Who will be blinded {17a}
BLIND
All site research personnel (site PI, research coordinator, research nurses), the clinical team (physicians, nurse practitioners, physician assistants, house-staff, medical students), family members, care givers legally responsible for the infant, hospital personnel (nurses, nursing assistants, clinical nurse managers, respiratory therapists, etc.), and any other personnel working in the area of the hospital where the infants is cared for will be blinded to the treatment intervention (rate of weaning). Only pharmacy personnel will not be blinded. All site research personnel responsible for administering questionnaires after discharge or performing evaluations at 2 years of age will be blinded. Participating hospitals will be responsible for in-services of all involved staff regarding blinding.To maintain treatment blind, the volume of opioid will remain constant throughout the intervention for the rapid-wean and slow-wean intervention arms. At the time of opioid dosing, infants will receive one syringe with study drug at a volume equivalent to the volume of the stabilization dose, or a volume greater than the stabilization to facilitate maintaining a set volume (e.g., a stabilization dose of 0.28 ml may be set at 0.5 ml for ease of drawing up medication with saline during weaning). As infants progress through the dose levels, the research pharmacist will reduce the opioid volume and the pharmacist will make up the difference by normal saline so that the volume of the syringe is constant throughout all dose levels. To ensure that infants in the rapid-wean intervention arm have an equal number of study steps as infants in the slow-wean intervention arm, the pharmacy will use a placebo (normal saline without opioid) for three dose levels. Depending on the timing of escalations, the three placebo dose levels do not need to occur consecutively. We will label the study drugs as either morphine/study drug and the respective volume or methadone/study drug and the respective volume.