What is the safety of peripheral administration of hypertonic saline (HTS) solutions containing sodium chloride 3% as intravenous (IV) boluses and continuous IV infusions, considering the potential risks of phlebitis and IV site reactions?

From the Guidelines

The committee should maintain the current policy allowing peripheral administration of 3% sodium chloride solutions, as reducing the maximum concentration to 2% could compromise patient care without providing additional safety benefits. The concerns about peripheral administration of hypertonic saline (HTS) are primarily derived from recommendations for parenteral nutrition solutions, which have not been shown to apply equally to hypertonic saline solutions containing 3% sodium chloride or greater 1. It's essential to note that 2% sodium chloride is not commercially available and would require compounding, potentially delaying treatment in emergency situations. Both 2% and 3% solutions are hyperosmolar and carry similar theoretical risks of phlebitis and IV site reactions. For treating elevated intracranial pressure and other neurologic emergencies, concentrations of 3% or higher are typically required for effective management. Some key points to consider include:

• The use of hypertonic saline solutions in critical care, particularly for raised intracranial pressure, has been reviewed in several studies 1.
• These studies suggest that hypertonic saline solutions are effective at reducing intracranial pressure, but the evidence for improved neurological outcomes or survival benefits is limited 1.
• The safety concerns associated with hypertonic saline solutions, such as osmotic demyelination syndrome, have been investigated, and the available evidence suggests that these solutions can be used safely in clinical practice 1.
• The Association of Anaesthetists of Great Britain and Ireland has provided guidelines for safe vascular access, including recommendations for peripheral cannulation and the use of hypertonic solutions 1. Overall, the available evidence supports the continued use of 3% sodium chloride solutions for peripheral administration, and reducing the maximum concentration to 2% could compromise patient care without providing additional safety benefits.

From the FDA Drug Label

WARNINGS: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration. Sodium Chloride Injection, USP, 23. 4% is hypertonic and must be diluted prior to administration. Inadvertent direct injection or absorption of concentrated sodium chloride solution may give rise to sudden hypernatremia and such complications as cardiovascular shock, central nervous system disorders, extensive hemolysis and cortical necrosis of the kidneys.

The FDA drug label does not answer the question.

From the Research

Response to Committee Member's Concerns

The committee member's concerns about the safety of peripheral administration of hypertonic saline (HTS) solutions containing sodium chloride 3% can be addressed by considering the following points:

• Concerns about peripheral administration of HTS stem from recommendations for the maximum osmolarity of parenteral nutrition solutions administered peripherally, which have not translated to equivalent safety concerns for HTS containing sodium chloride 3% or greater 2.
• Sodium chloride 2% is not commercially available and must be compounded for extemporaneous use, which could delay care in emergent situations.
• Both 2% sodium chloride and 3% sodium chloride solutions are hyperosmolar and thus associated with an equivalent theoretical risk of phlebitis and IV site reactions.
• The 2% sodium chloride concentration cannot be used for the treatment of elevated intracranial pressure (ICP); a concentration of 3% or higher is required in emergent situations, as supported by studies on the use of hypertonic saline in treating elevated ICP 3, 4.
• Requiring the use of a 22-gauge or smaller needle or catheter in an antecubital or wrist vein for peripheral administration of HTS containing sodium chloride 3% would mitigate the theoretical concerns about IV site reactions.

Key Points to Consider

• The use of hypertonic saline solutions, including 3% sodium chloride, has been studied in various clinical settings, including the treatment of elevated ICP and shock resuscitation 2, 3, 4.
• The benefits of using hypertonic saline solutions, including their ability to reduce intracranial pressure and improve outcomes in patients with traumatic brain injury, should be weighed against the potential risks of peripheral administration 2, 3, 4.
• The mechanism of action of hypertonic saline solutions, including their effects on cytokine production and immune response, may also be relevant to their use in clinical practice 5.
• The comparison of hypertonic saline solutions with other treatments, such as mannitol, may provide additional insights into their safety and efficacy 4.