|Year : 2019 | Volume
| Issue : 3 | Page : 62-68
Hyponatremia: A clinician's perspective
Department of Medicine, Kasturba Medical College, Manipal, Karnataka, India
|Date of Submission||26-Oct-2018|
|Date of Acceptance||01-Apr-2019|
|Date of Web Publication||15-Jul-2019|
Dr. Sudha Vidyasagar
Department of Medicine, Kasturba Medical College, Manipal, Karnataka
Source of Support: None, Conflict of Interest: None
Hyponatremia is a commonly encountered clinical problem by all physicians. It is classified according to volume status as hypovolemic, euvolemic, or hypervolemic hyponatremia. The clinical presentation depends on the type of hyponatremia and the speed of onset. Acute hyponatremias can result in altered sensorium, convulsions, and coma, making it a medical emergency. Chronic hyponatremias can be due to drugs and several systemic illnesses. The syndrome of inappropriate secretion of antidiuretic hormone is common and can occur in several diseases as euvolemic hyponatremia. Its onset can be deceptively slow but needs attention to prevent complications. Investigations of serum and urine, osmolality and sodium, help in classification of this condition. Apart from intravenous correction with hypertonic saline, which may be urgently needed in acute hyponatremia to prevent mortality, vaptans offer an oral option in chronic hyponatremia. Care must be taken to avoid rapid correction of serum sodium, to prevent osmotic demyelination syndrome.
Keywords: Correction of hyponatremia, Hyponatremia, SIADH
|How to cite this article:|
Vidyasagar S. Hyponatremia: A clinician's perspective. APIK J Int Med 2019;7:62-8
| Introduction|| |
Hyponatremia is commonly encountered in clinical practice and can be due to varied clinical conditions. It is especially common in critically ill patients and can account for 15%–30% of admissions in intensive care units. Patients can have serious consequences due to hyponatremia, including coma and death. Further, the causes of hyponatremia are varied, and the treatment varies according to the etiology and clinical setting. Hence, it is challenging for the physician, to find the cause of hyponatremia and treat on time, to save life.
Hyponatremia is defined as sodium concentration in the serum of <135 meq/L. The body maintains this concentration within this narrow range (normal range 135–145 meq/L) by a carefully coordinated system of water balance. All hyponatremia is due to problem in water balance and the inability of the kidney to handle water excretion, which is in turn dependent on the function of the antidiuretic hormone (ADH).
The osmoreceptors in the hypothalamus release ADH from the posterior pituitary in response to increasing osmolality. The ADH then leads to increased expression of aquaporin channels on the collecting duct cells which have V2 receptors. This leads to increased water absorption from the collecting ducts and restores the vascular volume. In addition, when osmolality is increased, the thirst mechanism is put in place, and the individual consumes more water. Both these mechanisms lead to restoration of osmolality, and thirst is then abolished. Hyponatremia is thus due to persisting ADH response which may be appropriate or inappropriate.
| Classification of Hyponatremia|| |
The first step in the approach to hyponatremia is the determination that the hyponatremia is real, and not apparent or pseudohyponatremia. This tends to occur when the plasma contains high amount of solutes, which could occupy plasma volume. These are triglycerides (TGs), plasma proteins, or glucose. However, the levels of these have to be very high, such as TG >1500 mg/dl, and proteins >10 g/dl, to affect the serum sodium.
Redistributive hyponatremia occurs when the blood sugar levels increase or due to the presence of substances such as mannitol, and the plasma contains more solutes. For example, when blood sugar levels rise, water is drawn into the vascular compartment expanding it, causing fall in sodium level.
For correction of blood sugar levels for assessing serum sodium, the formula used is as follows: the sodium concentration will fall by approximately 2 meq/L for each 100 mg/100 mL (5.5 mmol/L) increase in glucose concentration. However, these errors are avoided by using direct ion photometry, with ion selective electrodes. For TG, the formula will be 1 meq fall in serum sodium for every 500 mg/dl rise in TG above 100 mg/dl. For serum proteins, the serum sodium will fall by 4 meq/l for every 1 g rise in protein above 8 g/dl. The recognition of pseudohyponatremia is important to prevent unintentional aggressive correction, leading to complications.
Serum sodium and osmolality
Serum osmolality is calculated from the formula:
Calculated serum osmolality = (2 × SNa) + Glu + blood urea nitrogen
The absolute sodium concentration is not important in the diagnosis of hyponatremia, as the serum sodium concentration is a function of the volume status of the individual. Hence, hyponatremia is classified as hypovolemic hyponatremia, euvolemic hyponatremia, and hypervolemic hyponatremia. The normal serum osmolality is between 280 and 295 mosm/kg.
This occurs when the body loses water and sodium, but the sodium loss is more than the water loss. This leads to activation of ADH, which leads to water retention through the V2 receptors on the collecting ducts, leading to restoration of vascular volume and blood pressure. The causes of this condition can be renal losses or nonrenal losses.
The renal causes of hyponatremia are due to loss of sodium from the kidney. Causes such as use of diuretics is a classical example. Interstitial nephritis also leads to salt wasting due to tubular dysfunction, and the recovering phase of acute kidney injury also leads to loss of sodium in urine. Mineralocorticoid deficiency leads to sodium loss and potassium retention. Osmotic diuresis is due to loss of solutes in the urine dragging along water and salt. This happens in glucosuria, ketonuria in diabetes, alcoholism, starvation and bicarbonaturia in renal tubular acidosis.
A word of caution about considering all diuretics as having similar effects on serum sodium concentration. Thiazide diuretics cause much more sodium loss, as they do not inhibit the action of ADH on the distal tubules, leading to severe hyponatremia. Whereas loop diuretics do not cause much hyponatremia as they act on the thick ascending loop of Henle, inhibiting the counter current mechanism, and interfere with the concentrating capacity of the kidney, leading to a dilute urine. If at all it occurs, furosemide-induced hyponatremia tends to occur in the presence of another illness causing ADH rise and hyponatremia. Further, diuretic-induced hyponatremia occurs in the first 1–2 weeks of use and maintains a steady state after that.
Cerebral salt wasting syndrome is a specific entity, which causes inappropriate sodium loss from the kidney due to increased ADH. It is due to causes such as infections of central nervous system (CNS) such as meningitis and encephalitis, subarachnoid hemorrhage, and surgeries on the brain. The mechanism of this condition has been variously speculated as due to decreased sympathetic drive, and lower renin and aldosterone, leading to nonabsorption of sodium for proximal convoluted tubule. Another theory is that brain natriuretic peptide decreases sodium absorption and renin release causing the same consequences of salt wasting. All of these causes lead to hypovolemic hyponatremia, and this responds to rehydration with sodium chloride.
This is the most common cause of hyponatremia, accounting for about 60% of cases. The most important cause of this is syndrome of inappropriate ADH (SIADH). The diagnosis of this condition is based on several criteria which were described by Bartter and Schwartz. They are displayed in [Table 1]. The criteria are a mixture of exclusions such as establishing normal thyroid and adrenal functions, excluding diuretic use, renal dysfunction which could cause a rise in urea, normal potassium level, and normal acid–base balance.
|Table 1: Diagnostic criteria of syndrome of inappropriate antidiuretic hormone|
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However, the most important criterion is euvolemia. Thus, dehydration and edema would be major exclusions for this diagnosis. The serum osmolality is <275 mOmol/kg, establishing the dilution of the serum. This leads to hyponatremia, as the serum sodium is always in context with the amount of the water that is present in the extra cellular compartment. The urine is however hyperosmolar. ADH secretion should be shut off when the serum osmolality is below 280 mOsmols/kg. This will ensure that excess water is excreted and the serum osmolality is restored. However, in SIADH, the inappropriate secretion of ADH continues uninhibited, leading to retention of more water, making the serum hypoosmolar and decreasing the serum sodium. The urine osmolality is thence high, due to increased ADH.
There are four different types of SIADH, depending on the reason for the inappropriate secretion.
- Type A – Unregulated ADH, unrelated to serum osmolality
- Type B – Leak of ADH which is modest
- Type C – The serum sodium reset at a lower level at 125–135 meq/l and hence responds only at this level
- Type D – Due to a product other than ADH, acting like ADH, as these levels are normal. This is least common.
| Etiology of Syndrome of Inappropriate Anti Diuretic Hormone|| |
The causes of SIADH are as listed below:
- CNS disturbances
- Stroke, hemorrhage, trauma, psychosis
- Malignancies (ectopic production of antidiuretic hormone)
- Small cell carcinoma of lung, other lung tumors
- Head and neck cancer, olfactory neuroblastoma
- Extrapulmonary small cell carcinomas.
- Selective serotonin reuptake inhibitor, tricyclic antidepressants, antipsychotics, carbamazepine
- Vincristine, nonsteroidal anti-inflammatory drugs, ecstasy-3,4-methylenedioxymethamphetamine (MDMA), vasopressin analogs.
- Pulmonary disease
- Pneumonia (viral, bacterial, and tuberculosis [TB]), asthma, atelectasis
- Acute respiratory failure, pneumothorax, TB.
- Hormone deficiency
- Hypothyroidism, hypopituitarism.
- HIV, surgery, hereditary SIADH
- Nephrogenic syndrome of inappropriate antidiuresis
- Gain-of-function mutation in V2 receptor gene on X chromosome
- Exercise-associated hyponatremia
- Primary polydipsia.
The most common cause of ectopic ADH secretion is small cell carcinoma of the lung. Other causes include tumors of the head and the neck and olfactory tumors. Several drugs such as carbamazepine and fluoxetine can increase ADH release or action, whereas MDMA or ecstasy increases water intake, thus causing SIADH.
It is a syndrome associated with many psychiatric illnesses. In this condition, the patient continues to drink excess amount of fluids due to the primary psychiatric illness. The ADH secretion is suppressed, and the patient can produce up to 400–600 ml of urine per hour. This leads to excretion of excess water, leaving the serum sodium concentration only slightly above normal. However, if the patient continues to drink large amounts of water, the excretion capacity of the kidneys is exceeded and hyponatremia can occur. Since hypothalamic infiltrative diseases such as sarcoidosis can also present with primary polydipsia, these must be ruled out with a magnetic resonance imaging scan.
Patients who consume a lot of beer and have a low protein diet do not excrete much solute in the urine. These patients consume less salt (containing only 1–2 mEq) and low protein and excess carbohydrates which suppresses protein breakdown leading to very low urine solute load. In addition, these patients drink large amounts of beer which causes hyponatremia, especially if the fluid intake exceeds 4 L a day. It can also occur in patients who are nutritionally deprived, and those on extreme vegetarian diet. These patients have very low urine osmolarity (<100–200 mOsm/kg) with urine sodium of 10–12 mEq. The treatment of this condition is saline rehydration which leads to rapid correction of sodium levels. Resumption of normal diet is also helpful in reversing the condition.
| Hypervolemic Hyponatremia|| |
This occurs in conditions with fluid overload such as chronic kidney disease, nephrotic syndrome, congestive cardiac failure (CCF), and cirrhosis. In these conditions, there is retention of salt and water, the amount of water exceeding the amount of salt retained leading to hyponatremia. These disorders can be discriminated by measuring the urinary sodium, which is more than 20 mEq in patients with acute and chronic renal failure suggestive of inability of the kidney to reabsorb sodium. In conditions such as CCF and nephrotic syndrome and cirrhosis, the urinary sodium is <20 meq/L showing that the kidney is able to reabsorb sodium; however, the water content in the vascular compartment is in excess. Hyponatremia in these patients is associated with a bad prognosis as it indicates neurohormonal activation and dilution of vascular compartment. In cirrhosis too, hyponatremia added to other risk factors is a predictor of increased mortality.
However, the classification of hyponatremia is not as simple as described above, as there are practical problems in identifying the subgroups of patients. This is summarized in [Table 2].
| Clinical Features of Hyponatremia|| |
Hyponatremia causes movement of water from the vascular compartment into the cells causing swelling of the cells. The most dangerous consequence of this occurs in the brain as cerebral edema occurs inside a rigid skull. The adaptive response for this change would be to an increase in the interstitial pressure leading to shunting of solutes into the cerebrospinal fluid and thence into the systemic circulation. However, if there is no time given for this adaptation as in acute hyponatremic encephalopathy, which occurs within 48 h, the patient faces consequences of severe cerebral edema. The earliest symptoms are headache, nausea, and vomiting. If left untreated, the more serious complications such as altered sensorium, convulsions, coma, and herniation of brain stem can result leading to mortality.
One of the common causes of acute hyponatremia is postoperative administration of hypotonic solutions. This is compounded by the additional component of SIADH, due to the pain of the postoperative state. Other iatrogenic causes are recent administration of thiazides and preparation of colonoscopy. Exercise-induced hyponatremia is seen in marathon runners, due to excessive intake of water, with persistent ADH secretion.
Chronic hyponatremia is better adapted by the body by an efflux of solutes such as creatinine, glutamate and myoinositol and taurine from the brain cells. This leads to lesser water entry into the brain, over a longer period of time that is more than 48 h. This protection is however not complete and can be overwhelmed over a period of time. Patients with chronic hyponatremia thus present with nonspecific gastrointestinal symptoms such as loss of appetite, nausea, and vomiting at sodium levels of above 120 mEq/L. When the sodium dips below this, elderly patients may manifest instability and gait disturbances which can lead to falls. The causes of chronic hyponatremia are those described under SIADH.
| Diagnostic Workup of Hyponatremia|| |
The first step is to measure the serum sodium, with ion-specific electrode, with direct potentiometry. This will eliminate the causes of pseudohyponatremia. The second step is to measure the serum osmolality; along with this, blood sugars, TG, and proteins must be measured as routine as these may contribute to osmolality. Then, we have to measure the urine osmolality. When there is hyponatremia, there must be suppression of ADH secretion leading to excretion of very dilute urine that is <100 mOsm/kg, with a specific gravity of <1.003. In patients with urine osmolality of <100 mOSm/kg, a diagnosis of polydipsia must be entertained. If urine osmolality is more than 400, SIADH is strongly suggested.
Urine sodium must be measured next to determine the cause of hyponatremia. For this, we need to know the volume status of the patient. If the patient is hypovolemic, then we need to analyze if the loss of sodium is from renal or nonrenal sources. The nonrenal causes of hyponatremia are the gastrointestinal losses such as vomiting and diarrhea, or third space losses such as pancreatitis or burns. In all these, the urine sodium is <20 meq/l.
If there is renal loss of sodium, the urine sodium is >20 mEq/L. These causes include diuretic- or osmotic-induced sodium loss in urine, mineralocorticoid deficiency, proximal renal tubular acidosis, and cerebral salt wasting syndrome. In addition in patients with thiazide induced hyponatremia can have a higher than expected urine sodium concentration, confusing it with SIADH. To differentiate these conditions, the urine sodium must be interpreted only after 1–2 weeks of discontinuation of thiazides.
If the patient is euvolemic, the urine sodium is usually >20 meq/L, suggesting SIADH. Before labeling this as SIADH, hormonal deficiencies such as hypothyroidism, hypopituitarism, and hypocortisolism must be ruled out, stress and drugs being other important causes. Serum urea and uric acid are decreased in SIADH due to the water retention. Serum urea is usually <5 mg/d, and uric acid is <4 mg/dl. Patients with beer potomania have urine sodium <20 and urine osmolarity between 100 and 200 mosm/L.
In hypervolemic states such as renal failure, the urine sodium is >20 meq/L, whereas in conditions such as cardiac failure with the kidney reabsorbing the sodium, the urine sodium is <20 meq/L.
The urine to serum electrolyte ratio is the sum of urine sodium plus potassium concentration divided by serum sodium concentration. A ratio of <0.5 (high urine electrolyte-free water) suggests that the fluid restriction is adequate. If the ratio is more than 1, that is the urine is hypotonic in respect to serum, it suggests that the water restriction is not adequate and other measures will be needed to correct the hyponatremia.
Measurement of potassium levels may give a clue to the cause of the hyponatremia. A metabolic alkalosis and hypokalemia will suggest a diuretic use and vomiting, whereas a metabolic acidosis and hypokalemia may be due to diarrhea. Hyperkalemia and metabolic acidosis are features of primary adrenal insufficiency. In SIADH, the potassium is normal and there is no acid–base disorder.
Measurement of copeptin, which is cleaved from vasopressin precursor, has been used as a surrogate to measure the levels of vasopressin. This novel marker has been used recently to differentiate hypovolemic and euvolemic hyponatremia. However, the specificity and sensitivity of this is yet to be determined.
| Treatment of Hyponatremia|| |
The treatment of hyponatremia depends on several factors such as if the hyponatremia is acute or chronic and the severity of the hyponatremia. The division between acute and chronic is 48 h. Severe hyponatremia is a serum sodium concentration of <120 mEq/L, moderate is between 120 and 129 mEq/L, and mild is between 130 and 134 mEq/L.
Obviously the symptoms of hyponatremia will have a huge role on the urgency of correction; severe hyponatremia manifests as seizures and altered sensorium and coma, which can lead to death. This is especially true in acute hyponatremia where the brain does not have the time to adapt to cerebral edema and may result in coning and death.
Formulae used for calculation of sodium deficit
Several formulae have been used to calculate the total amount of sodium to be infused for correction of hyponatremia. The most common is the Adrogue–Madias formula which is:
Increase in serum sodium = (infusate sodium − serum sodium)/(total body water [TBW] +1)
TBW = lean body mass × 0.5 in women, and lean body mass × 0.6 in men.
Yet another formula is sodium deficit = TBW × (desired sodium − actual sodium)
Currently, these formulae are not in favor, as the estimated deficit may vary, and the calculations may not reflect the actual rise in sodium. Hence, it is better to monitor frequently, and adjust, rather than depend on a single formula. Further, it is well known that infusing normal saline for hyponatremia may worsen the hyponatremia, a process called desalination. Hence, there is consensus that the deficit should not be corrected using normal saline.
| Treatment of Acute Hyponatremia|| |
This is usually due to unusual exercise, psychogenic polydipsia, postoperative state (especially in women and children), use of drugs such as MDMA (ecstasy), haloperidol, desmopressin, thiazide diuretics, and intravenous (IV) cyclophosphamide.
The treatment recommended for these patients is rapid treatment with boluses of 3% saline (100 ml over 10 min × 3) according to the United States guidelines. The European guidelines recommends a higher dose of 3% saline (150 ml over 20 min, 2–3 times). This treatment strategy has changed from continuous infusion of saline to boluses because in acute hyponatremia, we need fast correction. Further boluses avoid the overcorrection that can happen with continuous infusion since they correct only partially and the rate of correction can be readjusted after measuring sodium levels.
| Treatment of Chronic Hyponatremia|| |
In chronic hyponatremia, if the patient is symptomatic neurologically or has serum sodium <125 mEq/L, aggressive therapy with 3% saline is indicated; however, the speed of correction has to be monitored as patients run the risk of osmotic demyelination syndrome (ODS). This was previously called central pontine myelinolysis, and the name was changed as it was recognized that the demyelination could be elsewhere in the brain also.
Osmotic demyelination syndrome
As mentioned above, this could be a consequence of overzealous correction of hyponatremia. It can have disastrous permanent consequences such as quadriparesis and locked in syndrome. The risk is greatest when the sodium concentration is really low, that is, below 120 meq/L. It is also more common in chronic hyponatremia than in acute hyponatremia. In addition, alcoholics and malnourished patients have a much higher risk compared to normal hosts. Further, ODS typically occurs 2–6 days after rapidly corrected sodium values.
There has been considerable debate regarding what should be the ideal rise in serum sodium per day in patients with chronic hyponatremia. Both the American and the European guidelines agree that this should be around 10 mEq/L/day.,, Patients with alcoholism and malnutrition and hypokalemia are at higher risk for ODS; hence, the USA guidelines recommend a lower rate of correction at 8 meq/L/day in this subgroup. Adrogue and Madias have proposed even lower limit such as 6–8 mEq/L/day to avoid ODS. It is well known that serum sodium concentration during correction is not predictable even with calculated formulae and hence must be monitored every 4–6 h, and correction rate readjusted. Sometimes, hyponatremia can autocorrect unexpectedly, especially in patients with cortisol deficiency. It is also important to monitor relief of symptoms with the correction of hyponatremia; we expect patients to regain sensorium with the rise in serum sodium. However, if this does not occur, another cause of alteration in sensorium should be thought of. This is especially true in CNS causes of hyponatremia such as stroke, subarachnoid bleeds, and tumors.
For patients with moderate hyponatremia, the treatment would be fluid restriction as first-line therapy. This should be to the tune of <1 l/day. The urine to serum electrolyte ratio (urine sodium + urine potassium concentration/serum sodium concentration) is a valuable indicator of the patient being in the antidiuretic phase or the aquaretic phase. If this ratio is more than 1, this means that the urine is still concentrated, and fluid restriction be brought down to 500ml/day. This has been shown to be effective in 59% of patients by Winzeler et al.
Other measures for raising the serum sodium include the use of salt tablets, or urea. The loop diuretics such as furosemide are useful as they cause more water loss that sodium, as they act on the thick ascending loop of Henle, inducing a state of ADH resistance distally.
The role of vaptans in patients with hyponatremia is now being increasingly well recognized. Vaptans act on Type 2 vasopressin receptors in the collecting duct and thus cause water loss. They are the most appropriate treatment of hyponatremia as they do not cause electrolyte loss, and restriction of fluids is not needed. Further, they neither cause renal impairment nor cause neurohormonal interference. At present, only tolvaptan and conivaptan are available in India.
Prevention of osmotic demyelination syndrome
Strategies to prevent ODS include more careful and slower correction of hyponatremia, with regular monitoring of serum sodium, especially in the above-mentioned high-risk groups.
Once the correction has overshot the target, it can be attempted to reverse it by administration of 5% dextrose to lower the sodium at the rate of 6 ml/kg, infused slowly over 2–3 h. At this rate, the sodium is lowered gently by 2 meq/L and will reach the therapeutic goal. The next strategy could be replacement with desmopressin at dose of 1–2 μg iv or subcutaneously every 6–8 h. This is called the rescue strategy for ODS, and this relowering of sodium is useful to prevent further deterioration of clinical status.
Therapy with glucocorticoids such as dexamethasone and antibiotics such as minocycline and myoinositol has been tried, but not found to be of much use.
For established ODS, too relowering of sodium has been associated with improvement of neurological status in anecdotal patients. This is especially true if the relowering happens early in the course of ODS.
| Treatment of Mild Hyponatremia|| |
In this group of patients is mainly restriction of fluids and withdrawing the affecting cause, like discontinuing the culprit drugs, or hypotonic solutions during surgery. Oral salt tablets which can increase serum sodium have been found to be useful. Though hyponatremia would probably be mild in this subgroup, it is well known that elderly patients may have distressing symptoms. Cognition might be impaired in these patients and may lead to falls or imbalance during walking; hence, detection and early intervention may be of great clinical use in these patients.
Role of vaptans in hyponatremia
There has been some debate regarding the positioning of vaptans for the treatment of moderate hyponatremia. The European guidelines do not recommend their use in this group of patients. This is because some clinical trials did not show much improvement with vaptans though these were not randomized control trials. Further, there has been fear of overcorrection of severe hyponatremia with vaptans. Tzoulis etal. however reported good results with the use of tolvaptan in SIADH. The average rise in sodium did exceed more than the suggested 10 mEq/L/day in quarter of the patients though none developed ODS. The efficacy has been demonstrated by the SALT 1 and SALT 2 trials (study of ascending levels of tolvaptan in hyponatremia.) In these trials, the serum sodium and mental score for cognition did increase simultaneously.
Further, vaptans have been used for longer periods of time, up to a year in SALTWATER trial (safety and sodium assessment of long-term tolvaptan with hyponatremia trial). The serum sodium did normalize in about 60% of the patients. In the TEMPO 3:4 trial, liver function abnormalities with a rise in aspartate transaminase and alanine aminotransferase was known to occur in several patients. Hence, it is important to monitor liver enzymes periodically every 2–3 months, after starting tolvaptan. The starting dose of tolvaptan is 15 mg on day 1, and the dose can be increased to 30–60 mg/day thereafter with monitoring sodium on a regular basis. Fluid restriction should not be advised while correcting with vaptans, thus allowing the patients' thirst to compensate for the water loss.
Conivaptan is advised for euvolemic hyponatremia and is available only as IV preparation. It is given as 20 mg IV loading dose followed by 20 mg IV continuous infusion for 24 h. If the serum sodium rise in <5 mEq/L, then the infusion rate can be stepped up to 40 mg/day for a maximum of 4 days. Though the vaptans do not cause renal dysfunction, they do not work when the creatinine is more than 2.5 mg/dl.
| Potassium Replacement in Hyponatremia|| |
In patients with hyponatremia, potassium replacement serves to raise the serum sodium concentration. This is because when the potassium moves into the cell, sodium is exchanged into the extra cellular fluid. The chloride which moves with potassium into the cell causes increase in cell osmolarity promoting water entry in the intracellular compartment. Hence, potassium chloride administration is recommended in all patients with hypokalemia with hyponatremia.
| Treatment of Hypovolemic Hyponatremia|| |
This is due to water and sodium loss and can be reversed by the administration of 0.9% NaCl. This raises the serum sodium by 1 mEq/L for fluid infused since NaCl has higher concentration of sodium than the plasma (154 mEq/L); it may raise the serum sodium and remove the stimulus for release of ADH.
In vomiting and diarrhea, it may be needed to correct the volume status, serum sodium and potassium deficits and the bicarbonate deficit. In cerebral salt wasting, normal saline is used to correct the hyponatremia. If thiazides are the cause, then the hyponatremia must be corrected slowly along with potassium correction. Dietary salt addition may help in this situation. Mineralocorticoid deficiency is corrected by normal saline and fludrocortisone.
| Treatment of Hypervolemic Hyponatremia|| |
This is seen in volume-overloaded states such as cirrhosis, cardiac failure, and renal failure. The treatment involves water restriction to less 750 ml/day and addition of loop diuretics.
Hyponatremia is thus a very common clinical problem encountered by physicians. The management of this condition involves assessing the background in which hyponatremia occurred and understanding the volume status of the patient. Based on this, judicious investigations can be asked, and then, a correct diagnosis can be made. This will pave the way for correction, which can in some instances be lifesaving, and definitely rewarding in all other patients.
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| References|| |
Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med 2006;119:S30-5.
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al.
Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. Am J Med 2013;126:S1-42.
Nguyen MK, Ornekian V, Butch AW, Kurtz I. A new method for determining plasma water content: Application in pseudohyponatremia. Am J Physiol Renal Physiol 2007;292:F1652-6.
Soupart A, Penninckx R, Stenuit A, Perier O, Decaux G. Treatment of chronic hyponatremia in rats by intravenous saline: Comparison of rate versus magnitude of correction. Kidney Int 1992;41:1662-7.
Ashraf N, Locksley R, Arieff AI. Thiazide-induced hyponatremia associated with death or neurologic damage in outpatients. Am J Med 1981;70:1163-8.
Sonnenblick M, Friedlander Y, Rosin AJ. Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. Chest 1993;103:601-6.
Ti LK, Kang SC, Cheong KF. Acute hyponatraemia secondary to cerebral salt wasting syndrome in a patient with tuberculous meningitis. Anaesth Intensive Care 1998;26:420-3.
Berendes E, Walter M, Cullen P, Prien T, Van Aken H, Horsthemke J, et al.
Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997;349:245-9.
Sahay M, Sahay R. Hyponatremia: A practical approach. Indian J Endocrinol Metab 2014;18:760-71.
Johnson BE, Chute JP, Rushin J, Williams J, Le PT, Venzon D, et al.
Aprospective study of patients with lung cancer and hyponatremia of malignancy. Am J Respir Crit Care Med 1997;156:1669-78.
Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis 2008;52:144-53.
Alexander RC, Karp BI, Thompson S, Khot V, Kirch DG. A double blind, placebo-controlled trial of demeclocycline treatment of polydipsia-hyponatremia in chronically psychotic patients. Biol Psychiatry 1991;30:417-20.
Fox BD. Crash diet potomania. Lancet 2002;359:942.
Heuman DM, Abou-Assi SG, Habib A, Williams LM, Stravitz RT, Sanyal AJ, et al.
Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death. Hepatology 2004;40:802-10.
Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML. Postoperative hyponatremia despite near-isotonic saline infusion: A phenomenon of desalination. Ann Intern Med 1997;126:20-5.
Almond CS, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, et al.
Hyponatremia among runners in the Boston Marathon. N
Engl J Med 2005;352:1550-6.
Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006;119:71.e1-8.
Fenske WK, Christ-Crain M, Hörning A, Simet J, Szinnai G, Fassnacht M, et al.
Acopeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 2014;25:2376-83.
Berl T. The Adrogue-Madias formula revisited. Clin J Am Soc Nephrol 2007;2:1098-9.
Hanna RM, Yang WT, Lopez EA, Riad JN, Wilson J. The utility and accuracy of four equations in predicting sodium levels in dysnatremic patients. Clin Kidney J 2016;9:530-9.
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al.
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014;29 Suppl 2:i1-39.
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al.
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170:G1-47.
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al.
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Intensive Care Med 2014;40:320-31.
Adrogué HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol 2012;23:1140-8.
Winzeler B, Lengsfeld S, Nigro N, Suter-Widmer I, Schütz P, Arici B, et al.
Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis. J Intern Med 2016;280:609-17.
Li C, Wang W, Summer SN, Westfall TD, Brooks DP, Falk S, et al.
Molecular mechanisms of antidiuretic effect of oxytocin. J Am Soc Nephrol 2008;19:225-32.
Derubertis FR Jr., Michelis MF, Bloom ME, Mintz DH, Field JB, Davis BB. Impaired water excretion in myxedema. Am J Med 1971;51:41-53.
Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol 2009;5:270-6.
Corona G, Giuliani C, Verbalis JG, Forti G, Maggi M, Peri A. Hyponatremia improvement is associated with a reduced risk of mortality: Evidence from a meta-analysis. PLoS One 2015;10:e0124105.
Tzoulis P, Waung JA, Bagkeris E, Carr H, Khoo B, Cohen M, et al
. Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion. Clinical endocrinology 2016;84:620-6.
Higashihara E, Torres VE, Chapman AB, Grantham JJ, Bae K, Watnick TJ, et al
. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clinical Journal of the American Society of Nephrology 2011;6:2499-507.
Arieff AI, Ayus JC. Endometrial ablation complicated by fatal hyponatremic encephalopathy. JAMA 1993;270:1230-2.
[Table 1], [Table 2]