Opioid Rotation Dr Bruno Gagnon, M.D., M.Sc - Associate Professor Department of Family Medicine and Emergency Medicine, Faculty of Medicine ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Opioid Rotation
Dr Bruno Gagnon, M.D., M.Sc.
Associate Professor
Department of Family Medicine and Emergency Medicine,
Faculty of Medicine, Université Laval
Consultant in Palliative Medicine
CHU de Québec-Université Laval, L’Hôtel-Dieu de Québec
Disclosure of Financial Support
• This program has not received financial support
• This program has not received in-kind support
• No conflict of interest
www.ulaval.ca
Faculty/Presenter Disclosure
• Faculty:
§Faculty of Medicine, Laval University
• Relationships with financial sponsors:
§None
www.ulaval.ca
As a result of attending this presentation, the learner will
• become competent with the rationale
for the practice of rotating narcotics
• when, how and why one would choose
to alter treatment in this manner.
• be able to discuss the most common
pitfalls in rotating narcotics.
www.ulaval.ca
Plan
• Definition
• Brief explanation of scientific basis
• Indications and process
• 3 clinical vignettes
• Comments on methadone
• Take home tips
www.ulaval.caLevel of evidences
• Animal studies
• Retrospective cohort studies
• Experts’ opinions
www.ulaval.caOpioid rotation (switching)
• Process of substituting on opioid to another
• Objectives:
§ Improve pain control
§ Reduce intensity of adverse effects
Mercadante S., Cancer, 1999
www.ulaval.caGenetic variabilities in opioid receptors
Tolerance development to analgesic and toxic
effects ≠ time; analgesic ≠ toxic effects
↑ morphine dose → analgesic < toxic
≠ between different opioids
Analgesic/toxic is influenced by:
• Exposure time
• Illness progress
→ Incomplete cross tolerance
Opioid switching or rotation
www.ulaval.caIn conclusion: opioids differ in
Effectiveness Ability to induce toxicity
www.ulaval.caFractional Receptor Occupancy
Minimum % of receptors
occupancy necessary
Efficacy
Efficacy is inversely
proportional to
receptor occupancy
Receptor Occupancy
www.ulaval.ca June
24th,
2012Receptor Occupancy and Efficacy
Fentanyl (F)
% Receptor occupancy
High efficacy/Low occupancy
requirement
80 %
Morphine (M)
Low efficacy/High occupancy
requirement
Efficacy
www.ulaval.ca June
24th,
2012Trials and errors www.ulaval.ca
Indications and Process
• Clinical Vignette 1
• Clinical Vignette 2
• Clinical Vignette 3
www.ulaval.caClinical Vignette 1
• You are seen M. John in outpatient clinic
• 62 year’s old man
• Diagnosed 6 months previously with NSCLC
RLL
• Chest wall invasion and liver metastases
• No comorbidities
• Chimotx as a palliative modality
www.ulaval.caClinical Vignette 1
• Initially R lateral chest wall pain 7/10 (7th-
8th ribs)
• Mildly burning
• BTP: electric shocks like
• Initiation and titration up of morphine
• Gabapentin
www.ulaval.caClinical Vignette 1
• No more chemotherapy
• Diffuse R chest wall pain 9/10
• From sternum to back
• Burning pain 3/10 in both arms and legs
• No other complaints
www.ulaval.caClinical Vignette 1
• Gabapentin 75 mg PO BID
• Morphine LA 120 mg PO BID
• Since 4 days, 5-6 BTA of 25 mg of IR
Morphine/day
www.ulaval.caClinical Vignette 1
What is the underlying pathophysiological process
responsible for the sudden worsening of the pain
syndrome?
1. Opioid neurotoxicity
2. Opioid tolerance
3. Specific opioid low responsiveness
4. Hyperalgesia
5. Progression of disease
www.ulaval.caQuestion
What is the underlying pathophysiological process
responsible for the sudden worsening of the pain
syndrome?
1. Opioid neurotoxicity
2. Opioid tolerance
3. Specific opioid low responsiveness
4. Hyperalgesia
5. Progression of disease
www.ulaval.caHyperalgesia: Rotation from Morphine to
Hydromorphone
Hydromorphone
% of Response
Morphine
80 % Hyperalgesia
Ratio 1 Ratio 2
Ratio 1 < Ratio 2
Dosage
www.ulaval.ca June
24th,
2012
20Decision to switch to hydromorphone
What is the conversion ratio of Morphine to
hydromorphone?
1. 2:1
2. 3:2
3. 5:1
4. 10:1
www.ulaval.caDecision to switch to hydromorphone
What is the conversion ratio of Morphine to
hydromorphone?
1. 2:1
2. 3:2
3. 5:1
4. 10:1
www.ulaval.caHow do we proceed?
• Many ways to skin a cat!
• Morphine: 240 (325 BTA) mg orally/day
• = 48 (65) mg of hydromorphone orally/day
• Discontinue morphine
• Start HM at 36 mg orally/day (↓25 – 40 %) (6
mg q 4 hrs) BTA: 4 mg q 1 hr
% of ↓ is a clinical judgement issue
Pitfall: too much or not enough
www.ulaval.caClinical Vignette 2
• Clara is 42 year old
• 12 months previously recurrence of breast
cancer with 4 bone metastases
• Treated with chemotherapy
• No comorbidities
• Bisphosphonate I.V.
www.ulaval.caClinical Vignette 2
• 3 weeks previously
• Apparition bone pain (6-7/10) multiple sites
• Bone scan confirmed now wide spread bone
metastases
• Prescription:
• NSAID
• Hydromorphone 2 mg PO q 4hrs and BTA 2
mg q 1 hr PRN
www.ulaval.caClinical Vignette 2
• 2 weeks previously:
• Her Pain 6/10 despite 4-5 BTA per day
• Increase Oral HM to 4 mg q 4 hrs and
3 mg q 1 hr PRN
www.ulaval.caClinical Vignette 2
• 1 weeks previously:
• Her Pain 7/10 despite 3-4 BTA per day
• Increase Oral HM to 6 mg q 4 hrs and
3 mg q 1 hr PRN
www.ulaval.caClinical Vignette 2
• Today
• Pain 6/10; somnolence +
• Hydromorphone 6 mg PO q 4 hrs with BTA 4 mg
(5-6/day)
§ (36+20=46 mg/day)
• Mild constipation
• No other complains
www.ulaval.caQuestion
Why is the pain not responding to opioid
treatment?
1. Opioid neurotoxicity
2. Opioid tolerance
3. Specific type of opioid low responsiveness
4. Opioid Hyperalgesia
5. Progression of disease
www.ulaval.caQuestion
Why is the pain not responding to opioid
treatment?
1. Opioid neurotoxicity (A)…
2. Opioid tolerance
3. Specific type of opioid low responsiveness
4. Opioid Hyperalgesia
5. Progression of disease
www.ulaval.caPoor response to one opioid/uncontrolled pain
Oxycodone
% of Response Morphine
80 %
Important side effects
Dosage
www.ulaval.ca June
24th,
2012Rotating to oxycodone
What is the conversion ratio of oxycodone to
hydromorphone?
1. 4.3:1
2. 6.3:1
3. 1.3:2
4. 3.3:1
www.ulaval.caRotating to oxycodone
What is the conversion ratio of oxycodone to
hydromorphone?
1. 4.3:1
2. 6.3:1
3. 1.3:2
4. 3.3:1
www.ulaval.caHow do we proceed?
• Hydromorphone 46 mg orally/day
• Morphine 230 mg orally/day
• Oxycodone 154 mg orally/day (M/0: 1.5 (2)/1;
230/1.5=154)
• Oxycodone 20 mg (↓20%) orally q 4 hrs and 12
mg q 1 hr PRN
Pitfall: Risk of undertreatment
www.ulaval.caClinical Vignette 3
• Asked to see Robert on the oncology floor
• 72 years old
• Found to have a metastatic pancreatic cancer
• Tumor resistant to chemotherapy
• Previously had a well controlled pain
• Now:
• Epigastric pain 7/10, knife like
• Fentanyl patch 100 mcg/hr q 3 days
www.ulaval.caClinical Vignette 3
• Cachectic
• Confused with mild agitation
• Hallucinations
• Myoclonus +++
• Dehydrated
• Chest X-Ray normal
• Urine culture positive
• High WBC and creatinine
www.ulaval.caQuestion
Why is the pain not responding anymore to
opioid treatment?
1. Opioid neurotoxicity
2. Opioid tolerance
3. Hyperalgesia
4. Progression of disease
5. Delirium
www.ulaval.caQuestion
Why is the pain not responding anymore to
opioid treatment?
1. Opioid neurotoxicity
2. Opioid tolerance
3. Hyperalgesia
4. Progression of disease
5. Delirium
www.ulaval.caDelirium: Rotation from Fentanyl
Fentanyl
% of Response
Morphine
Delirium threshold
Dosage
www.ulaval.ca June
24th,
2012
39Clinical Vignette 3
• Complex situation
• Rotation to morphine s/c
• Fentanyl to morphine: 25 mcg/hr = 25 mg (25-50) morphine
s/c daily
• Fentanyl 100 mcg/hr = morphine 100 mg (100-200) s/c daily
• ↓ by at least 50% (50-100 mg s/c)
• Patient is cachectic (absorption?) further decrease, how
much?
• Fentanyl remains available 12 hrs (fat reserve?)
www.ulaval.caPersonnal approach
• ↓ by 50-60 % the lower equivalent ratio (morphine
100 mg)
• Start Morphine 8 mg s/c q 4hrs (48 mg/day) 12 hrs
after removal of Fentanyl patch
• Immediately allow Morphine 5 mg s/c q 1 hr for BTA
• Treat delirium (symptoms+infection+Hydration)?
Pitfall: dose still too high; multiple rotations
Rotating to fentanyl: keep original opioid
for 12 hrs; more chalenging
www.ulaval.caRotation to Methadone
• Indications
§ Failure of multiple rotations
§ High doses of opioids
§ Neuropathic pain
§ Hyperalgesia
§ Severe renal failure
www.ulaval.caMorphine/Methadone
Previous dose of
morphine not
predictive of final
methadone dose
R = 0,11 p=0,5
Bruera E, et al. Pal www.ulaval.ca
Med, 2002.Switching to Methadone
Age Daily Dose of Methadone
Day 0 Day 1α Day 2α Day 3α Day 4α
MEDD* 2/3** 1/3** 0/3** Final Dose
< 65 > 60 and 3 mg TID ↑↓ ↑↓ 9-15 mg
≤ 200 mg
≥ 65 > 60 and 2 mg TID ↑↓ ↑↓ 6-15 mg
≤ 200 mg
All# > 200 and 5 mg TID ↑↓ ↑↓ 15-30 mg
≤ 600 mg rarely > 45
mg
* Morphine Equivalent Daily Dose ** = of initial MEDD # Get help
www.ulaval.caTake home tips
• Indications of switching opioids
§ Poor pain control (↓ 20%)
§ Hyperalgesia (↓ 20-40%)
§ Delirium (≥ ↓ 50%)
• Rotation form and to Fentanyl patch more complex
• Rotation to Methadone
§ Expertise needed
§ Expert’s support
§ Could be quite beneficial
www.ulaval.caEnjoy Quebec City!!!
www.ulaval.caOpioid switching in cancer pain: From the beginning to nowadays; Sebastiano Mercadante, Eduardo Bruera,
Critical Reviews in Oncology/Hematology 99 (2016) 241–248
www.ulaval.caYou can also read
