Hypernatremia

Solute Distribution

Extracellular vs Intracellular

Na is the primary extracellular solute

K is the primary intracellular

distribution is maintained by NaK ATPase

Normal Serum Sodium

135-145 mEq/L

Why is serum sodium so important?

sodium is the major determinant of plasma osmolarity

What controls the serum sodium concentration?

Serum sodium concentrations are controlled by water balance (not necessarily indicative of the total body sodium)

Sodium Intake

~150 mEq/day

Sodium Loss

Renal and Extrarenal

Renal

~150 mEq day

Extrarenal

Stool ~10 mEq/day

Insensible ~10 mEq/day

1 g of NaCl is how many mEq?

17 mEq Na+

Sodium Reabsorption in the Nephron

PCT, Loop, DCT, Collecting Duct

Hypernatremia Serum Sodium

>145 mEq/dL

Hypernatremia is always a ________osmolar state.

HYPERosmolar

sodium is the primary determinant of serum osmolarity....

What total body water imbalance causes HYPERnatremia?

total body water DEFICIT

Moderate Hypernatremia

Serum Sodium, Symptoms

150-160 mEq/L

Muscle weakness

Restlessness

N/V

Severe Hypernatremia

Serum sodium, symptoms

>160 mEq/L

Confusion

Irritability

Lethargy

Stupor

Coma

3 Etiologies/Categories of Hypernatremia

Hypovolemic Hypernatremia

Euvolemic Hypernatremia

Hypervolemic Hypernatremia

Hypervolemic Hypernatremia

TBW, TBNa

TBNa ↑, TBW ↑↑↑

Sodium gain > water gain

Hypervolemic Hypernatremia Causes

Iatrogenic (most common)

hyperaldosteronism

cushing's syndrome

Iatrogenic Causes

Sodium overload (3% NaCl)

Excessive sodium ingestion

Antibiotic containing Na

Hypertonic dialysis

Hypervolemic Hypernatremia Treatment

1. D/c offending agent.

2. Diuretics to eliminate excessive sodium and water. (hemodialysis if renal failure)

--> Furosemide, 20 to 40 mg given orally or intravenously every 6 hours

3. Replace free water deficit.

Euvolemic Hypernatremia

TBW, TBNa

TBNa no change, TBW ↓

slight water loss

Euvolemic Hypernatremia

Renal Causes

Diabetes Insipidus

Signs and Symptoms of Diabetes Insipidus

polyuria, polydipsia, urine specific gravity < 1.005 (ref 1.010)

Why are DI patients typically euvolemic?

Patients with untreated AVP disorder excrete large volumes (320 L/day) of dilute urine, resulting in hypernatremia.

Renal water loss is compensated for by intense thirst (mild overall TBW loss).

Types of Diabetes Insipidus

Central DI: decreased AVP secretion leads to water loss.

Nephrogenic DI: resistance to AVP.

Central DI Causes

Caused by TBI, pituitary surgery, stroke.

Nephrogenic DI Causes

Caused by kidney disease.

Caused by medications: Lithium, Foscarnet, Clozapine

Euvolemic Hypernatremia

Non-Renal Causes

fever

hyperventilation

Euvolemic Hypernatremia Treatment

1. Replace free water deficit (PO if possible, IV if not)

2. If applicable, treat diabetes insipidus.

Central Diabetes Insipidus

Pharmacologic Treatment Options

Aqueous Vasopressin

Desmopressin

Aqueous Vasopressin

Place in Therapy

Only used for initial treatment due to short duration of action.

Aqueous Vasopressin

Route of Admin

IM or SC

Aqueous Vasopressin

SEs

Fluid overload with excessive dosing

Smooth muscle contractions

- Abdominal pain

- HTN

- Angina

- Uterine contractions

Aqueous vasopressin should be avoided in patients with hypersensitivity to what?

bovine or porcine agents

Desmopressin

Place in Therapy

Has increased potency, longer duration, and less smooth muscle effects

preferred agent

Desmopressin

Routes of Administration

nasal spray

rhinal tube

IV

oral

Desmopressin

Converting between dosage forms

10 mcg nasal spray = 1 mcg IV/SC = 0.05-0.1 mg tablet

Desmopressin

SEs

HA

HTN

Angina

Abd pain

conjunctivitis (nasal spray only)

oral tablet typically well -tolerated

Nephrogenic Diabetes Insipidus

Pharmacologic Treatment Options

hydrochlorothiazide, amiloride, indomethacin

HCTZ MOA

Has a paradoxical effect that results in enhanced proximal tubular Na/H2O reabsorption.

must be combined w sodium restriction

HCTZ Dosing

25 mg QD or BID

HCTZ SEs

Hypokalemia

Hypomagnesmia

Hypercalcema

Gout

Amiloride MOA

Inhibits Lithium reabsorption (Li inhibits ADV effect).

Amiloride Dosing

5-10 mg QD

Amiloride SEs

Mild hyperkalemia

HA

Weakness

Indomethacin MOA

Blocks prostaglandin (prostaglandins antagonize AVP effect)

Indomethacin

Dosing, Place in Therapy

Used as adjunctive therapy

100-150 mg/day (2-3 divided doses)

Indomethacin SEs

GI ulcer

AKI

Hypovolemic Hypernatremia

TBW, TBNa

TBNa ↓, TBW ↓↓↓

Water loss > sodium loss

Hypovolemic Hypernatremia

Renal Causes

Osmotic diuresis

Diuretic use

Acute/chronic kidney disease

Hypovolemic Hypernatremia

Non-Renal Causes

Diarrhea

Vomiting

Fistulas

Excessive sweating

Burns

Hypovolemic Hyponatremia

Treatment

1. If in hypovolemic shock, ALWAYS RESUCITATE FIRST.

250-1000 mL NS over 30-60minutes

2. Then replace free water deficit (see below)

Dehydration vs. Hypovolemia vs. Shock

Dehydration refers to a loss of TBW producing hypertonicity

Hypovolemia (volume depletion) is a symptomatic ECF volume deficit.

Shock hypotension + tachycardia.

Why must sodium level correction rate be monitored?

rapid correction can cause cerebral edema

Brain Compensation in Hypernatremia

plasma hyperosmolarity --> brain generates organic solutes to prevent water loss --> rapid correction of plasma osmolarity --> brain swelling

Maximum Correction Rate

Acute Hypernatremia

< 48 hours

1 mEq/L/hr

Maximum Correction Rate

Chronic Hypernatremia

> 48 hours

0.5 mEq/L/hr

Maximal Daily Sodium Correction

10 mEq/L

What is the goal serum sodium?

To prevent overcorrection, goal serum sodium is 145-150 mEq/L.

Equation to Calculate an IV Fluid's Correction Rate

What fluids are used to correct hypernatremia?

D5W, 0 mEq/L

0.45% NaCl, 77 mEq/L

Free Water Deficit Equation

TBW Deficit = Normal TBW - Current TBW

Normal TBW = BW*(%water)

Current TBW = (140/serum sodium)*Normal TBW

How do you replace the free water deficit?

Replace ½ of the deficit in the first 24 hours THEN replace the remainder in the next 24-72 hours.

Always report fluid replacement calculations in L/hour!