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Dysnatremias: why are patients still dying?

Abstract: Dysnatremias are a common clinical entity that are often associated with poor outcomes. This review takes a case study approach to understand how dysnatremias can result in devastating neurologic consequences. Concrete guidelines are provided for prevention, early recognition and treatment along with a discussion of how urinary electrolytes and osmolality can be used to guide therapy. Case studies in hyponatremic encephalopathy include the postoperative state, thiazide diuretics, extreme exercise and DDAVP[R] use. Reasons to avoid using hypotonic parenteral fluids, risk factors for hyponatremic encephalopathy such as age, gender, and hypoxia, and the appropriate use of 3% sodium chloride are discussed. Case studies in hypernatremia include hypernatremia in the ICU setting and the emerging condition of breastfeeding-associated hypernatremia in infants.

Key Words: hyponatremia, hypernatremia, hypertonic saline, cerebral demyelination, cerebral edema, breastfeeding


Dysnatremias are among the most common electrolyte disturbances and are commonly associated with poor outcomes. Despite significant literature dedicated to the recognition, treatment and prevention of dysnatremias, poor outcomes still occur. A factor in the persistence of this problem is failure to promptly recognize a life threatening condition and initiate appropriate treatment. This review will focus on the pathogenesis, treatment and prevention of dysnatremias with an emphasis on the common presentations of the diseases in a case-based format.

Physiology of Water Balance

The concentration of sodium in the serum reflects total body exchangeable sodium and potassium relative to total body water (1) and consequently, disturbances in serum sodium indicate disorders in water balance. Water balance is achieved through the actions of antidiuretic hormone (ADH), a.k.a. arginine vasopressin (AVP), (2,3) which under normal conditions maintains a near constant plasma osmolality. This is accomplished through osmoreceptors in the brain that affect ADH secretion, which in turn acts through aquaporin in the kidney collecting tubules to affect urine concentration (Fig. 1). (4-7)

Thus, maintenance of water balance requires an intact thirst mechanism and the ability of the kidneys to vary urinary concentration. In the absence of ADH activity (as in diabetes insipidus), urine concentration will be very low (50-80 mOsm/kg). When ADH activity is maximal, urinary concentration can increase to 1,200 mOsm/kg. Because of the wide range of urinary concentrations and the powerful stimulus of the thirst mechanism, plasma osmolality is generally kept within a narrow range.

In the evaluation of the dysnatremic patient, the urine electrolytes and not the urine osmolality determine the free water excretion of the patient. If the concentration of sodium ([[Na.sup.+]][.sub.u]) plus the concentration of potassium ([[K.sup.+]][.sub.u]) in the urine exceed the concentration of the sodium ([Na+][]) plus potassium ([[K.sup.+]][]) in the plasma, then the patient is in a state of free water retention. Conversely, if the [[Na.sup.+]][.sub.u] + [[K.sup.+]][.sub.u] is less than [Na+][] + [[K.sup.+]][] the patient is losing free water in the urine. This information is most useful in two circumstances: 1) in cases of water loss secondary to an osmotic load (such as urea or glucose) and 2) in assessing free water losses following correction of hyponatremia in a case where a free water diuresis can ensure. These scenarios and the utility of this approach are illustrated in more detail in Cases #4 and #6.



The definition of hyponatremia is a serum sodium of < 135 mEq/L. The kidney's ability to dilute the urine and thus excrete free water is the primary defense against the development of hyponatremia. Excess ingestion of water as the sole cause of hyponatremia is rare outside the setting of mental illness, since the typical adult with normal renal function can excrete a massive free water load (15 L of water per day) without diluting the serum. The factors necessary for the development of hyponatremia are free water intake in the setting of an underlying condition that impairs free water excretion (Fig. 2).

Symptoms of hyponatremia are due to osmotic swelling of the brain as plasma tonicity decreases. Hyponatremia can be asymptomatic, as is usually the case for chronic hyponatremia secondary to heart failure or cirrhosis, or it can present with life threatening complications of cerebral edema. Hyponatremic encephalopathy, the clinical manifestation of cerebral edema secondary to hyponatremia, can have a wide range of presentations. The early signs are usually nonspecific: nausea, vomiting, and headaches (Table 1). (8) Worsening of brain swelling then leads to decreased mental status and seizures. If the situation is not corrected, the final manifestations are coma, respiratory arrest and death (Table 1).

Hospital-acquired Hyponatremia

Hospital-acquired hyponatremic encephalopathy is most commonly encountered following the administration of hypotonic fluids to a patient with an impairment of free water excretion. A common clinical setting in which this occurs is in the postoperative state. About 1% of patients develop a serum sodium of < 130 mEq/L following surgery and clinically significant hyponatremia complicates 20% of these cases. (9,10) The postoperative state is characterized by multiple stimuli for ADH release including pain, stress, nausea, vomiting, narcotic medications, and volume depletion. (9,11) The administration of a hypotonic fluid in this setting can have disastrous consequences.

Case #1. A 34-year-old female with no significant past medical history underwent elective laparoscopic bilateral tubal ligation at 9:00 AM. During the surgery, D5 1/4 normal saline was started and maintained at 125 cc per hour. The patient remained in recovery until late afternoon as she was too sedated to go home. IV meperidine was given, with adequate relief of her pain. Because she was not tolerating oral intake, IV fluids were continued at 125 cc/h. At 2:45 AM the following day, the patient complained of a headache and a verbal order for Tylenol #3 was given. At 9:00 AM, the nursing staff notified the surgeon of a sodium of 127 mEq/L. No new orders were received, and IV fluids were continued. At 1:30 pm, she was noted to be lethargic and pain medications were held. At 3:30 pm, she had a generalized seizure and went into respiratory failure. The patient was intubated and mechanical ventilation was initiated. Serum sodium at this time was 122 mEq/L.

Why did this patient develop hyponatremia? This patient had multiple stimuli for ADH release, resulting in an impairment of free water excretion (Fig. 2). Therefore, administration of a hypotonic fluid was not appropriate and placed the patient at risk for hyponatremia.

How could this have been prevented? The most important measure to prevent postoperative hyponatremia is to avoid the use of a hypotonic fluid in a postsurgical patient and administer 0.9% sodium chloride when parenteral fluids are indicated. In addition, neither the nursing staff nor the clinicians in case #1 recognized the early signs of hyponatremic encephalopathy (headache, nausea and vomiting), which occurred when the patient's sodium was 127 mEq/L. The presence or absence of symptoms of hyponatremic encephalopathy and not the absolute level of the serum sodium determines whether or not a life threatening condition exists. Risk factors for poor outcomes from hyponatremic encephalopathy must be understood to fully appreciate this crucial point (Table 2).

Risk Factors for Hyponatremic Encephalopathy

The brain has several defense mechanisms that counteract the increase in brain volume associated with hyponatremia. The major defense of the cell against volume perturbations is the extrusion of sodium, potassium and organic osmolytes from inside brain cells. (12) These latter adaptations decrease intracellular brain osmolality and reduce osmotic influx of water. There are three important risk groups for poor outcomes in hyponatremic encephalopathy that merit particular attention as failure to appreciate the seriousness of hyponatremia in these settings can be lethal. These are hypoxic patients, menstruating females and children. (13-15) These patients are all at higher risk for poor outcomes and require prompt attention.

Hypoxia is a major risk factor for the development of hyponatremic encephalopathy and is associated with poor outcomes. (14) Hypoxia impairs the ability of brain cells to use the [Na.sup.+]/[K.sup.+] ATPase to extrude solutes (15,16) and thus equivalent decreases in serum sodium lead to worse cerebral edema in hypoxic patients because of the diminished capacity of the brain to adapt to hyponatremia (Fig. 3). Thus, an important adjunctive measure in the treatment of hyponatremic encephalopathy is to avoid hypoxia by ensuring adequate ventilation, including prophylactic intubation in a patient with a depressed mental status and convulsions as these are harbingers of impending respiratory arrest.

In epidemiologic studies, premenopausal females have been found to have worse outcomes following hyponatremic encephalopathy than males or postmenopausal females. (9) Female rats appear to have a similar impairment in brain adaptation to cerebral edema (17); thus, it is believed that the susceptibility of premenopausal females to hyponatremic encephalopathy is related to a decreased ability to adapt to hyponatremia.

Finally, physical characteristics of the brain and cranial vault make children more susceptible to cerebral edema and hyponatremic encephalopathy. (18) The skull reaches full size at age 16 whereas the brain is adult sized by age 6. (19,20) Therefore, children have a much higher ratio of brain size to cranial vault size and cannot accommodate as much increase in brain size as adults. Thus, an important aspect of the evaluation of the hyponatremic patient is to identify risk factors for a poor outcome and treat hypoxia if present.

Prevention of Hospital-acquired Hyponatremia

The most important measure is to eliminate the use of hypotonic IV fluids except in the setting of water deficit replacement (ie, hypernatremia). The prevalence of impaired water excretion in hospitalized patients makes the injudicious use of hypotonic fluids dangerous. Normal saline (0.9% NaCl) is the most appropriate parenteral fluid when IV fluids are indicated in the postoperative period. (21) In addition, any patient receiving parenteral fluid therapy should have the serum sodium measured at least daily.

Hyponatremic Encephalopathy in the Outpatient Setting

Hyponatremia occurs more frequently in hospitalized patients; however, it is being increasingly recognized in the outpatient setting, (22,23) as seen in the following cases.

Case #2. A 78-year-old female was brought to the emergency room by her daughter. The patient was incoherent with left-sided facial bruising and she walked with a limp. The patient was unable to give a history, but the daughter stated that she was normally very conversant and alert. On examination, she was noted to have severe bruising over her left hip with severe hip pain. The patient's past medical problems included only hypertension and she had been started two weeks previously on a new blood pressure medication. She was not oriented to time or place. No seizure activity was noted and the neurologic examination was otherwise unremarkable. X-rays revealed a left femoral neck fracture. Serum sodium was 104 mEq/L.

What is the etiology of hyponatremia in this patient? Use of thiazide diuretics.

How could this outcome have been prevented? A patient started on a thiazide diuretic should be weighed 48 hours after therapy is initiated. A patient that gains weight after starting the medication is likely to be developing water retention and is at high risk for hyponatremia. In addition, serum chemistries should be routinely checked following initiation of diuretics. The elderly are at increased risk of developing hyponatremia during therapy with a thiazide diuretic.

Why do thiazides lead to this complication, while loop diuretics typically do not? Thiazide diuretics act in the cortical collecting duct and thus impair urinary diluting capacity, but maintain concentrating ability, whereas loop diuretics, which act in the thick ascending limb of Henle, impair both urinary diluting and concentrating capacity.

Case #3. A 21-year-old female, who collapsed 30 minutes after completing a marathon, was brought to the emergency department. She was found to be disoriented and severely short of breath at arrival. Physical examination revealed a normal cardiac examination, crackles in all lung fields and a nonfocal neurologic examination. Chest x-ray revealed pulmonary edema. Serum electrolytes included a sodium of 126 mEq/L and a potassium of 3.0 mEq/L with a normal glucose level.


What is the etiology of hyponatremia in this patient? Exercise-associated hyponatremia. Marathon runners who develop this problem consume large amounts of water throughout the race, in excess of the water lost through sweating. (23,24) It is proposed that significant portions of consumed water remain sequestered in the gut as there is divergence of blood flow from the splanchnic circulation during the race. In addition, ADH is released during the extreme physical exertion of the race. Following completion of the race, the ingested water is absorbed and acute hyponatremia ensues, which can be fatal.

What is the etiology of pulmonary edema in this patient? Neurogenic pulmonary edema induced by cerebral edema. Paradoxically, treatment with 3% saline leads to resolution of the pulmonary edema by resolving the underlying cerebral edema. (23)

How could this outcome have been prevented? Limiting fluid intake is necessary as hypotonic electrolyte sports drinks or salt consumption appear to have no role in the prevention of this condition. (25) In addition, nonsteroidal anti-inflammatory drug use has been associated with the development of severe hyponatremia, so this practice must be discouraged among participants in sporting events. (23)

Case #4. A 72-year-old nursing home patient had a history of neurogenic bladder, and had recently become incontinent following transurethral resection of the prostate. Six weeks before presentation, he had been placed on intranasal DDAVP[R] 10 [micro]g each night before sleep. He tolerated this treatment well and on a routine chemistry panel one week before admission, his sodium was 139 mEq/L. At the request of the staff, two days before presentation he was started on DDAVP[R] 10 [micro]g in late morning before his afternoon physical therapy. The patient was subsequently noted to be lethargic and unresponsive and was transported to an emergency room where workup revealed a serum sodium of 108 mEq/L and serum potassium of 3.1 mEq/L. He was treated with a 75 cc bolus, then infusion of 3% saline which brought about a prompt neurologic recovery. Three percent saline was stopped when the serum sodium reached 121 mEq/L and DDAVP[R] was withheld because it was deemed the cause of the hyponatremia. Overnight the urine output increased significantly. The following morning, the patient's urine sodium was 17 mEq/L and his urine potassium was 11 mEq/L. Serum sodium at that time was 137 mEq/L.

What is the cause of hyponatremia in this case (DDAVP[R] or excess water ingestion)? Both of these factors contributed. DDAVP[R] alone will not cause hyponatremia, so it is not correct to say that this patient "overdosed" on DDAVP[R] DDAVP[R] will cause retention of free water and thus the dosing needs to be titrated in conjunction with the patient's fluid intake.

Why did the patient's serum sodium increase so quickly after the hypertonic saline was stopped? Once the stimulus for free water retention was removed (exogenous DDAVP[R]), the patient began to excrete the large free water load as endogenous ADH secretion was suppressed by the plasma hypotonicity. The large free water losses are indicated by the low sodium plus potassium in the urine compared with the plasma ([[Na.sup.+]][.sub.u] + [[K.sup.+]][.sub.u] which was significantly less than [Na+][] + [[K.sup.+]][]).

What change should have been made in the management of this case? The DDAVP[R] should have been continued, and all fluid intake restricted during the correction of the hyponatremia. The DDAVP[R] must be continued to prevent over correction of the serum sodium secondary to water diuresis. Consultation with a specialist is mandatory in a complex case such as this.

Case #5. A 69-year-old female whose medical history included only hypertension was scheduled for an elective colonoscopy as a screening for colon cancer. She was prescribed polyethylene glycol bowel preparation. She became nauseated and vomited several times throughout the day while drinking the preparation. Upon developing diarrhea, she increased her fluid intake concomitantly. That evening the nausea continued, and she developed a headache. On the morning of the test, her husband found her unconscious and she had several tonic-clonic seizures. Serum sodium on presentation to the hospital was 114 mEq/L.


Why did this patient increase fluid intake during the bowel preparation? The reduction in plasma volume associated with diarrhea from a bowel preparation can lead to increased thirst. (26)

Why did this patient have impaired free water clearance? The high levels of ADH from volume depletion. In addition the patient had a history of hypertension and may have been taking a thiazide diuretic.

Treatment of Hyponatremic Encephalopathy

The management of hyponatremic encephalopathy is based upon the clinical symptoms and not on the serum sodium. The correction of hyponatremia with hypertonic saline is reserved for patients with signs of hyponatremic encephalopathy (Table 1) and should not be used in asymptomatic patients regardless of serum sodium. (11,14,27) In addition, the serum osmolality should be measured before instituting therapy with hypertonic saline to verify that a hypotonic state exists. (18) Fluid restriction alone should never be used to manage a patient with hyponatremic encephalopathy. Early recognition and prompt treatment are the most important factors associated with successful intervention and good neurologic outcomes. (18)

The algorithm shown is a useful guide (Fig. 4). The goals of therapy with hypertonic saline can be summarized as 1) first, to remove patients with severe manifestations from immediate danger, 2) to correct the patient to a mildly hy-ponatremic level and 3) maintain this level of serum sodium allowing time for the brain to adjust to the change in serum osmolality. Prompt therapy with hypertonic saline should be instituted in all patients with hyponatremic encephalopathy, regardless of the underlying etiology of the disorder. In patients with severe manifestations (active seizures or respiratory failure), a bolus of 100 cc of 3% saline can be given to remove the patient from immediate danger. The bolus can be repeated if seizures or respiratory failure persist with a goal of an initial change in the serum sodium by about 2 to 4 mEq/L. Following this initial therapy, an infusion should begin to raise the serum sodium to mildly hyponatremic levels; however, the total change in serum sodium should not exceed 15 to 20 mEq/L over 48 hours. (14) For patients with hyponatremic encephalopathy without active seizures or respiratory arrest, an infusion of 3% saline should be given to raise the serum sodium to mildly hyponatremic levels; again the total change in serum sodium should not exceed 15 to 20 mEq/L over 48 hours. (14) In addition, the serum sodium should never be corrected to normonatremic or hypernatremic levels and patients should be maintained at mildly hyponatremic levels for a few days following hyponatremic encephalopathy. This maintenance period will allow the patient to adjust to the new plasma tonicity. In patients with impaired cardiac output in whom pulmonary edema may develop with vigorous volume expansion, IV furosemide should be given.

We do not endorse the use of formulae to determine infusion rates. This practice can have disastrous consequences when a calculated rate is used as a substitute for proper patient monitoring. Any patient receiving 3% saline should have the serum sodium checked every 2 hours until the patient is clinically stable and the serum sodium values are stable, at which time monitoring can be less frequent. In addition, all patients with severe manifestations must be placed in an intensive care setting. Close monitoring is essential because equations cannot predict ongoing urinary water losses and failure to closely monitor serum sodium and urine output can lead to dangerous over correction. Settings in which this is important include interruption of DDAVP therapy, psychogenic polydipsia, and drug-induced hyponatremia when the offending agent is stopped; these and other clinical scenarios are listed (Table 3). An assumption that can be used to guide initial therapy is that an infusion of 3% saline of 1 mL/kg will raise the serum sodium by approximately 1 mEq/L.

During the correction of hyponatremia, care must be taken to be sure that a free water diuresis following treatment does not occur. In this setting, DDAVP can be given to increase urinary concentration and reduce free water losses. Administration of DDAVP must be done carefully, with the patient strictly fluid restricted or NPO in an intensive care unit setting. This is necessary to prevent hyponatremia from developing from unrestricted fluid intake during DDAVP administration. An increase in urine output is the first sign that a water diuresis is ensuing and thus urine output needs to be followed closely in all patients with hyponatremic encephalopathy.

Risk Factors for the Development of Cerebral Demyelination

Cerebral demyelination is a rare but potentially serious complication associated with the correction of severe hyponatremia. It can be either symptomatic or asymptomatic. When symptoms occur, it is usually a delayed phenomena occurring days to weeks following correction of hyponatremia. Classic symptoms are a pseudocoma with a "locked in stare." The potential for cerebral demyelination mandates that therapy with hypertonic saline be undertaken with appropriate monitoring. The rate of correction of serum sodium alone does not predict the development of cerebral demyelination; rather, providers need to evaluate the absolute change in serum sodium over 48 hours. In addition, other clinical factors such as liver disease and hypoxia increase the risk of demyelination (Table 4). (14) The serum sodium can be quickly corrected in an acutely symptomatic patient without increasing the risk of demyelination as long as the absolute change over 48 hours does not exceed 15 to 20 mEq/L. Patients with liver disease are particularly susceptible to cerebral demyelination and caution should be exercised in this setting.


The definition of hypernatremia is a serum sodium greater than 145 mEq/L. Because thirst is a powerful protective mechanism, restricted access to water is nearly always necessary for the development of hypernatremia. This can occur in a variety of clinical settings: patients who are debilitated by an acute or chronic illness, in neurologic impairment such as dementia, in infants, in moribund patients or in those on mechanical ventilation. Hypernatremia occurs commonly in the intensive care unit with most patients either intubated or with altered mental status and thus having restricted access to fluids. In addition, many other factors in the ICU contribute to hypernatremia: significant renal water losses are driven by solute diuresis (mainly urea) in patients on high protein feeds or in a hypercatabolic state; excess hypertonic sodium bicarbonate administration, use of loop diuretics, renal concentrating defects, and gastrointestinal fluid losses (especially nasogastric suction and lactulose administration) can all contribute. Thus, most patients with hypernatremia have some combination of impaired water access and significant ongoing free water losses; however, if access to water is not limited, patients with normal mental status will rarely develop this disorder regardless of the amount of ongoing water losses. The common etiologies of hypernatremia usually involve states of impaired water access in conjunction with excessive free water losses (Table 5).

A precise history focusing on fluid intake is necessary to determine if the patient has impaired access to fluids, an abnormal thirst mechanism, or is not receiving sufficient free water in enteral or parenteral form. Water losses in the urine, from the GI tract (diarrhea and nasogastric suction) and insensible losses (fever, sepsis, massive diaphoresis, burns) should be calculated or estimated if accurate counts are unavailable. The urine osmolality and electrolytes should be measured to assess urinary concentrating ability and to estimate the electrolyte free water losses in the urine. Caution needs to be exercised in the interpretation of the urine osmolality, as this is an area where error is common. The urine osmolality alone cannot be used to determine if there is free water loss in the urine. This is because water can be excreted with nonelectrolyte osmoles (under physiologic conditions, this nonelectrolyte osmole in the urine is typically urea). In cases of a high urea load, massive amounts of water can be lost in the urine despite maximal urinary concentration. Urinary water loss occurs when the urine sodium plus potassium ([[Na.sup.+]][.sub.u] + [[K.sup.+]][.sub.u]) is less than the plasma sodium plus potassium ([[Na.sup.+]][] + [[K.sup.+]][]). Failure of a patient to concentrate the urine at a time when the patient is hypernatremic should raise suspicion of a urinary concentrating defect.

Clinical Manifestations of Hypernatremia

As cell membranes are permeable to water, hypernatremia leads to an efflux of fluid from the intracellular space to the extracellular space to maintain osmotic equilibrium across the cell membranes. Cerebral dehydration with cell shrinkage ensues. The primary clinical manifestations are due to central nervous system depression. Patients have decreased mental status, confusion, abnormal speech and obtundation with stupor or coma in severe cases. The mortality of patients with hypernatremia can be as high as 40 to 70%. (28,29) Patients with end-stage liver disease are another group at particular risk for complications from hypernatremia. Patients with hepatic encephalopathy frequently develop hypernatremia from an osmotic diarrhea due to the oral administration of lactulose.

Hospital-acquired Hypernatremia

Case #6. A 46-year-old was admitted with severe necrotizing pancreatitis. He had a history of alcohol abuse, hepatitis C and chronic liver disease. The patient weighed 76 kg. (Admission labs are listed in Table 6). The patient was kept NPO overnight, and volume was expanded with 6 L of normal saline. Twenty-four hours after admission, his abdominal pain worsened and nasogastric suction was initiated. Serum sodium was 145. Over the next 24 hours, his urine output increased, and isotonic saline was continued at 100 cc per hour. Total parenteral nutrition was initiated with a total volume of 2 L, 120 mEq of sodium and high amino acid content. The chemistries and urine studies 48 hours after admission are listed in Table 6.

Was this patient losing water in his urine? Yes, he was losing electrolyte-free water in the urine. The ratio of the urine sodium + potassium in the urine is lower than that in the blood. In this case, the ratio was 70/154 = 0.45. This means that 45% of his urine was "electrolyte containing" and conversely, that 55% of the urine was electrolyte-free water. Thus, at his current urine output, he was losing (0.55 X 150 cc/h) = 82.5 cc of water per hour in the urine.

If the patient is losing water in the urine, why is the urine osmolality high? The urine osmolality is high because ADH is being secreted and is having an effect on the urine concentration. Low urine sodium and potassium, combined with high urine osmolality, signifies that there is a nonelectrolyte osmole in the urine that is 'obligating' water loss. This is a classic presentation of an osmotic diuresis secondary to urea.

What is the source of the high urea load in this patient? A hypercatabolic state secondary to critical illness/stress and the high protein in the total parenteral nutrition.

What other osmole can commonly cause significant free water losses? Glucose.

Outpatient Hypernatremia

In adults, hypernatremia develops outside of the hospital most commonly in the elderly, usually a nursing home resident. (29) In children, breastfeeding-associated hypernatremia in infants is being increasingly recognized as a potentially lethal, preventable form of hypernatremia. (30)

Case #7. A 22-year-old returned for a one week follow-up visit after the uncomplicated spontaneous delivery of her first child. The baby had been receiving phototherapy for neonatal jaundice which was slowly resolving. The highest total bilirubin had been 17 mg/dL and was now 13 mg/dL. The mother was concerned about her daughter's feedings. Over the first several days she described the baby as crying all the time and always hungry. On the advice of her lactation consultant, she had refrained from supplementing with formula. Weight loss following birth was 12% of the child's body weight and she had only gained a small amount of that back. At the clinic visit, the child was found to have a mild fever and was admitted to the hospital. Serum sodium was found to be 156 mEq/L.

What was the cause of the hypernatremia? Hypernatremia is increasingly recognized as a complication of breast-feeding and is usually not suspected by clinicians before laboratory evaluation. The most common presenting symptoms are jaundice, lethargy and fever. (30) The etiology is linked to failure to establish proper breastfeeding, which is associated with increased sodium concentration of the breast milk. (31) The clinical sequelae are volume depletion and hypernatremia.

What were the clues to the diagnosis in this patient? The history is strongly suggestive of poor enteral intake and the weight loss corroborates this. In addition, the presence of jaundice is a historical factor that should raise suspicion for the presence of hypernatremia.

What are the potential complications of this disorder? Severe brain damage, vascular thrombosis and death have all been reported. (32)

Prevention of Hypernatremia

The prevention of hypernatremia is best accomplished by recognizing patients at risk for this disorder and a thorough understanding of those at risk for a poor outcome. It is not necessary to memorize a list of conditions that put a patient at risk as long as it is understood that hypernatremia requires at least one of the following to occur: impaired access to water (dementia, mental illness, hepatic encephalopathy, child/infant, critically ill patient, patient who is kept NPO and using a feeding tube) or a massive sodium load (improper infant formula mixture, administration of large amounts of hypertonic sodium solutions such as sodium bicarbonate or sodium phosphate).

The syndrome of breastfeeding-associated hypernatremia needs to be appreciated by any physician that will encounter neonates, as the condition is currently thought to be under recognized, and therefore may be significantly underreported. (30) With breastfeeding actively encouraged by the medical community and governmental health organizations, the incidence will undoubtedly increase. This condition primarily affects first-time breastfeeding mothers. This condition can be prevented by the judicious supplementation of infant formula or expressed milk. Restrictive breastfeeding practices that do not allow supplementation when excessive weight loss has occurred should be abandoned and breast-fed infants should be weighed on day 3 of life. All breast-fed infants with weight loss of > 10% of birth weight, jaundice or fever should have serum electrolytes checked until successful lactation can be established. In all breast-fed infants in whom successful lactation has not been established, supplementation should be considered.

Treatment of Hypernatremia

Treatment of hypernatremia is directed at maintenance of a normal circulatory volume while correcting the serum sodium with free water replacement (Table 7). The first step is to assess the current water deficit (Fig. 5). This value is a guide for therapy that represents the amount of water necessary to correct the serum sodium to a desired value, assuming a closed system (ie, ignoring ongoing losses). Ongoing losses need to be accounted for in the replacement fluids to achieve the goals of correction. Clinically, this corresponds to the electrolyte free water excretion. In volume depleted patients, fluid resuscitation with normal saline (0.9% NaCl) or colloid should precede correction of the water deficit (Table 7). Enteral hydration is preferable to parenteral and should be used when possible. Plasma electrolytes should be checked every two hours until the patient is neurologically stable.

In the absence of hypernatremic encephalopathy, the serum sodium should not be corrected more quickly than 1 mEq/h or 15 mEq/24 hours. In severe cases (>170 mEq/L), sodium should not be corrected to below 150 mEq/L in the first 48 to 72 hours. (8)



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Friendship is a single soul dwelling in two bodies.

Steven G. Achinger, MD, Michael L. Moritz, MD, and Juan Carlos Ayus, MD, FACP, FASN

From the Division of Nephrology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, and the Division of Nephrology, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA.

Reprint requests to Juan Carlos Ayus, MD, FACP, FASN, Professor of Medicine, Director of Dialysis Services, Texas Diabetes Institute, University of Texas Health Science Center San Antonio, 7703 Floydcurl Drive, San Antonio, TX 78229. Email:

Accepted January 13, 2006.

The authors have no disclosures to declare.


* Normal saline (0.9% NaCl) should be given in the postoperative setting, and hypotonic fluids should never be administered following surgery.

* Hyponatremic encephalopathy should be recognized promptly and treated with 3% hypertonic saline.

* Risk factors for poor outcomes with hyponatremic encephalopathy are menstruating females, hypoxic patients and children. Hypoxia should be corrected during treatment of hyponatremic encephalopathy.

* Urine electrolytes should be measured in conjunction with urine osmolality as they are a better reflection of water losses in the urine.
States of impaired water excretion

Hypovolemic States
* Volume depletion
* Diuretics

Euvolemic States
* Postoperative state
* Cortisol deficiency
* Pain
* Hypothyroidism
* Nausea

Hypervolemic States
* Cirrhosis
* Nephrosis

Fig. 2 States of impaired free water excretion.

Table 1. Manifestations of hyponatremic encephabpathy

Clinical manifestation CNS events

Headache, nausea and vomiting Brain swelling
Seizures Pressure on rigid skull
Respiratory arrest Brainstem herniation

Table 2. Risk groups for hyponatremic encephalopathy

* Menstruant females
* Children
* Hypoxic Patients

Table 3. Common clinical scenarios of hyponatremic encephalopathy and
the risk of over correction of serum sodium secondary to water diuresis

Causative agent Clinical scenario

Postsurgical Postoperative hypotonic fluid administration
Thiazide diuretic Elderly patient treated for hypertension
Exercise-induced Young female, marathon runner, excess fluid
 hyponatremia intake with NSAID use
DDAVP[R]-associated Perioperative DDAVP[R] and hypotonic fluid
 hyponatremia administration; urinary incontinence
SIADH Malignancies, pulmonary and CNS disorders
Cerebral salt wasting Neurosurgical and head trauma patients
Water intoxication Psychogenic polydipsia, water intoxication in
Volume depletion Diarrheal dehydration in infants receiving
 hypotonic feeds
Renal failure Hypotonic parenteral fluid administration

 Time course to
 development of
 hyponatremic Risk of water diuresis
Causative agent encephalopathy following correction

Postsurgical 72 hours [up arrow]
Thiazide diuretic 1 week [up arrow] [up arrow] [up arrow]
Exercise-induced 30 minutes to [up arrow] [up arrow]
 hyponatremia hours
DDAVP[R]-associated any [up arrow] [up arrow] [up arrow]
SIADH any minimal
Cerebral salt wasting any minimal
Water intoxication any [up arrow] [up arrow] [up arrow]
Volume depletion any [up arrow] [up arrow] [up arrow]
Renal failure any -

NSAID, nonsteroidal anti-inflammatory drugs; SIADH, syndrome of
inappropriate antidiuretic hormone secretion; CNS, central nervous

Table 4. Risk factors for the development of cerebral demyelination
after correction of symptomatic hyponatremia

* Hypoxic-anoxic episode
* Increase in serum sodium to normal or to hypernatremic levels in the
 first 48 hours
* A change in the serum sodium concentration of more than 15-20 mEq/L
 per liter in the first 48 hours
* Liver disease

Table 5. Common etiologies of hypernatremia

1. Impaired water intake (usually occurs in dementia)
2. Solute diuresis secondary to tube feedings or hyperalimentation
3. Nasogastric suction
4. Nonketotic hyperosmolar coma
5. Insufficient lactation in breast fed infants
6. Loop diuretics
7. Gastrointestinal losses
8. Diabetes insipidus

Table 6. Admission labs for case #6

 48 hours
 Admission after admission

Sodium (mEq/L) 141 151
Potassium (mEq/L) 3.2 3.0
Chloride (mEq/L) 103 110
Bicarbonate (mmol/L) 22 24
Urea nitrogen (mg/dL) 25 48
Creatinine (mg/dL) 1.4 1.2
Urine output (cc per hour) 45 150
Urine sodium (mEq/L) - 50
Urine potassium (mEq/L) - 20
Urine osmolality (mOsm/kg) - 620

Table 7. Treatment of hypernatremia

1. Replete intravascular volume with colloid solution, isotonic saline
 or plasma
2. Estimate water deficit. Deficit should be replaced over 48-72 hours,
 aiming for a correction of 1 mEq/L per hour. In severe hypernatremia
 (> 170 mEq/L), serum sodium should not be corrected to below 150
 mEq/L in the first 48-72 hours. Replacement of ongoing water losses
 are given in addition to the deficit.
3. Hypotonic fluid should be used. Usual replacement fluid is 77 mEq/L
 (0.45%) saline; a lower sodium concentration may be needed if there
 is a renal concentrating defect or sodium overload. Glucose-
 containing solutions should be avoided and an oral route of
 administration should be used.
4. Plasma electrolytes should be monitored every two hours until patient
 is neurologically stable.
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Title Annotation:continuing medical education
Author:Ayus, Juan Carlos
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Apr 1, 2006
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