2. Introduction
Hyponatremia is commonly defined as a serum sodium
concentration below 135meq/L but can vary to a small
degree in different clinical laboratories.
3. DETERMINANTS OF THE SERUM SODIUM
CONCENTRATION
"tonicity" (effective plasma osmolality) refers to the osmotic activity of
solutes that do not easily cross cell membranes and therefore determine the
transcellular distribution of water
The extracellular and intracellular fluids are in osmotic equilibrium,
so plasma tonicity is equal to the effective intracellular osmolality and to the
effective osmolality of the total body water (TBW)
Plasma tonicity = (Extracellular solute + Intracellular solute)
——————————————————————
TBW
4. Exchangeable sodium salts (Nae) are the primary effective extracellular
solute and exchangeable potassium (Ke) and its associated intracellular anions
are the primary intracellular solutes; these solutes are the major
determinants of the effective plasma osmolality
Approximately 30 percent of total body sodium and a smaller fraction of total
body potassium are nonexchangable and therefore not osmotically active
Thus, plasma tonicity (effective plasma osmolality) can be expressed as:
Plasma tonicity ≈ (2 x Nae + 2 x Ke)
———————————
TBW
5. CLASSIFICATION
According to serum ADH levels — Urinary excretion of a water load
requires the suppression of ADH release, which is mediated by the reduction
in serum osmolality . An inability to suppress ADH release is the most common
cause of hyponatremia and can be seen in the following settings:
HYPONATREMIA
INABILITY TO
SUPRESSS ADH
release
1. True volume depletion-
GI losses vomiting, diarrhea.
Renal losses- thiazide and loop diuretic.
2.Decrease tissue perfusion-
reduce CO in HF
systemic vasodilation in cirrhosis.
3.Primary increase in ADH increase- SIADH
Appropriate
suppression of
ADH
1. Primary polydipsia
2low dietary sodium intake
3 advance renal failure
6. According to volume status
According to
volume status
Hypovolumia
1. GI losses
2. Renal losses
Normovolumia
1.SIADH
2.Primary polydipsia
3.Low dietary solute
Hypervolumia
1.Heart failure
2.cirrhosis
8. Signs and symptom
Primarily neurological.
Related to severity and particularly rapidity of changes in
the serum sodium concentration.
9. Clinical manifestations of acute
hyponatremia
<125 -130 meq/L Nausea malaise
<115 -120 meq/L Headache, lethargy, obtundation
and eventually seizures, coma,
and respiratory arrest, non
cardiogenic pulmonary edema is
also described.
Acute hyponatremic encephalopathy may be reversible, but permanent
neurologic damage or death can occur, particularly in premenopausal women
11. Osmolytes and cerebral adaptation to
hyponatremia
The initial cerebral edema raises the interstitial
hydraulic pressure, creating a gradient for extracellular
fluid movement out of the brain into the cerebrospinal
fluid
Then brain cell looses solute K+ through normally
quiescent cation channel and subsequently organic
osmolytes are lost via swelling –activated membrane
channels
Substantial depletion of brain organic osmolytes
occure within 24 hours,and additional losses occurs
over 2-3 days owing to downregulation of synthesis and
uptake of these osmolytes.
12. Clinical manifestations of chronic
hyponatremia
The cerebral adaptation permits patients with chronic hyponatremia to
appear to be asymptomatic despite a serum sodium concentration below
120mmol/L. When symptoms occurs they are relatively nonspecific.
Fatigue
Nausea
Dizziness
Gait disturbances
Forgetfulness
Confusion
Lethargy
Muscle cramps
13. Evaluation of patient with hyponatremia
• A history of fluid loss (eg, vomiting, diarrhea, diuretic therapy) and,
on examination, signs of extracellular volume depletion, such as
decreased skin turgor, a low jugular venous pressure (which is not
diagnostic), or orthostatic or persistent hypotension.
● A history of low protein intake and/or high fluid intake.
● A history consistent with one of the causes of SIADH, such as small cell
carcinoma or central nervous system disease
● Use of medications associated with hyponatremia.
● Signs of peripheral edema and/or ascites, which can be due to heart
failure, cirrhosis, or renal failure
● Symptoms and signs suggestive of adrenal insufficiency or
hypothyroidism.
HISTORY AND EXAMINATION
15. Finding in SIADH
A low serum osmolality
An inappropriately elevated urine osmolality (above 100 mosmol/kg and
usually above 300mosmol/kg)
A urine sodium concentration usually above 40 meq/L
Low blood urea nitrogen and serum uric acid concentration
A relatively normal serum creatinine concentration
Normal acid-base and potassium balance
Normal adrenal and thyroid function
16. MANAGEMENT
SODIUM DEFICIT FORMULA
Although sodium itself is restricted to the extracellular fluid, changes in the
serum sodium concentration reflect changes in osmolality and are distributed
through the total body water. TBW is estimated as lean body weight times
0.5 for women and 0.6 for men
Sodium deficit = TBW x (desired serum Na - actual serum Na)
17. Approach therapy of Hyponatremia
Patient risk stratification:
1. duration of hyponatremia
2. severety of hyponatremia
3. symptom of patient
18. Duration of hyponatremia
Hyperacute Within previous few hours
Acute Within previous 24 hr
Subacute Within 24- 48 hours
Chronic Within >48 hours
19. 2. Severity of hyponatremia
Mild hyponatremia Serum sodium between 130-135
meq/L
Moderate hyponatremia Serum sodium between 121-129
meq/L
Severe hyponatremia Serum sodium between
<120meq/L
20. 3. Presence of symptoms
Absent symptoms Frequently
Mild to moderate symptoms Non specific nausea vomiting
fatigue gait disturbance and
confusion
Severe symptoms Seizure , obtundation, coma ,
respiratory arrest.
21. Disposition
Acute or hyperacute hyponatremia,
most patients with severe
hyponatremia, and many
symptomatic patients with
moderate hyponatremia
In patient department
Mild hyponatremia and
asymptomatic patients with
moderate hyponatremia
Usually donot require
hospitalisation
22. Hyponatremia therapy
Emergent therapy
1. Severe symptomatic- seizure ,
obtundation
2 .Patients with acute hyponatremia
who have symptoms due to
hyponatremia, even if such symptoms
are mild
3 .Patients with hyperacute
hyponatremia due to self-induced water
intoxication, even if there are no
symptoms at the time of initial
evaluation
4 .Symptomatic patients who have
either acute postoperative
hyponatremia or hyponatremia
associated with intracranial pathology
Non-emergent therapy
1. Asymptomatic patients with acute or
subacute hyponatremia
2.Patients with severe hyponatremia
(ie, serum sodium ≤120 meq/L) who
have either absent or mild to moderate
symptoms
3.Patients with moderate
hyponatremia who have mild to
moderate symptoms
23. Goals of therapy
Emergent therapy
rapidly increase the serum
sodium by 4 to 6 meq/L over a
period of several hours. However,
the increase in serum sodium
should not exceed 8 meq/L in
any given 24-hour period.
Non-emergent therapy
slowly raise the serum sodium
and alleviate symptoms. In
general, raising the serum
sodium by 4 to 6 meq/L should
improve a patient's symptoms.
The increase in serum sodium
should not exceed 8 meq/L in
any given 24-hour period
24. Choices of initial therapy
Emergent therapy
(4 to 6 meq/L increase should be
achieved as soon as possible.)
100 mL of 3 percent saline given as
an intravenous bolus. If severe
neurologic symptoms persist or
worsen, or if the serum sodium is
not improving, a 100 mL bolus of 3
percent saline can be repeated one
or two more times at 10-minute
intervals.
Non emergent therapy
choice of therapy depends the
severity and underlying cause.
chronic severe hyponatremia who
have mild to moderate symptoms ,
*initially with hypertonic saline slow
infusion at 15 to 30 mL/hour, or 50
mL bolus can be used.
*concurrent hypertonic saline and
desmopressin (1 to 2 mcg I.V or S/C
every eight hours for 24 to 48
hours).
25. :Chronic moderate hyponatremia who have mild to moderate symptoms,
and in asymptomatic patients with chronic severe hyponatremia,our choice
of initial therapy depends upon the underlying disease
Patient with edematous
states(HF/cirrhosis),SIADH,advanc
e renal disease,primary polydipsia
Fluid restriction with fluid intake
less than 800ml/day
Patient with heart failure and
patient with SIADH who have high
urinary cation concentration
Loop diuretic ,
Vassopressin receptor antagonist
Patient with true volume
depletion
Isotonic saline.
Diuretic induced hyponatremia or
drug induced SIADH
Discontinue responsible
medication.
26. Regimen of hypertonic saline with or without
desmopressin in the nonemergent setting
Asymptomatic patients with acute hyponatremia and mildly or moderately
symptomatic patients with chronic severe hyponatremia should generally
receive hypertonic saline. the total elevation in serum sodium should be 4 to
6 meq/L and no more than 8 meq/L in any given 24-hour period
Acute asymptomatic hyponatremia 50 mL hypertonic saline over 10
minutes. Two or three additional
boluses of 50 to 100 mL can be given
if symptoms develop and/or the
serum sodium does not improve.
Severe chronic hyponatremia with
mild or moderate symptoms
I.V. inf. hypertonic saline at 15 to
30 mL/hour, usually in combination
with desmopressin at 1 to 2 mcg IV or
SC q8h for 24 to 48 hours. The
infusion rate should be titrated,
aiming for a correction rate of
6 meq/L per day.*
*Frusemide can be given with hypertonic saline in edematous patient
*Desmopressin should not be used in self induced water intoxication edematous pt and pt with known chronic SIADH.
27. CONDITION IN WHICH HYPERTONIC SALINE IS NOT REQUIRED
chronic moderate hyponatremia who have mild to moderate
symptoms,
asymptomatic patients with severe hyponatremia.
*Fluid restriction,±loop
diuretic,vasopressin receptor
antagonist occasionally
28. PREDICTING THE RATE OF CORRECTION
Predictive formulas and their limitations — Formulas have been proposed to
estimate the direct effect of a given fluid (eg, hypertonic saline) on the serum
sodium (SNa) concentration, for example
Potassium added to the solution should be included in formula
Because TBW in liters is approximately 0.5 x body weight in kg and because each
mL of 3 percent (hypertonic) saline contains 0.5 meq of sodium, a simplified
version of the formula predicts:
Increase in SNa = (Infusate [Na] – SNa) ÷ (TBW + 1)
Increase in SNa = (Infusate [Na + K] – SNa) ÷ (TBW + 1)
1 mL/kg body weight of 3 percent saline = 1 meq/L increase in SNa
29. Osmotic demyelination syndrome
Overly rapid correction of hyponatremia(almost
always 120 meq/L or less and 115 meq/L
Demyelination is more diffuse and does not
neccesorly involve pons.
manifestations of ODS are typically delayed for
two to six days after overly rapid elevation of the
serum sodium concentration
dysarthria, dysphagia, paraparesis or
quadriparesis, behavioral disturbances, lethargy,
confusion, disorientation, obtundation, and
coma; seizures may also be seen but are less
common. Severely affected patients may become
"locked in"; they are awake, but are unable to
move or communicate
30. Monitoring of therapy
Patients receiving emergent therapy should have their serum sodium
measured every two hours.
patients who are treated for chronic hyponatremia in the hospital should
have their serum sodium measured every four hours.
the urine output should be monitored, and, if increasing, the urine osmolality,
urine sodium, and urine potassium should be measured. An increase in urine
output and a decrease in the urine cation concentration can signify that the
rate of correction is accelerating.
If the risk of overly rapid correction is low, the frequency of measurements
can be reduced, but measurements should still be taken at least every 12
hours until the serum sodium is 130 meq/L or higher.
If desmopressin is given concurrently with hypertonic saline, the
frequency of monitoring can be reduced to every six hours once the desired
rate of correction has been achieved because, with this regimen, there is a
lower likelihood of inadvertent overly rapid correction.
31. Choice of therapy in case of SIADH
SEVERE SYMPTOMS Hypertonic saline (100 ml I.V. 3% NaCl given as
bolus increases S. Na approximately 1.5 meq/L in
men and 2 meq/L in women.)
MILD TO MODERATE
SYMPTOMS
Initially hypertonic saline to raise the S. sodium @
1meq/L/hr may be justified in first 3-4 hours then
maintainance therapy
MAINTAINANCE THERAPY Fluid restriction 800 ml/day
Oral salt 3 grams or one and half tsf TDS, total dose
of 9 gms/day
33. PSEUDOHYPONATREMIA
Pseudohyponatremia, which is associated with a normal
serum osmolality, refers to those disorders in which
marked elevations in serum lipids or proteins result in a
reduction in the fraction of serum that is water and an
artificially low serum sodium concentration
Editor's Notes
N RANGE 275-290.
Desmopressin should not be used in self induced water intoxication edematous pt and pt with known chronic siadh.
