Phenobarbital and Clonidine as Secondary Medications for Neonatal Opioid Withdrawal Syndrome

Author:

Merhar Stephanie L.1,Ounpraseuth Songthip2,Devlin Lori A.3,Poindexter Brenda B.1,Young Leslie W.4,Berkey Sean D.5,Crowley Moira6,Czynski Adam J.7,Kiefer Autumn S.8,Whalen Bonny L.9,Das Abhik10,Fuller Janell F.11,Higgins Rosemary D.12,Thombre Vaishali2,Lester Barry M.13,Smith P. Brian14,Newman Sarah15,Sánchez Pablo J.16,Smith M. Cody17,Simon Alan E.18,

Affiliation:

1. Perinatal Institute, Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio;

2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas;

3. Department of Pediatrics, University of Louisville, Louisville, Kentucky;

4. Larner College of Medicine at the University of Vermont, Burlington, Vermont;

5. Alaska Native Tribal Health Consortium, Anchorage, Alaska;

6. Rainbow Babies and Children’s Hospital, Cleveland, Ohio;

7. Department of Pediatrics, Women and Infant’s Hospital, Providence, Rhode Island;

8. Department of Pediatrics, West Virginia University School of Medicine, Morgantown, West Virginia;

9. Children’s Hospital at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;

10. RTI International, Rockville, Maryland;

11. University of New Mexico Health Sciences Center, Albuquerque, New Mexico;

12. National Institute of Child Health and Human Development, Bethesda, Maryland and George Mason University, Fairfax, Virginia;

13. Center for the Study of Children at Risk, Department of Pediatrics, Brown Alpert Medical School and Women and Infants Hospital, Providence, Rhode Island;

14. Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina;

15. Nebraska Medical Center, Omaha, Nebraska;

16. Nationwide Children’s Hospital, College of Medicine, The Ohio State University, Columbus, Ohio;

17. Department of Pediatrics, School of Medicine, West Virginia University, Morgantown, West Virginia; and

18. Environmental Influences on Child Health Outcomes Program, Office of the Director, National Institutes of Health, Rockville, Maryland

Abstract

BACKGROUND AND OBJECTIVES: Despite the neonatal opioid withdrawal syndrome (NOWS) epidemic in the United States, evidence is limited for pharmacologic management when first-line opioid medications fail to control symptoms. The objective with this study was to evaluate outcomes of infants receiving secondary therapy with phenobarbital compared with clonidine, in combination with morphine, for the treatment of NOWS. METHODS: We performed a retrospective cohort study of infants with NOWS from 30 hospitals. The primary outcome measures were the length of hospital stay, duration of opioid treatment, and peak morphine dose. Outcomes were compared by group by using analysis of variance and multivariable linear regression controlling for relevant confounders. RESULTS: Of 563 infants with NOWS treated with morphine, 32% (n = 180) also received a secondary medication. Seventy-two received phenobarbital and 108 received clonidine. After adjustment for covariates, length of hospital stay was 10 days shorter, and, in some models, duration of morphine treatment was 7.5 days shorter in infants receiving phenobarbital compared with those receiving clonidine, with no difference in peak morphine dose. Infants were more likely to be discharged from the hospital on phenobarbital than clonidine (78% vs 29%, P < .0001). CONCLUSIONS: Among infants with NOWS receiving morphine and secondary therapy, those treated with phenobarbital had shorter length of hospital stay and shorter morphine treatment duration than clonidine-treated infants but were discharged from the hospital more often on secondary medication. Further investigation is warranted to determine if the benefits of shorter hospital stay and shorter duration of morphine therapy justify the possible neurodevelopmental consequences of phenobarbital use in infants with NOWS.

Publisher

American Academy of Pediatrics (AAP)

Subject

Pediatrics, Perinatology and Child Health

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