Download Approach To A Patient With Hyponatremia

Approach To A Patient With Hyponatremia
A Muruganathan
INTRODUCTION
H
yponatremia is defined as a decrease in the serum sodium
concentration to a level below 136 mmol per liter. Whereas
hypernatremia always denotes hypertonicity, hyponatremia
can be associated with low, normal, or high tonicity. Serum
sodium concentration and serum osmolarity normally
are maintained under precise control by homeostatic
mechanisms involving stimulation of thirst, secretion of
antidiuretic hormone (ADH), and renal handling of filtered
sodium.
FREQUENCY
 Most common electrolyte disorder
 Incidence of approximately 1%
 Prevalence of approximately 2.5%
 Surgical ward, approximately 4.4%
 30% of patients treated in the intensive care unit
 Hyponatremia's prevalence is lower in the ambulatory
setting.
SEX
No sexual predilection exists. However, symptoms are more
likely to occur in young women > men
AGE
 Infants fed tap water in an effort to treat symptoms of
gastroenteritis.
 Infants fed dilute formula in attempt to ration.
 Elderly patients with diminished sense of thirst,
especially when physical infirmity limits independent
access to food and drink.
 More common in elderly persons.
 Due to increased incidence of comorbid conditions (eg,
cardiac, hepatic, or renal failure)
PATHOPHYSIOLOGY
Increases in serum osmolarity above the normal range
(280-300 mOsm/kg) stimulate hypothalamic osmoreceptors,
which, in turn, cause an increase in thirst and in circulating
levels of ADH. ADH increases free water reabsorption from
the urine, yielding urine of low volume and relatively high
osmolarity and, as a result, returning serum osmolarity to
normal. ADH is also secreted in response to hypovolemia,
pain, fear, nausea, and hypoxia.
Aldosterone, synthesized by the adrenal cortex, is regulated
primarily by serum potassium but also is released in response
to hypovolemia through the renin-angiotensin-aldosterone
axis. Aldosterone causes absorption of sodium at the
distal renal tubule. Sodium retention obligates free water
retention, helping to correct the hypovolemic state. The
healthy kidney regulates sodium balance independently
of ADH or aldosterone by varying the degree of sodium
absorption at the distal tubule.
Hyponatremia Types and Causes
Hypovolemic hyponatremia, Euvolemic hyponatremia,
Hypervolemic hyponatremia, Redistributive hyponatremia,
Pseudohyponatremia
Hypovolemic hyponatremia
Hypovolemic hyponatremia develops as sodium and free
water are lost and replaced by inappropriately hypotonic
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fluids, such as tap water, half-normal saline, or dextrose
in water.
Total body water (TBW) decreases. Total body sodium (Na+)
decreases to a greater extent. The extracellular fluid (ECF)
volume is decreased.
Nonrenal loss:
GI losses, Vomiting, Diarrhea, fistulas, Third spacing of
fluids, Ascites, peritonitis, pancreatitis, and burns, Excessive
sweating.
Cerebral salt-wasting syndrome seen in patients
with traumatic brain injury, aneurysmal subarachnoid
hemorrhage, and intracranial surgery. Prolonged exercise
in a hot environment, especially in patients who hydrate
aggressively with hyposmolar fluids during exertion. Severe
symptomatic hyponatremia has been reported in marathon
runners and in recreational hikers.
Renal Loss
Acute or chronic renal insufficiency, in which the patient
may be unable to excrete adequate amounts of free water
Salt-wasting nephropathy
Euvolemic hyponatremia
TBW increases while total sodium remains normal. The ECF
volume is increased minimally but without the presence of
edema.
Causes
Drugs/Tumors  continuous ADH secretion or increased
action of ADH
Associated with …
CNS:
Encephalitis, Meningitis, Head trauma, Brain Abscess,Brain
tumors, CVA. Peripheral neuropathy, Subarachnoid Hge,
Guillian Barre Syndrome, Multiple sclerosis.
Carcinomas:
Bronchogenic Ca, Mesothelioma. Ca duodenum, pancreas,
stomach, Bladder, ureter, prostate.
Pulmonary:
Pneumonias,Tuberculosis, Asthma, Pulmonary abscess,
Positive pressure Ventilation, Pneumothorax.
Others:
HIV, Idiopathic (elderly), Prolonged Exercise. Acute
intermittent porphyria Surgery.
MEDICATIONS
Known offenders include acetazolamide, amiloride,
amphotericin, aripiprazole, atovaquone, thiazide diuretics,
amiodarone, basiliximab, angiotensin II receptor blockers,
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angiotensin-converting enzyme inhibitors, bromocriptine,
carbamazepine, carboplatin, carvedilol, celecoxib,
cyclophosphamide, clofibrate, desmopressin, donepezil,
duloxetine, eplerenone, gabapentin, haloperidol, heparin,
hydroxyurea, indapamide, indomethacin, ketorolac,
levetiracetam, loop diuretics, lorcainide, mirtazapine,
mitoxantrone, nimodipine, oxcarbazepine, opiates,
oxytocin, pimozide, propafenone, proton pump inhibitors,
quetiapine, sirolimus, ticlopidine, tolterodine, vincristine,
selective serotonin reuptake inhibitors, sulfonylureas,
trazodone, tolbutamide, venlafaxine, zalcitabine, and
zonisamide. Psychogenic polydipsia, often in psychiatric
patients. Administration of hypotonic intravenous or
irrigation fluids during procedures or in the immediate
postoperative period
Infants who may have been given inappropriate amounts
of free water. Ingestion of sodium phosphate or sodium
picosulfates and magnesium citrate combination as a bowel
preparation before colonoscopy or colorectal surgery.
Uncorrected hypothyroidism or cortisol deficiency (adrenal
insufficiency, hypopituitarism). Consumption of large
quantities of beer or use of the recreational drug MDMA
(ecstasy)
Hypervolemic hyponatremia
Total body sodium increases. TBW increases to a greater
extent. The ECF is increased markedly, with the presence of
edema. This may result from renal causes such as acute or
chronic renal failure, when dysfunctional kidneys are unable
to excrete the ingested sodium load. It also may occur in
response to states of decreased effective intravascular
volume. History of hepatic cirrhosis, congestive heart
failure, or nephrotic syndrome, in which patients are subject
to insidious increases in total body sodium and free water
stores
Redistributive hyponatremia
Water shifts from the intracellular to the extracellular
compartment, with a resultant dilution of sodium. The TBW
and total body sodium are unchanged. This condition occurs
with hyperglycemia. Administration of mannitol
Pseudohyponatremia
The aqueous phase is diluted by excessive proteins or lipids.
The TBW and total body sodium are unchanged.
Hypertriglyceridemia. Multiple myeloma
Approach to Hyponatremia
For the diagnosis and treatment of a given hyponatremia
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the clinical evaluation has to include a careful medical
history, a physical examination with attention to the
patient’s extracellular fluid volume status and laboratory
measurements.
Symptoms:
Patients with clinically significant hyponatremia present
with nonspecific symptoms attributable to cerebral
edema. These symptoms, especially when coupled with a
peripheral edema, or ascites suggest hypervolemic
hyponatremia due to excess retention of sodium and free
water (ie, cirrhosis, nephrotic syndrome, congestive heart
failure). Other nonspecific signs include muscle weakness
and cramping. Rhabdomyolysis is an occasional consequence
of hyponatremia and should be considered in patients with
muscle pain or tenderness.
LABORATORY TESTS FOR THE DIFFERENTIAL DIAGNOSIS
OF HYPONATREMIA
Preliminary tests
Serum osmolality Urine osmolality or urine specific gravity
Urine levels of sodium and creatinine, and calculation
of fractional excretion of sodium (FENa+)* Serum levels
of potassium, chloride and bicarbonate Serum levels of
glucose, urea, creatinine, total proteins, triglycerides and
uric acid Serum levels of thyroid-stimulating hormone and
cortisol.
Brain CT Scans
Effects of Hyponatremia on the Brain and Adaptive
Responses.
recent history of altered fluid balance, should suggest the
possibility of hyponatremia. Anorexia, Nausea and vomiting,
Difficulty concentrating, Confusion, Lethargy, Agitation,
Headache, Seizures.
Physical
Most abnormal findings on physical examination are
characteristically neurologic in origin. Level of alertness
ranging from alert to comatose. Variable degrees of
cognitive impairment (eg, difficulty with short-term recall;
loss of orientation to person, place, or time; frank confusion
or depression). Focal or generalized seizure activity. In
those patients with acute severe hyponatremia, signs of
brainstem herniation, including coma; fixed, unilateral,
dilated pupil; decorticate or decerebrate posturing;
sudden severe hypertension and respiratory arrest. In
addition to neurologic findings, patients may exhibit signs
of hypovolemia or hypervolemia. Dry mucous membranes,
tachycardia, diminished skin turgor, and orthostasis suggest
hypovolemic hyponatremia due to excessive loss of body
fluids and replacement with inappropriately dilute fluids.
Pulmonary rales, S3 gallop, jugular venous distention,
Normal Study
Fataly Hyponatremia
CT head, EKG, CXR
Additional tests
Arterial blood gases if serum bicarbonate level is abnormal
Urine levels of urea and uric acid, and calculation of
their fractional excretion for the differential diagnosis of
hypovolemia versus SIADH.
Plasma osmolality: Normally ranges from 275 to 290 mosmol/
kg. If >290 mosmol/kg: Hyperglycemia or administration
of mannitol. If 275 - 290 mosmol/kg: Hyperlipidemia or
Hyperproteinemia
In the hypo-osmolar state (serum osmolality less than 280
mOsm/kg), urine osmolality is used to determine whether
water excretion is normal or impaired. A urine sodium level
less than 20 mmol/L is indicative of hypovolemia, whereas a
level greater than 40 mmol/L is suggestive of the syndrome
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of inappropriate antidiuretic hormone secretion.
Urine osmolality: Normal value is > 100 mosmol/kg. Normal
to high: Hyperlipidemia, hyperproteinemia, hyperglycemia,
SIADH. FeNa-Help to determine pre-renal from renal causes
MANAGEMENT
The key to effective management of hyponatremia is
establishing the type and its cause, so that the cause can
be removed, if possible, and the management will be
appropriate. The treatment of hyponatremia is determined
by 3 major factors: severity of hyponatremia, that is, the
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presence or absence of severe central nervous system
symptoms such as lethargy, delirium, seizure, and coma;
onset of hyponatremia: acute (within 48 hours) or chronic
(_48 hours); and volume status.
Prehospital Care
Hyponatremia is necessarily a hospital-based diagnosis, but
patients may exhibit signs of severe neurologic dysfunction
during prehospital evaluation and transport. Address acute
life-threatening conditions and initiate supportive care.
Diagnosis-Algorithm
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Establish reliable intravenous access and give supplemental
oxygen to patients with lethargy or obtundation. In these
patients, evaluate the possibility of hypoglycemia with
a rapid glucose check. Administer intravenous glucose to
hypoglycemic patients.
Administer standard prehospital anticonvulsant therapy
to patients experiencing seizures. Seizures secondary to
hyponatremia are unlikely to respond to this therapy, but
it should be administered until a definitive diagnosis and
therapy are available.
Intubate and initiate hyperventilation to reduce intracranial
pressure in patients exhibiting signs of brainstem herniation
(eg, obtundation; fixed, unilateral, dilated pupil; decerebrate
or decorticate posturing) until a more definitive therapy
can be initiated. Avoid giving hypotonic intravenous fluids
because they may exacerbate cerebral edema.
Emergency Department Care
The ultimate danger for these patients is brainstem
herniation when sodium levels fall below 120 mEq/L. The
source of free water must be identified and eliminated.
Patients with seizures, severe confusion, coma, or signs of
brainstem herniation should receive hypertonic (3%) saline to
rapidly correct serum sodium level toward normal but only
enough to arrest the progression of symptoms. An increase
in serum sodium level of 4-6 mEq/L is generally sufficient.
Any further correction is potentially dangerous and must be
avoided unless necessary to correct continued seizures or
other severe CNS abnormality.
Chronic hyponatremia must be managed with extreme care.
Treatment of chronic hyponatremia has been associated with
the development of the osmotic demyelination syndrome
(also known as central pontine myelinolysis) characterized
by focal demyelination in the pons and extrapontine areas
associated with serious neurologic sequelae.
The estimated total body water (in liters) is calculated as a
fraction of body weight. The fraction is 0.6 in children; 0.6
and 0.5 in nonelderly men and women, respectively; and 0.5
and 0.45 in elderly men and women, respectively. Normally
extracellular and intracellular fluids account for 40 and 60
percent of total body water, respectively.
The syndrome is caused by overly rapid correction or
overcorrection of chronic hyponatremia. Some investigators
note that osmotic demyelination often develops when
chronic hyponatremia is complicated by hypoxia and
believe that osmotic demyelination may be a form of
hypoxic encephalopathy associated with hyponatremia
and not a complication of therapy. Until further data are
available, management should include meticulous attention
to adequate oxygenation and a gradual increase in serum
sodium level to 120-125 mEq/L. Serum sodium level should
not be allowed to reach normal levels or hypernatremic
levels within the first 48 hours.
Symptoms of osmotic demyelination (eg, dysarthria,
Formulas For Use In Managing Hyponatremia And Charecteristics Of Infusates
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dysphagia, seizures, altered mental status, quadriparesis,
hypotension) typically begin 1-3 days after correction of
serum sodium level. Patients with hypokalemia, female
gender, or history of alcoholism or liver transplant seem to
be particularly prone to develop osmotic demyelination.
Exercise extreme caution in treating hyponatremia in these
subgroups.
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Pharmacological Rx of Chronic Asymptomatic
Hyponatremia
Patients with chronic hyponatremia and severe symptoms
(eg, severe confusion, coma, seizures) should receive
hypertonic saline but only enough to raise the serum sodium
level by 4-6 mEq/L and to arrest seizure activity.
Anecdotal reports suggest that therapeutic relowering of the
serum sodium level with hypotonic fluids and desmopressin
(DDAVP) may help avert neurologic sequelae in patients
whose chronic hyponatremia is inadvertently corrected
too quickly.
Regardless of the therapeutic approach, serum sodium
must be monitored closely and corrected no faster than
10-12 mEq/L in the first 24 hours and 18 mEq/L in the first
48 hours.
Hypovolemic hyponatremia: If symptoms are mild to
moderately severe, treat with isotonic saline; monitor serum
sodium levels frequently to ensure that the serum sodium
level increases slowly.
Because most hyponatremia is caused by the non-osmotic
release of vasopressin, the availability of vasopressin
antagonists is exciting and may change the management
of hyponatremia completely. V2-receptor antagonists are
not suitable for certain causes of hyponatremia, such as
cerebral salt wasting syndrome, psychogenic polydipsia/
potomania, and others.
Hypervolemic hyponatremia: Treatment consists of sodium
and water restriction and attention to the underlying
cause. The vasopressin receptor antagonists conivaptan
(Vaprisol) and tolvaptan (Samsca) are now approved for use
in hospitalized patients with hypervolemic hyponatremia,
though clinical experience is scant.
Euvolemic hyponatremia: Treatment consists of free water
restriction and correction of the underlying condition.
convivaptan, tolvaptan show promise as effective and welltolerated intravenous therapy for SIADH.
Clozapine appears to be effective in the long-term
treatment of schizophrenic patients with compulsive
water drinking.
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
hospitalization as a result of several antidiuretic influences
(e.g., medications, organ failure, and the postoperative
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.
Prognosis
Prognosis is dependent on the underlying condition and the
severity of disease.
Medicolegal Pitfalls
Failure to consider the possibility of sampling or analysis
error, hyperglycemia, hyperproteinemia, or hyperlipidemia
before making the diagnosis of hypovolemic hyponatremia
Failure to recognize high-risk groups, including elderly
patients, patients on diuretics, infants, postoperative
patients, and patients with malignancy. Failure to quickly
recognize severe acute hyponatremia and to correct it
promptly, allowing ongoing risk of brainstem herniation.
Correcting serum sodium level too rapidly in patients with
chronic hyponatremia (in excess of 0.5 mEq/L/h or 12 mEq/
L/d), thereby incurring the risk of osmotic demyelination
syndrome.
TAKE HOME MESSAGES
It is a more a disorder of water balance than sodium itself.
Look for hyponatremia in a drowzy patient when cause is
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unclear. Always look for in an unconscious icu patient. Look
for offending drugs (diuretics ..,). “Start low - go slow”
applies for hypertonic saline treatment. Avoid hypertonic
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Hyponatremia: Clinical Diagnosis and Management By Yeong-Hau
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Medicine Aug.2007
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