eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Neonatal Abstinence Syndrome: Treatment & Medication

Author: Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Mid Tennessee Neonatology Associates.
Contributor Information and Disclosures

Updated: Jun 18, 2009

Treatment

Medical Care

  • The large number of infants who suffer from neonatal abstinence syndrome (NAS) and the associated long-term morbidity mandate that affected infants be accurately identified and their treatment and support should be optimized.
  • The assessment and management of neonatal abstinence syndrome pose difficulties for staff and families and have been hampered by a lack of prospective studies and by few research studies that specifically assess the merits of one management approach over another.
  • Vomiting and diarrhea leading to dehydration and poor weight gain, in the absence of other diagnoses, are indications for treatment, even in the absence of a high drug-withdrawal score.
  • In the delivery room, naloxone use is contraindicated in infants whose mothers are known to be dependent on opioids because of the risk of neonatal seizures from abrupt drug withdrawal. However, in the absence of a specific history of opioid abuse, naloxone treatment remains a reasonable option in the delivery room management of a depressed infant whose mother recently received a narcotic.
  • Primary treatment of neonatal symptoms related to prenatal substance exposure should be supportive because pharmacologic therapy can prolong hospitalization and exposes the infant to additional agents that are often not necessary. The treatment for morphine administration has been reported to last 8-79 days.16 This length of hospitalization interferes with maternal bonding, has potential for nosocomial infection, and is a major use of resources.17  
  • Pharmacotherapy for infants with more severe expression of neonatal abstinence syndrome is necessary to allow them to feed, sleep, gain weight, and interact with care givers. Approximately 30-91% of infants who exhibit signs of neonatal abstinence syndrome receive pharmacological treatment.
  • Nonpharmacologic approaches include the following:
    • Assess daily for signs of withdrawal, including sleeping habits, feeding patterns, and weight gain.
    • Reduce the degree of ambient light exposure, minimize excessive noise, avoid unnecessary handling, and provide swaddling for settling.
    • Provide frequent small feeds of hypercaloric formula.

Diet

  • Frequent small feedings are preferable and should provide 150-250 kcal/kg per 24 hours for proper growth of the infant undergoing significant withdrawal.

Activity

  • Swaddling, pacifiers, low lighting, oscillating cribs, and avoidance of abrupt changes in the infant’s environment can be helpful.

Medication

Medications used in patients with neonatal abstinence syndrome (NAS) should be considered when supportive measures fail to ameliorate the infant's withdrawal. This may be manifested early on as difficulty with feeding, extreme irritability, and poor sleeping. If a scoring system is used, pharmacological treatment is commonly started when the average of 3 scores is 8 or more on the Finnegan scale11 or 4 or more on the Lipsitz scale.

The optimal treatment for neonatal abstinence syndrome has not been established. This is reflected in the considerable heterogeneity in the pharmacologic treatment of neonatal abstinence syndrome among different institutions. Many pharmacological agents have been used to treat neonatal abstinence syndrome. However, few randomized trials have compared the efficacy of the various pharmacological treatments. For opioid related neonatal abstinence syndrome, morphine and methadone are given as substitutes. Nonmorphine treatments (eg, phenobarbital, chlorpromazine, diazepam, clonidine) provide symptomatic relief.

Agthe et al studied 80 infants who were exposed in utero to methadone or heroin and subsequently had neonatal abstinence syndrome to determine if oral clonidine would reduce the duration of opioid detoxification.18 Each infant received oral diluted tincture of opium (dosage according to standardized algorithm) and also either oral clonidine (1 mcg/kg every 4 h) or placebo. Duration of opioid therapy was measured. Median length of therapy was 27% shorter in the clonidine group (11 d) compared with placebo (15 d). 

Seven infants in the clonidine group required restarting opium after initial discontinuation, compared with none in the placebo group, although the total length of treatment was significantly less in the clonidine group. Higher opium doses were required by 40% of infants in the placebo group compared with 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group compared with none in the clonidine group. The addition of clonidine to standard opioidtherapy reduced the duration of pharmacotherapy for neonatal abstinence syndrome.

A US survey reported that opioid medications are the most commonly used medications for the treatment of both opioid and polydrug withdrawal.19 Diluted tincture of opium is recommended by the American Academy of Pediatrics for the treatment of neonatal abstinence syndrome due to opioid withdrawal.20 Diluted tincture of opium is a 25-fold dilution of deodorized tincture of opium. Deodorized tincture of opium is equivalent to anhydrous morphine 10 mg/mL, whereas diluted tincture of opium is equivalent to anhydrous morphine 0.4 mg/mL. As a tincture, opium contains a high amount of alcohol. Diluted tincture of opium (Paregoric) contains 45% alcohol. The Institute for Safe Medication Practices considers this a high alert medication because of the confusion if abbreviated as DTO because the abbreviation could mean deodorized or diluted tincture of opium. 

Many neonatal units use proprietary oral or intravenous morphine solutions, and methadone is also used. A recent study showed chlorpromazine to be efficacious, with no adverse effects in neonates with neonatal abstinence syndrome and shorter treatment time when compared with morphine. A large multicenter trial was recommended by the author to confirm the safety and efficacy of chlorpromazine.21

Currently, many infants are exposed to polydrug abuse. Unfortunately, evidence from randomized studies is insufficient to determine the best management for these patients. In 2 randomized trials, phenobarbital (rather than diazepam or paregoric) was best at controlling symptoms in infants exposed to polydrugs. The results of another study suggested that the combination of phenobarbital with diluted tincture of opium may be more effective than diluted tincture of opium alone because the combination was associated with a shorter hospital stay.15

Antiepileptic agents

These drugs have a long half-life and can be orally administered, allowing for the neonate to be discharged and treated as an outpatient.

Disadvantages include lack of effect on GI symptoms and ineffectiveness in treating seizures secondary to withdrawal. In addition, antiepileptics contain 14-25% alcohol, and larger doses are required to achieve the desired effect.


Phenobarbital (Luminal)

Interferes with transmission of impulses from thalamus to cortex of brain. Used as a sedative. Irritability and insomnia are controlled. Available in PO and IV preparations.

Adult

Pediatric

Loading dose: 5-10 mg/kg PO/IV/IM
Maintenance: 3-6 mg/kg/d PO once a day; maintenance dose usually initiated 24 h following loading dose; increase by 10% when NAS score is consistently >8; wean by decreasing dose 20% qod

May decrease serum concentration or effect of lamotrigine, ethosuximide, warfarin, chloramphenicol, beta-blockers, theophylline, corticosteroids, TCA, cyclosporine, and quinidine
Metabolism of phenobarbital may be inhibited by chloramphenicol and felbamate, resulting in increased serum levels; coadministration with benzodiazepines or alcohol may increase CNS and respiratory depressant effect

Documented hypersensitivity; preexisting CNS depression, severe uncontrolled pain, porphyria, marked impairment of liver function, severe respiratory disease with dyspnea or obstruction

Pregnancy
Precautions

Slow IV infusion not to exceed 0.5-1 mg/kg/min to minimize potential hypotension; abrupt withdrawal results in status epilepticus

Opiates

These agents are the mainstay of treatment for opiate withdrawal, either alone or in combination with other medications. These agents are CNS depressants with advantages that include oral administration, mild sedation that improves the effectiveness of sucking, and effectiveness in treating seizures secondary to opiate withdrawal.


Morphine sulfate (Roxanol, Astramorph PF)

PO solutions are available in concentrations of 2 mg/mL, 4 mg/mL, and alcohol-free 20 mg/mL. Administered to neonates as diluted PO solution containing 0.4 mg/mL.
Bioavailability is 20-40% when administered orally. Elimination half-life is approximately 9 h. Recommended that Neonatal Abstinence Scoring System be used to guide treatment management of NAS.

Adult

Pediatric

Initial: 0.03-0.1 mg/kg PO q3-4h, increase as needed by 0.02-0.04 mg/kg PO until abstinence scores are <8
Maintenance dose: 0.03-0.1 mg/kg PO q3-4h; once scores stabilized for 3-5 d; gradually wean by 10-20% qod; discontinue when total single dose <0.08 mg

Alcohol, phenothiazine, TCAs, or other CNS depressants may cause additive effects

Documented hypersensitivity; severe respiratory depression; increased intracranial pressure; and severe liver or renal insufficiency

Pregnancy
Precautions

Opioid analgesics are powerful respiratory depressants and must be used with caution; caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate


Methadone

Long-acting narcotic analgesic. PO bioavailability is 50%, with peak plasma levels obtained in 2-4 hours. Serum half-life ranges from 16-25 hours in neonates and is prolonged in patients with renal failure. Available as PO solutions in 1-mg/mL and 2-mg/mL concentrations containing 8% alcohol and 10-mg/mL alcohol-free solution.

Adult

Pediatric

Initial dose: 0.05-0.2 mg/kg/dose PO q12-24h; reduce dose by 10-20% per week over 4-6 wk; adjust weaning schedule based on signs and symptoms of withdrawal.
Severe cases: 0.05-0.1 mg/kg/dose PO q6h initially; may increase by 0.05 mg/kg/dose until signs are controlled; once controlled, administer q12-24h and discontinue after weaning to daily doses of 0.05 mg/kg

Phenytoin, rifampin may decrease blood levels of methadone and can precipitate withdrawal symptoms; CYP450 inhibitors (eg, ketoconazole, erythromycin) may decrease elimination

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in severe liver disease; because of relatively long half-life, slowly titrate dose; respiratory depression in excessive doses; ileus; delayed gastric emptying

More on Neonatal Abstinence Syndrome

Overview: Neonatal Abstinence Syndrome
Differential Diagnoses & Workup: Neonatal Abstinence Syndrome
Treatment & Medication: Neonatal Abstinence Syndrome
Follow-up: Neonatal Abstinence Syndrome
Multimedia: Neonatal Abstinence Syndrome
References
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Further Reading

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Keywords

neonatal abstinence syndrome, neonatal withdrawal syndrome, NAS, prenatal NAS, postnatal NAS, maternal substance abuse, low birth weight, prematurity, intrauterine growth retardation, IUGR, hypoglycemia, hypocalcemia, sepsis, hypoxic encephalopathy, intracranial hemorrhage, jitteriness, neonatal adaptation syndrome, maternal drug use, pregnant drug use, placental abruption, fetal alcohol syndrome, maternal substance abuse, drug use in pregnancy, sudden infant death syndrome, SIDS, depression, fetal alcohol syndrome, treatment, diagnosis

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Contributor Information and Disclosures

Author

Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP, Clinical Assistant Professor of Pediatrics, Vanderbilt University Medical Center; Neonatologist, Mid Tennessee Neonatology Associates.
Ashraf H Hamdan, MB, BCh, MSc, MD, MRCP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Brian S Carter, MD, FAAP, Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Co-director, Pediatric Advance Comfort Team, Monroe Carell Jr Children's Hospital at Vanderbilt
Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Society for Bioethics and Humanities, American Society of Law Medicine and Ethics, National Hospice and Palliative Care Organization, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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