Neonatal Abstinence Syndrome(Assessment of Neonatal Withdrawal)

Neonatal Abstinence Syndrome(Assessment of neonatal withdrawal)

Opiates are powerful pain relievers, leading to increases in opiate dependency with morphine, codeine, methadone, meperidine, oxycodone, propoxyphene, hydromorphone, fentanyl, and heroin. (Hughes, A., Sathe, N., & Spagnola, K. 2009). There is a rise in use of non-medical use of prescription-type psychotherapeutic drugs.(SAMHSA ,2007).Opiate replacement for addiction is methadone and buprenorphine (Suboxone or Subutex)

Non-opiate withdrawal is found with benzodiazepines, barbiturates or alcohol. Discontinuation syndrome may occur in up to 30% of babies born to women who use antidepressants, particularly SSRIs . Onset of symptoms in babies varies depending on the specific pharmacological properties of the medications or illicitdrugs used. Reports of jitteriness and an enhanced startle response can be observed with symptoms ceasing within 1 to 2 weeks. Cocaine, amphetamines, PCP or Marijuana exposure symptoms may be related to direct effects of the drug and not abstinence syndrome and do not require treatment.

Maternal indicatorsof substance use include: lack of antenatal care; previous unexplained fetal demise or repeated spontaneous abortions; precipitous labour; abruptio placentae, hypertensive episodes; severe mood swings; MI; cerebrovascular accidents.Repeated maternal withdrawal can cause adverse effects on the fetus.

Neonatal indicators of maternal substance use include: Preterm birth, unexplained IUGR, seizures, apnea,jitteriness with normal glucose level , neurobehavioural or congenital abnormalities, marked irritability, necrotizing enterocolitis in otherwise healthy term infants , atypical vascular incidents or MI, or signs of neonatal abstinence syndrome (NAS). In the preterm infant, symptoms of NAS are generally milder, with alternating periods of hyperactivity and lethargy.

As a multisystem disorder, NAS is characterized by signs and symptoms of central nervous hyperirritability, gastrointestinal dysfunction, respiratory distress and vague autonomic symptoms that include yawning, sneezing, mottling and fever. Assessing severity and need for treatment of NAS is based on use of a scoring tool such as themodified Finnegan Neonatal Abstinence Score or the Neonatal Narcotic Withdrawal Index (AAP, 1998). Scoring should be performed 30 minutes to one hour after a feed, before the baby falls asleep.

Onsetusually occurs within the first 24 to 72 hours (with methadone, the onset of symptoms may be delayed until 96 hours). Late withdrawal may occur with infants whose mothers have been on high maintenance doses of methadone with onset 10 days. Symptoms of narcotic withdrawal from Heroin are often evident within 4-8 hours after birth. REMEMBER the half life of the drug elimination influences onset.

Differential diagnosis should include consideration of Rule out other potential causes of jitteriness and irritability: hypoglycemia, hypocalcemia, hypomagnesaemia, sepsis, or meningitis.

Maternal History of prenatal care, drug use and evaluate medications administered in pregnancy and delivery.

Maternal High risk screens include:

• Syphilis--RPR within 6 weeks of delivery/VDRL titer and FTA-AB result if previously positive.

• Hepatitis B--HB surface antigen within 6 weeks of delivery unless previously known to be a positive carrier or vaccinated.

• Hepatitis C screening--Hepatitis C within 6 weeks of delivery if history of cocaine (any route) or intravenous drug use.

• HIV--Refer for HIV counseling and screening if not done within 6 weeks of delivery unless previously known to be positive.

• Tuberculosis--Check for documented PPD in pregnancy.

Toxicology Workup (Only what is tested can give you a positive or a negative)we don’t test for Fentyl or Versed

• Collect as soon as possible! Beforeany medications given. NO consent is required to order aninfant’s toxicology.
• For mom screen for a history of drug or alcohol abuse within minimum last 2 years. ACOG recommends a history of use in the last 5 years.
• For infant collect urine and meconium. Medical team will evaluate if need to be ordered. Check to see if one was done on mom in pregnancy and in labor upon admission. Maternal Newborn Drug care set. What were the results?
• Infant Urine toxicology specimen requires first void. If missed document! Need 5-10 cc for testing. Only documents maternal use/infant exposure for the last 24-48 hours before delivery.
• Meconium toxicology screen is optimal to collect 24 hours worth of meconium and to be sent off as one specimen. ( requires 10 gms weight; if preterm 5 gms maybe acceptable) Identifies uses in the last trimester.
• ARUP 9 panel tests include: (Buprenorphine coming)

–Marijuana metabolites (9-carboxy-THC, 11-hydroxy-THC),

–Cocaine metabolites benzoylecgonine, meta-hydroxy-benzoylecgonine, and cocaethylene

–Opiates (codeine,morphine, hydrocodone, hydromorphone, and oxycodone),(herion metabolite) Soon buprenorphine.

–Phencyclidine (PCP),

–Amphetamines and methamphetamine

–Barbiturates (amobarbital,butalbital,pentobarbital, phenobarbital, secobarbital)

–Methadone and its metabolite EDDP.

–Benzodiazepines

• Alcohol for an infant requires infant or cord blood levels , rarely can be reported in urine.
• All positive tox screens regardless of confirmation, drug use or abuse by mother MUST be reported to social worker and documented.
• Methadone and Buprenorphine use for treatment of substance abuse is CPS reportable or any infant withdrawing
• Ant toxicclogy ordered on Mom or baby REQUIRES a Social Work Referal.

Monitoring:

1. Weigh daily. If significant wt loss then BID. (Adjust feedings for increased calories)

2. Use the Modified Neonatal Abstinence Scale Scoring tool every 3 hours post feeds (hunger signs can be confused with withdrawal) while in the observation period or on medication. Accuracy of scoring using parameters to be reviewed with staff of signs and symptoms.

3. Do not hold off a feeding if the infant acts hungry prior to completion of the previous post-test interval.

Standard of Care/ Orders

Admitted to the Newborn Nursery if clinically stable from the Delivery Room.

VS, Scoring NAS Evaluation every 3 hours.

Consults

1. Social Workevaluation required

2. Physical Therapy evaluation due to increased tone.

3. Lactation if breast feeding

Skin care – Calmosetine, critcaid.

1. Mineral oil topical 10 cc to 10 oz (peri bottle) clean perineum each diaper change.

2. Duoderm to knees, chin and areas of excoriation.

3. Prevention of diaper erosion/dermatitis. Every diaper change use Aquphor, or critcaid.

Treatment

a. apply 3M Cavilon No Sting Barrier Film (drip do not rub)

b. moisture barrier ointment, ie Calmoseptine Ointment apply ¼ in thick.

c. if diaper area erosion apply Vaseline dressings each diaper change.

Labs

1. Toxicology’s: Urine, Mec or cord blood as indicated.

2. CBCwith Diff, bedside glucose monitoring, chem 8 with Magnesium, Ionized Calcium or caffeine level if indicated.

Nutritional management:

• Feeding - 24 cal/oz formula or fortified breast milk, 80cc/kg/day and increase 10 cc/kg/day. Anticipate increased caloric needs and feed on early hunger cues. Some infants may require feedings Q 2 hours. If 36 weeks gestation or below use preterm formula.Assess coordination of suck/swallow reflex – support cheeks and jaw if necessary.
• Breastfeeding is generally not discouraged. Small amounts of methadone are transmitted to the baby in breast milk, but not usually in sufficient quantities to affect the baby clinically. No breast feeding for illicit drugs; Cocaine, Marijuana, Amphetamine, Phencyclidine, or Heroin.Assess risk for breast feeding with opiate medications, Antidepressants-SSRIs: Fluoxetine or citalopram, Sedatives-barbiturates, benzodiazepines and anticonvulsants.
• Supplement breast milk calories to 24/ cal/per oz.

Comfort care:

Involvement of mother in the care

Reduce environmental stimuli:

• Place infant in a quiet room with dim lighting and low activity

• Move infant away from telephone, sink, high traffic areas
• Use slow movements and avoid talking at the bedside
• Prepare everything prior to disturbing the infant to minimize handling
• Present one stimulus at a time (rocking, voice, soft music, etc)

Supportive therapy

• Wrap or swaddle infant
• Hold newborn infant firmly and close to the body
• Promote skin to skin contact
• Massage infant or try relaxation baths
• Rock gently up right, back and forth, talk, sing or hum softly
• Play heart beat audiotapes, music
• Decrease stimulation at first signs of distress
• Use of pacifier for excessive sucking, use mittens to prevent trauma to fingers & wrists

Pharmacotherapy:Dosage is calculated on birth weight and not current weight.

1. Indications: Opiate withdrawal (methadone, heroin, morphine, codeine)

a. If adequate supportive care is in place and infant has:

Three consecutive Finnegan scores or mean of 3 consecutive scores greater than or equal to 8; or Two consecutive scores or mean of 2 consecutive greater than 12.

b. Infant fails to gain weight on 24-calorie formula every 3 hours.

c. Intractable diarrhea.

2. Goals:

a. Reduce severity of withdrawal symptoms (Finnegan score less than 8).

b. Enable the infant to sleep and be soothed.

c. Reduce diarrhea.

d. Promote appropriate weight gain.

3. Principles:

Initial drug of choice – start with a single drug as follows:

• Opiate dependency – Opiate

• Mixed opiate and non-opiate dependency – Opiate

• Non-opiate dependency – Phenobarbital.

4. Oral morphine (0.4 mg/ml) – drug of choice at SUNYSB for opiate withdrawal. The Pharmacy will provide an oral morphine solution of 0.4 mg/ml for use in patients being treated for withdrawal. This concentration should allow for the small dose increments to be accurately measured.

Dosing of oral morphine:

1) Starting dose = 0.35 (range of 0.3- 0.4) mg/kg/day ( divided by the number of anticipated feedings per day (usually every 3 hours), i.e., 8 feedings = 0.04 mg/kg/dose. Some infants may need dosing every 2 hours if symptomatic prior to 3 hours. (AAP 2013 recommendations 0 .03 mg/kg/day)

2) Increments: If Finnegan withdrawal scores remain high (greater than 8), consult the attending about increasing the dose, usually by 0.02mg/kg/dose every 3 hours or 0.16mg/kg/24 hours until scores are less than 8 or a maximum dose of 0.8mg/kg /day is reached.

Cautions: 1) Monitor the infant closely for signs of over-sedation, decreased arousal or respiratory depression. CardioResp Monitor is required for dosing at 0.8mg/kg /day is reached.

2) To reverse: Administer Naloxone (Narcan) 0.01mg/kg/dose IM, IV, or by ETT. If there is no response at this dose, a subsequent dose of 0.1mg/kg can be given in 3 to 5 minutes.

IV conversions to PO start with amount of morphine in 24 hour and divided into q3 hour. Increase as needed see dosing.

Weaning:

1) When control is achieved (Finnegan scores are less than 8) . Monitor infant’s weight. For consistent weight gain for 2 days, wean by 10% of daily dose every 24hours (24-48) as tolerated (scores remain less than 8 and adequate weight is maintained).

2) Continue decreasing the total daily dose by 10%-20% every 48 hours (range24-72 hours)

when dosage levels reach less than 0.2mg/kg/day change from 3 hourly to 4 hourly dosage regime (same dose) for 24-48 hours prior to ceasing all medication.

Can be 10 to 20%. But usually standard

if starting at 0.16 , wean to 0.128 ,then .10 , .08 , 0.06 , 0r 04. D/C.

if starting at 0.14 , wean to 0 .106, then 0.08, 0.06, 0 .04 D/C

if starting at0..12, wean to 0.10, then 0.08, 0.06, 0.04D/C

When to D/C it is based on birth weight when the total daily morphine is 0.18 mg kg a day or less.

The baby usually won't rebound .if sensitive go to .04 mg q3 hr then stop . Based on BW.

Starting at higher numbers consistently over 12 hrs 10-13.

Discontinuing morphine:

1) Discontinue once at the presumed sub-therapeutic dose of 0.2 mg/kg/day if tolerated. Some infants may need to taper further. Continue NAS scoring and observe for 24-48 hours off morphine. Consider discharge.

5. Phenobarbital:

a. Primary agent in non-opiate withdrawal but not in opiate withdrawal due to its greater sedating effect, depression of sucking behavior, lack of effect on diarrhea, and the potential to precipitate opiate withdrawal seizures.

b. Oral loading doses: 10mg/kg/dose every 12 hours for 3 consecutive doses (total loading dose = 30mg/kg).

c. Oral maintenance dose: 5 mg/kg once a day starting 12 hours after the last loading dose. Obtain a serum level if infant has excessive sleepiness or no reduction in Finnegan scores. A therapeutic serum level (based on seizures) is 20-30mcg/ml.

d. Increments – If the Finnegan scores remains greater than 8, consider combination therapy (see 6 below), or give additional loading doses of 10mg/kg Phenobarbital every 12 hours, guided by serum levels until:

• Control is achieved, or

• Serum phenobarbital level of 40mcg/ml – maximum limit, or clinically toxic.

e. Weaning: Once symptoms scores fall below treatment level for 48 hours wean by 25% per week.

f. Discontinue when the serum level is less than 10mcg/ml.

6.Clonidine as an alternative to phenobarbital.

Clonidine is given in addition to morphine for polysubstance-dependency in term neonates with severe NAS uncontrolled after initial treatment with oral morphine .1 mg/kg/day (NEVER used alone for NAS)Clonidine reduces CNS sympathetic outflow and palliates symptoms of autonomic over activity such as tachycardia, hypertension, diaphoresis, restlessness, and diarrhea.

A. Dose .05to 1 mcg/kg PO every 6 hours.

B. Adverse effects include hypotension, rebound hypertension if clonidine is not tapered off over more than a week, AV-block, and bradycardia. MUST be on CR monitor.

C. MUST taper clonidine off over 10-14 days. Wean interval of dosing of clonidine and before decreasing morphine. (by 0.25 mcg/kg every 6 hours) There is no antidote for clonidine. Although some patients have responded to naloxone.

AAP guidelines illustrate oral morphine and methadone as first-line therapies based on current evidence and practice in the United States. Clonidine is also suggested as adjunctive therapy based on new literature illustrating its efficacy (Hudak & Tan, 2012). This is a change from AAP (1998) recommendations, which included tincture of opium as the preferred choice of treatment for opiate withdrawal.Phenobarbital is the preferred choice for sedative/hypnotic withdrawal. Other sedating medications, such as benzodiazepines such as diazepam, have been recommended in the past. However, AAP does not currently recommend their use due to their sedating effects and decreased ability to metabolize the drug with an immature liver (Hudak & Tan, 2012). Phenobarbital continues to be a better adjunct than benzodiazepines (Bio et al., 2011). Naloxone is also a contraindicated medication for infants with known opioid-dependent mothers due to the risk for seizure per the AAP (Hudak & Tan, 2012). However, despite the recent research, there is still no clear answer to standardized therapy for NAS. Table 1 compares drugs available for NAS treatment.

Discharge: 1.Infants should be observed for a minimum of :

2 days – cocaine, alcohol ; For SSRI( until stable)

5 days min – heroin/ Opiates ;

7 days – methadone and buprenorphine

2. Social Work and/or Child Protective Service (CPS) clearance

3. NAS scores 5 or below, feeding without difficulty and gaining weight consistently.

4. WIC, Public Health Nursing ICHAP, or Home nursing depending on insurance.

5. Documented plan for follow up and sign out to the Physician or Clinic

6. Parent/ guardian education of preparation of formula, reducing SIDS precautions, comfort measures, skin care as needed.

Documentation: This may be utilized in family court.

A. Document screening and health history information on the appropriate intake form(s).

B. Develop plans of care according to the criteria outlined, revise as appropriate.

C. Carefully record the infant’s behavior and responses to interventions and course of withdrawal.

D. Chart all NAS score values. ( new scale now with higher values)

E. Carefully describe all parent-infant interactions and visitation.

Evaluation of a positive toxicologyEvaluation of a positive toxicology

Maternal

Drug history or medication history.

Date and time of admission

Date and time of collection

Labor

Medications (what type)

How long medication was given. ? By 12 hours can get into infants meconium.

We don’t test for fentanyl , oxy not usually given in labor due to S/E, Duramorph is morphine. Now anesthesia is electronic. Easy to read.

Evaluation of a positive toxicology

Mother’s urine positive

Is it prescribed?

Did the doctor know she was pregnant?

Did OB know she was taking medication/drug legally or illegally?

Obtained or using some someone elses medication is illegal in NY.

Reducing or increasing medication with out management.

This is MEDICAL MISMANAGEMENT of Medication

Synthetic opiates do NOT test for Opiate positive.



Methadone Withdrawal

Two types of methadone withdrawal:

Early onset- symptoms appear shortly after birth, improve, and can recur at 2 to 4 weeks

Late onset- No symptoms at birth, but develop 2 to 3 weeks later.

The duration of these symptoms is commonly eight weeks, with irritability, poor sleeping persisting for three to four months

The maternal methadone dosage does not correlate with neonatal withdrawal; therefore, maternal benefits of effective methadone dosing are not offset by neonatal harm. Berghella V; et al, 2003.



Buprenorphine hydrochloride
Subutex® and Suboxone® tablets (+ naloxone)

a potent long acting (72 h) synthetic opioid with partial μ-receptor agonist and κ-receptor antagonist properties.

Symptoms appear at 12 hours, peak at around 72 hours and alleviate at 120 hours after the last buprenorphine dose

Dose 0.4-24mg/day

An alternative to methadone for MAT for opiate-dependency

Easily able to be converted to IV use

Methadone remains the only recommended MAT for opiate dependence during pregnancy

Not routine tested. Must be sent out separately.

Withdrawal day 3 and 6 due to metabolites.

Drugs not associated with NAS

Symptoms appear to be the result of the toxic effects of these drugs on the CNS rather than symptoms of withdrawal.

cocaine,

antidepressants, and/or

amphetamines

SSRI

(due to rebound cholinergic effect) , or maybe the Serotonin syndrome.

caffeine, marijuana, tobacco, and volatile substances

Isbister GK, Dawson A, Whyte IM, Prior FH, Clancy C, Smith AJ. Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch Dis Childhood: Fetal Neonatal Ed 2001;85:F147-148

Substances of abuse that may cause abstinence in the newborn include:

•Opiates/Opioids -- (Heroin, Morphine, Codeine, Opium, methadone, Fentanyl, Demerol, Percodan, Darvon, Oxycodone, buprenorphine, and others)

•Alcohol

•Benzodiazepine -- (Valium & other derivatives and related drugs including Librium, Placidyl, Xanax, Ativan)

• Barbiturates

False Positives- Review with mom drug and medication history.

Sertraline (ZOLOFT) can produce sporadic false-positive benzo ~26% of patients (typically at least 100 mg daily).

Testing can only identify drugs in panel. SEND OUT FOR CONFIRMATION to ARUP.

SBUH drug of abuse does not confirm.

Can send out to ARUP but results take 3 days .

You can confirm with toxicology lab as to testing and confirmations. or go to the lab user manual.