Revised Neonatal Opioid Withdrawal Syndrome (NOWS) Protocol PDF

## NAS Saturday, November 9, 2024 1:08 PM **TO:** - Neonatologists - Neonatal Nurse Practitioners - Pediatric Residents - Family Medicine Faculty and Residents - NICU and Newborn Charge Nurses - Pharmacy Staff - Neonatal Data Base - Renee Rogers - Cathy McCurley - Ellen Dean - Jennifer Shariat...

## NAS Saturday, November 9, 2024 1:08 PM **TO:** - Neonatologists - Neonatal Nurse Practitioners - Pediatric Residents - Family Medicine Faculty and Residents - NICU and Newborn Charge Nurses - Pharmacy Staff - Neonatal Data Base - Renee Rogers - Cathy McCurley - Ellen Dean - Jennifer Shariat - Karen Williams - Brooke Olson **FROM:** Richard M. Whitehurst Jr., M.D. Professor of Pediatrics Division of Neonatology **DATE:** July 1, 2022 **RE:** REVISED PROTOCOL FOR NEONATAL ABSTINENCE SYNDROME (NAS) Attached is the REVISED protocol for Neonatal Opioid Withdrawal Syndrome (NOWS) to improve the treatment for these infants. Revised as of July 1, 2022. **To summarize:** 1. Changing the name to NOWS. 2. Changing our pharmacological therapy to one based on the Finnegan score. 3. The weaning procedure has changed. 4. Adding Phenobarbital therapy to the protocol. 5. Adjusting the timing of when to start and maintain Finnegan scoring. ## **Management of Neonatal Opioid Withdrawal Syndrome** ### **Neonatal Opioid Withdrawal Syndrome Overview** Neonatal opioid withdrawal syndrome (NOWS) refers to a constellation of clinical findings associated with opioid withdrawal in newborn infants that had in utero exposure to opioid (naturally occuring, synthetic, or semi-synthetic) medications. In most cases, exposure occurs during pregnancy, but NAS may also describe a syndrome secondary to withdrawal of opioids and sedatives administered postnatally to infants with serious illnesses. ### **Opioid Addiction** The over-prescription, diversion and illegal use of opiate medications is a major public health burden for maternal and child health. Data from the National Survey on Drug Use and Health indicates that the rate of non-medical use of analgesics in pregnancy since 2012 (Substance Abuse and Mental Health Services Administration, 2014) has increased by 31% with no change in the use rate in the non-pregnant population. Heroin use has dramatically increased in the United States over the last 10 years and we have begun seeing heroin use in our pregnant population. Acute use of heroin and other opioids stimulate the opiate receptors in the brain which may result in symptoms including euphoria, respiratory depression, analgesia, and nausea. Chronic use of opioids is associated with tolerance; higher doses of the drug are required to obtain the same effect. Tolerance leads to dependence, in which the neurochemical balance of the drug leads to a withdrawal syndrome during abstinence. Opioid withdrawal is characterized by a constellation of symptoms including agitation, nasal congestion, yawning, diaphoresis, muscle cramps, diarrhea, nausea, vomiting, and depression. Several mechanisms have been proposed to explain the phenomena of tolerance, dependence and withdrawal in the setting of chronic opioid exposure. These include: - Increased metabolic breakdown of opioid compounds, - Decreased neurotransmitter release resulting in an increased number and sensitivity of post-synaptic receptors, - Down-regulation of opioid receptors resulting in decreased production of endogenous endorphins. Due to these changes, some opioid dependent patients will need medication-assisted treatment for prolonged periods, possibly for the rest of their life. The standard of care for opioid-dependent pregnant patients is medication-assisted treatment with opioid-agonists in conjunction with counseling and supportive services. (US Department of Health and Human Services, Substance Abuse and Mental health Services Administration, 1993). Methadone and buprenorphine are the most commonly prescribed medications for these patients. ### **Opioids and Pregnancy** The cycle of opioid use and withdrawal is particularly devastating for the developing fetus. The repetitive pattern of use and withdrawal leads to fetal hypoxia and utero-placental insufficiency resulting in an increased risk of prematurity, fetal demise, and low birth weight. Comprehensive prenatal care is essential for these patients. Medication-assisted treatment has been the standard of care for pregnant opioid-dependent patients. At appropriate dosages, methadone, a synthetic opioid, will eliminate signs and symptoms of withdrawal. It will reduce cravings and block the euphoric effects should supplemental opioids be used. The long life and predictable dosing prevents erratic opioid levels in the fetus, and is associated with a longer duration of pregnancy and improved fetal growth. As the pregnancy progresses, methadone is metabolized more rapidly and higher doses are required. Although there were early reports suggesting that the dose of methadone correlated with the incidence and severity of neonatal withdrawal signs, recent evidence does not demonstrate such a relationship. It is well accepted that lowering the dose during pregnancy may lead to increased illicit drug use, thus exposing the mother and fetus to more harm. Buprenorphine, a partial opioid-agonist, has recently been approved by the United States Food and Drug Administration for treatment of opioid addiction in outpatient office setting. Buprenorphine is associated with a decreased incidence of neonatal withdrawal when compared with methadone. In addition to the concern regarding withdrawal theprevalence of hepatitis B, hepatitis C, and human immune-deficiency virus (HIV) is elevated in pregnant opioid-dependent patients, primarily due to needle sharing and unsafe sexual practices. Women should be screened for these infections, and in the case of HIV infection, treatment should be initiated. The management of addiction in pregnancy is highly complex and attention must be focused not only on medication, but also on the complicated psychological and social needs of these women. A high number of these women have a history of domestic violence, are poorly educated, financially constrained, and have poor relationships with partners who may also be substance abusers. They frequently have dysfunctional families with a high prevalence of substance abuse and alcoholism. Many of these women have co-morbid psychiatric conditions, most commonly depression and bipolar disorder, and suffer low self-esteem. ### **Neonatal Opioid Withdrawal Syndrome: Clinical Presentation** The newborn with opioid withdrawal presents with central nervous system excitability, vasomotor signs and gastrointestinal signs. The timing of onset varies. Infants exposed to heroin or other short-acting opiates will typically presents within the first 48-72 hours. Infants exposed to methadone or buprenorphine will often present later, usually within the first 5 days. The infant is assessed using a standardized scoring system, such as the system developed by Finnegan in 1975 and modified by Jansson in 2009, that quantifies the severity of signs of withdrawal. When scores are elevated, the infant may be a candidate for pharmacologic treatment. Newborn urine and meconium drugs screens may aid in the diagnosis when the mother has not been in a treatment program. Urine testing generally reflects drug exposure within several days, depending up on the drug. Results of urine testing are rapidly available; however, there is a high false negative rate given the rapid clearance of most drugs and the difficulty in obtaining sufficient urine from a newborn in the first day of life. Meconium testing offers the advantage of assessing drug exposure during the previous several months. However, meconium test results are frequently not available before discharge. The differential diagnosis should include sepsis, hypoglycemia, hypocalcemia, hypomagnesemia, hyperthyroidism, perinatal asphyxia, and intracranial hemorrhage Recent maternal serologies for hepatitis B, hepatitis C and HIV should be determined. ### **Treatment** Approximately 35 percent of infants born at USACWH to women on opioids will receive treatment for opioid withdrawal. At the delivery of a known or suspected opioid-dependent mother, naloxone should be avoided in resuscitation of the infant because it's administration may precipitate seizures. Supportive care and breastfeeding are essential in the management of infants exhibiting signs of withdrawal. Keeping the mother and baby together at all times is critical in the care of NAS. Therefore all physician and nursing assessments should be done in the patient's room in the company of the parents. Decreased stimulation, swaddling, and frequent on demand feedings are beneficial. Pharmacologic therapy is indicated for infants with increasing severity of signs and in cases of significant vomiting, diarrhea, or excessive weight loss. Infants may be treated with a variety of medications including short acting opioids such as morphine sulfate, clonidine, and phenobarbital. The latter two are usually reserved for use when the symptoms are so severe that morphine alone is not sufficient. Breastfeeding is always encouraged unless the mother is HIV positive or has ongoing illicit drug use with no signs of recovery. ### **Discharge Considerations** The opioid-dependent new mother undergoes significant stress during the post - postpartum period. A comprehensive discharge plan that addresses maternal substance abuse treatment, a safe environment, parenting and community support are essential. ## **Protocol for the management of NAS at USA CWH** **Revised 07/2022** 1. Infants born to mothers taking a long-acting opioid (such as methadone or buprenorphine) will be observed for 5 days in the hospital and for 3 days for mothers taking short acting opioid (such as hydrocodone). 2. Mothers should be encouraged to keep the infant in their rooms at all times. 3. Physician and Nursing assessments should be done in the patient's room at all times. This includes NAS scoring. ### **Supportive Care** 1. Feeding should be by breast and on demand if possible. 2. Minimal stimulation. Keep the room darkened, quiet and reduce noxious stimuli as much as possible. 3. Swaddling and positioning: use gentle swaddling with positioning that encourages flexion rather than extension. 4. Prevent excessive crying with a pacifier, kangaroo care, cuddling and rocking. ### **Site of Care for opioid-exposed Newborn** Unless otherwise indicated the infant will stay in the mother's room until she is discharged. If the infant needs continued observation time and/or is requiring pharmacological therapy, he/she will be transferred to the NICU private room so mother can continue to provide most of the care for her infant. ### **Neonatal Abstinence Syndrome (NAS) Scoring** 1. Use modified Finnegan Neonatal Abstinence scoring system. (See Appendix 1 Adopted from L. Jansson, 2009) 2. NAS score at 06:00 and 18:00 hours daily begin with the first time that occurs after birth. 3. Once the infant reaches a score of 9 or greater the infant should then be scored after every feed. If the infant is feeding every hour then scoring will be done every two hours. 4. NAS scoring should occur in the mother's room, whenever possible. 5. Do not wake infant for scoring unless the interval is > 5 hours. ### **Treatment** 1. If infant has 2 consecutive scores of > 9 with no confounding variables, or 3 scores ≥ 9 in a 24 hour period, consider pharmacologic treatment. 2. If the infant has a seizure, begin pharmacologic treatment regardless of what the NAS score is. 3. If the infant has significant GI symptoms, is losing weight consistently and not tolerating PO feeding, begin pharmacologic treatment regardless of what the NAS score is. 4. If the infant meets criteria for pharmacologic treatment, the infant should be treated with morphine sulfate. | Score | Morphine loading dose | Morphine maintenance dose | |---|---|---| | 9-11 | 0.08 mg/Kg q 3hr x2 | 0.04 mg \ Kg q 3hr | | 12-14 | 0.1 mg/Kg q 3hr x2 | 0.06 mg \ Kg q 3hr | | 15-17 | 0.12 mg/Kg q 3hr x2 | 0.08 mg \ Kg q 3hr | | > 18 | 0.14 mg/Kg q 3hr x2 | 0.1 mg/Kg q 3hr | After the maintenance dose has been reached and the NAS score remains equal to or greater than 9: increase the dose as follows. | Score | Morphine New Dose | |---|---| | 9-11 | Previous dose + 0.02 mg \ Ng | | 12-14 | Previous dose + 0.04 mg \ Kg | | 15-17 | Previous dose +0.06 mg \ Kg | | > 18 | Previous dose + 0.08 mg/Kg | Do not exceed a maximum of 0.14 mg \ Kg \ dose unless there is approval by the attending Neonatologist. Vital signs will be done with each Finnegan scoring and either cardiorespiratory or pulse oximetry monitoring will be done until 24 hours of good control of the NAS symptoms has been obtained, then monitoring with Pulse Oximetry only when the infant is prone. ### **Clonidine PO** For infants requiring morphine 0.14mg/kg every 3 hours and scores that continue to be ≥ 9, clonidine (1.5 micrograms/kg/dose) will be added divided every 6 hours. Continue with the morphine schedule as described in the initial therapy. Blood pressure is to be monitored prior to each dose and the dose of clonidine should be held if the mean blood pressure is less than 40 in term infants and 30 in preterm infants. ### **Phenobarbital PO** Treatment failure is defined as any infant with two consecutive Finnegan scores > 9 while receiving morphine 0.14mg/kgevery 3 hours and after receiving clonidine for at least 48 hours (1.5 micrograms/kg/dose every 6 hours). Therapy for treatment failure will include the current medications (morphine and clonidine) with the addition of phenobarbital. Give a phenobarbital loading dose of 10 mg/kg (if symptoms have not improved within 12 hours after loading with 10mg/kg Phenobarbital another 5 mg/kg bolus may be given). A maintenance dose of 2mg/kg/dose every 12 hours will begin after loading. Check phenobarbital levels weekly to assure the level is <20 mcg/ml. ### **Weaning** 1. We will begin weaning when the NAS scores have remained < 9 for 48 hours 2. If started, maintain clonidine at current dose and begin weaning morphine by 0.01-0.02 mg/kg every 24 hours until the morphine dose has reached 0.04 mg/kg. Once the morphine dose has reached 0.04 mg/kg/dose stop weaning morphine and begin weaning clonidine. Begin weaning clonidine by 50% then discontinue clonidine the next day. Blood pressure must be monitored for 48 hours after discontinuing clonidine. 3. Once the clonidine has been weaned off for 24 hours resume weaning morphine 4. If morphine is the only medication use, then wean morphine dose by 0.01-0.02 m every 24 hours until discontinued. 5. Increase Morphine dose back to previous dose (mg/kg) if there are two consecutive scores of ≥ 9 or three times in a 24-hour period. 6. Phenobarbital will be discontinued after discharge. 7. Infant may be discharged when off morphine for 24 hours with a score of <9. ### **Discharge Instructions for infants on Phenobarbital.** No need to obtain Phenobarbital levels As part of the discharge planning, alert the PCP not to weight adjust or increase the Phenobarbital. Recommend the PCP to cut the dose of Phenobarbital by half at 2 weeks post discharge and discontinue completely at 1 month. **Appendix 1: Neonatal Abstinence Syndrome Scoring Form** | Score | Time | Time | Time | Time | Time |Time | Time | Time | |---|---|---|---|---|---|---|---|---| | 2 | | | | | | | | | | 3 | | | | | | | | | | 3 | | | | | | | | | | 2 | | | | | | | | | | 1 | | | | | | | | | | 1 | | | | | | | | | | 2 | | | | | | | | | | 1 | | | | | | | | | | 2 | | | | | | | | | | 1 | | | | | | | | | | 2 | | | | | | | | | | 1 to 2 | | | | | | | | | | 1 to 2 | | | | | | | | | | 8 | | | | | | | | | | 1 | | | | | | | | | | 1 | | | | | | | | | | 1 | | | | | | | | | | 1 | | | | | | | | | | 2 | | | | | | | | | | 2 | | | | | | | | | | 2 | | | | | | | | | | 2 | | | | | | | | | | 2 | | | | | | | | | | 1 to 3 | | | | | | | | | **Appendix 2: neonatal Abstinence Syndrome (NAS) Scoring** *For every sign except sleeping, a score of 0- not present. **Sleeping ** - Sleeps 3 or more hours continuously (score 0) - Sleeps 2-3 hours after feeding (score-1) - Sleeps 1-2 hours after feeding (score-2) - Sleeps less than 1 hours after feeding (score-3) - When repeating a score with I hour after feeding: use the same score obtained before the feeding. - Do not score for sleep if the infant is > 1 month of age **Moro Reflex** - Cup infant's head in your hand and raise his/her head about 2-3 inches above the mattress, the drop your hand while holding the infant. - The infant should be quieted if irritability or crying is present. This will insure that the jitteriness, if present, is due to withdrawal rather than agitation. - Hyperactive Moro: arms stay up 3-4 sec with or without tremors (score=1) - Markedly Hyperactive MORO: arms stay up > 4 sec with or without tremors (score = 2) **Sweating** - Wetness felt on the infant's forehead, upper lip (score 1) - Sweating on the back of the neck may be from overheating such as swaddling. **Nasal Stuffiness** - Any nasal noise when breathing (score-1) - Runny nose may or may not be present **Sneezing** - Infant sneezes 4 or more times in the scoring interval of 3-4 hours (score-1) **Tachypnea** - Tthe infant must be quieted if crying first; count respirations for full minute - Respiratory rate > 60/min (score =2) **Nasal Flaring** - Outward spreading of the nostrils during breathing (score=1) **Poor Feeding** - Poor feeding is defined as any 1 of the following (score 2) - Infant demonstrates excessive sucking prior to feeding yet sucks infrequently while feeding and takes small amount of formula/breast milk. - Demonstrates as uncoordinated sucking reflex (difficulty sucking and swallowing) - Infant continuously gulps while eating and stops frequently to breathe. - Inability to close mouth around bottle breast. - Feeding takes more than 20 minutes. **Tremors** - Tremors jitteriness - Involuntary movements that are rhythmical. - If the infant is asleep, it is normal to have a few jerking movements of the extremities. - Mild tremors: hands or feet only, last up to 3 seconds (score=1) - Moderate-severe tremors: arms or legs, last more than 3 seconds (score 2) - Undisturbed: tremors that occur in the absence of stimulation **Increased Muscle Tone** - While the infant is lying supine, extend and release the infant's arms and legs to observe for recoil. - Infant supine, grasp arms by wrists and gently lift infant, looking for head lag. - Difficult to straighten arms but is possible, and head las is present (score=1) - No head lag noted or arms or legs won't straighten (score=2) **Excoriation** - Red or broken skin fromexcessiverubbing (eg: extremities or chin against lines). - Skin red but intact or is healing and no longer broken (score=1) - Skin breakdown present (score=2) - Only score once unless area worsens or enlarges - Consoling calms infant in 5 minutes or less (score=1) - Consoling calms infant in 6-15 minutes or less (score = 2) - Consoling takes more than 15 minutes or no amount of consoling calms infant (score 3) **Regurgitation/ Vomiting** - Frequent regurgitation (vomits whole feeding or vomits 2 or more times during feed) not associated with burping (score-2) **Loose Stools** - Infant has a stool that is at least half liquid (score = 2) - When repeating a score within 1 hour after feeding: use the same stool score obtained before feeding. **Current Weight> 90% of Birth Weight** - Infant is weighed once a day then score is carried through the rest of the day. - Weight is <90% of birth weight (score=2)