Symptom-Based Dosing Gets Infants With Opioid Withdrawal Out of the Hospital Faster

Infants with neonatal opioid withdrawal syndrome (NOWS) saw a decreased time to hospital discharge with symptom-based dosing versus scheduled opioid tapering, according to the OPTimize NOW trial.

The 383 infants were at risk of pharmacologic treatment and were cared for with the Eat, Sleep, Console (ESC) approach. Their mean time to medical readiness for discharge was significantly shorter with ESC at 9.18 days compared with the scheduled opioid tapering group at 11.61 days, for an adjusted mean ratio (aMR) 0.79 (95% CI 0.65-0.96, P=0.02), reported Lori Devlin, DO, of the University of Louisville School of Medicine in Kentucky, and colleagues.

Infants were considered medically ready for discharge (primary outcome) either by a medical team or when they were at least 96 hours of age and 48 hours from their last dose of opioid medication, whichever occurred first, they explained in JAMA. Trial data were presented at the Pediatric Academic Societies annual meeting in Boston.

The authors also reported that in the ESC cohort, there was no significant difference between the symptom-based dosing group or the scheduled opioid tapering group when it came to likelihood of initiating pharmacologic treatment (0.4 vs 0.41, aMR 0.99, 95% CI 0.77-1.27) or length of hospital stay (10.91 vs 12.09 days, aMR 0.9, 95% CI 0.72-1.13).

And among infants in the symptom-based dosing group, 35% required scheduled opioid dosing due to “persistently elevated signs of withdrawal, which equates to a number needed to treat of 1.5…to prevent 1 infant from receiving scheduled opioids,” the authors said, although they emphasized that “65% of pharmacologically treated infants in the symptom-based dosing group were successfully treated without the use of scheduled opioid dosing.”

Though nonpharmacologic care is the first line of treatment for infants with NOWS, pharmacologic care is indicated if infants do not adequately respond to initial care, Devlin and colleagues noted.

In traditional scheduled opioid tapering “low-dose opioids are initiated for infants meeting a severity threshold and escalated until the signs of withdrawal improve,” they wrote. Then, dosing is “slowly weaned while withdrawal severity is monitored.”

ESC, which focuses on functional well-being, uses a “single opioid dose when a specified withdrawal threshold is met,” and “additional opioid doses are administered only if the infant’s withdrawal severity remains above or escalates back to this treatment threshold,” the researchers said.

To date, there have been limited data to support one dosing approach over the other, Devlin and colleagues noted. OPTimize NOW findings “support the premise that opioid withdrawal follows a severity continuum to which pharmacologic treatment should be matched,” and provide “evidence to move beyond the all or nothing approach inherent in the use of a scheduled opioid taper,” they wrote.

The trial’s primary outcome came from a cohort of infants at 15 U.S. hospital who were first cared for with the ESC approach. Devlin’s group also examined 243 infants with NOWS who were at risk of pharmacologic treatment and cared for with the Finnegan approach, a comprehensive scoring system to quantify severity of symptoms. Infants in the Finnegan cohort were from 8 U.S. hospitals.

In the Finnegan cohort, there was no significant difference in time to medical readiness for discharge between a symptom-based dosing group and a scheduled opioid tapering group at 15.99 versus 17.56 days, respectively (aMR 0.91, 95% CI 0.72-1.15).

Also, in Finnegan, the risk of initiating pharmacologic treatment was higher in the symptom-based dosing group than in the scheduled opioid tapering group with an adjusted risk ratio of 1.21 (0.76 vs 0.63, 95% CI 1.03-1.42), although there was no significant difference in length of stay between the groups (17.38 vs 19.39 days, aMR 0.9, 95% CI 0.69-1.16).

Just three patients in the ESC cohort symptom-based dosing group and two in the scheduled opioid tapering group experienced the inpatient composite safety outcome of seizures or weight loss >15% from birth weight, the authors reported.

The mean gestational age of all trial infants (n=626) was 38 weeks, and 49% were male. Mean maternal age was 32 and more than three-fourths were white. Around 65% had adequate prenatal care, while about 38% were on prescribed buprenorphine for opioid dependency, while roughly 40% were on prescribed methadone.

Study limitations included that “contamination between groups was a potential risk,” Devlin and colleagues noted. However, this aspect of the study was “tempered by limiting access to training materials for the symptom-based dosing approach until just prior to each site’s transition and inclusion of a washout period,” they added.

Both the newer ESC approach and Finnegan are currently used in clinical practice, the authors noted.

In an accompanying editorial, Matthew Grossman, MD, of Yale School of Medicine in New Haven, Connecticut, and colleagues, said that the “implications for practice are clear. Symptom-based dosing in conjunction with ESC-based assessment should now be considered the evidence-based standard for pharmacologic management of NOWS.”

“For institutions that have already adopted ESC, the transition represents an incremental but impactful update, one supported by the strongest evidence this field has produced,” they contended. “For institutions still relying on Finnegan-based care, the OPTimize NOW trial adds urgency to a transition that is already overdue. Scheduled opioid tapers for every pharmacologically treated infant were never evidence based. They were a habit, inherited from an era when we had neither the tools nor the data to do better. We have both now.”