- Email: [email protected]
Hypernatremia in Adults
H y p e r n a t rem i a i n A d u l t s Jesse Theisen-Toupal,
MD
a,
*, Melissa L.P. Mattison,
MD
b
KEYWORDS Sodium Hypernatremia Electrolyte disorders Diabetes insipidus
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Hypernatremia is diagnosed by increased serum sodium concentration. 2. Attempt to identify the cause of hypernatremia. Pay special attention to water intake, water loss, and sodium intake. 3. Treat the underlying cause of hypernatremia if possible. 4. Determine the rate of onset of hypernatremia. If unclear, assume chronic hypernatremia. 5. Determine the goal rate of correction. In acute hypernatremia, the goal rate of correction should be 1.0 mmol/L/h. In chronic hypernatremia, the goal rate of correction should be 0.4 mmol/L/h for a maximum decrease of 10.0 mmol/L/d. 6. Pick the type of infusate and calculate the rate of infusion to meet goal rate of correction. 7. Remeasure laboratory results frequently to ensure proper rate of correction.
DEFINITION
What is a normal sodium level? Sodium is actively pumped out of cells, with 85% to 90% of sodium contained in the extracellular space. The normal plasma sodium concentration is 135 mmol/L to 145 mmol/L. Hypernatremia is defined as a plasma sodium concentration of greater than 145 mmol/L.1,2 There is no widely accepted definition of severe hypernatremia; however, medical literature generally defines severe hypernatremia as a plasma sodium concentration higher than 155 mmol/L3–5 or 160 mmol/L.6,7
Disclosure statement: the authors have no funding sources or other conflicts of interest to disclose. a Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Span-2, Boston, MA 02215, USA; b Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Span-2, Boston, MA 02215, USA * Corresponding author. E-mail address: [email protected] Hosp Med Clin 4 (2015) 230–242 http://dx.doi.org/10.1016/j.ehmc.2014.12.003 2211-5943/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
Hypernatremia in Adults
EPIDEMIOLOGY
How common is hypernatremia in hospitalized patients? The rates of hypernatremia at the time of admission and acquired during the hospitalization are listed in Table 1. What factors are associated with the development of hypernatremia? Multiple factors have been associated with hypernatremia, including central nervous system disease, previous brain injury, diabetes insipidus, diabetes mellitus, diuretic therapy, surgery, hypokalemia, hypercalcemia, hypoalbuminemia, renal dysfunction, febrile illness, cardiovascular disease, older age, admission from a nursing home, hospitalization, and mechanical ventilation.6,8–10,12,13 What is the mortality for hospitalized patients with hypernatremia? The mortality of hospitalized patients with hypernatremia is listed in Table 2. The mortality in hypernatremia is increased when compared with normonatremic control groups.11,13,14 In addition, hypernatremia that develops during the hospitalization is associated with increased mortality compared with hypernatremia that is present at the time of admission.10,11 PHYSIOLOGY OF SODIUM REGULATION
What is the physiology of sodium regulation? Sodium concentrations are determined by a complex interplay between water, cell permeability, transporters, and active pumps. In general, water is freely permeable across cells, which leads to osmotic equilibrium between extracellular and intracellular fluids. Sodium is the primary effective extracellular solute, with glucose being other major solute. However, in the absence of hyperglycemia, sodium has a higher concentration than glucose.1,2 Table 1 The rates of hypernatremia at admission and acquired during hospitalization Study
Definition
Admission Rate (%)
Hospitalization Rate (%)
General Medical and Surgical Patients Snyder et al,8 1987
>148 mmol/L
0.5
1.1
Pavelsky et al,9 1996
>149 mmol/L
0.2
1.0
Polderman et al,10 1999
>149 mmol/L
8.9
5.7
Lindner et al,11 2007
>149 mmol/L
2.1
7.0
Funk et al,4 2010
>145 mmol/L
6.9
a
Intensive Care Unit Patients
The definition is the concentration of plasma sodium used for inclusion criteria in the study. The admission rate is the rate of hypernatremia on admission, and the hospitalization rate is the percentage of patients who developed hypernatremia at any point during their hospitalization. The hospitalization rate signifies at any point in hospitalization for general medicine and surgical patients and for the duration of intensive care unit stay for intensive care unit patients. a Funk (2010) did not study hypernatremia that developed during hospitalization. Data from Refs.4,8–11
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Table 2 Mortality of hospitalized patients with hypernatremia Study
Hypernatremia Mortality (%)
Snyder et al,8 1987
42
Long et al,6 1991
54
Pavelsky et al,9 1996
41
Mandal et al,15 1997
66
Polderman et al,10 1999
20, 32a,b 39, 43a,b
24
2008
48a
10
Stelfox et al,14 2008
34a
16
Alshayeb et al,5 2011
37
Lindner et al, Hoorn et al,
11
Control Mortality (%)
13
2007
a The first percentage is mortality associated with hypernatremia on admission; the second percentage is mortality associated with hypernatremia that developed during the hospitalization. b Study exclusively of intensive care unit patients. Data from Refs.5,6,8–11,13–15
Hypernatremia usually develops by a decrease in water volume but can also occur by an increase in sodium solutes. Either of these scenarios leads to an increase in plasma osmolality. Osmoreceptors located in the hypothalamus are stimulated by this increased osmolality and lead to a release of antidiuretic hormone from the posterior pituitary gland and stimulation of thirst. The antidiuretic hormone release leads to decreased water loss from the kidneys, and the thirst sensation results in increased water intake, which normalizes the sodium concentration.1,2 What is the cerebral adaptation to hypernatremia? Acute hypernatremia (hypernatremia that develops in <24 hours) leads to a loss in brain volume as a result of an osmotic shift of free water out of the cells. This situation can lead to demyelinating brain lesions, intracerebral hemorrhage, or subarachnoid hemorrhage.16 The brain attempts to prevent volume loss through the following mechanisms: Free water from the cerebrospinal fluid moves into the interstitial space and increases the interstitial volume. In addition, cells respond by an uptake of sodium and potassium salts. These responses limit the free water loss from the cells and preserve brain volume2,12 In prolonged hypernatremia, cells accumulate osmolytes (myoinositol, glutamine, glutamate, and taurine) to increase the amount of intracellular solutes and further prevent intracellular free water loss.2,12 MECHANISMS AND CAUSES OF HYPERNATREMIA
What are the mechanisms of hypernatremia? The main mechanisms that lead to hypernatremia are listed in Box 1.2,7,12,17 Sustained hypernatremia requires that thirst or access to water is impaired.12 What are the causes of hypernatremia? The causes of hypernatremia are listed in Box 2.2,7,12,17
Hypernatremia in Adults
Box 1 Mechanisms of hypernatremia Water loss: Pure water loss: water loss in absence of sodium loss, such as insensible respiratory losses12 Hypotonic fluid loss: fluid loss with a sodium plus potassium concentration less than that in the plasma, such as urinary losses2,7,12 Water loss into cells: transient hypernatremia can occur when intracellular osmolality is increased and leads to water influx into cells and increased extracellular sodium concentrations; this transient hypernatremia can be caused by activities, such as severe exercise, and on cessation of activities the sodium returns to normal within 5 to 15 minutes17,18 Sodium overload: hypertonic sodium administration without appropriate water intake leads to hypernatremia2,7,12 Data from Refs.2,7,12,17,18
CLINICAL FEATURES, HISTORY, AND EXAMINATION
What are the clinical features of hypernatremia? The clinical features are correlated with the severity (usually >158–160 mmol/L) and rapidity of onset of hypernatremia.12,17,19 The features are mainly neurologic and are listed in Box 3. It is often difficult to determine the clinical manifestations of hypernatremia from the underlying predisposing conditions that led to the development of hypernatremia. What historical information and physical examination components are important?
The goals of the history and physical examination are to determine the cause (listed in Box 2) and severity of clinical manifestations (listed in Box 3) of hypernatremia. The history should focus on access to water, amount of water intake, loss of fluids (renal or gastrointestinal), ingestions, and medications. The physical examination should include a volume assessment and neurologic examination. What other workup is necessary? In most cases, further workup is not necessary, because the cause of the hypernatremia is clear based on history and physical examination. However, if the underlying cause is not clear, further workup may be necessary. The next test is to evaluate the urine osmolality.20 Low urine osmolality (<300 mosmol/kg) suggests central or nephrogenic diabetes insipidus (especially when the urine osmolality is less than the plasma osmolality). These entities can be distinguished by administration of exogenous antidiuretic hormone (desmopressin) and monitoring urine osmolality.17,20 Intermediate urine osmolality (300–600 mosmol/kg) can be seen in osmotic diuresis or central or nephrogenic diabetes insipidus. If the total solute excretion is more than 1000 mosmol in a 24-hourperiod, there is an increased solute excretion, which suggests an osmotic diuresis.20
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Box 2 Main causes of hypernatremia Water loss: Pure water loss: Insensible losses Impaired thirst (ie, hypodipsia) Neurologic deficit Hypotonic fluid loss: Renal losses Diabetes insipidus Diuretics Osmotic diuresis Polyuric phase of acute tubular necrosis Intrinsic renal disease Gastrointestinal losses Vomiting Nasogastric drainage Enterocutaneous fistula Diarrhea Osmotic laxatives Cutaneous losses Burns Sweating Water loss into cells: Severe exercise Seizures Sodium overload: Hypertonic sodium chloride or sodium bicarbonate intravenous infusion Hypertonic feeding preparation Hypertonic saline enemas Ingestion of sodium chloride Ingestion of sea water Hypertonic dialysis Primary hyperaldosteronism Cushing syndrome Data from Refs.2,7,12,17
High urine osmolality (>600 mosmol/kg) shows that the secretion of and response to antidiuretic hormone is intact. This factor suggests that the cause is unreplaced pure water loss, hypotonic fluid loss, or less commonly, sodium overload. Urine sodium concentration can further differentiate between pure
Hypernatremia in Adults
Box 3 Clinical manifestations of hypernatremia Thirst Anorexia Lethargy Irritability Muscle weakness Restlessness Nausea Vomiting Twitching Hyperreflexia Seizures Encephalopathy Stupor Coma Demyelinating brain lesions Intracerebral or subarachnoid hemorrhage Data from Refs.2,12,17,19
water or hypotonic fluid loss and sodium overload. In pure water or hypotonic fluid loss, the urine sodium is generally less than 25 mmol/L; however, in sodium overload, the urine sodium is generally greater than 100 mmol/L.17,20 In addition to these evaluations, further workup may be necessary to diagnose specific underlying conditions that predispose the individual to hypernatremia (eg, evaluation for hypothalamic lesion in an individual with hypodipsia or stool evaluation in an individual with infectious diarrhea).20 TREATMENT OF HYPERNATREMIA
What is the general approach to treat hypernatremia? The general approach to treatment requires addressing the underlying predisposing condition (if possible) and correcting the hypertonicity. The following factors must be considered: Underlying cause(s) of hypernatremia Rate of development of hypernatremia Severity of hypernatremia The identification and treatment (if possible) of the underlying cause of hypernatremia is essential. Any modifiable contributing factors or reversible barriers to water access should be addressed. The rate of development of hypernatremia is important, because it determines the appropriate rate of sodium correction. In cases of acute hypernatremia (present for <24 hours), such as salt poisoning, a rapid sodium correction (see later discussion)
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is appropriate to avoid complications from acute hypernatremia.2,12 In chronic hypernatremia (present for >24 to 48 hours; more common than acute hypernatremia), the rate of correction is slower (see later discussion). The slower rate of correction serves to prevent the complication of cerebral edema, which can occur in cases of overly rapid hypertonicity correction.2,12 How do you estimate water deficit? The total free water replacement needed to return serum sodium concentration to 140 mmol/L is estimated by the following formula2,12,21,22: Water deficit 5 total body water x ([serum sodium concentration/140]
1)
The current total body water estimate is as follows2,12,21,22:
Young men 5 60% of lean body weight Young women 5 50% of lean body weight Elderly men 5 50% of lean body weight Elderly women 5 45% of lean body weight
However, many individuals with hypernatremia are also water depleted, so values of 10% less than these figures are often used.20,23 See Box 4 for an example of the water deficit calculation. How do you choose a rate of correction? The key factor that determines the rate of correction is whether the hypernatremia is acute or chronic. In acute hypernatremia, the rate of correction should be relatively rapid to avoid the neurologic damage from acute hypernatremia. In addition, in acute hypernatremia, the cerebral adaptation response is incomplete, which means that rapid correction does not result in cerebral edema. In chronic hypernatremia, the rate of correction should be relatively slow, because rapid correction can lead to cerebral edema. The goal rate of correction for acute and chronic hypernatremia are listed as follows2,12,23: Acute hypernatremia: reduce serum sodium concentration by 1 mmol/L/h Chronic hypernatremia: reduce sodium 0.4 mmol/L/h for a maximum of 10 mmol/L/d Box 4 Calculating total water deficit What is the estimated water deficit of an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? The total body water is estimated by using 40% of the body weight (determined by total body water estimate elderly man and subtracting 10% for water depletion). Water deficit 5 0.4 60 kg ([168 mmol/L/140 mmol/L]
1) 5 4.8 kg
Given the density of water, this calculation equates to a total free water deficit of 4.8 L.20,23 Without any further loss of free water, it would take an estimated 4.8 L of free water to return the serum sodium concentration to 140 mmol/L. Data from Sterns RH. Etiology and evaluation of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014; and Sterns RH. Treatment of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.
Hypernatremia in Adults
What is the risk of a rapid correction of chronic hypernatremia? The main risk of a rapid correction of chronic hypernatremia is the development of cerebral edema. As discussed earlier (see section on cerebral adaptation to hypernatremia), the brain responds to chronic hypernatremia by accumulating osmolytes in brain cells to prevent intracellular water loss. With rapid decrease of the serum sodium concentration, further water moves into brain cells, which can result in cerebral edema and encephalopathy, seizures, or rarely, permanent neurologic damage or death.12,23 How do you determine the rate of intravenous infusion? The rate of intravenous infusion can be determined by the following equation, which estimates the effect of 1 L of infusate on serum sodium concentration12: Change in serum sodium concentration 5 (infusate sodium concentration sodium concentration)/(total body water 1 1)
serum
The infusate sodium concentrations of commonly used infusate solutions are listed in Table 3. The change in serum sodium concentration can be used to determine the rate of infusion. This point is best shown through the example in Box 5. This equation does not account for ongoing free water losses. Water losses from sweat and stool are routinely 30 to 40 mL per hour and may be higher in some conditions.23 Thus the rate of infusion based on these calculations likely underestimates the true rate of infusion need. What do you do in concurrent hypovolemia or hypokalemia? The addition of sodium or potassium to the infusate decreases the amount of free water provided. In the treatment of hypovolemia and hypernatremia, one can use infusate with hypotonic sodium chloride concentration (such as 0.45% sodium chloride in water) or give 2 infusate solutions (1 isotonic and 1 hypotonic) to correct for the hypovolemia and hypernatremia at the same time.12,23 In the setting of hypokalemia and hypernatremia, potassium can be added to the infusate. To determine the change in serum sodium concentration with an infusate containing potassium, the following equation can be used (also shown in Box 6)12: Change in serum sodium concentration 5 ([infusate sodium concentration 1 infusate potassium concentration] serum sodium concentration)/(total body water 1 1) Table 3 Infusate sodium concentrations Infusate
Infusate Sodium Concentration (mmol/L)
D5W
0
0.2% sodium chloride in D5W
34
0.45% sodium chloride in water
77
Ringer lactate solution
130
0.9% sodium chloride in water
154
Abbreviation: D5W, 5% dextrose in water. Data from Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000;342:1493–9.
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Box 5 Calculating rate of infusion What is the appropriate rate of 5% dextrose in water (D5W) infusion for an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? This is known to be chronic hypernatremia. Change in serum sodium concentration 5 (0 mmol/L Change in serum sodium concentration 5
168 mmol/L)/(60 0.4 1 1)
6.7 mmol/L per 1 L of D5W infused
Given this is chronic hypernatremia, our goal is to decrease the serum sodium concentration by 10 mmol/L in 24 hours. Using the above information, the patient needs an estimated 1.49 L of D5W in 24 hours, or 62 mL of D5W per hour. This example assumes no ongoing water losses.
How do you treat hypernatremia in a patient with diabetes insipidus? This is a brief discussion on the treatment of diabetes insipidus, because a full discussion is outside the scope of this article. The proper treatment of diabetes insipidus is dependent on whether it is central or nephrogenic. Central Diabetes Insipidus
Central diabetes insipidus is characterized by a deficiency in antidiuretic hormone (also known as vasopressin). These individuals have an inability to concentrate urine, which results in polyuria. If the individual has a normal mental status and access to water, they can maintain a relatively normal or mildly increased serum sodium concentration. However, if individuals have altered mental status, impaired thirst mechanism, or no access to water, hypernatremia can develop. In general, hypernatremia can be treated with antidiuretic hormone analogues, such as desmopressin.24 This medication serves to concentrate the urine and prevent free water loss. However, sometimes, additional medications are necessary (Table 4). The major risk of desmopressin therapy is hyponatremia.24 We recommend specialist involvement when initiating the medications outlined earlier. Nephrogenic Diabetes Insipidus
Similar to central diabetes insipidus, nephrogenic diabetes insipidus results in an inability to concentrate urine, which results in polyuria. Individuals with normal mental
Box 6 Calculating rate of infusion with potassium containing infusate What is the appropriate rate of D5W plus 40 mmol/L KCl infusion for an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? This is known to be chronic hypernatremia. Change in serum sodium concentration 5 ([0 mmol/L 1 40 mmol/L] Change in serum sodium concentration 5 plus 40 mmol/L of potassium infused
168 mmol/L)/(60 0.4 1 1)
5.1 mmol/L/L of 5% dextrose in water (D5W)
Given this is chronic hypernatremia, our goal is to decrease the serum sodium concentration by 10 mmol/L in 24 hours. Using the above information, the patient needs an estimated 1.96 L of D5W with 40 mmol/L KCl in 24 hours, or 81 mL per hour.
Hypernatremia in Adults
Table 4 Treatment of central diabetes insipidus Medication
Route; Dosea; Frequency
Antidiuretic Hormone Analogues Desmopressin (dDAVP)
Oral; 0.05 mg; 2 times per day (can be increased to 3 times daily) Intranasal spray; 10–40 mg per day; 1–3 times per day Subcutaneous; 2–4 mg per day (alternatively, 1/10 maintenance intranasal dose); 2 times per day The above doses should be adjusted to antidiuretic response. Fluid restriction should be observed
Enhance Renal Response to Arginine Vasopressin Clofibrate Chlorpropamide Carbamazepine
Oral; 500 mg; every 6 h Oral; 125 mg; 1–2 times per day Oral; 100–300 mg; 2 times per day
Reduce Urine Output Hydrochlorothiazide Nonsteroidal antiinflammatory drugs
Oral; 25–50 mg; 1–2 times per day Variable based on specific nonsteroidal antiinflammatory drug used
a
Dose recommendations for adults with normal renal function. Data from Bichet DG. Treatment of central diabetes insipidus. In Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014; and Singer I, Oster JR, Fishman LM. The Management of diabetes insipidus in adults. Arch Intern Med 1997;157:1293–301.
status and access to water maintain a relatively normal or mildly increased serum sodium concentration. However, with altered mental status or limited access to water, hypernatremia develops. The treatment of nephrogenic diabetes insipidus is challenging, because the kidneys do not respond, or have a limited response, to antidiuretic hormone. A search for revisable causes (such as chronic lithium use or hypercalcemia) should be undertaken, with modification in management as necessary. The goal of treatment is to decrease polyuria. Individuals need to maintain a lowsolute diet, which decreases the urine output (when compared with a high-solute diet). In addition, some patients require medical management. The options include thiazide diuretics (hydrochlorothiazide 25 mg orally 1 or 2 times per day), potassium-sparing diuretics (given along with thiazide diuretic therapy; such as amiloride), or nonsteroidal antiinflammatory drugs.25,26 How do you treat hypernatremia in a patient with volume overload? Hypernatremia in a patient with volume overload is usually secondary to sodium overload (such as administration of hypertonic sodium-containing solutions). Loop diuretics (such as furosemide) can be administered with free water infusate to improve volume status and serum sodium concentration. In patients with renal failure, renal replacement therapy may be necessary.12,17 When should serum sodium concentration be remeasured? The equations outlined earlier that are used to calculate the rate of infusion are just estimates. These estimates can be inaccurate (they usually underestimate the necessary rate of infusion). Given this factor, serum sodium concentrations need to be remeasured
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frequently, and the rate of infusion needs to be modified based on the results. The suggested initial frequency of serum sodium concentration remeasurement is listed as follows: Acute, severe hypernatremia: every 1 to 2 hours23 Chronic, severe hypernatremia: every 4 to 623 or 6 to 812 hours Once the rate of infusion is determined to be accurate (based on remeasurement of serum sodium concentrations), the frequency of remeasurement may be prolonged. In addition to remeasurement of serum sodium concentration, evaluation for hyperglycemia is also appropriate when using infusate with dextrose. Hyperglycemia can lead to osmotic diuresis, which limits the reduction of serum sodium concentration. It may be necessary to treat with insulin or modify the infusate solution to contain less dextrose.12,23
What follow-up is necessary after discharge? The necessary follow-up must be based on the underlying condition that predisposed the patient to hypernatremia. In cases in which the underlying condition has completely resolved (such as infectious diarrhea), no specific discharge follow-up may be necessary. However, in cases with continued underlying condition, close follow-up with ongoing measurement of serum sodium concentration may be necessary. For instance, in patients with impaired thirst, frequent serum sodium concentrations may need to be measured, with forced free water intake based on the results. What should discharge instructions include for patients with hypernatremia? Discharge instructions for patients admitted with hypernatremia must be tailored to the cause of the condition. For example, older patients with dementia often lack ready access to water. Their fluid intake can be further hindered by a blunted thirst response. Thus, discharge instructions for the caretaker of this patient should include promoting regular and sufficient intake of free water each day. When should specialists be consulted? Renal specialists should be consulted whenever the cause of the hypernatremia is not clearly understood, or if the clinician feels that their expertise would be valuable to the care of the patient. Examples might include times when medication is required for central diabetes insipidus. Other instances might be when the serum sodium level begins to correct too quickly or does not correct as anticipated. PRACTICE IMPROVEMENT
There are no published practice improvement metrics for hypernatremia. CLINICAL GUIDELINES
Although there are no consensus guidelines regarding the diagnosis or management of hypernatremia, many institutions have developed internal, local guidelines. Attention to the local guidelines, when present, is advised.
Hypernatremia in Adults
REFERENCES
1. Singer GG, Brenner BM. Fluid and electrolyte disturbances. In: Kasper DL, Fauci AS, Longo DL, et al, editors. Harrison’s principles of internal medicine. 16th edition. New York: McGraw-Hill; 2005. p. 252–8. 2. Dennen P, Linas SL. Hypernatremia. In: Gilbert SJ, Weiner DE, editors. National kidney foundation’s primer on kidney diseases. 6th edition. Philadelphia: Elsevier Saunders; 2014. p. 71–9. 3. Daggett P, Deanfield J, Moss F, et al. Severe hypernatraemia in adults. Br Med J 1979;1:1177–90. 4. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med 2010;36:304–11. 5. Alshayeb HM, Showkat A, Babar F, et al. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci 2011;341:356–60. 6. Long CA, Marin P, Bayer AJ, et al. Hypernatraemia in an adult in-patient population. Postgrad Med J 1991;67:643–5. 7. Wakil A, Atkin SL. Serum sodium disorders: safe management. Clin Med 2010;10: 79–82. 8. Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients: a heterogeneous, morbid and iatrogenic entity. Ann Intern Med 1987;107:303–19. 9. Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med 1996;124:197–203. 10. Polderman KH, Schreuder WO, Strack van Schijndel RJ, et al. Hypernatremia in the intensive care unit: an indicator of quality of care? Crit Care Med 1999;27:1105–8. 11. Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an independent risk factor for mortality. Am J Kidney Dis 2007;50:952–7. 12. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000;342:1493–9. 13. Hoorn EJ, Betjes MG, Weigel J, et al. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant 2008;23:1562–8. 14. Stelfox HT, Ahmed SB, Khandwala F, et al. The epidemiology of intensive care unit-acquired hyponatremia and hypernatremia in medical-surgical intensive care units. Crit Care 2008;12:R162. 15. Mandal AK, Saklayen MG, Hillman NM, et al. Predictive factors for high mortality in hypernatremic patients. Am J Emerg Med 1997;15:130–2. 16. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill; 2001. p. 716–61. 17. Bagshaw SM, Townsend DR. Disorders of sodium and water balance in hospitalized patients. Can J Anaesth 2009;56:151–67. 18. Felig P, Johnson C, Levitt M, et al. Hypernatremia induced by maximal exercise. JAMA 1982;248:1209. 19. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ 2006; 332:702–5. 20. Sterns RH. Etiology and evaluation of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014. 21. Soo SW. Hypernatremia: successful treatment. Electrolyte Blood Press 2006;4: 66–71. 22. Pavelsky PM. Hypernatremia. Semin Nephrol 1998;18:20–30. 23. Sterns RH. Treatment of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014. 24. Bichet DG. Treatment of central diabetes insipidus. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.
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25. Singer I, Oster JR, Fishman LM. The management of diabetes insipidus in adults. Arch Intern Med 1997;157:1293–301. 26. Bichet DG. Treatment of nephrogenic diabetes insipidus. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.
MD
a,
*, Melissa L.P. Mattison,
MD
b
KEYWORDS Sodium Hypernatremia Electrolyte disorders Diabetes insipidus
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Hypernatremia is diagnosed by increased serum sodium concentration. 2. Attempt to identify the cause of hypernatremia. Pay special attention to water intake, water loss, and sodium intake. 3. Treat the underlying cause of hypernatremia if possible. 4. Determine the rate of onset of hypernatremia. If unclear, assume chronic hypernatremia. 5. Determine the goal rate of correction. In acute hypernatremia, the goal rate of correction should be 1.0 mmol/L/h. In chronic hypernatremia, the goal rate of correction should be 0.4 mmol/L/h for a maximum decrease of 10.0 mmol/L/d. 6. Pick the type of infusate and calculate the rate of infusion to meet goal rate of correction. 7. Remeasure laboratory results frequently to ensure proper rate of correction.
DEFINITION
What is a normal sodium level? Sodium is actively pumped out of cells, with 85% to 90% of sodium contained in the extracellular space. The normal plasma sodium concentration is 135 mmol/L to 145 mmol/L. Hypernatremia is defined as a plasma sodium concentration of greater than 145 mmol/L.1,2 There is no widely accepted definition of severe hypernatremia; however, medical literature generally defines severe hypernatremia as a plasma sodium concentration higher than 155 mmol/L3–5 or 160 mmol/L.6,7
Disclosure statement: the authors have no funding sources or other conflicts of interest to disclose. a Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Span-2, Boston, MA 02215, USA; b Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Span-2, Boston, MA 02215, USA * Corresponding author. E-mail address: [email protected] Hosp Med Clin 4 (2015) 230–242 http://dx.doi.org/10.1016/j.ehmc.2014.12.003 2211-5943/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
Hypernatremia in Adults
EPIDEMIOLOGY
How common is hypernatremia in hospitalized patients? The rates of hypernatremia at the time of admission and acquired during the hospitalization are listed in Table 1. What factors are associated with the development of hypernatremia? Multiple factors have been associated with hypernatremia, including central nervous system disease, previous brain injury, diabetes insipidus, diabetes mellitus, diuretic therapy, surgery, hypokalemia, hypercalcemia, hypoalbuminemia, renal dysfunction, febrile illness, cardiovascular disease, older age, admission from a nursing home, hospitalization, and mechanical ventilation.6,8–10,12,13 What is the mortality for hospitalized patients with hypernatremia? The mortality of hospitalized patients with hypernatremia is listed in Table 2. The mortality in hypernatremia is increased when compared with normonatremic control groups.11,13,14 In addition, hypernatremia that develops during the hospitalization is associated with increased mortality compared with hypernatremia that is present at the time of admission.10,11 PHYSIOLOGY OF SODIUM REGULATION
What is the physiology of sodium regulation? Sodium concentrations are determined by a complex interplay between water, cell permeability, transporters, and active pumps. In general, water is freely permeable across cells, which leads to osmotic equilibrium between extracellular and intracellular fluids. Sodium is the primary effective extracellular solute, with glucose being other major solute. However, in the absence of hyperglycemia, sodium has a higher concentration than glucose.1,2 Table 1 The rates of hypernatremia at admission and acquired during hospitalization Study
Definition
Admission Rate (%)
Hospitalization Rate (%)
General Medical and Surgical Patients Snyder et al,8 1987
>148 mmol/L
0.5
1.1
Pavelsky et al,9 1996
>149 mmol/L
0.2
1.0
Polderman et al,10 1999
>149 mmol/L
8.9
5.7
Lindner et al,11 2007
>149 mmol/L
2.1
7.0
Funk et al,4 2010
>145 mmol/L
6.9
a
Intensive Care Unit Patients
The definition is the concentration of plasma sodium used for inclusion criteria in the study. The admission rate is the rate of hypernatremia on admission, and the hospitalization rate is the percentage of patients who developed hypernatremia at any point during their hospitalization. The hospitalization rate signifies at any point in hospitalization for general medicine and surgical patients and for the duration of intensive care unit stay for intensive care unit patients. a Funk (2010) did not study hypernatremia that developed during hospitalization. Data from Refs.4,8–11
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Table 2 Mortality of hospitalized patients with hypernatremia Study
Hypernatremia Mortality (%)
Snyder et al,8 1987
42
Long et al,6 1991
54
Pavelsky et al,9 1996
41
Mandal et al,15 1997
66
Polderman et al,10 1999
20, 32a,b 39, 43a,b
24
2008
48a
10
Stelfox et al,14 2008
34a
16
Alshayeb et al,5 2011
37
Lindner et al, Hoorn et al,
11
Control Mortality (%)
13
2007
a The first percentage is mortality associated with hypernatremia on admission; the second percentage is mortality associated with hypernatremia that developed during the hospitalization. b Study exclusively of intensive care unit patients. Data from Refs.5,6,8–11,13–15
Hypernatremia usually develops by a decrease in water volume but can also occur by an increase in sodium solutes. Either of these scenarios leads to an increase in plasma osmolality. Osmoreceptors located in the hypothalamus are stimulated by this increased osmolality and lead to a release of antidiuretic hormone from the posterior pituitary gland and stimulation of thirst. The antidiuretic hormone release leads to decreased water loss from the kidneys, and the thirst sensation results in increased water intake, which normalizes the sodium concentration.1,2 What is the cerebral adaptation to hypernatremia? Acute hypernatremia (hypernatremia that develops in <24 hours) leads to a loss in brain volume as a result of an osmotic shift of free water out of the cells. This situation can lead to demyelinating brain lesions, intracerebral hemorrhage, or subarachnoid hemorrhage.16 The brain attempts to prevent volume loss through the following mechanisms: Free water from the cerebrospinal fluid moves into the interstitial space and increases the interstitial volume. In addition, cells respond by an uptake of sodium and potassium salts. These responses limit the free water loss from the cells and preserve brain volume2,12 In prolonged hypernatremia, cells accumulate osmolytes (myoinositol, glutamine, glutamate, and taurine) to increase the amount of intracellular solutes and further prevent intracellular free water loss.2,12 MECHANISMS AND CAUSES OF HYPERNATREMIA
What are the mechanisms of hypernatremia? The main mechanisms that lead to hypernatremia are listed in Box 1.2,7,12,17 Sustained hypernatremia requires that thirst or access to water is impaired.12 What are the causes of hypernatremia? The causes of hypernatremia are listed in Box 2.2,7,12,17
Hypernatremia in Adults
Box 1 Mechanisms of hypernatremia Water loss: Pure water loss: water loss in absence of sodium loss, such as insensible respiratory losses12 Hypotonic fluid loss: fluid loss with a sodium plus potassium concentration less than that in the plasma, such as urinary losses2,7,12 Water loss into cells: transient hypernatremia can occur when intracellular osmolality is increased and leads to water influx into cells and increased extracellular sodium concentrations; this transient hypernatremia can be caused by activities, such as severe exercise, and on cessation of activities the sodium returns to normal within 5 to 15 minutes17,18 Sodium overload: hypertonic sodium administration without appropriate water intake leads to hypernatremia2,7,12 Data from Refs.2,7,12,17,18
CLINICAL FEATURES, HISTORY, AND EXAMINATION
What are the clinical features of hypernatremia? The clinical features are correlated with the severity (usually >158–160 mmol/L) and rapidity of onset of hypernatremia.12,17,19 The features are mainly neurologic and are listed in Box 3. It is often difficult to determine the clinical manifestations of hypernatremia from the underlying predisposing conditions that led to the development of hypernatremia. What historical information and physical examination components are important?
The goals of the history and physical examination are to determine the cause (listed in Box 2) and severity of clinical manifestations (listed in Box 3) of hypernatremia. The history should focus on access to water, amount of water intake, loss of fluids (renal or gastrointestinal), ingestions, and medications. The physical examination should include a volume assessment and neurologic examination. What other workup is necessary? In most cases, further workup is not necessary, because the cause of the hypernatremia is clear based on history and physical examination. However, if the underlying cause is not clear, further workup may be necessary. The next test is to evaluate the urine osmolality.20 Low urine osmolality (<300 mosmol/kg) suggests central or nephrogenic diabetes insipidus (especially when the urine osmolality is less than the plasma osmolality). These entities can be distinguished by administration of exogenous antidiuretic hormone (desmopressin) and monitoring urine osmolality.17,20 Intermediate urine osmolality (300–600 mosmol/kg) can be seen in osmotic diuresis or central or nephrogenic diabetes insipidus. If the total solute excretion is more than 1000 mosmol in a 24-hourperiod, there is an increased solute excretion, which suggests an osmotic diuresis.20
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Box 2 Main causes of hypernatremia Water loss: Pure water loss: Insensible losses Impaired thirst (ie, hypodipsia) Neurologic deficit Hypotonic fluid loss: Renal losses Diabetes insipidus Diuretics Osmotic diuresis Polyuric phase of acute tubular necrosis Intrinsic renal disease Gastrointestinal losses Vomiting Nasogastric drainage Enterocutaneous fistula Diarrhea Osmotic laxatives Cutaneous losses Burns Sweating Water loss into cells: Severe exercise Seizures Sodium overload: Hypertonic sodium chloride or sodium bicarbonate intravenous infusion Hypertonic feeding preparation Hypertonic saline enemas Ingestion of sodium chloride Ingestion of sea water Hypertonic dialysis Primary hyperaldosteronism Cushing syndrome Data from Refs.2,7,12,17
High urine osmolality (>600 mosmol/kg) shows that the secretion of and response to antidiuretic hormone is intact. This factor suggests that the cause is unreplaced pure water loss, hypotonic fluid loss, or less commonly, sodium overload. Urine sodium concentration can further differentiate between pure
Hypernatremia in Adults
Box 3 Clinical manifestations of hypernatremia Thirst Anorexia Lethargy Irritability Muscle weakness Restlessness Nausea Vomiting Twitching Hyperreflexia Seizures Encephalopathy Stupor Coma Demyelinating brain lesions Intracerebral or subarachnoid hemorrhage Data from Refs.2,12,17,19
water or hypotonic fluid loss and sodium overload. In pure water or hypotonic fluid loss, the urine sodium is generally less than 25 mmol/L; however, in sodium overload, the urine sodium is generally greater than 100 mmol/L.17,20 In addition to these evaluations, further workup may be necessary to diagnose specific underlying conditions that predispose the individual to hypernatremia (eg, evaluation for hypothalamic lesion in an individual with hypodipsia or stool evaluation in an individual with infectious diarrhea).20 TREATMENT OF HYPERNATREMIA
What is the general approach to treat hypernatremia? The general approach to treatment requires addressing the underlying predisposing condition (if possible) and correcting the hypertonicity. The following factors must be considered: Underlying cause(s) of hypernatremia Rate of development of hypernatremia Severity of hypernatremia The identification and treatment (if possible) of the underlying cause of hypernatremia is essential. Any modifiable contributing factors or reversible barriers to water access should be addressed. The rate of development of hypernatremia is important, because it determines the appropriate rate of sodium correction. In cases of acute hypernatremia (present for <24 hours), such as salt poisoning, a rapid sodium correction (see later discussion)
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is appropriate to avoid complications from acute hypernatremia.2,12 In chronic hypernatremia (present for >24 to 48 hours; more common than acute hypernatremia), the rate of correction is slower (see later discussion). The slower rate of correction serves to prevent the complication of cerebral edema, which can occur in cases of overly rapid hypertonicity correction.2,12 How do you estimate water deficit? The total free water replacement needed to return serum sodium concentration to 140 mmol/L is estimated by the following formula2,12,21,22: Water deficit 5 total body water x ([serum sodium concentration/140]
1)
The current total body water estimate is as follows2,12,21,22:
Young men 5 60% of lean body weight Young women 5 50% of lean body weight Elderly men 5 50% of lean body weight Elderly women 5 45% of lean body weight
However, many individuals with hypernatremia are also water depleted, so values of 10% less than these figures are often used.20,23 See Box 4 for an example of the water deficit calculation. How do you choose a rate of correction? The key factor that determines the rate of correction is whether the hypernatremia is acute or chronic. In acute hypernatremia, the rate of correction should be relatively rapid to avoid the neurologic damage from acute hypernatremia. In addition, in acute hypernatremia, the cerebral adaptation response is incomplete, which means that rapid correction does not result in cerebral edema. In chronic hypernatremia, the rate of correction should be relatively slow, because rapid correction can lead to cerebral edema. The goal rate of correction for acute and chronic hypernatremia are listed as follows2,12,23: Acute hypernatremia: reduce serum sodium concentration by 1 mmol/L/h Chronic hypernatremia: reduce sodium 0.4 mmol/L/h for a maximum of 10 mmol/L/d Box 4 Calculating total water deficit What is the estimated water deficit of an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? The total body water is estimated by using 40% of the body weight (determined by total body water estimate elderly man and subtracting 10% for water depletion). Water deficit 5 0.4 60 kg ([168 mmol/L/140 mmol/L]
1) 5 4.8 kg
Given the density of water, this calculation equates to a total free water deficit of 4.8 L.20,23 Without any further loss of free water, it would take an estimated 4.8 L of free water to return the serum sodium concentration to 140 mmol/L. Data from Sterns RH. Etiology and evaluation of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014; and Sterns RH. Treatment of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.
Hypernatremia in Adults
What is the risk of a rapid correction of chronic hypernatremia? The main risk of a rapid correction of chronic hypernatremia is the development of cerebral edema. As discussed earlier (see section on cerebral adaptation to hypernatremia), the brain responds to chronic hypernatremia by accumulating osmolytes in brain cells to prevent intracellular water loss. With rapid decrease of the serum sodium concentration, further water moves into brain cells, which can result in cerebral edema and encephalopathy, seizures, or rarely, permanent neurologic damage or death.12,23 How do you determine the rate of intravenous infusion? The rate of intravenous infusion can be determined by the following equation, which estimates the effect of 1 L of infusate on serum sodium concentration12: Change in serum sodium concentration 5 (infusate sodium concentration sodium concentration)/(total body water 1 1)
serum
The infusate sodium concentrations of commonly used infusate solutions are listed in Table 3. The change in serum sodium concentration can be used to determine the rate of infusion. This point is best shown through the example in Box 5. This equation does not account for ongoing free water losses. Water losses from sweat and stool are routinely 30 to 40 mL per hour and may be higher in some conditions.23 Thus the rate of infusion based on these calculations likely underestimates the true rate of infusion need. What do you do in concurrent hypovolemia or hypokalemia? The addition of sodium or potassium to the infusate decreases the amount of free water provided. In the treatment of hypovolemia and hypernatremia, one can use infusate with hypotonic sodium chloride concentration (such as 0.45% sodium chloride in water) or give 2 infusate solutions (1 isotonic and 1 hypotonic) to correct for the hypovolemia and hypernatremia at the same time.12,23 In the setting of hypokalemia and hypernatremia, potassium can be added to the infusate. To determine the change in serum sodium concentration with an infusate containing potassium, the following equation can be used (also shown in Box 6)12: Change in serum sodium concentration 5 ([infusate sodium concentration 1 infusate potassium concentration] serum sodium concentration)/(total body water 1 1) Table 3 Infusate sodium concentrations Infusate
Infusate Sodium Concentration (mmol/L)
D5W
0
0.2% sodium chloride in D5W
34
0.45% sodium chloride in water
77
Ringer lactate solution
130
0.9% sodium chloride in water
154
Abbreviation: D5W, 5% dextrose in water. Data from Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000;342:1493–9.
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Box 5 Calculating rate of infusion What is the appropriate rate of 5% dextrose in water (D5W) infusion for an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? This is known to be chronic hypernatremia. Change in serum sodium concentration 5 (0 mmol/L Change in serum sodium concentration 5
168 mmol/L)/(60 0.4 1 1)
6.7 mmol/L per 1 L of D5W infused
Given this is chronic hypernatremia, our goal is to decrease the serum sodium concentration by 10 mmol/L in 24 hours. Using the above information, the patient needs an estimated 1.49 L of D5W in 24 hours, or 62 mL of D5W per hour. This example assumes no ongoing water losses.
How do you treat hypernatremia in a patient with diabetes insipidus? This is a brief discussion on the treatment of diabetes insipidus, because a full discussion is outside the scope of this article. The proper treatment of diabetes insipidus is dependent on whether it is central or nephrogenic. Central Diabetes Insipidus
Central diabetes insipidus is characterized by a deficiency in antidiuretic hormone (also known as vasopressin). These individuals have an inability to concentrate urine, which results in polyuria. If the individual has a normal mental status and access to water, they can maintain a relatively normal or mildly increased serum sodium concentration. However, if individuals have altered mental status, impaired thirst mechanism, or no access to water, hypernatremia can develop. In general, hypernatremia can be treated with antidiuretic hormone analogues, such as desmopressin.24 This medication serves to concentrate the urine and prevent free water loss. However, sometimes, additional medications are necessary (Table 4). The major risk of desmopressin therapy is hyponatremia.24 We recommend specialist involvement when initiating the medications outlined earlier. Nephrogenic Diabetes Insipidus
Similar to central diabetes insipidus, nephrogenic diabetes insipidus results in an inability to concentrate urine, which results in polyuria. Individuals with normal mental
Box 6 Calculating rate of infusion with potassium containing infusate What is the appropriate rate of D5W plus 40 mmol/L KCl infusion for an elderly 60-kg man with a serum sodium concentration of 168 mmol/L? This is known to be chronic hypernatremia. Change in serum sodium concentration 5 ([0 mmol/L 1 40 mmol/L] Change in serum sodium concentration 5 plus 40 mmol/L of potassium infused
168 mmol/L)/(60 0.4 1 1)
5.1 mmol/L/L of 5% dextrose in water (D5W)
Given this is chronic hypernatremia, our goal is to decrease the serum sodium concentration by 10 mmol/L in 24 hours. Using the above information, the patient needs an estimated 1.96 L of D5W with 40 mmol/L KCl in 24 hours, or 81 mL per hour.
Hypernatremia in Adults
Table 4 Treatment of central diabetes insipidus Medication
Route; Dosea; Frequency
Antidiuretic Hormone Analogues Desmopressin (dDAVP)
Oral; 0.05 mg; 2 times per day (can be increased to 3 times daily) Intranasal spray; 10–40 mg per day; 1–3 times per day Subcutaneous; 2–4 mg per day (alternatively, 1/10 maintenance intranasal dose); 2 times per day The above doses should be adjusted to antidiuretic response. Fluid restriction should be observed
Enhance Renal Response to Arginine Vasopressin Clofibrate Chlorpropamide Carbamazepine
Oral; 500 mg; every 6 h Oral; 125 mg; 1–2 times per day Oral; 100–300 mg; 2 times per day
Reduce Urine Output Hydrochlorothiazide Nonsteroidal antiinflammatory drugs
Oral; 25–50 mg; 1–2 times per day Variable based on specific nonsteroidal antiinflammatory drug used
a
Dose recommendations for adults with normal renal function. Data from Bichet DG. Treatment of central diabetes insipidus. In Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014; and Singer I, Oster JR, Fishman LM. The Management of diabetes insipidus in adults. Arch Intern Med 1997;157:1293–301.
status and access to water maintain a relatively normal or mildly increased serum sodium concentration. However, with altered mental status or limited access to water, hypernatremia develops. The treatment of nephrogenic diabetes insipidus is challenging, because the kidneys do not respond, or have a limited response, to antidiuretic hormone. A search for revisable causes (such as chronic lithium use or hypercalcemia) should be undertaken, with modification in management as necessary. The goal of treatment is to decrease polyuria. Individuals need to maintain a lowsolute diet, which decreases the urine output (when compared with a high-solute diet). In addition, some patients require medical management. The options include thiazide diuretics (hydrochlorothiazide 25 mg orally 1 or 2 times per day), potassium-sparing diuretics (given along with thiazide diuretic therapy; such as amiloride), or nonsteroidal antiinflammatory drugs.25,26 How do you treat hypernatremia in a patient with volume overload? Hypernatremia in a patient with volume overload is usually secondary to sodium overload (such as administration of hypertonic sodium-containing solutions). Loop diuretics (such as furosemide) can be administered with free water infusate to improve volume status and serum sodium concentration. In patients with renal failure, renal replacement therapy may be necessary.12,17 When should serum sodium concentration be remeasured? The equations outlined earlier that are used to calculate the rate of infusion are just estimates. These estimates can be inaccurate (they usually underestimate the necessary rate of infusion). Given this factor, serum sodium concentrations need to be remeasured
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frequently, and the rate of infusion needs to be modified based on the results. The suggested initial frequency of serum sodium concentration remeasurement is listed as follows: Acute, severe hypernatremia: every 1 to 2 hours23 Chronic, severe hypernatremia: every 4 to 623 or 6 to 812 hours Once the rate of infusion is determined to be accurate (based on remeasurement of serum sodium concentrations), the frequency of remeasurement may be prolonged. In addition to remeasurement of serum sodium concentration, evaluation for hyperglycemia is also appropriate when using infusate with dextrose. Hyperglycemia can lead to osmotic diuresis, which limits the reduction of serum sodium concentration. It may be necessary to treat with insulin or modify the infusate solution to contain less dextrose.12,23
What follow-up is necessary after discharge? The necessary follow-up must be based on the underlying condition that predisposed the patient to hypernatremia. In cases in which the underlying condition has completely resolved (such as infectious diarrhea), no specific discharge follow-up may be necessary. However, in cases with continued underlying condition, close follow-up with ongoing measurement of serum sodium concentration may be necessary. For instance, in patients with impaired thirst, frequent serum sodium concentrations may need to be measured, with forced free water intake based on the results. What should discharge instructions include for patients with hypernatremia? Discharge instructions for patients admitted with hypernatremia must be tailored to the cause of the condition. For example, older patients with dementia often lack ready access to water. Their fluid intake can be further hindered by a blunted thirst response. Thus, discharge instructions for the caretaker of this patient should include promoting regular and sufficient intake of free water each day. When should specialists be consulted? Renal specialists should be consulted whenever the cause of the hypernatremia is not clearly understood, or if the clinician feels that their expertise would be valuable to the care of the patient. Examples might include times when medication is required for central diabetes insipidus. Other instances might be when the serum sodium level begins to correct too quickly or does not correct as anticipated. PRACTICE IMPROVEMENT
There are no published practice improvement metrics for hypernatremia. CLINICAL GUIDELINES
Although there are no consensus guidelines regarding the diagnosis or management of hypernatremia, many institutions have developed internal, local guidelines. Attention to the local guidelines, when present, is advised.
Hypernatremia in Adults
REFERENCES
1. Singer GG, Brenner BM. Fluid and electrolyte disturbances. In: Kasper DL, Fauci AS, Longo DL, et al, editors. Harrison’s principles of internal medicine. 16th edition. New York: McGraw-Hill; 2005. p. 252–8. 2. Dennen P, Linas SL. Hypernatremia. In: Gilbert SJ, Weiner DE, editors. National kidney foundation’s primer on kidney diseases. 6th edition. Philadelphia: Elsevier Saunders; 2014. p. 71–9. 3. Daggett P, Deanfield J, Moss F, et al. Severe hypernatraemia in adults. Br Med J 1979;1:1177–90. 4. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med 2010;36:304–11. 5. Alshayeb HM, Showkat A, Babar F, et al. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci 2011;341:356–60. 6. Long CA, Marin P, Bayer AJ, et al. Hypernatraemia in an adult in-patient population. Postgrad Med J 1991;67:643–5. 7. Wakil A, Atkin SL. Serum sodium disorders: safe management. Clin Med 2010;10: 79–82. 8. Snyder NA, Feigal DW, Arieff AI. Hypernatremia in elderly patients: a heterogeneous, morbid and iatrogenic entity. Ann Intern Med 1987;107:303–19. 9. Palevsky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med 1996;124:197–203. 10. Polderman KH, Schreuder WO, Strack van Schijndel RJ, et al. Hypernatremia in the intensive care unit: an indicator of quality of care? Crit Care Med 1999;27:1105–8. 11. Lindner G, Funk GC, Schwarz C, et al. Hypernatremia in the critically ill is an independent risk factor for mortality. Am J Kidney Dis 2007;50:952–7. 12. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000;342:1493–9. 13. Hoorn EJ, Betjes MG, Weigel J, et al. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant 2008;23:1562–8. 14. Stelfox HT, Ahmed SB, Khandwala F, et al. The epidemiology of intensive care unit-acquired hyponatremia and hypernatremia in medical-surgical intensive care units. Crit Care 2008;12:R162. 15. Mandal AK, Saklayen MG, Hillman NM, et al. Predictive factors for high mortality in hypernatremic patients. Am J Emerg Med 1997;15:130–2. 16. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill; 2001. p. 716–61. 17. Bagshaw SM, Townsend DR. Disorders of sodium and water balance in hospitalized patients. Can J Anaesth 2009;56:151–67. 18. Felig P, Johnson C, Levitt M, et al. Hypernatremia induced by maximal exercise. JAMA 1982;248:1209. 19. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ 2006; 332:702–5. 20. Sterns RH. Etiology and evaluation of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014. 21. Soo SW. Hypernatremia: successful treatment. Electrolyte Blood Press 2006;4: 66–71. 22. Pavelsky PM. Hypernatremia. Semin Nephrol 1998;18:20–30. 23. Sterns RH. Treatment of hypernatremia. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014. 24. Bichet DG. Treatment of central diabetes insipidus. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.
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25. Singer I, Oster JR, Fishman LM. The management of diabetes insipidus in adults. Arch Intern Med 1997;157:1293–301. 26. Bichet DG. Treatment of nephrogenic diabetes insipidus. In: Basow DS, editor. UpToDate. Waltham (MA): UpToDate; 2014.