Sodium Disorders I

Serum Na (135–145 mEq/L)

Lab Values

• Normal range serum Na: 135–145 mEq/L

• Hyponatremia = Na <135 mEq/L

  • <130 mEq/L – clinically significant

• Hypernatremia = Na >145 mEq/L

  • >150 mEq/L – clinically significant

Hyponatremia (<135 mEq/L)

• Sodium

  • Accounts for 90% of osmotic activity in the ECF

  • Plasma sodium concentration reflects water balance

• Most common electrolyte disorder

  • Common in both inpatient and ambulatory settings

  • 1–6% of hospitalized patients

Diagnostic Algorithm for Hyponatremia

Step 1: Assess Serum Osmolality

• Low (<280 mOsm/kg)
  → Hypotonic hyponatremia

• Normal (280–285 mOsm/kg)
  → Isotonic hyponatremia (pseudohyponatremia)

• Elevated (>285 mOsm/kg)
  → Hypertonic hyponatremia

Step 1: Assess Volume Status

After identifying hypotonic hyponatremia, assess clinical volume status:

Hypovolemic Hypotonic Hyponatremia

• Diminished skin turgor

• Decreased intraocular tension

• Dry mucous membranes

• Orthostatic hypotension

• Tachycardia

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Isovolemic (Euvolemic) Hypotonic Hyponatremia

• Normal pulse

• Normal blood pressure

• Normal skin turgor

• No edema

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Hypervolemic Hypotonic Hyponatremia

• Edema

• Dyspnea on exertion

• Pulmonary rales

• Ascites

• Anasarca

Clinical Manifestations

• Primary system affected: Central nervous system (CNS)

• General

  • Many patients are asymptomatic when Na⁺ > 120 mEq/L

  • Symptoms are more pronounced with:

    • Large decreases in sodium

    • Rapid decreases in sodium

• Symptoms

  • Mild

    • Nausea

    • Malaise

  • Moderate

    • Disorientation

    • Headache

    • Restlessness

    • Lethargy

  • Severe

    • Seizures

    • Coma

    • Respiratory arrest

    • Permanent brain damage

    • Brainstem herniation

    • Death

Pathophysiology

Initial effect

• Hypotonic state → water moves into brain cells

• Results in brain swelling (low osmolality)

Brain adaptation

• Rapid adaptation

  • Loss of sodium, potassium, and chloride

• Slow adaptation

  • Loss of organic osmolytes

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Correction Considerations

Proper correction

• Slow correction of hypotonic state

• Allows restoration of normal brain osmolality

Improper correction

• Rapid correction of hypotonic hyponatremia

• Leads to osmotic demyelination

Non-Hypotonic Hyponatremia

Isotonic Hyponatremia

Serum osmolality

• Normal (~280 mOsm)

Description

• Normal plasma osmolality

• Low serum sodium

Associated condition

• Pseudohyponatremia

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Hypertonic Hyponatremia

Serum osmolality

• Elevated (>280 mOsm)

Causes

• Hyperglycemia

• Unmeasured effective osmoles

  • Glycine

  • Mannitol

Isotonic Hyponatremia

Plasma findings

• Normal plasma osmolality

• Low serum sodium

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Pseudohyponatremia

Mechanism

• Sodium is displaced in the extracellular fluid (ECF)

Causes

• Hypertriglyceridemia

• Hyperproteinemia

  • Multiple myeloma

---

Treatment

• None

• Correct underlying problem

Hypertonic Hyponatremia

Definition

• Increase in plasma osmolality

• Decrease in sodium (Na⁺) levels

Mechanism

• Caused by a shift of water from the ICF → ECF

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Causes

• Mannitol administration / infusions

• Hyperglycemia

  • ↓ Na⁺ by 1.6 mEq/L for each 100 mg/dL increase in blood glucose over 100 mg/dL

  • Corrected sodium formula

    • Corrected Na⁺ = measured Na⁺ + [0.016 × (serum glucose − 100)]

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Treatment

• Manage underlying cause (e.g., Diabetic Ketoacidosis)

• Example:

  • Hyperglycemia → give insulin

Calculation: Hyperglycemic Hyponatremia

Patient

• 45-year-old male

• 70 kg, 5’10”

• Type 1 diabetes mellitus (T1DM)

• Presents with lethargy, nausea/vomiting, increased thirst

• Insulin pump malfunctioned 2 days ago

Labs

• Glucose: 528 mg/dL

• Na⁺: 124 mEq/L

• K⁺: 5.4 mEq/L

• Beta-hydroxybutyrate: 4.5

Diagnosis

• Diabetic ketoacidosis (DKA)

Corrected Serum Sodium Calculation

• 124 + [0.016 × (528 − 100)] = 131 mEq/L

Management

Fluid to start

• 0.9% NaCl

Treatment for underlying problem

• Insulin infusion

Hypotonic Hyponatremia

Overview

• Most common cause of hyponatremia

• “True” hyponatremia

Approach

• Differentiate by volume status

Urine Chemistries

Urine Osmolality

< 100 mOsm/kg

• Normal water excretion

• Intake problem:

  • Polydipsia

  • Low solute intake

> 100 mOsm/kg

• Impaired water excretion

• Rule out:

  • Hypothyroid

  • Adrenal insufficiency

• Evaluate urine sodium

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Urine Sodium

> 20 mEq/L

• Renal losses

• Diuretics

• Adrenal insufficiency

• SIADH

< 20 mEq/L

• Extrarenal losses:

  • GI

  • Skin

  • Lung

• Heart failure

• Cirrhosis

• Nephrosis

• Polydipsia

• Low solute intake

  • “Tea & toast”

  • “Beer potomania”

Hypovolemic Hypotonic Hyponatremia

Loss of Water and Sodium

GI salt loss

• Diarrhea

• Vomiting

• NG suction

• Fluid sequestration

  • Bowel obstruction

  • Peritonitis

  • Pancreatitis

Skin losses

• Excessive sweating (marathon runners)

• Burns

Renal losses

• Renal disease

• Mineralocorticoid deficiency

• Cerebral salt wasting syndrome

• Diuretics

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Characteristics

Water and Sodium

• Sodium loss >>> water loss

Causes

• Renal: thiazide diuretics

• Nonrenal: diarrhea, vomiting

Effect on Total Body Water (TBW)

• ↓ ↓

Effect on Total Body Sodium (TBNa)

• ↓

Laboratory Findings

• Renal: urine osmolality high, urine sodium high

• Nonrenal: urine osmolality high, urine sodium low

Clinical Presentation

• Orthostasis

• Hypotension

• Tachycardia

• Dry mucous membranes

• CNS changes

Chronic Treatment

• 0.9% NaCl until vital signs stable

• Then maintenance fluid (e.g., D5–½

Diuretic-Induced Hypovolemic Hypotonic Hyponatremia

Overview

• Very common

• Most cases of severe hyponatremia are due to a thiazide-type diuretic

Risk Factors

• Elderly

• Low body mass

• Low potassium

Thiazide Mechanism

• Interferes with sodium reabsorption in the distal convoluted tubule (DCT)

  • Blocks Na⁺ reabsorption at the Na⁺/Cl⁻ cotransporter in the DCT

• Produces volume depletion → stimulates ADH release

• Enhanced water reabsorption

  • Medullary concentration gradient unaffected (unlike loop diuretics)

Hypovolemic Hypotonic Hyponatremia – Treatment

Goals

• Reverse hypotonicity without causing osmotic demyelination

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Assess Acuity and Symptoms

• Acute: < 48 hours

• Chronic: > 48 hours

  • Chronic cases have higher risk of osmotic demyelination

• Symptomatic?

  • Severe or moderate symptoms

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Treatment (Chronic Cases)

• 0.9% NaCl

• Correct at a maximum rate of 10–12 mEq/L/day

  • Slower rate for more severe cases

• Monitor sodium every 4 hours

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Treat Underlying Cause

• Permanently discontinue thiazide diuretics

• Treat vomiting, diarrhea, etc.

Hypovolemic Hypotonic Hyponatremia – Acute or Life-Threatening

Indications

• Seizures or coma

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Treatment

• 3% NaCl

  • Risk of cerebral edema or brain herniation outweighs risk of correcting sodium too rapidly

  • Monitor Na every 2 hours

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Severe Symptoms (Seizures or Coma)

• Hypertonic saline (3% NaCl) bolus 100 mL over 10 minutes

  • May repeat up to 3 times as needed

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Moderate Symptoms (Confusion or Lethargy)

• Hypertonic saline (3% NaCl) continuous infusion

  • 0.5–2 mL/kg/hr

Euvolemic Hypotonic Hyponatremia

Overview

• Water retention

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Causes

• Primary polydipsia

• “Tea & toast” or “beer potomania”

• Hypothyroidism

• Hypocortisolism

• SIADH

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Characteristics

Water and Sodium

• Water gain or retention

Causes

• SIADH

• Polydipsia

Effect on Total Body Water (TBW)

• ↑ ↑ ↑

Effect on Total Body Sodium (TBNa)

• ↔

Laboratory Findings

• SIADH: urine osmolality high, urine sodium high

• Polydipsia / low solute intake: urine osmolality low, urine sodium low

Clinical Presentation

• Depends on severity of hyponatremia

• Seizures

• Lethargy

Chronic Treatment

• Water restriction

• Salt tablets

• Urea

• Loop diuretics

• Vaptans

Euvolemic Hypotonic Hyponatremia

SIADH – Syndrome of Inappropriate Antidiuretic Hormone Secretion

• Most common cause

• Elevated levels of ADH that are inappropriate based on osmotic and volume stimuli

• Induces reabsorption of water from the collecting duct, which further increases hyponatremia

• Leads to a reduction in aldosterone secretion

  • Induces urinary sodium excretion (high urine Na)

• Component of increased water intake also involved

SIAD (SIADH): Drug-Induced Causes — MOA

Mechanisms

Stimulate ADH release (Central)

• Serotonin may stimulate ADH release

  • 5HT₂C, 5HT₄, & 5HT₇ implicated in DI-SIADH

• Antidepressants (SSRIs), antipsychotics, cyclophosphamide, vinca alkaloids, carbamazepine, & MDMA

Potentiate the action of ADH (Renal)

• Chlorpropamide, carbamazepine, oxcarbazepine, & cyclophosphamide

SIAD (SIADH): Drug-Induced Causes — Drug classes with strongest association

Antidepressants

• SSRIs (Celexa, Prozac, Zoloft, Lexapro, Paxil)

• Tricyclics

• Venlafaxine

Chemotherapy

• Vincristine/Vinblastine, Cisplatin, & Cyclophosphamide

Anticonvulsants

• Carbamazepine & Oxcarbazepine

Euvolemic Hypotonic Hyponatremia – Treatment

⭐ Fluid Restriction

• Less than 1 liter per day

Life-threatening SIADH (coma/seizures) or Acute (<48 hrs)

• 3% saline plus IV furosemide

• Treat until any one of the following occur:

  • Asymptomatic

  • Serum Na level >120 is achieved

• Monitor serum Na levels every 2 hours

Euvolemic Hypotonic Hyponatremia – Treatment

Chronic SIADH with mild to moderate symptoms

• Stop causative agent or treat underlying cause

• Fluid restriction: less than 1 liter per day

• Patients who do not respond to fluid restriction

  • (about 1 to 2 weeks) may need chronic medication treatment

• Correct at a maximum rate of 10–12 mEq/L/day

• Monitor sodium every 4 hours

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Medications

• Urea

• Salt tablets

• Demeclocycline

  • May take 1 to 2 weeks for peak effects

• Vasopressin receptor antagonists (vaptans)

  • Conivaptan – IV formulation

    • Risk of osmotic demyelination

  • Tolvaptan – PO formulation

    • Hepatoxic, excessive thirst, $$

    • Don’t use more than 30 days

Hypervolemic Hypotonic Hyponatremia

Increase in water and sodium

Mechanism

• Angiotensin II

• Aldosterone

• Norepinephrine

• ADH

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Characteristics – Hypervolemic

Water and Sodium

• Water gain >>> sodium gain

Causes

• Heart failure

• Liver cirrhosis

• Kidney failure

Effect on TBW

• ↑ ↑ ↑

Effect on TBNa

• ↑ ↑

Laboratory

• UOsm high

• UNa high

Clinical Presentation

• Peripheral and pulmonary edema

• Variable blood pressure (BP)

Chronic Treatment

• Na restriction

• Water restriction

• Loop diuretics

• Vaptans

Hypervolemic Hypotonic Hyponatremia: Treatment

Treatment in Heart Failure

• Fluid restriction

• Sodium restriction

  • Less than 2 grams/day

• Loop diuretics

• Treat heart failure – Cardiology section of Therapeutics I

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Treatment in Cirrhosis

• Fluid restriction

• Sodium restriction

  • Less than 2 grams/day

• Diuretics (loop + mineralocorticoid receptor antagonist)

• Treat ascites – GI section of Therapeutics I

Summary of Hypotonic Hyponatremia

A 21-year-old male with type 1 diabetes mellitus presents to the emergency department with:

• Nausea

• Vomiting

• Confusion

He ran out of insulin 3 days ago.

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Laboratory Results

• Na: 122

• K: 3.9

• Cl: 101

• CO₂: 13

• BUN: 32

• Cr: 0.9

• Glucose: 600

• Ketones: 4.7

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Question

Which of the following most likely describes this type of hyponatremia?

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Answer choices:

• A. Isotonic hyponatremia

• B. Hypertonic hyponatremia

• C. Hypotonic hyponatremia

B. Hypertonic hyponatremia

A 57-year-old female with:

• Stage IV breast cancer

• Depression

• Trigeminal neuralgia

presents to the emergency department after a new-onset witnessed seizure at home.

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Recent Chemotherapy

• Vincristine

• Cyclophosphamide

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Home Medications

• Zoloft 200 mg daily

• Carbamazepine 900 mg TID

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Laboratory Results

• Na: 108

• K: 3.7

• Cl: 87

• CO₂: 20

• BUN: 65

• SCr: 2.3

• Glucose: 105

• Urine osmolality (UOsm): 248

• Urine sodium (UNa): 62

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Question

What is the most likely underlying cause(s) of hyponatremia?
(Select all that apply.)

Answer choices:

• A. Vincristine

• B. Cyclophosphamide

• C. Zoloft

• D. Carbamazepine

All of the above.

A 57-year-old female with:

• Stage IV breast cancer

• Depression

• Trigeminal neuralgia

presents to the emergency department after a new-onset witnessed seizure at home.

---

Recent Chemotherapy

• Vincristine

• Cyclophosphamide

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Home Medications

• Zoloft 200 mg daily

• Carbamazepine 900 mg TID

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Laboratory Results

• Na: 108

• K: 3.7

• Cl: 87

• CO₂: 20

• BUN: 65

• SCr: 2.3

• Glucose: 105

• Urine osmolality (UOsm): 248

• Urine sodium (UNa): 62

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Question

Interpret the urine chemistries.

A. UOSm is high. UNa is high.

B. UOSm is high. UNa is low.

C. UOSm is low. UNa is high.

D. UOSm is low. UNa is low.

A. UOSm is high. UNa is high.

A 57-year-old female with:

• Stage IV breast cancer

• Depression

• Trigeminal neuralgia

presents to the emergency department after a new-onset witnessed seizure at home.

---

Recent Chemotherapy

• Vincristine

• Cyclophosphamide

---

Home Medications

• Zoloft 200 mg daily

• Carbamazepine 900 mg TID

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Laboratory Results

• Na: 108

• K: 3.7

• Cl: 87

• CO₂: 20

• BUN: 65

• SCr: 2.3

• Glucose: 105

• Urine osmolality (UOsm): 248

• Urine sodium (UNa): 62

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Question

After holding home medications, what is the first-line treatment option, and what frequency of laboratory monitoring should be ordered?

Answer choices:

• A. Give 0.45% NaCl, monitor every 4–6 hours

• B. Fluid restriction, give 3% NaCl, monitor every 2–4 hours

• C. Give 0.9% NaCl, monitor once daily

• D. Fluid restriction, give tolvaptan, monitor every 8–12 hours

• B. Fluid restriction, give 3% NaCl, monitor every 2–4 hours

An 85-year-old female with hypertension presents to the emergency department with:

• Nausea and vomiting

• Orthostatic hypotension

• Confusion for 3 days

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• Family reports she may have caught a “stomach bug.”

• She has not been able to keep liquids down.

• She continued taking hydrochlorothiazide (HCTZ) 25 mg daily as prescribed.

• Her mucous membranes are dry.

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Laboratory Results

• Na: 119

• K: 3.7

• Cl: 96

• CO₂: 24

• BUN: 65

• SCr: 2.3

• Glucose: 87

• Urine osmolality (UOsm): 532

• Urine sodium (UNa): 46

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Question

What is the most likely type of hyponatremia, and what is the most likely underlying cause?

Answer choices:

• A. Euvolemic; SIADH

• B. Hypervolemic; stomach bug

• C. Hypovolemic; HCTZ

• D. SIADH; HCTZ

• C. Hypovolemic; HCTZ

An 85-year-old female with hypertension presents to the emergency department with:

• Nausea and vomiting

• Orthostatic hypotension

• Confusion for 3 days

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• Family reports she may have caught a “stomach bug.”

• She has not been able to keep liquids down.

• She continued taking hydrochlorothiazide (HCTZ) 25 mg daily as prescribed.

• Her mucous membranes are dry.

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Laboratory Results

• Na: 119

• K: 3.7

• Cl: 96

• CO₂: 24

• BUN: 65

• SCr: 2.3

• Glucose: 87

• Urine osmolality (UOsm): 532

• Urine sodium (UNa): 46

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Question

How should the urine chemistries be interpreted?

Answer choices:

• A. UOsm is high; UNa is high

• B. UOsm is high; UNa is low

• C. UOsm is low; UNa is high

• D. UOsm is low; UNa is low

• A. UOsm is high; UNa is high

An 85-year-old female with hypertension presents to the emergency department with:

• Nausea and vomiting

• Orthostatic hypotension

• Confusion for 3 days

---

• Family reports she may have caught a “stomach bug.”

• She has not been able to keep liquids down.

• She continued taking hydrochlorothiazide (HCTZ) 25 mg daily as prescribed.

• Her mucous membranes are dry.

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Laboratory Results

• Na: 119

• K: 3.7

• Cl: 96

• CO₂: 24

• BUN: 65

• SCr: 2.3

• Glucose: 87

• Urine osmolality (UOsm): 532

• Urine sodium (UNa): 46

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Question

What is the best treatment option, and what is the maximum correction rate?

Answer choices:

• A. Fluid restriction, 10–12 mEq/L/day

• B. Stop HCTZ, give 3% NaCl, 15–20 mEq/L/day

• C. Stop HCTZ, give salt tablets, 4–6 mEq/L/day

• D. Stop HCTZ, give 0.9% NaCl, 10–12 mEq/L/day

D. Stop HCTZ, give 0.9% NaCl, 10–12 mEq/L/day

A 32-year-old previously healthy female collapses at the finish line of a marathon with a new-onset, witnessed seizure.

In the emergency department:

• Na: 117 mEq/L

• Vital signs are stable

Yesterday, her Na was 137 mEq/L on a routine lab draw.

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Question

What is the most appropriate treatment and monitoring?

Answer choices:

• A. Lactated Ringer’s, check electrolytes in 4 hours

• B. 0.9% NaCl, check electrolytes in 24 hours

• C. D5W, check electrolytes in 12 hours

• D. 3% NaCl, check electrolytes in 4 hours

D. 3% NaCl, check electrolytes in 4 hours

A 48-year-old male with a 30-year history of alcohol use presents to the emergency department with:

• Shortness of breath

• Abdominal ascites

He reports a 20-pound weight gain over the last 3 weeks and is diagnosed with new-onset cirrhosis.

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Laboratory Results

• Na: 118

• K: 3.4

• Cl: 104

• CO₂: 22

• BUN: 20

• SCr: 1.2

• Glucose: 193

• Urine osmolality (UOsm): 170

• Urine sodium (UNa): 16

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Question

What is the most likely type of hyponatremia and underlying cause?

Answer choices:

• A. Hypovolemic; SIADH

• B. Euvolemic; hyperglycemia

• C. Hypervolemic; cirrhosis

• D. Pseudohyponatremia; “beer potomania”

C. Hypervolemic; cirrhosis

A 48-year-old male with a 30-year history of alcohol use presents to the emergency department with:

• Shortness of breath

• Abdominal ascites

He reports a 20-pound weight gain over the last 3 weeks and is diagnosed with new-onset cirrhosis.

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Laboratory Results

• Na: 118

• K: 3.4

• Cl: 104

• CO₂: 22

• BUN: 20

• SCr: 1.2

• Glucose: 193

• Urine osmolality (UOsm): 170

• Urine sodium (UNa): 16

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Question

What are the best treatment options? (Select all that apply)

A. Fluid restriction

B. Salt restriction

C. Start Bumex

D. Start Aldactone

All of the above.