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Normal Saline
Indications
Normal saline is a cornerstone of intravenous (IV) solutions commonly used in the clinical setting. This crystalloid fluid is administered through an IV route. Normal saline is used to treat both adult and pediatric populations as a source of hydration and electrolyte disturbances. Normal saline is available in various concentrations, with the 2 most commonly used being 0.9% and 0.45%.
The following are primary indications for using normal saline infusion that have been approved by the Food and Drug Administration:
- Extracellular fluid replacement, such as dehydration, hypovolemia, hemorrhage, and sepsis
- Treatment of metabolic alkalosis in the presence of fluid loss
- Mild sodium depletion
In addition, normal saline is used as a priming solution for various procedures, such as hemodialysis, and for initiating and terminating blood transfusions. Indications for sodium chloride infusions also include pharmaceutical aids and diluents for infusing compatible drug additives.[1]
0.9% Sodium Chloride (Normal Saline)
An isotonic concentration of sodium chloride is ideal for the parenteral replacement of chloride losses that exceed or equal the sodium loss. Each 100 mL of 0.9% sodium chloride injection USP contains 15.4 mEq of sodium ions and 15.4 mEq of chloride ions, with an osmolarity of 308 mOsmol/L and a pH ranging from 4.5 to 7.[1]
According to the Endocrine Society guidelines, normal saline, steroids, and other measures are used for acute adrenal insufficiency.[2] The Infectious Diseases Society of America recommends isotonic fluids, such as normal saline, for infectious diarrhea when patients present with severe dehydration, shock, or failure of oral rehydration solution treatment.[3]
Volume loading with normal saline and N-acetylcysteine prevents the occurrence of contrast-induced nephropathy.[4]
A systematic review shows that normal saline is as effective as heparin in preventing central venous catheter complications such as occlusion, catheter-related infections, and thrombosis.[5] However, additional research is required.
Saline nasal irrigation is a safe and effective method for relieving nasal symptoms in children with acute upper respiratory infections, although its impact on respiratory symptoms is limited. In addition, it may reduce the need for other medications.[6]
0.45% Sodium Chloride
0.45% sodium chloride is a hypotonic solution. This concentration is ideal for parenteral maintenance fluids rather than aggressive intravascular volume repletion. Each 100 mL of 0.45% sodium chloride Injection USP contains 7.7 mEq of sodium ions and 7.7 mEq of chloride ions, with an osmolarity of 154 mOsmol/L and a pH range similar to that of the 0.9% sodium chloride.[1][7]
Half-normal saline used as an irrigation fluid during burr hole craniostomy for chronic subdural hematoma significantly decreased postoperative effusion and hospital stay. The efficacy and safety of half-normal saline were comparable to normal saline, with no increase in recurrence or complications.[8]
Radiofrequency ablation using half-normal saline irrigation has shown acceptable complication rates and acute procedural success while significantly reducing the total volume of saline administered compared to normal saline irrigation.[9] According to the Heart Rhythm Society, half-normal saline can be used but can result in steam pops.[10]
Hypertonic saline can be used during tumor craniotomy, offering superior brain relaxation, enhanced diuretic effects, and more stable blood flow compared to mannitol. However, it may lead to an increase in plasma sodium levels, requiring careful monitoring.[11][12]
Mechanism of Action
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Mechanism of Action
Normal saline is a crystalloid fluid. By definition, it is an aqueous solution of electrolytes and other hydrophilic molecules.[1] The primary reason for using crystalloid fluids in humans is their isotonic nature, which makes them comparable to serum plasma. Compared to other types of fluids, such as hypertonic and hypotonic, normal saline does not cause a strong osmotic effect.[7] Normal saline contains electrolytes, such as sodium and chloride ions, which dissociate in solution.
Sodium ions are the main electrolytes of extracellular fluid and are integral in the distribution of fluids and other electrolytes. Another essential ion is chloride, which serves as a buffering agent within the lungs and tissues. Chloride helps to facilitate the binding between oxygen and carbon dioxide to hemoglobin. These ions are primarily under the regulation of the kidneys, which control homeostasis by absorption or excretion within the tubules.
In addition, water plays an equally vital role, constituting more than two-thirds of the total body weight. Similarly, the balance of water is primarily controlled by the lungs and kidneys. Water distribution depends mainly on the concentration of these electrolytes within various compartments. Sodium plays a significant role in sustaining homeostatic concentrations and water distribution within these compartments. Normal saline functions to expand intravascular volume without disturbing ion concentration or causing large fluid shifts between intracellular, intravascular, and interstitial spaces.[7]
Administration
Available Dosage Forms and Strengths
Normal saline solution can be administered through IV, intraosseous, or nasal routes. Hypertonic saline can be administered through the central line. However, the peripheral line can also be used.[7][13][14][15] Normal saline is available at 0.9% concentration, whereas nebulization is available in different strengths, including 3.5% and 7%.[16][17] Intraosseous administration is primarily used in resuscitation.[18]
Adult dosage: When determining the appropriate dosage, healthcare providers must consider various patient factors such as weight, age, clinical presentation, and laboratory findings. Therefore, monitoring should focus on laboratory results and clinical evaluation (please refer to the Monitoring section for more information). Normal saline is typically administered in 2 ways:
- Fluid bolus: This route is normally used in the acute care setting when a rapid infusion of fluids is necessary, such as in cases of hypovolemia. Fluid delivery should be administered through large-bore peripheral lines or central-line access.[19]
- Maintenance fluid: The calculation of daily fluid requirements is achievable in various ways. Common practices use the formulas developed by Drs Holliday and Segar, which suggest using the 100-50-25 or 4-2-1 rules.[20]
For a 50 kg patient, the following maintenance fluid calculations apply:
100-50-25 rule
First 10 kg weight = 1000 mL (100 mL/kg × 10)
Second 10 kg weight = 500 mL (50 mL/kg × 10)
Remaining 30 kg weight = 750 mL (25 mL/kg × 30)
Total = 2250 mL/d or 94 mL/h
4-2-1 rule
First 10 kg weight = 4 mL/kg/h × 10 = 40 mL/h
Second 10 kg weight = 2 mL/kg/h × 10 = 20 mL/h
Remaining 30 kg weight = 1 mL/kg/h × 30 = 30 mL/h
Total = 90 mL/h [21]
Specific Patient Populations
Hepatic impairment: Normal saline should be used with extreme caution in patients with cirrhosis due to the risk of exacerbating ascites and edema.[22]
Renal impairment: Caution is advised due to the increased risk of volume overload
Pregnancy considerations: Normal saline can be used during pregnancy as needed. Oxytocin diluted in normal saline or Ringer lactate is used for labor induction.[23]
Breastfeeding considerations: In infants and children, nasal saline is useful for controlling rhinitis symptoms but does not alleviate respiratory symptoms.[6] Normal saline can be used during lactation based on clinical needs.
Pediatric patients: According to the American Academy of Pediatrics, normal saline at 10 to 20 mL/kg may be used for volume expansion in neonates during resuscitation when hypovolemia is presumed.[24] Pediatric patients receiving IV fluids are at risk for fluid accumulation, volume overload, and hyperchloremic metabolic acidosis.[25]
Older patients: Normal saline should be cautiously administered to geriatric patients due to impaired cardiac or renal function.
Adverse Effects
The use of normal saline can contribute to iatrogenic fluid overload. This complication is particularly concerning in patients with impaired kidney function, such as acute kidney injury and chronic kidney disease. In these populations, IV fluids should be administered judiciously.[7]
Patients with congestive heart failure are at an increased risk of the detrimental effects of normal saline administration. In these patients, fluid overload poses a significant risk, leading to life-threatening pulmonary edema, the worsening of diastolic or systolic heart failure, and end-organ damage or even death.[7] Careful monitoring and administering the minimum effective volume are essential to maintain hemodynamic stability and avoid complications.
Normal saline has a relatively low pH of around 5.5. When large volumes of normal saline are administered, it can lead to non-anion gap hyperchloremic metabolic acidosis and potential kidney injury. These effects are particularly important in the context of acute pancreatitis, where a low pH can contribute to the early activation of trypsinogen—a key factor in disease progression. In addition, high-volume normal saline infusions have been linked to abdominal discomfort. Therefore, the American College of Gastroenterology recommends using lactated Ringer solution instead of normal saline for fluid resuscitation in cases of acute pancreatitis.[26]
Adverse effects of normal saline may occur secondary to the solution or technique of administration. Potential complications include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia. In addition, if infusing normal saline in large quantities, chloride ions in the blood may rise significantly. This influx of hyperchloremia causes an intracellular shift of bicarbonate ions to allow for equilibria. Overall, this decreases the number of bicarbonate ions available for buffering.[27] As a result of this metabolic acidosis, serum potassium levels may increase due to a transcellular shift of potassium from the intracellular to the extracellular space.
Although overuse of 0.45% sodium chloride can cause hyponatremia and cerebral edema, this results from its hypotonic nature, creating a migration of water molecules into areas of higher sodium concentration. Therefore, if an adverse effect does occur, discontinuation of the infusion is strongly suggested. The patient should undergo a thorough clinical evaluation, and appropriate therapeutic interventions should be initiated. If contamination is suspected, the remaining fluid should be preserved for analysis.
Intravenous Incompatibilities/Interactions
Parentral diazepam can precipitate in a standard saline solution.[28] Amphotericin B is incompatible with sodium chloride; therefore, it should not be infused with normal saline.[29]
Contraindications
Contraindications for using normal saline are assessed on a case-by-case basis. If normal saline causes dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema, its use is strongly discouraged.[1]
Warning and Precautions
As discussed earlier, infusion of normal saline can lead to normal anion gap acidosis. Other causes of normal anion gap acidosis include diarrhea, ileostomy, and renal tubular acidosis, making differential diagnosis essential.[30]
Air embolism represents a rare but potentially fatal condition that can develop when patients receive pressurized IV fluids. The situation demonstrates the need for proper precautions when performing basic procedures such as removing air from IV containers and relieving pressure after patient repositioning. The patient requires immediate left-sided Trendelenburg positioning with the left side down as part of the emergency response.[31]
Monitoring
When monitoring the use of normal saline, periodic assessments of the patient's clinical and laboratory findings are essential. Specifically, any changes in electrolyte concentrations, volume status, and acid-base disturbances should be closely observed. Significant deviations from normal concentrations may necessitate adjusting the electrolyte pattern in these or alternative solutions.
Patients should be assessed for signs and symptoms of dehydration and fluid overload. Patients with elevated lactate and creatinine concentrations are signs that they may not be receiving an adequate amount of volume. In addition, the patient's volume status is assessable by monitoring urine output. Ideally, a urine output target of 0.5 mL/kg/h indicates adequate hydration but may not be useful to determine volume status in patients with renal impairment.[1] In such cases, healthcare providers must utilize other objective findings, such as orthostatic measurements and physical examination, to evaluate fluid status.
Patients at high risk of developing fluid overload should receive frequent re-evaluation, especially patients with known cardiopulmonary diseases. Signs and symptoms of fluid overload should be assessed through a comprehensive physical exam. Clinicians should assess for pulmonary edema, such as new or worsening crackles on lung exam, and monitor for any new or worsening peripheral edema in the extremities.
In addition, the infusion of more than 1 L of isotonic (0.9%) sodium chloride per day may supply more sodium and chloride than physiological levels, potentially leading to hypernatremia and hyperchloremic metabolic acidosis. Therefore, patients receiving large volumes of normal saline require monitoring for electrolyte imbalances. To minimize the risk of possible contamination, the final solution should be inspected for ambiguity or precipitation immediately after mixing, before administration, and periodically during administration.[32]
An inferior vena cava ultrasound examination can decrease the likelihood of overt intravascular hypervolemia or hypovolemia.[33] In addition, monitoring vital signs, including heart rate and blood pressure, is essential. Critically ill patients may require arterial lines for accurate blood pressure measurement to guide fluid and vasopressor therapy.[34]
Toxicity
Signs and Symptoms of Overdose
The primary toxicities associated with overdose are hyperchloremic metabolic acidosis and volume overload.[35] Patients may present with pulmonary edema.[36] Sodium disorders can lead to central nervous system dysfunction and lethargy. Clinicians should obtain a chest x-ray, two-dimensional echocardiogram, 12-lead electrocardiogram, complete blood count to assess changes in hematocrit, and a comprehensive metabolic panel. Arterial blood gas analysis should be obtained.[30]
Management of Overdose
The saline drip should be discontinued. Bicarbonate or sodium citrate can be used to treat metabolic acidosis in stable patients without severe volume contraction. However, due to the sodium content, it should only be used under expert supervision. Volume overload should be treated if present.[37][36]
Enhancing Healthcare Team Outcomes
Normal saline is the standard administration during resuscitation and may be delivered at various concentrations. In most clinical settings, normal saline is the choice of fluid for many indications for fluid resuscitation, maintenance, or as a solvent for medication delivery. Without proper management, the consequences of adverse effects increase. Therefore, clinicians and nursing staff must monitor and reassess the patient and coordinate the reporting of abnormal findings. Key objective parameters that should be evaluated include the following:
- Ordering basic metabolic laboratory tests, specifically identifying any elevations in electrolytes, such as sodium, chloride, and bicarbonate
- Urinary output (over 0.5 mL/kg/h)
- Physical examination findings that may indicate fluid status, such as peripheral edema, lung crackles, dry or moist oral mucosa
- Patient composition, such as body weight and mass [38]
- Continuous assessment of the patient and their requirements for normal saline
The management of normal saline requires evaluation alongside the patient's clinical status. Clinicians, including nurses, must recognize the indications for its use and the potential for adverse effects, particularly from overhydration. Due to normal saline's well-known adverse effects, there have been concerns regarding its use in critically ill patients. Thus, nursing staff should promptly report any unexpected findings to the clinical team. Hyperchloremia has been significantly associated with increased mortality.[39][40] Pharmacists also play a critical role in the safe administration of IV fluids. They should collaborate with the ordering physician, offering recommendations based on the clinical scenario, and advise nursing staff on appropriate dosing and administration techniques. Therefore, using normal saline in critically ill patients is being re-evaluated. Several studies have compared using balanced crystalloid fluids, showing promising results in reducing mortality and complication rates.[41] In particular, the 2018 SMART study showed a significant reduction in mortality and improved renal outcomes in critically ill patients treated with balanced crystalloids compared to normal saline.[42] Although further prospective studies are needed, one principle remains clear—normal saline should be prescribed, just like all other medications, considering individual patient factors, disease processes, and other treatments.[43]
Despite its widespread use in clinical practice, administering and dosing normal saline require a coordinated interprofessional approach involving physicians, specialists, nurses, and pharmacists. Collaborative teamwork is essential to ensure safe and effective use and to optimize patient outcomes.
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Level 3 (low-level) evidence