ALTAMIST

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-May administer without regard to meals.
Oral Liquid Formulations
-Sodium chloride injection solution may be administered enterally if necessary.
-In general, hypertonic solutions should be utilized to minimize volume. If a 23.4% solution is used, dilute in feedings or water prior to administration.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions when possible.
-When administering sodium chloride from flexible plastic containers, do not connect in series, pressurize without fully evacuating the container's residual air, or use a vented intravenous administration set with the vent in the open position. Such use could result in air embolism.
Intravenous Administration
-Central line administration is preferred for hypertonic sodium chloride solutions; however, peripheral administration is acceptable in critically ill patients who require immediate therapy. Central access should be obtained for continued use. Monitor peripheral administration of hypertonic solutions carefully for potential extravasation and local tissue damage.
-0.45% Sodium Chloride Injection (without additional additives) is the most hypotonic sodium chloride solution that can be safely administered without risking cell lysis. Additional solutes such as dextrose or other electrolytes (e.g., potassium chloride) can be added to hypotonic sodium chloride solutions to increase their tonicity and make intravenous administration feasible without causing cell lysis.
-Do not mix or administer hypotonic or hypertonic sodium chloride injection solutions through the same administration set with whole blood or cellular blood components.

IV Push/Bolus
0.9% Isotonic Solution (for emergent fluid resuscitation [e.g., severe hypovolemia or shock])
-Neonates: Administer bolus over 5 to 10 minutes. Premature neonates younger than 30 weeks gestation should receive fluid resuscitation over a longer duration of time. Avoid very rapid administration; some evidence suggests that rapid administration may increase the risk of intracranial hemorrhage.
-Infants, Children, and Adolescents: Administer bolus over 5 to 10 minutes; patients with cardiogenic shock or cardiac dysfunction (e.g., calcium channel blocker or beta-blocker overdose) should receive boluses over 10 to 20 minutes.
3% or 5% Hypertonic Solution (for increased ICP)
-Administer over 5 to 20 minutes.
23.4% Hypertonic Solution (for increased ICP)
-Administer via central line over 10 to 20 minutes.

Intermittent IV Infusion
0.9% Isotonic Solution (for urgent fluid replacement [e.g., dehydration or diabetic ketoacidosis with compensated shock])
-Administer over 1 hour.
3% Hypertonic Solution (for Hyponatremia)

-Administer over 20 to 30 minutes.

Continuous IV Infusion
3% Hypertonic Solution (for Hyponatremia or increased ICP)
-Usual rates vary from 0.5 to 3 mL/kg/hour.
-ASHP Recommended Standard Concentration for Pediatric Continuous Infusion: 0.5 mEq/mL (3%).

Other Injectable Administration
Intraosseous Administration
-For emergent fluid resuscitation, 0.9% Sodium Chloride Injection may be given via the intraosseous route when IV access is not available. Of note, intraosseous lines are not commonly used in neonates because of the availability of the umbilical vein, the fragility of small bones, and the small intraosseous space available.



Inhalation Administration
Oral Inhalation Administration
Inhalation Solution for Nebulization
-To minimize or prevent bronchospasm, administer a bronchodilator (e.g., albuterol) 15 to 60 minutes prior to inhalation of hypertonic sodium chloride.
-Inhaled hypertonic sodium chloride has been administered via jet and ultrasonic nebulization.

Intranasal Inhalation Administration
-Infants and Small Children: Lay the child on their back. Laying the patient on the caregiver's lap and positioning their head between the caregiver's knees may assist administration. Put drops in each nostril and have the child remain on their back for 1 to 2 minutes. Gently wipe the nose with a tissue or use a nasal aspirator/bulb syringe to remove mucus.
-Older Children and Adolescents: Hold bottle upright. Give short, firm squeezes into each nostril. Do not aspirate nasal contents back into bottle.
-Rinse bottle tip with hot water and wipe with a clean towel after each administration.
-To avoid contamination and prevent the spread of infection, do not use the bottle dispenser for more than 1 person to prevent the spread of infection.

Possible adverse reactions to intravenous hypertonic sodium chloride include rebound increased intracranial pressure (ICP), subarachnoid hemorrhage, natriuresis, high urinary water losses, severe electrolyte abnormalities, hyperchloremic acidosis, and masking of the development of diabetes insipidus. In addition, administration of intravenous hypotonic sodium chloride solutions in pediatric patients, particularly postoperatively or in the presence of dehydration, may result in significant dilutional hyponatremia and encephalopathy. Acute symptomatic hyponatremic encephalopathy is a medical emergency. Monitor daily weights, fluid balance, and serum sodium concentrations closely in patients receiving parenteral fluid therapy.

Central pontine myelinolysis (CPM) is a noninflammatory demyelinating condition associated with the rapid correction of hyponatremia. Though the neurologic deficits of hyponatremia often improve initially after rapid sodium correction, new, progressive, and sometimes permanent neurologic effects (e.g., quadriparesis, pseudobulbar paralysis, pseudocoma/'locked in syndrome', coma, seizures) present within several days. Higher incidences of spastic cerebral paralysis, neurosensorial auditory damage, and behavioral problems have been observed in former very low birth weight preterm neonates with a history of rapid correction of chronic hyponatremia. Though there is no specific treatment for CPM, neurologic sequelae may be avoided with slow correction of hyponatremia, allowing the brain to better adjust to shifting osmolalities. In neonates, serum sodium should not increase by more than 8 to 10 mEq/L in the first 24 hours. In infants, children, and adolescents, serum sodium should not increase by more than 10 to 12 mEq/L in the first 24 hours and 18 mEq/L in the first 48 hours. Patients with severe malnutrition, alcoholism, or advanced liver disease may be more susceptible to CPM and sodium replacement therapy should be tailored to stay well below established limits.

Hemolysis of red blood cells can occur during the infusion of hypotonic saline solutions. In the presence of a hypotonic fluid, water enters the red blood cells across a diffusion gradient, causing the cells to swell and burst. After lysis, the intracellular contents of the cells (e.g., potassium, phosphate) are released into the extracellular space; in the most severe cases, this can result in hyperkalemia and potentially cardiac arrhythmias (arrhythmia exacerbation) and even death. Because of this phenomenon, isotonic or near-isotonic solutions are preferred for fluid administration. The most hypotonic fluid that can be safely administered is 0.45% sodium chloride (154 mOsm/L); solutions with an osmolarity less than this are not recommended. Mixing hypotonic saline solutions with dextrose or other solutes increases their tonicity and makes the overall solution approach isotonicity, making it feasible to administer an intravenous infusion with a lower sodium content. For example, 0.225% sodium chloride with dextrose 5% has an osmolarity of 329 mOsm/L. Because hemolysis is accentuated by an increased ratio of hypotonic solution to blood and prolonged cell contact time with the solution, it has been suggested that administering hypotonic solutions at a slower rate or through a central line may decrease the risk of cell lysis; however, hemolysis can still occur with such precautionary measures and use of any hypotonic solution in pediatric patients should be used with extreme caution.

Cough, bronchospasm/chest tightness, pharyngitis, hemoptysis, sinusitis, and sneezing have been reported in stable cystic fibrosis patients receiving inhaled hypertonic 7% sodium chloride solution. In patients who did not discontinue treatment, resolution of events occurred after a mean of 15 days with no change in therapy. Hoarseness, lasting for 3 to 4 days, has also been described with nebulized saline use. In general, inhaled hypertonic sodium chloride is well-tolerated and most adverse reactions are not clinically significant. Pretreatment with a bronchodilator (e.g., albuterol) may minimize or prevent bronchospasm.

Hypertonic sodium chloride solutions have been associated with renal impairment/insufficiency and acute renal failure (unspecified) in pediatric patients being treated for increased intracranial pressure. Consensus guidelines recommend maintaining serum osmolarity less than 360 mOsm/L; however, some experts recommend maintaining serum sodium less than 160 mEq/L and serum osmolarity less than 320 mOsm/L to prevent acute renal failure.

The use of systemic sodium chloride could result in hypernatremia, hyperchloremia, and sodium and/or fluid retention. Systemic sodium chloride administration and subsequent sodium retention can exacerbate hypertension, edema, and heart failure; symptoms of intolerance may include dehydration, weakness, disorientation, anorexia, nausea, distention, oliguria, and increased blood urea nitrogen. In addition, excessive administration of potassium-free solutions may result in significant hypokalemia. During fluid resuscitation, rapid infusion of a large volume of fluids in patients with compromised cardiac or renal function may result in decreased cardiac output and pulmonary edema. Hepatomegaly occurs in children who are fluid overloaded and can be a sign of the adequacy of fluid resuscitation. In addition, rapid volume expansion has been associated with intraventricular hemorrhage in neonates. Carefully monitor for signs of fluid overload (e.g., increased work of breathing, rales, gallop rhythm, hepatomegaly). In general, volume expansion should only be used in neonates when clearly needed (e.g., acute blood loss). Premature neonates younger than 30 weeks gestational age should receive fluid resuscitation over a longer duration of time.

Injection site reaction, including infection, phlebitis, venous thrombosis, and extravasation, has occurred with administration of intravenous sodium chloride. Infusion site erythema, injection site streaking, burning sensation, and infusion site urticaria have also been reported. In addition, fever has been reported in patients receiving intravenous sodium chloride and may be due to the solution or the administration technique used. Because of the potential for local tissue damage, central line administration of hypertonic solutions is recommended. If a local reaction occurs, discontinue the infusion, evaluate the patient, and institute appropriate countermeasures.

Hypersensitivity and infusion-related reactions, including hypotension, pyrexia, tremor, chills, urticaria, rash, and pruritus, have been reported with intravenous sodium chloride. Stop the infusion immediately if signs or symptoms of a hypersensitivity reaction occur (e.g., sinus tachycardia, chest pain (unspecified), dyspnea, flushing). Institute appropriate therapeutic countermeasures as clinically indicated.

Hypersensitivity and infusion reactions may occur with intravenous sodium chloride infusion. Immediately stop the infusion and institute appropriate therapeutic countermeasures if signs or symptoms of hypersensitivity occur.

Use sodium chloride with great caution in patients with preexisting hypernatremia, hyperchloremia, metabolic acidosis, or risk factors for such conditions. Intravenous solutions should be used with particular care in patients at risk for hypervolemia or other conditions that may cause sodium retention and fluid overload such as patients with primary or secondary hyperaldosteronism. In patients with cardiac disease, sodium chloride administration and subsequent sodium retention can exacerbate hypertension, edema, and heart failure. In addition, because sodium chloride is primarily excreted by the kidney, administration to patients with renal disease, including renal artery stenosis, nephrosclerosis, renal impairment, or renal failure may result in significant sodium and chloride retention. During fluid resuscitation, rapid infusion of a large volume of fluid in patients with hypoxia and/or compromised cardiac or renal function may result in decreased cardiac output and pulmonary edema. In addition, it is recommended to avoid routine volume expansion in newborns without evidence of acute blood loss. Monitor fluid balance, electrolyte concentrations, and acid base balance during prolonged therapy or whenever the patient or dosage and/or rate of administration warrants such evaluation. In patients with organ dysfunction, monitor respiratory status and tissue perfusion, as well as changes in clinical condition.

When providing fluid resuscitation with sodium chloride for patients with diabetic ketoacidosis (DKA), avoid rapid administration and monitor the patient very carefully. Limit individual boluses to 10 to 20 mL/kg and infuse over 1 hour. Patients with DKA are often significantly dehydrated and have a high serum osmolality due to hyperglycemia. Rapid fluid administration may contribute to cerebral edema. In addition, children who have ingested significant doses of calcium-channel blockers or beta-blockers (i.e., overdose) may have myocardial dysfunction and may not be able to tolerate rapid fluid administration; these patients should be resuscitated with smaller than normal volumes and at a slower rate.

Bacteriostatic sodium chloride products contain benzyl alcohol and are contraindicated in neonates and premature neonates. Large amounts of benzyl alcohol (more than 99 mg/kg/day) have been associated with gasping syndrome in this population. Gasping syndrome is characterized by central nervous depression, metabolic acidosis, and gasping respirations. If a sodium chloride solution is required for preparing medications or intravascular flush, only preservative-free injection should be used. Maintaining appropriate sodium balance can be very challenging for some neonates. Many physiological changes occur during the first weeks of life that affect the neonate's handling of fluid and sodium, especially in premature neonates. Carefully assess fluid and sodium status and adjust therapy as appropriate. In addition, fluid resuscitation in neonates, particularly premature neonates, may cause rapid volume expansion and has been associated with intraventricular hemorrhage. In general, volume expansion in neonates should only be used when clearly needed (e.g., evidence of acute blood loss). Premature neonates younger than 30 weeks gestational age should receive fluid resuscitation with 0.9% NaCl Injection over a longer duration of time. Closely monitor serum electrolytes in pediatric patients who may have an impaired ability to regulate fluid and electrolyte balance. Children, including neonates and infants, are at increased risk of developing hyponatremia and hyponatremic encephalopathy.

To avoid sodium and/or water toxicity, it is essential to correct hyponatremia at an appropriate rate. In addition, central pontine myelinolysis (CPM), a noninflammatory demyelinating condition, can occur when hyponatremia is corrected too quickly. In the neonatal population, serum sodium should not increase by more than 8 to 10 mEq/L in the first 24 hours. In infants, children, and adolescents, serum sodium should not increase by more than 10 to 12 mEq/L in the first 24 hours and 18 mEq/L in the first 48 hours. Patients with severe malnutrition, alcoholism, or advanced liver disease may be more susceptible to CPM and sodium replacement therapy should be tailored to stay well below established limits. In addition, administration of hypotonic sodium chloride solutions in pediatric patients, particularly in the presence of dehydration or in the postoperative or critical care setting, may result in significant dilutional hyponatremia, encephalopathy, and death. The risk of hospital-acquired hyponatremia is increased in patients with cardiac or pulmonary failure and in those with non-osmotic vasopressin release (including SIADH). Risk for developing hyponatremia is also increased in those with psychogenic polydipsia and those who are receiving concurrent medications that increase the risk of low serum sodium. Patients with hypoxemia and those with underlying central nervous system disease are at risk for developing hyponatremic encephalopathy. Females (particularly premenopausal) are also at higher risk; whether this risk extends to female children is not known. Monitor daily weights, fluid balance, and serum sodium concentrations closely in patients receiving parenteral fluid therapy. Although there is no ideal maintenance fluid for all children in terms of fluid composition and the rate and duration of administration, isotonic fluids may be a safer alternative to hypotonic fluids. The American Academy of Pediatrics recommends that patients 28 days to 18 years of age (in the postoperative and acute care setting) requiring maintenance fluids receive isotonic solutions with appropriate potassium chloride and dextrose. The addition of dextrose to hypotonic saline solutions (e.g., 5% Dextrose and 0.45% NaCl Injection) increases tonicity; however, these solutions are still effectively hypotonic because of rapid dextrose metabolism. In a retrospective cohort study of hospitalized children with normal serum sodium values at admission (n = 1,048), administration of hypotonic fluids was associated with a greater risk of developing hyponatremia, even after adjusting for admission diagnosis, age, surgical admission, and diuretic use (adjusted OR 1.37, 95% CI 1.03 to 1.84). Patients with a surgical (adjusted OR 1.44, 95% CI 1.09 to 1.91), cardiac (adjusted OR 2.08, 95% CI 1.34 to 3.2, p = 0.001), or hematology/oncology (adjusted OR 2.37, 95% CI 1.74 to 3.25, p less than 0.001) admission diagnosis were at greatest risk. Meta-analysis of 10 randomized controlled trials involving 855 pediatric subjects associated hypotonic fluids with a higher risk for hyponatremia (RR 2.24, 95% CI 1.52 to 3.31, p less than 0.0001) and more severe hyponatremia (serum sodium less than 130 mEq/L; RR 5.29, 95% CI 1.74 to 16.06, p = 0.003). No significant difference was found between the use of hypotonic or isotonic fluids and the risk of hypernatremia (RR 0.73, 95% CI 0.22 to 2.48; p = 0.62). Subgroup analysis of another meta-analysis (10 trials; n = 893) found that hypotonic sodium chloride fluids containing at least 0.45% NaCl Injection carried similar risk for hyponatremia (RR 2.42, 95% CI 1.32 to 4.45) compared to the group overall (e.g., 0.13% to 0.45% NaCl Injection with dextrose; serum sodium less than 135 mEq/L: RR 2.37, 95% CI 1.72 to 3.26; serum sodium less than 130 mEq/L: RR 6.1, 95% CI 2.2 to 17.3).

Carefully consider fluid status in hyponatremic patients with hepatic disease (e.g., cirrhosis) before using sodium chloride supplementation. Water retention and dilutional hyponatremia are common in patients with advanced disease and should be treated with sodium and fluid restriction, as well as diuretics. Sodium supplementation may aggravate edema. In addition, patients with advanced liver disease may be more susceptible to central pontine myelinolysis (CPM); sodium replacement therapy should be tailored to stay well below established limits.

Hemolysis of red blood cells can occur during the infusion of hypotonic solutions. In the presence of a hypotonic fluid, water enters the red blood cells across a diffusion gradient, causing the cells to swell and burst. After lysis, the intracellular contents of the cells (e.g., potassium, phosphate) are released into the extracellular space, resulting in hyperkalemia and potentially cardiac arrhythmias and death. Because of this phenomenon, isotonic solutions are preferred for fluid administration. For intravenous fluids, isotonicity is defined as a solution that has equal osmotic pressure to that of the serum (285 to 295 mOsm/L). Normal saline (0.9% Sodium Chloride Injection) contains 308 mOsm/L and is considered isotonic. In contrast, 0.45% Sodium Chloride Injection (154 mOsm/L) and 0.225% Sodium Chloride Injection (77 mOsm/L) are hypotonic. Hypotonic solutions should never be used for fluid resuscitation or rehydration; however, they are sometimes used in patients with high serum osmolarity (e.g., hypernatremia, diabetic ketoacidosis) in carefully monitored clinical settings. Additionally, hypotonic saline solutions offer a maintenance infusion option with less sodium content, which may be desirable in specific circumstances (e.g., newborns). However, the most hypotonic fluid that can be safely administered is 0.45% Sodium Chloride Injection (154 mOsm/L); solutions with an osmolarity less than this are not recommended. The risk of hemolysis increases as the tonicity decreases; of the commercially available saline products, 0.225% Sodium Chloride Injection carries the greatest risk of hemolysis with infusion. Mixing hypotonic saline solutions with dextrose increases their tonicity and makes the overall solution approach isotonicity, making it feasible to administer an intravenous infusion with a lower sodium content. For example, 5% Dextrose and 0.225% Sodium Chloride Injection has an osmolarity of 329 mOsm/L. Because hemolysis is accentuated by an increased ratio of hypotonic solution to blood and prolonged cell contact time with the solution, it has been suggested that administering hypotonic solutions at a slower rate or through a central line may decrease the risk of cell lysis; however, hemolysis can still occur with such precautionary measures and use of any hypotonic solution in pediatric patients should be used with extreme caution.

Rapid correction of hypo- or hypernatremia requires an experienced clinician. Due to the risk of serious neurologic complications, dosage, rate, and duration of administration should be determined by a physician experienced in intravenous fluid therapy.

Description: Sodium and chloride are the principle cation and anion, respectively, of extracellular fluid. They play a major role in fluid regulation and tissue hydration. Sodium chloride is available in a variety of concentrations and dosage forms. It has a plethora of indications but is commonly used in intravenous (IV) maintenance fluids and as an isotonic crystalloid for volume resuscitation in dehydration and shock. Pediatric traumatic brain injury guidelines recommend intermittent or continuous IV infusion of 3% hypertonic saline for the management of intracranial hypertension and intermittent 23.4% hypertonic saline for refractory intracranial pressure. Hypertonic saline is also used intravenously to correct acute, symptomatic hyponatremia and via nebulization to increase mucociliary clearance and improve lung function in patients with cystic fibrosis. Although the American Academy of Pediatrics (AAP) states that nebulized hypertonic saline may be administered to infants and young children hospitalized for bronchiolitis, use in the emergency department is not recommended. Sodium and water regulation is an intricate balance and systemic administration of sodium chloride solutions, particularly in the pediatric population, should be handled with care. Potential complications include fluid overload, pulmonary edema, and intraventricular hemorrhage (particularly in neonates). Rapid correction of hyponatremia may result in severe electrolyte abnormalities and neurologic deficits; adherence to recommended correction rates is essential. In addition, administration of hypotonic saline in pediatric patients, particularly postoperatively or in the presence of dehydration, may result in significant hyponatremia, encephalopathy, and death. To reduce this risk, the AAP recommends infants, children, and adolescents who require IV maintenance fluids receive isotonic solutions. Most non-hypertonic sodium chloride formulations can be used in pediatric patients as young as neonates.

Sodium content and osmolarity:
-0.9% sodium chloride solution = 154 mEq/L (0.154 mEq/mL) sodium; osmolarity of 308 mOsm/L.
-3% sodium chloride solution = 513 mEq/L (0.513 mEq/mL) sodium; osmolarity of 1,027 mOsm/L.
-23.4% sodium chloride solution = 4,000 mEq/L (4 mEq/mL) sodium; osmolarity of 8,008 mOsm/L.
-1 gram sodium chloride tablet = 17.1 mEq sodium/tablet.

Safety Considerations:
-Concentrated sodium chloride solutions (more than 0.9% NaCl) are included on the High Alert Medication list by The Institute for Safe Medication Practices (ISMP). Carefully consider dosing, preparation, administration, and monitoring when using concentrated electrolyte solutions.
-Inappropriate use of low-sodium (e.g., hypotonic sodium chloride) or sodium-free IV fluids (e.g., 5% Dextrose Injection) in pediatric patients can lead to a serious decrease in serum sodium concentrations, which may result in major morbidity and mortality. Monitor patients receiving IV fluids with low sodium concentrations carefully. The American Academy of Pediatrics recommends infants, children, and adolescents who require IV maintenance fluids receive isotonic solutions.

For the treatment of dehydration or hypovolemia, including during cardiopulmonary resuscitation and shock (e.g., septic shock, anaphylactic shock, diabetic ketoacidosis with compensated shock, cardiogenic shock):
Intravenous dosage:
Neonates: 10 mL/kg IV bolus. Administer over 5 to 10 minutes for near-term neonates; slower administration is recommended for neonates younger than 30 weeks gestation because rapid administration has been associated with intraventricular hemorrhage. May repeat once if significant improvement does not occur; further volume should only be considered in cases of documented large blood loss.
Infants, Children, and Adolescents (dehydration, non-emergent): 20 mL/kg IV bolus (Usual Max: 1,000 mL/bolus) over 1 hour, followed by appropriate rehydration fluids over the next 24 to 48 hours.
Infants, Children, and Adolescents (hypovolemic or distributive [e.g., septic, anaphylactic] shock): 20 mL/kg IV bolus (Usual Max: 1,000 mL/bolus) over 5 to 20 minutes. Children with septic shock often have a large fluid deficit and may require 40 to 60 mL/kg during the first hour and 200 mL/kg or more during the first 8 hours of therapy. May repeat as needed to restore blood pressure and tissue perfusion.
Infants, Children, and Adolescents (cardiogenic shock or poisonings [e.g., calcium channel blocker, beta-blocker]): 5 to 10 mL/kg IV bolus over 10 to 20 minutes. Carefully monitor for signs of worsening respiratory status and pulmonary edema. May repeat as needed to restore blood pressure and tissue perfusion.
Infants, Children, and Adolescents (diabetic ketoacidosis with compensated shock): 10 to 20 mL/kg IV bolus (Usual Max: 1,000 mL/bolus) over 1 hour. Thereafter, therapy should be guided by hemodynamic status and serum electrolytes; subsequent fluid replacement should be completed with 0.45% or 0.9% Sodium Chloride Injection over the next 24 to 48 hours.

For the treatment of hyponatremia, including patients with syndrome of inappropriate antidiuretic hormone (SIADH):
-for the treatment of acute or symptomatic hyponatremia:
Intravenous dosage (3% hypertonic solution):
Neonates: 3 to 5 mL/kg IV over 20 to 30 minutes; may repeat dose as needed until target of 4 to 6 mEq/L increase in serum sodium concentration is achieved. On average, 1 mL/kg of 3% sodium chloride raises the serum sodium concentration by 1 mEq/L. Alternatively, 0.5 to 3 mL/kg/hour continuous IV infusion (2 to 3 mL/kg/hour for those with active seizures or signs of brain herniation). Monitor serum sodium concentrations every 1 to 2 hours during infusion. In general, do not exceed a correction of 10 to 12 mEq/L in the first 24 hours (8 mEq/L for those at high risk for osmotic demyelination syndrome) and 18 mEq/L within 48 hours.
Infants, Children, and Adolescents: 3 to 5 mL/kg IV over 20 to 30 minutes; may repeat dose as needed until target of 4 to 6 mEq/L increase in serum sodium concentration is achieved. On average, 1 mL/kg of 3% sodium chloride raises the serum sodium concentration by 1 mEq/L. Alternatively, 0.5 to 3 mL/kg/hour continuous IV infusion (2 to 3 mL/kg/hour for those with active seizures or signs of brain herniation). Monitor serum sodium concentrations every 1 to 2 hours during infusion. In general, do not exceed a correction of 10 to 12 mEq/L in the first 24 hours (8 mEq/L for those at high risk for osmotic demyelination syndrome) and 18 mEq/L within 48 hours.
-for the treatment of asymptomatic or chronic hyponatremia:
Intravenous dosage (0.9% isotonic solution):
Neonates: Dose (mEq sodium) = [desired serum sodium (mEq/L) - actual serum sodium (mEq/L)] x weight (kg) x 0.6. In general, do not exceed a correction of 10 to 12 mEq/L in the first 24 hours (8 mEq/L for those at high risk for osmotic demyelination syndrome) and 18 mEq/L within 48 hours.
Infants, Children, and Adolescents: Dose (mEq sodium) = [desired serum sodium (mEq/L) - actual serum sodium (mEq/L)] x weight (kg) x 0.6. In general, do not exceed a correction of 10 to 12 mEq/L in the first 24 hours (8 mEq/L for those at high risk for osmotic demyelination syndrome) and 18 mEq/L within 48 hours.
Oral dosage:
Neonates: 1 mEq/kg/dose PO 2 to 4 times daily. Alternatively, the following formula may be used: Dose (mEq sodium) = [desired serum sodium (mEq/L) - actual serum sodium (mEq/L)] x weight (kg) x 0.6. Oral sodium chloride is recommended in combination with a low-dose loop diuretic as second-line treatment after fluid restriction for SIADH.
Infants, Children, and Adolescents: 1 mEq/kg/dose PO 2 to 4 times daily. Alternatively, the following formula may be used: Dose (mEq sodium) = [desired serum sodium (mEq/L) - actual serum sodium (mEq/L)] x weight (kg) x 0.6. Oral sodium chloride is recommended in combination with a low-dose loop diuretic as second-line treatment after fluid restriction for SIADH.

For the treatment of increased intracranial pressure (ICP)*:
NOTE: Monitor ICP, serum osmolarity, and sodium concentrations (every 4 to 6 hours) during treatment.
Intravenous dosage (3% sodium chloride):
Infants, Children, and Adolescents: 2 to 10 mL/kg/dose IV over 5 to 20 minutes; may repeat dose as needed to maintain target ICP, serum osmolarity, and serum sodium concentrations. Avoid prolonged hypernatremia (serum sodium concentrations more than 160 mEq/L).
Intravenous dosage (5% sodium chloride):
Infants, Children, and Adolescents: 2.5 to 5 mL/kg/dose IV over 5 to 20 minutes; may repeat dose as needed to maintain target ICP, serum osmolarity, and serum sodium concentrations. Avoid prolonged hypernatremia (serum sodium concentrations more than 160 mEq/L).
Intravenous dosage (23.4% sodium chloride):
Infants, Children, and Adolescents: 0.5 mL/kg/dose (Max: 30 mL/dose) IV over 10 to 20 minutes. Higher doses based on weight bands have also been reported; a protocol used standard doses of 10 mL for patients weighing 10 to 19 kg, 20 mL for patients weighing 20 to 29 kg, and 30 mL for patients weighing 30 kg or more. May repeat dose as needed to maintain target ICP, serum osmolarity, and serum sodium concentrations. Avoid prolonged hypernatremia (serum sodium concentrations more than 160 mEq/L).
Continuous Intravenous Infusion dosage (3% sodium chloride):
Infants, Children, and Adolescents: 0.5 to 1 mL/kg/hour continuous IV infusion, initially; titrate dose to maintain target ICP, serum osmolarity, and serum sodium concentrations. Doses as high as 3 mL/kg/hour continuous IV infusion have been reported. Avoid prolonged hypernatremia (serum sodium concentrations more than 160 mEq/L).

For mucolysis and sputum induction in persons with cystic fibrosis:
Respiratory (Inhalation) dosage (7% nebulizer solution):
Children and Adolescents 6 to 17 years: 4 mL/dose inhaled by nebulizer twice daily. Mucus clearance is dose-dependent for hypertonic saline concentrations up to 7%; lesser concentrations (e.g., 3%) may be considered for persons who do not tolerate the 7% solution.

For the inpatient management of viral bronchiolitis*:
Oral inhalation dosage (3% nebulized solution):
Neonates: 4 mL/dose via oral inhalation every 2 hours for 3 doses, then every 4 hours for 5 doses, and finally every 6 hours until discharge. To prevent bronchospasm, administer after a bronchodilator (e.g., albuterol). Evidence suggests hypertonic saline is effective in improving symptoms of non-severe bronchiolitis after 24 hours of use and reducing hospital length of stay when the admission exceeds 3 days. Although data has been contradictory, meta-analysis suggests use in areas where the length of administration is brief (e.g., the emergency department) does not improve short-term outcomes or decrease hospitalization rates.
Infants and Children 1 to 2 years: 4 mL/dose via oral inhalation every 2 hours for 3 doses, then every 4 hours for 5 doses, and finally every 6 hours until discharge. To prevent bronchospasm, administer after a bronchodilator (e.g., albuterol). Of note, although the American Academy of Pediatrics states that nebulized hypertonic saline may be administered to infants and children 1 to 23 months of age hospitalized for bronchiolitis, use in the emergency department is not recommended. Evidence suggests hypertonic saline is effective in improving symptoms of non-severe bronchiolitis after 24 hours of use and reducing hospital length of stay when the admission exceeds 3 days. Although data has been contradictory, meta-analysis suggests use in areas where the length of administration is brief (e.g., the emergency department) does not improve short-term outcomes or decrease hospitalization rates.

For nutritional supplementation:
-for nutritional supplementation in persons with cystic fibrosis:
Oral dosage:
Neonates: 1 to 2 mEq/kg/day PO in divided doses; up to 4 mEq/kg/day PO in divided doses may be needed for infants living in hot ambient temperatures, with increased fluid loss due to vomiting, fever, diarrhea, or tachypnea, or with ostomies. Routine supplementation is recommended for all infants.
Infants: 1 to 2 mEq/kg/day PO in divided doses; up to 4 mEq/kg/day PO in divided doses may be needed for infants living in hot ambient temperatures, with increased fluid loss due to vomiting, fever, diarrhea, or tachypnea, or with ostomies. Routine supplementation is recommended for all infants.
Children: Up to 4 g/day PO in divided doses may be needed in stress situations when excessive sweating is expected (i.e., fever, exercise/sports, hot weather). Most older children will generally get adequate sodium from consuming a high-sodium diet and supplementation is generally only needed in stressful situations.
Adolescents: Up to 6 g/day PO in divided doses may be needed in stress situations when excessive sweating is expected (i.e., fever, exercise/sports, hot weather). Most adolescents will generally get adequate sodium from consuming a high-sodium diet and supplementation is generally only needed in stressful situations.
-for nutritional supplementation to prevent sodium deficiency and maintain nutritional status in persons receiving parenteral nutrition (PN):
Intravenous dosage:
Neonates: 2 to 5 mEq/kg/day IV. Adjust dosage as needed based on serum sodium concentrations.
Infants, Children, and Adolescents weighing 50 kg or less: 2 to 5 mEq/kg/day IV. Adjust dosage as needed based on serum sodium concentrations.
Children and Adolescents weighing more than 50 kg: 1 to 2 mEq/kg/day IV. Adjust dosage as needed based on serum sodium concentrations.

For the treatment of nasal congestion and dryness:
Intranasal dosage (0.65% nasal solution):
Neonates: 2 to 6 drops in each nostril as needed. Drops are recommended for neonates.
Infants, Children, and Adolescents: 2 to 6 drops in each nostril as needed. For nasal sprays, 2 sprays in each nostril as needed. Drops are recommended for infants.

Maximum Dosage Limits:
-Neonates
For hypovolemia, do not exceed 10 mL/kg IV per bolus of a 0.9% isotonic solution. For sodium replacement, dosage must be individualized based on serum sodium concentrations and patient requirements.
-Infants
For hypovolemia, do not exceed 20 mL/kg IV per bolus of a 0.9% isotonic solution. For sodium replacement and management of ICP, dosage must be individualized based on serum sodium concentrations and patient requirements. For management of ICP, do not exceed 10 mL/kg/dose IV of a 3% hypertonic solution.
-Children
For hypovolemia, do not exceed 20 mL/kg IV per bolus (Usual Max: 1,000 mL/bolus) of a 0.9% isotonic solution. For sodium replacement and management of ICP, dosage must be individualized based on serum sodium concentrations and patient requirements. For management of ICP, do not exceed 10 mL/kg/dose IV of a 3% hypertonic solution.
-Adolescents
For hypovolemia, do not exceed 20 mL/kg IV per bolus (Usual Max: 1,000 mL/bolus) of a 0.9% isotonic solution. For sodium replacement and management of ICP, dosage must be individualized based on serum sodium concentrations and patient requirements. For management of ICP, do not exceed 10 mL/kg/dose IV of a 3% hypertonic solution.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available. Carefully consider fluid status in patients with hepatic impairment and hyponatremia.

Patients with Renal Impairment Dosing
Dosage should be modified based on clinical response, but no quantitative recommendations are available. Avoid or use systemic therapy with great caution in patients with severe renal impairment. If use is necessary, monitor serum sodium concentrations and renal function carefully to avoid sodium retention.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Sodium is the principal cation of the extracellular fluid, while chloride is the principal anion. Both ions are physiologically important. Sodium functions as the primary osmotic determinant in extracellular fluid regulation and tissue hydration. Additionally, sodium regulates the membrane potential of cells and the active transport of molecules across cell membranes. Chloride is also responsible for maintaining fluid balance, but it is also essential in the maintenance of acid-base balance. Low plasma chloride concentrations cause an increase in bicarbonate, producing alkalosis. Sodium is a unique electrolyte because, in general, water balance is directly related to its concentration. High sodium concentrations and an increase in plasma osmolality stimulate mechanisms that increase the water content of the body, such as increased thirst and increased antidiuretic hormone (ADH) secretion, which leads to renal conservation of water. During hyponatremia, the decrease in plasma osmolality stops ADH secretion; therefore, renal water excretion leads to an increase in sodium concentration. Although sodium and water balance is usually regulated by osmolality, volume depletion also stimulates thirst and ADH secretion; ADH secretion is triggered even if the patient is hyponatremic.

For use as IV fluids:
Isotonic IV fluids have an osmotic pressure that is approximately equal to that of serum (285 to 295 mOsm/L). Normal saline (0.9% NaCl) has an osmolality of 308 mOsm/L and is considered isotonic. In contrast, 0.45% NaCl (154 mOsm/L) and 0.225% NaCl (77 mOsm/L) are hypotonic. The initial goal of treating dehydration and shock is to restore intravascular volume, which improves perfusion to critical organs. Because 0.9% NaCl is isotonic, administered fluid remains in the extracellular compartment (comprised of interstitial and intravascular spaces) where it helps restore blood volume and supports peripheral perfusion. Hypotonic solutions should not be used for initial fluid resuscitation because a significant portion of the administered fluid distributes outside the intravascular compartment. Hypotonic solutions are sometimes used in patients with high serum osmolarity (e.g., hypernatremia, diabetic ketoacidosis). In addition, hypotonic saline solutions offer a maintenance infusion option with less sodium content, which is desirable in certain patient populations. However, the most hypotonic fluid that can be safely administered without risking cell lysis is 0.45% NaCl (154 mOsm/L). Mixing hypotonic saline solutions with dextrose or other electrolytes increases their tonicity and makes the overall solution approach isotonicity, making it feasible to administer an intravenous infusion with lower sodium content.

For the reduction of increased intracranial pressure:
In patients with head trauma, administration of intravenous hypertonic solutions (e.g., 3% NaCl) reduces intracranial pressure by creating an osmotic gradient across the blood-brain barrier. Penetration of sodium across the blood-brain barrier is low, which results in water passively diffusing into the intravascular space. This reduction of fluid within the cerebral tissue decreases intracranial volume, cerebral edema, and intracranial pressure. Other theoretical benefits involved in the reduction of intracranial pressure include restoration of normal cellular resting membrane potential and cell volume, stimulation of arterial natriuretic peptide release, inhibition of inflammation, and enhancement of cardiac output.

To increase hydration of viscous respiratory secretions:
Local application of sodium chloride to the respiratory epithelium creates an osmotic gradient, allowing water to diffuse onto the airway surface and rehydrate the periciliary fluid. In patients with cystic fibrosis, orally inhaled hypertonic saline (e.g., 6% to 7% sodium chloride) has been proposed to increase the hydration of airway secretions, which enhances mucociliary clearance and improves sputum expectoration, reducing the risk of infection and progressive airway destruction. Though the exact mechanism is unknown, osmotic hydration, disruption of mucus strand cross-linking, and reduction of mucosal edema may facilitate such improvement. Additionally, because viral bronchiolitis is characterized by airway plugging and edema, nebulized hypertonic saline may be beneficial in hospitalized infants with moderate to severe symptoms.

Pharmacokinetics: Sodium chloride is administered orally, intravenously, via inhalation, intranasally, and topically to the eye. Sodium chloride distributes primarily to extracellular compartments, including plasma and interstitial fluid; sodium is maintained outside the cell via the Na+/K+-ATPase pump, which exchanges intracellular sodium for extracellular potassium. Penetration across the blood-brain barrier is low. Sodium chloride is excreted primarily in the urine, but it is also excreted in sweat and stool. In healthy patients at steady state with minimal sweat losses, sodium excreted in urine is roughly the same as dietary intake. Sweat sodium concentration is increased in children with cystic fibrosis, aldosterone deficiency, or pseudohypoaldosteronism.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Approximately 98% of sodium chloride is absorbed in the small intestine. The presence of glucose enhances sodium absorption, providing rationale for including glucose and sodium in oral rehydration solutions.


-Special Populations
Pediatrics
Neonates
Neonates, particularly premature neonates, have rapidly changing fluid and sodium homeostasis. During the first week of life of premature neonates, urinary sodium excretion and fractional sodium excretion are high and inversely proportional to gestational age. As gestational age and post-natal age increase, renal sodium conservation improves. Many factors, such as renal immaturity, changing urine output (e.g., diuresis around day of life 2 to 3), and the administration of IV fluids, affect sodium balance.