatremia?

CNS symptoms from cerebral edema (nausea, malaise, headache, lethargy, restlessness, disorientation)

If severe = seizure, coma, respiratory arrest, brainstem herniation, death

What is the treatment for severe hypervolemic hypotonic hyponatremia?

3% NaCl, fluid restriction

May require loop diuretic or VRA therapy to facilitate urinary free water excretion

DO NOT correct Na too quickly!

What is the treatment for non-severe hypervolemic hypotonic hyponatremia?

Volume and sodium restriction

Address underlying cause

DO NOT correct Na too quickly!