Download Management of Neonatal Drug Withdrawal

Management of Neonatal Abstinence
Syndrome and Iatrogenic
Drug Withdrawal
Kirsten H. Ohler, Pharm.D., BCPS
Clinical Assistant Professor
Neonatal / Pediatric Clinical Pharmacist
University of Illinois at Chicago
Objectives
 Define tolerance, dependence, addiction, and
withdrawal.
 Describe the available scoring systems for
assessing drug withdrawal.
 Discuss the pharmacologic management of
narcotic / opioid withdrawal.
 Discuss the management of other possible
causes of neonatal & pediatric drug withdrawal.
 Describe the pharmacist’s role in the care of a
neonate or child experiencing withdrawal.
Definitions
 Tolerance


increasing dosage requirement to achieve the
same pharmacologic effect that was
previously achieved with a lower dose
tolerance potential of various opioid agents
 fentanyl
> morphine > methadone
Definitions
 Physical dependence

physiological state produced by repeated
exposure to a drug which necessitates the
continued administration of the drug to
prevent withdrawal symptoms

related to cumulative dose and duration

occurs in up to 2/3 of patients
Definitions
 Addiction

complex behavior pattern of drug use
involving both physical and psychological
dependence including drug-seeking behavior
Definitions
 Withdrawal

a syndrome manifested by the occurrence of
symptoms characteristic of the drug

self-limited process

may be life-threatening
Opioid Withdrawal
 Neonatal Abstinence Syndrome (NAS)

occurs in ~ 60 - 90% of neonates born to
narcotic-addicted mothers
 Iatrogenic tolerance / withdrawal



more likely with fentanyl vs. morphine
more likely with infusions vs. bolus doses
incidence with use > 5 - 7 days
Opioid Withdrawal
 Signs and symptoms



Neurologic - tremors, irritability, high-pitched
cry, tone, wakefulness, yawning,
sneezing, seizures
Gastrointestinal - vomiting, diarrhea
Autonomic - sweating, nasal stuffiness,
tachycardia, fever / temperature instability,
hypertension, mottling
“Diagnosis” of Withdrawal
 Toxicology screening


meconium – fetal drug exposure after 12th week
urine – drug exposure w/in hours to a few days
 “False” positive test
 “False” negative test
 May withdrawal without
toxicology screen
“Diagnosis” of Withdrawal
 No validated assessment tool for iatrogenic
drug withdrawal
 Several scales for neonatal abstinence
syndrome
Finnegan Scale
A score of < 7 = absent, 8-12 = mild, 13-16 = moderate, > 17 = severe
Sign / Symptom
Score
High-pitched cry

excessive
2

continuous
3
Sleep after feeding

< 1 hour
3

< 2 hours
2

< 3 hours
1
Moro reflex

hyperactive
2

markedly hyperactive
3
Tremors

mild when disturbed
1

marked when disturbed
2

mild when undisturbed
3

marked when undisturbed 4
Increased muscle tone
2
Sign / Symptom
Seizure
Excessive sucking
Poor feeding
Regurgitation
Projectile vomiting
Stools

loose

watery
Sweating
Fever

< 101 F (38.2C)

> 101 F (38.4C)
Yawning / Sneezing (> 4x)
Respiratory rate


Score
5
1
2
2
3
2
3
1
1
2
1 each
>60 breaths / min
1
>60 / min w/ retractions 2
Finnegan Scale
 Advantages



reliable and valid for assessment of NAS
most comprehensive assessment of symptoms
bed-side nurse driven
 Disadvantages




not validated in the ICU setting
not validated for agents other than opioids
not validated in pre-term infants
cumbersome
Lipsitz Tool
Score > 4 = significant withdrawal
Score
Signs
0
1
2
3
Tremors
Normal
Min ↑, disturbed
Mod-Marked ↑, undisturbed
Marked ↑,
undisturbed
Irritability
None
Slight ↑
Mod-Marked, disturbed
Marked, undisturbed
Reflexes
Normal
↑
Markedly ↑
Stools
Normal
Explosive,
normal freq
Explosive, > 8/day
Muscle tone
Normal
↑
Rigidity
Skin abrasions
No
Redness
Skin breakdown
Respiratory rate
< 55
55 – 75
76 – 95
Repetitive sneezing
No
Yes
Repetitive yawning
No
Yes
Vomiting
No
Yes
Fever
No
Yes
Lipsitz Tool
 Advantages


simple numeric scale
bed-side nurse driven
 Disadvantages




more subjective evaluation of symptoms
not validated in the ICU setting
not validated for agents other than opioids
not validated for pre-term infants
Other Withdrawal Scales
 Kahn system & Ostrea system

subjective / descriptive assessments
 Neonatal Narcotic Withdrawal Index (Green)


objective scoring of 7 elements
physician-based
 Moro Scale Score


primarily assesses muscle tone / tremor
physician-based scale for chronic withdrawal
Withdrawal Management
 Goals



severity of symptoms to a tolerable level
allow adequate sleep between feeds
agitation & distress caused by procedures
Withdrawal Management
 Prevention strategies

NAS
 use

lowest possible maternal methadone dose
Iatrogenic withdrawal
 use
lowest effective analgesic / sedative dose
 wean continuous infusions after long-term use
 low dose naloxone infusion
Withdrawal Management
 Prevention strategies

Low dose naloxone infusion
 AC-cAMP
superactivation: chronic opioid
administration activates G1 and Gs proteins →
upregulation of AC-cAMP → ↑ neuron action
potential duration and neurotransmitter release
decreased analgesia & possibly tolerance
 naloxone
blocks Gs binding → theoretical
decrease in tolerance
• randomized, placebo-controlled trial showed no
difference in total fentanyl dose received
Withdrawal Management
 Weaning Strategies

identify patients at risk for withdrawal

duration of exposure

long half-life agent

utilize withdrawal scoring tool
rate / length of wean
less frequent weaning
Withdrawal Management
 Non-pharmacologic vs. pharmacologic

Indications for drug therapy: seizures,
excessive weight loss / dehydration, inability
to sleep, fever
 Use an agent in the same drug class from
which the infant is withdrawing
Opioid Withdrawal Management
 Paregoric


46% alcohol, camphor, benzoic acid, & others
no longer recommended
 Tincture of opium


17-21% alcohol
requires a 25-fold dilution for dosing
Opioid Withdrawal Management
 Morphine oral solution




alcohol free
short half-life
conversion from fentanyl or IV morphine
usual initial dose for NAS
 0.1
– 0.2 mg/kg/dose PO q 6 hours
 Methadone


8% alcohol
long half-life
Opioid Withdrawal Management
 Benzodiazepines



increased sedation and poor sucking
poor control of GI and autonomic symptoms
adjunct for controlling irritability
 Phenobarbital



greater sedation and poor sucking
does not control vomiting and diarrhea
hyperalgesia, drug interactions, long half-life
Opioid Withdrawal Management
 Clonidine




may suppress autonomic symptoms
may not effect GI symptoms or poor sleeping
may produce hypotension
extemporaneous liquid preparation
 Naloxone


opioid antagonist
may precipitate withdrawal symptoms
Other Withdrawal Syndromes
 Benzodiazepines


no validated assessment tool
treatment principles similar to opioid withdrawal
 Barbiturates
Other Withdrawal Syndromes
 Nicotine


conflicting data
supportive management
 Caffeine


scant reports
supportive management
Other Withdrawal Syndromes
 Alcohol


tremors, sleep, crying, tone,
supportive management
sucking
 Inhalants



solvents, paint thinner, glue
high-pitched cry, sleeplessness, tremors,
hypertonia, poor feeding
case report using phenobarbital for
management
Other Withdrawal Syndromes
 Selective Serotonin Reuptake Inhibitors (SSRI)




~30% of infants with in utero exposure have
withdrawal symptoms
withdrawal vs. serotonin toxicity (?)
GI symptoms, tremors, sleep, high-pitched cry
supportive management
Role of the Pharmacist
 Recognize signs / symptoms of withdrawal
 Educate the healthcare team on the use of
withdrawal scores
 Assist in the selection of the most
appropriate pharmacological agent for the
management of withdrawal
 Develop a weaning plan to minimize the
occurrence of withdrawal
Questions
Case Discussion #1
A male infant is born at 35 5/7 weeks gestation, birth weight
2430 grams


Maternal history: IV drug abuse (heroin & cocaine),
methadone treatment program (80 mg/day), bipolar disease
(alprazolam, quetiapine, sertraline)
Maternal urine toxicology screen positive for benzodiazepine
and methadone one week prior to delivery.
Physical exam at birth: hypertonic, nasal flaring / grunting,
microcephalic, bilateral club feet
Admitted to NICU for respiratory support & monitoring for
withdrawal symptoms
Case Discussion #1
DOL 3: reported to be hypertonic, jittery, intolerant of oral
feeds, meconium toxicology screen reported negative

Finnegan score: 6 – 7
DOL 6: questionable seizure activity overnight

Neurology consult recommends EEG (no focal findings)
DOL 7: generalized seizure

Phenobarbital initiated per neurology recommendation
DOL 11: remains jittery, multiple loose stools

Finnegan score: 11 - 12
Case Discussion #1
 Thoughts….

regarding patient presentation?

regarding management thus far?
Case Discussion #1
DOL 11: oral morphine ordered
DOL 12-13: requiring escalating doses of morphine to
control symptoms (1 mg/kg/dose q6 hours)
DOL 15 – 17: Finnegan scores improving (7 – 8), feeding
tolerance improving
Case Discussion #1
DOL 43: weaned morphine to 0.1 mg/kg/dose q 8 hours

Finnegan scores 8 – 13

irritable cry, hypertonic, jittery
 Thoughts…

regarding patient status at this point?

regarding management / weaning strategies?
Case Discussion #2
Six days ago, a 2 year old, 12 kg girl underwent the Fontan
procedure for HLHS. She was placed on a fentanyl drip postoperatively and the dose was escalated (initial 1 mcg/kg/hr,
max 5 mcg/kg/hr). Her current fentanyl dose is 3 mcg/kg/hr.
Her vasopressor support was weaned off and she is ready for
extubation.
What recommendation would you make regarding her
fentanyl drip?
Case Discussion #2
 Discontinue fentanyl drip?
 Wean fentanyl drip?
 Convert to another agent?
Opioid Comparison
Drug
Fentanyl
Methadone
Morphine
Equianalgesic IM
Dose (mg)
Equianalgesic PO
Dose (mg)
Parenteral : Oral
ratio
0.1
--
--
Acute: 10
Chronic: 2 – 4
Acute: 20
Chronic: 2 – 4
--
10
30
1:6
1:1.5 – 2.5 chronic
Case Discussion #2
 Current fentanyl dose:

12 kg x 3 mcg/kg/hr x 24 hr/day = 864 mcg/day
= 0.864 mg/day
 Conversion to morphine:
0.1 mg fentanyl
10 mg morphine
=
X = 86 mg morphine
** CAUTION**
0.864 mg fentanyl
X