A Clinical Approach to the Treatment of Chronic Hypernatremia

Transcription

1 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, MD 1,2 Hypernatremia is a commonly encountered electrolyte disorder occurring in both the inpatient and outpatient settings. Community-acquired typically occurs at the extremes of age, whereas hospitalacquired 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 and the rate of correction of are associated with significant morbidity and mortality, prompt effective treatment is crucial. Chronic 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, which occurred in the same patient during the course of a prolonged illness. Am J Kidney Dis. 60(6): 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. From the 1 Nephrology Division, University of Wisconsin Madison, WI; and 2 Nephrology Division, Veteran Affairs Medical Center, Memphis, TN. * Current affiliation: Nephrology Division, University of Wisconsin, Madison, WI. Received February 1, Accepted in revised form June 13, Originally published online September 10, Address correspondence to Barry M. Wall, MD, Nephrology Division, Veterans Affairs Medical Center and University of Tennessee Health Sciences Center, Memphis, TN. barry. wall@va.gov 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 /$ 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, invariably denotes hypertonicity and results in cellular dehydration. 1 In the setting of sustained, 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 is required to avoid cerebral edema and serious neurologic complications. 5 Chronic can be categorized into hypovolemic, euvolemic, and hypervolemic forms, 1 with each form requiring markedly different treatment. CASE REPORT 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 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 with sodium level of meq/l ( 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 and recurrent AKI (Table 1). The diagnosis of hypovolemic 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. 1032

2 Treatment of Chronic Hypernatremia Parameter Admission Values Table 1. Serial Laboratory Data 1 Week After Admission After Rehabilitation Second Admission Discharge Values Sodium (meq/l) Potassium (meq/l) Chloride (meq/l) Bicarbonate (meq/l) SUN (mg/dl) Creatinine (mg/dl) egfr (ml/min/1.73 m 2 ) Glucose (mg/dl) Urine osmolality (mosm/kg) NA NA NA Urine sodium (meq/l) NA 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 m 2 to ml/s/1.73 m 2, ; glucose in mg/dl to mmol/l, 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 over a 48-hour period. Diagnosis Hypervolemic followed by hypovolemic. 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 m 2 [0.77 ml/s/1.73m 2 ] calculated by the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation) 6 and a defect in urinary concentration (maximum urine osmolality, mosm/kg [ mmol/kg]) persisted. He continues to have limited mobility and decreased sensation of thirst, leaving him at high risk of recurrent. 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 Madias 1 with permission from the Massachusetts Medical Society. 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 1033

3 Al-Absi, Gosmanova, and Wall Table 2. Hypernatremia Overview Problem Total-Body Water Total-Body Na Clinical Features Renal and Extrarenal Causes and Respective Laboratory Findings Treatment Hypovolemic Euvolemic Hypervolemic Loss of free water and sodium (hypotonic solution loss) 22 2 Orthostasis, hypotension, tachycardia, dry mucous membranes Loss of free water 2 N Normal vital signs, no edema Gain of free water and sodium (gain of hypertonic solution) 1 11 Peripheral edema, blood pressure may be variable 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 Renal causes: central or nephrogenic diabetes insipidus; 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 Extrarenal causes: 3% sodium chloride, sodium bicarbonate, salt tablets, tube feeding, hypertonic dialysate, sodium-containing antibiotics; laboratory findings: UOsm high, UNa high Abbreviations: 1, increase; 2, decrease; ATN, acute tubular nephropathy; N, normal; UNa, urine sodium; UOsm, urine osmolality. 0.9% saline solution until vital signs stable, along with free water Free water replacement Loop diuretics and free water replacement; hemodialysis if nothing works tremia typically result from a relative deficit in totalbody water in relation to total-body sodium content (Fig 1). All forms of 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 ; therefore, 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 The general principles of treating 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 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 accounts for the occurrence of fewer neurologic symptoms compared with acute of similar magnitude. 5,11 As a patient recovers from chronic, brain organic solute content is restored to normal levels slowly over hours. Therefore, correction of chronic 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 meq/l/d in patients with 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 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 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 equations 7 : water deficit total-body water (current serum sodium 1034

4 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; 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; meq 200 meq Net positive cation balance: meq Net positive water balance: 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 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 meq/l 400 meq Net water balance: 0 4L 4L New total-body cation content: 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/ meq/l Administration and retention of 4.0 L of water: 9,528/ meq/l with no change in TBW Alternative analysis (assuming a 4.0-L relative water deficit): furosemide yields a urine Na Kof 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 1Lofurine 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 during aggressive volume resuscitation with isotonic saline solution during initial treatment of lower gastrointestinal bleeding. Additional calculations, performed after the development of hypervolemic, 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 hours. 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 and has been studied prospectively in the management of. 17 Na Na K infusate Na 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. 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, considered to be the least common form of, has been attributed to excessive sodium administration (hypertonic sodium bicarbonate, hypertonic saline solution infusion, and accidental salt overloading) 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

5 Al-Absi, Gosmanova, and Wall Box 2. Treatment of Hypovolemic Hypernatremia in Our Patient Na serum Na infusate Na serum TBW 1 Setting 1: 73-year-old man with [Na ] of 163 mmol/l, body weight of 94 kg, TBW L a ; selected solution is 0.9% normal saline (sodium concentration, 154 meq/l) Na serum 0.23 meq L per 1Lofinfusate 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 Na serum mEq Lper1Lofinfusate For a goal of [Na ] serum of 10 meq/l/24 h, 10/ 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 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. 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 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 showed that in 92% of cases, was acquired during an intensive care unit stay, and the main factor associated with 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 is 2-fold: (1) to achieve negative sodium and water balance to correct hypervolemia and (2) to gradually correct. This can be achieved with sodium restriction, diuresis with loop diuretics accompanied by water replacement, or hemodialysis. 20,21 Correction of both hypervolemia and 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. Administration of 5% dextrose in water and furosemide can lead to resolution of both hypervolemia and. 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. However, administration of a loop diuretic with 2 L of water results in a negative water balance of 2.0 L and correction of 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/. 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. 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 Identify and reverse the underlying cause(s) of Determination of volume status (euvolemic, hypovolemic, or hypervolemic) is essential in the treatment of. 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 1036

6 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 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. AKI frequently accompanies, 30 particularly in the settings of diarrhea or osmotic diuresis with intravascular volume depletion. 30 AKI is rarely the direct cause of, but may contribute to the development of through limited urinary concentrating ability from impaired generation of medullary hypertonicity. 31 The initial therapy consisted of isotonic saline solution for 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 has been emphasized, observational studies also have suggested that a slow rate of correction of 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. 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 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 can be treated safely and effectively using sound clinical reasoning and quantitative assessment of intake and output, particularly urinary output. All forms of are associated with a relative or absolute deficiency of water. Initial management includes identification of the underlying cause of 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 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): Kumar S, Berl T. Sodium. 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