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. History of fluid loss: vomiting, diarrhea, diuretic therapy History of low protein intake and/or high fluid intake. History consistent with one of the causes of SIADH Use of medications associated with hyponatremia Symptoms and signs suggestive of adrenal insufficiency or hypothyroidism Signs of peripheral edema and/or ascites, which can be dueto heart failure, cirrhosis, or renal failure

Signs & Symptoms : Absent symptoms – Asymptomatic, if the hyponatremia is chronic and of mild or moderate severity (i.e., serum sodium >120 meq/L). Patients may have subclinical impairments in mentation and gait. Mild to moderate symptoms –Relatively nonspecific and include: Headache Nausea, vomiting Fatigue Gait disturbances Confusion in patients with chronic hyponatremia (i.e., >48 hours duration). Severe symptoms – Severe symptoms of hyponatremia include: Seizures Obtundation Coma Respiratory arrest More profound when the decrease in sodium is very large or occurs rapidly (i.e. over hours)

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 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 In all hyponatremia patients the serum sodium initially be increased by 4 to 6 mEq/L during the first 24 hours Patients receiving emergency therapy their serum sodium measured every two hours to ensure increase at the desired rate Hyponatremia: Hyper-acute Acute Severe Moderate symptomatic Severe symptoms: 100 mL of 3% NaCl infused intravenously over 10 minutes × 3 as needed Mild to moderate symptoms, Patients at low risk for herniation: 3% NaCl infused at 0.5–2 mL/kg/h   All admitted to hospital

Treatment Hyponatremia Chronic hyponatremia: (known duration >48 hours) Avoid osmotic demyelination syndrome the treatment includes: High risk of ODS: Minimum correction of serum Na by 4-8 mmol/L per day, with a lower goal of 4-6 mmol/L per day. Normal risk of ODS: Maximum correction of 10-12 mmol/L in any 24-hour period; 18 mmol/L in any 48-hour period Patients should have their serum sodium measured often enough to ensure an appropriate rate of correction  Chronic hyponatremia is more at risk from rapid correction of hyponatremia The urine output should also be monitored

Treatment Hyponatremia Hypervolemic Hyponatremia (SIADH) First-line treatment for patients with SIADH and moderate or profound hyponatremia should be fluid restriction. (500 mL/d below the 24-hour urine volume) Second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day of urea or combined treatment with low-dose loop diuretics and oral sodium chloride Hypovolemic Hyponatremia: For patients with reduced circulating volume, extracellular volume should be restored with an intravenous infusion of 0.9% saline or a balanced crystalloid solution at 0.5 to 1.0 mL/kg per hour

Treatment Hyponatremia Normovolemic Hponatremia: For normovolemic (euvolemic), asymptomatic hyponatremic patients, free water restriction (<1 L/d) is generally the treatment of choice. Pharmacologic treatment: Demeclocycline is a drug of choice to increase the diluting capacity of the kidneys, by achieving vasopressin antagonism and a functional diabetes insipidus. Demeclocycline is contraindicated in cirrhotic patients.

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