Evaluation of a Morphine Weaning Protocol
in Pediatric Intensive Care Patients
Alyssa Cavanaugh, PharmD
PGY1 Pharmacy ResidentChildren’s Hospital of Michigan
**The speaker has no actual or potential conflict of interest in relation to this presentation**
1
Background
• Long-term opioid infusions are needed for
intensive care unit (ICU) patients to manage pain
• Sedation used to prevent
– Accidental self-extubation
– Catheter removal
– Reduce morbidity associated with inadequate
management of distress
Can J Hosp Pharm 2012. Vol 65(1):12-18 2
Background
• Withdrawal: Clinical syndrome that manifests
after stopping or reversing a drug after
prolonged exposure
– Primary Mechanism
• Opioid receptor coupling to Gs protein • Superactivation of cAMP pathway • Activation of excitatory amino acid receptors
Pediatrics 2010. Vol 125:e1208-e1225 3
Signs and Symptoms of Withdrawal
3 Categories of Symptoms
CNS irritability GI dysfunction Autonomic dysfunction
Anxiety Agitation Tremors Seizures Vomiting Diarrhea Poor feeding Fever Sweating High blood pressure
Yawning
Can J Hosp Pharm 2012. Vol 65(1):12-18 4
Learning Question #1
• Which of the following are signs and symptoms
of opioid withdrawal?
A.
Tremor
B.
High blood pressure
C.
Vomiting
D.
All of the above
5
Withdrawal Assessment
• Withdrawal is a common side effect of prolonged
sedation in a pediatric intensive care unit (PICU)
• Method of assessment and monitoring is
warranted
– Withdrawal Assessment Tool-1 (WAT-1): evaluates
withdrawal symptoms in a PICU setting
Pediatr Crit Care Med. 2008. Vol 9(6): 573–580. 6
Withdrawal Assessment
Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients Purpose • To investigate the validity and generalizability of the Withdrawal
Assessment Tool-1 (WAT-1) in children during weaning of analgesics and sedatives
Methods • All subjects exposed to 5 or more consecutive days of opioids had been assessed for withdrawal symptoms twice daily at 8 am and 8 pm (and at other times if clinically indicated) from the day that opioid weaning started until 72 hours after last opioid dose
Results • 308 children throughout 22 centers
• Higher WAT-1 scores (> 3) had a longer PICU length of stay than those with WAT-1 scores (<3)
Conclusion • WAT-1 demonstrated feasibility and utility as evidenced by its successful implementation and use by nurses in major pediatric centers across the USA
• WAT-1 shows good generalizability when used to assess clinically important withdrawal symptoms in the PICU
Pain 2012 January. Vol 153(1):142-148 7
Withdrawal Assessment Tool-1
Pain 2012 January. Vol 153(1):142-148 8
Opioid Pharmacokinetics
• Half-life
Am J Dis Child. 1992 August. Vol 146: 972-976 9
Learning Question #2
• What is the half-life of oral morphine?
A.
4-62 hours
B.
1-10 hours
C.
11-13 hours
D.
All of the above
10
Previous Studies
Children’s Hospital of Michigan – Historical Controls (unpublished data)
January 1st, 2010 to September 30th, 2012 October 1st, 2012 to March 1st, 2013 Methadone wean Morphine 2-arm wean
(10 day and 20 day) Retrospective
n=64 Prospective n=24 • Average wean: 26.14 days (1-111)
• Average rescue doses: 42 doses/wean (0-695)
• Average cost/wean: $4.52 (0.01-25.45)
• Average wean: 8.75 days (2-19) • Average rescue doses: 3.3 doses/wean (0-15) • Average cost/wean: $3.15 (0.06-22.12) • Longer weans
• Multiple rescue doses needed during wean
• Patients finished wean faster than allotted time
• WAT-1 scores were not accurately recorded or lack of recordings
Evaluation of a Morphine Weaning Protocol
in Pediatric Intensive Care Patients
Primary investigator: Alyssa Cavanaugh, PharmD Secondary investigators: Joanna Ditouras, PharmD, Kevin Valentine, MD
Children’s Hospital of Michigan
Detroit Medical Center
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Purpose
Describe the incidence of opioid withdrawal in
pediatric patients using a 3-arm morphine
weaning protocol
15
Study Outcomes
• Primary Outcome
– Incidence of opioid withdrawal in pediatric patients
• Secondary Outcomes
– Identify adherence to protocol
– Compare the duration of medication therapy and cost
– Compare the length of ICU stay
16
Methods
17
Methods
• All patients were placed in a wean protocol if
they had been on continuous infusion morphine
for > 5 days
• Patients were divided into 3 different groups
– 5 day wean
– 10 day wean
– 15 day wean
18Methods
5-10 days
5 day
11-15 days
10 day
> 16 days
15 day
# of Infusion Days
Wean
Methods
• Calculate the Original Daily Dose (ODD)
– Morphine Oral (mg) ODD= 2X (Total of IV bolus +
infusion from previous day)
• Example: 10 kg pt Infusion: 40 mCg/kg/hr Bolus: 0.4 mg IV q2hr = 6 bolus/24hrs 20
Methods
21Methods
5 DAY MORPHINE WEAN
Day Original Daily Dose (ODD)=
2X(Total of IV bolus+infusion from previous day) 1 Divide ODD every 6 hours
2 Decrease to 80% of ODD and divide every 6 hours
3 Decrease to 60% of ODD and divide every 8 hours
4 Decrease to 40% of ODD and divide every 12 hours
5 Decrease to 20% of ODD and divide every 12 hours
6 Discontinue morphine
22
Methods
10 DAY MORPHINE WEAN
Day Original Daily Dose (ODD)=
2X(Total of IV bolus+infusion from previous day) 1 Divide ODD every 4 hours
2 Decrease to 90% of ODD and divide every 4 hours
3 Decrease to 80% of ODD and divide every 6 hours
4 Decrease to 70% of ODD and divide every 6 hours
5 Decrease to 60% of ODD and divide every 8 hours
6 Decrease to 50% of ODD and divide every 8 hours
7 Decrease to 40% of ODD and divide every 12 hours
8 Decrease to 30% of ODD and divide every 12 hours
9 Decrease to 20% of ODD and give every 12 hours
10 Decrease to 10% of ODD and give every 12 hours
11 Discontinue morphine
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Methods
15 DAY MORPHINE WEAN
Day Original Daily Dose (ODD)=
2X(Total of IV bolus+infusion from previous day)
1 Divide ODD every 4 hours
2 Decrease to 90% of ODD and divide every 4 hours
3 no change
4 Decrease to 80% of ODD and divide every 6 hours 5 Decrease to 70% of ODD and divide every 6 hours
6 no change
7 Decrease to 60% of ODD and divide every 8 hours 8 Decrease to 50% of ODD and divide every 8 hours
9 no change
10 Decrease to 40% of ODD and divide every 12 hours 11 Decrease to 30% of ODD and divide every 12 hours
12 no change
13 Decrease to 20% of ODD and divide every 12 hours 14 Decrease to 10% of ODD and divide every 12 hours
15 no change
Methods
• WAT-1 scoring from the 1st day of wean
• Scored twice daily (once per nursing shift)
• Continued until 72 hours after the last dose
Methods
• Rescue Dose
– If patients received 3 or more doses for breakthrough
in a 24 hour period with appropriate WAT-1 score
confirmation, then patients were moved back by 2
days
• Example: A child on day 3 of a wean received 3 breakthrough (not counting for pain or procedures) doses of morphine with confirming WAT-1 scores, then go back to day 1 of protocol
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Statistical Analysis
• Descriptive statistics were used to:
– Evaluate demographic and visit characteristics
– Identify incidence of withdrawal
– Identify adherence to protocol
– Describe the duration of therapy, cost, and length of
ICU stay
27
Background Demographics
28
Results
• Primary Outcome: Incidence of opioid withdrawal
in pediatric patients
– WAT-1 scores
– # of rescue doses/wean
29Results
• WAT-1 Scores
– 100% had at least one WAT-1
– 78% had a daily WAT-1
– 56% had a twice daily WAT-1
• Rescue Doses
– 14 total doses (0.52 doses/wean)
• 9/14 had a documented WAT-1 > 3 and gave rescue dose • 4/14 described signs and symptoms of withdrawal and gave
rescue dose
• 1/14 had rescue dose given with no signs and symptoms or WAT-1 score
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Adherence to Protocol
Results
Secondary outcomes
Duration of medication therapy
Continuous infusion • Average = 10.2 days (4-40) Taper• Average = 9.52 days (4-25)
Cost of therapy
Average = $7.97/wean (6.75-26.69)Length of ICU stay
Average = 32.3 days (9-148)Length of hospital stay
Average = 36.1 days (12-148)32
Confounders
33
Discussions
Morphine comparisons
Outcomes (Historical Controls) October 1st, 2012 to March 1st, 2013 (Current Data) October 1st, 2013 to March 1st, 2014 Length of
continuous infusion 12.25 days (5-23) 10.2 days (4-40) Duration of
medication therapy 8.75 days (2-19) 9.52 days (4-25) # of morphine doses 33.05 doses (4-78) 28.96 doses (8-73) Cost of therapy $3.15 (0.06-22.12) $7.97 (6.75-26.69) Length of ICU stay 21 days (8-44) 32.3 days (9-148) 34
Conclusions
• 67% adherence to protocol
– Cardiovascular patients had longer weans than those
admitted for a respiratory diagnosis
• Better compliance for completion of WAT-1
scores by PICU staff
• 93% rescue doses given were addressed either
through WAT-1 score or described signs and
symptoms
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Conclusions
• Compared to 2-arm wean
Limitations
• Small study, n = 27
• Single center
• Excluded patients on high dose opioid infusions
• WAT-1 is a subjective scale assessed by
multiple RNs in PICU and floor
• Patients transferred to floor
Future Directions
• WAT-1 scores to be incorporated on flow sheets
for PICU and EMR for floor patients
• Formal teaching will be expanded beyond PICU
to floor teams and nurses
• Evaluate if a cardiovascular specific wean needs
to be created
• Evaluate if high WAT-1 scores on day 1 require
an increased ODD or a move up to next wean
category
38
Acknowledgements
• Dr. Joanna Ditouras, PharmD and Dr. Kevin
Valentine, MD
• Children’s Hospital of Michigan PICU staff
• Selmir Mahmutovic, PharmD Candidate 2015
and Matthew Duprey, PharmD Candidate 2014
39
