Cancer pain management Dr. Varun Goel MEDICAL ONCOLOGISTRAJIV 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-Chemotherapy b-Radiotherapy c-Post surgical syndromeTotally unrelated: 3-10%
Pain syndromes unrelated to cancer orcancer therapy• Lumbar disk disease• Osteoarthitis
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
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
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.
VERBAL DESCRIPTOR SCALES Five word scaling MILD DISCOMFORTING DISTRESSING HORRIBLE EXCRUCIATINGDISADV: Limited selection of descriptors Pt. tend to select moderate grades than extremes.
VERBAL NUMERIC RATING SCALE On a numeric scale 0 to 100-no pain10-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 scaleexcept that the pt. marks on a measuredline, one end of which is labeled NO PAINand other end WORST IMAGINABLEPAIN, where the pain falls
MULTIDIMENSIONAL INSTRUMENTS• Provides more complex information about pt pain• Time consuming
Measurement Tools Multidimensional 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
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 eachmeasure is presented to the patient separately inthe numbered order
Barriers to Effective Cancer Pain Management despite the availability of straight forward, cost effective therapies, Cancer Pain remains undertreated
BarriersRelated 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
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 Pain1) Eliminating or modifying the source of pain2) Modifying the interpretation of the pain message at the level of CNS3) 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.
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)
WHO Analgesic Ladder Pain persisting or increasing Severe Pain Opioid for moderate to severe pain Step 3 Nonopioid Adjuvant Pain persisting or increasingModerate Pain Opioid for mild to moderate pain Nonopioid Adjuvant Step 2 Pain persisting or increasingMild Pain Nonopioid Adjuvant Step 1 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 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 trisalicylatep-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 1,000COX-2 inhibitor Celecoxib qd–q12 100 200
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 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)
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.
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 administrationUse of morphine equivalents
Equianalgesic I.V. or I.M. Dose Drug (mg) Morphine 10Oxymorphone 1Hydromorphone 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. to from 50% of new 100% 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 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 pain25% increase 4-6/10 Mild pain 1-3/10
If pain constant/chronic – use long-acting opioids with short-acting for breakthroughBaseline Pain = Extended release morphineBreakthrough = 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 Can be divided good adhesion Guarantee stable Fentanyl in dissolved blood fentanyl level state with no ethanol for 72 h as permeation enhancer
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 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.
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
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.
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 PainDeer, et al., 1999