HYPONATREMIA IN CRITICALLY

ILL PATIENTS

Dr Nevin S Thomas
Guide:Dr Bhaimangesh Naik
 Hyponatremia is defines as a serum Sodium <
135me /L.
 Hyponatremia is seen in 15-30% in hospital
setting especially in intensive care units.
PATHOGENESIS

 Results from the inability of the kidney to

excrete a water load or excess water intake.
 Water intake depends upon thirst
mechanism.
 Thirst is stimulated by increase in osmolality.
 Thirst is sensed by osmoreceptors located in
the hypothalamus and it leads to the release
of anti diuretic hormone ( vasopressin) from
the posterior pituitary
 Vasopressin(ADH) acts on the V2 receptors
located in the collecting duct cells and leads
to increased aquaporin expression on the
luminal aspect of the collecting duct cells
which increases water absorption and
abolishes thirst.
Hyponatremia occurs if there is persistent ADH
stimulation which is seen in the following
conditions.
1. Normal but persistent ADH secretion –In
volume depletion, the effect of decreased
volume counteracts the effect
hypoosmolality and ADH stimulation
continues to occur.
 Effective arterial blood volume depletion occurs
by 2 mechanisms: True volume depletion; and in
edematous patients with heart failure or
cirrhosis in whom tissue perfusion is reduced
because of a low cardiac output or arterial
vasodilation, respectively.
 The reduction in tissue perfusion is sensed by
baroreceptors at 3 sites : In the carotid sinus and
aortic arch, glomerular afferent arterioles, atria
and ventricles
 As a result there is water retention
2. Abnormal ADH secretion e.g; SIADH
Symptoms

 Acute hyponatremia is characterized by onset

of symptoms < 48 hrs. Patients with acute
hyponatremia develop neurologic symptoms
resulting from cerebral edema induced by
water movement into the brain.
 Chronic hyponatremia: Serum Sodium
concentration is usually above 120mew/L.
Mild hyponatremia – nausea, vomiting, loss
of appetite. Hypontremia in the elderly may
manifest with frequent falls and git
disturbances.
CLASSIFICATION

HYPONATREMIA

Normal serum High serum osmolality

Low serum osmolality
osmolality
Hypo-tonic Hypertonic
Iso-tonic
True hyponatremia >295 mosm/kg
280-296 mosm/kg

Hyperlipidemia Hyperglycemia
True hyponatremia
Hyperproteinemia Mannitol
 Normal serum osmolality is 280-295
mosm/kg.
 The serum osmolality (S Osm) can be
calculated by the concentration in millimoles
per liter of the major serum solutes according
to the following equation:
 Sosm (mmol/kg) = (2 × serum [Na]) + (serum
[glucose]/18) + (blood urea nitrogen/2.8).
 Pseudo (normo-osmolal) or isotonic
hyponatremia is due to presence of
hypertriglyceridemia or increase in plasma
proteins in conditions such as multiple myeloma.
 In normal subjects, the plasma water is 93
percent of the plasma volume, fats and proteins
account for the remaining 7 percent.
 Plasma water fraction falls below 80 percent in
cases with marked hyperlipidemia (triglycerides
>1500 mg/dL) or hyperproteinemia (protein >10
g/dL).
 Here, the plasma water sodium concentration
and plasma osmolality are unchanged, but
the measured sodium concentration in the
total plasma volume is reduced since the
specimen contains less plasma water.
 Translocational (hyperosmolal) or hypertonic
or redistributive hyponatremia is due to
presence of osmotically active solutes in the
serum e.g., mannitol or glucose.
 True (hypoosmolal) hyponatremia is
associated with reduction in serum osmolality
and is further classified as
 Euvolemic,
 Hypervolemic
 Hypovolemic
Diuretic-induced
hyponatremia:
 Hyponatremia is common with use of thiazides,
begins soon after initiation of thiazides, may be
severe and is common in elderly females.
 Thiazide-induced hyponatremia, occurs due to
increased water intake, reduction in diluting
ability and water excretion in distal tubule.
 Sodium plus potassium concentration in urine
exceeds that in the plasma, which directly lowers
plasma sodium concentration.
Hypervolemic hyponatremia

 It is seen in congestive heart failure and

cirrhosis of liver, nephrotic syndrome and
chronic kidney disease.
 Even though the plasma and extracellular
volumes is increased in heart failure and
cirrhosis, there is ADH stimulation.
 The development of hyponatremia is a poor
prognostic sign.
Diagnosis of hyponatremia

 Drug and diet history, history of volume loss

i.e. diarrhea, vomiting should be noted.

Determination of volume status i.e.

dehydration, oedema, ascites should be
carried out. Patients with clinical signs of
volume depletion (e.g. orthostatic decreases
in blood pressure and increases in pulse rate,
dry mucus membranes, decreased skin
turgor) should be considered hypovolemic.
Management
The ultimate danger is brain stem herniation when
sodium levels
 <120 meq/l. The source of free water identified and
eliminated.
Patients with seizures, severe confusion, coma or signs of
brain stem herniation should receive hypertonic (3%)
saline to correct serum sodium level towards normal but
only enough to arrest the progression of symptoms.
An increase in serum sodium level of 4-6 meq/l is
sufficient.
Any further correction is dangerous and be
avoided unless necessary to correct continued
seizures or other severe CNS abnormality.
Patients with chronic hyponatremia and severe
symptoms(severe confusion, coma, seizures) should
receive hypertonic saline only to raise the serum
sodium level by 4-6 meq/l and to arrest seizure .
Regardless of the therapy, serum sodium be
monitored and corrected no faster than 10-12 meq/l
in the first 24hrs and 18 meq/l in the first 48 hours.
A goal increase of 1.5-2meq/l/hr for 3-4 hours until
symptoms resolve but not to exceed 10meq/l in the first
24 hours appears to be safe.
The 3% saline infused at the rate of <0.05ml/kg body
wt per min; the effect be monitored every 2 hrs and
infusion be stopped when serum sodium increases by 12
meq/l or to 130meq/l, whichever comes first.
Formulas for
correcting
Hyponatremia
1. Sodium Deficit is calculated as: TBW * (140-serum sodium)
2. To estimate the effect of 1 litre of any infusate containing Na+
and K+ on serum Na+ is : Change in serum Na+= (infusate
sodium + infusate potassium)- serum sodium / (Total Body
Water +1)
1. ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
2. ΔSNa is a change in Serum Na
3. [Na + K]inf is infusate Na and K concentration in 1 liter of
solution
3. TBW=0.6 body weight for males and 0.5 body weight for
females.
 Hyponatremia

Infusate Infusate Na+ Infusate K+

5% Saline 855 mmol/L 0

3% 513 mmol/l 0

0.9% Saline 154mmol/l 0

Ringer Lactate 130mmol/l 4

0.45% saline 77mmol/l 0

5% Dextrose 000 0
Example
If one wants to correct a Na+= 108 meq/l in a 70 kg man
with hypertonic saline, then the change in serum sodium
with 1 L of this fluid will be {(513+0)-108} /
(0.6*70+1)= +9.4 meq/L

This means to correct Na+ at rate of 2meq/L/hr, 200

ml/hr of hypertonic saline needs to be given as
(2meq/l/hr)/(9.4meq/l)per thousand ml of saline =
200ml/hr approx.
But not to exceed 1000ml [(10meq/l/hr) / 9.4
meq/l per thousand ml of saline] in 24 hours.
Osmotic demyelination
syndrome
The syndrome is due to rapid correction
or overcorrection of chronic
hyponatremia.
Chronic hyponatremia causes efflux of organic osmolytes
(creatine,betaine,glutamate,myo-inositol and taurine)
from brain cells to reduce the intracellular osmolality and
osmotic gradient favouring water entry.
However re-accumulation of these organic osmolytes
by brain cells is delayed and not in sync with the
correction of hyponatremia,resulting in loss of
oligodendrogliocytes and ODS.
Osmotic demyelination syndrome
Some investigators note that osmotic demyleination
may be a form of hypoxic encephalopathy associated
with hyponatremia and not a complication of therapy.
Symptoms of osmotic demyelination - dysarthria,
dysphagia, diplopia, seizures, altered mental status,
quadriparesis (locked in syndrome), hypotension, begin
1-3 days after correction of serum sodium .
Patients with hypokalemia, female gender,
malnutrition or history of alcoholism or liver
transplant, seem to be particularly prone to develop
osmotic demyelination.
Treatment of chronic
Hyponatremia

Water deprivation is cornerstone of therapy.

The urine:plasma electrolyte ratio(urine Na+urine K/plasma Na) is
indicator of electrolyte free water excretion
Patients with ratio >1 require aggressive fluid restriction of <500
ml/day, with ratio 1 need restriction to 500-700ml/day and <1 ratio
requires fluid restriction to <1L /day
In hypokalemia potassium replacement increases plasma sodium
concentration as plasma sodium is a function of both exchangable Na
and exchangable K divided by total body water.
Plasma sodium concentration also responds to an increase in dietary
solute intake as it increases the ability to excrete free water.
Chronic Hyponatremia
Patients in whom fluid restriction, potassium replacement and
increased dietary solute intake fails may require pharmacological
therapy.
SIADH respond to a combination of oral furosemide 20 mg twice
a day ; furosemide inhibits the countercurrent mechanism and
blunts the urinary concentrating ability while salt tablets
counteract diuretic associated natriuresis.
Vasopressin(V2 receptor) antagonists(conivaptan and
tolvaptan)are highly effective in treating SIAD and hypervolemic
hyponatremia due to heart failure or cirrhosis by increasing
free water clearance.
Demeclocycline antagonises the effect of ADH and can also be
used, azotemia and photosensitivity being its side effects.
 Hypovolemic
Hyponatremia
If symptoms are mild to moderate, treat with
isotonic saline, monitor serum sodium levels
frequently to ensure that serum sodium level
increases slowly.
Correcting any K+ deficit ,as occurs, not uncommonly
in this type, will further increase plasma sodium.
V2 receptor antagonists are not suitable for
hypovolemic causes of hyponatremia, acute
hyponatremia, cerebral salt wasting syndrome,
psychogenic polydypsia/protamania and others.
Hypervolemic
hyponatremia
Treatment consists of restriction of sodium and
water intake, correcting K+, promotion of water
loss in excess of Na using loop diuretics and
correcting the underlying cause.
The vasopressin antagonists conivaptan and
tolvaptan are now approved for use in
hospitalised patients with hypervolemic
hyponatremia, though clinical experience is
scant.
Euvolemic
hyponatremia
Treatment consists of free water restriction,
promoting free water excretion using loop
diuretics and correction of the underlying
condition causing SIAD.
Conivaptan (vaprisol) given I.V and Oral
tablets of tolvaptan(samsca) show promise as
effective and well tolerated therapy for SIAD.
Demeclocycline 150-300 mg TDS and
Fludracortisone 0.05-0.2 mg BD are also used.
Prevention
Hyponatremia that is acquired in the hospital is
largely preventable.
A defect of water excretion can be present on
admission, or it can worsen or develop during the
course of hospitalisation as a result of hypotonic fluids
and several anti-diuretic influences (e.g. medications,
organ failure and the post-operative state).
The presence of such a defect notwithstanding
hyponatremia will not develop as long as the intake of
electrolyte free water does not exceed the capacity for
water excretion plus insensible losses.