Neonatal Abstinence Syndrome:

Neonatal Abstinence Syndrome: Rethinking Our Approach Matthew Grossman, M.D. Assistant Professor of Pediatrics Yale School of Medicine Quality and Safety Officer Yale-New Haven Children s Hospital

Patrick, et al. Journal of Perinatology. 2015; 35:650-655 Source: http://familytalk.ca/heroin/

Patrick, et al Journal of Perinatology, 2015

Source: Grossman Family Album

Source: http://wings.buffalo.edu/aru/preprohibition.htm Langenfeld, et al. Drug and Alcohol Dependence 2005;77:31 6.

Source: http://olivier-dogot.blogspot.com Jackson L, et al. Archives of Disease in Childhood 2004;89: F300 4.

Source: http://www.bad-drug.net Coyle MG. Journal of Pediatrics 2002;140:561 4

Source: http://www.projectknow.com MS Brown et al. Journal of Perinatology 2014; (1-6)

Agthe, et al. Pediatrics 2009;123:e849 56. Source: http://www.recovery.org

Standard Approach Medications NICU Finnegan Scores Medication Dosing Staff cares for the baby

Length of Stay: Methadone-Exposed Infants 30 25 LOS (days) 20 15 P <.02 10 5 0 2003-June 2006 July 2006-2009

Medication Studies DTO vs. DTO plus clonidine: 17 days vs. 12 days Morphine vs. Phenobarbitone: 8 days vs. 12 days Morphine vs. DTO 30 days vs. 27 days DTO vs. DTO plus Phenobarbitone 79 days vs. 38days Methadone vs. Morphine 17 days vs. 24 days

Percent of NAS Patients Treated with Morphine 100.0% 90.0% 80.0% % Treated with Morphine 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% 2003 2004 2005 2006 2007 2008 2009 2010 Year

Length of Stay: Methadone exposed infants 70.0 60.0 50.0 Mean=22.5 UCL 47.1 LENGTH OF STAY (Days) 40.0 30.0 20.0 10.0 0.0 LCL 0.0 ADMIT DATE

Asti, et al., Pediatrics 2015;135

The standard approach: why? Medications

Source: Grossman Family Album Abraham, et al. J Obstet Gynaecol Can 2010;32(9):866 871

Intervention 1 Focus on non-pharmacologic care 24

Length of Stay: Methadone exposed infants 70.0 Standardized non-pharm care 60.0 50.0 UCL Mean=22.5 LENGTH OF STAY (Days) 40.0 30.0 Mean=13.2 29.1 20.0 10.0 0.0 LCL 0.0 ADMIT DATE

The standard approach: why? Medications NICU

Source: http://medicine.yale.edu

Source: http://adamandsarahcoats.blogspot.com

Intervention 2 Direct transfer to the general inpatient unit 30

Length of Stay: Methadone exposed infants 70.0 60.0 Standardized non-pharm care Direct transfer to inpatient unit 50.0 UCL Mean=22.5 LENGTH OF STAY (Days) 40.0 30.0 CL Mean=13.2 Mean=10.2 32.5 20.0 10.0 10.2 0.0 LCL 0.0 1/30/08 6/12/08 7/18/08 10/15/08 12/1/08 1/13/09 2/7/09 4/6/09 5/13/09 6/14/09 9/10/09 10/5/09 12/18/09 2/23/10 3/19/10 6/23/10 9/23/10 11/23/10 12/18/10 2/17/11 3/8/11 4/27/11 5/19/11 7/26/11 9/16/11 10/7/11 12/1/11 12/26/11 2/11/12 4/17/12 5/13/12 6/8/12 7/16/12 9/27/12 10/14/12 11/17/12 1/25/13 2/23/13 3/21/13 4/15/13 5/21/13 6/9/13 8/21/13 9/26/13 11/21/13 11/30/13 12/30/13 2/4/14 3/26/14 4/19/14 5/10/14 ADMIT DATE

The standard approach: why? Medications NICU Finnegan Scores

The infant with a score of 7 or less was not treated with drugs for the abstinence syndrome because, in our experience, he would recover rapidly with swaddling and demand feedings. Infants whose score was 8 or above were treated pharmacologically Finnegan LP, et al. Assessment and treatment of abstinence in the infant of the drug- dependent mother. Int Clin Pharmacol Biopharm. 1975;12(1 2):19 32

Problems with the Finnegan Long lengths of stay and lots of meds Purpose of treatment is to get the scores below threshold Must disturb the infant and exacerbate signs of withdrawal Can be slow to respond Powerful and potentially harmful meds to give to treat a sneeze or a yawn

Intervention 3 Discontinuation of the Finnegan Scoring tool and adoption of a functional scoring approach 36

1)Can the baby eat? 2)Can the baby sleep? 3)Can the baby be consoled?

ESC Study Analyzed 50 consecutive NAS babies admitted to our general inpatient unit from March 2014 to August 2015 Assessed every 2-6 hours using the FNASS, but did not guide management Management decisions based on ESC

Outcomes 1. Proportion of infants treated with morphine vs. proportion predicted to be treated with morphine using the FNASS approach 2. Days the two approaches disagreed 3. FNASS scores the day after the two approaches disagreed

Results Proportion of Infants that Received Morphine 80% 70% 60% 50% p<.001 62% 40% NAS infants (n=50) 30% 20% 10% 12% 0% Received Morphine (ESC) Would Have Received Morphine (Finnegan)

Results by Hospital Day Hospital Days (n=296): ESC Approach FNASS Approach Predicted P value Increased Morphine 8 (2.7%) 76 (26%) <0.01 No Morphine 258 (87.2) 156 (52.7%) <0.01 Decreased Morphine 21 (7.1%) 35 (11.8%) <0.01 Same Morphine 9 (3%) 29 (9.8) <0.01

Results On 78 days (26.4%) the ESC Led to LESS Morphine than Predicted by The Finnegan The following day, the average Finnegan score decreased by 0.9 points, and decreased in 69% of cases. On 2 days (0.7%) the ESC Led to MORE Morphine than Predicted by The Finnegan In both cases the average Finnegan score increased by 1.7 Points the next day

Results No readmissions No seizures No ICU transfers

Withdrawal from opioids or sedative-hypnotic drugs may be life-threatening, but ultimately, drug withdrawal is a selflimited process. Unnecessary pharmacologic treatment will prolong drug exposure and the duration of hospitalization to the possible detriment of maternalinfant bonding. The only clear benefit of pharmacologic treatment is the short-term amelioration of clinical signs. Hudak ML, Tan RC; COMMITTEE ON DRUGS; COMMITTEE ON FETUS AND NEWBORN; American Academy of Pediatrics: Neonatal drug withdrawal. Pediatrics 2012; 129:e540 e560

Source: http://www.mdnews.com

The standard approach: why? Medications NICU Finnegan Scores Medication Dosing

Intervention 5 Decrease in morphine up to 3 times per day 48

Intervention 6 PRN Dosing

Length of Stay: Methadone exposed infants 70.0 Standardized non-pharm care Novel assessment tool on inpatient unit 60.0 Direct transfer to inpatient unit Spread to NICU team Prenatal counseling 50.0 UCL Mean=22.5 Rapid med weaning LENGTH OF STAY (Days) 40.0 30.0 Mean=13.2 Mean=10.2 Mean=7.7 20.0 16.9 10.0 0.0 LCL 0.0 1/30/08 7/2/08 8/30/08 11/19/08 1/13/09 2/19/09 5/5/09 6/13/09 9/10/09 10/21/09 2/2/10 3/12/10 6/23/10 10/10/10 12/10/10 2/9/11 3/8/11 5/10/11 6/10/11 9/10/11 10/7/11 12/1/11 1/5/12 4/3/12 5/13/12 6/26/12 8/20/12 10/12/12 11/17/12 1/25/13 3/6/13 4/4/13 5/21/13 7/4/13 9/10/13 11/20/13 11/30/13 1/12/14 2/19/14 4/12/14 5/10/14 6/14/14 6/26/14 8/7/14 9/23/14 11/19/14 1/6/15 2/16/15 4/14/15 ADMIT DATE

The standard approach: why? Medications NICU Finnegan Scores Medication Dosing Staff cares for the baby

Cleveland, et al., JOGNN;43(3): 318-329

How do moms feel? Addiction is misunderstood Guilty Judged Mistrusting of nurses

I would just tell (the nurses) to take it easy (on the mother). You know, after being addicted, I realized that this is really a disease. There are some who abuse, but if you re using while you re pregnant, you have a problem; a big problem and you need help

His nurse was like his muscles are locking up because of his junkie mom. I didn t want to visit, I would call before and if that nurse was there, I wouldn t even go.

because we re gonna leave and he s gonna cry and they re gonna leave him crying because they re gonna be like, you know what? His parents are jerks!

Intervention 7 Empowering messaging

Source: http://potomachospital.blogspot.com

Source: http://potomachospital.blogspot.com

Old Protocol Goal: suppress withdrawal signs NICU: Mom visits Finnegan Scores: treat the number supportive care feed on demand Morphine Surprise! Staff takes care of infant New Protocol Goal: have infant function as a normal neonate Mother and child together Eat/Sleep/Console: treat the infant SUPPORTIVE CARE No feeding schedule Meds on page 3 Prenatal preparation Staff coaches parents

Length of Stay: Methadone exposed infants 70.0 Standardized non-pharm care 60.0 Direct transfer to inpatient unit 50.0 UCL Mean=22.5 Novel assessment tool on inpatient unit Prenatal counseling LENGTH OF STAY (Days) 40.0 30.0 Mean=13.2 Mean=10.2 Spread to NICU team Rapid med weaning Mean=7.7 Meds as needed Empowering messaging Mean=5.9 20.0 10.0 10.8 0.0 LCL 1/30/08 7/12/08 11/10/08 1/21/09 4/6/09 6/13/09 9/18/09 12/23/09 3/19/10 9/18/10 12/10/10 2/21/11 4/27/11 7/4/11 9/29/11 12/1/11 2/11/12 5/7/12 6/26/12 10/9/12 11/17/12 2/23/13 3/28/13 5/22/13 8/21/13 11/20/13 12/10/13 2/11/14 4/19/14 6/8/14 6/26/14 9/8/14 11/14/14 1/9/15 3/11/15 5/26/15 7/17/15 8/22/15 10/21/15 12/4/15 4/28/16 7/7/16 8/31/16 9/27/16 10/29/16 12/21/16 1/19/17 3/3/17 4/3/17 4/30/17 5/28/17 6/25/17 ADMIT DATE 0.9

Average Length of Stay - Methadone Exposed Infants 35 30 Average Length of Stay (Days) 25 20 15 10 Protocol Change: More aggressive weans Focus on supportive management Transfers directly from WBN to Floor Discontinued Finnegan Scoring NICU included in effort Length of Stay (days) 5 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year More aggressive weans

Percent of NAS Patients Treated with Morphine 100.0% 90.0% 80.0% % Treated with Morphine 70.0% 60.0% 50.0% 40.0% 30.0% % Treated with Morphine 20.0% 10.0% 0.0% 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year

Percent Treated with Morphine 100.0% 90.0% 80.0% 70.0% Percent Treated 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% 2008 2009 2010 2011 2012 2013 2014 2015 2016 Date

Percent of NAS Patients Treated with Morphine 100.0% 90.0% 80.0% % Treated with morphine 70.0% 60.0% 50.0% 40.0% 30.0% NICU non-nicu 20.0% 10.0% 0.0% 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year

Average Length of Stay - Methadone Exposed Infants 35 30 25 Average Length of Stay 20 15 Average Length of Stay 10 5 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year

Average Length of Stay - Methadone Exposed Infants 35 30 25 Average Length of Stay 20 15 NICU non-nicu 10 5 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year

Average Maximum Morphine Dose 0.6 Average maximum morphine dose (mg/dose) 0.5 0.4 0.3 0.2 0.1 p <.001 Average maximum morphine dose (mg/dose) 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year

60.0% Breastfeeding Rate 50.0% 40.0% % Breastfeeding 30.0% 20.0% % Breastfeeding 10.0% 0.0% 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year

Total Average Cost of NAS Care 60000 50000 40000 p <.001 Total Cost ($) 30000 Total Cost ($) 20000 10000 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year

BMC QI Initiative 2016-2017 Cycle 1: May 2016 Staff education Prenatal messaging Non-pharm care bundle Finnegan symptom prioritization Cycle 2: July 2016 Methadone No Tx in the first 24 hours Cycle 3: Dec 2016 Eat, Sleep, Console (ESC) Cuddlers

Symptom Prioritization Central Nervous System Disturbances Excessive High Pitched Crying 2 Continuous High Pitched Crying - 3 Sleep < 1 Hr After Feeding 3 Sleep < 2 Hr After Feeding 2 Sleep < 3 Hr After Feeding 1 Hyperactive Moro Reflex 2 Markedly Hyperactive Moro 3 Mild Tremors Disturbed 1 Mod Sev Tremors Disturbed 2 Mild Tremors Undisturbed 3 Mod Sev Tremors Undisturbed - 4 Metabolic, Vasomotor, and Respiratory Disturbance Gastrointestinal Disturbance Sweating 1 Excessive Sucking 1 Fever < 101 (37.2 38.3 C) 1 Fever > 101 (38.4 C) 2 Poor feeding 2 Frequent Yawning (>3) 1 Regurgitation 2 Projective Vomiting 3 Mottling 1 Loose Stools 2 Watery Stools 3 Nasal Stuffiness 1 Increased Muscle Tone - 2 Sneezing (>3) 1 Excoriation 1 Nasal Flaring 2 Myoclonic Jerk 3 Respiratory Rate (>60) 1 Respiratory Rate (>60 Retractions) 2 Seizures 5

ESC EPIC flowsheet

ESC EPIC Flowsheet

Percent of infants pharmacologically treated _ _ % Treated Average - - - UCL and LCL Percent 100% UCL Non-Pharm Care Bundle Symptom prioritization Prenatal education 90% 80% Percent treated 70% 60% 50% 40% 30% LCL ESC Care Tool Cuddlers 20% 10% Mean 86% Staff QI education 0% 1/1/14 2/1/14 3/1/14 4/1/14 5/1/14 6/1/14 7/1/14 8/1/14 9/1/14 10/1/14 11/1/14 12/1/14 1/1/15 2/1/15 3/1/15 4/1/15 5/1/15 6/1/15 7/1/15 8/1/15 9/1/15 10/1/15 11/1/15 12/1/15 1/1/16 2/1/16 3/1/16 4/1/16 5/1/16 6/16/16 7/16/16 8/1/16 9/1/16 10/1/16 11/1/16 12/1/16 1/1/17 2/1/17 3/1/17 Mean 44% Month of admission

Pharmacologically treated infants who received adjunctive medication _ _ % Adjunctive Medications Average - - - UCL Percent Percent with adjunctive medication 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1/1/14 UCL LCL 2/1/14 3/1/14 4/1/14 5/1/14 6/1/14 7/1/14 8/1/14 9/1/14 10/1/14 Mean 34% 11/1/14 12/1/14 1/1/15 2/1/15 3/1/15 4/1/15 5/1/15 6/1/15 7/1/15 8/1/15 9/1/15 10/1/15 11/1/15 12/1/15 Month of admission Non-Pharm Care Bundle Symptom prioritization Prenatal education Staff QI education 1/1/16 2/1/16 3/1/16 4/1/16 5/1/16 Methadone 6/16/16 7/16/16 8/1/16 9/1/16 ESC Care Tool Cuddlers 10/1/16 11/1/16 12/1/16 Mean 0% 1/1/17 2/1/17 3/1/17

Length of hospital stay for all opioid-exposed infants Measure Hospital days 60 50 40 30 20 UCL Mean 18.4 days Non-Pharm Care Bundle Symptom prioritization Prenatal education _ _ LOS Average - - - UCL and LCL Staff QI Education Methadone ESC Care Tool Cuddler s Mean 10.4 days 10 0 LCL Jan 2014 Feb 2014 March 2014 April 2014 May 2014 June 2014 July 2014 Aug 2014 Sept 2014 Oct 2014 Nov 2014 Dec 2014 Jan 2015 Feb 2015 March 2015 April 2015 May 2015 June 2015 July 2015 Aug 2015 Sept 2015 Oct 2015 Nov 2015 Dec 2015 Jan 2016 Feb 2016 March 2016 April 2016 May 2016 June 2016 July 2016 Aug 2016 Sept 2016 Oct 2016 Nov 2016 Dec 2016 Jan 2017 Feb 2017 March 2017 Month of admission

LCL 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% 22 24 26 28 30 32 34 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 102 104 106 108 110 112 114 116 118 120 122 124 126 128 130 132 134 136 138 140 142 144 146 148 150 152 154 156 158 160 162 164 166 168 170 172 174 176 178 180 182 184 186 188 190 Measure Mean 80% Percent Parental Presence Mean 50%

New ESC Tool

Additional Spread

Long-Term Outcomes?

Conclusions Hugs before drugs Empower families Rooming-in Non-Pharmacologic care as 1 st line treatment ESC approach PRN meds Ask why Source: Grossman Family Album

Acknowledgements David Hersh, MD Adam Berkwitt, MD Erin Nozetz, MD Marcelle Applewaite, RN Kim Carter, RN Liz O Mara Matt Bizzarro, MD Yogangi Malhotra, MD Jonathan Miller, MD Camisha Taylor, RN Rachel Osborn, MD