Parenteral nutrition (PN) is a high alert medication that is key to improving premature infants’ health outcomes.1 In fact, 43% of inpatients receiving PN are children and infants, as this medication plays an important role in supporting growth and development in preterm newborns who face challenges due to premature gastrointestinal tracts, a high risk of developing nutrition deficits, and intolerance of enteral feedings.2 Despite the known benefits of PN in this patient population, an increasing body of evidence suggests that various components of PN, including vitamins and injectable lipid emulsions (ILEs), are susceptible to oxidation when exposed to light (photooxidation).3 This subject continues to be of interest to the nutrition community and recently was investigated by the American Society for Parenteral and Enteral Nutrition (ASPEN). ASPEN’s latest position paper provides recommendations for photoprotection of PN in premature infants that can be applied in the pharmacy setting.4

Dangers of Photooxidation

PN exposure to light sources such as sunlight, ambient light, and even phototherapy can lead to the production of oxidants such as hydrogen peroxide, lipoperoxides, and ascorbylperoxide.5-7 Preterm infants are considered more susceptible to oxidative stress than adults and children. Morbidities associated with prematurity and oxidative stress include bronchopulmonary dysplasia (BPD), retinopathy of prematurity, necrotizing enterocolitis (NEC), and intestinal failure-associated liver disease (IFALD).4

Light protection is one method for protecting against photooxidation. A 2017 meta-analysis evaluated the effect of light exposed versus light protected PN on neonatal mortality.8 Four clinical trials were included in the meta-analysis for a total of 800 premature infants. Mortality in the light protected group was half that of the light exposed group in the meta-analysis. A significant reduction in mortality was not seen in the individual studies.8 Associated limitations include:

• None of the studies were blinded
• The Laborie et al trial contributed 587 infants to the total number9

Photoprotection Challenges

The ideal scenario would be complete photoprotection of PN. However, there are a few challenges to achieving this goal. Clear tubing is standard among automated compounding device manufacturers in the United States, and often individual PN components are packaged in clear containers.

Despite these challenges, there are products that can help aid in photoprotection when compounding and administering PN mixtures. Materials currently available in the US include amber overwrap/cover bags, amber sleeves for administration tubing, amber tubing (this option is available in larger diameters, but not for microbore tubing for use in infants).4

ASPEN Recommendations

ASPEN published a position paper in 2021 for photoprotection of PN for premature infants. The paper advocates for as close to complete photoprotection as possible, and provides the following recommendations toward meeting this goal:4

1. ASPEN recommends photoprotection of PN admixtures and injectable lipid emulsions (ILEs) for infants. Insufficient literature exists to recommend photoprotection of PN and ILE administered to older children or adults. Sufficient evidence suggests that PN components utilized in children and adults are susceptible to photooxidation.
2. Health care organizations should convene key stakeholders to define which steps in photoprotection can be achieved and implement such strategies.
3. Outsourcing sterile compounding facilities should review processes to assist in reducing light exposure.
4. Research and development of cost-efficient materials will be necessary for complete photoprotection of PN admixtures and ILEs.
5. ASPEN and the authors understand that implementation of complete photoprotection may not currently be feasible. Recommendations serve to represent the goal to which to strive as well as to highlight the importance of product availability.

Photoprotection Case Study

Following the ASPEN position paper, Mississippi Baptist Medical Center (MBMC), a 500-bed facility, began by reaching out to other institutions to learn about their practices for photoprotection of neonatal parenteral nutrition.4 Research indicated that the institutions photoprotecting their PN bags were placing them in an amber bag after compounding, but prior to delivery. However, due to product availability, photoprotection of IV tubing and compounding syringes proved to be a challenge. Once we felt we had a grasp on products available to our institution and feasibility of protection throughout the compounding, transport, delivery, and administration processes, we proceeded with a plan for implementation. This included covering the PN bag and lipid syringe with an amber bag after compounding, ensuring that light protection is maintained throughout transportation and delivery, and securing an amber tubing sleeve to the IV tubing before administration.

After presenting data and discussing the photoprotection implementation plan with several neonatologists at MBMC, approval was obtained to begin the photoprotection process. Sufficient supplies of amber bags and amber tubing covers were ordered. Pharmacy and nursing staff were educated on the new process, and photoprotection was implemented. Pharmacists were instructed to place PN bags in an amber bag after compounding and place an extra label for the patient’s PN on the outside of the amber bag (ensuring that the two labels match). For all NICU orders, a second check is required by another pharmacist after the PN/lipids are compounded as an additional safeguard. This second check involves the pharmacist verifying the compounding ingredients, verifying the lipid volume, confirming there are no particulates in the PN bag, and verifying the PN bag and lipid syringe are placed in an amber bag with an additional label on the outside of the amber bag. Changes in the NICU included receiving PN bags and lipid syringes covered in bags from pharmacy, covering the IV tubing with amber tubing sleeves, and administering the PN/lipid while maintaining photoprotection throughout administration.

Summary

A growing body of literature has demonstrated that com-ponents of PN are susceptible to oxidation when exposed to light, and that premature infants are at the highest risk for harm from peroxides if PN is not photoprotected. Per ASPEN’s recommendation, health professionals should review current procedures and implement strategies to photoprotect PN to the best of their abilities in the premature population.

References

1. ISMP. High Alert Medications in Acute Care Settings. Accessed May 25, 2022. ismp.org/recommendations/high-alert-medications-acute-list.
2. National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) from the Agency for Healthcare Research and Quality (AHRQ). Accessed May 26, 2022. hcupnet.ahrq.gov.
3. Steger PJ, Mühlebach SF. J Parenter Enteral Nutr. 2000;24(1):37-41.
4. Robinson DT et al. Nutr Clin Pract. 2021;36:927–94.
5. Bronsky J et al. Clin Nutr. 2018;37(6Pt B):2366-2378.
6. Ferguson TI et al. e-SPEN Journal. 2014;9(2):e49-e53.
7. Elremaly W et al. Redox Biol. 2014;2:725-731.
8. Chessex P et al. J Parenter Enteral Nutr. 2017;41(3):378-383.
9. Laborie S et al. J Parenter Enteral Nutr. 2015;39(6):729-737.

Phil Ayers, PharmD, BCNSP, FMSHP, FASHP, is chief, clinical pharmacy services, Mississippi Baptist Medical Center (MBMC) in Jackson, Mississippi.

Laura Nerren, PharmD, BCPS, works as a clinical staff pharmacist at MBMC. She obtained her doctor of pharmacy degree in 2019 from the University of Mississippi.