1. Cancer pain management
Dr. Varun Goel
MEDICAL ONCOLOGIST
RAJIV GANDHI CANCER INSTITUTE, DELHI
2. INTRODUCTION
After Incurability, Pain the most fearful and the
most distressful symptom.
Inadequate Pain control profound alteration in
nearly all aspect of wellness( activity-mood-rest-
nutrition-sexuality..etc)
Optimal Pain control, may hasten a return to
normality (function-physiologic-spiritual-
psychologic,economic,vocational,survivorship)
3. INTRODUCTION
Def. - A unpleasant sensory and emotional
experience associated with actual or potential
tissue damage or described in terms of such
damage.
~25% - newly diagnosed patients
~ 33% - patients undergoing treatment
~ 75% - with advanced disease.
Fortunately, 70-90% of pt. got adequate pain
control with stabilized guideline
The rest 10-30% of pt. need more invasive
procedures
4. Origin either (T-T-T)
Tumor related: 60-80% of patients
Therapy induced: 20-25% of patients
a-Chemotherapy
b-Radiotherapy
c-Post surgical syndrome
Totally unrelated: 3-10%
8. NOCICEPTIVE NEUROPATHIC
Injury – somatic and Injury – PNS or CNS
visceral structure
So subdivided into
somatic - Sharp, well Burning, sharp or
localized, throbbing shooting
and pressure like
visceral pain – diffuse,
aching or cramping
After surgical
Adverse effects of
procedures, bone
chemothepray or
metastasis,
radiotherapy
infilteration or
distension of viscera
9. Physiological effects of Pain
Increased catabolic demands: poor wound
healing, weakness, muscle breakdown
Decreased limb movement: increased risk of
DVT/PE
Respiratory effects: shallow breathing,
tachypnea, cough suppression increasing risk of
pneumonia and atelectasis
Increased sodium and water retention (renal)
Decreased gastrointestinal mobility
Tachycardia and elevated blood pressure
11. Immunological effects of Pain
Decrease natural killer cell counts
Effects on other lymphocytes not yet
defined
12. ASSESSMENT OF PAIN
no objective measurement of pain
pain history is the key to assess it
Intensity of pain is the most difficult and frustrating
characteristics of pain to pinpoint
Few scales and tests are available.
13. COMPREHENSIVE PAIN
ASSESSMENT
Detailed history
type and quality of pain,
onset, duration, course,
intensity (i.e., pain experienced at rest; with movement; interference
with activities);
location,
radiation of pain;
the associated factors that exacerbate or relieve the pain,
current pain management plan and patient’s response
prior pain therapies;
important psychosocial factors
patient distress,
family and other support,
psychiatric history
Diagnose the etiology and pathophysiology (somatic,
visceral, or neuropathic) of the pain.
15. VERBAL DESCRIPTOR SCALES
Five word scaling
MILD
DISCOMFORTING
DISTRESSING
HORRIBLE
EXCRUCIATING
DISADV:
Limited selection of descriptors
Pt. tend to select moderate grades than
extremes.
16. VERBAL NUMERIC RATING SCALE
On a numeric scale 0 to 10
0-no pain
10-worst pain imaginable
ADVANTAGES:
• Simplicity, reproducibility, easy comprehensibility
• Sensitivity to small changes in pain
• Children at 5 years, who can count and have concept
about numbers can use this scale
17. VISUAL ANALOG SCALE(VAS)
Similar to verbal numerical scale
except that the pt. marks on a measured
line, one end of which is labeled NO PAIN
and other end WORST IMAGINABLE
PAIN, where the pain falls
21. McGILL PAIN QUESTIONNAIRE (MPQ)
• Most frequently used multidimensional test
• Descriptive words from three major
dimensions of pain (sensory, affective,
evaluative) are further sub-divided into 20
sub-classes each containing words of various
degrees
• 3 scores are obtained one from each
dimension and total score is calculated
• Reliable and used in clinical research
22.
23. BRIEF PAIN IN VENTORY (BPI)
• Patients are asked to rate the severity of their
pain at its “worst “,”least” or “average” within
the past 24 hrs. and at the time the rating is
done.
• It also requires the patient to represent the
location of their pain on a schematic diagram of
the body
• BPI correlates with activity, sleep and social
interaction.
25. Card is folded along broken line so that each
measure is presented to the patient separately in
the numbered order
26. Barriers to Effective Cancer Pain
Management
despite the availability of straight
forward, cost effective therapies, Cancer
Pain remains undertreated
27. Barriers
Related to Health Care Professionals
Inadequate knowledge of management
Poor assessment of pain
Concern about:
regulation of controlled substances
side effects of analgesics
tolerance to analgesics
Fear of patient addiction
28. common patient-related barriers to pain
management
Drugs ..
are addicting
should be saved for
when it is really
needed
have unpleasant or
dangerous side
effects
pills are not as
effective as a shot
narcotics are only for
dying people
29. Institutional barriers
Lack of commitment to make pain treatment
a priority
Lack of resources
Lack of use of instruments for pain
assessment
30. Strategies to Attack Cancer
Pain
1) Eliminating or modifying the source of pain
2) Modifying the interpretation of the pain
message at the level of CNS
3) Interrupting the pain signal
En route from periphery to the CNS
It has been proved that pain modification
at multiple site is an effective therapy.
31. Modify the source of pain
Surgery (acute pain-post surgical pain syndrome)
Radiotherapy(post radiation pain)
Chemo and Hormonal Therapy
Modify the interpretation of pain message
Pharmacological Analgesics
Psychological support and Relaxation tech.
32. Pharmacological Analgesics
First line of treatment
WHO Analgesic Ladder and NCCN guideline
Oral route as long as possible
Three levels of pain intensity
Mild pain (1-3)
Moderate pain (4-6)
Severe pain (7-10)
33. WHO Analgesic Ladder
Pain persisting or increasing
Severe Pain Opioid for moderate to severe pain
Step 3
Nonopioid Adjuvant
Pain persisting or increasing
Moderate Pain Opioid for mild to moderate pain
Nonopioid Adjuvant Step 2
Pain persisting or increasing
Mild Pain
Nonopioid
Adjuvant
Step 1
Pain
34. Step 1: Acetaminophen & NSAID
Acetaminophen (paracetamol,).
Equipotent to aspirin
no anti-inflammatory or antiplatelet actions.
The starting dose is 650 mg PO q.i.d. and the
maximum is 4,000 mg/day.
35. NSAIDS
Mechanism: Cyclooxygenase inhibitor (COX-1
and COX-2)
PG E2 degradation
Decrease pain by reducing pain receptor
sensitivity, reduce the inflammatory process
and edema
36. Salicylates
Aspirin is the standard against which other NSAIDs
are compared.
Aspirin should not be used in patients with a h/o the
syndrome of nasal polyps and asthma, gastritis, peptic
ulcer disease, or bleeding diathesis (including severe
thrombocytopenia or concomitant use of
anticoagulants).
Cyclo-oxygenase (COX) inhibitors
divided into nonselective and selective COX-2
inhibitors.
COX-1 - present in most tissues, helps maintain
gastric mucosa, and influences kidney and platelet
function.
COX-2 - induced in response to injury and involved
in the inflammatory cascade
37. The nonselective inhibitors can cause
gastric ulcers and GI bleeding as well as
affect platelet function.
The selective COX-2 inhibitors have
relatively reduced the risk of GI toxicity
and reduced antiplatelet effect.
38. NSAID-induced ulcer disease may be
reduced by the
Co-administration of H2 blockers or proton
pump inhibitors such as omeprazole (20 mg PO
daily).
Misoprostol 100 mcg PO q.i.d. can also
ameliorate the GI side effects.
39. Nonopioid Analgesics for Mild to Moderate Pain
Recommended Starting Dose
Class Generic Name Dosing Schedule Maximum Dose (mg)
(mg)
Salicylates Aspirin q4–6h 2,600 6,000
Choline magnesium
q12h 200 600
trisalicylate
p-Aminophenol Acetaminophen
q4–6h 2,600 4,000
derivative (paracetamol)
Propionic acids Ibuprofen q4–8h 1,200 3,200
Fenoprofen q4–6h 800 3,200
Ketoprofen q6–8h 150 300
Naproxen q12h 550 1,100
Naproxen sodium q12h 550 1,100
Acetic acids Etodolac q6–8h 600 1,200
Ketorolac q6h 15–30 q6h IV, IM 10 q6h PO 120 IV, IM 40 PO
Fenamates Meclofenamic acid q6–8h 150 400
Mefenamic acid q6h 500 × 1, then 250 q6h 1,000
COX-2 inhibitor Celecoxib qd–q12 100 200
41. Alter the unpleasant emotional experience
associated with pain
provide pain relief through the interaction with
specific opioid receptors - primary effect centrally.
The only significant differences among the various
opioids are duration of action and the dose needed
to produce the same analgesic effect.
No “ceiling” to opioid doses exists. Doses can be
escalated to provide analgesia as long as there are
no unacceptable toxicities.
Ineffectiveness observed while using opioids
usually indicates underdosing; Ineffectiveness may
also reflect progression of the underlying disease
42. Can be classified into three groups:
1) Morphine-like opioid agonists that bind
competitively with μ and κ receptors (e.g.,
codeine, fentanyl, hydromorphone, morphine,
oxycodone, and methadone)
2) Opioid antagonists that have no agonist receptor
activity (e.g., naloxone)
3) Mixed agonists-antagonists (e.g., pentazocine and
butorphanol) or partial agonists (e.g.,
buprenorphine)
44. Meperidine -repetitive intramuscular administration
is associated with local tissue fibrosis and sterile
abscess.
Repetitive dosing can also lead to accumulation of
normeperidine, an active metabolite that can
produce central nervous system hyperexcitability.
characterized by subtle mood effects followed by
tremors, multifocal myoclonus, and occasional seizures.
It occurs most commonly in patients with renal
disease
Naloxone does not reverse meperidine-induced
seizures, some case reports that the use of naloxone
has precipitated generalized seizures in individual
patients
45. Converting from an agonist to an agonist-
antagonist could precipitate a withdrawl
crisis in the opioids dependent patient.
46. Non opioids combinations containing
codeine, oxycodone, and propoxyphene are
available, but these combinations often
contain less than the full dose of 650 mg of
aspirin or acetaminophen.
Prescribing each drug separately provides a
better method for individualizing pain
control
47. Opioid combination products
Typically used for
Moderate episodic (PRN) pain
Breakthrough pain in addition to a long-acting
opioid.
Never prescribe more than one combination
drug at any one time.
50. How To Use Opioids?
Pure agonist as first line of therapy. Higher
incidence of psychotomimetic effect (dysphoria-
hallucination) and nausea and vomiting with A-A
Never mix agonist with agonist-antagonist
Don’t mix two agonist
Oral route whenever possible
Round the clock strategy-----important
51. Continue……
NEVER PRN. Continuous pain need
continuous analgesic.
Prevent resurgence of pain rather to treat it.
It is only acceptable for break through pain.
53. Equianalgesic I.V. or I.M. Dose
Drug
(mg)
Morphine 10
Oxymorphone 1
Hydromorphone 1.5
Methadone 10
Levorphanol 2
Fentanyl 250 mcg
54. Incomplete cross-tolerance
If a switch is being made from one opioid to another it
is recommended to start the new opioid at ~50% of
the equianalgesic dose.
This is because the tolerance a patient has towards one
opioid, may not completely transfer (“incomplete
cross-tolerance”) to the new opioid.
to
from 50%
of new
100% Opioid
55. In the opioid naive patient, the initial dose of MS
- 5 to 30 mg depending on the severity q4h.
In the opioid naive patient with severe pain, initial
MS doses of 2 to 4 mg IV or SQ can be given every
15 minutes as necessary to control pain.
When pain is controlled, total dose given becomes
the q4h dose
In the elderly patient, it is always best to “go low”
and “go slow.”
56. Once the optimal dose is found, the total
opioid amount is calculated and then
divided by two to yield the q12h, long-acting
dose.
57. Opioid Dose Escalation
Always increase by a percentage of the present dose based
upon patient’s pain rating and current assessment
50-100% increase
25-50% increase Severe pain
7-10/10
Moderate pain
25% increase 4-6/10
Mild pain
1-3/10
58. If pain constant/chronic – use long-acting opioids
with short-acting for breakthrough
Baseline Pain = Extended release morphine
Breakthrough = 10-20% increase.
59. Other routes for opioids
Rectal The oral–rectal potency ratio is 1:1.
Oxymorphone, hydromorphone and morphine
suppository
Sublingual and buccal more lipophilic
opioids such as fentanyl and methadone.
The buccal–oral potency ratio is 1:1.
Topical opioids. It is available in a 1 mg/mL
gel vehicle
60. Fentanyl patch
Simple, thin Can be divided
good adhesion Guarantee stable
Fentanyl in dissolved blood fentanyl level
state with no ethanol for 72 h
as permeation
enhancer
61.
62. Opioid Side Effects
Constipation – need proactive laxative use
Oral naloxone effective in treating constipation, but it may reverse
analgesic effect of opioids.
methylnaltrexone and alvimopan are peripherally acting antagonists.
Prevent constipation without interfering analgesia
Nausea/vomiting – consider treating with dopamine
antagonists and/or prokinetics (metoclopramide,
domperidone, prochlorperazine [Stemetil], haloperidol)
Urinary retention
Itch/rash – worse in children; may need low-dose
naloxone infusion. May try antihistamines, however not
great success.
Oxymorphone has reduced histaminic effects.
63. Respiratory depression – uncommon
when titrated in response to symptom
naloxone to reverse it. But an ET tube
should be placed before giving this.
Drug interactions
Neurotoxicity (OIN): delirium,
myoclonus seizures
64.
65. Drug interactions with opioids
Potentiators -by interfering with morphine
metabolism.
H2 blockers, antidepressants, phenothiazines,
and antianxiety agents.
decrease – by induce the metabolism of
morphine.
phenytoin, barbiturates, and rifampin.
MS effect on other agents. Morphine can
increase gabapentin levels
66. Co Analgesics
Definition
Agents which enhance analgesic efficacy,
have independent analgesic activity for specific
types of pain, and / or
relieve concurrent symptoms which exacerbate
pain
69. Adjuvant drugs
Corticosteroids are indicated in
refractory neuropathic pain,
bone pain,
pain associated with capsular distension (painful
hepatomegaly),
duct obstruction
headache associated with central nervous system (CNS)
metastasis,
bowel obstruction, and
ascites.
70. Adjuvant drugs
Bisphosphonate
for bone pain and fracture prevention from
osteolytic lesions of multiple myeloma.
may also be helpful in controlling bone pain in
up to 25% of patients with breast cancer or
prostate cancer.
72. Neuropathic pain syndromes
Typical doses are as follows:
Gabapentin starting dose is 300 mg PO HS. The maximal dose is
6,000 mg/day with q.i.d. dosing.
Phenytoin(Dilantin), 100 mg b.i.d.; increase by 100-mg
increments q3-7d.
Carbamazepine(Tegretol), 100 mg b.i.d.; increase by 100-mg
increments q3-7d.
Lamotrigine(Lamictal), 25 mg PO h.s.; increase dose q3d
Topiramate(Topamax), 25 mg PO h.s.; increase dose q3d
Valproic Acid(Depakote), 200 to 400 mg PO b.i.d. or t.i.d.
73. Neuropathic pain syndromes
Antidepressants are useful adjuvant analgesics
at doses below that needed to treat depression.
Tricyclic antidepressants, include amitriptyline ,
desipramine , nortriptyline , doxepin , and
imipramine .
These are started at 10 to 25 mg h.s. and titrated
upward at 10- to 25-mg increments every 5 to 7
days.
Selective serotonin reuptake inhibitors (SSRIs)
include fluoxetine , paroxetine , sertraline ,
citalopram , and fluvoxamine .
These drugs have performed inconsistently in
neuropathic pain trials.
74. Neuropathic pain syndromes
Systemic local anesthetics
IV lidocaine.
Response occurs at sub–anti-arrhythmic doses but lasts only a few
hours.
Mexiletine(Mexitil)
The starting dose is 50 mg t.i.d. PO (taken with meals) with
titration upward every 5 to 7 days.
Topical agents
Lidocaine patch, 5%(Lidoderm). On 12hrs off 12 hours (but can
leave on 24)
Topical capsaicin depletes substance P and may act as a
counterirritant.
Results in trials are mixed for peripheral neuropathy and pain may
actually worsen. It is not recommended.
Topical opioids
76. Transcutaneous electrical nerve stimulation
(TENS) has demonstrated efficacy in the
treatment of malignant disease,
problems encountered were waning effect and
sudden termination of effect.
The results of clinical trials on acupuncture
have been conflicting;
retrospective data suggest - any efficacy of
acupuncture for cancer pain is short lived.
77. Psychological methods of pain
control.
Behavioral modification
not generally effective for moderate to severe chronic
cancer pain, may be helpful for mild pain.
Operant conditioning,
hypnosis,
guided imagery, and
biofeedback are techniques that can be helpful for
chronic mild pain,
78. Role of Invasive Procedures
Optimal pharmacologic management
can achieve adequate pain control in
80-85% of patients
The need for more invasive modalities
should be infrequent
When indicated, results may be gratifying
These procedures are not for patients
a short life expectancy
in poor physical condition
79. Neuroablative procedures
Unilateral chordotomy - most effective
neuroablative procedure
useful for patients with unilateral cancer pain below the
shoulder.
Radiofrequency lesions to spinothalamic tracts of
the spinal cord are generally placed at the C-1 to
C-2 level.
80. Contralateral loss of superficial, deep, and visceral
pain is produced in >75% of patients treated with
percutaneous chordotomy.
The duration of analgesia is limited to only a few
months;
incapacitating dysesthesia may develop after
several months.
Sleep apnea, fecal and urinary incontinence, loss of
orgasm, and muscle weakness, on the other hand,
frequently complicate bilateral chordotomy.
81. Neuroablative procedures
Nerve blocks may be useful in patients with pain
restricted to a single somatic nerve or adjacent
nerves (e.g., postthoracotomy pain may be
relieved by subcostal blocks).
Celiac plexus nerve block - effective in up to 85%
of patients for treating upper abdominal visceral
pain, particularly from cancers of the pancreas or
stomach.
Lumbar sympathetic blockade - for pelvic visceral
pain.
It affects sphincter tone or lower extremity strength
uncommonly.
82. Modified WHO Analgesic Ladder
Invasive treatments
Proposed 4th Step Opioid Delivery
Pain persisting or increasing
Step 3
Opioid for moderate to severe pain
Nonopioid Adjuvant
Pain persisting or increasing
Step 2
Opioid for mild to moderate pain
The WHO Nonopioid Adjuvant
Ladder Pain persisting or increasing
Step 1
Nonopioid
Adjuvant
Pain
Deer, et al., 1999
