(17) Optimal Morphine Dosing for Neonatal Opioid Withdrawal Syndrome

Anna Thomas, Indiana University School of Medicine, Indianapolis, IN, United States; Katherine Malloy, Medical University of South Carolina, United States; Gregory Sokol, Indiana University School of Medicine, United States; Scott Denne, Indiana University School of Medicine, United States

Background: Neonatal opioid withdrawal syndrome (NOWS) has been steadily increasing in prevalence over the last two decades in the United States. While we have made strides in understanding this population and improving non-pharmacologic care of the mother-infant dyad, there is currently no widely-accepted consensus on pharmacologic treatment for babies with severe withdrawal symptoms. The Eat, Sleep, Console method of monitoring NOWS has been gaining popularity and many centers who use morphine have opted to shift to symptom-based dosing. However, evidence to support this is limited to quality improvement.

Objectives: The primary objective of the study was to determine feasibility of conducting a large randomized trial by examining enrollment. Secondary outcomes included length of hospital stay (LOS), total cumulative morphine exposure, and length of morphine treatment.

Design/Methods: A pilot trial was conducted in a busy urban hospital from March 2020 through December 2021. Neonates with known intrauterine opioid exposure were monitored for NOWS using the modified Finnegan score (MFS). Patients were eligible for enrollment if they were ≥ 35 weeks gestation and met criteria for pharmacologic treatment of severe NOWS with two consecutive MFS ≥ 9 . The standard arm received oral morphine 0.05 mg/kg/dose every 3 hours, which was then weaned by 10% of the peak dose every 24 hours until the dose was < 0.02 mg/kg, and then discontinued. The study arm received the same dose of oral morphine only as-needed every 3 hours with subsequent doses given if the MFS was ≥ 9.

Results: A total of 17 newborns were enrolled out of the goal 24 subjects; 9 randomized to the standard arm and 8 to the study arm. There were no significant differences between the groups. The mean LOS in the standard group was 14.2 days versus 11.6 days for the symptom-based group (p-value 0.23). The mean days on morphine was lower for the symptom-based dosing group, 2.9 days versus 11.5 days (p-value < 0.0001). The cumulative morphine exposure was also lower in the symptom-based group, 0.2 mg/kg versus 3.6 mg/kg (p-value 0.0029). Of the 11 subjects for which follow-up information was able to be obtained, there were no readmissions.

Conclusion: Symptom-based dosing of morphine for NOWS reduced total morphine exposure and number of treatment days without apparent adverse effects. Further investigation is required to determine the optimal morphine dosing regimen for NOWS. Given the challenges with recruitment in this patient population, innovative clinical trial design will be essential.