Infants exposed to painful procedures experience acute physiologic responses and increased morbidity; opioids are often prescribed for these patients. However, extended opioid prescribing after surgery is associated with prolonged ventilation, total parenteral nutrition use, and hospitalization. Pain management in hospitalized infants needs to balance these two considerations to prevent long-term adverse health and developmental consequences.

A retrospective cohort study examined data on high-risk infants younger than age 1 from January 2016 through December 2022 at 47 U.S. children's hospitals participating in the Pediatric Health Information System. The study identified 132,658 high-risk infants, median gestational age, 34 weeks; 54.5% male, with a median birth weight of 1,741 grams. Researchers identified high-risk infants by ICD-10 codes that enabled them to study newborns with substantial neonatal/perinatal morbidities, who needed to undergo multiple procedures and required prolonged intubation and therefore were at risk for prolonged opioid exposure. They included infants with congenital heart disease requiring surgery (CHD), necrotizing enterocolitis (NEC), extremely-low- or very-low-birthweight (ELBW or VLBW), hypoxemic-ischemic encephalopathy (HIE), and those requiring extracorporeal membrane oxygenation (ECMO) or abdominal surgery. They excluded infants with ICD-10 codes for neonatal opioid withdrawal syndrome, in utero exposure to opioids, or malignant tumors. The records of these infants were examined to determine opioid exposure during hospitalization. Researchers determined cumulative days of opioid exposure, methadone treatment after short-acting opioid exposure during hospitalization, and cumulative days of methadone exposure.

During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median length of any opioid exposure was 5 cumulative days (range, 2 to 12 days), and the median length of methadone treatment was 19 cumulative days (range, 7 to 46 days). The methadone use observed by researchers is in part attributable to its use while tapering opioids to minimize withdrawal signs and symptoms.

When stratified by age at birth, premature infants had fewer days of opioid exposure than term infants (13% lower). Prematurity occurred in 30.3% of infants. Clinical factors associated with higher cumulative opioid days included mechanical ventilation and Intensive Care Unit stay. Cumulative opioid days were 104% higher with surgical NEC, 52% higher with medical NEC, 82% higher in those undergoing abdominal surgery, 25% higher in ELBW infants, 105% higher in those undergoing CHD-related procedures, and 177% higher in those receiving ECMO than in those without these conditions.

Significant variability was noted in opioid and methadone exposure across regions and institutions. Opioid exposure among this cohort was 74.2% in the Northeast, 78.6% in the South, 71.6% in the Midwest, and 81.2% in the West; similarly, methadone exposure among this cohort was 4.6% in the Northeast, 10.3% in the South, 6.6% in the Midwest, and 7.1% in the West. Once the researchers controlled for hospital- and patient-level characteristics, only the variation in the Northeast was significant. An estimated 16% of the variability in opioid exposure and 20% of the variability in methadone exposure can be attributed to the individual hospital.

The observed institutional-level variability in opioid and methadone prescribing in high-risk hospitalized infants underscores the need for standardized prescribing in this vulnerable population. Understanding the factors that result in these regional and institutional variations can inform best practices and encourage practitioners to carefully consider whether alternative pain management strategies may be an appropriate approach in some of these vulnerable patients.

Hadland, S. E., & Schiff, D. M. (2024). Opioids in hospitalized infants–Managing pain and sedation while avoiding overuse. JAMA Netw Open, 7(3), Article e240523. Retrieved March 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815953

Keane, O. A., et al. (2024). Institutional and regional variation in opioid prescribing for hospitalized infants in the US. JAMA Netw Open, 7(3), Article e240555. Retrieved March 2024 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815949

Released: April 2024

Nursing Drug Handbook

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The study included 105 children, median age, 5.4 years (range, 3.0 to 18.8 years) who were treated according to a Dutch ALL protocol; all had entered the maintenance phase of treatment after cessation of doxorubicin treatment. Dexamethasone (6 mg/m²/day) was administered for 5 days at the start of each 3-week cycle. Data and blood samples were collected before and after the 5-day course; BMI, fat mass, and leptin were measured, and parents completed questionnaires regarding hunger, fatigue, and sleep in the children.

Leptin and fat mass, as well as hunger, fatigue, and sleep scores, deteriorated after 5 days of high-dose dexamethasone. After 5 days, mean leptin standardized deviation score (SDS) changed from −0.09 to 1.8, fat mass from 5.1 kg to 5.6 kg, fatigue score (median score on Pediatric Quality of Life Inventory SDS) from −0.5 to −3.5. BMI remained stable, from 17.3 to 17.7. However, no significant correlations were found between the change in leptin SDS and changes in these other measures.

Because children with ALL are at increased risk for metabolic adverse events, it's important to understand the mechanisms behind these changes. These results hint that a dexamethasone-induced state of leptin resistance might play a role.

van Hulst, A. M., et al. (2024). Leptin increase during dexamethasone and its association with hunger and fat in pediatric acute lymphoblastic leukemia. J Clin Endocrinol Metab, 109(3), 631–640. Retrieved March 2024 from https://academic.oup.com/jcem/article/109/3/631/7329845

Released: April 2024

Nursing Drug Handbook

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The New Vaccine Surveillance Network (NVSN), a population-based, prospective surveillance platform for acute respiratory illnesses in infants, children, and adolescents, evaluated the effectiveness of nirsevimab among infants in their first RSV season, from October 1, 2023, through February 29, 2024. NVSN collected demographic, clinical, and immunization data through parent interviews, medical records, and state information systems. Among 1,036 eligible infants, 699 met the inclusion criteria (verified nirsevimab status, reported gestational age at birth, and a medical record review to assess for underlying medical conditions), and were designated as case patients (n = 407; 58%) or control patients (n = 292; 42%) based on a positive RSV result on PCR testing.

Administration of nirsevimab was shown to be 90% effective against RSV-associated hospitalizations in infants in their first RSV season. Ultimately, 6 case patients (1%) and 53 control patients (18%) received nirsevimab. The median time from receipt of nirsevimab to symptom onset was 45 days (range, 7 to 127 days).

This early effectiveness estimate supports the current recommendations for prevention of severe RSV disease in infants and has implications for public health practice. Adding use of nirsevimab in infants to the protocol that includes maternal RSV vaccination will reduce the risk of RSV-associated hospitalizations. The researchers note that the 90% efficacy seen in this study may be higher than expected in a real-world setting, as nirsevimab effectiveness is expected to decrease with increasing time after receipt over a full RSV season because of antibody decay. Median duration of RSV season in the United States is 189 days. Still, in clinical trials it did remain effective through 150 days after receipt.

Moline, H. L., et al. (2024). Early estimate of nirsevimab effectiveness for prevention of respiratory syncytial virus-associated hospitalization among infants entering their first respiratory syncytial virus season—new vaccine surveillance network, October 2023–February 2024. MMWR, 73(9), 209–214. Retrieved March 2024 from https://www.cdc.gov/mmwr/volumes/73/wr/mm7309a4.htm?s_cid=mm7309a4_w

Released: April 2024

Nursing Drug Handbook

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Report of a study examining the effectiveness of the monoclonal anti-IgE antibody omalizumab was published in the New England Journal of Medicine and was featured in a symposium at the 2024 American Academy of Allergy, Asthma, and Immunology annual meeting. OUtMATCH (Omalizumab Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults) demonstrated that use of omalizumab increased the amount of foods containing allergens (peanuts, tree nuts, eggs, milk, and wheat) that individuals as young as 1 year with multifood allergies could consume without an allergic reaction.

OUtMATCH has three stages; this report describes stage 1, which aims to evaluate the efficacy and safety of omalizumab in patients allergic to peanuts and at least two other common foods. Researchers enrolled 180 patients ages 1 to 55 who were unable to tolerate 100 mg of peanut protein and 300 mg of at least two other food proteins (milk, eggs, cashews, walnuts, hazelnuts, or wheat). Each participant completed four separate blended food challenges (including a placebo challenge) to assess their ability to consume a single dose of at least 600 mg of peanut protein (primary endpoint) and a single dose of at least 1,000 mg of the other proteins (secondary endpoint) without experiencing moderate to severe allergic reactions. Patients were assigned to subcutaneous omalizumab or placebo, with dose based on weight and IgE levels every 2 to 4 weeks for 16 to 20 weeks, after which the food challenges were repeated.

Compared to placebo, a statistically significantly higher proportion of patients receiving omalizumab were able to consume a greater quantity of peanuts, milk, eggs, and cashews without moderate to severe reactions. Although not statistically significant, a higher proportion of patients on omalizumab were able to consume at least 1,000 mg of walnuts, hazelnuts, and wheat. For peanuts, 67% of treated patients were able to consume the target quantity versus 7% on placebo; for cashews, 41% versus 3%; for eggs, 67% versus 0%; for milk, 66% versus 10%. The values for walnuts were 64% versus 13%, for hazelnuts were 65% versus 14%, and for wheat were 75% versus 13%. Treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergies.

Results of this study show that anti-IgE therapy could significantly reduce the occurrence of allergic reactions across multiple foods in the event of accidental exposure, and thereby improve nutrition, quality of life, personal finances, and health care utilization.

Genentech. (2024, February 25). New England Journal of Medicine publishes phase III data showing Xolair significantly reduced allergic reactions across multiple foods in people with food allergies [Press release]. Retrieved March 2024 from https://www.gene.com/media/press-releases/15020/2024-02-25/new-england-journal-of-medicine-publishe

Wood, R. A., et al. (2024). Omalizumab for the treatment of multiple food allergies. N Engl J Med, 390, 889–899. Retrieved March 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2312382

Released: April 2024

Nursing Drug Handbook

© 2024 Wolters Kluwer