2Sources of Pain in Cancer Patients Cancer pain comprises:Acute painChronic painTumor-specific painTreatment-related painCarr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD: Agency for Healthcare Research and Quality. July Downloaded aton 4/22/ Accessed 03/23/2009
3Existence of pain due to cancer More than two thirds of cancer patients report pain which they attribute to their cancerFrom S5 - Patients currently suffering from painMore than 50% of patients with the following types of cancer currently suffer from pain:LungPancreaticBrain TumourBone/MuscleBlood BorneNon-HodgkinsHead/NeckLeukaemiaBase: all screened – (individual base sizes shown on chart)S4. Have you suffered any pain due to your cancer?European Pain in Cancer (EPIC) Global Results Presentation, July 2007
4Where We Are Today in Managing Cancer Pain? Minorities, women, and the elderly are particularly at risk for cancer-related pain.1One survey found that while health care providers believe they are doing a good job at managing pain and its symptoms, families do not.2Cancer pain still pervasive in adults and children.3Cancer pain is undertreated in all settings where patients with cancer are managed.31. Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD:Agency for Healthcare Research and Quality. July Downloaded at on 4/22/ Accessed 03/23/20092. Tolle SW. Family reports of pain in dying hospitalized patients: a structured telephone survey. West J Med. 2000;172:3. Guideline for the Management of Cancer Pain in Adults and Children p x.
5You Are The Patient’s Advocate Patients with cancer are often reluctant to report the extent of their pain1Fear that reporting pain will take physician time away from their treatmentConcern about addictionBeliefs that “good” patients do not complain about painConcern about side effects with escalating dosesResult = under-treatment of pain1. Ward S, Goldberg N, Miller-McCauley V, et al. Patient-related barriers to management of cancer pain. Pain. 1993;52:
6The Effects of PainA majority of patients experience pain at some point during their course of cancer treatment.1Cancer pain impairs quality of life and functionality.1The cost of inadequate pain control and related side effects (of pain medications) is high, both in terms of impaired function and quality of life.2-4Pain interferes with all activities of daily living.51. Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD:Agency for Healthcare Research and Quality. July Downloaded at on 4/22/ Accessed 03/23/20092. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):3. Cleeland, CS. Undertreatment of cancer pain in elderly patients. JAMA 1998;279(23):4. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal drug delivery for the management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol. 2005;3(6):5. Mystakidou K, Tsilika E, Parpa E, et al.: Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs 29 (5): 400-5, 2006 Sep-Oct.
7Pain as the “Fifth Vital Sign” The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) issued a comprehensive description of patients’ rights and standards of care for pain management.Recommendation: make pain assessment/management priority in daily practiceConsider pain intensity the 5th vital sign: measure along with temperature, pulse, respiration, and blood pressurePatients’ rights: full pain workup when pain is not easily characterized or treatedJCAHO,
8Start with a Comprehensive Pain Assessment The National Cancer Institute recommends that the clinician help the patient describe pain1:LocationChanges in patternIntensity or severityAggravating and relieving factorsCognitive response to painGoals for pain controlThese are essential to the initial assessment:1Detailed history1Physical examination1Psychosocial assessment2Diagnostic evaluation1An accurate pain assessment helps to select an appropriate treatment for the patient’s pain level.Traditionally, the Visual Analog Scale (VAS) has measured intractable pain. Today, pain management specialists incorporate additional methods of analysis. The National Cancer Institute recommends that to enhance pain management, clinicians teach families to use pain assessment tools in their homes. The clinician should help the patient describe pain using the steps outlined above.1. National Cancer Institute Accessed May 12, 20092. Otis-Green S, Sherman R, Perez M, et al.: An integrated psychosocial-spiritual model for cancer pain management. Cancer Pract 10(Suppl 1): S58-65, 2002 May-Jun.
9Characterize the pathophysiology of pain Determine intensity of pain Assessment GoalsCharacterize the pathophysiology of painDetermine intensity of painDetermine impact on patient’s ability to function1. National Cancer Institute Accessed May 12, 2009
10Cancer Pain Therapy: The Oncologist’s Perspective Systemic pharmacologic therapyCollaboration with pain medicine and palliative care specialistsGood pain management facilitates good cancer managementSystemic pharmacologic therapy is the mainstay of cancer pain management, but oncologists need to explore other options for patients with intractable pain.Despite the appropriate use of pharmacologic guidelines, there will be a subset of patients whose comfort and function is unacceptable. For these patients, oncologists should consult and collaborate with a pain or palliative care specialist.Good pain management facilitates good cancer management. If patients are in too much pain, it can cause difficulty in lying on the radiation table or even in getting to chemotherapy appointments. In addition, there are a significant number of cancer survivors who have chronic treatment-related pain.Levy MH. Pain control in patients with cancer. Oncology. 1999;13(5 suppl 2):9-14.Levy MH. Pain control in patients with cancer. Oncology. 1999;13(5 suppl 2):9-14.
11Multidisciplinary Approach to Chronic Pain Management Multidisciplinary SolutionPhysiologicalfactorsSocialPsychologicalComplex ProblemPain specialistsPsychologistsNursesSocial workersRehabilitationspecialistsMultidisciplinary Approach to Pain ManagementChronic pain is a complex phenomenon and is best managed by amultidisciplinary team.Primary coordination of treatment may depend on the individual patient’sneeds and may change over time.For example, at one point the pain specialist’s input may be most urgent;subsequently, the rehabilitation specialist’s efforts may be mostimportant, while at another point psychological therapy may bewhat the patient needs most.Pain management challenges these disciplines to work together, oftenfor long periods of time.
12Cancer Pain Management Strategies Pharmacologic strategiesNonopioid analgesicsAcetaminophenNonsteroidal anti-inflammatory drugsOpioid analgesicsCoanalgesics (adjuvant analgesics)Physical strategiesMassageExerciseTranscutaneous electrical nerve stimulation (TENS)AcupuncturePsychological strategiesHypnosis or relaxation with imageryCognitive-behavioral methodsNerve blocksRadiation therapyChemotherapy1. Guideline for the Management of Cancer Pain in Adults and Children p
13Opioid Analgesics for the Treatment of Cancer Pain Used most often in the management of severe pain because:1EffectivenessEase of titrationFavorable risk-to-benefit ratioRoutes of administration2OralTransdermalParenteral: Intravenous or subcutaneousIntraspinal: Epidural or intrathecalConsider when other routes of administration cannot control pain or when side effects limit further dose escalationGuideline for the Management of Cancer Pain in Adults and Children p 53Ibid., p 64.
14Advanced Strategies for Intractable Cancer Pain Management 10-20% Invasive Therapy NeededPatients receiving oral/transdermal opioids and adjuvant therapy may experience adequate pain control in 80-90% of the cases.Thus in 10-20% of the patients, some form of invasive therapy will be needed to control refractory pain, despite aggressive titration.Invasive therapy may include:Nerve blocksEpidural analgesiaIntrathecal analgesia80-90% Adequate Pain ControlJacox A, et al. AHCPR, 1994.Portenoy R. Oncology 1999;S2:7.
15Spinal Anatomy Intrathecal Space (Subarachnoid Space) Epidural Space Arachnoid MembraneDuraPia MaterSpinal CordNerve RootTo understand the physiology of intraspinal opioids, it is helpful to review spinal anatomy.The spinal cord is surrounded by three meningeal layers:The outermost layer is the dura mater, or dura, which is a thick, dense membrane that protects the brain and spinal cord.An epidural space separates the dura and the vertebrae. The epidural space is composed of fatty tissue and can be used as a site for drug delivery with opioid therapy.The dura is adhered to the next meningeal layer, the arachnoid membrane.The arachnoid membrane is separated from the pia mater by a large subarachnoid, or intrathecal, space filled with cerebrospinal fluid. This clear, colorless fluid bathes the spinal cord and the brain, cushioning them from impact. The intrathecal space can also be used in intraspinal drug delivery.The third meningeal layer of the spine is the pia mater which covers the spinal cord.
16Epidural vs. Intrathecal Space (SubarachnoidSpace)EpiduralSpaceKeep in mind that the term “intraspinal administration” can refer to the delivery of analgesia to either the intrathecal or epidural space.It is extremely important to be able to differentiate the epidural and intrathecal spaces for intraspinal analgesia because:Some systems are designed for use in only the epidural space.The potency of an analgesic varies greatly when dosing for intrathecal versus epidural delivery. For example, a dose of preservative-free intrathecal morphine is approximately one-tenth of an equianalgesic epidural dose.The rate of drug absorption differs with epidural and intrathecal delivery.There are pros and cons to each delivery route, which we will overview in a moment.
17Physiology of Spinal Opioids Nociceptors carry a “pain” signal to the dorsal horn.In the dorsal horn neurons release substance P.Substance P triggers ascending neurons that carry this signal to the brain.Opioids inhibit the release of substance P, blocking the pain transmission.Perceived pain is reduced.Pain Signal InitiatedPain PerceivedThe physiology of pain begins with sensory neurons called nociceptors. A pain message is transmitted along these neurons to the dorsal horn of the spinal cord. 1In the dorsal horn, sensory neurons release several neurotransmitters that act on the dendrites of ascending neurons. Eventually, these ascending neurons carry the signal to the brain where it is perceived as pain. 1One of the key neurotransmitters in pain transmission is substance P. Opioids inhibit the release of substance P by bonding to sensory neurons. This, in effect, blocks the message before it reaches the brain and is perceived as pain. 11 Gianino, J., York, M., Paice, J. Intrathecal Drug Therapy for Spasticity and Pain. New York, NY: Springer-Verlag; 1996.
18Epidural vs. Intrathecal Opioids Some physicians prefer epidural delivery because there is a lower risk of respiratory depression than with intrathecal delivery.1There may also be a lower risk of serious complications because the dura is not punctured with epidural catheter placement.However, if analgesic is delivered epidurally, 80 to 90% of the drug is absorbed systemically. Therefore, more drug reaches the systemic circulation, which may lead to a greater incidence of side effects such as constipation and urinary retention.1In addition, epidural catheter placement has been associated with dural scarring, which inhibits opioid effectiveness.IntrathecalSome clinicians feel that intrathecal delivery is the preferred route for intraspinal drug delivery. 1Intrathecal administration has the advantage of lower drug dose and faster onset of analgesia. With intrathecal delivery there is also the option of CSF sampling for culture, diagnosis, and drug levels. 1Opioids delivered directly to the intrathecal space are particularly effective because they do not have to circulate systemically to reach the CSF and the dorsal horn of the spinal cord. 2 As a result, patients treated with this therapy generally experience fewer side effects than with epidural administration. 1The disadvantages of intrathecal delivery include the risk of CSF leakage (leading to spinal headaches), respiratory depression and an increased risk of meningeal infection. 11 Levy, R. Implanted Drug Delivery Systems for Control of Chronic Pain. Chapter 19 of Neurosurgical Management of Pain. New York, NY: Springer-Verlag; 1997.2 Gianino, J., York, M., Paice, J. Intrathecal Drug Therapy for Spasticity and Pain. New York, NY: Springer-Verlag; 1996.1. Levy, R. Implanted drug delivery systems for control of chronic pain. Chapter 19 of Neurosurgical Management of Pain. New York, NY: Springer-Verlag;1997.
19What is successful pain management? Success = Pain relief – Unmanageable side effects
20Side Effects of Cancer Pain Medications Fatigue: more prevalent than pain in patients with metastatic cancerDepressed level of consciousness, sedation: dose-limiting problems, may be treated with methylphenidate (Ritalin*)Constipation: managed with laxativesNausea: managed with antiemeticsDelirium, confusion: relatively rareRespiratory depression: very unusualFatigue is more prevalent than pain in patients with metastatic cancer. Pain, anxiety, depression, and insomnia all contribute to fatigue, as do drug side effects, infection, and neurologic problems.Depressed level of consciousness and sedation are serious dose-limiting side effect of opioids. However, these symptoms can be treated with methylphenidate (Ritalin).Constipation is the most frequent side effect of opioid therapy but one that is usually treated prophylactically. Because opioids permanently slow gut motility, laxatives should be prescribed for any patient taking opioids. In general, the higher the opioid dose, the more laxative/stool softener is necessary. The incidence of opioid induced nausea has been estimated to be 10%-40% and tolerance usually develops rapidly,typically 3-5 days or less.Cherny, N., Foley, K. Nonopioid and Opioid Analgesic Pharmacotherapy of Cancer Pain. In Hematology/Oncology Clinics of North America Vol.10. NO1, 2/96 PPAntiemetics should be available prophylactically if needed.Delirium and confusion are rarely caused by opioids alone. Contributing factors include brain lesions, oxygen depravation, metabolic or electrolyte imbalances, infections, or drug interactions. Sometimes delirium resolves if the opioid medication or dose is changed.Respiratory depression is rare.Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients. Baltimore, Md: The Johns Hopkins University Press; 2000.Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients*Ritalin is a registered trademark of Novartis Pharmaceuticals Corporation.
21Route of Administration Relative Potency (mg)* Approximate Equivalent Daily Doses of Morphine Administered by Various RoutesRoute of AdministrationRelative Potency (mg)*OralIntravenousEpiduralIntrathecal300100201*Relative approximations based on clinical observationsLamer TJ: Mayo Clin Proc.1994 May;69(5): Review.21
22Reduce Dose → Reduce Side Effects 1 mg intrathecal morphine = 300 mg oral morphineThe primary advantage of intrathecal pain therapy is the dramatic reduction in the amount of medication required for pain relief.Because medication goes directly into the spinal cord, much smaller doses are required than with oral or intravenous methods.Typically, the intrathecal to oral dose conversion is 1:300.Patients treated with this therapy can experience fewer side effects than with oral drug delivery.Krames ES. J Pain Symptom Manage Jun;11(6):Krames ES. J Pain Symptom Manage Jun;11(6):
23Intrathecal Drug Delivery: Patient Selection Criteria I. Symptoms of pain due to advanced stage cancer at presentation, with a minimum life expectancy of >3 months1-4II. Refractory to conventional pain management because of drug toxicity or unsatisfactory analgesia1-4III. Visual analog scale (VAS) of ≥ 5, despite 200 mg/day of oral morphine or the analgesic equivalent1,3,41. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refactory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):2. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal Drug Delivery for the Management of Cancer Pain: A Multidisciplinary Consensus of Best Clinical Practices. J Support Oncol. 2005;3(6):3. Smith TJ, Coyne PJ. Implantable Drug Delivery Systems (IDDS) After Failure of Comprehensive Medical Management (CMM) Can Palliate Symptoms in the Most Refractory Cancer Pain Patients. J Pall Med. 2005;8(4):4. Brogan, SE. Intrathecal Therapy for the Management of Cancer Pain. Curr Pain Head Rep. 2006;10:
24Intrathecal Drug Delivery: Patient Selection Criteria continued Consider those on lower doses if opioid side effects are refractory to conservative treatment and severe enough to prevent upward titration.1,3,4IV. Consider early evaluation of intrathecal drug delivery for those with pelvic tumors who may have eventual nerve compression.21. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refactory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):2. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal Drug Delivery for the Management of Cancer Pain: A Multidisciplinary Consensus of Best Clinical Practices. J Support Oncol. 2005;3(6):3. Smith TJ, Coyne PJ. Implantable Drug Delivery Systems (IDDS) After Failure of Comprehensive Medical Management (CMM) Can Palliate Symptoms in the Most Refractory Cancer Pain Patients. J Pall Med. 2005;8(4):4. Brogan, SE. Intrathecal Therapy for the Management of Cancer Pain. Curr Pain Head Rep. 2006;10:
25Contraindications to Intrathecal Drug Delivery When infection is presentWhen pump implant depth exceeds depth specified in pump labelingIntrathecal Drug Delivery ContraindicationsWhen body size is not sufficient to accept pump bulk and weightWhen contraindications exist relating to the drugDrugs with preservativesDo not use the patient control device, if applicable, to administer opioid to opioid-naïve patients or to administer ziconotideFor a complete list of contraindications, refer to the manufacturer labeling for the specific device.
26Initiating Intrathecal Drug Delivery Goals of care:clearly expressed in regard to invasive therapyPain-related factors:pathophysiology amenable to intrathecal therapyTreatment-limiting side effects from systemic therapy:somnolence or cognitive impairmentThe goals of care should be clear to both patient and physician.The pain must be potentially amenable to intrathecal therapy. The preimplantation trial allows pain relief and side effects of intrathecal therapy to be evaluated before committing to implantation.Central nervous system toxicity–such as sedation, mental clouding, or frank confusion–more strongly suggest the utility of intrathecal drug delivery than do gastrointestinal toxicity side effects, such as nausea.Portenoy RK. Managing pain in patients with advanced cancer: the role of neuraxial infusion. Oncology. 1999;13(5suppl 2):7-8.Portenoy RK. Managing pain in patients with advanced cancer; the role of neuraxial infusion. Oncology. 1999;13(5 suppl 2):7-8.
27Trial for Intrathecal Drug Delivery To evaluate patient’s responseAssess pain reliefEvaluate side effects50% pain reductionconsidered a positive resultOne of the advantages of implantable drug delivery systems is that the patient can be tested for responsiveness before a system is implanted.When you identify an appropriate cancer patient, the patient is informed of treatment options. If the patient and clinician decide to proceed, the patient is referred to a pain specialist or other implanting physician for a trial of intrathecal therapy.In a trial, a dose of medication is administered intrathecally or epidurally to determine if the patient may get pain relief with an implanted system.If the patient achieves pain relief of ≥50% with tolerable side effects, the trial is considered successful and the patient and physician may decide to proceed with the implantation of a drug delivery system.Hassenbusch SJ, Stanton-Hicks M, Covington EC. Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. J Pain Symptom Manage. 1995;10(5):Hassenbusch SJ, Stanton-Hicks M, Covington EC. Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. J Pain Symptom Manage. 1995;10(5):
28Intrathecal Drug Delivery: SynchroMed® II Infusion System The SynchroMed® infusion system from Medtronic became commercially available for the administration of intrathecal morphine for chronic pain in More than 75,000 patients worldwide have had the SynchroMed Infusion System implanted.It is totally implantable, offering greater convenience for the patient, assured patient compliance with dosing regimen, fewer complications compared with external systems, and maintenance of continuous drug levels.The programmability of the SynchroMed pump allows the clinician to titrate the drug dosage and delivery time to meet the needs of the individual patient.A programmer communicates to the pump via telemetry, allowing the clinician to alter the dose rate or amount of drug delivered non-invasively.
29Implanted Pump and Catheter Intraspinal CatheterPumpPump placementLeft or right abdomenEnough tissue for supportCatheter placementTunnel between spinal column and pumpmyPTM®Optional feature that gives patients the control and ability to respond to intermittent pain of varying intensityIndicated only for preservative-free morphineIntrathecal pain therapy is delivered by an implanted catheter connected toan implanted pump that releases prescribed amounts of medication –commonly morphine – into the spinal fluid.Intrathecal delivery enables the medication to reach the opiate receptors in the dorsal horn of the spinal cord almost immediately.By avoiding systemic distribution of medication, many side effects can be greatly reduced.
30Patient Management and Refills Refills and programming performed by trained clinicianRefill complete in minutesReimbursed procedureThe interval between refills varies according to the prescribed drug and dose.Some oncologists prefer to refill the pump at their offices. Others choose to have the pain specialist perform pump refills.Only a trained clinician (physician or nurse) may perform the refill, which typically takes 15 to 30 minutes. During a refill the clinician:Aspirates unused drug from the SynchroMed® infusion system.Fills the pump with the prescribed drug using a special refill kit.Programs new prescription information using a specialized N’Vision® programmer (physician only).Records the aspirated drug volume in patient’s records.Compares the expected residual drug volume with actual residual drug volume.Records the amount of new drug in the patient’s records.Schedules the next refill.
31Adverse Events with Intrathecal Drug Delivery Therapy There may be complications. The most frequently reported problems following intrathecal drug delivery system implant surgery include:InfectionSpinal fluid leakPump inversionSkin erosionDrug side effectsLoss of therapy effectTherapy that did not meet the patient’s expectationsSome of the most severe reported problems associated with intrathecal drug delivery therapy for intractable pain include:Inflammatory mass (a mass near the tip of the catheter)Spinal cord damageMeningitisLife-threatening drug adverse effects due to over infusion as a result of programming or patient monitoring errors or device malfunctionComplications due to use of unapproved drugs or not using drugs in accordance with drug labeling
32myPTM®* for Management of Intermittent Pain The Medtronic myPTM® is an optional feature of the SynchroMed II infusion system that allows patients to respond to intermittent pain of varying intensity with a physician-prescribed dose of medication from the pump. It is not for use with ziconotide.Prevalence of Intractable Pain74% of patientsThe percentage of patients with chronic non-cancer pain who experienced severe to excruciating breakthrough pain (n = 228).12.4 episodes/dayThe mean number of breakthrough pain episodes (defined as transitory exacerbation of pain that occurs on a background of otherwise controlled pain).160 minutes/pain episodeMedian duration of breakthrough pain episodes.1*In some cases, myPTM is a self-pay device. Check with your patient’s insurance before prescribing.1. Portenoy RK, Bennett DS, Rauck R, et al. Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain. J Pain. August 2006;7(8):
33myPTM®* for Management of Intermittent, Variable Pain The nature of pain is that it is variable. The occurrence and severity may change at particular times of the day, may be associated with particular activity, or may be unpredictable and have no pattern.myPTM® is an innovative enhancement to SynchroMed® II infusion system that gives patients the control and ability to respond to symptoms of episodic pain at onset.*In some cases, myPTM is a self-pay device. Check with your patient’s insurance before prescribing.
34Pump used for chemotherapy since 1988 ReimbursementPump used for chemotherapy since 1988FDA-approved for use with morphine in 1991Implant, refills, and programming covered by Medicare and most private carriers (check regional carriers for coverage)Medtronic offers assistance with coding, coverage, and payment informationImplanted pump technology has been used for chemotherapy since 1988 and was approved for use with morphine in 1991.The implant procedure and ongoing therapy — including pump refills and programming — are covered by Medicare in all 50 states and by most private insurers.Levels of coverage do vary, so check with carriers before implantation.Medtronic offers assistance with coding, coverage, and payment information.Most reimbursement issues can be resolved, so candidates for implant should not be ruled out due to economic constraints.
35Cost Effectiveness of Intrathecal Therapy in Cancer Pain Infusion costs are generally comparable for externalized intraspinal and parental drug delivery because similar equipment is used.1One cost model showed the break even point at which it becomes less expensive to administer opioids with an intrathecal/implanted pump (rather than an epidural/external pump) is between three and six months after the start of pain management.2After approximately 12 weeks, an exteriorized system loses its cost advantage, mainly due to higher maintenance needs and higher drug costs.3By addressing pain sooner, side effeects may be reduced, quality of life improved, and there may be cost advantages.1. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal drug delivery fo rthe management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol 2005;3(6):2. Hassenbusch SJ. Cost modeling for alternate routes of administration of opioids for cancer pain. Oncol 1999 May;13(5 suppl 2):63-7.3. Brogan SE. Intrathecal therapy for the management of cancer pain. Curr Pain Head Rep 2006;10:
36Clinical Outcomes Cancer Pain Trial, 2002 RandomizedProspectiveInternational (5 countries)Multicenter (21 centers)Clinical trial of efficacy of combining IDDS (Medtronic SynchroMed® infusion system) and Comprehensive Medical Management (CMM) vs. CMM alone for patients with persistent cancer painThe Cancer Pain Trial was an international, multicenter, randomized clinical trial designed to evaluate the clinical effectiveness of intrathecal drug delivery using the Medtronic SynchroMed® Infusion System and comprehensive medical management vs. CMM alone for patients with persistent cancer pain.Clinical effectiveness was measured using outcomes of pain and opioid side effects. In addition to pain control, the trial also documented other outcomes, including persistence and changes in side effects over time, patient and caregiver quality of life, cost of care, and survival.Journal of Clinical Oncology, Vol 20, No 19, October 1, 2002:
37Conventional Medical Management Per AHCPR Guidelines First, by mouthBy the clock, not p.r.n.By the WHO analgesic ladderFor the individual, as pain perception is highly individualWith attention to drug titration, side effects, and patient’s assessment of painCMM consisted of comprehensive pain management delivered in accordance with guidelines published by the Agency for Health Care Policy and Research, an agency of the Federal Government. Patients assigned to the CMM group received all the pain therapy routinely administered at the participating cancer centers except spinally administered drugs or cordotomy. CMM included: Other opioids Other non-opioids Combinations of drugs Higher doses Drug therapy for opioid side effects.Agency for Health Care Policy and Research. Management of Cancer Pain: Clinical Practice Guideline, Number 9, AHCPR Pub. No , 1994:42-45.Agency for Health Care Policy and Research. Management of Cancer Pain: Clinical Practice Guideline, Number 9, AHCPR Pub. No , 1994:42-45.
38Outcomes/Measures Primary Objective Measurement Methods Efficacy:≥20% reduction in pain VAS orequal VAS with ≥20% reduction in mean toxicity score or≥20% reduction in both pain VAS and toxicity Visual analog scale (VAS)Common Toxicity CriteriaComposite scores from 15 measures of toxicitySecondary ObjectivesMeasurement MethodsSide effectsPersistence and changes in side effects over timeQuality of life (QOL): measured for both patients and caregiversBrief Pain InventorySF-12 Health SurveyCaregiver Quality of LifeClinical endpoints in the Cancer Pain Trial included:Primary objective endpoint – combined pain relief and opioid side effectsEffectiveness – whether or not the treatment works.Secondary endpoints included:Side effects – the harmful effects of a drug or treatment.Quality of life – an assessment of the patient's and caregiver’s ability to function and cope.Cost – how much a treatment costs.Survival – coincidental finding, not a planned endpoint. It was monitored for safety reasons.Resource utilization/costNCI-ASCO Economics WorkbookFindingsMeasurement MethodsSurvivalKaplan-Meier life tablesSmith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
39Mean Reduction in VAS at 1 Month Pain ReliefMean Reduction in VAS at 1 Month6.005.004.00VAS: Mean Change3.002.001.00“As treated” analysis was done to better understand “as randomized” results. Five CMM patients had systems implanted and 22 IDDS patients did not.The “as treated” reduction in mean VAS pain score, regardless of randomized assignment, was estimated by the regression model to be 1.4 points greater in patients with a pump implant than in those without (P=0.007).Within the group randomized to IDDS, those who actually received IDDS experienced a reduction in mean pain VAS score 1.97 points larger than those who did not receive a pump (P=0.01).0.00CMMIDDSNon-Non-(n=72)(n=71)ImplantedImplantedImplantedImplanted(n=89)(n=54)(n=22)(n=49)As RandomizedAs TreatedIDDS As TreatedError bars are +/- 2 standard errors(adjusted)(adjusted)Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
40Types of Patient PainApproximately 75% of patients in both arms of the Cancer Pain Trial had neuropathic pain, with either pure neuropathic pain, or mixed (neuropathic-nociceptive) pain.Neuropathic pain was much more commonly seen in patients in the Cancer Pain Trial than in many previously published studies.Neuropathic pain is one of the primary reasons for failure of cancer pain therapy following the WHO ladder.††Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KL, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain. 93: , 2001.Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
41Results at 4 Weeks Clinical Success* 84.5% of IDDS patients experienced clinical success vs. 70.8% in CMM armPain reduction (VAS) 39.1% for CMM, 51.5% for IDDSComposite toxicity (CTC) 17.1% for CMM, 50.3% for IDDS (P=0.004)Side effects (CTC)Fatigue and reduced consciousness significantly less with IDDS than CMM (P<0.05)Impotence and pruritis worsened with CMM4 week data showed significant improvements for patients treated with IDDS over those receiving CMM only.At 4 weeks, for CMM patients the mean VAS pain score fell from 7.81 to 4.76, a reduction of 3.05 (39.1%). For IDDS patients, the VAS pain score fell from 7.57 to 3.67, a difference of 3.90 (51.5%). The VAS change at 4 weeks was larger by 12.4% in the IDDS group, but not statistically significant (P=0.055).The CMM group mean composite toxicity scores fell from 6.36 to 5.27, a reduction of 1.09 (17.1%), and in the IDDS group from 7.22 to 3.59, a reduction of 3.63 (50.3%). The 33.2% larger reduction in the IDDS group was statistically significant (P=0.004).All of the measured toxicities that could be attributed to opioids and other drugs used in pain therapy were reduced more in the IDDS group than in the CMM group. Significantly larger reductions (P<0.05) in the IDDS group were noted for fatigue and reduced consciousness.Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):* Defined as a ≥20% reduction in VAS pain score or equal pain with a ≥20% reduced toxicity.
42Reduction in 15 Toxicities (as randomized) *Statistically significant (P<0.05)Individual ToxicityReduction in Mean SeverityCMMIDDS-0.3-0.2-0.10.10.20.18.104.22.168.70.8Reduced libidoUrticariaPruritusWeight lossVomitingNauseaDehydrationConstipationAnorexiaPersonalityMemory lossReduced level of consciousnessConfusionFatigue*ImpotenceReduction occurred in all opioid side effects, not just one or two, in IDDS patients.Significantly larger reductions (P<0.05) in the IDDS group were noted for fatigue and depressed level of consciousness/sedation.Impotence and pruritus actually worsened in the CMM group but not in the IDDS group.Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
43Serious Adverse Events Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
44Cancer Pain Trial Results Reduced painReduced side effects like fatigue and sedationPositive trend toward QOL*This clinical study showed that intrathecal drug delivery offered advantages to individuals with severe, intractable cancer pain.When comparing patients who received infusion therapy with those who received conventional medical management alone, the study showed those receiving infusion therapy had statistically significant decreases in composite drug toxicity scores.Significantly more patients achieved clinical success (greater than or equal to 20% better pain relief and/or toxicity) with IDDs than with CMM alone.All toxicities were reduced with the most significant reductions in fatigue and sedation/drowsiness. The infusion therapy group also demonstrated improved pain control.More patients achieved clinical success with IDDSSmith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):* Based on the Brief Pain Index Interference scores
45Medtronic Resources Patient Services Online Resources at professional.medtronic.comPractice Development ToolkitReimbursement SupportPatient Education MaterialsMedtronic technical servicesMonday-Friday 7:00am-6:00pm CSTEmergency technical support 7 days a week, 24 hours a dayPatient ServicesMonday-Friday 8:00am-5:00pm CSTCoverage and Authorization ServicesMedical Education and Training CoursesA variety of training and education opportunities to keep clinicians current with pain therapiesTalk to your local Medtronic representative or visit professional.medtronic.comLocal Medtronic Representative
46SynchroMed® II Drug Infusion System Please refer to the product disclosure for complete productdetails.Enclose or attach the SynchroMed II System disclosure with lecture handouts.
47SynchroMed® II Drug Infusion System Brief Summary Product technical manuals and the appropriate drug labeling must be reviewed prior to use for detailed disclosure.Indications:US: Chronic intraspinal (epidural and intrathecal) infusion of preservative-free morphine sulfate sterile solution in the treatment of chronic intractable pain, chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain, and chronic intrathecal infusion of Lioresal® Intrathecal (baclofen injection) for the management of severe spasticity; chronic intravascular infusion of floxuridine (FUDR) or methotrexate for the treatment of primary or metastatic cancer. Outside of US: Chronic infusion of drugs or fluids tested as compatible and listed in the product labeling.Contraindications:Infection; implant depth greater than 2.5 cm below skin; insufficient body size; spinal anomalies; drugs with preservatives, drug contraindications, drug formulations with pH < 3, use of catheter access port (CAP) kit for refills or of refill kit for catheter access, blood sampling through CAP in vascular applications, use of Personal Therapy Manager to administer opioid to opioid-naïve patients or to administer ziconotide.Warnings:Non-indicated formulations may contain neurotoxic preservatives, antimicrobials, or antioxidants, or may be incompatible with and damage the system. Failure to comply with all product instructions, including use of drugs or fluids not indicated for use with system, or of questionable sterility or quality, or use of non-Medtronic components or inappropriate kits, can result in improper use, technical errors, increased risks to patient, tissue damage, damage to the system requiring revision or replacement, and/or change in therapy, and may result in additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug under- or overdose. Refer to appropriate drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, screening procedures and underdose and overdose symptoms and methods of management. Physicians must be familiar with the drug stability information in the product technical manuals and must understand the dose relationship to drug concentration and pump flow rate before prescribing pump infusion. Implantation and ongoing system management must be performed by individuals trained in the operation and handling of the infusion system. An inflammatory mass that can result in serious neurological impairment, including paralysis, may occur at the tip of the implanted catheter. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms, change in underlying symptoms, or need for rapid dose escalation.Inform patients of the signs and symptoms of drug under- or overdose, appropriate drug warnings and precautions regarding drug interactions, potential side effects, and signs and symptoms that require medical attention, including prodromal signs and symptoms of inflammatory mass.
48SynchroMed® II Drug Infusion System Brief Summary, Continued Failure to recognize signs and symptoms and seek appropriate medical intervention can result in serious injury or death. Instruct patients to notify their healthcare professionals of the implanted pump before medical tests/procedures, to return for refills at prescribed times, to carry their Medtronic device identification card, to avoid manipulating the pump through the skin, to consult with their clinician if the pump alarms and before traveling or engaging in activities that can stress the infusion system or involve pressure or temperature changes. Strong sources of electromagnetic interference (EMI), such as short wave (RF) diathermy and MRI, can negatively interact with the pump and cause heating of the implanted pump, system damage, or changes in pump operation or flow rate, that can result in patient injury from tissue heating, additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug underdose or overdose. Avoid using shortwave (RF) diathermy within 30 cm of the pump or catheter. Effects of other types of diathermy (microwave, ultrasonic, etc.) on the pump are unknown. Drug infusion is suspended during MRI; for patients who can not safely tolerate suspension, use alternative drug delivery method during MRI. Patients receiving intrathecal baclofen therapy are at higher risk for adverse events, as baclofen withdrawal can lead to a life threatening condition if not treated promptly and effectively. Confirm pump status before and after MRI. Reference product labeling for information on sources of EMI, effects on patient and system, and steps to reduce risks from EMI.Precautions:Monitor patients after device or catheter replacement for signs of underdose/overdose. Infuse preservative-free (intraspinal) saline or, for vascular applications, infuse heparinized solutions therapy at minimum flow rate if therapy is discontinued for an extended period of time to avoid system damage. EMI may interfere with programmer telemetry during pump programming sessions. EMI from the SynchroMed programmer may interfere with other active implanted devices (e.g., pacemaker, defibrillator, neurostimulator).Adverse Events:Include, but are not limited to, spinal/vascular procedure risks; infection; bleeding; tissue damage, damage to the system or loss of, or change in, therapy that may result in additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug underdose or overdose, due to end of device service life, failure of the catheter, pump or other system component, pump inversion, technical/programming errors, or improper use, including use of non-indicated formulations and/or not using drugs or system in accordance with labeling; pocket seroma, hematoma, erosion, infection; post-lumbar puncture (spinal headache); CSF leak and rare central nervous system pressure-related problems; hygroma; radiculitis; arachnoiditis; spinal cord bleeding/damage; meningitis; neurological impairment (including paralysis) due to inflammatory mass; potential serious adverse effects from catheter fragments in intrathecal space, including potential to compromise antibiotic effectiveness for CSF infection; anesthesia complications; body rejection phenomena; local and systemic drug toxicity and related side effects; potential serious adverse effects from catheter placement in intravascular applications.USA Rx Only Rev 0809