REVIEW ARTICLE

Risk Factors, Complication and Measures to Prevent or Reverse Catastrophic Sodium Overcorrection in Chronic Hyponatremia Kamel A. Gharaibeh, MD, Joseph M. Brewer, DO, Mohit Agarwal, MD and Tibor Fülöp, MD

Abstract: Hyponatremia is the most common electrolyte disorder encountered in clinical practice. Patients who develop this condition for more than 48 hours are at risk for severe neurological sequelae if correction of the serum sodium occurs too rapidly. Certain medical disorders are known to place patients at an increased risk for rapid correction of serum sodium concentration. Large-volume polyuria in this setting is an ominous sign. For these patients, early identification of risk factors, close monitoring of serum sodium correction and the use of 5% dextrose with or without desmopressin to prevent or reverse overcorrection are important components of treatment. Key Indexing Terms: Desmopressin; Hyponatremia; Osmotic demyelination syndrome; Polyuria; Syndrome of inappropriate antidiuretic hormone secretion. [Am J Med Sci 2015;349(2):170–175.]

H

yponatremia is typically defined as a serum sodium concentration ,135 mEq/L and is the most common electrolyte disorder encountered in clinical practice.1–3 The condition can develop in ,24 hours and can cause profound neurological disturbances that require emergent treatment.4 Chronic hyponatremia lasting more than 48 hours can be caused by a host of distinct entities, including diuretic use, inappropriate antidiuresis or a number of chronic medical conditions.4

CHRONIC HYPONATREMIA Most cases of chronic hyponatremia are relatively asymptomatic5 because of the chronic nature of hyponatremia developing over a period of time sufficient for cerebral adaptation. Notwithstanding, recent research has reported increased odds of falls6,7 and higher all-cause mortality6 in elderly persons with mild hyponatremia. Other studies of large cohorts have demonstrated significantly higher in-hospital mortality in persons with hyponatremia at3,8 or during8 admission. Chronic hyponatremia has also been reported to cause impaired cognition, gait disturbance and (rarely) seizures.9 Perhaps, the greatest danger for patients with chronic hyponatremia concerns the correction and recovery phase, as a rapid or extreme increase in serum sodium may lead to neurological injury in brain cells that may have become adapted to low serum osmolality over time.2,9–11 Current understanding of hyponatremia treatment is generally guided by the principles of increasing exchangeable electrolytes (namely sodium), decreasing total body water or both.10 The method, and most importantly the rate,9 of correction is usually determined by the onset and duration of hyponatremia. From the Department of Internal Medicine, University of Mississippi Medical Center, Jackson, Mississippi. Submitted February 15, 2013; accepted in revised form July 11, 2014. The authors have no financial or other conflicts of interest to disclose. Correspondence: Kamel A. Gharaibeh, MD, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505 (E-mail: [email protected]).

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At this time, there is no single ideal treatment owing to the association of hyponatremia with multiple etiologies and different pathophysiological mechanisms.10 There are no randomized controlled trials to guide treatment of hyponatremia.5,9 Instead, evidence for current treatment practice rests in observational studies and experimental animal models.5,9 Patients with symptoms as a result of hyponatremia are treated with a brief infusion of 3% saline with the goal of increasing the serum sodium concentration 2 to 4 mEq/L over 2 to 4 hours followed by slow correction maintained at ,10 mEq/L in 24 hours or ,18 mEq/L in 48 hours.10 Multiple equations are available to help calculate the initial rate of fluids to be administered. A widely used formula is the Adrogue-Madias formula12: Change in serum Na+ with infusing solution 5 (infusate Na+ + infusate K+) 2 serum Na+/ (total body water +1). Accuracy of this formula, however, is disputed and investigators have reported conflicting results.13,14 The initial infusion rate (mL/hr) of 3% saline can also be simply calculated as a product of patients’ weight (kg) and desired correction rate (mEq$L21$hr21) as demonstrated by Verbalis et al.5 In an emergent situation, a rapid infusion of 100 mL of 3% saline can be used to acutely raise the sodium concentration by 2 to 4 mEq/L. This infusion can be repeated in about half an hour if no clinical improvement is seen. Frequent monitoring of serum sodium concentration must be performed to adjust this initial infusion rate to prevent inadvertent rapid correction. Patients with asymptomatic chronic nonhypovolemic hyponatremia may be treated with fluid restriction to less than the rate of urinary water excretion5 though adherence to this treatment is often difficult,4 and the rate of correction is often a paltry 1 to 2 mEq$L21$d21. Fluid restriction is unlikely to work if the effective urine osmolality (twice the sum of urine sodium and potassium) is greater than twice the serum sodium concentration. An accurate assessment of the volume status in hyponatremic subjects is crucial to optimize the treatment strategy in affected individuals. Isotonic saline is the recommended therapy for hypovolemic hyponatremia; however, saline infusion could worsen hyponatremia especially if a patient has elevated levels of arginine vasopressin (AVP) as may be the case in a patient who develops hypovolemic hyponatremia secondary to gastroenteritis associated with nausea.4 Normal saline should be avoided in hypervolemic hyponatremia due to potential worsening of volume overload. A loop diuretic such as furosemide is sometimes prescribed with saline or salt tablets in patients with a syndrome of inappropriate antidiuresis to facilitate excretion of hypotonic urine.15 In Belgium, urea has been used to correct severe hyponatremia, but the effect is not predictable because the increase in serum sodium level depends on urea excretion and kidney function, which would be expected to vary with volume status and AVP level. Decaux et al16 reported the use of intravenous or oral urea to treat patients with a serum sodium level ,115 mEq/L, but more than one-third of the patients with a serum sodium level ,120 mEq/L had excessive correction. Use of mineralocorticoids for the management of hyponatremia is limited in the United

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States, in part because of concerns about mineralocorticoid-associated fluid overload. A tetracycline antibiotic, demeclocycline, exhibits vasopressin-2 receptor antagonist (V2RA) properties and has been used successfully in syndrome of inappropriate antidiuresis.17 It is, though, not FDA approved for this indication and can cause reversible nephrotoxicity, especially in people with cirrhosis and heart failure.18,19 Intravenous conivaptan and oral tolvaptan are 2 V2RA currently available in the United States. They are FDA approved for the management of hypervolemic and euvolemic hyponatremia, though some restrictions apply, including treatment durations limited to 4 days for conivaptan to minimize the possibility of CYP3A4 drug interactions and 30 days for tolvaptan to minimize the risk of liver injury. In a metaanalysis that included 15 randomized controlled trials, vasopressin receptor antagonists were shown to have early and late efficacy in normalizing or significantly increasing serum sodium concentration. The same meta-analysis also identified an increased rate of rapid sodium correction without neurological injury20 with the use of V2RA, though the latter might have been averted during the controlled trials because of the exclusion of high-risk patients and the careful monitoring of the study subjects. In patients with chronic and otherwise asymptomatic hyponatremia, the approximate limits of osmolality change are less than 10 to 12 mEq/L in 24 hours4,5,9,10,21 and less than 18 mEq/L in 48 hours with a tendency toward less correction over time in patients at risk for neurological injury.5,9,10,21 To further decrease risk and to afford margins of safety, Adrogue and Madias22 suggested to correct hyponatremia by maximum increment of 8 mEq/L in the sodium level in 24-hour period.

chronic hyponatremia.4,10 Symptom development begins with lethargy and behavioral changes, followed by mutism or dysarthria, spastic quadriparesis and pseudobulbar palsy.2,4,20 Numerous risk factors for the development of ODS have been identified (Table 1).2,5,9,10,21,23 Patients with these risk factors should have serum sodium correction carefully monitored with a maximum correction of 8 mEq$L21$d21. Outcomes in patients with ODS vary. Some reports describe patients having transient, reversible neurological dysfunction,1,4,10 whereas other authors describe frequent aspiration with the need for mechanical ventilation in patients with ODS.10 Overall, most patients survive,5,10 although death has been reported.11 Upon presentation of severe chronic symptomatic hyponatremia, the concern about ODS does not justify therapeutic inaction, but the fear of complications from hyponatremic encephalopathy does not justify therapeutic excess. Some patients with symptomatic chronic hyponatremia develop cerebral edema, which makes it a medical emergency. Fortunately, we need minimal correction in serum sodium concentration by 4 to 6 mEq/L to take these patients out of the risk zone and reverse the cerebral edema or relieve the symptoms24 while we are trying not to overcorrect and put the patients at risk of ODS. In fact in a study by Koenig et al,25 rapid rise in serum sodium by 5 mEq/L was shown to significantly reduce intracranial pressure. Unfortunately, it is challenging to keep most hyponatremic patients in the safe zone of correction, especially if unexpected water diuresis emerges during correction, making it difficult to control sodium level and the calculations will be more complicated.

BRAIN RESPONSE TO HYPONATREMIA

MECHANISMS OF HYPONATREMIA OVERCORRECTION

The brain has mechanisms that allow it to adapt to a changing osmotic environment. Sodium is an effective solute and does not cross cell membranes easily; thus, acutely, only water can flow in and out of brain cells in response to changes of extracellular tonicity.9,10 Brain cells also contain high concentrations of organic osmolytes that can be translocated to the extracellular space in the setting of hyponatremia.10 When hyponatremia develops in ,24 hours, this may lead to brain edema due to the inability of compensatory mechanisms to adapt quickly (osmolytes shift). When, however, hyponatremia develops chronically, brain cells are able to export osmolytes and import water to equilibrate intracellular osmolality with extracellular osmolality without cellular swelling.5,7,9,10 Once adapted to a state of chronic hyponatremia, rapid correction of serum sodium concentration may overwhelm the ability of brain cells to regain lost osmolytes,2,4,5,10 which may take up to 1 week to occur.10

OSMOTIC DEMYELINATION SYNDROME

Osmotic demyelination syndrome (ODS) is a rare1,9 but well-established complication of rapid correction of chronic hyponatremia that was reported by Sterns et al11 in a seminal article describing 8 patients who developed cerebral demyelination. Adaptation that allows the brain to survive chronic hyponatremia makes the brain more susceptible to cellular damage when serum sodium concentration is increased quickly because of the impairment of normal defenses that prevent osmotic shrinking as a result of prolonged hyponatremia.4 ODS is marked by programmed death of oligodendrocytes in myelin-rich areas of the brain.23 Patients with ODS have variable presentations ranging from relatively few symptoms9 to new progressive neurological deficits5 that develop 1 to several days after correction of

Hyponatremia overcorrection can occur as a result of excess free water loss, extra sodium load to the extracellular volume or unexpected intracellular free water uptake. Excessive Free Water Loss Some factors that cause or maintain hyponatremia, when corrected, allow significant diuresis that leads to a rapid increase in serum sodium concentration in a process known as “autocorrection.”5,10,26,27 This can occur because of eliminating the stimulus for secretion of AVP, for example, by correction of hypovolemia with isotonic saline administration, cessation of nausea after anti-emetics administration28 or replacement of cortisol in Addison’s disease, with resultant water diuresis giving a picture similar to diabetes insipidus. Fraser and Arieff29

TABLE 1. Risk factors for the development of ODS Hyponatremia .48 hr Initial serum sodium ,105 mEq/L Development of hypernatremia during treatment Rapid (.0.5 mEq$L21$hr21) and/or large increase (.25 mEq/L per 48 hr) in serum sodium Severe malnutrition (low blood urea nitrogen) Alcoholics Advanced liver disease Hypokalemia Hypoxemia Use of diuretics (especially thiazides) Cancer Seizure on presentation

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reported cases of severe cerebral edema that led to cerebral herniation and pituitary infarction resulting in failure of pituitary antidiuretic hormone release. The serum sodium can increase by .2 mEq$L21$hr21 once urine is maximally dilute.5,10 Patients with risk factors for autocorrection (Table 2) should have serum sodium correction carefully monitored with a correction goal of approximately 8 mEq$L21$d21 along with close observation and measurement of urine output.5 Difficult-to-control increases in serum sodium can be treated by matching urine water losses with 5% dextrose and/or by giving desmopressin.10,20,26 Sodium Overload Extra sodium supplementation may occur as a result of dosing miscalculation or nursing error. Most commonly, the sources of extra sodium come from either undocumented exogenous administration, for example, intravenous medications or intake by patients orally without documentation, or unsuspected endogenous extracellular sodium shift. The first reason may occur when physicians fail to take into account the amount of sodium already given to patients in the emergency room or when the patients get transferred from an outside facility when the corrections are calculated. The latter condition may occur, for example, when potassium is administered simultaneously, as sodium is shifted to the extracellular compartment in exchange for cellular potassium uptake. A more comprehensive explanation of this phenomenon is described below. Intracellular Free Water Uptake Intracellular free water uptake results in a net extracellular sodium concentrating effect. Intracellular free water uptake may be of clinical relevance when there is significant intracellular uptake of osmotically effective molecules such as potassium and glucose during intravenous administration of potassium in hypokalemic patients and insulin administration in diabetic patients, respectively. Blood urea nitrogen is an osmole that contributes to the serum and urine osmolality but not to serum tonicity because urea is a relatively ineffective osmole because of its ability to cross cell membranes relatively easily. For example, a person with acute kidney injury and hyponatremia will have a high urea (resulting in potentially normal serum osmolality), but low-effective serum tonicity still renders the brain susceptible to overcorrection injury (ODS).22

SPECIAL CONSIDERATIONS Malnutrition A malnourished state due to avoidance of solid food and excessive fluid intake may lead to the development of an

TABLE 2. Risk factors for excessive “autocorrection” of hyponatremia, upon resolution of excessive AVP secretion Syndrome of inappropriate antidiuretic hormone secretion related to nausea, vomiting, hypoxia or medications Brain edema Excessive fluid intake, when combined with stress/excessive AVP release (eg, marathon runners) Stress Neurological disease Nociceptive stimuli Cortisol deficiency Thiazide diuretics

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effective protein deprivation status, which has been reported to impair the concentration capacity of the kidneys.30 Under these circumstances, rapid restoration of protein nourishment (eg, enteric feeding with high-protein formula) while correcting hyponatremia may place patients at risk of hyponatremia overcorrection. Electrolyte-free water excretion is dependent on the total rate of solute excretion, which is a product of obligatory metabolism of nutrients especially the proteins. Accordingly, in malnourished patients, serum sodium may increase when solute intakes are increased because of the increased electrolyte-free water secretion. Hypokalemia The presence of hypokalemia is an independent concern during development and correction of hyponatremia. Because intracellular and extracellular osmolarity are always equal, loss of sodium or potassium without significant water loss will lead to shift of osmoles to maintain osmolar balance between the intracellular and extracellular compartments. Potassium depletion results in a shift of sodium into the cell with equal exit of potassium from the cell into the extracellular fluid.31,32 The opposite phenomenon occurs during potassium repletion as described by Laragh33 when potassium chloride administration resulted in an increase in serum sodium levels in hyponatremic patients in the absence sodium supplement. Edelman et al34 showed that serum sodium concentration is a function not only of total exchangeable sodium and total body water but also of total exchangeable potassium. Taken together, one may conclude that potassium depletion could be associated with hyponatremia, and potassium repletion results in an increase in serum sodium concentration. Nguyen and Kurtz35 described how potassium repletion results in an increase in serum sodium concentration by way of enhanced entry of chloride into the cell along with the potassium, which leaves the cell hypertonic and draws water from the extracellular fluid. The authors also described how potassium entry into the cell may also be accompanied by the movement of hydrogen ions from the intracellular to extracellular space, where they are buffered and thereby rendered osmotically inactive. This would decrease effective extracellular tonicity, again causing water to move into the cells and, increasing the extracellular concentration of sodium. In cases of simultaneous correction of hypokalemia and hyponatremia, Berl and Rastegar36 concluded that the increase in serum sodium plus potassium levels should not exceed 12 mEq/L in the first 24 hours and 18 mEq/L in the first 48 hours. In other words, the increase in serum sodium level caused by 1 mEq/L of potassium is equivalent to that caused by 1 mEq of sodium. Severe hypokalemia (serum potassium ,2.5 mEq/L) at presentation implies profound and long-term total body potassium depletion, which is a known cause of relative deficiency of urinary concentration (“nephrogenic” diabetes insipidus).37 Prolonged hypokalemia causes substantial morphologic changes in kidney ultrastructure38,39 and is associated with renal functional abnormalities including a relative vasopressin resistance with decrease in urinary concentrating ability and downregulation of aquaporin-2 water channel expression.40 Indeed, some patients with severe prolonged hypokalemia may fail to fully concentrate urine despite maximal dose of desmopressin (ie, partial nephrogenic diabetes insipidus). Sood et al41 provide a practical example of how to consider potassium supplementation during hyponatremia correction. In their paper, they suggested that if a patient is receiving 3% saline solution at 20 mL/hr and is given 20 mEq of potassium chloride orally or in a 400-mmol/L intravenous solution, Volume 349, Number 2, February 2015

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the saline solution infusion should be discontinued for 2 hours (20 mEq of potassium chloride is equivalent to 40 mL of 3% saline solution).

PREVENTION AND TREATMENT OF HYPONATREMIA OVERCORRECTION 5% Dextrose in Water Solution Matching electrolyte-free water losses in the urine with intravenous 5% dextrose in water (D5W) is seemingly an easy way to prevent rapid autocorrection. In a rat model, Soupart et al42 demonstrated that in cases of rapid self-correction, ODS can be successfully prevented by subsequent lowering of serum sodium by administration of free water in a timely manner. However, high-volume continued intravenous administration of D5W alone to match urine output can lead to hyperglycemia (which lowers the plasma sodium by shifting water out of cells) and glycosuria, particularly in patients who are under stress and metabolize glucose slowly. Additionally, electrolyte-free water losses from a glucose-induced osmotic diuresis may exacerbate the problem of polyuria and in some subjects will be difficult to keep up with the large urine output. Oral Hydration Therapy Oral intake is generally difficult because hyposmolality suppresses thirst and patients may refuse water intake. Furthermore, in patients with altered mental status, oral intake in general may not be a viable option at all. Finally, attempting to match urinary water losses with intravenous or orally administered electrolyte-free water requires intensive monitoring of fluid balance, that is, very labor intensive and often impractical. Because of these obvious disadvantages of 5% dextrose and oral hydration therapy, administration of a vasopressin analog such as desmopressin may be a more attractive strategy. We recently had a case in our hospital further strengthening the limited published experience to date with the use of desmopressin to reverse overcorrection of hyponatremia, in face of coexisting complex electrolyte disturbances.28 Desmopressin Natural AVP has a short half-life of approximately 10 to 20 minutes in plasma and, therefore, not useful for therapeutic purposes in these case. Desmopressin (1-deamino-8-D-arginine vasopressin; DDAVP) is a synthetic analog of the natural hormone AVP with enhanced antidiuretic effect and longer duration of action. Because of a relative specificity for vasopressin-2 receptor, desmopressin has only a limited effect on the blood pressure. The usual dose is 2 to 4 mg/d intravenously every 6 to 12 hours. Administration of desmopressin can be a successful strategy to both ameliorate sodium overcorrection and avoid inadvertent overcorrection of hyponatremia,43 especially in patients with risk factors for excessive free water diuresis during recovery from hyponatremia (Table 2). Inadvertent overcorrection of hyponatremia is, in fact, common13 and ought to be viewed as a medical emergency.43 To state it differently, hypertonic saline administration may result in more than expected increases in serum sodium due to an unanticipated water diuresis that may develop during the course of therapy.44 Perianayagam et al45 reported a series of 20 patients where preemptive administration of desmopressin prevented excessive water diuresis, and fewer patients required 5% dextrose administration for therapeutic relowering of the sodium. In their prospective study, desmopressin was given to a group of patients (group 1) prophylactically when sodium concentration increased by 8 mEq/L in 24 hours in patients at high risk for

ODS (Table 1), sodium concentration increased by more than 1.5 mEq/L per hour or urine output exceeded more than 250 mL per hour. The second group of patients (group 2) received desmopressin only when the correction of sodium exceeded 12 mEq/L in 24 hours or 18 mEq/L in 48 hours. Both groups were given 5% dextrose after desmopressin in a purposive effort to relower their plasma sodium to a safer level. Treatment for group 1 resulted in a decrease of sodium from its peak value before desmopressin to a value that was 4 to 9 mEq/L lower than the peak, at an average rate of 0.6 mEq$L21$hr21. None of the patients in group 1 exhibited any worsening of their neurologic symptoms before, during or after the relowering of serum sodium concentration, and all were discharged from the hospital at their baseline level of health. The sodium concentration for patients in group 2 decreased from its peak value before desmopressin at a rate of 0.66 mEq$L21$hr21 to a value that was 2 to 7 mEq/L lower than the peak serum sodium. The results of desmopressin administration to group 2 patients maintained correction rates below the 24-hour limit in 93% and below the 48-hour limit in 100% of cases, and in no case did correction exceed either limits and no patients developed ODS. Sood et al41 concluded that combined infusion of 3% saline solution and desmopressin seems to be a valid strategy for correcting severe hyponatremia effectively and safely and reduces the chances of inadvertent overcorrection. In their retrospective study, they reviewed 25 patients who were admitted with sodium ,120 mEq/L and undergone concurrent administration of desmopressin and hypertonic saline solution. Mean changes in serum sodium levels during the first and second 24 hours of therapy were 5.8 and 4.5 mEq/L, respectively, without correction by .12 mEq/L in 24 hours or .18 mEq/L in 48 hours and without a decrease during therapy. There was no significant difference between actual and predicted increases during the first 24 hours. There was no adverse effect associated with therapy. They concluded that administration of desmopressin in combination with hypertonic saline might result in a more controlled rate of correction of hyponatremia, avoiding the unanticipated emergence of water diuresis in patients at high risk for overcorrection (Table 2). A very recent similar paper also confirmed this experience in the intensive care unit setting.46 Of note, Oya et al47 reported a case demonstrating successful reversal of ODS symptoms by prompt reversal of rapid correction with free water and desmopressin. This example demonstrates that permanent neurological sequelae can be averted even in symptomatic patients by rapid amelioration of osmotic stress with the use of free water administration to achieve a therapeutic relowering of sodium. This particular strategy of replacing the calculated deficit of water, along with desmopression administration, can also be used under selected circumstances preemptively to prevent neurologic complications.28 Desmopressin administration should continue until the serum sodium normalizes or becomes close to normal. Desmopressin should be given with extreme caution in the case of psychogenic polydipsia because once desmopressin is given the patient will be unable to diurese and will be unable to excrete ingested water, especially if psychogenic polydipsia is not well controlled yet. Life-threatening self-induced water intoxication could potentially result; therefore, administration of desmopressin must be carefully supervised, and the patient’s access to fluid supposed to be well controlled.

CONCLUSIONS Important strategies to avoid inadvertent overcorrection of the serum sodium concentration in hyponatremic patients include early identification of patients with risk factors for

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excessive water diuresis (Table 2) and close monitoring of urine output and serum sodium correction in a critical care setting. Desmopressin can be administered prophylactically to prevent polyuria and rapid uncontrolled correction of the serum sodium resulting in ODS. Patients in whom the serum sodium has already increased by more than 10 to 12 mEq/L in 24 hours or 18 mEq/L in 48 hours may be treated simultaneously with an infusion of 5% D5W along with desmopressin to reduce the volume of diuresis, resulting in therapeutic relowering of the serum sodium concentration to a safe level. REFERENCES

19. Curtis NJ, van Heyningen C, Turner JJ. Irreversible nephrotoxicity from demeclocycline in the treatment of hyponatremia. Age Aging 2002;31:151–2. 20. Esposito P, Piotti G, Bianzina S, et al. The syndrome of inappropriate antidiuresis: pathophysiology, clinical management, and new therapeutic options. Nephron Clin Pract 2011;119:c62–73. 21. Sterns RH, Cappuccio JD, Silver SM, et al. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol 1994;4:1522–30. 22. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342: 1581–9.

1. Hoorn EJ, Zietse R. Hyponatremia and mortality: moving beyond associations. Am J Kidney Dis 2013;62:139–49.

23. Mount DB. The brain in hyponatremia: both culprit and victim. Semin Nephrol 2009;29:196–215.

2. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 2007;356:2064–72.

24. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol 2009;29:282–99.

3. Zilberberg MD, Exuzides A, Spalding J, et al. Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients. Curr Med Res Opin 2008;24:1601–8.

25. Koenig MA, Bryan M, Lewin JL III, et al. Reversal of transtentorial herniation with hypertonic saline. Neurology 2008;70: 1023–9.

4. Sterns RH. Severe symptomatic hyponatremia: treatment and outcomes. A study of 64 cases. Ann Intern Med 1987;107:656–64.

26. Moritz ML, Ayus JC. New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatr Nephrol 2010;25:1225–38.

5. Verbalis JG, Goldsmith SR, Greenberg A, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med 2007; 120:S1–21.

27. Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin North Am 1997;81:585–609.

6. Hoorn EJ, Rivadeneira F, van Meurs JB, et al. Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J Bone Miner Res 2011; 26:1822–8.

28. Gharaibeh KA, Craig MJ, Koch CA, et al. Desmopression is an effective adjunct treatment for reversing excessive hyponatremia overcorrection. World J Clin Cases 2013;1:155–8.

7. Renneboog B, Musch W, Vandemergel X, et al. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006;119:71.e1–e8.

29. Fraser CL, Arieff AI. Fatal central diabetes mellitus and insipidus resulting from untreated hyponatremia: a new syndrome. Ann Intern Med 1990;112:113–9.

8. Wald R, Jaber BL, Price LL, et al. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010;170: 294–302.

30. Thaler SM, Teitelbaum I, Berl T. “Beer potomania” in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis 1998; 31:1028–31.

9. Moritz ML, Ayus JC. The pathophysiology and treatment of hyponatraemic encephalopathy: an update. Nephrol Dial Transplant 2003;18: 2486–91.

31. Heppel L. The electrolytes of muscle and liver in potassium-depleted rats. Am J Physiol 1939;127:385–92.

10. Sterns RH, Hix JK, Silver SM. Management of hyponatremia in the ICU. Chest 2013;144:672–9. 11. Sterns RH, Riggs JE, Schochet SS Jr. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med 1986;314: 1535–42. 12. Agrawal V, Agarwal M, Joshi SR, et al. Hyponatremia and hypernatremia: disorders of water balance. J Assoc Physicians India 2008;56: 956–64. 13. Mohmand HK, Issa D, Ahmad Z, et al. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clin J Am Soc Nephrol 2007;2:1110–7.

32. Ferrebee J, Parker D, Carnes WH, et al. Certain effects of desoxycorticosterone. Am J Physiol 1941;135:230–7. 33. Laragh JH. The effect of potassium chloride on hyponatremia. J Clin Invest 1954;33:807–18. 34. Edelman IS, Leibman J, O’Meara MP, et al. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest 1958;37:1236–56. 35. Nguyen MK, Kurtz I. Role of potassium in hypokalemia-induced hyponatremia: lessons learned from the Edelman equation. Clin Exp Nephrol 2004;8:98–102.

14. Liamis G, Kalogirou M, Saugos V, et al. Therapeutic approach in patients with dysnatraemias. Nephrol Dial Transplant 2006;21:1564–9.

36. Berl T, Rastegar A. A patient with severe hyponatremia and hypokalemia: osmotic demyelination following postassium repletion. Am J Kidney Dis 2010;55:742–8.

15. Decaux G, Waterlot Y, Genette F, et al. Inappropriate secretion of antidiuretic hormone treated with frusemide. Br Med J (Clin Res Ed) 1982;285:89–90.

37. Beck N, Webster SK. Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney. Am J Physiol 1976;231: 1204–8.

16. Decaux G, Andres C, Gankam KF, et al. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care 2010;14: R184.

38. Schwartz WB, Relman AS. Effects of electrolyte disorders on renal structure and function. N Engl J Med 1967;276:383–9.

17. Singer I, Rotenberg D. Demeclocycline-induced nephrogenic diabetes insipidus. In-vivo and in-vitro studies. Ann Intern Med 1973;79: 679–83. 18. Carrilho F, Bosch J, Arroyo V, et al. Renal failure associated with demeclocycline in cirrhosis. Ann Intern Med 1977;87:195–7.

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39. Riemenschneider T, Bohle A. Morphologic aspects of lowpotassium and low-sodium nephropathy. Clin Nephrol 1983;19: 271–9. 40. Marples D, Frokiaer J, Dorup J, et al. Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex. J Clin Invest 1996;97:1960–8.

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41. Sood L, Sterns RH, Hix JK, et al. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis 2013;61:571–8. 42. Soupart A, Penninckx R, Crenier L, et al. Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering. Kidney Int 1994;45:193–200. 43. Soupart A, Ngassa M, Decaux G. Therapeutic relowering of the serum sodium in a patient after excessive correction of hyponatremia. Clin Nephrol 1999;51:383–6.

44. Sterns RH, Hix JK. Overcorrection of hyponatremia is a medical emergency. Kidney Int 2009;76:587–9. 45. Perianayagam A, Sterns RH, Silver SM, et al. DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clin J Am Soc Nephrol 2008;3:331–6. 46. Rafat C, Schortgen F, Gaudry S, et al. Use of desmopressin acetate in severe hyponatremia in the intensive care unit. Clin J Am Soc Nephrol 2014;9:229–37. 47. Oya S, Tsutsumi K, Ueki K, et al. Reinduction of hyponatremia to treat central pontine myelinolysis. Neurology 2001;57:1931–2.

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Risk factors, complication and measures to prevent or reverse catastrophic sodium overcorrection in chronic hyponatremia.

Hyponatremia is the most common electrolyte disorder encountered in clinical practice. Patients who develop this condition for more than 48 hours are ...
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