© copyright annals of internal medicine, 2015 ann int med. 163 (3): itc3-1. * for best viewing:...
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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
in the clinic
Hyponatremia
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is hyponatremia?
Disorder of water balance
Occurs when more water ingested than kidneys can excrete
Ability to excrete a large volume of dilute urine is compromised
Kidney disease
Diuretics
Low protein intake
Presence of arginine vasopressin
Amount of free water excreted is determined by urine volume, sodium, and potassium
Free water is excreted if urinary sodium + potassium < plasma sodium
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Who is at risk for hyponatremia?
Endurance athletes
Institutionalized patients with schizophrenia
People who consume large quantities of fluid but little protein
People with severe kidney disease
Certain drugs (diuretics, particularly thiazide; SSRIs; SNRIs)
If posterior pituitary secretes AVP despite low plasma sodium
Hypovolemia or heart or liver disease
AVP secretion without osmotic and hemodynamic stimulus
Syndrome of inappropriate antidiuretic hormone secretion
Common in hospitalized patients
Hospitalized children receiving hypotonic fluids
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What potential measures can prevent or limit the severity of hyponatremia?
Encourage runners to drink fluids only when thirsty
Monitor body weight to avoid weight gain during exercise
Check plasma sodium after initiating thiazides, SNRIs, SSRIs
Check 1 to 2 weeks after initiating therapy
Avoid thiazides in persons with high fluid or low protein intake and during acute illness
Measure plasma sodium in hospitalized patients on admission
Treat low sodium based on the underlying cause
Avoid hypotonic fluids and thiazides
Monitor daily in patients with hyponatremia and in those at increased risk
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
CLINICAL BOTTOM LINE: Prevention... Hyponatremia is common in patients who:
Participate in endurance exercise
Receive thiazides, SSRIs, or SNRIs
Have congestive heart failure, cirrhosis, or pneumonia
Admitted to the ICU
Elderly patients
Avoid hypotonic fluids in hospitalized patients at increased risk
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What characteristic symptoms or physical findings should alert clinicians to the diagnosis of hyponatremia?
Mild hyponatremia
Subtle neurocognitive deficits
Deficits improve when plasma sodium is normalized
Moderate hyponatremia
Nausea, confusion, headache, vomiting
Severe hyponatremia
Delirium; impaired consciousness; seizures
Rarely: cardiorespiratory arrest
Consider hyponatremia in the differential diagnosis of patients with osteoporosis, falls, and hip fractures
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What conditions should clinicians consider when evaluating patients with hyponatremia?
Major Causes of Hyponatremia Based on Volume Status
Hypovolemia: Extrarenal losses
Vomiting, diarrhea, sweating
Pancreatitis
Small bowel obstruction
Hypovolemia: Renal losses
Diuretics, osmotic diuresis
Cerebral salt wasting, salt-losing nephritis
Addison disease—continued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Hypervolemia
Heart failure
Liver disease with cirrhosis
Nephrotic syndrome
Chronic kidney disease
Euvolemia
Primary polydipsia
Decreased solute excretion
Diuretics
Hypothyroidism
Cortisol deficiency
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Essential
Decreased effective osmolality of the extracellular fluid
Inappropriate urinary concentration in presence of decreased effective serum osmolality
Clinical euvolemia, as defined by the absence of signs of hypovolemia or hypervolemia
Absence of urinary sodium conservation when salt and water intake are normal
Absence of other potential causes of euvolemic hypoosmolality: hypothyroidism, hypocortisolism, diuretics
—continued
Criteria for the Diagnosis of SIADH
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Supplemental
Plasma uric acid <4 mg/dL
Blood urea nitrogen <10 mg/dL
Fractional sodium excretion >1%; fractional urea excretion >55%
Abnormal water load test
Plasma AVP level inappropriately elevated relative to plasma osmolality
No significant correction of plasma sodium with volume expansion but improvement after fluid restriction
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Common Causes of SIADHTumors
Pulmonary/mediastinal (e.g., small cell carcinoma)
Other cancers (e.g., duodenal, stomach, pancreatic, bladder)
Lymphoma
Ewing sarcoma
Central nervous system disorders
Mass lesions (e.g., tumors, brain abscesses)
Inflammatory diseases (e.g., encephalitis, meningitis)
Degenerative or demyelinating diseases
Miscellaneous: subarachnoid hemorrhage, head trauma, psychosis, delirium tremens, pituitary stalk section, transsphenoidal adenomectomy, hydrocephalus, cerebrovascular accident, cavernous sinus thrombosis
—continued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Drug-induced
Stimulated AVP release (narcotics, nicotine, phenothiazines)
Direct renal effects or potentiation of AVP antidiuretic effects (desmopressin, oxytocin, prostaglandin synthesis inhibitors)
Mixed/uncertain actions (carbamazepine, chlorpropamide, SSRI, clofibrate, clozapine, cyclophosphamide, ecstasy, vincristine)
Pulmonary diseases
Infections
Mechanical or ventilatory (e.g., acute respiratory failure, asthma)
Other
Rocky Mountain spotted fever
AIDS and AIDS-related complex
Nausea, pain, stress, prolonged strenuous exercise
Mutations of the aquaretic vasopressin receptor Idiopathic
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is the overall approach to the diagnosis of hyponatremia?
Initial evaluation
Measure plasma osmolality, glucose, urea, creatinine, and potassium
Measure urine osmolality, sodium, and chloride (if the patient is vomiting)
Base further diagnostic workup on initial evaluation results
Identifying cause of hyponatremia is often difficult
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is the role of volume status, urine osmolality, and urinary sodium in the evaluation of patients with hyponatremia? Measure urine osmolality in hypotonic hyponatremia
<100 mOsm/kg H2O: polydipsia, decreased solute excretion usual cause
<100 mOsm/kg H2O: may also occur after volume resuscitation with hypovolemic hyponatremia (if measured after administration of isotonic saline)
>200 mOsm/kg H2O: AVP playing a role if kidney function normal and patient not receiving diuretics
Determine cause of AVP secretion
Classify volume status based on history and physical: hypovolemia, clinical euvolemia, or hypervolemia
Subdivide hypovolemia: extrarenal or renal sodium losses
—continued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Clinical euvolemia vs. mild hypovolemia
Water retention may make patient seem euvolemic
Hypovolemia: urinary sodium <30 mEq/L
Euvolemia: urinary sodium >30 mEq/L
Hypovolemic hyponatremia vs. SIADH with salt depletion
If urinary sodium <20 and >20 mEq/L or <40 mEq/L
Hypovolemic hyponatremia: improves after normal saline
Salt-depleted SIADH: plasma sodium doesn’t normalize after administration of normal saline
Hypervolemia due to HF, cirrhosis, nephrotic syndrome
Base diagnosis on history and physical exam
Urinary sodium <30 mEq/L unless on diuretics
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is the role of imaging studies in the diagnosis of hyponatremia?
Chest radiography
Unexplained SIADH: to identify potential underlying cause
Chest computed tomography
Consider for smokers
Magnetic resonance imaging of the brain
If physical exam reveals neurologic abnormalities after plasma sodium is normalized
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
When should clinicians consult with a nephrologist or endocrinologist?
Cause of hyponatremia is unknown
Guidance for evaluation of SIADH
Guidance on use of normal saline in patients with possible SIADH and plasma sodium levels <120 mEq/L
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
CLINICAL BOTTOM LINE: Diagnosis... Identifying the cause of hyponatremia can be challenging
Often difficult to distinguish whether patient is slightly volume depleted or euvolemic
If volume status uncertain, saline infusion may be useful
Before diagnosing SIADH
Stop thiazides to determine effect on plasma sodium
Rule out secondary adrenal insufficiency and hypothyroidism
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is the overall approach to treatment of hyponatremia?
Acute: duration known to be <48 h
Endurance exercise, psychogenic polydipsia, drug use, colonoscopy preparation, and postoperative states
Can lead to cerebral edema with risk for brain herniation
Urgent normalization of sodium levels is needed
Chronic: duration unknown or >48 h
Patients predisposed to brain damage if hyponatremia corrected too rapidly
Hyponatremia severity classification (mEq/L)
U.S.: mild: 130-135, moderate 120-129, severe <120
European: mild 130-135; moderate 125-129, severe <125
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
How should sodium levels be corrected in acute and severely symptomatic hyponatremia?
Difficult to predict rate of correction of plasma sodium
Acute or severely symptomatic chronic hyponatremia
Rapidly reverse cerebral edema by increasing plasma sodium by 5 mEq/L
Chronic hyponatremia
Do not raise plasma sodium level >10 mEq/L within 24 h and/or >18 mEq/L within 48 h
Set goal of therapy well below therapeutic limit
Recommended rates of correction in patients at high risk for osmotic demyelination: 4-6 mEq/L per day
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What is the treatment of patients with chronic asymptomatic hyponatremia?
Hypovolemia due to GI losses and sweating
Isotonic saline; consider concomitant desmopressin
Diuretics
Discontinue; if no improvement administer isotonic saline
Addison disease
Isotonic saline; glucocorticoid and mineralocorticoid replacement
Glucocorticoid insufficiency
Glucocorticoid replacement
—continued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Primary polydipsia
Restrict water; discontinue diuretics and any drug known to cause SIADH
If volume-depleted or decreased solute excretion, cautiously administer isotonic saline and consider desmopressin (if no access to fluids) initially or if rapid increase in urine output and/or plasma sodium
Decreased solute intake
Same treatment as for polydipsia
Additionally: increase electrolytes and protein in the diet
Heart failure
Restrict water, salt; loop diuretics in fluid overload cases
Cirrhosis with ascites
Restrict water and salt; administer diuretics; possible albumin infusion with diuretics
—continued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
Nephrotic syndrome
Restrict water and salt; diuretics
If clinically decreased effective circulating volume, administer albumin with diuretics
Chronic kidney disease
Restrict water, salt; loop diuretics if fluid overload present
SIADH
Discontinue diuretics and any drug known to cause SIADH
Restrict water but not salt; consider oral urea, salt tablets, furosemide with salt tablets, and demeclocycline if water restriction ineffective
Don’t use vaptans unless benefit is greater than risk and only approved for 1 month of use (FDA guidelines)
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What are manifestations of the osmotic demyelination syndrome and who is at risk?
If chronic hyponatremia is corrected too rapidly
Brain unable to rapidly recover organic solutes lost in adaptation to hyponatremia
Neurologic symptoms occur 2-6 days after correction
Risk factors
Initial plasma sodium <105 mEq/L; hypokalemia
History of alcoholism, malnutrition, advanced liver disease
Increase in plasma sodium >10 mEq/L within 24 h and >18 mEq/L within 48 h
If cause of hyponatremia reversible, plasma sodium may increase more than intended
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
When should patients be hospitalized for management of hyponatremia?
Hyponatremic patients who are symptomatic
Confusion, headache, vomiting, and seizures
Acute hyponatremia
Plasma sodium level <125 mEq/L
Risk factors for ODS
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
How should clinicians counsel patients about salt and fluid intake and when to seek clinical care?
Treatment of hypervolemic hyponatremia due to HF
Restrict dietary salt to 1.5 to 3.0 g/day
Restrict fluids to 1.5 to 2 L/day unless hyponatremia worsens
Treatment of SIADH
Limit fluids ≈800 mL/day
Do not restrict salt intake
Patients should seek care if they experience altered mental status, falls, or persistent nausea
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
What other therapies are used in the management of hyponatremia?
Sodium chloride tablets
Furosemide (Lasix)
Urea
Demeclocycline
Tolvaptan
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
If fluid restriction unsuccessful in managing plasma sodium in hyponatremia
Concerns about increased risk for rapid correction of plasma sodium and lack of mortality benefit
Concerns about hepatotoxicity
US FDA: Limit use to 1-month
US FDA: Limit use with plasma sodium <125 mEq/L unless symptomatic + no response to fluid restriction
To avoid overcorrection, use vaptans alone
Not in conjunction with other treatment for hyponatremia
Check plasma sodium levels every 6-8 h during initiation and don’t initially restrict fluid intake
When should clinicians consider use of vasopressin-receptor antagonists?
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
When should clinicians consult a nephrologist or endocrinologist for treatment of hyponatremia?
Considering administration of hypertonic saline or vaptans
Hyponatremia is acute, severe, or symptomatic
Patients have risk factors for ODS
Patients have had overly rapid correction
Patients require long-term therapy
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 163 (3): ITC3-1.
CLINICAL BOTTOM LINE: Treatment... Hospitalization
Patients with acute or severe hyponatremia Patients with moderate to severe symptoms
Acute hyponatremia Administer hypertonic saline to rapidly correct plasma sodium
levels even if asymptomatic Monitor closely Don’t increase >10 mEq/L within 24 h or 18 mEq/L within 48 h Use lower rates of sodium correction in those at risk for ODS Risk factors for ODS Initial plasma sodium level <105 mEq/L Hypokalemia Alcoholism or malnutrition Advanced liver disease