Cancer Pain Management 101 Sarah Beth Harrington, MD Internal Medicine Noon Conference November 30, 2007

Objectives Review primary causes of cancer-related pain. Recognize effects of pain on cancer patients. Understand basic concepts of pharmacologic management techniques with opioids and non-opioids. Discuss non-pharmacologic techniques in cancer pain management.

Causes of Cancer-Related Pain Tumor / Mass effect Post-chemotherapy Post-radiation Post-surgical

Somatic Pain Tumor / Mass effect Musculoskeletal Dull, sharp, localized We can also break down cancer pain into somatic, visceral, and neuropathic & I’ll give some examples of these. Somatic pain is usually from tumor or mass effect – cutaneous pain receptors activated if tumor is more superficial (ex. Chest wall pain) We see bone metastastases, or tumors affecting anywhere in the pt’s muskuloskeletal system – usually come across as somatic pain. Pts describe this pain as dull, sometimes sharp, but very well localized

Pt with breast ca with bone mets – came in with R hip and pelvis pain –met extending into the joint space- see R superior and inferior pubic ramus fx/ischial spine – large met + fracture

Pt with H&N cancer – large R sided mass – ex. Somatic pain

Visceral Pain infiltration, compression, extension, or stretching of the thoracic, abdominal, or pelvic viscera pressure, deep, squeezing not well-localized referred Most cancer pts have some sort of combination of somatic and visceral pain Most common examples – pancreatic, liver mets, malignant pl effusion

Colorectal CA with liver met – left lobe of liver – visceral pain

Lady with cervical CA with diffuse carcinomatosis

Same lady with cervical CA – what else to you see Same lady with cervical CA – what else to you see?? Vertebral met – localized somatic pain to vertebrae, visceral pain in abdomen – and neuropathic pain from nerve root involvement – ex – many cancer pts will have several sources and can have a combination of how they’re experiencing pain

Neuropathic Pain CA compressing or infiltrating nerves/nerve roots/blood supply to nerve Nerve damage from treatments Shooting, sharp, burning, “pins & needles” Cranial neuropathies Post-herpetic neuropathies Brachial plexus neuropathies Post-radiation Can arise anywhere in nervous system, central, spinal cord, peripheral nerves – ca compressing or infiltrating nerves/nerve roots/ nerve damage from ca Descriptions – Ex. Some common syndromes that you may see – cranial neuruopathy – pt with skull based mets or brain mets, post-herpetic neuropathies – at high risk with immunosuppression for acute zoster infection or recurrence of latent zoster (Always always look at skin) Brachial plexus neuropathies – infiltration of #1 Breast #2 NSCLC After radiation – especially to brachial plexus, lumbar plexus, post-radiation mucositis in head and neck, ex. Young pt we’re following with cervical ca – post-radiation cystitis; overall seeing less of this as radiation techniques have become more sophisticated and precise

Neuropathic Pain Chemotherapy-induced neuropathies Cisplatin, Oxaliplatin Paclitaxil, Thalidomide Vincristine, Vinblastine Surgical Neuropathies Phantom limb pain Post-mastectomy syndrome Post-thoracotomy syndrome Pts can have chemo-related neuropathies – cisplatin, taxol, the vinca alkaloid are well known players – Pts usually have a symmetrical polyneuropathy – localized in hands and feet SURGICAL neuropathies – have distinct pain syndromes – phantom limb pain s/p amputation Post-mastectomy syndrome – neuropathic pain in posterior arm, axilla and anterior chest wall – due to the interruption of the intercostal brachial nerve (cutaneous sensory branch of T1-2) – little bit of a misnomer – you see this syndrome in women who have undergone a radical mastectomy, lumpectomy, even just an axillary node dissection ; 5% of women who undergo any of those procedures will have this syndrome (ex. Lady with dcis – b mastectomy- did fine (felt a lump in her axilla – lymph node dissection (fortunately benign) and since then has had debilitating neuropathic pain) Same with post-thoracotomy – neuropathic pain along the distribution of an intercostal nerve following injury or surgery – ex. Lung ca pts s/p lobectomy

Lastly – what type of neuropathic pain does this picture demonstrate Lastly – what type of neuropathic pain does this picture demonstrate?? – CORD compression – which we’ll talk about later

Summary Causes Descriptors Tumor size may not correlate with pain intensity Causes of cancer pain – tumor itself, post-chemo, post-radiation, post surgical ; somatic, visceral, neuropathic or a combination

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 Effects of pain in the cancer patient – all of these can increase pt’s mortality

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

What Does Pain Mean to Patients? Poor prognosis or impending death Particularly when pain worsens Decreased autonomy Impaired physical and social function Decreased enjoyment and quality of life Challenges to dignity Threat of increased physical suffering Equating pain with poor prognosis, impending death – often don’t bring it up

Principles of Assessment Ask Dispel myths/ misunderstandings Believe the patient Assess and REASSESS Use methods appropriate to cognitive status and context Assess intensity, relief, mood, and side effects Include the family A few basic principles of assessment – ASK Dispel myths / misunderstandings – often many of my pts don’t tell me about worsening pain because they’re afraid I will think they’re an addict – which cannot be further from the truth Assess and reassess – as outpt – if you start something new – have pt come and see you in another week or 2, or call them after a few days to see how the tx is working – don’t start a pain medication and not f/u for 2 months; same as inpt – see this all too often – pt is in terrible pain – put on a PCA at 6 pm – not reassessed until team rounds at 9 AM -& they’ve been in 10/10 pain all night pushing their button – must reassess every few hours at minimum - Use appropriate assessment techniques – the pain scale or faces don’t work for everyone – take function into account – often elderly pts won’t admit to “pain” – but may to “discomfort, aching, hurting”

Patient Pain History Site(s) of pain/radiation? Quality? Severity of pain? Onset / duration What aggravates or relieves pain? Impact on sleep, mood, activity? Effectiveness of medication?

Pharmacologic Management WHO Ladder Non-opioid therapy / Co-analgesics Opioids Now that we’ve gone thru causes and basics of assessment – we will touch on some of the most common treatments of cancer pain – won’t have the time to go through these in depth, but the point is to review what’s available and to give some basic pain management tips - Start with pharmacologic management – huge topic I know – what I hope to do is go over the WHO ladder of CA pain management, review non-opioid therapy, then touch on some basics when using opioids (which is usually your mainstay of therapy)

WHO Ladder Everyone should be familiar with this ladder – the world health organization put these guidelines together for cancer pain management – what I want you to take away from this (seems obvious, but you’d be surprised) – If pt is not relieved by one step – go up one – don’t waste your time or the pt’s time by staying on one step or going back a step – ex. – pt with prostate ca with bony mets – admitted through the ER with severe bone pain – had been on po dilaudid at home (strong opioid) with pain unrelieved – was admitted and what opioid do you think he was put on? Percocet – my favorite – does that make sense?? Seems obvious – right? But we see this every DAY on the pain consult service

Non-Opioids Practice Points: NSAIDS Mild pain Acetaminophen “ceiling” effect Start at lowest effective dose Review pt’s underlying medical illnesses NSAIDS Acetaminophen Topicals Lidocaine, Capsaicin NSAIDS/ acetaminophen alone usually do not provide sufficient relief for pts with cancer pain, although I have had some success with pts receiving hormonal tx for prostate ca/ NSAID alone for bone pain Acetaminophen – liver problems Topicals – lidocaine patch (fda approved for postherpetic neuralgia)can help pts with very focal pain, neuropathic pain – ex. Post-thoracotomy, post mastectomy, pain around a chest tube); if you use the lidocaine cream – tell pts to use recommended dosage – pretty small amount – one pt we consulted on in house – terrible neuropathic pain both legs and using handfuls – rubbing on both legs – can be absorbed and cause arrythmias PP – try alone for very mild pain, usually use these in combination with an opioid, understand that these have a ceiling effect, start at lowest effective dose, review pt’s underlying medical illnesses – NSAIDS I usually don’t give for pts > 70, renal insufficiency, heart failure, GI bleed hx

Adjuvants Antidepressants TCAs for neuropathic pain Anticonvulsants Corticosteroids Neuroleptics Alpha2 – agonists Benzodiazepines Antispasmodics Muscle relaxants NMDA-blockers Systemic local anesthetics Adjuvant analgesics are drugs with a primary indication other than pain, but have some analgesic properties in some painful conditions. These can be used alone, but are usually coadministered with other analgesics – particularly helpful in pts with neuropathic pain or bone pain Antidepressants – TCAs – have the most evidence of effectiveness on neuropathic pain, other antidepressants – SSRIs and those that affect uptake of serotonin and norepinephrine – studies have mostly been done in the nonmalignant pain population to show some pain relief, some of the newer ones – like duloxitine (cymbalta) has FDA approval for neuropathic pain – really helped some of our cancer patients Anticonvulsants – gabapentin, pregabalin (lyrica), keppra, dilantin Corticosteroids - inhibit prostaglandin synthesis – decrease firing from injured nerves – diminsh pain signals from periphery to spinal cord or from spinal cord to brain, also decrease capillary permeability thereby reduce edema - which is why these are used for cord compression, edema around brain mets, steroids are also good for pain due to peripheral nerve injury (breast cancer invading brachial plexus) Neuroleptics- few case studies of atypical neuroleptics – zyprexa – useful pain adjuvant Alpha blockers – clonidine – adjuvant Benzos – evidence is limited and often confusing; with the right pt Antispasmotics – baclofen (GABA – antagonist) Muscle relaxants - robaxin NMDA-blockers – ketamine Lidocaine infusion -

Adjuvants Bone pain Practice Points: Bisphosphonates Calcitonin Pain from malignant bowel obstruction Steroids Octreotide Anticholinergics Practice Points: Choose adjuvant carefully (risk:benefit) Start low and titrate gradually Avoid initiating several adjuvants concurrently Some specific clinical situations seen in cancer pts – bone pain – - use of calcitonin, bisphosphonates for bone pain – well established - Malignant bowel obstruction – very challenging to treat – steroids – mechanisms of action not exactly known, octreotide and anticholinergics (scopolamine, glycopyrrolate) can decrease gastric, pancreatic, and intestinal secretions and gut motility

Opioids Step 2 opioids Step 3 opioids Codeine, Oxycodone, tramadol, hydrocodone Step 3 opioids Oxycodone, morphine, dilaudid, fentanyl, methadone AVOID: meperidine, agonists/antagonists, combo agents, propoxyphene Step 2 opioids – in my experience – cancer pain is rarely mild enough to be managed with these – codeine is usually more trouble than it’s worth – nausea, constipation – to have any pain relief – it must be metabolically converted to morphine by a specific hepatic enzyme. Pts who either lack that enzyme or who are taking drugs that inhibit that function – will get no pain relief (would avoid altogether), oxycodone can be useful by itself (avoid combo agents – percocet – effectively put a celing on your drug w/ tylenol Tramadol – not technically an opioid, but binds to opioid receptors - can be good for mild pain, hydrocodone – usually the form is in vicodin or lortab – and is just not strong enough to affect cancer pain Examples of step 3 opioids – higher dose oxycodone, morphine, dilaudid, fentanyl, methadone – where we usually are when we talk about cancer pain; we’ll go over some basic prescribing practices DRUGS to avoid – Demerol – usually given for postop/postpartum pain – not recommended for cancer pain relief for a whole host of reasons – relieves pain for ~ 2 hrs, meperidine’s toxic metabolite is normeperidine – highserum levels – can cause seizures – accumulates rapidly with renal insufficiency; would avoid agonist/antagonists (stadol) – ceiling effect, can precipitate w/d when used with opioids, avoid combo agents with tylenol(- cets), propoxyphene (darvon/darvocet) – studies – no different than placebo, toxic metabolites

Opioids Practice Points: If pain constant/chronic – use long-acting opioids with short-acting for breakthrough Breakthrough dose - 10-20% of total daily dose Assess pt’s clinical and financial situation before prescribing Very few cancer pts with chronic pain will find adequate relief with just short acting opioids Figuring out a breakthrough dose – 10-20% of pt’s total daily dose clinical situation – able to swallow??, PEG tube??, what can they afford? Fentanl patch $25/patch, oxycontin is about 3x as much as MS contin

Mr. Smith 58 yo AAM with chronic bone pain from met. prostate CA. Prescribed Percocet (5/325) in the ER 2 weeks ago and is now in your clinic for f/u. Pain is well controlled, but tends to recur ~1 hr before the next dose. He takes 2 Percocets q4hrs around the clock, even at night.

Mr. Smith 10mg oxycodone 6 times/day = 60mg oxycodone in 24 hrs Equivalent SR oxycodone= Oxycontin 30mg q12h Rescue dose – 10% (60mg) = 6 mg 20% (60mg) = 12mg ANSWER: Oxycontin 30mg q12h with Oxycodone 5-10mg q4h prn Intern – what’s wrong with this picture – right away – Tylenol 3900mg /day, short acting for chronic pain –

Changing opioids Intolerable side effects, method of delivery, cost Practice points Incomplete cross-tolerance with different opioids Start new opioid at ½-⅔ of equianalgesic dose Cards – equal analgesic conversions – guides – always take into account pt’s age/comorbidities - calculate the new opioid dose, then reduce it by a half-2/3 – how do I decide? Depends on the pt / age/comorbidities– for elderly, those with bad lung function, kidney/liver dz, I usually go ½, everyone else usually go 2/3 (some pts who are very opioid tolerant or who have terrible pain, I may go 75% or not reduce at all – but 2/3 is a conservative place to start Cards – equalanalgesic dosing – lets do some examples

Ms. B 50 yo breast CA survivor with chronic neuropathic pain from her mastectomy. She currently is well-controlled on a 75 mcg/hr fentanyl patch. She lost her job and can no longer afford the patch. You want to switch her to MS Contin with MS IR for breakthrough. What dose?

Ms. B 75 mg po morphine/day 75 mcg/hr fentanyl patch ⅔ (225 mg) ≈ 150 mg morphine/day 75 mg MS Contin q12h Breakthrough - 10% 150 = 15 mg 20% 150 = 30 mg MS Contin 75 mg q12h with 15-30mg MS IR prn 75 mcg/hr fentanyl patch 75 mg po morphine/day 25 mcg/hr fentanyl patch 225 mg po morphine/day Lots of conversions – handout in the back with step by step instructions on how to do a variety of conversions using the ratios on the pink card – so recommend going through these when you have some free time - Summary – Use long acting opioids for chronic/constant pain, breakthrough pain meds should be at 10-20% of total daily dose, when changing opioids, use your equianalgesic dosing guides and reduce by ½-2/3 for cross-tolerance

Parenteral Opioids 1mg IV morphine = 3 mg po morphine 1mg IV dilaudid = 4-5 po dilaudid Rapid escalation, assess pt’s pain needs (PCA), fast-acting IV opioids – severe pain, need to be able to rapidly escalate pain medications

PCA tips How to order – IV PCA dose q6 min, basal, bolus q1hr prn If pt on a long-acting opioid – can continue po or convert all to IV basal (DO NOT STOP) REASSESS, REASSESS, REASSESS Double PCA and bolus dose if pain score worse or >50% original SQ option – morphine & dilaudid – higher concentration; PCA dose q15 min Do a skills session on PCA cases – guidelines– what I want you to take away from this is – don’t’ stop a pt’s long acting opioid, and reassess pt’s pain and level of sedation every 1-2 hrs until pain is under adequate control. The biggest mistake I see residents making is not reassessing. Pt gets admitted with terrible pain – team puts in a pca order –usually way underdosing – then goes home and pt doesn’t get seen until 12 hrs later. You can put in a very conservative PCA dose, but reassess the pt every 1-2 hrs and increase as needed

Opioid adverse effects Common Uncommon Constipation Bad dreams / hallucinations Dry mouth Dysphoria / delirium Nausea / vomiting Myoclonus / seizures Sedation Pruritus / urticaria Sweats Respiratory depression Urinary retention Constipation – easier to prevent than treat; all pts on opioids need a bowel regimen, dry mouth, nausea, sedation – usually go away in a few days; always clarify when a pt says they have an allergy to morphine More uncommon adverse effects can combat many side effects with medication, or with opioid rotation The big fear – respiratory depression – pts will fall asleep/somnolent before their resp drive is affected When we see it – pts continuing to get their opioids after they’ve become somnolent – RNs, family pushing pca, combining benzos and opiates; if vitals are stable and pt protecting airway – can just observe – if showing signs of resp depression – then give narcan

Radiation / Nuclear Medicine Radiation – curative treatment, adjuvant, palliative Bone metastases – pain response rate 35-60%, duration 12-24 wks Strontium-89 Radiation plays a very important role in the multidisciplinary management of pts with cancer. It can be local treatment with curative intent for a localized tumor, it can be adjuvant treatment after surgery, or can be palliative intent – relieve symptoms Bone mets – 40% palliative radiation workload – relief of bone pain, prevention of impending fractures, and can promote healing of pathalogic fractures – depending on what study you look at – 35-60% of pts with pain from bony mets get a complete response rate (most get at least a partial response, can lower opioid dose); other uses – whole brain, etc. Pts with bone mets – may benefit from strontium – structurally similar to calcium and is deposited in bone – give good pain relief for several months – consider this option when external beam radiation is maxed – side effects - myelosuppression

Non-Pharmacologic Management Acupuncture Yoga Guided imagery Cold/heat Massage Vibration TENS units Exercise programs Hypnosis Counseling Music Pet therapy

Cancer Pain Emergencies (a.k.a. things you can’t miss) Cord Compression Withdrawal Bone Mets/Impending Fractures Cord compression – pts with mets to spine – back pain is the 1st sign of cord compression – 70% of ca pts with new onset back pain or worsening back pain with abnormal spine films without neurological signs have an epidural metastases; the biggest mistake that most physicians make is waiting for abnormal physical findings before pursuing any diagnostic tests; BOTTOM line – if a cancer pt has new onset or worsening back pain – you are obligated to rule out cord compression with an MRI – if you wait until there are neurologic signs or b/b dysfunction – it’s usually too late – most will never be able to regain that function even if they are treated. What do you do if you suspect?? – MRI + steroids ; if + , get a stat neurosurg and rad/onc consult Pt accepted to our service from another hospital – finished chemo and was having intractable N/V – was on MS contin 200 q12h at home – at outside hospital, just couldn’t get his n/v undercontrol – had stopped his long-acting morphine since he couldn’t tolerate po – by the time he rolled in he was diaphoretic, full body tremors, n/v – now in withdrawal Impending fractures – bone mets – good rule of thumb – if more than 50% bone is affected – impending fracture; careful attention to femoral head – 2.5 cm lesion there – needs ortho consult – internal fixation or joint replacement

WHO Ladder We’ve reviewed some opioid/non-opioid, and nonpharmacalogic treatments for cancer-pain - Studies show that correctly using the WHO ladder with opioid titration – 80% of cancer pts will have good relief of their cancer pain

What about the 20%!? Have the opioids been titrated aggressively? Is the pain neuropathic? Has a true pain assessment been accomplished? Have you examined the patient? Is the patient receiving their medication? Is the medication schedule and route appropriate? What about the 20% who still have pain despite maximal treatment? Ask these questions That’s when I think you need to look outside the box, call in reinforcements/specialists – Pall care, radiation, orthopedics, interventional radiology

Modified WHO Analgesic Ladder Pain Step 1 ± Nonopioid Adjuvant Pain persisting or increasing Step 2 Opioid for mild to moderate pain Step 3 Opioid for moderate to severe pain Invasive treatments Opioid Delivery Quality of Life Proposed 4th Step The WHO Ladder Proposed 4th step – looking at quality of life, changing opioid delivery, looking at invasive treatments Deer, et al., 1999

Cancer pain management 201 Interventions Blocks Epidural Intrathecal pain pumps Lidocaine infusion Ketamine Sedation Go to CA pain management 201- beyond the scope of this talk – but realize that there are other options out there and for the vast majority – we can get their pain under control

Interventions Palliative surgery Nerve Blocks Kyphoplasty/Vertebroplasty Epidural Intrathecal pain pumps Skim over these briefly – Palliative surgery – ex. Diverting colostomy for malignant bowel obstruction Nerve blocks/neuroablation – regional anesthetic procedures that can include blocks of spinal nerves, peripheral nerves, and sympathetic ganglia Kyphoplasty or vertebroplasty – tecniques used by interventional radiology – mets to spine causing very focal pain – collapsed vertebrae – IR will go in with a needle into the vertebrae itself and inject cement – for stabilization and pain relief Epidural medications – steroids, local anesthetic – bupivicaine, ropivacaine – give it in such a way/ concentrations to preserve motor function; temporary – risk of infection Intrathecal pain pumps are small pumps – catheter is implanted into the intrathecal space – deliver multiple medications; pink card – 1:10:100 ratio – so if a pt is requiring 50mg/hr IV morphine = 5mg/hr epidural = 0.5 mg/hr intrathecal – good pain relief with just a small amount of medication and few side effects

Celiac Plexus Block Ex. – pt with very painful pancreatic CA – Celiac plexus block – anterior approach

Celiac Plexus Block Takes a talented radiologist – aorta Hypogastric block

Kyphoplasty/Vertebroplasty How it works – helps with axial load, cement is very hot and theory is that intraosseous nerve endings are burned and that helps with pain relief – usually immediate

Kyphoplasty/Vertebroplasty How it works – helps with axial load, cement is very hot and theory is that intraosseous nerve endings are burned and that helps with pain relief – usually immediate - Not much difference – vertebroplasty – insert needle and cement – kyphoplasty – use balloon 1st

Intrathecal Pain Pumps Pain pump is inserted under the skin – usually in abdomen/ catheter is threaded into the intrathecal space for continuous delivery

Intrathecal Pain Pumps Size of a hockey puck/ pacemaker (made by medtronic)– has access- pump usually has to be refilled as early as every 3 months – accessed like a port – medication can be reconstituted when refilled – morphine, dilaudid, baclofen, bupivicaine, clonidine, weird stuff like snail venom; we follow these pts in clinic

Lady with met breast ca – had an intrathecal pain pump – fyi – if a pt comes into the hospital with one of these – please let us know

Conclusion Cancer pain can be from the cancer itself, or from cancer-related treatments Can be somatic, visceral, or neuropathic Negative effects of cancer-related pain can effect QOL, mortality Ask the patient about pain and REASSESS!

Conclusion Choose non-opioid / adjuvants carefully paying close attention to side effect profile Use WHO ladder guidelines when titrating pain medications Use long-acting opioids for chronic cancer pain Recognize “4th step” in WHO ladder and utilize your multidisciplinary resources Resources – radiation, surgery, anesthesia, neurosurgery, palliative care service – help with some non-traditions things like ketamine, lidocaine infusions

Palliative Care Service N4N – 6-1295 Fellows: Dr. Paresh Patel, Dr. Keith Swetz NPs – Pat Coyne and Bart Bobb

Questions?