Evaluation of a Morphine Weaning Protocol in Pediatric Intensive Care Patients

Evaluation of a Morphine Weaning Protocol in Pediatric Intensive Care Patients Jennifer Kuhns, Pharm.D. Pharmacy Practice Resident Children s Hospital of Michigan **The speaker has no actual or potential conflict of interest in relation to this presentation Opioid Withdrawal Syndrome Three categories of symptoms: CNS irritability Anxiety, agitation, tremors, seizures, etc. GI dysfunction Vomiting, diarrhea, poor feeding Autonomic dysfunction Fever, sweating, hypertension, yawning etc. Diagnosis of exclusion 2 Crit Care Med. 2008:36:8:2427-2432 1

Risk Factors for Withdrawal Prolonged opioid use (> 5-7 days) Abrupt discontinuation of opioids High opioid total cumulative doses Fentanyl > 2.5 mg/kg total dose 3 Crit Care Med. 2008:36:8:2427-2432 Intensive Care Med 2007;33:1396-1406 Withdrawal Assessment Tool (WAT-1) 83 pediatric patients Score 0-12 < 3: low chance of withdrawal > 3: higher chance of withdrawal Study published showing no age differences and good reproducibility 4 Pediatr Crit Care Med 2008;9(6):573-580 2

Withdrawal Assessment Tool (WAT-1) 0-12 scoring system (No=0, Yes=1) Patient record Loose watery stool, vomiting, temperature >37.8 C Pre-stimulus Awake/distressed, tremor, sweating, repetitive movements, yawning/sneezing Stimulus Startle to touch, increased muscle tone Post-stimulus Time to calm state (< 2 mins=0, 2-5 mins=1, > 5 mins=2) 5 Pediatr Crit Care Med 2008;9(6):573-580 Learning Question 1 What are the different components of the withdrawal assessment tool (WAT-1)? A. Patient record B. Pre-stimulus C. Stimulus D. All of the above 6 3

Learning Question 1 What are the different components of the withdrawal assessment tool (WAT-1)? A. Patient record B. Pre-stimulus C. Stimulus D. All of the above 7 Pharmacologic Weaning Options Oral opioids: Methadone vs. Morphine 4

Oral Weaning Options Methadone Advantages High bioavailability Prolonged half-life Disadvantages Drug-drug interactions Drug accumulation Unpredictable opioid equivalent doses Black-box warning 9 Acta Anaesthesiol Scand 2008;52:879-889 Oral Weaning Options Morphine Advantages Predictable pharmacokinetic profile Disadvantages Drug accumulation in renal dysfunction Opioid equivalent dosing Few drug-drug interactions 10 Pain Physician 2008:11:S133-S153 5

Learning Question 2 What is a limitation for using methadone in opiate withdrawal? A. Drug accumulation after prolonged dosing B. Short half-life C. Excellent oral bioavailability D. No black-box warnings 11 Learning Question 2 What is a limitation for using methadone in opiate withdrawal? A. Drug accumulation after prolonged dosing B. Short half-life C. Excellent oral bioavailability D. No black-box warnings 11 6

Evaluation of a Morphine Weaning Protocol in Pediatric Intensive Care Patients Primary Investigator: Jennifer Kuhns, Pharm.D. Secondary Investigators: Joanna Ditouras, Pharm.D. and Kevin Valentine, M.D. Detroit Medical Center Children s Hospital of Michigan Study Design Institutional review boards at DMC and Wayne State University approved the study Single-center prospective observational study with retrospective historical controls Pediatric intensive care unit (PICU) patients admitted to CHM January 1 st, 2010 through March 1 st, 2013 Retrospective: January 1 st 2010 - September 30 th 2012 Prospective: October 1 st 2012 - March 1 st 2013 15 7

Purpose Purpose To conduct a pilot study comparing a prospective morphine taper to a historical methadone taper previously used in the PICU 16 Outcomes Primary outcome Incidence of opioid withdrawal Utilizing WAT-1 Secondary outcomes Duration/doses of medication therapy Cost of therapy Length of ICU/hospital stay Benzodiazepine doses/concurrent taper 17 8

Inclusion Criteria Patients < 18 years of age Admitted to the PICU between January 1, 2010 and March 1, 2013 Methadone or morphine taper after prolonged opioid continuous infusion of > 5 days Methadone taper (01/01/2010-09/30/2012) Morphine taper (10/01/2012-03/01/2013) 18 Exclusion Criteria Patients > 18 years of age Patients receiving chronic opioids prior to current PICU admission 19 9

Methods All patients were started on protocol if they had been on continuous infusion (CI) opioids > 5 days 10 day wean 5-10 days on CI 20 day wean 11+ days on CI 20 Morphine Protocol Calculate the original daily dose (ODD): Morphine oral mg ODD= (Morphine CI mg daily dose) x (3) CI wean: Day 1: Wean drip by 33% every 8 hours Day 2: CI drip is stopped 21 10

22 10 DAY ORAL MORPHINE WEAN DAY ORAL 1 Divide ODD every 4 hours 2 Decrease day 1 TDD by 10% and administer every 4 hours 3 Decrease day 2 TDD by 10% and administer every 6 hours 4 Decrease day 3 TDD by 10% and administer every 6 hours 5 Decrease day 4 TDD by 10% and administer every 8 hours 6 Decrease day 5 TDD by 10% and administer every 8 hours 7 Decrease day 6 TDD by 10% and administer every 12 hours 8 Decrease day 7 TDD by 10% and administer every 12 hours 9 Decrease day 8 TDD by 10% and administer every 24 hours 10 Decrease day 9 TDD by 10% and administer every 24 hours 11 Discontinue morphine ODD=Original daily dose TDD=Total daily dose 23 20 DAY ORAL MORPHINE WEAN DAY ORAL 1-2 Divide ODD every 4 hours 3-4 Decrease day 2 TDD by 10% and administer every 4 hours 5-6 Decrease day 4 TDD by 10% and administer every 6 hours 7-8 Decrease day 6 TDD by 10% and administer every 6 hours 9-10 Decrease day 8 TDD by 10% and administer every 8 hours 11-12 Decrease day 10 TDD by 10% and administer every 8 hours 13-14 Decrease day 12 TDD by 10% and administer every 12 hours 15-16 Decrease day 14 TDD by 10% and administer every 12 hours 17-18 Decrease day 16 TDD by 10% and administer every 24 hours 19-20 Decrease day 18 TDD by 10% and administer every 24 hours 21 Discontinue morphine ODD=Original daily dose TDD=Total daily dose 11

Methods WAT-1 scale to be used Rescue doses Contact physician if WAT-1 > 3 Per physician discretion Morphine 0.1 mg/kg IV x 1 dose 20 day 10 day wean Zero rescue doses and two consecutive WAT-1 scores < 3 10 day 20 day wean 4+ rescue doses in 24 hours and two consecutive high WAT-1 scores (> 3) 24 Statistical Analysis Sample size Pilot study Fisher s exact test or Pearson Chi-Square Demographic and visit characteristics Statistical significance p value < 0.05 Mann-Whitney U Test PICU/hospital days Morphine/methadone doses/taper days Continuous infusion days Opioid/benzodiazepine rescue doses 25 12

Sample Size Retrospective N=62 10 day wean N=6 (25%) Prospective N=24 20 day wean N=18 (75%) Included N=14 (78%) Excluded** N=4 (22%) 26 **Patients were excluded from primary and secondary statistical analysis if they did not finish their morphine wean by 03/01/2013 Patient Characteristics Baseline Characteristics Mean (range) Retrospective (n=62) Prospective (n=24) P-value Age (years) 1.47 (0.03-15) 0.83 (0.08-10) p=0.29 Sex Male 27 (43.5%) Female 35 (56.5%) Male 6 (25%) Female 18 (75%) p=0.14 Height (cm) 67.1 (36.5-154) 58.8 (44-127) p=0.12 Weight (kg) 9.35 (2.7-56.9) 6.27 (2.7-36.6) p=0.12 Service CV 35 (56.5%) Med 27 (43.5%) Admitting Dx Cardiac 33 (53.2%) Resp 19 (30.6%) Other 10 (15.3%) CV 20 (83.3%) Med 4 (16.7%) Cardiac 6 (25%) Resp 15 (62.5%) Other 3 (12.5%) p=0.03 p=0.03 27 13

Patient Characteristics Baseline Characteristics Mean (range) Retrospective (n=62) Prospective (n=24) P-value Age (years) 1.47 (0.03-15) 0.83 (0.08-10) p=0.29 Sex Male 27 (43.5%) Female 35 (56.5%) Male 6 (25%) Female 18 (75%) p=0.14 Height (cm) 67.1 (36.5-154) 58.8 (44-127) p=0.12 Weight (kg) 9.35 (2.7-56.9) 6.27 (2.7-36.6) p=0.12 Service CV 35 (56.5%) Med 27 (43.5%) Admitting Dx Cardiac 33 (53.2%) Resp 19 (30.6%) Other 10 (15.3%) CV 20 (83.3%) Med 4 (16.7%) Cardiac 6 (25%) Resp 15 (62.5%) Other 3 (12.5%) p=0.03 p=0.03 28 Primary Outcome Primary Outcome Incidence of opioid withdrawal Unknown WAT-1 scale documented ~18% of the time Limitations: Lack of WAT-1 scores» Separate flow sheet» RN not consistently recording Patient transferred out of PICU 29 14

Primary Outcome Prospective patients that finished within their assigned protocol < 5 days N=3 (50%) 6-10 days N=3 (50%) 11-19 days N=0 (0%) 10 day wean N=6 20 day wean N=14 < 5 days N=3 (21%) 6-10 days N=5 (36%) 11-19 days N=6 (43%) 30 Results Secondary Outcomes Mean (range) Retrospective (n=62) Prospective (n=20) P-value PICU days 61.19 (2-229) 21.5 (8-44) p<0.001 Hospital days 74.77 (4-246) 29.7 (12-51) p<0.001 Taper days 25.39 (1-111) 9.14 (2-19) p=0.003 31 15

Doses 120 114 (0-695) 100 80 60 40 20 0 53 (1-234) Meth/morph Doses 35 (4-78) 40 (0-315) Opioid rescue doses 3.4 (0-15) 12 (0-70) Benzodiazepine doses Retrospective Prospective 32 p=0.97 p<0.001 p<0.001 Additional Results Secondary Outcomes Mean (range) Retrospective (n=62) Prospective (n=20) P-value Benzodiazepine taper concurrently Deceased during taper Yes 18 (29%) No 44 (71%) Yes 6 (9.7%) No 56 (90.3%) Yes 5 (27.9%) No 19 (79.2%) Yes 0 (0%) No 24 (100%) p=0.59 p=0.18 Cost of drug $4.52 (0.01-25.45) $3.15 (0.06-22.12) n/a Days on CI prior to wean 19.95 (5-98) 12.25 (5-23) p=0.03 33 16

Conclusion Implementing a morphine weaning protocol in our PICU was associated with significantly decreased: Taper days Opioid/benzodiazepine rescue doses 34 Limitations Lack of WAT-1 scores WAT-1 on a separate nursing flow sheet Transferred out of the PICU prior to completion of morphine wean No patients followed the protocol as written Patients required shorter morphine weans than 10 and 20 days 35 17

Future Directions WAT-1 scale on nursing flowsheet/emr Modifying to a 5 and 10 day morphine wean 36 Evaluation of a Morphine Weaning Protocol in Pediatric Intensive Care Patients Jennifer Kuhns, Pharm.D. Pharmacy Practice Resident Children s Hospital of Michigan **The speaker has no actual or potential conflict of interest in relation to this presentation 18