Approach to Hyponatremia- Summary!

Hi Team,

We recently reviewed Hyponatremia (Na<135 mmol/L).

A few key points to keep in mind:

THE ISSUE: hyponatremia is a disorder of WATER balance, not sodium. In virtually all patients, this results from the intake (oral or IV) and subsequent retention of water. Normally, patients can handle a “water load” via renal excretion, as the dilutional fall in serum osmolality suppresses the release of ADH, thus, allowing excretion of the excess water in the form of a dilute urine. The maximum attainable urine volume in normal people on a regular diet is >10 L/day. This provides us with an enormous range of protection against the development of hyponatremia since the daily fluid intake in most healthy individuals is <2-2.5 L/day

DON’T FORGET THE HORMONES THAT GOVERN WATER AND SODIUM HOMEOSTASIS:

-Antidiuretic Hormone (ADH): synthesized in the hypothalamus, secreted to the posterior pituitary where it is stored and subsequently released. Stimulus for secretion include:

1) High Plasma Osmolality

2) Low intra-vascular volume/volume depletion

ADH increases water permeability in the collecting tubules of the kidney (via aqua-porin 2 channels), increasing water absorption and thus increasing urine osmolality but decreasing serum osmolality

-Aldosterone: regulated by intra-vascular volume via the renin-angiotensin system (RAS) and also regulated by sodium levels and hyperkalemia. Aldosterone stimulates the Na-K+ exchange pump in the distal tubule, to increase sodium reabsorption and decrease urine sodium.

THE APPROACH

-Determine Osmolality & Exclude “Pseudo-hyponatremia” Causes

1) ISO-OSMOLAR HYPONATREMIA

·       “Pseudo-hyponatremia”: sodium may be falsely elevated in the setting of paraproteinemia (elevated plasma proteins) and hypertriglyceridemia. This occurs, because sodium is only present in the aqueous portion of the blood, whereas, protein and lipids are present in the non-aqueous portion. The lab analyzer measures sodium over the entire blood volumes—and not just the aqueous portion. Thus, with a higher proportion of protein and triglycerides, the sodium value is divided over a larger total blood volume, creating a hyponatremic value

·          -Theoretical concern that utilizing glycine or sorbital flushing during a TURP can cause hyponatremia

2) HYPEROSMOLAR HYPONATREMIA

·        Hyperglycemia: for every glucose value increase of 10 mmol/L above the level of 10 mmol/L, add 3 mmol/L to the Na value; high serum osmolesà increase water absorption in the intravascular spaceà dilutes the Na *(this is a true hypoNa); once the glucose is corrected, the Na will naturally move back towards it’s baseline value

3) HYPOOSMOLAR HYPONATREMIA

·       Assess volume status: Hypovolemia, Euvolemia, Hypervolemia

·       The volume status governs your differential diagnosis (DDx)

Hypovolemic: renal loss (diuretics, hypoadrenalism, Bartter’s, hypomagnesemia), GI loss (N/V/Diarrhea), 3^rd spacing, blood loss, skin loss (sweat, burns).

·       Exam: tachycardia, hypotension, orthostatic VS, dry MM, poor skin turgor;

·       Investigations: elevated Urea:Cr ratio;

·       Decrease in intravascular volume à Increases ADHà  Increases urine osmolality (>100, often higher)

·       Decrease in intravascular volume à  Increases aldosterone à decreases urine Na (<20)

·       Treatment: NS infusion. Can consider hypertonic saline + furosemide (More water loss relative to Na loss) if severe- but use caution!

Euvolemic: Non-SIADH (Low solute diet, Hypothyroidism, Adrenal Insufficiency, Psychogenic Polydipsia) versus SIADH causes (Physiological-pain, nausea, stress, anxiety; Cancer-SCLC, duodenum, thyoma, pancreatic, lymphoma; Lung- cancer, TB, pneumonia, abscess, empyema; CNS- skull fracture, SDH, SAH, meningitis, mass/neoplasm, GBS, acute intermittent porphyria; Drugs-opioids (i.e. morphine), carbamazepine, SSRIs, TCAs, vincristine, oxytocin, general anesthetic)

·       Exam: euvolemic

·       SIADH: diagnosis requires a cause available, a clinically euvolemic patient, High Urine Na (>40), high urine osmolality (>100, but, usually >300), usually a high specific gravity. Need to rule out AI, hypothyroidism, PP, and diuretic use

·        Increases ADHà  Increases urine osmolality (>100, but usually, >300)

·        Increase ADHà  Increases intravascular volume à Decreases aldosterone à Increases urine Na (>40)

·       Treatment: Free Water Restriction <1 L/day; for SIADH, may consider Demeclocycline (tetracycline that inhibits action of ADH); NS may be needed, but, tx the underlying cause

In Psychogenic Polydipsia: the primary problem is an increase in intravascular volume d/t water intoxication:

 Increase in Intravascular volume à Decreases ADHà Decreases Urine Osmolality (<100)

 Increase in Intravascular volume à Decreases Aldosterone à increases urine Na (>20)

Hypervolemic: CHF, GI protein losing enteropathy, cirrhosis, nephrotic syndrome, malnutrition (can decrease albumin, effecting oncotic pressure)

·       On exam: elevated JVP, Crackles, edema, ascites

·       Investigations: pulmonary edema on CXR;

·       Actual Decrease in intravascular volume à Increases ADHà Increases urine osmolality (>100, often higher)

·       Actual Decrease in intravascular volume à increases aldosterone à Decrease in urine Na (<20)

·       Treatment: sodium & Free Water restrict (<1L/d). Treat the underlying cause. May need Lasix.

NOTE: urine osmolality & urine Na levels are the same in hypovolemia and hypervolemia; the only way to tell the difference is with clinical exam

TREATMENT GUIDELINES: Correction Rate should correct 0.5 mmol/h or 12 mmol/24h to reduce the risk of Osmotic Demylination Syndrome (formerly known as Central Pontine Myelinolysis). Note that these correction rules are not perfect, but are merely a guideline and help you conceptualize your rate of correction.

Steps & Example: Patient with a sodium of 119 mmol/L that you want to raise to 123 mmol/L over a defined time period with plans to re-assess the electrolytes and rate of infusion of IV fluid

STEPS

1.Calculation of Na deficit per liter= Na goal – Current Sodium (i.e. 123-119= 4 mmol/L

2.Calculation of Total Body Water (L)= 0.5 (female) x weight (kg); use 0.6 for men

i.e. 60 kg x0.5= 30 L TBW

3.Calculate Total Sodium Deficit per liter for Initial Therapy= sodium deficit/L x TBW (L)i.e. 4 mmol/L x 30 L= 120 mmol

4. Calculate the Total Amount of IVF to be given: i.e. for NS (1L= 154 mmol Na); 1L/154 mmol= x/120 mmol = 0.779 = ~ 800mL of 0.9 NS

5. Calculate the Infusion Rate: 800 mL/desired time (i.e. 6h)= 133.3 mL/h for 6h then reassess

Recall Concentrations: D5W (dextrose 5% in water)=0 mmol/L; ½ NS (0.45 NaCL)= 77 mmol/L; Ringer’s Lactate= 130 mmol/L; NS= 154; Hypertonic (3%)= 513 mmol/L

What if the patient was seizing and this was an acute drop in Na?

-Give HYPERTONIC saline! Slow, once in the moderate range of 125-129

RISK FACTORS FOR OSMOTIC DEMYLINATION SYNDROME?

3 MAJOR RF: serum [Na+] at presentation, duration of hyponatremia, & rate of correction

·          More common if presenting Na 120 or less

·         More common in chronic cases, or even >2-3 days

·         More common with elevation of Na >10 mmol in a 24h period and >18 in 48h

Prevention is key!

NOTE: if you over-correct, consider Desmopressin (ADH): 2 mcg IV or SC q6h, or therapeutically lower the Na with IVF (i.e. 5% dextrose in water (D5W), 6 ml/kg lean BW, infuse over 2h, which should lower the Na by 2 mmol/L)