You Have A New Patient!
An 87-year-old male patient with a past medical history of hypertension, stroke, and depression presents to the ED with lethargy and altered mental status. He was brought in by his daughter, who states that she has been visiting him at the nursing home over the past three days, during which he has appeared progressively weaker and more confused.
The nursing home staff report that the patient has had poor oral intake and multiple episodes of non-bloody diarrhea. He has not been participating in his usual activities and appeared more lethargic today, which prompted his daughter to bring him to the ED.
Initial triage vital signs are as follows: BP 92/60, HR 134, RR 18, SpO₂ 99%, Temp 36.8°C.
Exam findings are notable for a cachectic elderly male who is not oriented to person or place. He appears clinically dehydrated, with dry mucous membranes and poor skin turgor with tenting. He is able to follow basic commands but appears weak and confused. Laboratory findings were notable for a sodium of 165 mEq/L, chloride of 120 mEq/L, potassium of 4.0 mEq/L, and creatinine of 2.1 mg/dL.
What is the diagnosis for this patient, and what additional labs, treatment options, and potential complications should be considered?
What Do You Need To Know?
Importance and Epidemiology
Hypernatremia is defined as a serum sodium ([Na+]) level greater than 145 mEq/L [1]. It is a common electrolyte abnormality seen in elderly, pediatric, and critically ill patients, as these populations are more prone to impaired thirst regulation [2]. Hypernatremia occurs due to net water loss, excess sodium intake, or a combination of both [1]. Accurate diagnosis and appropriate treatment are crucial, as both undercorrection and overcorrection of hypernatremia are associated with poor prognosis and a high mortality rate of 40–60%, which is often underappreciated [1].
Pathophysiology
Understanding hypernatremia requires comprehension of the main body fluid compartments as well as the basic concepts of normal body water balance [1]. Since sodium is important for maintaining extracellular fluid (ECF) volume, any change in ECF volume can result in increased or decreased sodium excretion in the urine. Sodium excretion is regulated by mechanisms such as the renin-angiotensin-aldosterone system [1]. When there is a rise in serum sodium, plasma osmolality also increases, triggering the thirst response and antidiuretic hormone (ADH) secretion. This leads to renal water conservation and the production of concentrated urine [1].
Severe hypernatremia occurs when serum sodium rises rapidly or exceeds 160 mEq/L [2]. Most patients will be symptomatic at this level due to central nervous system dysfunction. Hypovolemic hypernatremia is the most common presentation of hypernatremia seen in the ED, as net water loss accounts for the majority of cases [3]. Determining the patient’s volume status is one of the most important steps in managing hypernatremia. A thorough history, clinical exam, and laboratory testing are used in conjunction to establish the etiology of hypernatremia.
Medical History
As stated previously, a thorough history is essential to determining a potential etiology for hypernatremia and guiding management [1]. For example, patients who have sustained a traumatic brain injury may be more likely to have central diabetes insipidus (DI), while a patient with an underlying psychiatric condition on lithium may be more likely to have nephrogenic DI [1]. The timing of symptoms is also relevant in determining whether the hypernatremia is acute or chronic. Hypernatremia that develops within the previous 48 hours is considered acute, while patients with symptoms lasting longer than 48 hours or with unknown timing of symptom onset are considered to have chronic hypernatremia [1]. The severity of symptoms is determined by both the speed and magnitude of the Na+ change.
The history should include detailed information about the patient’s fluid and salt intake, urine output, past medical history, and current medications [4]. Medications often implicated in hypernatremia include loop diuretics, lithium, phenytoin, lactulose, aminoglycosides, mannitol, and hypertonic saline [3,5]. Ask about any recent head trauma or surgeries, such as pituitary macroadenoma removal. Patients may report polyuria, polydipsia, confusion, or generalized weakness. If the patient is altered, the caregiver or family member (if available) should be interviewed to determine any specific mental or behavioral changes that are acute.
Physical Examination
Assess the patient’s volume status by checking skin turgor and capillary refill, in addition to examining for edema or elevated jugular venous pressure [1]. Vital sign abnormalities may include tachycardia or orthostatic hypotension. Check for signs of trauma, burns, infection, or skin breakdown, which may contribute to insensible water losses.
Patients with underlying hypernatremia may present with a broad range of signs and symptoms, including lethargy, irritability, restlessness, altered mental status, poor skin turgor, hyperactive reflexes, and increased muscle tone [5]. Hypovolemic patients are usually tachycardic, with decreased capillary refill and peripheral perfusion, while hypervolemic patients may appear edematous and have rales on exam.
Perform a complete neurologic exam on all patients presenting with hypernatremia, as altered mental status, seizures, and a comatose state are associated with greater risk of morbidity and mortality [5]. Cerebral adaptation to hypernatremia generally starts on the first day and results in a reduction of brain volume that is reversed by water movement from the cerebrospinal fluid into the brain [1].
Check for somnolence, disorientation, increased muscle tone, or spasticity. Patients may often appear weak and lethargic.
Classifications of Hypernatremia & Alternative Diagnoses
Following the initial history and assessment as detailed above, patients with hypernatremia can be categorized into one of the following three groups depending on their volume status.
Hypovolemic Hypernatremia (Concomitant Loss of Water and Salt):
Patients with hypovolemic hypernatremia experience both a loss of water and salt, but with a relatively larger loss of total body water (TBW) [1]. This is most commonly due to gastrointestinal losses (e.g., diarrhea, vomiting), skin losses (e.g., burns or excessive sweating), and renal losses (e.g., intrinsic renal disease, mannitol, and loop diuretics) [5].
Patients with hypovolemic hypernatremia should first be given normal saline solution or lactated Ringer’s to restore volume, followed by hypotonic saline solutions (e.g., half-isotonic saline or quarter-isotonic saline). Hypovolemic hypernatremia is the most common presentation of hypernatremia seen in the ED [3].
Euvolemic Hypernatremia (Water Loss with Normal Salt Content):
This results from decreased TBW without any accompanying loss of salt [1]. Euvolemic hypernatremia is caused by extrarenal losses from the respiratory tract or skin (e.g., excessive sweating or fever), renal losses (e.g., central diabetes insipidus [DI] or nephrogenic DI), and other causes such as medications [5].
Medications often associated with euvolemic hypernatremia include lithium, amphotericin, phenytoin, and aminoglycosides [3,5]. Treatment for euvolemic hypernatremia is aimed at free water replacement, which can be provided orally or through intravenous glucose solution.
Diabetes Insipidus (DI): Also known as arginine vasopressin deficiency (AVP-D), DI is characterized by the passage of large volumes (>3 L/24 hours) of dilute urine [6]. The classic presentation of DI in the ED includes symptomatic hypernatremia (e.g., polyuria, polydipsia, lethargy, and weakness) and an inappropriately low urine osmolality (<300 mOsm/kg) [6].
DI refers to an absolute or relative antidiuretic hormone (ADH) deficiency and can be further classified into two major forms:
- Central DI: Characterized by an absolute ADH deficiency caused by inadequate ADH secretion. Common etiologies include malignant diseases, head trauma, pituitary surgery, infiltrative diseases, or idiopathic conditions [6].
- Nephrogenic DI: Characterized by a relative ADH deficiency due to a lack of renal response to ADH. Common etiologies include chronic renal insufficiency, polycystic kidney disease, hypercalcemia, hypokalemia, lithium toxicity, or familial diseases [6].
Hypervolemic Hypernatremia (Relative Water Deficit with Concomitant Gain in Salt):
This less common form of hypernatremia results from increased sodium with normal or increased TBW [1]. Hypervolemic hypernatremia often has an iatrogenic cause, such as hypertonic fluid administration (e.g., hypertonic saline, sodium bicarbonate, or total parenteral nutrition) in hospitalized patients [1]. It can also result from ingestion of saltwater or large amounts of salt, as well as mineralocorticoid excess (e.g., adrenal tumors or congenital adrenal hyperplasia) [4].
Patients with hypervolemic hypernatremia will often appear volume overloaded. Many of these patients may have conditions contributing to salt retention, such as congestive heart failure, liver dysfunction, renal disease, or hypoalbuminemia [1]. Treatment involves free water replacement and the use of diuretics such as furosemide to promote sodium excretion [4]. Diuretics should be titrated as necessary to maintain a negative fluid balance [3].
Acing Diagnostic Testing
Laboratory testing is another essential component for determining the causative factors of hypernatremia, especially in patients with altered mental status who cannot provide a thorough history [1]. Obtain a full set of serum electrolytes (including magnesium, calcium, and phosphate), liver function tests, renal function tests, urine electrolytes, and calculate serum osmolality. A serum osmolality of >430 mOsm/L is often associated with seizures and death [5].
The urine osmolality is one of the most useful initial tests to order, as it can further categorize the etiology and determine whether or not the renal water-concentrating ability is preserved [1]. If the urine osmolality is less than 300 mOsm/kg, this favors a diagnosis of central or nephrogenic DI. Desmopressin (DDAVP) should be administered to differentiate between the two types of DI. In patients with central DI, DDAVP will result in an increase in urine osmolality [1,6]. If the urine osmolality is high (greater than 800 mOsm/kg), this suggests that the secretion and response to AVP are normal, indicating preserved renal concentrating ability. In such cases, the hypernatremia is most likely due to extrarenal losses [1].
Imaging can also be useful in determining other etiologies of hypernatremia and ruling out potentially life-threatening conditions. Obtain a chest x-ray to rule out congestive heart failure, pneumonia, malignancy, pulmonary edema, and cardiomegaly as potential contributing disease processes. A non-contrast CT scan of the head is recommended in all patients with severe hypernatremia, especially if focal neurologic findings are present on exam. Hypernatremia results in traction on dural bridging veins and sinuses, which can lead to intracranial hemorrhage, most often in the subdural space [3]. Hemoconcentration from total body water loss may also lead to dural sinus thrombosis.
Risk Stratification
As mentioned previously, the severity of symptoms is often determined by both the speed and magnitude of the Na+ change. Acute symptoms are usually noted when Na+ >160 mEq/L [2]. Patients with acute hypernatremia are more likely to present with neurologic manifestations such as confusion, altered mental status, seizures, or ataxia. In cases of rapid and severe hypernatremia that develops over minutes to hours, there is an increased risk of acute intracranial hemorrhage due to the accompanying rapid decrease in brain volume, which causes rupture of cerebral veins [3].
Patients with chronic hypernatremia are typically less likely to exhibit neurologic symptoms due to the brain’s compensatory mechanisms. The brain can adapt by generating intracellular osmogenic compounds, which increase osmolality in the cells and thereby maintain brain volume, resisting shrinkage [1].
Management
The ED management of hypernatremia revolves around two key tasks: treating the inciting cause and correcting the hyperosmolality [1,3]. It is important to note that correcting sodium either too quickly or too slowly is associated with an increased risk of death and cerebral edema [3]. Therefore, the treatment of hypernatremia requires appropriate timing and a systematic approach. The classic recommendation for the management of hypernatremia is to replace the calculated free water deficit over 48 hours, with a decrease in serum Na+ not to exceed 0.5 mEq per hour (or 10–12 mEq total per 24 hours) [2,7].
ED management of hypernatremia can be further broken down into the following steps:
1) Resuscitate:
Following the initial evaluation, patients who are hemodynamically unstable should be resuscitated with intravenous fluids to stabilize abnormal vital signs [7]. The initial goal is to address the underlying hypovolemia and tissue hypoperfusion. Unless this is corrected, the body’s normal response will be to increase sodium concentration to maintain intravascular volume, which will worsen hypernatremia. Fluid resuscitation can be initiated with an isotonic fluid such as normal saline (0.9%) or lactated Ringer’s for volume repletion [2].
While it may seem counterproductive to administer a sodium-containing fluid to a hypernatremic patient, the goal is to restore homeostatic mechanisms of sodium balance before free water correction [2]. If the patient is not hypovolemic, use D5W for fluid resuscitation.
2) Investigate:
Evaluate for and treat the underlying cause of hypernatremia [2,7]. Review the patient’s weight, intake and output, and current medications. Consider potential etiologies of hypernatremia, such as electrolyte imbalances, gastrointestinal losses, diabetes insipidus, and others as described above. Look for potential sources of infection.
Obtain additional labs to help identify the etiology of hypernatremia and direct management. Rule out other electrolyte abnormalities, such as hypokalemia and hypercalcemia, which may point to renal causes of hypernatremia [3]. Calculate the serum osmolality (normal reference range: 275–295 mOsm/L), as elevations may correlate with the degree of symptoms [5]. Once the cause of hypernatremia has been identified, treat the underlying condition.
3) Rehydrate:
Water replacement should address the total body water (TBW) deficit in addition to any ongoing losses of water. Each liter of water deficit raises the serum Na+ by approximately 3–5 mEq/L [1]. Calculate the free water required to achieve the target sodium level [7]. The choice of replacement solution and infusion rates are critical factors to avoid overcorrection of hypernatremia.
It is essential to know the sodium concentration in different solutions to accurately correct water and sodium imbalances [3]. The sodium concentrations in commonly used solutions are listed below [3]:
- 0.9% NaCl: 154 mmol/L
- Ringer’s Lactate: 130 mmol/L
- 0.45% NaCl: 77 mmol/L
- 5% Dextrose in water (D5W): 0 mmol/L
To determine the TBW and water deficit:
- Calculate TBW:
The total body water (TBW) is estimated as 50% or 60% of lean body weight in women and men, respectively, which is why different correction factors are used in TBW calculation. Below are the recommended correction factors for calculating TBW based on age and gender [7]:
- Children and adult males: 0.6 × weight (kg)
- Adult females: 0.5 × weight (kg)
- Elderly males: 0.5 × weight (kg)
- Elderly females: 0.45 × weight (kg)
- Calculate water deficit:
The water deficit as a function of sodium concentration is calculated using the formula [1,3]:
TBW deficit = TBW × [(serum sodium/140) – 1]
This equation approximates the amount of water required to decrease sodium concentration to 140 mEq/L [3]. Note that this equation does not account for ongoing water losses or coexisting isosmotic fluid deficits, such as in patients with ongoing vomiting or diarrhea.
Rate and Volume of Correction:
Once the water deficit has been calculated, determine the rate and volume of correction. Several free online calculators, such as those available on MedCalc, can be used as reference tools.
- Acute hypernatremia: Do not lower sodium by more than 1–2 mEq/L/hr.
- Chronic hypernatremia: The goal is to lower Na+ by 10–12 mEq over 24 hours [5].
Avoid rapid overcorrection of hypernatremia, as this can result in cerebral edema, especially in children, who are more prone to this complication. Many patients with hypernatremia will also have reduced extracellular fluid (ECF) volume and other electrolyte abnormalities, which may require hypotonic fluids.
Treatment of Central DI:
The main treatment modality for patients with central DI is to supplement ADH in the form of desmopressin (DDAVP) [1]. Patients with known central DI should be given desmopressin, which may improve symptoms.
The initial dose of DDAVP is 1–2 micrograms (administered orally, intranasally, subcutaneously, or intravenously) and then up-titrated as necessary to reach the goal sodium level [6].
Special Patient Groups
Pediatrics
Hypernatremia is predominantly seen in infants and the elderly population due to their impaired thirst regulation [1]. Infants and small children are more vulnerable to hypernatremia because of their greater insensible water losses and their inability to communicate their need for fluids and/or access fluids independently. Two common presentations for infants at risk of hypernatremia include those receiving inadequate hydration in the setting of gastroenteritis or ineffective breastfeeding [2]. Furthermore, premature infants are at higher risk due to their relatively small mass-to-surface area ratio and their dependency on caregivers for fluid intake [2].
In breastfed infants, a relevant history should focus on whether there is a successful latch at the start of breastfeeding, the frequency and duration of feedings, the mother’s sensation of milk letdown, and whether the infant appears satiated after feeding. Common symptoms of hypernatremia in infants may include lethargy, weakness, restlessness or agitation, and a characteristic high-pitched cry [3]. It is important to remember that the degree of dehydration can be underestimated in children with hypernatremia due to a shift of water from the intracellular space to the extravascular space [2]. Children are often more susceptible to adverse effects from rapid correction of hypernatremia.
Pregnant Patients
Pregnant patients may develop hypernatremia due to transient diabetes insipidus, which affects approximately 4 out of 100,000 pregnancies [6]. Between the eighth gestational week and midpregnancy, the metabolic clearance of ADH increases 4- to 6-fold because of an increase in the enzyme vasopressinase, which is produced by the placenta. Vasopressinase activity peaks in the third trimester, remains high during labor and delivery, and then falls to undetectable levels two to four weeks postpartum [6]. Transient DI is caused by an amplification of the normal pregnancy-related increase in vasopressinase levels. Patients generally report increased thirst and urinary output that are out of proportion to those normally seen in pregnancy.
Patients with preeclampsia or HELLP syndrome are at increased risk for transient DI of pregnancy [8]. Transient DI should also be considered in the differential diagnosis of severe hypernatremia in obstetric patients with restricted oral intake after a Caesarean section [8]. Treatment options for transient DI of pregnancy include desmopressin and free water replacement [6]. Transient DI typically resolves postpartum and does not usually recur in subsequent pregnancies.
Geriatrics
Hypernatremia is also a relatively common electrolyte disorder in the elderly and critically ill patients. Approximately 27% of patients admitted to an intensive care unit (ICU) develop hypernatremia of variable severity during their ICU stay [9]. Additionally, studies have found that hypernatremia is an independent predictor of mortality and length of stay after controlling for illness severity and other ICU-acquired conditions and complications [9]. Even mild hypernatremia, with serum sodium levels between 145 and 149 mEq/L, is associated with a 28% increase in mortality risk and a 19% increase in ICU length of stay [9].
In the elderly population, the causes of hypernatremia tend to be multifactorial and include a decrease in thirst sensation, polypharmacy, and pre-existing comorbidities [10]. Renal function, concentrating abilities, and hormonal modulators of salt and water balance are often impaired in the elderly, making them more susceptible to hypernatremia and the associated morbidities and iatrogenic events involving salt and water [10]. The age-related decrease in TBW and concomitant impairment in thirst mechanisms also make elderly individuals more vulnerable to stresses on water balance [10]. By age 75 to 80 years, total body water content declines to approximately 50%, and even lower in elderly women. Providers should maintain a high index of suspicion for hypernatremia in elderly patients presenting from long-term care facilities, nursing homes, or after prolonged inpatient hospitalizations.
When To Admit This Patient
Patients with symptomatic hypernatremia or a serum sodium level greater than 150 mEq/L should be admitted to the hospital for further evaluation and treatment, as the free water deficit will generally need to be replaced gradually [1]. Those with severe neurological symptoms should be admitted to the ICU for regular neurologic exams. If available, a nephrology consult may be required for recommendations on dialysis and fluid regimens in more severe cases of hypernatremia. Sodium and electrolyte levels should be closely monitored every 2 to 4 hours during the acute phase of correction [2]. If a patient develops seizures during the course of treatment, this may indicate cerebral edema caused by rapid shifts in osmolality [2].
Hemodynamically stable and asymptomatic patients with mild hypernatremia from benign causes may be discharged with outpatient follow-up. Any medications contributing to the hypernatremia should be appropriately tapered or discontinued. Patients should be given specific instructions on the appropriate daily fluid intake and advised to avoid foods high in sodium (such as soy sauce, canned soups, chips, and processed foods) [1]. A plan should be in place to obtain follow-up sodium levels within 5 to 7 days or sooner if the patient becomes symptomatic.
Patients should also be instructed to return for any worsening fatigue, altered mental status, increased thirst, or confusion. Serum sodium and drug levels should be periodically monitored in patients taking medications known to cause nephrogenic DI. For elderly patients, a coordinated discharge plan involving the discharging physician, primary care physician, and nursing home staff is essential to prevent readmission due to hypernatremia [2].
Revisiting Your Patient
This case presents a common scenario where an elderly nursing home resident with poor oral intake presents to the ED with altered mental status and lethargy due to decreased oral intake and diarrhea. Vital signs are notable for tachycardia and hypotension, along with physical exam findings of dry mucous membranes and poor skin turgor. The patient was found to be hypernatremic, with a sodium level of 165 mEq/L and an elevated creatinine of 2.1 mg/dL. These findings are consistent with a clinical picture of hypovolemic hypernatremia.
Additional history obtained from the patient’s daughter and a review of nursing home records revealed medications that included lisinopril, aspirin, and sertraline. There were no recent medication changes, and the patient was still taking all of his medications despite the reported decrease in oral intake. Regarding his baseline mental status, the patient is typically communicative and usually awake, alert, and oriented to person, place, and time. He is now more confused and only oriented to person. There was no reported trauma or recent surgeries.
The patient was initially fluid resuscitated with 1 L of normal saline to stabilize the tachycardia and hypotension. Given the change in mental status, a head CT was performed, which did not show any acute intracranial hemorrhage or brain mass. A chest x-ray revealed no acute cardiac disease, focal consolidation, or pulmonary edema. Additional labs did not reveal any other electrolyte abnormalities. His serum osmolality was calculated to be 352 mOsm/kg, and his urine osmolality was elevated at >800 mOsm/kg.
Following initial fluid resuscitation, the patient’s calculated water deficit was estimated to be 5.35 L using the formula:
TBW deficit = TBW × [(serum sodium/140) – 1]
Using a weight of 60 kg:
(0.5 × 60 kg) × [(165/140) – 1] = 30 × (1.18 – 1) = 5.35 L
Given the patient’s altered mental status, degree of dehydration, and significant hypernatremia, he was admitted to the hospital for additional monitoring and fluid management. His IV fluids were adjusted to achieve a goal of decreasing the Na+ by 0.5 mmol/L/hr.
The patient responded well to treatment, and his confusion gradually resolved. He was discharged back to the nursing home within 3 days and did not experience any adverse outcomes.
Author
Theresa Nguyen
Dr. Theresa Nguyen is an Associate Professor of Emergency Medicine and the Director of the Center for Community and Global Health at Loyola University Medical Center in Maywood, IL. She also co-founded the Loyola Street Medicine program, which is dedicated to providing medical care and social outreach to individuals experiencing homelessness. Dr. Nguyen has international fieldwork experience in Haiti, Peru, Guatemala, Dominican Republic and Vietnam. Over the course of her global health work, Dr. Nguyen developed a strong interest in tropical diseases and obtained her Certificate of Knowledge in Clinical Tropical Medicine and Travelers' Health in 2014. Dr. Nguyen's current interests include ultrasound teaching in resource-limited settings, addressing language barriers, providing access to care for the homeless population, increasing awareness and education surrounding human trafficking, and international EM development.
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References
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- Sherer DM, Cutler J, Santoso P, et al. Severe hypernatremia after cesarean delivery secondary to transient diabetes insipidus of pregnancy. Obstet Gynecol. 2003;102(5):1166-1168.
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Reviewed and Edited By
Arif Alper Cevik, MD, FEMAT, FIFEM
Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.
