A Clinical Approach to the Treatment of Chronic Hypernatremia

Acid-Base and Electrolyte Teaching Case A Clinical Approach to the Treatment of Chronic Hypernatremia Ahmed Al-Absi, MD,1* Elvira O. Gosmanova, MD,1 and Barry M. Wall, MD1,2 Hypernatremia is a commonly encountered electrolyte disorder occurring in both the inpatient and outpatient settings. Community-acquired hypernatremia typically occurs at the extremes of age, whereas hospitalacquired hypernatremia affects patients of all age groups. Serum sodium concentration is linked to water homeostasis, which is dependent on the thirst mechanism, arginine vasopressin, and kidney function. Because both hypernatremia and the rate of correction of hypernatremia are associated with significant morbidity and mortality, prompt effective treatment is crucial. Chronic hypernatremia can be classified into 3 broad categories, hypovolemic, euvolemic, and hypervolemic forms, with each form having unique treatment considerations. In this teaching case, we provide a clinically based quantitative approach to the treatment of both hypervolemic and hypovolemic hypernatremia, which occurred in the same patient during the course of a prolonged illness. Am J Kidney Dis. 60(6):1032-1038. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. INDEX WORDS: Hypernatremia; osmolarity; salt; water loss.

Note from Feature Editor Jeffrey A. Kraut, MD: This article is part of a series of invited case discussions highlighting either the diagnosis or treatment of acid-base and electrolyte disorders. Advisory Board member F. John Gennari, MD, served as the Consulting Editor for this case.

logic complications.5 Chronic hypernatremia can be categorized into hypovolemic, euvolemic, and hypervolemic forms,1 with each form requiring markedly different treatment.

CASE REPORT INTRODUCTION Hypernatremia, defined as serum sodium concentration ⬎145 mEq/L, is a commonly encountered electrolyte disorder.1 Sodium and its attendant anions, as the primary determinants of extracellular tonicity, affect the movement of water across cellular membranes.2-4 Thus, hypernatremia invariably denotes hypertonicity and results in cellular dehydration.1 In the setting of sustained hypernatremia, neuronal cells undergo adaptive processes involving increases in intracellular solutes that minimize cellular water loss. Because these intracellular solutes cannot be dissipated rapidly, controlled gradual correction of chronic hypernatremia is required to avoid cerebral edema and serious neuroFrom the 1Nephrology Division, University of Wisconsin Madison, WI; and 2Nephrology Division, Veteran Affairs Medical Center, Memphis, TN. * Current affiliation: Nephrology Division, University of Wisconsin, Madison, WI. Received February 1, 2012. Accepted in revised form June 13, 2012. Originally published online September 10, 2012. Address correspondence to Barry M. Wall, MD, Nephrology Division, Veterans Affairs Medical Center and University of Tennessee Health Sciences Center, Memphis, TN. E-mail: barry. [email protected] Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. 0272-6386/$0.00 http://dx.doi.org/10.1053/j.ajkd.2012.06.025 1032

Clinical History and Initial Laboratory Data A 73-year-old obese man presented with severe hypotension due to acute lower gastrointestinal bleeding. He required aggressive intravenous resuscitation with normal saline solution and red blood cell transfusions. Arteriography did not localize the site of bleeding. Subsequently, the patient developed nonoliguric acute kidney injury (AKI) related to hypotension and radiocontrastinduced nephrotoxicity. Due to continued lower gastrointestinal bleeding, total colectomy with ileorectal anastomosis was performed, after which total parental nutrition was necessary. Hypernatremia and extensive generalized edema developed during the initial week of hospitalization (Table 1). Hypervolemic hypernatremia was treated with intermittent administration of furosemide and 5% dextrose in water. Kidney function gradually improved and the patient resumed oral intake. He was transferred to a rehabilitation unit for 30 days, where he had persistent watery stools accompanied by poor appetite and a 12-kg weight loss during the course of the illness. Upon discharge from the rehabilitation unit, he was edema free with mild hypernatremia with sodium level of 145-147 mEq/L (145-147 mmol/L) and urine osmolality of 432 mOsm/kg (432 mmol/kg). He denied thirst and insisted on living independently after discharge.

Additional Investigations The patient was readmitted 4 weeks later reporting generalized weakness, poor oral intake, and persistence of loose stools. Blood pressure was 100/60 mm Hg and heart rate was 98 beats/min. Body weight had decreased 7 kg, and no peripheral edema was present. Admission laboratory studies showed severe hypernatremia and recurrent AKI (Table 1). The diagnosis of hypovolemic hypernatremia was made and treated with administration of isotonic saline solution for 24 hours. This resulted in improvement in his generalized weakness, an increase in blood pressure, and improvement in kidney function, with no change in serum sodium concentration. Am J Kidney Dis. 2012;60(6):1032-1038

Treatment of Chronic Hypernatremia Table 1. Serial Laboratory Data

Parameter

Sodium (mEq/L) Potassium (mEq/L) Chloride (mEq/L) Bicarbonate (mEq/L) SUN (mg/dL) Creatinine (mg/dL) eGFR (mL/min/1.73 m2) Glucose (mg/dL) Urine osmolality (mOsm/kg) Urine sodium (mEq/L)

Admission Values

1 Week After Admission

After Rehabilitation

Second Admission

Discharge Values

142 3.8 106 25 26 0.89

150 3.8 117 23 46 4.65

147 4.2 113 26 19 2.04

163 3.5 129 23 76 3.19

145 4.2 113 26 21 1.78

102 98 NA NA

— 107 315 74

— 100 432 81

— 91 NA NA

46 131 NA NA

Note: Because eGFR is valid for only steady-state conditions, it has been calculated for only admission and discharge. Conversion factors for units: SUN in mg/dL to mmol/L, ⫻0.357; serum creatinine mg/dL to ␮mol/L; ⫻88.4; eGFR in mL/min/1.73 m2 to mL/s/1.73 m2, ⫻0.01667; glucose in mg/dL to mmol/L, ⫻0.05551. No conversion necessary for sodium in mEq/L and mmol/L; potassium in mEq/L and mmol/L; chloride in mEq/L and mmol/L; bicarbonate in mEq/L and mmol/L; and osmolality in mOsm/kg and mmol/kg. Abbreviations: eGFR, estimated glomerular filtration rate; NA, not available; SUN, serum urea nitrogen.

Subsequent intravenous fluid therapy with 5% dextrose in water led to gradual resolution of hypernatremia over a 48-hour period.

Diagnosis Hypervolemic hypernatremia followed by hypovolemic hypernatremia.

Clinical Follow-up Chronic kidney disease with serum creatinine concentration of 1.8 mg/dL (159.1 ␮mol/L; estimated glomerular filtration rate, 46 mL/min/1.73 m2 [0.77 mL/s/1.73m2] calculated by the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation)6 and a defect in urinary concentration (maximum urine osmolality, 350-400 mOsm/kg [350-400 mmol/kg]) persisted.

He continues to have limited mobility and decreased sensation of thirst, leaving him at high risk of recurrent hypernatremia. He is living with family members who are providing scheduled fluid intake. Follow-up serum sodium concentration was 145 mEq/L (145 mmol/L).

DISCUSSION Serum sodium concentration is a function of the total-body content of exchangeable sodium and potassium divided by total-body water.7 All dysnatremic disorders therefore are due to alterations in the normal relationship between total-body cations and totalbody water. Clinical disorders leading to hyperna-

Total Body Water ECF

ICF Normal TBW, Normal TBNa, Normal PNa

Figure 1. Hypernatremia as a result of changes in total-body water (TBW) and total-body sodium (TBNa). Black circles in figure represent sodium (Na). Abbreviations: ECF, extracellular fluid; ICF, intracellular fluid; PNa, plasma sodium. Adapted from Adrogue and Madias1 with permission from the Massachusetts Medical Society.

Am J Kidney Dis. 2012;60(6):1032-1038

Euvolemic Hypernatremia TBW ↓, TBNa unchanged, PNa ↑ Loss of free water ICF >>ECF; therefore, little or no signs of volume depletion

Hypovolemic Hypernatremia TBW ↓↓ > TBNa ↓, PNa ↑ Loss of free water from both ECF and ICF, loss of Na from ECF leads to hypovolemia Hypervolemic Hypernatremia TBW ↑ << TBNa ↑↑, PNa ↑ Addition of Na and water into ECF leads to hypervolemia ↑ in PNa leads to reduction in ICF

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Al-Absi, Gosmanova, and Wall Table 2. Hypernatremia Overview Problem

Total-Body Water

Total-Body Na

22

2

Orthostasis, hypotension, tachycardia, dry mucous membranes

Renal causes: osmotic diuresis (mannitol, glucose, urea), loop/ thiazide diuretics, postobstructive diuresis, diuresis phase of ATN; laboratory findings: UOsm high, UNa high Extrarenal causes: sweating, burns, diarrhea, vomiting, nasogastric suction, lactulose; laboratory findings: UOsm high, UNa low

Normal vital signs, no edema

Renal causes: central or Free water nephrogenic diabetes insipidus; replacement laboratory findings: UOsm low, UNa variable Extrarenal causes: hypodipsia, inability to access water (physical or mental), increased insensible losses (fever, hyperventilation, mechanical ventilation); laboratory findings: UOsm high, UNa variable

Peripheral edema, blood pressure may be variable

Extrarenal causes: 3% sodium chloride, sodium bicarbonate, salt tablets, tube feeding, hypertonic dialysate, sodium-containing antibiotics; laboratory findings: UOsm high, UNa high

Hypovolemic hypernatremia

Loss of free water and sodium (hypotonic solution loss)

Euvolemic hypernatremia

Loss of free water

2

N

Hypervolemic hypernatremia

Gain of free water and sodium (gain of hypertonic solution)

1

11

Clinical Features

Renal and Extrarenal Causes and Respective Laboratory Findings

Treatment 0.9% saline solution until vital signs stable, along with free water

Loop diuretics and free water replacement; hemodialysis if nothing works

Abbreviations: 1, increase; 2, decrease; ATN, acute tubular nephropathy; N, normal; UNa, urine sodium; UOsm, urine osmolality.

tremia typically result from a relative deficit in totalbody water in relation to total-body sodium content (Fig 1). All forms of hypernatremia represent a hypertonic state leading to vasopressin secretion and activation of the thirst mechanism.1 Volume status may modulate the response in vasopressin secretion so that one would potentially expect higher vasopressin secretion in hypovolemia than in hypervolemia. Thirst is highly effective in correcting hypernatremia; therefore, hypernatremia rarely develops unless the thirst mechanism is impaired or access to water is limited, as in young children, the elderly, and patients with impaired consciousness.8-10 The general principles of treating hypernatremia include diagnosis of the underlying cause, clinical assessment of volume status, estimation of water deficit, choosing a rate of correction, selecting a fluid repletion regimen, and subsequent monitoring and adjustments during therapy. Increased plasma osmolality due to hypernatremia results in water movement out of brain cells, causing cell shrinkage. The brain then undergoes adaptive processes that involve accumulation of additional solutes to restore brain volume. This consists of rapid accumulation of inorganic ions and slower accumulation of organic osmolytes.5 This adaptive process in chronic hypernatremia accounts for the occurrence of fewer neurologic symptoms compared with acute hypernatremia of similar magnitude.5,11 As a patient 1034

recovers from chronic hypernatremia, brain organic solute content is restored to normal levels slowly over 24-48 hours. Therefore, correction of chronic hypernatremia must occur gradually to prevent rapid fluid movement into the brain cells and the associated development of cerebral edema.12 Most experts recommend that the rate of sodium correction not exceed 0.5 mEq/L/h and 10-12 mEq/L/d in patients with hypernatremia for more than 24 hours.1,5 However, there are no randomized trials available to support this recommendation. Animal studies and case series in pediatric patients suggest that more rapid rates can lead to neurologic symptoms.13,14 Because hypernatremia is not a uniform disorder, the initial step in treatment is to correctly determine volume status and reverse the underlying cause(s) to prevent worsening of the condition (Table 2). The clinical approach to the assessment of hypovolemia and dehydration has been reviewed recently in this series.15 The general management principles of various types of hypernatremia are listed in Table 2. The composition of fluid that is given is largely dependent on the type of fluid that has been lost and any concurrent electrolyte disorders. The water deficit present with pure water loss (no change in total-body cation content) can be estimated from the following formula, derived from the Edelman equations7: water deficit ⫽ total-body water ⫻ (current serum sodium Am J Kidney Dis. 2012;60(6):1032-1038

Treatment of Chronic Hypernatremia Box 1. Development and Treatment of Hypervolemic Hypernatremia in Our Patient Effect of isotonic saline solution administration: 24-hour intake: 4.0 L of isotonic saline; 4 ⫻ 154 mEq/L ⫽ 616 mEq of sodium 24-hour output: 2.0 L of urine; urine osmolality 350 mEq/L Urine sodium plus potassium concentration (lost in urine) ⫽ ⬃100 mEq/L; 2 ⫻ 100 mEq ⫽ 200 mEq Net positive cation balance: 616 – 200 ⫽ 416 mEq Net positive water balance: 4.0 – 2.0 ⫽ 2.0 L Tonicity of retained fluid: 416 mEq/2.0 L ⫽ 208 mEq/L, which would increase [Na] ⬃ 1.0 mEq/L Effect of furosemide with either fluid restriction or water replacement: Prior to furosemide administration: serum sodium concentration: 146 mEq/L Body weight ⫽ 113 kg; TBW ⫽ 0.6 ⫻ 113 kg ⫽ 68 L; note: 0.6 ⫻ body weight used due to generalized edema Total-body cation content: 68 L ⫻ 146 mEq/L ⫽ 9,928 mEq 24-hour water intake: ⬍1.0 L, similar to insensible and stool losses 24-hour output: 4.0 L of urine; urine sodium plus potassium concentration ⫽ ⬃100 mEq/L Net cation balance: 0 intake ⫺ 4 ⫻ 100 mEq/L ⫽ ⫺400 mEq Net water balance: ⬃0 – 4 L⫽ ⫺4 L New total-body cation content: 9,928 – 400 ⫽ 9,528 mEq; new TBW ⫽ 64 L Predicted new serum sodium concentration: 9,528 mEq/64 L ⫽ 149 mEq/L Measured serum sodium concentration after furosemide was 149 mEq/L If 2 L of water were administered and retained, net water balance would be ⫺2.0 L New TBW ⫽ 66 L; predicted serum sodium concentration: 9,528/66 ⫽ 144 mEq/L Administration and retention of 4.0 L of water: 9,528/68 ⫽ 140 mEq/L with no change in TBW Alternative analysis (assuming a 4.0-L relative water deficit): furosemide yields a urine Na ⫹ K of ⬃100 mEq/L, which can be considered equivalent to excretion of 0.67 L of isotonic saline solution and 0.33 L of free water. Replacement of such urine output 1:1 with free water would result in the addition of 0.67 L of water per 1 L of urine output. Thus, replacement of 6.0 L of urine output with 6.0 L of free water would be necessary to correct the 4.0-L water deficit over the desired time frame, assuming no other losses. Note: Calculations are shown to demonstrate the mechanism for the development of hypernatremia during aggressive volume resuscitation with isotonic saline solution during initial treatment of lower gastrointestinal bleeding. Additional calculations, performed after the development of hypervolemic hypernatremia, demonstrate the changes in serum sodium concentration occurring with administration of furosemide, either with or without water replacement. Abbreviations: K, potassium; Na, sodium; TBW, total-body water.

concentration/140 ⫺ 1). This formula estimates the amount of positive water balance required to return serum sodium concentration to 140 mEq/L. Traditional recommendations suggest replacing 50% of the calculated water deficit over the first 24 hours, and the remainder over the subsequent 48-72 hours. Am J Kidney Dis. 2012;60(6):1032-1038

An additional equation, also derived from the Edelman equations, has been reported by Adrogue and Madias.1,16 This equation has been widely used clinically for the management of both hypo- and hypernatremia and has been studied prospectively in the management of hypernatremia.17 ⌬关Na兴 ⫽

关Na ⫹ K兴infusate ⫺ 关Na兴Serum Total body water ⫹ 1

The equation estimates the anticipated effect of retaining 1 L of the administered solution on serum sodium concentration. Application of either the first or second equation requires accurate measurement of body weight and related estimate of total-body water. In addition, these equations do not account for ongoing losses, which may vary markedly during the course of treatment. Both renal and extrarenal losses must be considered and added to the overall fluid prescription.1,11,16,18 In the absence of hyperthermia or diarrhea, urinary output represents the primary source of ongoing losses. Urinary losses will be increased in the setting of urinary concentrating defects (aging and acute and chronic kidney disease) and osmotic diuresis (hyperglycemia, mannitol, and urea).19 Accurate assessment of ongoing urinary losses requires measurements of urinary volume, osmolality, and cation (sodium and potassium) excretion. Insensible water loss, which in the absence of hyperthermia is ⬃0.5 L/d, also should be included. These data allow separate analysis of the net balance of sodium and potassium, as well as water. Appropriate adjustment in the fluid prescription must be guided by frequent assessment of the patient’s clinical status and serial monitoring of laboratory values during treatment.1,16,20,21 This often includes repeated measurements of serum sodium every 6-8 hours during initial therapy. There have been a number of additional published formulas that can be used in the management of chronic hypernatremia.7,22,23 These formulas are more mathematically complex and require detailed information about urinary excretion. It has been shown that these more complex formulas did not significantly differ from the Adrogue equation in their ability to predict changes in serum sodium concentration.17,23 Hypervolemic hypernatremia, considered to be the least common form of hypernatremia, has been attributed to excessive sodium administration (hypertonic sodium bicarbonate, hypertonic saline solution infusion, and accidental salt overloading).24-27 Hypernatremia with increased total-body water also can occur during administration of isotonic fluids to patients with salt-retaining states when there is impairment in urinary concentrating ability and limited access to water. In this setting, replacing hypotonic urinary or 1035

Al-Absi, Gosmanova, and Wall Box 2. Treatment of Hypovolemic Hypernatremia in Our Patient ⌬关Na⫹兴serum ⫽

关Na兴infusate ⫺ 关Na 兴serum ⫹

TBW ⫹ 1

Setting 1: 73-year-old man with [Na⫹] of 163 mmol/L, body weight of 94 kg, TBW ⫽ 0.4 ⫻ 94 ⫽ 37.6 La; selected solution is 0.9% normal saline (sodium concentration, 154 mEq/L)

⌬关Na⫹兴serum ⫽

154 ⫺ 163

⫽ ⫺0.23 mEq ⁄ L per 1 L of infusate 37.6 ⫹ 1 Patient received 3.0 L of 0.9% normal saline solution Predicted ⌬[Na⫹]serum ⫽ ⬃⫺0.7 mEq/L Observed ⌬[Na⫹]serum ⫽ ⬃0.0 mEq/L

Setting 2: Subsequent therapy with dextrose 5% in water as replacement solution 0 ⫺ 163 ⫽ ⫺4.2 mEq ⁄ L per 1 L of infusate 37.6 ⫹ 1 ⫹ For a goal of ⌬[Na ]serum of 10 mEq/L/24 h, 10/4.2 ⫽ 2.3 L of infusate required; given our patient’s estimated ongoing losses (GI and insensible losses of ⬃2.0 L), the rate of infusion becomes 4,300 mL/24 h ⫽ 179 mL/h Predicted ⌬[Na⫹]serum ⫽ ⬃⫺10 mEq/L Observed ⌬[Na⫹]serum ⫽ ⫺7.0 mEq/L ⌬关Na⫹兴serum ⫽

Note: Comparison of the effects on serum sodium concentration of isotonic saline solution infusion to those of 5% dextrose in water. Abbreviations: GI, gastrointestinal; Na, sodium; TBW, totalbody water. a Because of our patient’s age and the presence of dehydration, estimated TBW was taken as 40% of body weight.

nonrenal losses with isotonic solutions results in net retention of a hypertonic solution and development of hypernatremia. This scenario can occur during the treatment of a number of common disorders, including septic or hypovolemic shock, burns, uncontrolled diabetes, recovery from severe azotemia, and prolonged nasogastric suction.13,15 Hypervolemic hypernatremia has been recognized increasingly in the critical care setting.13,18,19 Balance studies of electrolytes and water (tonicity balance studies) have confirmed that this is due primarily to the administration of isotonic fluids in the context of impaired maximal urinary concentrating ability, with concomitant restriction of water intake.11 This has been described as “too little water and too much salt.”13 Analysis of 130 critically ill patients with hypernatremia showed that in 92% of cases, hypernatremia was acquired during an intensive care unit stay, and the main factor associated with hypernatremia was renal water loss. Inadequate correction, with too little free water and too much hypertonic solution, accompanied these cases.13 This mechanism is demonstrated in our patient in Box 1 during a representative 24-hour period when he was requiring aggressive fluid resuscitation. The goal of treatment of hypervolemic hypernatremia is 2-fold: (1) to achieve negative sodium and 1036

water balance to correct hypervolemia and (2) to gradually correct hypernatremia. This can be achieved with sodium restriction, diuresis with loop diuretics accompanied by water replacement, or hemodialysis.20,21 Correction of both hypervolemia and hypernatremia can occur only when a negative sodium and potassium balance exceeds a negative water balance.20 Administration of furosemide alone leads to excretion of urine with an osmolality of ⬃300 mOsm/kg and urinary sodium plus potassium concentrations of ⬃100 mEq/L. This demonstrates that water excretion exceeds cation excretion, leading to worsening of hypernatremia. Administration of 5% dextrose in water and furosemide can lead to resolution of both hypervolemia and hypernatremia. The predicted and observed effects of loop diuretics with either fluid restriction or concomitant water replacement in our patient are shown in Box 1. Note that furosemide administration in the presence of fluid restriction leads to a negative sodium and water balance, but worsened hypernatremia. However, administration of a loop diuretic with 2 L of water results in a negative water balance of 2.0 L and correction of hypernatremia to sodium level of 144 mEq/L. In both instances, extracellular fluid volume is decreased, whereas free water distributes to total-body water. A negative balance for both sodium and water can be achieved while simultaneously correcting hypertonicity/hypernatremia.28 The critical role of accurate measurement of body weight and subsequent estimation of total-body water is evident in observations during our patient’s second hospitalization, when he presented with hypovolemic hypernatremia. During the course of the prolonged Box 3. Key Teaching Points ● ● ●

●

Relative or absolute deficiency of electrolyte-free water is present in any form of hypernatremia Identify and reverse the underlying cause(s) of hypernatremia Determination of volume status (euvolemic, hypovolemic, or hypervolemic) is essential in the treatment of hypernatremia. Depending on the volume status of the patient, the specific solution needed to correct serum sodium concentration varies: 〫 Euvolemic form: use electrolyte-free water such as 5% dextrose 〫 Hypovolemic form: use 5% dextrose with quarter-normal saline or half-normal saline solution; isotonic saline solution should be used only if circulatory compromise is present and changed to hypotonic solution when vital signs are stable 〫 Hypervolemic form: use combination of hypotonic solutions as 5% dextrose and loop diuretics In the absence of interventional data, expert guidelines recommend to reduce serum sodium level by ⬃0.5 mEq/L per hour and no more than 10 mEq/L in 24 hours in chronic hypernatremia

Am J Kidney Dis. 2012;60(6):1032-1038

Treatment of Chronic Hypernatremia

illness, the patient had lost ⬃19 kg of body weight. Failure to obtain repeated measurements of body weight would have led to marked errors in total-body water estimate. Furthermore, total-body water, estimated as 0.6 ⫻ body weight, is accurate for only relatively healthy younger males.29 In females and the elderly, 0.5 ⫻ body weight is a closer approximation of total-body water under euvolemic conditions. In the setting of dehydration in an older patient, an additional adjustment of 0.4 ⫻ body weight more closely approximates true total-body water. Risk factors for the development of hypovolemic hypernatremia in our patient included impaired thirst, limited mobility restricting access to water, nonrenal losses from the ileostomy, and a urinary concentrating defect related to chronic kidney injury. At the time of the second hospitalization, he was hypovolemic with prerenal AKI and severe hypernatremia. AKI frequently accompanies hypernatremia,30 particularly in the settings of diarrhea or osmotic diuresis with intravascular volume depletion.30 AKI is rarely the direct cause of hypernatremia, but may contribute to the development of hypernatremia through limited urinary concentrating ability from impaired generation of medullary hypertonicity.31 The initial therapy consisted of isotonic saline solution for 18-24 hours to restore hemodynamics. As predicted from the Adrogue equation, this fluid therapy resulted in virtually no change in serum sodium concentration (Box 2). Subsequent therapy with 5% dextrose in water led to gradual correction of serum sodium concentration over 48 hours. Although the risk of overly rapid correction of chronic hypernatremia has been emphasized, observational studies also have suggested that a slow rate of correction of hypernatremia during the first 24 hours is also associated with increased mortality.32 Thus, an alternative treatment plan could have been administration of 1-2 L of normal saline solution acutely to rapidly restore plasma volume, followed by hypotonic fluids to promote correction of the hypernatremia.20,21 Intravenous free water replacement in the form of 5% dextrose in water generally is preferred over oral free water intake in the management of euvolemic hypernatremia in hospitalized patients. Hyperglycemia due to 5% dextrose in water is unlikely to occur when infusion rates are ⬍300 mL/h. However, insulin therapy may be necessary to avoid hyperglycemia and osmotic diuresis in diabetic patients. Intravenous 0.22% sodium chloride solution has been used successfully as replacement fluid, although there is a small risk of hemolysis with this solution. Chronic hypernatremia can be treated safely and effectively using sound clinical reasoning and quantitative assessment of intake and output, particularly Am J Kidney Dis. 2012;60(6):1032-1038

urinary output. All forms of hypernatremia are associated with a relative or absolute deficiency of water. Initial management includes identification of the underlying cause of hypernatremia and accurate determination of the patient’s volume status and body weight to allow calculation of the water deficit. Categorization into hypovolemic, euvolemic, and hypervolemic forms provides a starting point for formulating the type and rate of fluid to be administered. Frequent clinical assessment and serial laboratory data are essential to ensure gradual correction of hypernatremia by ⬃0.5 mEq/L per hour and no more than 10 mEq/L in 24 hours (Box 3).

ACKNOWLEDGEMENTS Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.

REFERENCES 1. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493-1499. 2. Kumar S, Berl T. Sodium. Lancet. 1998;352(9123):220-228. 3. Gennari FJ. Current concepts. Serum osmolality. Uses and limitations. N Engl J Med. 1984;310(2):102-105. 4. Feig PU, McCurdy DK. The hypertonic state. N Engl J Med. 1977;297(26):1444-1454. 5. Verbalis JG. Brain volume regulation in response to changes in osmolality. Neuroscience. 2010;168(4):862-870. 6. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1S266. 7. Edelman IS, Leibman J, O’Meara MP, Birkenfeld LW. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest. 1958;37(9):1236-1256. 8. Kenney WL, Chiu P. Influence of age on thirst and fluid intake. Med Sci Sports Exerc. 2001;33(9):1524-1532. 9. Phillips PA, Bretherton M, Johnston CI, Gray L. Reduced osmotic thirst in healthy elderly men. Am J Physiol. 1991;261(1, pt 2):R166-R171. 10. Stachenfeld NS, DiPietro L, Nadel ER, Mack GW. Mechanism of attenuated thirst in aging: role of central volume receptors. Am J Physiol. 1997;272(1, pt 2):R148-R157. 11. Carlotti AP, Bohn D, Mallie JP, Halperin ML. Tonicity balance, and not electrolyte-free water calculations, more accurately guides therapy for acute changes in natremia. Intensive Care Med. 2001;27(5):921-924. 12. Lien YH, Shapiro JI, Chan L. Effects of hypernatremia on organic brain osmoles. J Clin Invest. 1990;85(5):1427-1435. 13. Hoorn EJ, Betjes MG, Weigel J, Zietse R. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant. 2008;23(5):1562-1568. 14. Robertson G, Carrihill M, Hatherill M, Waggie Z, Reynolds L, Argent A. Relationship between fluid management, changes in serum sodium and outcome in hypernatraemia associated with gastroenteritis. J Paediatr Child Health. 2007;43(4):291-296. 15. Bhave G, Neilson EG. Volume depletion versus dehydration: how understanding the difference can guide therapy. Am J Kidney Dis. 2011;58(2):302-309. 1037

Al-Absi, Gosmanova, and Wall 16. Adrogue HJ, Madias NE. Aiding fluid prescription for the dysnatremias. Intensive Care Med. 1997;23(3):309-316. 17. Liamis G, Kalogirou M, Saugos V, Elisaf M. Therapeutic approach in patients with dysnatraemias. Nephrol Dial Transplant. 2006;21(6):1564-1569. 18. Sterns RH. Hypernatremia in the intensive care unit: instant quality—just add water. Crit Care Med. 1999;27(6):1041-1042. 19. Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124(2):197-203. 20. Rose BD. New approach to disturbances in the plasma sodium concentration. Am J Med. 1986;81(6):1033-1040. 21. Shafiee MA, Bohn D, Hoorn EJ, Halperin ML. How to select optimal maintenance intravenous fluid therapy. QJM. 2003; 96(8):601-610. 22. Nguyen MK, Kurtz I. Are the total exchangeable sodium, total exchangeable potassium and total body water the only determinants of the plasma water sodium concentration? Nephrol Dial Transplant. 2003;18(7):1266-1271. 23. Lindner G, Schwarz C, Kneidinger N, Kramer L, Oberbauer R, Druml W. Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients. Nephrol Dial Transplant. 2008;23(11):3501-3508. 24. Krige JE, Millar AJ, Rode H, Knobel D. Fatal hypernatraemia after hypertonic saline irrigation of hepatic hydatid cysts. Pediatr Surg Int. 2002;18(1):64-65.

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25. Mattar JA, Weil MH, Shubin H, Stein L. Cardiac arrest in the critically ill. II. Hyperosmolal states following cardiac arrest. Am J Med. 1974;56(2):162-168. 26. Meadow R. Non-accidental salt poisoning. Arch Dis Child. 1993;68(4):448-452. 27. Moder KG, Hurley DL. Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature. Mayo Clin Proc. 1990;65(12):1587-1594. 28. Nguyen MK, Kurtz I. Correction of hypervolaemic hypernatraemia by inducing negative Na⫹ and K⫹ balance in excess of negative water balance: a new quantitative approach. Nephrol Dial Transplant. 2008;23(7):2223-2227. 29. Fulop T Jr, Worum I, Csongor J, Foris G, Leovey A. Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects. Gerontology. 1985;31(1): 6-14. 30. Lindner G, Kneidinger N, Holzinger U, Druml W, Schwarz C. Tonicity balance in patients with hypernatremia acquired in the intensive care unit. Am J Kidney Dis. 2009;54(4):674-679. 31. Anderson RJ, Gordon JA, Kim J, Peterson LM, Gross PA. Renal concentration defect following nonoliguric acute renal failure in the rat. Kidney Int. 1982;21(4):583-591. 32. Alshayeb HM, Showkat A, Babar F, Mangold T, Wall BM. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci. 2011;341(5):356-360.

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