Considerations for Using Hypertonic Saline and Medications Containing Benzyl Alcohol in Neonates

Background:

A healthcare professional (HCW 1) sought advice from an expert network regarding the use of 3% sodium chloride (hypertonic saline) and medications containing benzyl alcohol in neonates.

Case Details:

HCW 1 inquired about the safety and appropriateness of administering 3% sodium chloride through a peripheral line in neonates and the use of medications containing benzyl alcohol, such as a specific amiodarone formulation, in this patient population.

Expert Opinions:

HCW 2 provided the following insights:

• 3% sodium chloride is a hypertonic solution with an osmolarity of 1,026 mOsm/L, making it contraindicated for peripheral administration in all ages unless in emergency cases, such as severe hyponatremia with neurological symptoms.
• The acceptable osmolarity for peripheral line administration should not exceed twice the serum osmolality (290-310 mOsm/kg).
• Medications containing solvents like propylene glycol or preservatives like benzyl alcohol are contraindicated in neonates due to the risk of complications such as seizures, sudden collapse, cardiac arrhythmia, blood hemolysis, and renal and hepatic failures.

HCW 3 suggested an alternative to the specific amiodarone formulation:

• The mentioned amiodarone formulation contains benzyl alcohol and should be avoided in neonates.
• An alternative benzyl alcohol-free formulation from a different manufacturer is available and can be considered.

HCW 4 provided additional information:

• Most hospital protocols require hypertonic saline to be administered via a central line or large bore catheter, with peripheral line use allowed only in emergencies.
• For children and neonates, it may be necessary to administer hypertonic saline through a Y-site with other fluids to reduce the high osmolarity.
• Recent publications suggest that peripheral administration of 3% sodium chloride in adults may be safer than previously thought, provided the infusion rate is lower than 50 mL/hr.
• The FDA considers benzyl alcohol toxic to neonates, as it can cause “gasping syndrome” and has been associated with deaths when it accumulates in the body.

Additional Information:

Benzyl alcohol toxicity in neonates:

• Benzyl alcohol has been associated with the “gasping syndrome” in neonates, characterized by metabolic acidosis, respiratory distress, gasping respirations, convulsions, intracranial hemorrhage, hypotension, and cardiovascular collapse.
• The American Academy of Pediatrics recommends that benzyl alcohol-containing products should be avoided whenever possible in infants.

Peripheral administration of 3% sodium chloride:

• A study by Jones et al. (2017) found that among 213 neurocritical care patients who received continuous peripheral infusions of 3% sodium chloride, only 5.7% experienced infusion-related reactions requiring a change to a central catheter.
• The study suggests that current recommendations for central catheter use for continuous 3% sodium chloride infusions should be reevaluated, as peripheral administration may be safer than previously thought, especially at rates below 50 mL/hr.

Electrolyte abnormalities associated with 3% sodium chloride infusions:

• Hyperchloremia (49.3%) and hypokalemia (46.9%) were the most common electrolyte abnormalities observed in patients receiving continuous 3% sodium chloride infusions, according to the study by Jones et al. (2017).
• The clinical importance of these electrolyte abnormalities remains unclear and requires further research.

Recent Research Insights

A study published in the American Journal of Critical Care in 2017 investigated the safety of continuous peripheral infusion of 3% sodium chloride solution in neurocritical care patients. The findings suggest that for adults, peripheral administration may be safer than previously thought, especially at infusion rates below 50 mL/hr. However, this study focused on adult patients and may not be directly applicable to neonates.

Conclusion:

When treating neonates, healthcare professionals should exercise caution when considering the use of 3% sodium chloride and medications containing benzyl alcohol.

Peripheral administration of hypertonic saline should be reserved for emergency cases, and benzyl alcohol-containing medications should be avoided due to the potential for serious adverse effects.

When peripheral administration is necessary for neonates, consider using a Y-site with other fluids to reduce osmolarity and closely monitor the infusion site for signs of extravasation or phlebitis.

Alternative formulations or administration techniques may be necessary to ensure the safety and well-being of neonatal patients.

Recent studies suggest that peripheral administration of 3% sodium chloride may be safer than previously thought in adults, but more research is needed to confirm these findings and assess the clinical significance of associated electrolyte abnormalities.