Opioid equipotency conversions for hospitalized infants: a systematic review.

Hospitalized infants commonly receive opioids to reduce pain and minimize distress during invasive procedures. However, infant neurodevelopment is significantly impacted by cumulative and prolonged opioid exposures. While opioid conversion has been studied extensively in adults, no standardized equipotency opioid conversions exist for hospitalized infants and opioid stewardship efforts are inconsistent. We performed a systematic review to identify opioid dosing conversions commonly used in hospitalized infants <1 year of age, finding fourteen articles which documented or cited a calculation of cumulative opioid exposure. Morphine milligram equivalents (MME) conversion factors varied widely, with nine studies citing conversion equivalent equations commonly used in adults. Efforts to expand safe opioid stewardship to hospitalized infants will require evidence-based consensus for opioid equipotency dose conversions which acknowledge the unique physiology of infants.

The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US.

Importance: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. Objective: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. Design, Setting, and Participants: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Exposure: Any opioid exposure and methadone treatment. Main Outcomes and Measures: Regional and institutional variations in opioid exposure. Results: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. Conclusions and Relevance: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Increases in pediatric cholecystectomy during the COVID-19 pandemic: An interrupted time series analysis.

BACKGROUND: Historically, cholecystectomy is infrequently performed in children. Lifestyle changes, delays in healthcare access, and increases in childhood obesity occurred during the COVID-2019 pandemic. It is unclear whether these changes impacted pediatric gallbladder disease and the need for cholecystectomy. METHODS: A retrospective study of children ≤18 years old undergoing cholecystectomy from January 1, 2016, to July 31, 2022, at a tertiary children's hospital was conducted. On March 19, 2020, a statewide mandatory coronavirus disease 2019 stay-at-home policy began. Differences in children undergoing cholecystectomy before and during the pandemic were identified using bivariate comparisons. An interrupted time series analysis identified differences in case volume trends. RESULTS: Overall, 633 children were identified-293 pre-pandemic and 340 pandemic. A majority were female sex (76.3%) and Hispanic (67.5%), with a median age of 15 years (interquartile range: 13.0-16.0). Children who underwent cholecystectomy during the pandemic had significantly higher body mass index (28.4 versus 25.8, P = .002), and obesity (body mass index >30) was more common (45.3% versus 31.7%, P = .001). During the pandemic, significant increases in complicated biliary disease occurred-symptomatic cholelithiasis decreased (41.5% versus 61.8%, P < .001) and choledocholithiasis (17.9% versus 11.6%, P = .026), gallstone pancreatitis (17.4% versus 10.6%, P = .015), and chronic cholecystitis (4.7% versus 1.0%, P = .007) increased. The number of cholecystectomies performed per month increased during the pandemic, and on interrupted time series analysis, there was a significant increase in month-to-month case count during the pandemic (P = .003). CONCLUSION: Cholecystectomy case volume significantly increased during the coronavirus disease 2019 pandemic, possibly secondary to increases in childhood obesity. Future studies are needed to determine whether this increased frequency of pediatric cholecystectomy is representative of broader shifts in pediatric health and healthcare use after coronavirus disease 2019.