What is the recommended route of administration for arginine in the Neonatal Intensive Care Unit (NICU)?

Recommended Route of Administration for Arginine in the NICU

Enteral administration of arginine is the preferred route when feeds are tolerated in neonates in the NICU, while intravenous administration should be reserved for situations where enteral feeding is contraindicated.

Route Selection Algorithm

Enteral Administration (First Choice)

• Enteral administration is preferred when feeds are tolerated in neonates with conditions such as NEC 1
• Enteral arginine has been associated with improved immune function in some patient groups 2
• Consider enteral arginine supplementation when reintroducing feeds after NEC to help prevent recurrence 3

Intravenous Administration (When Enteral Route Not Possible)

• Use intravenous route only when enteral feeding is contraindicated or not tolerated 4
• For pediatric patients, the recommended IV dose is 0.5 g/kg arginine hydrochloride administered over 30 minutes 4
• For patients weighing ≤59 kg, withdraw a weight-based dose from a sealed bottle and place in a separate container for intravenous infusion 4
• For patients weighing ≥60 kg, the recommended dose is 30 g arginine hydrochloride 4

Evidence Supporting Enteral Administration

• ESPGHAN/ESPEN/ESPR/CSPEN guidelines conditionally recommend arginine supplementation for prevention of NEC in preterm infants (Level of Evidence: 1-, Recommendation Grade B) 1
• Arginine is the substrate for nitric oxide production, which is important for glucose homeostasis and vascular perfusion in neonates 1
• Low plasma arginine levels are observed in preterm neonates and may predispose them to NEC 1, 5
• Arginine deficiency is related to immune suppression in newborn models of bacterial challenge 1

Important Clinical Considerations

• Ensure adequate non-protein caloric intake (minimum 30-40 kcal per 1g amino acids) to guarantee amino acid utilization in neonates receiving arginine supplementation 1, 3
• During active NEC, bowel rest is recommended with discontinuation of enteral feeds as part of comprehensive management 1, 3
• When reintroducing feeds after NEC, consider arginine supplementation to help prevent recurrence 3
• Arginine deficiency may contribute to hyperammonemia and cardiovascular, pulmonary, neurological, and intestinal dysfunction in preterm infants 5

Caveats and Potential Pitfalls

• Arginine supplementation could potentially lead to unwanted vasodilation and hypotension in septic patients 6
• Studies in septic patients have shown variable effects on mortality with some suggesting possible harm 6
• Current evidence does not strongly support intravenous or enteral supplementation of arginine as a single substance in critically ill patients 6
• Ensure proper handling of IV arginine: parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration 4

While there are theoretical benefits to arginine supplementation in neonates, the evidence supporting routine supplementation remains limited. The enteral route should be preferred whenever possible, with intravenous administration reserved for situations where enteral feeding is not feasible.