Treatment Guidelines for Neonatal Narcotic Abstinence Syndrome with Diluted Oral Morphine and Clonidine Background Morphine sulfate has been recommended by the AAP as the first-line agent for the pharmacologic treatment for neonatal narcotic abstinence syndrome (NNAS). Clonidine has been widely used as a non-opioid alternative for managing opioid withdrawal in adults. A recent study (Agthe et al, Pediatrics 2009) comparing Morphine with a combination of Morphine and Clonidine for the treatment of NNAS demonstrated shorter duration of therapy, lower Morphine doses, and shorter hospital stays for infants receiving combination therapy. Clonidine use has been shown to be associated with a clinically-insignificant lowering of the heart rate (5bpm) and blood pressure (5mmHg). No other adverse effects were noted. Management The pharmaceutical treatment should be used in combination with supportive measures including: swaddling, holding, decreasing environmental stimuli, pacifiers, and rocking. A. INITIATION 1. Begin NNAS scoring every 4-6 hrs (every other feeding). 2. Initiate combination therapy with oral Morphine and Clonidine for three consecutive withdrawal scores are 8 or any one time score is 12 using the Neonatal Withdrawal Inventory (NWI) scale. 3. Initial doses: a. Morphine at 0.05 mg/kg/dose PO every 3 hours with feedings. b. Clonidine at 0.75 mcg/kg/dose every 3 hours (rounded to nearest 0.1mcg) 4. Increase Morphine dose by 0.01mg/kg/dose every 12 hours until withdrawal symptoms are controlled (two consecutive NWI scores <8). Morphine dosing should be titrated to the desired effect, with a usual maximum dose of 0.2 mg/kg every 3 hours. 5. Adjust Clonidine dose to weight weekly to maintain daily dose of 6mcg/kg/day. 6. If maximum dose for Morphine is reached (0.2 mg/kg/dose): Consider adding Phenobarbital (loading dose 20mg/kg in two divided dose of 10mg/kg every 12 hours), followed by a maintenance dose of 5mg/kg/day once
daily. Clonidine should be discontinued 24 hours after completion of the Phenobarbital loading dose. B. WEANING 1. Weaning should begin after NNAS symptoms are controlled for 48 hrs (total NWI score 24 over three consecutive measurements). 2. Begin weaning Morphine by 0.04mg (flat dose) or by 10% of the highest dose, whichever is greater. Weaning can be done every day provided that the NWI scores are stable during weaning. If two scores in a 24-hour period are 8, consider increasing the dose back to the previous effective dose. 3. Morphine may be discontinued from a dose of 0.06mg (flat dose). 4. After 24 hours off Morphine, the Clonidine may be decreased by 50%. If NWI scores remain stable for 12 hours, the Clonidine may be discontinued. If total NWI scores exceed 24 over the next three measurements after stopping Clonidine, restart Morphine at 0.04mg every 3-4 hours with feeding. 5. Patient may be discharged if NWI scores remain stable (total NWI Score 24 over three consecutive measurements for 1-2 days) off medication and the following criteria are met - a. Infant is taking oral feeds and gaining weight b. All newborn assessments/procedures have been completed (Hepatitis B Vaccination, hearing screening test, State Screening Tests) c. Social work has cleared the infant and a suitable home is arranged d. VNA is set up if deemed necessary e. Follow-up with the PMD is arranged C. BP MONITORING 1. Monitor BP per unit protocol (at least q shift) for the first 48 hours after starting Clonidine. If blood pressure remains stable, continue BP measurements every 12 hours during treatment. 2. Monitor BP per unit protocol (at least q shift) when discontinuing Clonidine and for the first 24 hours off Clonidine.
References 1. AAP Committee on Drugs. Neonatal Drug Withdrawal. Pediatrics 1998; 101: 1079-1088. 2. Agthe AG, et al. Clonidine as an Adjunct Therapy to Opioids for Neonatal 3. Abstinence Syndrome: A Randomized, Controlled Trial. Pediatrics. 2009 May;123(5):e849-56. Epub 2009 Apr 27. 4. Opiate Treatment for Opiate Withdrawal in Newborn Infants. 2005 Cochrane Review. 5. Zahorodny W, Rom C, Whitney W, Giddens S, Samuel M, Maichuk G, Marshall R. The neonatal withdrawal inventory: a simplified score of newborn withdrawal. J Dev Behav Pediatr. 1998 Apr;19(2):89-93. Reviewed by Yogangi Malhotra, MD, Dael Nelson, PAC, David Cheromcha, MD, Richard Ehrenkranz, MD, Matthew Grossman, MD, Barbara Sabo, APRN
NEONATAL WITHDRAWAL INVENTORY SCALE Hypertonia 2 Regurgitaion/Vomiting 2 Loose,watery stool 2 Sneezing or yawning 1 Sweating or mottling 2 Hyperactive Moro Reflex 2 Tremors when disturbed OR 3 Tremors undisturbed 4 Irritability OR 1 Crying or frantic fist sucking OR 2 Excoriation OR 3 Continuous Crying (restless even after intervention) 4 TOTAL Score # 1 # 2 # 3 # 4 # 1 # 2 # 3 # 4 # 1 # 2 # 3 # 4 # 1 # 2 # 3 # 4 # 1 # 2 # 3 # 4 Morphine Dose Clonidine Dose Other: Dose Other: Dose Temperature Respiratory Rate DATE: TIME: INITIALS: mg/kg mcg/kg /kg /kg celcius
NEONATAL WITHDRAWAL INVENTORY SCALE HELPFUL HINTS: 1 2 3 4 5 STEPS IN SCORING Conduct scoring within one hour prior to every other feeding (a 6 hour caregiving interval). If NPO conduct scoring every 6 hours. Observe infant without disturbing the infant for 1 minute. Encourage the baby to a quiet awake state. Take note of the infant's ability to transition states smoothly. While in quiet awake state, assess moro reflex, measure axillary temperature, inspect skin for signs of excoriation and change diaper.. Following your observations, score the infant using the neonatal withdrawal inventory criteria. HYPERTONIA SCORING FYIs Score for increased tone that may interfere with suck swallow coordination as compared with a non-withdrawing newborn of comparable gestation and condition. For the intubated or NPO infant, this section should assess the infant's muscle tone as compared to the non-withdrawing newborn of comparable gestation and condition. REGURGIATION Score for true emesis of formula/bm seen in the mouth not associated with burping following a feeding. For the intubated who is feeding score for true emesis seen following a gavage feeding or for an aspirate prior to the feeding greater than 1/3 of the previous feeding For NPO infants, only score if infant has large aspirate or is vomiting. LOOSE, WATERY STOOLS Stools are minimally formed or no solid stool noted. Often you will see a water ring in the diaper. SNEEZING OR YAWNING Score if the baby sneezes or yawns at least 6-8 times in the 6 hour time frame. SWEATING OR MOTTLING Score if you see sweating on the upper lip or forehead. Ensure the infant is not over bundled and the isolette is not overheated. Score for mottling not associated with hypothermia/cold stress (axillary temp < 36.0). HYPERACTIVE MORO RELEEX A moro reflex is expected... Score infant if an exaggerated moro response is exhibited compared to the non-withdrawing newborn of comparable gestation and condition. For the intubated infant do a modified moro. TREMORS Tremors are high frequency, low amplitude "shaking" of the arms and/or legs. If tremors are only present when disturbed such as after a physical exam, unbundling, taking vital, etc. then score as 3. If the tremors are present without any stimulation, then score a 4. BEHAVIOR Choose the one description which describes the baby ANY TIME during the 6 hour scoring interval. Irritable: remains restless even after feeding or other intervention to calm infant such as swaddling, rocking,offering pacifier, kangaroo care. Crying or frantic fist sucking Fresh excorioation of chin, face, knees or elbows. This means the baby is so irritable he/she is rubbing the face or extremities on the bedding, causin excoriation of the points of contact. Do not score for a diaper rash. Continuous crying and an inability to sleep or feed dispite all interventions for calming the baby.