Lengthy Opioid Use After NEC Surgery Leads to Methadone Use in Infants

Prolonged non-methadone opioid use in infants after surgery for necrotizing enterocolitis (NEC) was linked to greater use of methadone and increased days of ventilation, total parenteral nutrition (TPN), and hospital stay, according to study findings published in JAMA Network Open.

Opioids are typically used to treat pain after surgery for necrotizing enterocolitis in preterm infants, but methadone may be needed to wean these infants from opioids during the recovery phase. Researchers therefore assessed infants who received opioids during surgery for NEC for post-surgical methadone use and other outcomes.

The investigators conducted a cohort study of  infants who had surgery for necrotizing enterocolitis from 2013 through 2022, using data from 48 US children’s hospitals participating in the Pediatric Health Information System. The researchers used mixed-effects multivariable logistic regression to determine thresholds for length of post-surgical opioid use in infants who later needed methadone treatment and to characterize clinical outcomes associated with methadone use.

Of the 2037 infants included in the study (45% White; 16.8% Hispanic) the mean birth weight was 920 g (interquartile range [IQR], 700 g to 1480 g), The infants received nonmethadone opioids for a median of 15 days (IQR, 6 to 30 days) after surgery, and 231 patients, or 11.3%, received methadone.

The likelihood of methadone treatment increased with the infant’s number of days on nonmethadone opioids. Compared with infants who received nonmethadone opioids for 1 to 5 days, those who received nonmethadone opioids for 16 to 21 days were more likely to need methadone treatment (odds ratio, 11.5; 95% CI, 6.31-20.77). Methadone use was associated with a 3-week longer length of stay (95% CI, 11-32 days), 11 more days on a ventilator (95% CI, 3.63-17.98), and 16 more days of TPN (95% CI, 6.34-26.10).

Study limitations include an absence of data on clinical indications for medication use, dosing, or pain scores; lack of data on the timing of NEC diagnoses and surgery, thereby limiting researchers’ ability to determine whether methadone was given to prevent vs respond to symptoms of opioid withdrawal. Moreover, infants who require intubation often receive opioids during intubation, which can result in respiratory depression and prolonged ventilation. Use of multimodal pain management techniques may have also confounded the study’s results.

“By identifying infants with surgically treated necrotizing enterocolitis at the highest risk of methadone use, these findings suggest an opportunity to expand neonatal opioid stewardship efforts to improve patient outcomes and health care use,” the researchers wrote. “Judicious use of opioids and multimodal pain management strategies in the postoperative period may reduce the need for methadone, improve patient outcomes, and decrease health care use for infants requiring surgical procedures.”