Continuing Education Activity

Fluid therapy is a critical component of the clinical management of patients. It consists of colloid therapy as well as crystalloid therapy. The most commonly used crystalloid worldwide is normal saline which is used in the management and treatment of dehydration (e.g., hypovolemia, shock), metabolic alkalosis in the presence of fluid loss, and mild sodium depletion. This activity describes the indications, action, and contraindications for normal saline as a valuable agent in the use of fluid and electrolyte resuscitation. This activity also highlights the mechanism of action, adverse event profile, and other key factors (e.g., administration, monitoring, relevant interactions) pertinent for members of the interprofessional team in the management of critically ill patients.

Objectives:

• Identify the indications for the various concentrations of normal saline.
• Describe the contraindications to normal saline.
• Review appropriate monitoring parameters for normal saline.
• Outline interprofessional team strategies for improving outcomes and decreasing adverse effects of normal saline when it is used in critically ill patients.

Indications

Normal saline is a cornerstone of intravenous solutions commonly used in the clinical setting. It is a crystalloid fluid administered via an intravenous solution. Its indications include both adult and pediatric populations as sources of hydration and electrolyte disturbances. It can come in various concentrations; the two specifically addressed are 0.9% and 0.45%. 

The following are primary indications for the use of normal saline infusion that have been approved by the FDA: 

• Extracellular fluid replacement (e.g., dehydration, hypovolemia, hemorrhage, sepsis)
• Treatment of metabolic alkalosis in the presence of fluid loss
• Mild sodium depletion

Additionally, it has a use as a priming solution for various procedures (e.g., hemodialysis procedures) and to initiate and terminate blood transfusions. Indications for sodium chloride infusions also include pharmaceutic aids and diluents for the infusion of compatible drug additives.[1]

0.9% Sodium Chloride (Normal Saline)

An isotonic concentration of sodium chloride is best suited for the parenteral replacement of chloride losses that exceed or equal the sodium loss. Within each 100 mL of 0.9% sodium chloride Injection USP, there is 15.4 mEq of sodium ions and 15.4 mEq of chloride ions. Additionally, the osmolarity is 308 mOsmol/liter, and it has a pH range of 4.5 to 7.[1]

0.45% Sodium Chloride

A hypotonic concentration of sodium chloride. Hypotonic concentrations of sodium chloride (0.45%) are best for parenteral maintenance fluids rather than aggressive intravascular volume repletion. Within each 100 mL of 0.45% sodium chloride Injection USP, there is 7.7 mEq of sodium ions and 7.7 mEq of chloride ions. The osmolarity is 154 mOsmol/liter and a pH range similar to the 0.9% concentration.[1][2]

Mechanism of Action

Normal saline is a crystalloid fluid. By definition, it is an aqueous solution of electrolytes and other hydrophilic molecules.[1] The main indication for the use of crystalloid fluids in humans is due to their isotonic nature when compared to serum plasma. In comparison to other types of fluids (e.g., hypertonic, hypotonic), there is less of an osmotic effect.[2] Normal saline contains electrolytes (sodium and chloride ions) which dissociate in solution.

Sodium ions are the main electrolytes of extracellular fluid, integral in the distribution of fluids and other electrolytes. Another important ion is chloride, which serves as a buffering agent within the lungs and tissues. Here 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.

Additionally, water plays an equally important role. Water is a necessary ingredient of the body and comprises more than two-thirds of total body weight. Similarly, the balance of water is primarily under the control of the lungs and kidneys.  The distribution of water depends mainly on the concentration of these electrolytes within various compartments. Within these compartments, sodium plays a significant role in sustaining homeostatic concentrations and the distribution of water. Normal saline functions to expand intravascular volume without disturbing ion concentration or causing large fluid shifts between intracellular, intravascular, and interstitial spaces.[2]

Administration

Normal saline solution can be administered only via intravenous access.[2] When deciding dosage, the provider must take into account various patient factors (e.g., weight, age, clinical presentation, laboratory findings). Therefore, monitoring should focus on laboratory results and clinical evaluation (see ‘Monitoring’ section). Naturally, there are two methods of administration for normal saline:

1) Fluid bolus

• This route is normally used in the acute care setting when a rapid infusion of fluids is necessary (e.g., hypovolemia). Delivery of fluid should be administered through large-bore peripheral lines or via central-line access.[3]

2) Maintenance

• The calculation of daily fluid requirements is achievable in various ways. Common practices utilize the formulas created by Drs. Holliday and Segar which indicate that one can use the "100-50-25" or "4-2-1" rules.[4]

Examples:

For a 50 kg patient

First 10 kg weight = 1000 mL (100 mL/kg x 10)

Second 10 kg weight = 500 mL (50 mL/kg x 10)

Remaining 30 kg weight = 750 mL (25 mL/kg x 30) 

Total = 2250 mL/day or 94 mL/hr 

First 10 kg weight = 4 mL/kg/hr x 10 = 40 mL/hr

Second 10 kg weight = 2 mL/kg/hr x 10 = 20 mL/hr

Remaining 30 kg weight = 1 mL/kg/hr x 30 = 30 mL/hr 

Total = 90 mL/hr

Adverse Effects

The use of normal saline can contribute to iatrogenic fluid overload. This complication is particularly concerning in patients with impaired kidney function (acute kidney injury, chronic kidney disease, etc.), and these patients should, therefore, receive treatment with judicious use of intravenous fluids.[2] 

Patients with congestive heart failure are at an increased risk for detrimental effects of normal saline administration. In these patients, fluid overload is a considerable concern; this can lead to life-threatening pulmonary edema and the worsening of diastolic or systolic heart failure, leading to end-organ damage or even death.[2] It is vital for the clinician to monitor these patients carefully and to administer the minimum required volume to maintain homeostasis.

Adverse effects of normal saline may occur secondary to solution or technique of administration. These effects include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia. Additionally, if infusing normal saline in large quantities, chloride ions will be vastly increased within the blood. This influx of hyperchlorhydria causes an intracellular shift of bicarbonate ions to allow for equilibria. Overall, this decreases the number of bicarbonate ions available for buffering.[5] Due to the net acidosis, this physiological change will also cause an increase in serum potassium levels due to the transcellular shift of potassium from within the cell into the extracellular space.

While the overuse of 0.45% sodium chloride can cause hyponatremia and cerebral edema, this is due to 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 then undergo a clinical evaluation and the proper therapeutic countermeasures engaged. All while, the remainder of the fluid should be saved for examination if contamination is suspected.

Contraindications

Contraindications for the use of normal saline are evaluated clinically from patient to patient. If the implementation of normal saline results in dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema, then its use is strongly discouraged.[1]

Monitoring

When monitoring the use of normal saline, there must be periodic assessments of the patient’s clinical and laboratory findings. Specifically, one must observe any changes in electrolyte concentrations, volume status, and acid-base disturbances. Significant deviations from normal concentrations may require tailoring of the electrolyte pattern in these or alternative solutions.

Patients require evaluation for signs and symptoms of dehydration and fluid overload. Patients with elevated lactate and creatinine concentration are signs that they may not be receiving an adequate amount of volume. Also, the patient's volume status is assessable by monitoring urine output. Ideally, a urine output target of 0.5 mL/kg/hr indicates adequate hydration but may not be useful to determine volume status in patients with renal impairment.[1] In such a case, providers must utilize other objective findings to evaluate fluid status (e.g., orthostatic, physical examination). 

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 can undergo an evaluation with a comprehensive physical exam. Clinicians should investigate for pulmonary edema (e.g., new or worsening crackles on lung exam), as well as any new or worsening peripheral edema in the extremities. 

Additionally, the infusion of more than one liter of isotonic (0.9%) sodium chloride per day may supply more sodium and chloride than physiological levels, which can lead to hypernatremia, as well as hyperchloremic metabolic acidosis. Therefore, patients receiving large volumes of normal saline require monitoring for electrolyte imbalances. 

To minimize the risk of possible contaminations, the final solution should be inspected for ambiguity or precipitation immediately after mixing, before administration, and periodically during administration.

Enhancing Healthcare Team Outcomes

The implementation of normal saline is standard during resuscitation, and administration can be 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, the clinician and nursing staff must perform monitoring and reassessment of the patient and coordinate the reporting of abnormal findings. The following are objective findings that the provider and nursing staff must review:

• Ordering basic metabolic laboratory values, specifically identifying any elevations in electrolytes (e.g., sodium, chloride, bicarbonate)
• Urinary output (keep output over 0.5 mL/kg/hr)
• Physical examination findings that may indicate fluid status (e.g., peripheral edema, lung crackles, dry or moist oral mucosa)
• Patient composition (e.g., body weight, mass)[6]
• 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 on when to implement this IV solution and when there is a potential for untoward side effects from over-hydration. Due to normal saline's well-known side effects, there have been concerns regarding its use in critically ill patients. Thus nursing reporting to the clinical team unexpected findings is paramount. Hyperchloremia was significantly associated with increased mortality.[7][8] Pharmacists should have input on the implementation of IV fluids, make suggestions to the ordering physician based on the clinical situation, and provide counsel to nursing regarding dosing and administration. Therefore, the use of normal saline in critically ill patients is being re-investigated. There have been multiple studies comparing the use of other balanced crystalloid fluids that have shown promising results in decreasing mortality and complication rates.[9] In particular, the SMART study in 2018 showed a reduction in death incidence and protection of renal complications in critically ill patients with the use of balanced crystalloids over normal saline.[10] Although additional prospective studies are still needed. One fact is clear; normal saline should be prescribed, just like all other medications, taking into account individual patient factors, disease processes, and other treatments.[11]

Despite its ubiquity in clinical scenarios, normal saline requires an interprofessional approach to dosing and administration among physicians, specialists, nurses, and pharmacists, all working collaboratively as an interprofessional team to optimize patient outcomes. [Level 5]

Review Questions

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References

1.

Chang R, Holcomb JB. Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock. Shock. 2016 Jul;46(1):17-26. [PMC free article: PMC4905777] [PubMed: 26844975]

2.

Epstein EM, Waseem M. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 3, 2023. Crystalloid Fluids. [PubMed: 30726011]

3.

Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259-65. [PubMed: 20975548]

4.

Holliday MA, Ray PE, Friedman AL. Fluid therapy for children: facts, fashions and questions. Arch Dis Child. 2007 Jun;92(6):546-50. [PMC free article: PMC2066164] [PubMed: 17175577]

5.

Eisenhut M. Causes and effects of hyperchloremic acidosis. Crit Care. 2006;10(3):413; author reply 413. [PMC free article: PMC1550953] [PubMed: 16834765]

6.

Matějovič M, Horák J, Harazim M, Karvuni T, Raděj J, Novák I. Intravenous fluid therapy in acutely ill patients for non-intensivists. Vnitr Lek. 2019 Spring;65(3):187-192. [PubMed: 31088095]

7.

Neyra JA, Canepa-Escaro F, Li X, Manllo J, Adams-Huet B, Yee J, Yessayan L., Acute Kidney Injury in Critical Illness Study Group. Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med. 2015 Sep;43(9):1938-44. [PMC free article: PMC4537691] [PubMed: 26154934]

8.

Kellum JA, Song M, Almasri E. Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest. 2006 Oct;130(4):962-7. [PubMed: 17035425]

9.

Bhaskaran K, Arumugam G, Vinay Kumar PV. A prospective, randomized, comparison study on effect of perioperative use of chloride liberal intravenous fluids versus chloride restricted intravenous fluids on postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass grafting surgeries. Ann Card Anaesth. 2018 Oct-Dec;21(4):413-418. [PMC free article: PMC6206797] [PubMed: 30333337]

10.

Semler MW, Self WH, Wang L, Byrne DW, Wanderer JP, Ehrenfeld JM, Stollings JL, Kumar AB, Hernandez A, Guillamondegui OD, May AK, Siew ED, Shaw AD, Bernard GR, Rice TW., Isotonic Solutions and Major Adverse Renal Events Trial (SMART) Investigators. Pragmatic Critical Care Research Group. Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017 Mar 16;18(1):129. [PMC free article: PMC5356286] [PubMed: 28302179]

11.

Raghunathan K, Shaw AD, Bagshaw SM. Fluids are drugs: type, dose and toxicity. Curr Opin Crit Care. 2013 Aug;19(4):290-8. [PubMed: 23817025]

Disclosure: Paul Tonog declares no relevant financial relationships with ineligible companies.

Disclosure: Anand Lakhkar declares no relevant financial relationships with ineligible companies.