Changes in opioid dose
The following are general considerations for The clinical team will use hospital-specific tools to determine the severity of NOWS signs (Finnegan; modified Finnegan; Eat, Sleep, Console; etc.).The clinical team will assess infants for NOWS signs every 3 or 4 h prior to care times (clinical assessment, vital signs, and feeding).The clinical team will use hospital thresholds of NOWS signs (e.g., wean if all Finnegan scores are < 8, escalate for an average of three scores ≥ 8 or two scores ≥ 12) to trigger changes in study drug dose.We will have one exception to hospital thresholds for changes in opioid dose based on a prior randomized trial [We will provide each hospital’s pharmacy a dosing calculator. After randomization, the pharmacy will input the weaning intervention (wean by 10 or 15% of the stabilization dose), the stabilization dose (mg/kg/day), the infant’s weight, and the dosing interval (every 3, 4, 8, or 12 h) to identify the steps of the intervention arm. The dosing calculator will provide the absolute dose (mg) at each step of the intervention arm.Frequency of dose changes for We will encourage clinical teams to wean study drug at least every 24 h.Clinical teams may wean infants at ≤ 24 h of a given dose (< 8 doses when given every 3 h, < 6 doses when given every 4 h, < 3 doses when given every 8 h, and < 2 doses when given every 12 h), per Infants not weaned by 24 h of a given dose will enter a 12-h period of The clinical team will order, “wean opioid per protocol” to trigger weaning.Frequency of dose changes for Clinical teams may escalate the opioid at any time during the study intervention based on hospital guidelines; clinical teams do not need to wait for 24 h of dosing.The clinical team will order, “Escalate opioid per protocol” to initiate escalation.When the clinical team orders opioid escalation, the pharmacy will resume the preceding step of the intervention arm. For example, an infant receiving placebo in the rapid-wean intervention arm will escalate to the last opioid dose (25% of the stabilization dose). The clinical team will maintain the escalated dose for 24 h, and then follow hospital guidelines to evaluate subsequent changes in drug dose.There are no limits on the number of escalations or resumptions of opioid for either intervention arm.Escalation of the study drug dose is the mechanism to address NOWS signs that require additional pharmacotherapy per each hospital’s specific assessment tool. Spot doses or rescue doses are not part of this trial interventionThe pharmacy will inform the clinical team when an infant has two dose levels remaining, which will allow the clinical team to be timely with discharge preparation.Overview of the time periods used by clinical team to either wean or escalate study drug. A 24-hour period for weaning or escalation, per hospital guidelines (light blue bar). Multiple vertical green lines represent dosing intervals; in this example the infant is receiving an opioid every 3 h. If the opioid dose does not change after 24 h of dosing, the infant enters a 12-h period of study protocol guideline (purple bar) to ensure that hospitals either wean or escalate and do not remain on the same dose. This approach will be applied to both weaning interventions