NEONATAL CLINICAL PRACTICE GUIDELINE

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1 NEONATAL CLINICAL PRACTICE GUIDELINE Title: Neonatal Substance Exposure: Assessment and Clinical Management Approval Date: February 2018 Approved by: Neonatal Patient Care Teams, HSC & SBH Child Health Standards Committee Women s Health Maternal Newborn Committee Women s Health Standards Committee Pages: 1 of 15 Supercedes: HSC: PURPOSE AND INTENT 1.1 To identify infants who may be at risk for Neonatal Abstinence Syndrome (NAS) and assess their symptoms using a standardized objective scoring tool. 1.2 To outline the steps for infant management and monitoring. Note: All recommendations are approximate guidelines only and practitioners must take in to account individual patient characteristics and situation. Concerns regarding appropriate treatment must be discussed with the attending neonatologist. 2.0 PRACTICE OUTCOME 2.1 Infants experiencing NAS will have their symptoms managed safely with minimize interruption in the maternal-newborn bonding process. 3.0 DEFINITIONS 3.1 Neonatal Abstinence Syndrome (NAS): The physiologic response of infants who are withdrawing from addictive drugs or substances they were exposed to in utero. 3.2 Neonatal Substance Exposure (NSE): When the neonate has been exposed to substances in utero that may not cause withdrawal symptoms, but may cause adverse neurological symptoms or have other effects on their development. 3.3 Healthcare Provider: refers to Pediatrician, Family Physician or Midwife who is responsible for routine infant care. 4.0 GUIDELINES 4.1 Identify infants at risk for NAS who are born to mothers with known or suspected use of addictive drugs, substances or alcohol during their pregnancy, and especially but not exclusively within 72 hours prior to delivery. See Appendix A for lists of potential drugs that may cause withdrawal in the infant. 4.2 Document known maternal drug or substance use or suspicious events or behaviors in the infant s health record and initiate social work consult. 4.3 Provide routine care to the infant and admit to the postpartum unit with the mother unless the baby has other health issues that require neonatal intensive care. See Appendix B for an algorithm for the process for infants at risk on the post-partum unit. 4.4 Upon admission, initiate assessment using either the Finnegan Neonatal Abstinence Score Short Form (see Appendix C) or The Modified Finnegan Neonatal Abstinence Score (see Appendix D). Determine frequency of scoring based on the criteria outlined below. Refer to the back of the form for descriptions of scoring criteria. 4.5 For the first 2 hours of life observe for clinical features and symptoms of NAS. (see Appendix E)

2 2 of At 2 hours of age calculate NAS Score use the sum of values for all symptoms observed since birth to determine ongoing frequency of scoring: 7 or less score every 4 hours 8 or higher score every 2 hours AND notify healthcare provider. 4.7 For newborns who remain on the mother-baby unit, communicate the baby s status to the charge nurse in the NICU once a shift with the following categories: Green: scores are less than 5 Amber: Scores are 5-7 Red: Scores are 8 or higher and baby may meet admission criteria (see below). 4.8 Discontinue scoring when scores are 7 or less for 72 hours AND the infant is on no medication. Maintain infant with mother on postpartum unit for at least 7 days if exposure is to methadone or other long acting opioids. 4.9 Admit baby to NICU if three successive scores are 8 or higher or two successive scores are 12 or higher. (Call the NICU and admit baby directly). In NICU score using the long form Modified Finnegan Neonatal Abstinence Score Call physician or in-house healthcare provider immediately if infant exhibits myoclonic jerking while awake or exhibits convulsions or seizures at any time Determine nature of pharmacologic intervention and management based on the type of drug or substance exposure as outlined in Appendix F. and according to scores: Consider pharmacologic support if scores are or average 8 or higher for 3 consecutive intervals Provide pharmacologic support if scores are or average 12 or higher for 2 consecutive intervals Select medications in the same class as the causative agent. Titrate dose to achieve treatment goals but do not increase faster than the time it takes to achieve or get close to steady state, to avoid drug accumulation and undesirable effects that may delay infant discharge Morphine is the first line treatment for infants withdrawing from methadone or suboxone/subutex. Symptoms presenting in the first 72 hours may be related to benzodiazepines or antidepressents the mother has been prescribed to treat comorbidities. In these cases, consider phenobarbital as the first medication When scores are less than 8 for at least 48 hours follow drug weaning process outlined in APPENDIX G. See also APPENDIX H for algorithms for medication escalation and weaning For infants started on Phenobarbital to manage withdrawal from Methadone and antidepressants or Benzodiazepines, consider weaning the Phenobarbital first, within the first 10 days when the benzodiazepine/antidepressant withdrawal has finished For infants greater than 3 weeks of age, use 11 as the treatment threshold score rather than 8 and manage medication adjustments accordingly, to accommodate for natural changes in sleep wake patterns with age Provide a calm, quiet environment, facilitate skin to skin / kangaroo care. Decrease sensory stimulation and provide swaddling support when infant is in bed using safe swaddling. Bathing may be too stimulating, so provide bundle bath or waterless bath whenever possible Encourage frequent breastfeeding or provision of expressed breast milk to ensure high caloric needs are met. Consider hypercaloric formula or supplements to breast milk, and IV fluids and electrolytes as indicated Facilitate appropriate follow up after discharge with Public Health Nurse and within 1 week with Pediatrician.

3 3 of REFERENCES 5.1 Backes, CH., Backes, C.R., Gardner, D., Nankervis, C.A., Giannone, P.J. & Cordero, L. (2012) Neonatal abstinencs syndrome: transitioning methadone-treated infants from an inpatient to an outpatient setting. Journal of Perinatology, 32, Bio, L.L. & Poon, C.Y. (2011). Update on the pharmacologica management of neonatal abstinence syndrome. Journal of Perinatology. 31, Casper, T & Arbour, N. (2014). Evidence-based nurse-driven interventions for the care of newborns with neonatal abstinence syndrome. Advances in Neonatal Care, 14(6), Dow, K., Ordean, A., Murphy-Oikonen, J., Pereira, J., Koren, G., Roukema, H., Selby, P. & Turner, R. (2012). Neonatal abstinence syndrome clinical practice guidelines for Ontario. Journal of Popular Therapies in Clinical Pharmacology, 19(3), e488-e Gomez-Pomar, E., Christian, A., Devlin, L., Ibonia, K.T., Concina, V.A., Bada, H. & Westgate, P.M. (2017). Analysis of the factors that influence the Finnegan neonatal Abstinence Scoring System. Journal of Perinatology, 37, Hall, E.S. et al. (2015). Implementation of a neonatal abstinence syndrome weaning protocol: A multicenter cohort study. Pediatrics. 136(4), e803-e Hamilton Health Sciences Centre (2012). Neonatal Abstinence Syndrome (NAS): Identification, Assessment, Management of, in the High Risk Newborn. Clinical Practice Guideline. 5.8 Holmes, A.P., Schmidlin, H.N. & Kurzum, E.N. (2017). Breastfeeding considerations for mothers of infants with neonatal abstinence syndrome. Pharmacotherapy, 37(7), Homes, A.V., Atwood, E.C., Whalen, B., Beliveau, J., Jarvis, J., Matulis, J.C. & Ralston, S.L. (2016). Rooming-in to treat neonatal abstinences syndrome: Improves family-centered care at lower cost. Pediatrics, 137(6), e Maguire, D., Cline, G.J., Parnell, L. & Tai, C-Y. (2013). Validation of the Finnegan Neonatal Abstinences Syndrome Tool- Short Form. Advances in Neonatal Care. 13(6), McQueen, K. & Murphy-Oikonen, J.M. (2016). Neonatal abstinence syndrome. New England Journal of Medicine. 375, NSW Department of Health (2010). Neonatal abstinence syndrome guidelines. Obtained from Ohio Children s Hospital Neonatal Research Consortium (2013) Enteral Morphine or Methadone Protocol for Neonatal Abstinence Syndrome (NAS) from Maternal Exposure Queensland Maternity and Neonatal Clinical Guidelines Program (2015). Neonatal abstinence syndrome. Obtained from Raffaeli, G., Cavallaro, G., Allegaert, K., Wildschut, E.D., Fumagalli, M., Agosti, M., Tibboel, D. & Mosca, F. (2017). Neonatal abstinence syndrome: Update on diagnostic and therapeutic strategies. Pharmacotherapy, 37(7), Sutter, M.B., Leeman, L. & His, A. (2014). Neonatal opioid withdrawal syndrome. Obstetrics and Gynecology Clinics of North America, 41, Zimmermann-Baer, U., Notzli, U, Rentsch, K & Bucher, H.U. (2010). Finnegan neonatal abstinences scoring system: normal values for first 3 days and weeks 5-6 in non-addicted

4 4 of 15 infants. Addictions, 105, PRIMARY AUTHORS 6.1 Fabiana Postolow, Neonatologist 6.2 Lisa Merrill, Neonatal Patient Care Manager 6.3 Jarrid McKitrick, Child Health Pharmacy Manager 6.4 Cathy Sabiston, NICU Pharmacist

5 5 of 15 APPENDIX A Potential Drugs of Abuse Table 1: Drugs when used within 72 hours before birth place infant at risk for NAS Opioids Central Nervous System Depressants Hallucinogens Methadone Alcohol Inhalants ( sniff ): Morphine Barbiturates Solvents Codeine Benzodiazepines (eg. Valium) Aerosols Heroin Glue Hydromorphone (Dilaudid) Gasoline Meperidine (Demerol) Paint thinner Oxycodone (Percodan) Nail polish Pentazocine (Talwin) Fentanyl Buprenorphine/Naloxone (Suboxone) Buprenorphine (Subutex) Table 2: Drugs that may cause adverse neurological symptoms but not withdrawal symptoms Central Nervous Central Nervous Hallucinogens Other System Stimulants System Depressants Caffeine Cocaine Methamphetamine Marijuana Hashish Nitrites Nitrous Oxide Nicotine (in large quantities) Crystal meth speed Methylphenidate (Ritalin) Phenylpropanolamine

6 6 of 15 APPENDIX B

7 Score Title: 7 of 15 APPENDIX C Finnegan Neonatal Abstinence Scale Short Form Directions: Score infant every 3-4 hours on all items, adding the total score. Score 0 if not present. Choose only one item from crying, sleeps, tremors and respiratory rate to score (if not 0 ). NAS Signs AM PM COMMENTS Mild/Early Signs Crying: unable to console in 5 min 2 or cries 25-50% of the time Crying: unable to console > 5 min 3 or cries > 50% of the time Sleeps < 1 hour after feeding 3 Sleeps < 2 hours after feeding 2 Sleeps < 3 hours after feeding 1 Increased muscle tone 2 Moderate/Progressing Signs Mild tremors, undisturbed 3 Moderate-severe tremors, 4 undisturbed Respiratory rate > 60/min 1 Respiratory rate > 60/min with 2 retractions Sweating 1 Excessive sucking 1 Score (range 0 16) Average Daily Score Initials of Scorer 1 TOTAL SCORE Initials of Scorer 2 (optional) This scale was derived from the Modified Finnegan Neonatal Abstinence Scale (Finnegan & Kaltenbaach, 1992). Recommend: If the infant scores meet treatment criteria (see #4.9), switch to the full Neonatal Abstinence Scoring to capture the full range of additional withdrawal signs.

8 8 of 15 APPENDIX D

9 9 of 15 APPENDIX E Clinical Feature & Symptoms of NAS Clinical presentation of neonatal drug withdrawal is dependent upon the drug(s), timing and amount of the last maternal use, maternal and infant metabolism and excretion, and other less definable factors. W I T H D R A W A L Wakefullness Irritability Tremulousness, Temperature Instability, Tachypnea Hyperactivity, High-pitched Cry, Hyperacusia (sensitivity to sound), Hyper-reflexia, Hypertonia Diarrhea, Diaphoresis, Disorganized Suck Rub marks, Respiratory Distress, Rhinorrhea Apnea, Autonomic Dysfunction Weight Loss Apathy, Alkalosis, Acidosis, Appetite Increased or Decreased Lacrimation (tears), Lassitude (weariness) Neurologic Excitability Gastrointestinal Dysfunction Autonomic Signs Tremors Poor feeding Sweating Irritability Uncoordinated and constant Nasal stuffiness Increased Wakefulness sucking Fever High pitched cry Vomiting Mottling Increased muscle tone Diarrhea (leads to diaper Temperature instability Hyperactive deep tendon dermatitis) reflexes Dehydration Exaggerated moro reflex Poor weight gain Seizures Frequent yawning and sneezing

10 10 of 15 APPENDIX F Recommended Medication Management for Infants with NAS Select medication based on drug or substance neonate withdrawing from: Morphine is the initial drug of choice for opioid withdrawal. Use in cases where mother dependent on opioid due to: (i) (ii) (iii) illicit drug use treatment for addiction chronic pain Examples Buprenorphine (Suboxone, Subutex) Codeine (includes Tylenol #1, #2, #3 and 222 s) Fentanyl Heroin Hydromorphone (Dilaudid) Meperidine (Demerol) Methadone Morphine Oxycodone (OxyNeo, Percocet and Percodan) Pentazocine (Talwin) Phenobarbital should be the initial medication chosen for: (i) (ii) (iii) medical management of non-opioid withdrawal in cases were maternal drug(s) used are unknown there is polysubstance exposure Alcohol intoxication Amphetamines Benzodiazepines (Alprazolam, Clonazepam, Diazepam, Lorazepam, Temazepam) Inhalants: Solvents, aerosols (gasoline, glue, paint thinner) Antidepressants: SNRI: Venlafaxine (Effexor), SSRI: Citalopram (Celexa), Fluoxetine (Prozac), Sertraline (Zoloft)

11 11 of 15 Morphine-First line treatment for opioid withdrawal PO/ NG/ OG Dosing Information Load: milligrams/kg/dose q2h and PRN until symptoms controlled *Maximum of 3 initial loads with a maximum total dose of 1 milligram/kg/24h Maintenance dosing recommendations: (escalate to next step only if needed and only after giving a load) Step 1: 0.05 milligrams/kg/dose q4h Step 2: 0.1 milligrams/kg/dose q4 h Step 3: 0.15 milligrams/kg/dose q4 h Step 4: 0.2 milligrams/kg/dose q4 h In the first 24 hours of treatment: If infant s symptoms are controlled following 1 load then start maintenance at 0.05 milligrams/kg/dose q4h. If infant s symptoms are not controlled and the infant requires more than 1 load then start maintenance dose of 0.1milligram/kg/dose q4h. **Do not increase the maintenance past Step 2 in the first 24 hours. **Maximum oral dose (including loading doses) = 2 milligrams/kg/day Monitoring, Additional Information Establish continuous cardiorespiratory monitoring Note: risk of respiratory depression with doses greater than or equal to 1 milligram/kg/24h, especially in combination with other sedatives (e.g. phenobarbital, lorazepam) If the infant has a large emesis within 5-10 minutes of receiving the Morphine dose, repeat the dose. Note: to reduce the risk of the infant vomiting please give the dose before a feed and ensure the infant is not overfed. Clonidine- Second line treatment for opioid withdrawal in addition to Morphine. Add Clonidine when Morphine maintenance dose has reached 0.15milligrams/kg/dose q4h and three consecutive scores greater than 8 or two greater than 12. PO/ NG/ OG Dosing Information Maintenance: (escalate to next step only if needed and following 24 hours of a dose increase) Step 1: Start at 1 microgram/kg/dose q6h Step 2: (increase after 24 hours on Step 1): 1.5 micrograms/kg/dose q6h Step 3: (Increase after 24 hours on Step 2): 2 micrograms/kg/dose q6h Maximum daily dose: 8 micrograms/kg/24 hours Monitoring, Additional Information Monitor BP prior to dose and 1hr post dose: for the first 2 doses when therapy is initiated for 2 doses following each dosage increase

12 12 of 15 Phenobarbital- First choice for polysubstance exposure treatment Third line treatment for opioid withdrawal in addition to Morphine and Clonidine if NAS scores remain above the treatment threshold. PO/ NG/ OG Dosing Information Load: 20 milligrams/kg/dose (may administer as 10 milligrams/kg/dose X 2 doses given over 2 consecutive feeds) Maintenance: milligrams/kg/24h divided BID or TID start 12 hours after load Monitoring, Additional Information If patient sedated, consider obtaining a serum phenobarbital level. If patient receiving a dose of greater than 5mg/kg/day for longer than 1 week, consider obtaining a serum phenobarbital level. Lorazepam-Additional option for symptom management when infant not responding to other 3 recommended medications. PO/ NG/ OG Dosing Information 0.05 milligrams/kg/dose q4h PRN (Range milligrams/kg/dose q4h PRN) Monitoring, Additional Information

13 13 of 15 APPENDIX G Medication Weaning Protocol Once NAS scores have consistently been below 8 for hours, begin weaning. Please note ONLY ONE CHANGE per 48 hour until Morphine dose reaches 0.05 milligrams/kg/dose q4h Morphine: PO/NG/OG First step 0.15 milligrams/kg/dose q4h Do not change dosing Second step 0.12 milligrams/kg/dose q4h interval unless as indicated Third step 0.1 milligrams/kg/dose q4h in fifth step. Fourth step 0.08 milligrams/kg/dose q4h Notes: Fifth Step 0.05 milligrams/kg/dose q4h q6h q8h q 12h x 48 hours stop Follow step decreases as indicated or until the dose reaches a minimum volume of 0.1mL (of a 1mg/mL solution) then change the dosing interval to prevent the need for further dilution of the medication. If infant does not tolerate weaning: Consult pharmacist to adjust weaning schedule; Provide extra dose of Morphine (equal to the current maintenance dose) and then: 1. Continue with current maintenance dosing schedule OR 2. Go back to previous step of weaning protocol maintenance dose. If infant is sensitive to weaning or is not tolerating weaning well (i.e. scores are increasing) then consider weaning by 10% over a longer length of time (i.e. one change q72hours) If infant is receiving Morphine only for NAS treatment at 0.05 milligrams/kg/dose q4h consider weaning every 24 hours, if tolerated. Once infant reaches 0.05 milligrams/kg/dose q8h and after consultation with social work and family, consider possibility of discharge home on medication to complete weaning course of treatment. o Note: Slower weaning dose may be considered for all infant s discharged to community. Clonidine: PO/NG/OG Once Morphine dose reaches 0.05 milligrams/kg/dose q4h then: Decrease Clonidine by 0.5 micrograms/kg/dose q48hours until dose reaches 1 microgram/kg/dose q6h x 48 hrs then lengthen interval to 1 microgram/kg/dose q8h x 24 hours then discontinue. Note: If weaning is well tolerated then consider alternate weaning doses of Morphine and Clonidine q48hours (i.e. one change q24hours). If receiving Clonidine only then consider one change in weaning dose q24hours. Note: Monitor BP q6h x 48 hours once clonidine discontinued to monitor for rebound hypertension. Phenobarbital: PO/NG/OG Initiate weaning of Phenobarbital 24 hours after Clonidine is discontinued. If maintenance dose is 7.5 milligrams/kg/day BID or TID then decrease dose to 5 milligrams/kg/day BID for 5-7days. If maintenance dose is 5 milligrams/kg/day BID then decrease dose to 2.5 milligrams/kg/day once per day for 5-7days then discontinue.

14 14 of 15 APPENDIX H Algorithms for Medication Escalation and Weaning

15 15 of 15

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