Transcript Palliative Pain Management: An In

PEI Palliative Care Conference:
Uncontrolled Pain in Palliative Care – An
approach for when nothing seems to work !
Dr Edward J. Fitzgibbon
Palliative Care Physician
The Ottawa Hospital
June 11th 2015
Cecily Saunders
• “Palliative Care begins from the understanding
that every patient has his or her own story,
relationships and culture, and is worthy of
respect as a unique individual.
This respect includes giving the best available
medical care and making the advances of
recent decades available so that all have the
best chance of using their time well”.
Davies,E, Higginson, I.J. Palliative Care: the solid fact. WHO http://www.euro.who.int/document/E82931.pdf(2004)
Ready…..
Outline
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Pain in Palliative Care.
Pathophysiology
Assessment
An Approach to Management
Non-Opioids
Co-Analgesics
Opioids
Cases and discussion
Pain
• Pain is defined “as an unpleasant sensory and
emotional experience associated with actual
or potential tissue damage, or described in
terms of such damage” (IASP 1979)
• Pain is always subjective and each individual learns
the meaning of pain through their experiences of
injury or disease during early life.
• Pain is a very personal experience and is what the
patient says it is !
Cancer Pain: A Uniquely Individual Experience.
Bruera, E. et al. JAMA 2003;290:2476-2479.
Barriers to Pain Management
• In-hospital patients with pain from non-surgical conditions
are less likely to have their pain taken seriously enough to
be treated.
• Patient/ family reluctance to report pain and/or take
opioids
• Physician reluctance to prescribe opioids.
• There is a large gap between what is known and what is
practiced in the treatment of all kinds of pain
Prevalence of Pain
• ALS: 40 to 60%
• End stage heart failure: 45 to 60%
• AIDS: 50% + will have neuropathic pain syndrome
• ESRD: 60% +
• Cancer: 50% of all cancer patients
Cancer Pain : Defining the Challenge
• “Cancer Pain is a mixture of acute pain,
chronic pain, tumor specific pain and
treatment related pain, all compounded by
ongoing psychological responses of distress
and suffering.”
( Fitzgibbon D.R, Loeser J.D,: Cancer Pain (2010) Lippincott Williams)
Prevalence Of Pain With Stages of Cancer and It’s
Treatment
Stage of Disease
Prevalence of Pain
Active anti-cancer treatment
24% to 73%
Advanced Cancer
58% to 86%
Cured of Cancer ( in remission)
21% to 46%
* Pooled prevalence of pain was > 50% in all cancer types with the highest prevalence
in Head/neck cancer patients (70%; 95% CI 51-88%)
* Of the patients with pain, >1/3rd graded their pain as moderate or severe.
van den Beuken-van Everdingen MH et al. Ann Oncol 2007;18(9):1437-1449
Cancer Pain: Multiple Causes
10% Unrelated
Tumor related:
Compression
Infiltration
Destruction
23%
TreatmentRelated
Surgery,
Chemo,
XRT
67%
TumorRelated
Bonica J. The Management of Pain. Vol. 1. Phila: Lea & Febiger;
1990.
Complexity of Cancer Pain Syndromes
Frequent co-existence of
multiple pain etiologies in an
individual patient.
Neuropathic pain -10%
Somatic pain
- 41%
“ Mixed” pain
- 49%
Cherney et al 1989
 Multiple sites involved:
1 site - 30%
2 sites – 39%
3+ sites – 31%
 Frequent Sites: Lower back 36%, Abdomen
27%, Thorax 23%
Lower limbs 21%, Head 17%, pelvis 15%.
Grond. Pain 64 (1996) 107-114
Cancer Pain
Higher Pain Scores are associated with:
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Presence of Breakthrough Pain
Neuropathic pain
Lower Performance status ( KPS <70%)
Younger patient ( <60yrs)
More advanced disease.
Cognitive impairment
Caraceni. Pain 82 (1999) 263-274
Cancer Pain: ‘Hard to treat’
• Opioid responsiveness and optimal pain control is inversely
related to the presence of:
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Neuropathic pain.
Breakthrough pain.
Previous opioid exposure.
Cognitive impairment and Psychological distress.
Bruera . JPSM. 1989
Challenges in Managing Cancer Pain
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Features of both acute and chronic pain syndromes.
Multiple sites.
Multiple Pain Pathophysiologies
Sick population…unstable disease.
Multiple symptoms.
Multiple treatments: Polypharmacy
Multiple doctors!
RESULT = High Probability of Patients with complex Pain
Syndromes.
Assessment
An Approach to Managing Cancer Pain.
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History of Cancer + History of Pain.
Standard assessment tools (ESAS, BPI)
Document pain syndromes involved.
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Pain Assessment Tools
Pain Management Made Incredibly Easy Lippincott Williams & Wilkins (2003)
BABBS 59 yrs
NSCLCA
HDMContin 6 mgs q 12. Dil 2mgs q2h prn; TCA 60mgs; Laxatives; Chx ; Stemetil
Previously: OxyContin 20 mgs TID & OxyIR q4h PRN Pt was taking 40mg q4h straight = 500-600mgs morph/24hrs
Managing Cancer Pain.
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History of Cancer + History of Pain.
Standard assessment tools (ESAS, BPI)
Document pain syndromes involved.
Is cause known? – appropriate investigations.
Formulate Treatment plan - ‘realistic goals’.
Target Treatment @ Pain and Cause of Pain.
The Cause: Tumor Related Pain
After Chemo/XRT
Managing Cancer Pain.
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History of Cancer + History of Pain.
Standard assessment tools (ESAS, BPI)
Document pain syndromes involved.
Is cause known? – appropriate investigations.
Formulate Treatment plan - ‘realistic goals’.
Target Treatment @ Pain and Cause of Pain.
WHO analgesic ladder.
The WHO Analgesic Ladder
“This three-step
approach of administering the
right drug in the right dose at the
right time is inexpensive
and 80-90% effective.”
WHO advisory panel 2008
If Rx following the WHO ladder’
patients rated their pain relief :
Good 76%
Satisfactory 12%
Inadequate 12%
Zech DF, Grond s et al, Pain 1995;63:65-76
WHO Analgesic ladder : Principles of use
• By the mouth. Oral meds whenever possible
• By the clock. Continuous pain should be treated with regularly
scheduled meds + breakthrough meds as needed.
• By the ladder. Choose step appropriate for patient’s pain. No ceiling
for pure opioids as long as patient gets benefit and can tolerate side effects.
• For the individual. The “right dose” is the dose of the right drug
that adequately relieves the patients' pain with minimum side effects
• With attention to detail. Successful implementation requires
meticulous follow up once a new prescription is issued. Ascertain
compliance, drug efficacy and side effects.
Cancer pain relief , Geneva , Switzerland, WHO 1996.
WHO Ladder: Step 1: Non-Opioids
• Acetaminophen.
• NSAIDs
• Early use of CoAnalgesics
Acetaminophen
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N-Acetyl-Para-Amino-Phenol (APAP).
Potent antipyretic, weak anti-inflammatory
Mild to Moderate Analgesic actions...HOW?
Probable Central Cox 2 inhibitor
Serotonergic agent, acts via desc inhibitory pathways*
Blocks metabolism Cannabinoids.
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Oral bioavailabitlity: 70-100%. tmax: 0.5 to 1hr, t1/2: 1.5-2hrs
CYP metabolism : 4% to toxic metabolite NAPQI.
Caution: drug interactions,(Coumadin, and EtOH.)
Max daily dose 4gm/day.
Graham G G, et al. Mechanism of action of Paracetamol. Am J Ther 2005;12:46-55
NSAIDs
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Cox1 and Cox 2 inhibitors: Anti PGE2.
Opioid sparing.
Have both peripehral and central antihyperalgesic effects.
Poor correlation between anti-nociceptive effect and antiinflammatory effects and doses.
Anti-hyperalgesic effect related to ability to cross BBB.
Ceiling effect+ , must individualize dose.
Side effects: Renal, Cardiovascular, GI, CNS, Hypersensitivity
reactions, Platelet dysfunction,
Recommend: 2 week trial with close monitoring.
If ineffective the can try other NSAID
Burian M, Geisslinger G. Pharmacology and Therapeutics 107 (2005) 139-154
NSAIDs: Comparative Doses and Pharmacokinetics
(Lexicomp 2013)
Maximum
Recommended
Daily Dose (mg)
Time to peak levels
(hr)
Half life
(hr)
(ER)
225
2-3
1-2
Indomethacin
200
1-2
4.5
I.M/ I.V: 120
P.O: 40
400
0.5 - 1
2-6
3
11
15
4-5
15-20
Ibuprofen
3200
1-2
1.8-2.5
Naproxen
1500
2-4
12-15
1375
1-2
12-13
Drug
Diclofenac
( Voltaren)
(Indocid)
Ketoralac
( Toradol)
Celcoxib
(Celebrex)
Meloxicam
( Mobicox)
(Naprosyn)
Naproxen sodium
(Anaprox)
WHO Ladder: Step 2
‘Weak’ Opioids
• Codeine
• Tramadol
• Tapentadol
• Early use of appropriate Co analgesic
Tramadol
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Unique , Atypical opioid. Analgeisa=Codeine
4-phenyl-piperidine analogue of Codeine.
Partial μ opioid receptor agonist +
Serotonin and Norepinephrine reuptake inhibitor.
Oral bioavailaibility: 68 – 90%* ( *rpt dosing)
Metabolism : Hepatic CYP 2D6.active metabolites (M1)
Renal excretion……..dose reduce in CKD.
?Better tolerated in elderly…? Marketing hype.
Dosing: 50mg o.d. increase to maximum 400mg/d.
Available as Tramacet , + IR and ER formulations
WHO Ladder: Step 3
‘Stronger’ Opioids
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Morphine
Hydromorphone
Fentanyl
Oxycodone
• Early use of appropriate Co analgesic
Molecular Mechanisms of Opioid Receptor-dependent
Signaling and Behavior.
Al-Hasani, Ream; Bruchas, Michael
Anesthesiology. 115(6):1363-1381, December 2011.
DOI: 10.1097/ALN.0b013e318238bba6
Fig. 1 . Sites of action of opioid
analgesics. The gray pathway shows
the sites of action on the pain
transmission pathway from
periphery to central nervous system.
The red pathway shows the actions
on pain-modulating neurons in the
midbrain and medulla. GABA =
[gamma]-aminobutyric acid; MOR =
[mu] opioid receptor.
© 2011 American Society of Anesthesiologists, Inc. Published by American Society of Anesthesiologists, Inc.
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Essential Discussion of Opioids
Discuss the implications of the use of opioids.
• Patients and family members are fearful of impending
death, addiction, tolerance, and nothing left for ‘later.’
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Discuss the most common side effects.
Nausea - tolerance.
Constipation – rarely tolerance.
Drowsiness especially when initiating therapy or
increasing the dose – and tolerance.
– Drowsiness may be related to pain relief.
Organ System Effects of Morphine and it`s Surrogates
Central Nervous System
↑ Analgesia
↑ Euphoria*
↑ Sedation
↓ Respiratory rate
↓Cough reflex
↑ Miosis
↑ Truncal rigidity **
↑ Nausea and vomiting
Behavioural restlessness.
*addiction potential
** esp Fentanyl/ Sufentanyl
Peripheral
Gastrointestinal system:
↑Constipation
↓Gastric motility
↓Digestion in small intestine
↓Peristaltic waves in the colon
↑Constriction of biliary sphincter
↑Esophageal reflux
Other Smooth Muscle:
↑Depression of Renal function
↓Uterine tone
↑Urinary retention
Skin:
↑Itching and sweating
↑Flushing of face/neck.
Cardiovascular System:
↓Blood Pressure + heart rate
Immune System:
↓Lymphocyte function
↓Cytotoxic activity of natural killer cells
Al-Hasani, Ream et al. Anesthesiology. 115(6):1363-1381, Dec 2011. Molecular Mechanisms of Opioid receptor-dependant signaling and behaviour.
Factors Associated with Successful Opioid Therapy
Age and weight (pharmacokinetic/pharmacodynamic differences)
Severity and Pathophysiology of pain
Severity, nature, extent of disease.
Allergies or drug intolerances
Psychological factors + History of addiction (CAGE)
Response to previous opioid therapy ( patient’s preference)
Co existing disease ( cardiovascular, Pulmonary, GI etc)
Renal and Liver function
Drug Route: PO / IV/ SQ/ TD / IT etc.
Pharmacodynamic Factors and Pharmacologic Interactions
Fitzgibbon D, et al . Lippincott, Cancer Pain, 2010
Onset + Duration of Opioid Analgesia
Drug
Morphine +
other short
acting opioids
Fentanyl
Route
Onset of
analgesia
(minutes)
Time to Max
Analgesia
Duration of
action
(hours)
Oral
30 – 40
minutes
1 to 1.5 hours
3 to 5 hours
SQ
10 -15
minutes
30 to 40
minutes
4 hours
IV
5 - 8 minutes
10 to 20
minutes
3 to 4 hours
Buccal
3 to 5
5- 10 min
60 minutes
SQ
2 to 3
5-10 min
60 mins
IV
1 to 2
5-8 min
60 mins
(McCaffery & Pasero 1999)
Equianalgesic Tables
• “ When changing opioids, caution must be exercised
because the equianalgesic dose ratios that are found
on widely available published tables largely represent
average data from controlled single-dose studies in
selected populations.
The ratios fail to account for the incomplete cross
tolerance, which would render the new drug more
potent than anticipated”.
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Enting RH et al : A prospective study evaluating the response of patients with unrelieved cancer pain to parenteral opioids.
Cancer 94:3049-3056, 2002.
Equianalgesic Table
Drug
S/C (IV)
P.O.
Morphine
10mgs
20mg
Hydromorphone
2mgs
4mg
Oxycodone
N/A
10 to 15mg
Codeine
60mgs
120mg
Fentanyl
100 to 125 mcg sc
Tramadol
N/A
150mg
Merperidine
75mgs
300mgs
Methadone
N/A
2mgs
Top 10 drugs most frequently reported as causing
harm as a consequence of medication error
ISMP 2006
#1: Insulin (54)
#2: Morphine (43)
#3: Hydromorphone (32)***
#4: Heparin (unfractionated) (19)
#5: Fentanyl (11)
#6: Warfarin (10)
#7: Furosemide (9)
#8: Dalteparin‡ (7)
#9: Metoprolol‡ (7)
#10:Ramipril‡ (7)
These 10 drugs accounted for 199 of 465 harmful medication incidents that were
reported to ISMP Canada over a 5-year period (2001 to 2005).
5 mg
Hydromorphone 2013
ISMPCanada Safety Bulletin Vol 13 (10) Nov 4
th
2013.
• All opioid medications require attention to ensure patient safety.
HYDROmorphone, a potent opioid, is the most common medication
associated with harmful medication incidents voluntarily reported to ISMP
Canada.
• From January 2000 to September 2013, ISMP Canada received 233
incidents involving HYDROmorphone with an outcome of harm or death
via AnalyzeERR®* and individual practitioner reports.
Medical examiners identified 3 specific risk factors for harm with HDM:
1: continued presence of high-dose HYDROmorphone in patient care areas
leading to ten-fold overdoses.
2: Excessive starting doses of HYDROmorphone, and
3: inconsistent monitoring of patients receiving opioids
Time To Rehabilitate Morphine
“The Gold standard” ESMO 2012
2012:ESMO Clinical Practice Guidelines.
Ripamonti C.I, et al . Management of cancer pain: ESMO clinical practice Guidelines. Annals of Oncology 23
(Suppl):vii139-vii154, 2012.
• ``The opioid of first choice for moderate to
severe cancer pain is oral morphine.``
There is no evidence ...that other opioids are superior to
morphine in terms of efficacy and tolerability.
2012: Evidence based recommendations from the EAPC.
Caraceni A, et al Lancet Oncol 2012;13:e58-68.
• ``The data show no important differences between
Morphine, Oxycodone and Hydromorphone.... any of
them could be first choice. ``
Hydromorphone Vs Morphine
• “In conclusion there is evidence to support
the efficacy and tolerability of
hydromorphone for moderate to severe
cancer pain as an alternative to morphine and
oxycodone,
• while there is NO evidence to demonstrate it’s
superiority or inferiority in comparison with
Morphine as the first choice opioid for the
same indication.
Pigni A et al, Palliative Medicine 25(5) 471 -477 (2010)
Quigley C. Cochrane Database Syste Rev 2002 ( updated 2009)
Morphine
Named after Morpheus - God of dreams
Gold standard
Alkaloid from opium
Commercially sold 1827
Opiate/Narcotic
Hydromorphone
Dihydromorphinone
Morphine Derivative - semi synthetic
Hydrogenated ketone
Opiate/Narcotic
Clinical use - 1926
Pharmacology: Morphine Vs
Hydromorphone
Morphine
Hydromorphone
Bioavailability
25-35% Oral
30 -40% Oral
Protein Binding
30-40%
20%
Metabolism
Hepatic
Hepatic
Metabolites (major)
M3G, M6G
H3G, H6G
Half-life
2-3 hours
2-3 hours
Excretion
Renal
Renal
Route
PO/IV/IM/SC/IT/PR
PO/IV/IM/SC/IT/PR
Potency
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Major Opioid Metabolites
The Metabolism of Opioid Agents and the Clinical Impact of Their Active Metabolites.
Smith, Howard
Clinical Journal of Pain. 27(9):824-838, November/December 2011.
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Pharmacologic properties attributable to M3G, M6G, and
H3G (Care beyond cure p 52, 4 2010)
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M3G ( + H3G)
Central agitation
Hallucinations
Myoclonus
Convulsions
Coma
Hyperalgesia
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M6G ( + H6G)
Sedation
Nausea
Respiratory depression
Coma
Analgesic effect
Factors that may increase accumulation of Morphine/HDM metabolites
Age > 70yrs.
Renal failure ( factors that may ppt RF : urinary obstruction, Meds e.g. NSAIDs, ACE etc,
cancers: MM, Lymphoma]
Dehydration
Rapid + substantial increases in opioid doses
Long term use.
Key Principles of Opioid Use
• DOSE: look at the effect !!! NOT at the milligrams.
• The desired effect is pain relief with tolerable or
manageable side effects.
• Adequate trial by dose titration.
• Increase the dose up to the appearance of limiting
side effects. ( Effect OR Toxicity)
• Genetics of opioid receptors-variants determine
analgesic response to a greater degree than
differences in opioid metabolism and clearance
= Individualise treatment plan
Rationalizing Opioid Rotations
British Journal of Clinical Pharmacology
Volume 75, Issue 1, pages 60-78, 14 DEC 2012 DOI: 10.1111/j.1365-2125.2012.04317.x
Oxycodone
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Morphine like – but not ‘morphine’.
Twice the potency of morphine (1.5 to 2)
Combined product – Oxycodone 5 mg + acetaminophen
325 mg.
Oxycocet, Percocet, Percodan, endone, endocet.
Limited to 12 pills per day due to acetaminophen
(325mg/tab).
Expected duration of action 4 hours.
Pure Oxycodone – Peak time to effect 60 minutes
Partially Active metabolites. Noroxycodone +
oxymorphone
? Less toxic in renal failure
Long Acting – OxyNeo 10, 20, 40 & 80mgs.
Currently NO parenteral formulation in Canada.
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Fentanyl
NOT morphine like.
Inactive when swallowed.
Hepatic metabolism- metabolites are inactive + non-toxic
Renal excretion; < 10% of unchanged drug excreted in
urine.
? Safer in hepatic + renal failure.
Absorbed buccally, sublingually, subcutaneously,
intravenously.
75 times more potent than morphine.
VERY short acting.
SC dose peak time to effect 15-20mins.
SC dose duration of action 40-60 mins.
Long Acting Preparations
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Establish the dose.
Calculate the appropriate breakthrough dose.
Be aware of the slow rise in serum values.
Peak time to effect is about 8 hours.
However, provides constant opioid release.
Improved compliance and QoL.
• Not Indicated as First Option in Acute Pain !
Transdermal Fentanyl
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Fentanyl TD duration of action ~72 hours.
Slow onset of action when initiated.
Cachectic patients may require patch changes q48hours.
Apply above the waist.
Apply to an area that is well perfused.
Do not apply over a hairy area.
Do not shave - but clip if necessary.
Ensure good adhesion.
Dose dependent on surface area.
Rotate patch sites.
Managing Cancer Pain.
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History of Cancer + History of Pain.
Standard assessment tools (ESAS, BPI)
Document pain syndromes involved.
Is cause known? – appropriate investigations.
Formulate Treatment plan - ‘realistic goals’.
Target Treatment @ Pain and Cause of Pain.
WHO analgesic ladder.
Early use of Co-Analgesics: Multi-Modal Analgesia
Synaptic Nociceptive Receptors and Transmitters:
****Potential Targets for Multimodal Analgesics.
Mellar P. Davis
13 - Cancer pain
Supportive Oncology null 2011 122 - 135
Targets for Multimodal Analgesia
Mechanism
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Opioid Receptors
Prostaglandin synthesis
Na+ ion influx
Ca+ ion influx
NMDA receptor
Cannabinoid receptors
?..............................
Medication options
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mu opioid agonists
Cox -2 inhibitors/ NSAIDs
Na+ channel blocker ( Lidocaine)
Ca+ channel blocker (Gabapentoids)
NMDA-r antagonist (e.g.ketamine)
DTHC,
Tricyclic Antidepressants.
• TCA’s First line adjuvant in NCP.
• Actions: Monoamine reuptake inhibition
Na+ and Ca++ channel blocker
Antihistaminergic
Weak NMDA receptor antagonist
• Response rate: 51-87% in cancer pain
Sindrup, Pain (1999) ;83: 389-400
Antidepressants as Analgesics
Reuptake
inhibition
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Norepinephrine
Examples
Amitriptylline
Nortriptylline
Impiramine
Desipramine
SSRIs
Trazadone
Analgesic
efficacy
NNT
1.7
(1.4-2.6)
3.2
( 2.6-5)
6.7
(3.5-9)
Antichol
side effects
Norepinephrine
Serotonin
+
Serotonin
++
+
+/-
Sindrup Pain 1999;83: 389-400
Tricyclic Antidepressants
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Nortriptylline / Amitriptylline
Start:
10 mg/day
Titrate: 3 – 7 days by 10 – 25 mg/day
Max:
usual antidepressant dose
Limited by side effects
Alternatives
– Venlafaxine
– Duloxetine
– SSRIs of limited use.
University of Ottawa Institute of Palliative
Care
Gabapentoids
• Pregabalin + Gabapentin.
• α 2-δ calcium channel(N)blocker..widespread
throughout PNS and CNS
• Atypical anticonvulsants.
• Effective in neuropathic pain: DPN, PHN,
Incisional injury, Inflammatory injury,
• APS: Opioid sparing (periop).
• Generalized Anxiety Disorder ( mood stabiliser).
• Sleep modulating drug .
(Noor M.Gajraj. Anesth Analg 2007;105:1805-15)
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Pregabalin: Its Pharmacology and Use in Pain Management.
Gajraj, Noor; MD, FRCA
Anesthesia & Analgesia. 105(6):1805-1815, December 2007.
© 2007 by International Anesthesia Research Society. Published by Lippincott Williams & Wilkins, Inc.
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Comparison of Gabapentin
and Pregabalin
Pregabalin: Its Pharmacology and Use in Pain Management.Gajraj,
Noor; MD, FRCA. Anesthesia & Analgesia. 105(6):1805-1815, December 2007.
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Modified “WHO” Ladder
Mild
Pain
1-3
Moderate
Pain
4-6
Severe
Pain
7-10
Methadone
CADDs
Acetaminophen
ASA
NSAIDs
+/- Adjuvants
Combined meds
Codeine
Tramadol
Oxycodone
with
acetaminophen
Morphine
Oxycodone
Hydromorphone
Fentanyl
+/- adjuvants
Ketamine
Lidocaine
Neuraxial Options
Adapted from The WHO 3 Step Analgesic Ladder,
Cancer Pain Relief, 2nd Edition, WHO
Managing Cancer Pain.
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History of Cancer + History of Pain.
Standard assessment tools (ESAS, BPI)
Document pain syndromes involved.
Is cause known? – appropriate investigations.
Formulate Treatment plan - ‘realistic goals’.
Target Treatment @ Pain and Cause of Pain.
WHO analgesic ladder.
Early use of Co-Analgesics: Multi-Modal Analgesia
Balance treatment efficacy/side effects /cost.
Set dose and time limits for review.
Case: OPN
• 63yo lady with 2 week hx of gradually worsening low
back pain. 5/10, worse at night + with standing.
• Phx: Breast cancer 2005. Rx SX Chemo Xrt
• Dhx: Metoprolol, Acetaminophen 3gm/d.
• Ahx: nil known------ “nervous about narcotics”
• Psy/Soc hx: CAGE –ve.
• Exam: Well, localized tenderness D6/7, no neuro
deficit.
• Next steps………….
Case OPN contd….
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Impression: Predominantly somatic pain
Investigations: XRay/ Labs – Met D6
Treatment: Step2 WHO ladder.
Codeine/ Tramadol/ Morphine all reasonable
Laxative prescription……
Consider coanalgesics ( await KFT)
Refer Onc – restaging / PXRT ,Bisphos etc..
Case : HW
• HW 56 yo man with NSCLC , hepatic + bone mets+
• Presents with increasing pain (R) hip, , escalating
opioid intake, nausea, drowsy, myoclonic++
• Dhx: HDM Contin 12mg q 8hr + HDM 4mg prn, used
6 prns in past 24hrs ( Total HDM 60mg po/d).
Gabapentin 600mg t.id.
• Exam: PPS 50%. Dry+, drowsy, mumbling, anxious,
Myoclonic jerks, CAM+
• Tender ++R hip, unable to weight bear.
Case :HW
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Imp: Uncontrolled pain + Delirium
Dehydrated, Opioid toxic, ? Op induced hyperalgesia
X-rays: bone mets (R) Femur++. Labs-Ca/LFTs
Rx: IV Fluids, Haloperidol 1mg sq stat + q 12hr
d/c HDM Contin + po prn ( total oral HDM prev 24h=60mg).
↓Hydromorphone SQ 3 mg q 4hr straight ( = 40%↓),
prn 2mg sq q 1hr prn…check effect.
• Consult: Rad Onc ?PXRT . Consider ortho referral
• After 24hrs IVF + haldol, delirium ↓ but still CAM+
• Opioid rotation…..options Fentanyl / Morphine.
Case : HW
1) Continue Rehydration + Haloperidol
2) Calculate MEDD = 18mg HDM sq/d straight + 12mg prn
= 30mg parenteral HDM/d = 300mg MEDD.
3) Reduce MEDD x 25-50%, (we chose 180mg/d)
4) Morphine 15 mg SQ q 4hr straight + Morphine
10mg sq q 1hr prn.
5) Treat cause of pain (Prohphylactic Pin femur + XRT.)
6) After 48hrs, delirium resolved, pain control improved,
rotated to oral Morphine 30mg po q 4hr,, and finally to
Mesilon 90 mg b.i.d + 20 mg po q 2hr prn.
Setting the Scene:
• YOU!!
are called @ 01:00hrs to the ER
• 76 yo lady (AB) is screaming in pain.....writhing on
stretcher
• “nothing is working, you have got to do something”
• Family upset++ “she is a cancer patient and no one
cares”
• Phx: Breast cancer x years, known bone mets, Off rx.
• “Do something !!!”
Mrs AB contd
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Hx: Sudden onset Mid dorsal spine pain. Hx x 4 hrs
T3 x 6 po ..no effect
Dhx: Metoprolol/ Lipitor
AHx: Prior Opioids with surgery ..nausea++
Demerol 50mg im no analgesic effect…..vomiting++
Localized pain, no weakness or sensory deficit.
Phx: breast cancer.. OFF Rx………active+++
Cannot image …..cannot lie still
Exam: Distressed+, nutrition/hydration /color-normal
No obvious delirium, Moving all 4 limbs+
Remains Distressed ++++
Assessment: Acute Pain Crisis ( 10+)mainly Somatic ? Osp #
Mrs AB: A Pain In the ER contd…..
• Management: Morphine 2mg iv + Maxeran 10mg iv stat
• Reassess after 30 minutes:
Pain 8/10 : Increase (double) Morphine 4mg iv
• Reassess after 30 minutes: Pain 5/10: repeat Morphine 4mg
IV …..can be repeated q 30minutes prn.
• COMPLETE INVESTIGATIONS. Including lab/Xray-MRI
• MRI: Pathological fracture of T8 bony metastases.
NO SCC……….but major metastatic bone disease progression
• Rx: CADD Morphine, Dexamethasone, vertebroplasty.+/- XRT
Neil A. Hagen, Tom Elwood & Scott Ernst
Journal of Pain & Symptom management
Vol. 14 No. 1 July 1997.
DMD:
• 46yo F, with 3/12hx escalating back pain, now using walker……..pain
10/10+ ( + = “don’t ask anymore!)
• Exam: pale frail “small” lady….distress++,
• Multiple tender points on spine, ribs + pelvis.
• PPS 50%.
• Pain: somatic with ++++ incident pain, minor NP
• Labs; Hgb 70g/l, Creatinine 250umol/l
• Meds: Dex 8mg/d, HDM Contin 12mg b.i.d+ 4mg q 2hr, TCA
• Intolerant opioids…nauseating, drowsy, hallucinations+
• CADD Fentanyl 60ucg/hr…........helps but cannot move due to
pain!...increasing dose ….drowsy+ hallucinations.
• Dx: Multiple myeloma/ renal failure/ low opioid
threshold……………….MRI --
Xena “ Warrior Princess”
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PCA Ketamine 2mg /hr …no bolus
Day3 ..Combined Fentanyl (40) + Ketamine (2) per ml
Rate 1.5 mls /hr , 1 ml q 20mins prn.
Pain controlled at rest -- Start chemo + physio + TLSO brace.
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Day 80: PCA a nuisance. …..cant go to rehab with it.
Feeling better……….mobilising well……how about the PCA?
Start Methadone 2.5mg q 8hr……titrate PCA
Day 8 ..stop PCA, Methadone 10mg q 8hr + 5 mg q 3hrs prn
HOME.
Successful Treatment of Pain
Depends On …………
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Determining that pain is present!
Focused History and Physical Exam
Identifying + Charting Pain mechanisms involved
WHO analgesic ladder. Clear Treatment plan
Predominance of neuropathic or incident pain
Presence or absence of Delirium
Patient’s + family’s expectations and beliefs
Goals of Care clear.
Attitudes + Knowledge of Health Care Professionals
Leave your egos at the door!
Questions??
Dilemma in Palliative Care
I really think you should sue your doctor for
malpractice! Two years ago he only gave you six
months to live!
Another Case
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Mr. B is a 74 year old man with extensive
small cell cancer of the lung. (PPS 40%)
Multiple hepatic and bone metastases.
Hepatic and renal function normal.
Initially treated with chemotherapy and
radiation to the lung and the spine.
Presented to the clinic with complaints of
increasing ‘excruciating’ back pain (10+/10).
The Case Continued….
On initial assessment Mr B described the following:
• Constant aching pain in his mid back with bandlike pain across his chest
• Mild numbness and tingling from his waist down
• Pain rated at 6/10 that increased to 10/10 with
any movement or weight bearing.
• Sharp stabbing component of pain on movement
Current medication:
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MS Contin 75 mg Q12H (MEDD 150mg)
PO Morphine sulphate 15 mg Q2H PRN
PO Dexamethasone 2 mg daily
Acetaminophen 500mg q 6hr straight
Laxatives
• Pain 10+/10
How do we deal with his pain?
• What type(s) of pain does Mr. B describe?
- Somatic
- Neuropathic
• Emergency pain management
Management:• IV morphine 15 mg given stat ( Prior MS
Contin 150mg/d)
• Waited 30 minutes
• Pain rated at 7/10
• IV morphine doubled (30 mg)
• Pain reassessed – 4/10
• S/C Morphine 30mg ordered Q4H regularly
and Q1H PRN ( Ms Contin discontinued)
• Complete investigations: MRI spine
Causes of Mr. B’s Pain
• MRI spine: Progression of bone mets in
thoracic and lumbar spine with possible
compression fractures but no SCC
• CT scan also shows extensive progression of
lung and liver metastases
Additional Management
• Dexamethasone 16mg/d
• Pregabalin 25mg po stat + t.i.d.
• Titrated to 50mg t.i.d after 48hrs.
• Urgent PXRT
Continuation
• Mr. B’s baseline pain improved however
incidental pain remained challenging. He
required frequent breakthrough pain
medication but developed some confusion
and myoclonus, drowsiness +. Dry+
• Morphine changed to dilaudid SC infusion via
CADD (5 X stronger than morphine)
• IV hydration.
Continuation
• Mr. B was discharged home on Dec 23rd to
spend Christmas with his family @ home.
• Mr. B died on Dec 30th peacefully at home
surrounded by his family.
Vision for Palliative Care
Every person, when faced with an incurable disease,
has the opportunity to live life fully,
to receive timely and appropriate symptom management,
to be supported along with his/her family with dignity
and respect throughout the course of their illness,
and in the face of incurable disease,
to have the opportunity to die in a setting of his/her choice.
CCO Signature Event: Toronto March 2006
JAMA. 2008;299(12):1457-1467. doi:10.1001/jama.299.12.1457
From: Managing an Acute Pain Crisis in a Patient With Advanced Cancer: “This Is as Much of a Crisis as a
Code”
:
Copyright © 2012 American Medical
Association. All rights reserved.
Opioid Responsiveness
A patient in pain should not be
declared “unresponsive to opioids”
until he/she has failed a titrated,
sequential trial of all of the different
opioid analgesics.
DN4
Four questions that can elicit 10 different pain
sensations.
Each point that is positive is given a score of 1.
A score of >or=4 is positive for neuropathic
pain.
Sensitivity: 82.9%; Specificity:89.9%)
Bouhassira, D.(2005) Pain; 114:29-36
Ketoralac:
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parenteral NSAID analgesic
NSAID: non-selective reversible Cox1 +2 inhibitor.
30mg IV equianalgesic with 10-12mg Moprhine.
Oral bioavailability= 100%
Onset analgesia IV/IM = 30mins, Peak 2hrs, duration 8hrs.
Dosing: IV/IM 30mg q hr prn ( max 120mg/d)
Oral: 20mg stat, 10mg po q 4hr prn (max 40mg /d)
Max duration of use ( ≤5 days).
• Metabolism: 68-92% excreted unchanged in urine.
• Toxicity: Renal: increase risk ATN, ARF , esp if dehydrated.
CVS: increased risk thrombotic events (MI /CVA)
GI: increased peptic ulceration/perforation
*All side effects increased with prolonged use ≥5 days *