BALTIMORE – Some infants, especially among those with persistent pulmonary hypertension, are at risk for developing iatrogenic neonatal abstinence syndrome, according to , a neonatal-perinatal medicine fellow at Georgetown University Hospital in Washington.
Of 70 infants administered morphine or fentanyl for longer than a day in the neonatal ICU, almost a third (22, or 31%) developed iatrogenic neonatal abstinence syndrome (INAS). As a result, they needed prolonged respiratory support, more time to reach full feeds, and extended lengths of stay. Children exposed to opioids before birth were excluded from the analysis.
The greatest risk was in infants with persistent pulmonary hypertension; INAS was diagnosed in 13 of 22 (57%).
Opioid dosing also was all over the map for a given Neonatal Pain, Agitation, and Sedation Scale (N-PASS) score, Dr. Dave said. Some infants with an N-PASS pain score of 2, for instance, received no opioids, while others received up to 1,500 mg/kg morphine equivalents.
N-PASS is used in NICUs nationwide to guide dosing, but the variability seen in the study suggests that there’s need for a more objective measure of neonatal distress and for neonatologists to establish ground rules for NICU opioid use, she added.
The use of opioids has beenfor years (J Opioid Manag. 2015 Jul-Aug;11:305-12), and at least (J Perinatol. 2017 Sep;37:1038-42) already has established guidelines to curb overuse. Dr. Dave said that several neonatologists, after viewing her poster at the Pediatric Academic Societies annual meeting, told her that they probably had the same problem at their NICUs but had not examined their data.
“We are using” these medications more in the NICU, “but how much is too much? We need to find that balance. We need to improve our practice.”
“The overarching question is if there are better alternatives for treating pain and stress in critically ill neonates.” Dexmedetomidine, an opioid-sparing alpha-2 agonist adrenoreceptor sedative, analgesic, and anxiolytic, is one of several options “being looked at closely in this population. We also need to think of nonpharmacologic measures,” Dr. Dave said.
In addition to infants with persistent pulmonary hypertension, the 22 INAS cases at the study site included, among others, three children on extracorporeal membrane oxygenation, one with meconium aspiration syndrome, and one surgical case, out of the 15 included in the study. The common denominator was the need to keep infants calm and comfortable during prolonged intubation, which was a mean of 10.5 days among INAS infants versus 5 among children who didn’t go into opioid withdrawal.
INAS infants had a daily mean morphine-equivalent dose of 106.6 mg/kg, with a mean exposure of 17 days and mean cumulative dose of 1,515 mg/kg. The daily mean morphine-equivalent dose among infants who didn’t develop INAS was 42.4 mg/kg, with a mean exposure of 4 days and mean cumulative dose of 246 mg/kg.
INAS infants spent a mean of 27 days in the hospital, and it took them a mean of almost 6 days to reach full feeds, versus 15 days for the other infants full feeds by day 4. Over half of the INAS infants (12) also were on midazolam, and they had higher cumulative doses of the sedative than infants who didn’t develop INAS (mean, 2.64 mg/kg vs. 0.19 mg/kg). The findings all were statistically significant.
Dr. Dave said the most surprising finding was the variability in opioid dosing. In another example, some infants received up to 1,400 mg/kg morphine equivalents even when their fraction of inspired oxygen requirement fell below 60%, which meant that they were getting better. Other infants by that point were off opioids altogether.
“This has definitely brought awareness to my practice. Before I would say, ‘Okay, let’s just go up,’ ” when a nurse requested an opioid increase based on N-PASS scores. Now, “I try to really figure out why they think the baby needs an increase, and I may say ‘Actually, we are turning a corner now, and maybe the baby can be a little bit more awake. How do you feel about that?’ ” she said.
“My long-term goal for this project is putting some guidelines in place,” she said.
There was no industry funding for the work, and Dr. Dave didn’t have any disclosures.