Dr. M. A. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin HYPONATREMIA Dr. M. A. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin

HYPONATREMIA Hyponatremia is commonly defined as a serum sodium concentration below 135 meq/L but can vary to a small degree in different clinical laboratories. The dilutional fall in serum sodium is in most patients associated with a proportional reduction in the serum osmolality (i.e., to a level below 275 mosmol/kg), but there are some exceptions Hyponatremia represents a relative excess of water in relation to sodium. It can be induced: Marked increase in water intake (primary polydipsia) Impaired water excretion from advanced renal failure Persistent release of antidiuretic hormone (ADH).

Acute hyponatremia: Developed within the previous 24 hours Hyperacute hyponatremia Developed over just a few hours due to a marked increase in water intake (self-induced water intoxication, as may be seen in marathon runners, psychotic patients, and users of ecstasy) Sub-acute : Developed within the previous 24 to 48 hours. Chronic hyponatremia: Present for more than 48 hours, or if the duration is unknown (such as in patients who develop hyponatremia at home). Mild to moderate and sever hyponatremia: Mild: Serum Na concentration 130 - 135 meq/L; Moderate: Serum Na concentration 121 - 129 meq/L. Severe: Serum sodium of 120 meq/L or less.

EVALUATION — The diagnostic approach consists of a directed history and physical examination, appropriate laboratory tests. A history of fluid loss (e.g., vomiting, diarrhea, diuretic therapy) and, on examination, signs of volume depletion, such as decreased skin turgor, a low jugular venous pressure 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. 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.

Signs & Symptoms More profound when the decrease in sodium is very large or occurs rapidly (i.e. over hours) Generally asymptomatic if Na+ level >125 Symptoms include: Headache Nausea, vomiting Muscle cramps Disorientation, depressed reflexes, lethargy, restlessness Seizure, coma, permanent brain damage, respiratory arrest, brainstem herniation & death

Symptoms : Hyponatremia Absent symptoms – Patients are frequently asymptomatic, if the hyponatremia is chronic and of mild or moderate severity (i.e., serum sodium >120 meq/L). However, such patients may have subclinical impairments in mentation and gait. Mild to moderate symptoms –Relatively nonspecific and include headache, nausea, vomiting, fatigue, gait disturbances, and confusion in patients with chronic hyponatremia (i.e., >48 hours duration). In patients with more acute hyponatremia, such symptoms should be considered ominous and may evolve without warning to seizures, respiratory arrest, and herniation. Severe symptoms – Severe symptoms of hyponatremia include seizures, obtundation, coma, and respiratory arrest.

Approach to Hyponatremia 1st assess volume status Is the patient volume overloaded, depleted, or euvolemic? 2nd assess osmolality (hyper, iso, or hypo) Is the blood concentrated? For hypotonic hyponatremia, continue to 3rd step: 3rd assess urinary sodium excretion and FeNa % Is the urine concentrated? *Remember VOU – volume status, osmolality, and urine studies

Laboratory tests : Three laboratory tests provide important initial information in the differential diagnosis of hyponatremia : Serum osmolality Urine osmolality Urine Na+, K+, and Chloride concentrations Serum osmolality (Sosm), (NR 275 to 290 mosmol/kg) is reduced in most hyponatremic patients. In some patients Sosm is high or normal. The three most common causes of hyponatremia with a high or normal Sosm Marked hyperglycemia Severe azotemia Alcohol intoxication

STEP 1 – (V) Volume Status 1st assess volume status (extracellular fluid volume) Hypotonic hyponatremia has 3 main etiologies: Hypovolemic – both H2O and Na decreased (H20 < Na) Consider obvious losses from diarrhea, vomiting, dehydration, malnutrition, etc. Euvolemic – H20 increased and Na stable Consider SIADH, thyroid disease, primary polydipsia Hypervolemic – H20 increased and Na increased (H2O > Na) Consider obvious CHF, cirrhosis, renal failure

STEP 2 - (O) Osmolality 2nd assess osmolality hyper, iso, or hypo Hypotonic hyponatremia = warrants further workup, when there is no obvious fluid overload or depletion Serum Osmolality: Calculated serum osmolality (2 X serum [Na]) + [glucose, in mmol/L] + [urea, in mmol/L] Hypertonic - >295 hyperglycemia, mannitol, glycerol Isotonic - 280-295 pseudo-hyponatremia from elevated lipids or protein Hypotonic - <280 excess fluid intake, low solute intake, renal disease, SIADH, hypothyroidism, adrenal insufficiency, CHF, cirrhosis, etc.

STEP 3 – (U) Urine Studies For euvolemic hyponatremia, check urine osmolality Urine osmolality <100 - excess water intake Primary polydipsia, tap water enemas, post-TURP Urine osmolality >100 - impaired renal concentration SIADH, hypothyroidism, cortisol deficiency Check urine sodium & calculate FeNa % A low urine sodium (<10) and low FeNa (<1%) implies the kidneys are appropriately reabsorbing sodium A high urine sodium (>20) and high FeNa (>1%) implies the kidneys are not functioning properly

Diagnosis of the underlying aetiology of the hyponatraemia using this system relies on an accurate assessment of the patient's volume status and measurement of urinary [Na+].  Urine [Na+] <20 mmol/L Urine [Na+] >40 mmol/L Hypovolaemia (dry tongue, decreased CVP, increased urea, increased pulse, decreased BP) Vomiting, diarrhoea, skin losses, burns Diuretics, Addison's, cerebral salt-wasting syndrome, salt-losing nephropathy Euvolaemia Hypothyroidism Any cause + hypotonic fluids SIADH Glucocorticoid deficiency Drugs Hypervolaemia (oedema, ascites, LVF, increased JVP, increased CVP) CCF, cirrhosis Nephrotic syndrome Renal failure, any cause + diuretics BP = blood pressure; CCF = congestive cardiac failure; CVP = central venous pressure; LVF = left ventricular failure; JVP = jugular venous pressure; SIADH = syndrome of inappropriate secretion of antidiuretic hormone.

Treatment Hyponatremia Patients with acute or hyper-acute hyponatremia, most patients with severe hyponatremia, and many symptomatic patients with moderate hyponatremia should be treated in the hospital Emergency therapy Patients with severe symptoms such as seizures or obtundation. Patients symptomatic with acute hyponatremia. even if such symptoms are mild. Patients with hyperacute hyponatremia due to self-induced water intoxication, even if there are no symptoms at the time of initial evaluation. Symptomatic patients who have either acute postoperative hyponatremia or hyponatremia associated with intracranial pathology.

Treatment Hyponatremia Patients with acute or hyper-acute hyponatremia, most patients with severe hyponatremia, and many symptomatic patients with moderate hyponatremia should be treated in the hospital Patients with severe hyponatremia (i.e., serum sodium ≤120 meq/L) who have either absent or mild to moderate symptoms. initial treatment with hypertonic saline Patients with moderate hyponatremia who have mild to moderate symptoms. Initial therapy depends in large part upon the underlying etiology. Non-emergency therapy Asymptomatic patients with acute or sub-acute hyponatremia: Initial treatment with hypertonic saline rather than other therapies.

Treatment In all hyponatremic patients the serum sodium initially be increased by 4 to 6 meq/L during the first 24 hours and by less than 9 meq/L over any given 24-hour period. Patients receiving emergency therapy their serum sodium measured every two hours to ensure increase at the desired rate. Other patients who are treated for chronic hyponatremia in the hospital should have their serum sodium measured often enough to ensure an appropriate rate of correction and to allow the clinician to react quickly to impending overly rapid correction (e.g., every four hours). The urine output should also be monitored

Severe symptomatic hyponatremia If the patient is making large volumes of urine, serum sodium may be rising too quickly. This can be accomplished by giving desmopressin to slow urinary free water loss while simultaneously giving hypotonic fluids. An intravenous bolus of 100 mL of 3% saline is given and repeated if symptoms persist after 10 minutes. Once symptoms improve, the rate of sodium correction in 24 hours with this regimen should not exceed 6 to 8 mEq/L in 24 hours or 12 to 14 mEq/L in 48 hours. Check serum sodium every two hours and monitor urine output closely

Asymptomatic or mildly symptomatic hyponatremia Euvolemic Hyponatremia: Typically caused by SIADH- high Uosm (>100 mosm/L) and a high UNa (>30 mEq/L). Free water restriction, and fluid at least 500 mL below a patient’s urine output. If this is ineffective, salt tabs can be given to increase the solute load. Nine grams of salt tabs in 3 divided doses (equivalent to 1 L of NS). Patients with highly concentrated urine (Uosm >500 mosm/L) will not respond to the salt load. In such patients, a loop diuretic can be used to help excrete free water.

Asymptomatic or mildly symptomatic hyponatremia In addition, ACEI can improve hyponatremia in CHF by reducing ADH levels and improving cardiac output via after-load reduction. Hypervolemic Hyponatremia: caused by CHF, cirrhosis, or NS. ADH is in all cases. In CHF and cirrhosis, the degree of hyponatremia is a marker of disease. Fluid restriction is the cornerstone of therapy If the patient’s volume status is not optimized, then loop diuretics may improve hyponatremia through excretion of diluted urine.

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