cancer pain dr. varun
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Cancer pain management
Dr. Varun GoelMEDICAL ONCOLOGIST
RAJIV GANDHI CANCER INSTITUTE, DELHI
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)
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
Origin either (T-T-T)Tumor related: 60-80% of patientsTherapy induced: 20-25% of patients
a-Chemotherapyb-Radiotherapyc-Post surgical syndrome
Totally unrelated: 3-10%
Cancer Pain Syndromes
Pain syndromes associated with tumor infiltration • Metastatic bone pain • Retroperitoneal lymphadenopathy pain • Liver capsule pain • Headache • Cranial neuralgias • Glossopharyngeal neuralgia • Trigeminal neuralgia • Perineal pain
Postradiation pain syndromes
• Radiation fibrosis of brachial plexus
• Radiation fibrosis of lumbosacral plexus
• Radiation myelopathy
• Radiation-induced peripheral nerve tumors
Pain syndromes associated with cancer therapy Postsurgical pain syndromes
• Postmastectomy pain • Postradical neck dissection pain • Post-thoracotomy pain • Phantom limb and stump pain
Postchemotherapy Cisplatin, OxaliplatinPaclitaxil, ThalidomideVincristine, Vinblastine
• myalgias, arthralgias,
• peripheral neuropathy • Steroid pseudorheumatism • Aseptic necrosis of bone • Headache
Pain syndromes unrelated to cancer or
cancer therapy
• Lumbar disk disease • Osteoarthitis
NOCICEPTIVE
Injury – somatic and visceral structure
So subdivided into somatic - Sharp, well
localized, throbbing and pressure like
visceral pain – diffuse, aching or cramping
After surgical procedures, bone metastasis, infilteration or distension of viscera
NEUROPATHIC
Injury – PNS or CNS
Burning, sharp or shooting
Adverse effects of chemothepray or radiotherapy
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
Psychological effects of Pain
Negative emotions: anxiety, depression
Sleep deprivation
Existential suffering
Immunological effects of Pain
Decrease natural killer cell counts Effects on other lymphocytes not yet
defined
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.
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.
PAIN ASSESSMENT SCALES
UNIDIMENSIONAL SELF REPORT SCALES
Very simple, Useful
Valid method to assess
VERBAL DESCRIPTOR SCALES
Five word scaling
MILDDISCOMFORTINGDISTRESSINGHORRIBLEEXCRUCIATING
DISADV:
Limited selection of descriptorsPt. tend to select moderate grades than
extremes.
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
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
MULTIDIMENSIONAL INSTRUMENTS
• Provides more complex information about pt pain
• Time consuming
Multidimensional Tools
Measurement Tools
Validated pain and symptom assessment scales in adults and children
-- MPQ- McGill Pain Questionnaire
-- BPI - Brief Pain Inventory
-- MPAC - Memorial pain assessment card
-- MSAS - Memorial Symptom Assessment Scale
-- ESAS - Edmonton Symptom Assessment Scale
The McGill Pain Questionnaire
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
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.
Memorial pain assessment card
Rapid to use Correlated with other measures
Card is folded along broken line so that each measure is presented to the patient separately in the numbered order
Barriers to Effective Cancer Pain Management
despite the availability of straight forward, cost effective therapies, Cancer Pain remains undertreated
Related to Health Care Professionals
Barriers
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
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
Institutional barriers
Lack of commitment to make pain treatment a priority
Lack of resources Lack of use of instruments for pain
assessment
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 signalEn route from periphery to the CNS
It has been proved that pain modification at multiple site is an effective therapy.
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.
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)
Pain
Step 1Nonopioid± Adjuvant
Pain persisting or increasing
Step 2Opioid for mild to moderate pain±Nonopioid ± Adjuvant
Pain persisting or increasing
Pain persisting or increasing
Step 3Opioid for moderate to severe pain
±Nonopioid ±Adjuvant
WHO Analgesic Ladder
Mild Pain
Moderate Pain
Severe Pain
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.
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
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
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.
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.
Nonopioid Analgesics for Mild to Moderate Pain
Class Generic Name Dosing ScheduleRecommended Starting Dose
(mg)Maximum Dose (mg)
Salicylates Aspirin q4–6h 2,600 6,000
Choline magnesium
trisalicylateq12h 200 600
p-Aminophenol
derivative
Acetaminophen
(paracetamol)q4–6h 2,600 4,000
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
Step 2 and 3: Opioids
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
Can be classified into three groups:
1) Morphine-like opioid agonists that bind competitively with and receptors (e.g., μ κcodeine, 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)
Opioids
Step 2 opioids Codeine, Oxycodone, tramadol, hydrocodone
Step 3 opioids Oxycodone, morphine, fentanyl, methadone
AVOID: meperidine, agonists/antagonists, combo agents
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
Converting from an agonist to an agonist-antagonist could precipitate a withdrawl crisis in the opioids dependent patient.
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
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.
Common Weak Opioids Percodan Oxycodone
5mgASA 325mg
Percocet Oxycodone 5mg
Acetaminophen 325mg
Lorcet Hydrocodone 10mg
Acetaminophen 650mg
Tylenol#3 #4
Codeine 30mgCodeine 60mg
Acetaminophen300mg
DHC plus Dihydrocodeine 16mg
Acetam.356mgCaffeine 30mg
Common Strong OpioidsGeneric Trade Route Equi.doses Duration.av
g
Morphine(MS)
MSIR ParenteralOral
10mg30mg
3-4 hr
MS.(S.R) MS Contin Oral 30mg 8-12 hr
Hyro-Morphone
Dilaudid ParenteralOral
1.5mg7.5mg
3-4 hr
Methadone Dolophine ParenteralOral
20mg10mg
4-8 hr4-8 hr
Levorphanol
Levo-Dromoran
ParenteralOral
2mg2mg
4-8 hr
Oxycodon SR
Oxycontin Oral 30mg 12 hr
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
Continue…… NEVER PRN. Continuous pain need
continuous analgesic. Prevent resurgence of pain rather to treat it. It is only acceptable for break through pain.
Equianalgesia
- Determining equal doses when changing drugs or routes of administration
Use of morphine equivalents
Drug Equianalgesic I.V. or I.M. Dose (mg)
Morphine 10
Oxymorphone 1
Hydromorphone 1.5
Methadone 10
Levorphanol 2
Fentanyl 250 mcg
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.
from
100%
to
50%of new Opioid
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.”
Once the optimal dose is found, the total opioid amount is calculated and then divided by two to yield the q12h, long-acting dose.
Opioid Dose EscalationAlways increase by a percentage of the present dose based upon patient’s pain rating and current assessment
Mild pain 1-3/10
25% increaseModerate pain4-6/10
25-50% increase Severe pain7-10/10
50-100% increase
If pain constant/chronic – use long-acting opioids with short-acting for breakthrough
Baseline Pain = Extended release morphine
Breakthrough = 10-20% increase.
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
Fentanyl patch
Simple, thin good adhesion Fentanyl in dissolved state with no
ethanol as permeation enhancer
Can be divided Guarantee stable blood fentanyl level for
72 h
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.
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
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
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
Adjuvants
Antidepressants TCAs for neuropathic
pain Anticonvulsants Corticosteroids Neuroleptics Alpha2 – agonists
Benzodiazepines Antispasmodics Muscle relaxants NMDA-blockers Systemic local anesthetics Antihistaminics
Adjuvants Bone pain
Bisphosphonates Calcitonin
Pain from malignant bowel obstruction Steroids Octreotide Anticholinergics
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.
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.
Analgesics for Neuropathic Pain
Tricyclic antidepressants Anticonvulsants
Gabapentin, Carbamazepine, Pregaba Local anesthetics
Parenteral, oral, topical Topical capsaicin Opioids
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.
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.
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
Non-Pharmacologic Management
Acupuncture Yoga Cold/heat Massage Vibration TENS units
Exercise programs Hypnosis Counseling Music
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.
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,
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
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.
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.
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.
Pain
Step 1±Nonopioid± Adjuvant
Pain persisting or increasing
Step 2Opioid for mild to moderate pain
±Nonopioid ± Adjuvant
Pain persisting or increasing
Pain persisting or increasing
Step 3Opioid for moderate to severe pain
±Nonopioid ±Adjuvant
Invasive treatments
Opioid Delivery
Modified WHO Analgesic Ladder
Proposed 4th Step
The WHOLadder
Deer, et al., 1999
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