Sh. Pourarian Neonatologist Epidemiology A survey in 1985 by the national institute of drug Abuse...
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Transcript of Sh. Pourarian Neonatologist Epidemiology A survey in 1985 by the national institute of drug Abuse...
Epidemiology A survey in 1985 by the national institute of drug Abuse
(NIDA) showed.
23 million people in U.S. used illicit drugs
250000 women used intravenous drugs
90% of them were in reproductive age
6000-10000 newborns are born to opiate-addicted mother
each year.Cont.
Epidemiology
Marijuana and cocaine are the most frequently abused
illicit drugs in pregnancy.
Although opioid abuse in pregnancy is less common, but
their effect on mother and her fetus can be life threatening.
In utero exposure to opioids and other drugs may lead to fetal dependence and fetal and neonatal withdrawal.
Neonatal abstinence syndrome is a term generally applied to neonatal withdrawal from heroine or methadone, but similar signs are also seen in withdrawal from other substances:
Other narcotics, alcohol, benzodiazepines, barbiturates.
Narcotic Drugs Natural opiates:
Morphine Codeine
Synthetic opiates:Heroin Methadone Pentazocine (Talwin)Meperidine (Demerol)Oxycodone Morphinone (Dilaudid)Fentanyl (immovar)
Non- narcotic drugs Hypnosedatives
Barbiturate Nonbarbiturate sedatives and tranquilizers
Bromide Chloral hydrate Chlordiazepoxide (Librium) Diazepam (Valium)Ethchlorvynol (Placidyl)Glutethimide (Doriden)
Alcohol Ethanol
Cocaine (Crack)
Narcotics:Any natural or synthetic drug that has morphinlike
pharmacologic actions: opiate or narcotic .
Antenatal problems 1. Intrauterine asphyxia:
Still birth, Meconium- stained amniotic fluid Fetal distress, low apqar score, neonatal aspiration pneumonia.
Continuous fetal well being monitoring is needed.
Factors causes fetal asphyxia.a. Methadone sleep disturbances ↑REM > quite sleep ↑ hyperactive ↑20% in fetal O2 consumption.b.Fetal withdrawal coincides with maternal withdrawal hyperactivity ↑O2 consumption
Manifestations Bradycardia, ↑ sys. and dias. BP, continuous deep breathing movement,
neck tone, desynchronization of electrocortical activity.
2. Abruptia placenta, placenta previa, preeclampsia placental insufficiency fetal distress.
3. Meconium stained amniotic fluid
4. Intrauterine infection :
a. life style
b. ↑PROM CMI
c. Opiates compromise immune function d. Venereal dis., Hepatitis, AIDS response Humoral immune
Neonatal problems Heroin:Diacetylmorphine, is a semisynthetic opioid It has morphinlike properties but it’s crosses CNS more
rapidly. Deactivated in liver Morphine Readily across the placenta 30% LBW, 5% SGA (↓No. of cells, normal size) Direct growth inhibiting effect on the fetus No increase in congenital anomalies
Cont.
Heroin injected IV intensifies the risks due to :overdose acute bact. Endocarditis, Hep. B,C and HIV / AIDS, infections.
Heroin is also can snorted or smoked, make the drug even more attractive.
Facilitate contraction of sexually transmitted dis. ↑Prenatal risks: Extrauterine preg, PLP, PROM, uterine
irritability, breech presentation, antepartum hemorrhage, toxemia, anemia, bact. Infections, LBW, still birth
Clinical manifestations 50-75% of infants develop withdrawal syndrome.
Onset of symptoms : 24-48 hrs of life, or as late as 4wks, depend on several factors:
a. The dosage of heroine (<6 mg/day no or mild symptom)
b. The duration of maternal addiction:
(<1y 55%, >1y 73% incidence of withdrawal)
c. The time of last maternal dose:
↑incidence if drug taken within 24 hrs of birth.
Cont.
d. Type and amount of anesthesia or analgesia given to the mother, maturity and nutritional state of the infant. Less RDS due to accelerated lung maturation, surfactant Less Hyperbili. Due to induction of GT enzyme. Thrombocytosis, ↑ platelet aggregation Abnormal TFT: ↑ triiodothyronine and thyroxin levels Withdrawal symptoms
Cont.
MethadoneUsed for therapy for heroine addicted patient Block the
euphoric effects.Placental limitation of transport Incidence of withdrawal is 70-90%Higher birth weight, less IUGR< Heroin addicted Head circumference < 3% percentileNo congenital anomalies Thrombocytosis, ↑platelet aggregating activity, after the
first week, persisted for 16 wks.
Cont.
Methadone Abnormal thyroid function: ↑T3,T4 The time of onset of withdrawal symptoms depend:
a. The time of the last maternal dose
b. The dosage of drug: if > 20 mg/day symptoms Withdrawal symptoms Some infants have late withdrawal, which may be of two
types:a. Shortly after birth, improve, and recur at 2-4wks.
b. Are not seen at birth, but develop 2-3 wks later.
Non-Narcotic Hypnosedatives:Differences:
In adult:
1.Rate of developing physical dependent not ↑with the drug dose.
2.But ↑with prolonged and continuous administration over months or years produce addiction
In newborn
3. Passive addiction in therapeutic dose used by the mother.
4. The withdrawal manifestation: more intense and life threatening, Convulsion is more frequent
5. Unlike the narcotics, addiction may be induced by physicians.
Barbiturates Depends on their action classified to 3 groups: ultrashort,
intermediate, long acting The intermediate- acting are the most abused The long-acting (phenobarbital) is not abused,
mostly used for insomnia, relief of anxiety,
anticonvulsant, sedation for toxemia Barbiturate cross the placenta readily ↑Level found in brain, liver, adrenal of fetus
Cont.
The manifestations of W. symptoms are similar but with diff. onset:
Intermittent type: 1st day Long acting: 7 days (2-14 days) Metabolized in the liver, T ½ is twice in N.B. Infants are full term, AGA, Good apqar scores. 2 stages of phenobarbital withdrawal symptoms:Acute : irritability, hiccups, mouthing movements Subacute: voracious appetite, regurgitation, gagging,
sweating, disturbed sleep pattern, last 2-4m.
Cont.
Manifestations of neonatal narcotic withdrawal
Central nervous system signs Hyperactivity Hyperirritability – excess crying, high- pitched outcry Increased muscle tone Exaggerated reflexes Seizures 2-11%Tremors Sneezing, hiccups, yawning Short , non-quiet sleep Fever Respiratory sings Tachypnea Excess secretions
Manifestations of neonatal narcotic withdrawal
Gastrointestinal signsDisorganized, vigorous sucking Vomiting Drooling Sensitive gagHyperphagia Diarrhea Abdominal cramps (?) Vasomotor signs Stuffy nose Flushing Sweating Sudden, circumoral pallor Cutaneous sings Excoriated buttocks Facial scratches Pressure-point abrasion
Differential diagnosis1. Metabolic disturbances: ↓ Glu, ↓Ca, ↓ Mg, sepsis
meningitis, S.A Hemorrhage, Infectious diarrhea, intestinal obstruction.
2. CBC, X-ray, CSF and Blood culture
3. Mothers who took: tricyclic antidepressant and lithium during pregnancy toxicity= similar to withdrawal syndrome
4. Mothers on phenothiazine (chlorpromazine) extrapyramidal dysfunction Tremor, grimace, ↑muscle tone.
Lab test Thin – layer chromatography, immunoassay, gas
chromatography,…a. Urine
- limitations; benefits - False negative: 32-63% in N.B
b. Meconium Drug metabolized in liver bile GI In urine Amniotic fluid GI - Ideal specimen for drug testing till 3 days - Sensitive, quantitative, rapid c. Hair Mother, neonate: Mostly in chronic users.
Treatment 1. Management of the antenatal and neonatal
complications: Asphyxia, fetal distress, Mec. asp., cong. Anomalies
* Use of Narcan is contraindicated for birth asphyxia.
2. Routine serologic test: syphilis, HIV, Hepatitis B
TreatmentThe goal of Rx
1.↓ irritability
2.Feeding tolerance without vomiting or diarrhea
3.Sleeping between feedings without sedation
Symptomatic treatment
Supportive care:
Alone or together with pharmacotherapy
a. Quite environment, free from noxious stimuli
b. Tight swaddling, holding, rocking
c. Hand to mouth facilitor pacifier
d. Placing in a slightly darkened quiet area
e. Hypercaloric formula (24 cal/30 ml) as needed
f. Monitoring of temp, HR, RR, Q4h
g. Check for diarrhea, vomiting Q8h
h. Be aware of SIDS
Cont.
Infants should be scored at first appearance of NAS
Then repeated every 3-4 hrs based on feeding time
Pharmacotherapy is based on serial scoring of withdrawal signs:
8 or higher over three scoring intervals.
12 or higher over tow scoring intervals
If scores > 8 the scores must be checked Q 2hr
If the desired effect has been obtained for 72hrs,
the dosage must be tapered gradually without altering dosing interval D/C
B. Medications
1.Neonatal morphine solution (NMS): drug of choice for narcotic withdrawal
Preparation: 0.4 mg/ml oral morphine dilution: Add 1 ml of 4 mg/ml inject able solution of morphine + 9 ml
of normal saline.2. Neonatal opium solution (NOS): Hydroalcoholic solution 10 mg/ml + 25 Fold sterile water
0.4 mg morphine / ml The dilution is stable for 2 weeks 3. Paregoric: Contains : 0.4 % opium = 0.04% Morphine + other additives
Dose as for NMS or NOS Cont.
Dosing scheme for NMS or NOS
Score NMS or NOS
8-10 0.8 ml/kg/d divided Q4h/feeding
11-13 1.2 ml/kg/d divided Q4h/feeding
14-16 1.6 ml/kg/d divided Q4h/feeding
17 or greater 2.0 ml/kg/d divided Q4h/feeding
Increased by 0.4 ml until controlled
Cont.
a. Increase 2 drop/kg (0.1 ml/kg) Q 3-4 hr
b. If > 2.0 ml/kg/day add phenobarbital
c. If infant score remain < 8 for 72 hrs. wean by 10% of
total dose daily.
d. If weaning score > 8 restart the last effective dose
e. D/C NMS or NOS if the daily dose < 0.3 ml/kg/day
4.Phenobartital Is not the drug of choice of opiod withdrawal Recommended for anticonvulsant therapy. If NAS induced by sedative or hypnotics It may used as a second – line drug for NAS when NMS
fails to alleviate the symptoms Dose : 20 mg/kg ↑10 mg/kg Q 8-12 hr /dose
40mg/kg
Cumulative Sum of loading doses Maintenance phenobarbital
20 mg/kg 5 mg/kg/d
30 mg/ kg 6.5 mg/kg /d
40 mg/ kg 8 mg/kg/d
* Phenobarbital can be given PO or IM/24hr
* Taper by 10% every day after improving of symptoms
Cont.
5 .Morphine and phenobarbital Infants withdrawing from multiple drugs NMS dose: 0.05 ml/kg Q 4hr
phenobarbital dose: 10 mg/kg Q12Tapering of morphine first then phenobarbital Less sever withdrawal Shorter mean duration of hospital stay Reduced hospital cost.
Cont.
6 .Chlorpromazine
No longer used because of its side effects.
It is useful to control the vomiting. Diarrhea
Dose: 1.5-3 mg/kg / day Q4h , IM Po
7. Methadone - Is not used for withdrawal from narcosis - It is safe for methadone treated mother breast fed. - Dose 0.1 mg/kg/dose ↑0.025 mg/kg dose Q4h
8. Diazepam: Is not used because of side effects 0.1-0.3 mg/kg
IM till symptoms are controlled.
9. Lorazepam: Used for sedation alone or with NMS or NOS.
Dose: 0.05-0.1 mg/kg /dose/IV.
Complications
Alterations in serum electrolyte, pH, dehydration
Profound wt. loss
Aspiration pneumonia
Respiratory alkalosis
Neurobehavioral abnormalities
Long term outcome1. Syndrome of late-onset withdrawal
2-4 wks of age with or without previous
symptoms
Similar to early withdrawal symptoms
Voracious appetite, poor wt. gain for (8-16wks)
Cont.
2. Systemic hypertension
At 2 wks of age continue 12 wks
3. Child abuse and sudden infant death syndrome
Thermal burns, cigarette burns, traumatic ecchymosis in first 8 months and 8% ↑incidence of SIDS
Cont.
4. Growth and psychomotor development At 12 m. of age not differ from others At 3-6 y of age retardation in Ht, wt, HC
Neurologic abnormality, poor fine and gross motor
coordination, balance problem, delayed language
development Otitis media, abnormal eye movement.
Cont.
- At preschool age
↓ perception, ↓ short term memory, ↓ organization, behavioral
abnormality, aggressiveness, hyperactivity, socioeconomic
problem, poor school performance, no difference in IQ test.
5. Breast feeding
- D/C if the mother has been abused drug continuously
- If she is HIV positive
6. Maternal support