Teaching Module
Hyponatremia
A 3500 g, 40 week gestation male infant is born to a 32 year old G2 P1 lady with unknown GBS
screen. Infant had been on breast milk and 20 Calorie per ounce pre-prepared formula
supplementation since birth. At 48 hrs of age the infant is noted to be lethargic with poor cry and
activity. Weight is 3650 g, and exam shows poor tone and activity. CBC reveals 36,000 WBC
with 45% segments and 26% bands, and CSF analysis reveals proteins of 250 mg/dl, Glucose of
22 mg/dl, and 52 WBC cells per mm3. Serum electrolytes are remarkable for sodium of 125
mEq/L, chloride of 98 mEq/L, potassium 4.5 mEq/L and blood sugar of 68 mg/dl.
Question 1. The most probable cause of hyponatremia in this infant is:
a.
b.
c.
d.
dehydration
iatrogenic hyponatremia
congenital adrenal hyperplasia
inappropriate ADH secretion
Answer 1. d. Syndrome of Inappropriate secretion of Anti diuretic Hormone (SIADH).
The infant’s clinical symptoms, CBC and CSF analysis show evidence of meningitis, which is
seen in 1 in 2500 live births. SIADH has been shown to be associated with meningitis in infants
and children in as many as 28 to 36.7% cases. This syndrome is thought to be caused by
excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland
or another source. The syndrome is associated with hyponatremia, low serum osmolality,
inappropriately high urine osmolality and sodium excretion, despite low serum sodium. Since the
inappropriately high ADH hormone causes excess water retention, weight gain is seen in these
cases. More recently the term “Syndrome of Inappropriate Antidiuresis” (SIAD) has been
suggested for this condition since elevated circulating ADH levels are not always seen with the
syndrome. Short serum half life of ADH or alterations in aquaretics (water channel regulating)
vasopressin receptor may be responsible for this effect.
Hyponatremia (Usually referred to Serum sodium < 135 mEq/L, but some pediatric references
use <130 mEq/L) may be associated with hypertonic, isotonic or hypotonic serum (Serum
osmolality < 275 mOsm/L). Hypertonic hyponatremia is associated with severe hyperglycemia
or mannitol administration. Isotonic hyponatremia, also called pseudohyponatremia, can result
from hypertriglycedemia and paraproteinemia. Hypotonic hyponatremia can be seen in
conditions with water intoxication, diarrhea, renal disorders, adrenal disorders, premature
kidneys, and SIAD.
In dehydration the infant would have loss of weight and more often has hypernatremia, while
iatrogenic hyponatremia does not occur with breast feeding or pre prepared standard formulas.
Occasionally inappropriately constituted (dilute formulas) can result in hyponatremia but these
are also often associated with failure to thrive and weight loss due to inadequate calories. In
congenital adrenal hyperplasia other symptoms such as ambigius genitilia (virilized female),
hypoglycemia and hypotension will be seen with elevated serum potassium.
Question 2. All the following would support the diagnosis EXCEPT:
a. lower BUN at 48 hrs than at birth
b. urinary sodium >40 mEq/L
c. urinary osmolality >100 mOsm/L
Bindya S Singh, MD FAAP
d. serum creatinine >2 mg/dl
Answer 2. d. Serum Creatinine >2 mg/dl.
SIADH is associated with inappropriately secreted anti-diuretic hormone which causes body to
retain water in excess of electrolytes. Therefore signs of hemodilution, such as lower hematocrit
and BUN are often seen. Additionally, concentrated urine, such as high urinary sodium and
osmolality in the face of serum hyponatremia is evident.
As described by Schwartz and Bartter in 1967, SIADH is a syndrome with 1.Hyponatremia and
hypo-osmolality; 2.No evidence of dehydration or edema; 3.Hypertonic urine; 4.Absence of renal
and adrenal or thyroid dysfunction. Therefore abnormal serum creatinine would suggest renal
dysfunction and would exempt the diagnosis of SIADH. Acute Tubular Necrosis and resultant
renal failure has been seen with sepsis and can result in hyponatremia in diuretic phase of the
condition.
Question 3. The most appropriate way to manage this condition in addition to treating underlying
sepsis would be:
a.
b.
c.
d.
Administer hypertonic saline (3%)
Fluid restriction
Administer diuretics
Give 30 calories per ounce formula
Answer 3. b. Fluid restriction
Most cases of SIAD resolve with fluid restriction, which assists in lowering the availability of
excess free water. Hypertonic saline should be avoided in neonates for concerns of infusing
hyperosmolal solutions causing rapid shifts in fluid compartments in the body. Similarly 30
calories per ounce formula is rarely required in term neonates and only occasionally diuretics are
used for SIAD.
Question 4. At 96 hrs the infant is noted to be unresponsive and has generalized tonic, clonic
seizures. Baby now weighs 3800 g and Serum sodium is noted to be 120 mEq/L. All of the
following may be required to treat the condition EXCEPT:
a.
b.
c.
d.
Increase sodium and chloride in IV fluids
IV Phenytoin
IV Furesomide
Rapid correction of serum sodium to 135 mEq/L
Answer 4. d. Rapid correction of serum sodium to 135 mEq/L
Severe hyponatremia (Serum sodium < 125 mEq/L) can be a life threatening condition, especially
if it develops acutely (less than 48 hrs). It can cause coma, seizures, respiratory arrest and death.
In acute hyponatremia, rapid correction of serum sodium may be undertaken without concern of
major shifts in cerebral fluid compartments and resultant complications such as IVH in premature
Bindya S Singh, MD FAAP
neonates and pontine demyelination in older patients. However in prolonged hyponatremia, there
is ionic adaptations in cerebral cells, which allows the brain to accommodate to osmolality
changes in the serum and maintain cerebral fluid volume. However acute correction of serum
osmolality in such a situation can cause rapid shifts in body fluid compartments and result in
complications. Since it is often uncertain how long the patient may have had hyponatremia
(unless serum sodium has been noted to become low from a previously documented normal
value), it is preferable not to completely correct hyponatremia rapidly. Therefore serum sodium
should be corrected at the rate of 1mEq/L per hour initially till symptoms are controlled to lower
morbidity and mortality. Thereafter hyponatremia should be corrected slowly at 0.5 mEq/L per
hour till it gets to normal value of greater than equal to 130 mEq/L.
IV Phenytoin is a drug of choice in seizures associated with hyponatremia in SIAD, since among
its mechanisms of actions, it inhibits calcium influx into posterior pituitary calls and suppresses
the secretion of ADH. IV Lasix is sometimes used in cases of excess fluid accumulation in
SIAD, because even though it causes sodium excretion, its effect on water diuresis is greater than
sodium loss in urine. Since hyponatremia in SIAD is a result of water dilution rather than body
sodium deletion, this effect of furosemide is useful in lowering the electrolyte dilution in the
serum. Newer drugs which are vasopressin-receptor antagonist such as Conivaptan (V1 and V2
blocker) and selective V2 receptor blockers such as Tolvaptan are being evaluated for chronic
cases of SIAD in older patients.
Question 5. If the underlying condition is adequately treated, which of the following is the most
likely long term outcome of this condition causing hyponatremia?
a.
b.
c.
d.
Complete resolution of the condition by the end of first week
Resolution of the condition by the end of second week
Intermittent hyponatremia till the end of third week
Chronic hyponatremia
Answer 5. a. Complete resolution of the condition by the end of first week
Studies looking at onset and duration of SIAD in patients with acute bacterial meningitis have
observed that the condition tends to be coincide with the initial phase of meningeal inflammation.
The condition usually resolves by the end of the first week in these patients. In conditions of
tubercular meningitis it can be present for several weeks and it may become a chronic concern in
cases of carcinomas and heart failure.
References:
1. The syndrome of inappropriate antidiuresis. David H Ellison, Thomas Berl. New England
Journal of Medicine 2007. 356(20);2064
2. Inappropriate secretion of antidiuretic hormone in acute bacterial meningitis. Ashok K
Patwari, Bindya S Singh, Deb E Manorama. Annals of Tropical Pediatrics 1995. 15;179
3. Hyponatremia. Horacid J Adrougue, Nicolads E Madias. New England Journal of Medicine
2008. 342(21);1581
4. Efficacy of phenytoin against hyponatremic seizures due to SIADH after administration of
anticancer drugs in a neonate. Miho Okamato, Yasushi Nako, Atushi Tachibana et al. Journal of
Perinatology 2002. 22,247
Bindya S Singh, MD FAAP
5. Diseases of the fetus and infant. Richard J Martin, Avroy A Fanaroff, Michelle C Watch. 8th
Edition, 2006. Mosby Elsevier, Philadelphia, PA.
Bindya S Singh, MD FAAP