Hypernatremia (Clinical)

Water Regulation

Water regulation Water Regulation Renal Na+ and water regulation work in tandem to control how fluid is distributed throughout the compartments of the body. Sodium is the body’s dominant extracellular solute, and is responsible for the osmotic force that keeps differing amounts of water in each compartment. Changes in Na+ balance are sensed by the body through changes in blood volume. Renal Sodium and Water Regulation is controlled by the interplay between the osmoreceptors Osmoreceptors Renal Sodium and Water Regulation in the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and the response to antidiuretic hormone Antidiuretic hormone Antidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure. Hypernatremia (ADH) in the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, resulting in very tight control of serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and plasma osmolality Plasma osmolality Volume Depletion and Dehydration.

Hypothalamic osmoreceptors Osmoreceptors Renal Sodium and Water Regulation^{[2–5,16,17]}

• Detect changes in water balance as a result of changes in plasma osmolality Plasma osmolality Volume Depletion and Dehydration:
  • ↑ Water intake causes ↓ plasma osmolality Plasma osmolality Volume Depletion and Dehydration (↓ serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia) → ↓ ADH release and ↓ thirst
  • ↓ Water intake causes ↑ plasma osmolality Plasma osmolality Volume Depletion and Dehydration (↑ serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia) → ↑ ADH release and ↑ thirst
• Maintain the plasma osmolality Plasma osmolality Volume Depletion and Dehydration very tightly:
  • ADH levels are minimal when plasma osmolality Plasma osmolality Volume Depletion and Dehydration is normal (280–290 mmol/L).
  • ADH increases linearly in response to very small changes in plasma osmolality Plasma osmolality Volume Depletion and Dehydration.

Response to ADH in the kidney^[2–5,16]

• Aquaporin channels Channels The Cell: Cell Membrane are the target of ADH:
  • Allows water to move from the tubular fluid into the renal medulla via diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis
  • The renal medulla is hypertonic Hypertonic Solutions that have a greater osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation (due to the thick ascending limb Thick ascending limb Renal Sodium and Water Regulation and distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome).
• ADH stimulates the production and insertion of aquaporin channels Channels The Cell: Cell Membrane in the collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma:
  • High ADH levels → maximal levels of water reabsorption → concentrated urine
  • Low ADH levels → minimal levels of water reabsorption → dilute urine

Etiology

Etiologies of hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia are organized according to volume status Volume Status ACES and RUSH: Resuscitation Ultrasound Protocols.

Hypervolemic hypernatremia hypervolemic hypernatremia Hypervolemic hypernatremia is when the hypernatremia is cause by gain of more sodium than water. Hypernatremia^{[5,6,8,9,12,15,16]}

• Gain of more sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia than water
• Excessive intake of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia:
  • Infusion of isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation saline, hypertonic saline Hypertonic saline Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0. 9 g NaCl in 100 ml purified water). Hyponatremia, or sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes solutions
  • Oral ingestion of salt tablets (i.e., for the treatment of hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia)
  • Salt poisoning (i.e., excessive oral ingestion of table salt)
• Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia mediated:
  • Primary hyperaldosteronism Primary hyperaldosteronism Autonomous (renin-independent) secretion of aldosterone. Hyperaldosteronism
  • Cushing’s syndrome

Euvolemic Euvolemic Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^{[5,6,8,9,12–15]}

• Loss of water only
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus insipidus ( DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus) (both central and nephrogenic)
• Lack of access to water:
  • Infants
  • Elderly
  • Altered mental status Altered Mental Status Sepsis in Children
  • Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Mechanically ventilated patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Restrained patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Impaired thirst mechanism (more common in the elderly)
• Medications:
  • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
  • Aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides
  • Amphotericin
  • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs

Hypovolemic hypernatremia Hypovolemic Hypernatremia Osmotic Diuretics^{[5,6,8,9,12,15–17]}

• Loss of more water than sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia
• GI losses:
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Nasogastric tube Nasogastric tube Malnutrition in children in resource-limited countries drainage
• Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication 
• Osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration:
  • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
  • Mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics
  • Elevated urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle from excessive tube feeding
  • Recovery from AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
• Increased insensible water loss (i.e., sweat, burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
• Can also include central and nephrogenic DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus

Clinical Presentation

The primary clinical finding in hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia is thirst. If the patient is unable to ingest enough water to keep their serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia from rising significantly, dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration and neurologic findings may also occur. The severity of neurologic findings depends on the acuity and magnitude of the hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia.

Acute hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,10,16]

• Onset < 48 hours
• More likely to be symptomatic (due to less time for brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification adaptation)
• Less severe increases in serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia are needed to induce symptoms.

Chronic hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,10,16]

• Onset > 48 hours (or unknown)
• Less likely to be symptomatic (due to adequate time for brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification adaptation)
• More severe increases in serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia are needed before symptoms will appear.

Mild symptoms^[9]

• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
• Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia

Severe symptoms^[5,9,15]

• Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
• Confusion
• Neuromuscular irritability
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma

Diagnosis

In most cases, the etiology of hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia (Na⁺ > 145 mmol/L) will be clear and treatment can be initiated without any further testing.^[9,10,16] If the diagnosis is not clear, the following steps may be helpful:

1. Quickly identify acute causes and very severe cases:^[5,9,10]
   • Examples of acute causes: salt poisoning, DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without free access to water
   • Example of a very severe case: Na > 160 mmol/L
   • If acute, urgent and aggressive treatment is warranted.
   • If severe but not necessarily acute, prioritize urgent treatment over definitive diagnosis.
2. Identify reversible factors:^[5,9,10]
   • Access to water/ altered mental status Altered Mental Status Sepsis in Children (most likely lower the IV replacement rate once restored)
   • Ongoing losses: Address any other factors to limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation further free water replacement needs.
3. Etiology unknown and only mild hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia:^[5,9]
   • Consider aldosterone-mediated causes. 
   • Cushing’s syndrome diagnosis → check:
     • Late-night salivary cortisol Late-Night Salivary Cortisol Cushing Syndrome
     • 24-hour urine-free cortisol Cortisol Glucocorticoids
     • Overnight dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics suppression Suppression Defense Mechanisms test
   • Primary hyperaldosteronism Primary hyperaldosteronism Autonomous (renin-independent) secretion of aldosterone. Hyperaldosteronism diagnosis → check plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products levels of:
     • Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation
     • Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia
4. Etiology unknown and not aldosterone-mediated:^[9,10,16]
   • Measure urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation.
   • Urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation < 300 mOsm/kg (< plasma osmolality Plasma osmolality Volume Depletion and Dehydration): DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus
     • Give desmopressin Desmopressin Hemophilia (synthetic analogue of ADH).
     • Central DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus: urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation increases after desmopressin Desmopressin Hemophilia 
     • Nephrogenic DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus: no change in urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation after desmopressin Desmopressin Hemophilia
   • Urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation indeterminate (300–600 mOsm/kg): DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus vs. osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration
     • Check the response to desmopressin Desmopressin Hemophilia to diagnose possible DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus.
     • Check total solute load to assess for osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration.
   • Urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation > 600 mOsm/kg (usually nonrenal water loss (i.e., diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)):
     • Note: high urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation represents the appropriate response by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy to high plasma osmolality Plasma osmolality Volume Depletion and Dehydration in hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia

Management

Management may vary depending on practice location. The following information is based on US and UK literature.

General considerations

Hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia is treated by replacing the free water deficit by giving a hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation solution (i.e., 5% dextrose Dextrose Intravenous Fluids in water IV). Management is generally empirical with frequent monitoring of the serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and adjustment of the fluid rate.

Volume status Volume Status ACES and RUSH: Resuscitation Ultrasound Protocols considerations:

• If hypovolemic:^[9,13,15,16]
  • Management of hypovolemia Hypovolemia Sepsis in Children takes precedence.
  • Give isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation fluids.
  • After stabilization, switch to hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation fluids to address hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia.
  • Manage underlying conditions (e.g., hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus).
• If DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus ( euvolemic Euvolemic Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)):^[9,13,16]
  • Give hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation fluids to correct hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia.
  • Resume or start desmopressin Desmopressin Hemophilia to maintain normal serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia (for central DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus)
• If hypervolemic:^[13,15]
• If aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia mediated:
  • May only need free access to oral hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation fluids ( hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia should be mild)
  • Treat the underlying condition.
• Other causes:
  • Consider adding a loop diuretic with hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation fluid administration to induce natriuresis.
  • Consider hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome in end-stage renal disease or refractory cases.

Calculating free water deficit:^[9,10,12,16]

• Calculator
• Total body water Total body water Body Fluid Compartments ( TBW TBW Body Fluid Compartments) = (0.6 for men or 0.5 for women) x lean LEAN Quality Measurement and Improvement body weight in kg
• Free water deficit = TBW TBW Body Fluid Compartments x [(serum Na⁺ – 140) / 140]

Estimating sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia correction rate (based on fluids given):^[10,13]

• Calculator
• Change in serum Na⁺ = ([fluid Na⁺] – [serum Na⁺]) / ( TBW TBW Body Fluid Compartments + 1)
• Fluid rate (mL/hr) = (1,000 x desired rate of Na+ correction) / change in serum Na+
• Limitations Limitations Conflict of Interest:
  • Does not account for continued fluid loss (e.g., urine, insensible)
  • Not entirely reliable, but can be a starting point

Management according to acuity

For all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, the basic treatment strategy involves the following steps:^[9,13]

• Calculate the free water deficit
• Determine a suitable serum Na⁺ correction rate
• Estimate ongoing free water losses (e.g., renal, gastrointestinal, insensible)
• Create suitable fluid repletion program (including monitoring and adjustment)

Acute hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia:^[9,10]

• Uncommon (only occurs in specific situations):
  • Salt poisoning
  • DI DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus without appropriate compensatory water intake 
  • Severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus without appropriate compensatory water intake 
• Identify quickly due to the need for prompt and aggressive management.
• Goal:
  • A decrease in serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia by about 1 mmol/L/hr and a complete correction within 24 hours^{[5,9,14,15,16]}
  • Note: Some literature suggests not correcting > 10 mmol/L/day.^[13,15]
• Determine free water deficit 
• Determine the total amount of free water needed for the day:
  • Free water deficit + insensible water losses + renal/extrarenal water losses
  • Insensible losses Insensible losses Loss of water by diffusion through the skin and by evaporation from the respiratory tract. Volume Depletion and Dehydration ≃ 10 mL/kg/day
  • Febrile patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: add 3.5 mL/kg/day per 1℃
  • Renal free water loss = urine volume x [1 – (urine Na⁺ + urine K⁺)/serum Na⁺)]
• Initiate D5W IV infusion:^{[9,10,14–16]}
  • May be calculated (as above) → Note: Some recommend decreasing this by 75%‒50%.
  • May consider a starting rate of about 3‒6 mL/kg/hr^[7]
• Monitor serum Na⁺ closely and adjust the fluid rate as needed → initially monitor serum Na⁺ every 1‒2 hours^[2,15,16]

Chronic hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia: ^[9,10]

• Vast majority of hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia cases
• Goal: Decrease serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia by about 8‒10 mmol/L/day (< 0.5 mmol/L/hr) until normal.^[9,13,14,16] 
• Determine free water deficit
• Determine the total amount of free water needed for the day
• Begin D5W IV infusion:
  • May be calculated (as above) → Note: Some recommend decreasing this by 75%‒50%.
  • May consider a starting rate of 1.35 mL/kg/hr^[7]
• Oral free water is an option if hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia is not severe.^[9,16]
• Monitor serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and adjust the rate as needed:
  • Check serum Na⁺ every 2 hours initially, then space out to 4‒6 hours.^[15,16]
• Overcorrection Overcorrection Volume Depletion and Dehydration rarely causes clinical problems in adults, but it does in infants and children.^[3,14]

Complications

An acute rise in tonicity Tonicity Plasma tonicity refers to the concentration of only the osmotically active solutes in blood Renal Sodium and Water Regulation results in abrupt movement of fluid out of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. A slow rise in tonicity Tonicity Plasma tonicity refers to the concentration of only the osmotically active solutes in blood Renal Sodium and Water Regulation allows the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification to adapt and minimize the effect of fluid shifts. An overly rapid correction of hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia could result in abrupt movement of fluid into the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and cause cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP).

Acute hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,13,15]

• Sudden rise in plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products tonicity Tonicity Plasma tonicity refers to the concentration of only the osmotically active solutes in blood Renal Sodium and Water Regulation → rapid shift of water out of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• The brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification essentially shrinks in volume.
• If severe enough, the shrinking can tear the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification’s blood vessels → intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage and death

Chronic hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,13,15]

• Slower rise in plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products tonicity Tonicity Plasma tonicity refers to the concentration of only the osmotically active solutes in blood Renal Sodium and Water Regulation → slower shift of water out of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• The brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification responds with adaptive mechanisms to counter the water shift:
  • Takes about 48 hours: the distinction between acute (< 48 hours) and chronic (> 48 hours) hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia
  • Net effect is a much smaller loss of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification volume → no tearing of vessels
  • Does not, however, stop other symptoms from occurring (i.e., lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, confusion)

Overcorrection Overcorrection Volume Depletion and Dehydration of acute hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,14]

• Does not commonly cause clinical problems in adults
• Does commonly cause clinical problems in children and young adults (i.e., < 40 years old) with severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus (i.e., diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis)
• Severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus results in glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance contributing a significant amount to hypertonicity Hypertonicity Volume Depletion and Dehydration.
• Plasma osmolality Plasma osmolality Volume Depletion and Dehydration and serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance must be monitored very closely during treatment to prevent cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP):
  • Goal: decrease in plasma osmolality Plasma osmolality Volume Depletion and Dehydration by < 3 mmol/kg/hr
  • Goal: decrease in blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance by 50–75 mg/dL/hr

Overcorrection Overcorrection Volume Depletion and Dehydration of chronic hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia^[9,14,15,17]

• Water will always shift back into the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification as hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia improves.
• If the water shift occurs too abruptly, cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP) and/or osmotic demyelination Demyelination Multiple Sclerosis syndrome can occur.
• In practice, complications from hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia overcorrection Overcorrection Volume Depletion and Dehydration in adults are extremely rare:
  • Goal for adults: Decrease serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia by approximately 10 mEq/L/day.
  • Because overcorrection Overcorrection Volume Depletion and Dehydration is not detrimental, therapeutic reraising of serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia is not recommended if the target is exceeded.
• Overcorrection Overcorrection Volume Depletion and Dehydration is a common clinical problem with children and young adults:
  • Smaller skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy volume → less margin for error Error Refers to any act of commission (doing something wrong) or omission (failing to do something right) that exposes patients to potentially hazardous situations. Disclosure of Information if the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification shrinks or swells
  • Much closer monitoring of treatment is needed.
  • Goal for children and young adults: Decrease serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia by < 0.5 mmol/L/hr and < 10–12 mmol/L/day.