Published online April 27, 2009
PEDIATRICS Vol. 123 No. 5 May 2009, pp. e849-e856 (doi:10.1542/peds.2008-0978)

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ARTICLE

Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Alexander G. Agthe, MD^a,b, George R. Kim, MD^a, Kay B. Mathias, NNP^c, Craig W. Hendrix, MD^d, Raul Chavez-Valdez, MD^a, Lauren Jansson, MD^a,e, Tamorah R. Lewis, MD^a, Myron Yaster, MD^a,f and Estelle B. Gauda, MD^a,c,e

^a Departments of Pediatrics
^d Medicine
^f Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland
^b Department of Pediatrics, University of Maryland Medical Center, Baltimore, Maryland
^c Center for Neonatal Transitional Care, Mt Washington Pediatric Hospital, Baltimore, Maryland
^e Department of Pediatrics, Johns Hopkins Bayview Medical Center, Baltimore, Maryland

OBJECTIVE. To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome.

METHODS. Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of 9) were enrolled at 2 hospitals during 2002–2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 µg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation.

RESULTS. The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8–15 days]) than in the placebo group (15 days [95% confidence interval: 12–17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age.

CONCLUSIONS. In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

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Key Words: infants • opioid withdrawal • clonidine • tincture of opium

Abbreviations: NAS—neonatal abstinence syndrome • MFS—modified Finnegan score • DTO—diluted tincture of opium • ME—morphine equivalent • SVT—supraventricular tachycardia • JHH—Johns Hopkins Hospital • JHBMC—Johns Hopkins Bayview Medical Center • CI—confidence interval

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Accepted Jan 21, 2009.

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Clonidine as adjunct therapy for Neonatal Narcotic Abstinence, why not first-line therapy?

Peter Gal, et al.

Pediatrics Online, 7 Jun 2009 [Full text]