Hyponatremia

Hyponatremia Serum Sodium

Serum sodium < 135 mEq/L

Severe Hyponatremia

Serum sodium, symptoms

<110 mEq/L

Seizure

Coma

Brain damage

Brain stem herniation

Moderate Hyponatremia

Serum sodium, symptoms

110-125 mEq/L

Headache

Lethargy

Restlessness

disorientation

Mild Hyponatremia

Serum sodium, symptoms

<135 mEq/L

Nausea

Malaise

What total body water imbalance causes HYPOnatremia?

EXCESS free water

Why must sodium level correction rate be monitored?

rapid correction can cause osmotic demyelination

Brain Compensation in Hyponatremia

→ In hypotonic hyponatremia, the brain transports solutes extracellularly to reduce its osmolality and prevent swelling/herniation.

If serum sodium levels are corrected too rapidly, it can cause osmotic demyelination (brain loses water causing permanent brain damage).

Symptoms of Osmotic Demyelination

Dysarthria (difficulty speaking)

Dysphagia (difficulty swallowing)

Quadraplegia

Seizure

Coma

Death

What patients are at high risk for demyelination?

Na < 120 mEq/L

Duration > 48 hours (chronic)

What patients are at severe risk for demyelination?

Na < 105 mEq/L

Hypokalemia, alcoholism, malnutrition, advanced liver disease.

Hyponatremia is associated with what osmolar state(s)?

hypertonic

isotonic

hypotonic

Hypertonic Hypernatremia Causes

Caused by increases in plasma glucose or exogenous administration of mannitol (iatrogenic).

Relationship between blood glucose and serum sodium

For every 100 mg/dL increase in serum glucose, there is a loss of 1.7 mEq/L of serum sodium

Isotonic Hypernatremia Causes

A pseudohyponatremia usually caused by hyperlipidemia or hyperproteinemia.

3 Causes/Types of Hypotonic Hyponatremia

Hypervolemic

Euvolemic

Hypovolemic

Hypervolemic Hypotonic Hyponatremia

TBW, TBNa

TBW↑↑ , TBNa ↑

Water gain > sodium gain

Hypervolemic Hypotonic Hyponatremia

Causes

Congestive heart failure

Liver failure

Nephrotic syndrome

Acute or chronic renal failure

Hypervolemic Hypotonic Hyponatremia

Treatment

1. Treat the underlying cause.

2. Dietary sodium restriction/fluid restriction.

3. Loop diuretics to remove excess water.

4. Can consider vasopressin receptor antagonists

Why should sodium be restricted in hypervolemic hypotonic hyponatremia?

The hyponatremia is not caused by insufficient sodium intake, rather it is caused by fluid retention. Restrict sodium intake to prevent further fluid retention.

Vasopressor Receptor Antagonists Examples

conivapatan, tolvaptan

Vasopressor Receptor Antagonists MOA

Inhibits the action of AVP to reduce water reabsorption via aquaporins.

Conivaptan

Dose and Route

IV

20 mg bolus over 30min, then 20 mg/24hours

Conivaptan

Receptors, SEs

V1A, V2

Hypotension

Injection site reaction

Hypokalemia

Tolvaptan

Dose and Route

15 mg PO daily

Tolvaptan

Receptors, SEs

V2

Hypotension

Hypovolemia

GI hemorrhage

Euvolemic Hypotonic Hyponatremia

TBW, TBNa

TBW↑ , TBNa no change

Water gain > sodium gain

Associated with mild water retention.

Euvolemic Hypotonic Hyponatremia

Causes

Hypothyroidism

Adrenal Insufficiency/Addison's disease (insufficient aldosterone production)

Syndrome of inappropriate ADH (SIADH)

Why is SIADH associated with euvolemia?

A disorder that leads to inappropriate water reabsorption via aquaporins.

Enough water is retained to dilute serum sodium but not enough to affect overall volume status.

Causes of SIADH

CNS Disorders

Stroke

Trauma

Malignancy (lung tumors particularly)

Medications

Infections, HIV

Severe pain

Severe nausea**

Medications Associated with ADH (AVP) Release

Haloperidol, chlorpropamide, carbamazepine, TCAs, SSRIs, desmopressin

Euvolemic Hypotonic Hyponatremia

Mild-Moderate Symptoms Treatment

1. Fluid restriction

2. Furosemide with NaCl tablet or NS supplementation.

3. Demeclocycline if chronic SIADH.

Euvolemic Hypotonic Hyponatremia

Severe Symptoms Treatment

1. Furosemide

2. 3% NaCl infusion

Demeclocycline MOA

Inhibits the renal response to AVP by inhibition of cAMP.

Demeclocycline Dose

300-600 mg PO BID.

Take 1 hour ac or 2 hr pc.

Demeclocycline onset

Onset is 2-5 days.

only used in cases of chronic SIADH

Demeclocycline SEs

Photosensitivity

Nephrotoxicity

Nausea

Is demeclocycline more or less predictable that vasopressin receptor antagonists?

Has more predictable effect and less ADRs than the vasopressin receptor antagonists.

Demeclocycline DDIs

Separate administration from calcium and iron supplements.

Hypovolemic Hypotonic Hyponatremia

TBW, TBNa

TBW↓ , TBNa ↓↓

Sodium loss > water loss

Hypovolemic Hypotonic Hyponatremia

Renal Causes

Cerebral salt wasting (rare endocrine disorder)

Excessive diuresis (iatrogenic)

Adrenal insufficiency (Addison's Disease)

Hypovolemic Hypotonic Hyponatremia

Non-Renal Causes

Bleeding

Vomiting

Diarrhea

Burns

Sweating

Hypovolemic Hypotonic Hyponatremia

Mild-Moderate Symptoms Treatment

NaCl tablet

0.9% NaCl

Hypovolemic Hypotonic Hyponatremia

Severe Symptoms Treatment

3% NaCl

Goal Corrected Serum Sodium Level

goal serum sodium levels of 125-130 mEq/L.

A conservative goal to prevent overcorrection.

What fluids are used to treat hyponatremia?

(severe vs. mild-moderate symptoms)

Acute Hyponatremia

< 48 hours

Requires rapid intervention to prevent brain herniation

Severe, acute hyponatremia

Goal Na+ Increases

4-6 mEq/L in 1-2 hours

Severe, acute hyponatremia

Treatment

Bolus infusions of 3% NaCl

Severe, acute hyponatremia

Max sodium correction

varies

Mild-moderate, acute hyponatremia

Goal Na+ increases

4-6 mEq/L in 1-2 hours

Mild-moderate, acute hyponatremia

Treatment

Bolus infusions of 3% NaCl

Mild-moderate, acute hyponatremia

Max sodium correction

8 mEq/L per day

Chronic Hyponatremia

> 48 hours

Requires slow, conservative correction of serum sodium levels to prevent osmotic demyelination.

Moderate, chronic hyponatremia

Goal Na+ increases

4-6 mEq/L in 6-12 hours

Moderate, chronic hyponatremia

Treatment

Continuous infusion of 3% NaCl

Moderate, chronic hyponatremia

Max sodium correction

8 mEq/L per day

Mild, chronic hyponatremia

Goal Na+ increases

4-6 mEq/L in 24 hours

Mild, chronic hyponatremia

Treatment

Correct underlying causes

Mild, chronic hyponatremia

Max sodium correction

8 mEq/L per day

Monitoring Parameters

Monitor serum sodium

- After any 3% NaCl bolus

- Every 2-4 hours during continuous infusions

What fluid should be used to fix overcorrection?

D5W

What is the sodium content of 3% NaCl?

513 mEq/L sodium concentration

100% distribution into the ECF