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Multicenter Study
. 2021 Mar;147(3):e2020017830.
doi: 10.1542/peds.2020-017830.

Phenobarbital and Clonidine as Secondary Medications for Neonatal Opioid Withdrawal Syndrome

Stephanie L Merhar  1 , Songthip Ounpraseuth  2 , Lori A Devlin  3 , Brenda B Poindexter  4 , Leslie W Young  5 , Sean D Berkey  6 , Moira Crowley  7 , Adam J Czynski  8 , Autumn S Kiefer  9 , Bonny L Whalen  10 , Abhik Das  11 , Janell F Fuller  12 , Rosemary D Higgins  13 , Vaishali Thombre  2 , Barry M Lester  14 , P Brian Smith  15 , Sarah Newman  16 , Pablo J Sánchez  17 , M Cody Smith  18 , Alan E Simon  19 ; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT NEONATAL RESEARCH NETWORK AND THE NIH ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES (ECHO) PROGRAM INSTITUTIONAL DEVELOPMENT AWARDS STATES PEDIATRIC CLINICAL TRIALS NETWORK
Affiliations
Multicenter Study

Phenobarbital and Clonidine as Secondary Medications for Neonatal Opioid Withdrawal Syndrome

Stephanie L Merhar et al. Pediatrics. 2021 Mar.

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.

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Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: Dr Whalen is a codeveloper of the ESC Care Tool; Children’s Hospital at Dartmouth-Hitchcock is one of the institutions on the ESC Care Tool copyright; the other authors have indicated they have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Subject flow diagram. CE, Current Experience.
FIGURE 2
FIGURE 2
Comparison of unadjusted group means. Error bars reflect SEs. LOS, length of stay.
See this image and copyright information in PMC

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