OPIOIDS: USE WITH CAUTION - OHSU Home
Transcript of OPIOIDS: USE WITH CAUTION - OHSU Home
OPIOIDS: USE WITH CAUTION
Brett R. StaceyComprehensive Pain CenterOHSUwww.ohsu.edu/paincenter
Opioids for Acute and Chronic Pain
Treating these two different populations should be very differentCommon features: “pain” some of the tools (opioids)I will focus on Chronic Opioid Analgesic Therapy primarily
Chronic Pain
A leading cause of visits to a doctor, disabilityCosts the US economy more than $100 billion/yearMany etiologies, many treatmentsAppropriate treatment often focused on
Decreasing pain and sufferingImproving functionFostering self managementEnhancing control
One tool amongst many is the use of opioids…
Opioids
Can relieve all types of pain, not replaceable for acute and cancer painAvailable by many routes of administration: oral, TD, IV, epidural, intrathecal, buccal, rectal, etcMultiple formulations: short acting, long acting, abuse‐deterrent, combination, mixed‐agonists, “atypical”Huge dose rangeNo consensus on useMay not benefit many chronic pain patientsBONUS: can be abused, have street value, the DEA and states monitor use, special rules, kill people, may promote pain, many biases, etc
Opioid Myths
Pain medicine = narcotics = opioidsStrong opioids work the bestQuick acting is betterOnly opioids reallywork for painMore is better“Oxy” is the best“It’s just Vicodin®”“My narcotics work well for my fibromyalgia”
More opioid myths
Opioids do not
Eliminate painTake away problemsProvide normal sleep for most peopleMotivate a patient to participate in activityMake everything betterSimplify treatment
What is being treated?
PainSufferingDistressDepressionAnxietyPersonality issuesSleep disturbance
Progressive vs StableContinuous vs. intermittent painDeconditioning/ObesityWork issuesFamily issuesLimited coping skillsStress
Balancing Treatment: very few patients have complete pain relief
Psychological Treatment:CBT, Self Management, Acceptance, Control
Rehabilitation:Improve functionOvercome deconditioningSelf exercisePacing
Medical:Medication InterventionCoordinationReinforcement
Everything else: insurance, work, disability, family, leisure, meaning
CAM
Opioids
Opioids and chronic pain
10‐20 years ago: an interesting, controversial, unproven concept Somerville MA. Opioids for chronic pain of non‐malignant origin‐‐coercion or consent? Health Care Analysis. 3(1):12‐4, 1995 Feb.
Large RG. Schug SA. Opioids for chronic pain of non‐malignant origin‐‐caring or crippling. Health Care Analysis. 3(1):5‐11, 1995 Feb.
Now: an interesting, controversial concept with some data to support itAntoin H. Beasley RD. Opioids for chronic noncancer pain. Tailoring therapy to fit the patient and the pain. Postgraduate Medicine. 116(3):37‐40, 43‐4, 2004 Sep.
Christo PJ. Grabow TS. Raja SN. Opioid effectiveness, addiction, and depression in chronic pain. Advances in Psychosomatic Medicine. 25:123‐37, 2004.
Many studies of 1‐3 months duration show benefit.
IS THAT LONG ENOUGH?
Do opioids help back pain patients work?
Washington state: prospectively examined opioids prescribed within 6 weeks of the first medical visit for a back injury among 1843 workers with lost work‐time claims.After adjustment for pain, function, injury severity, and other baseline covariates, receipt of opioids for more than 7 days (odds ratio = 2.2; 95% confidence interval, 1.5‐3.1) and receipt of more than 1 opioid prescription were associated significantly with work disability at 1 year.1
Utah workers comp: retrospectively identified nonspecific back pain patients, looked for opioid vs no opioidsOdds of chronic work loss 6 times greater with CII opioidsOdds 11‐14 times greater for any opioids prescribed ≥ 90 days“for most workers opioid therapy did not arrest the cycle of work loss and pain.”
1. Franklin GM, et al. Spine. 33(2):199-204, 2008 Jan 15.2. Volinn E, et al. Pain. 142(3):194-201, 2009 Apr
Potential Shared GoalsEstablish the goals of treatment:
Decrease pain (intensity, frequency)Decrease sufferingEnhance self controlImprove functionImprove sleepImprove mood/decrease distressPrevent pain (prophylaxis)Increase activity (work, recreation, etc)Minimize iatrogenic complications
Initiating opioid therapy
GO to the DEA website and your state medical board website, familiarize yourself with the rules.DOCUMENT the history, physical, prior treatments, and your medical decision making Assess patient risk for diversion: an assessment tool or system of questionsUse consent form, document a PARQ discussion: http://egov.oregon.gov/BME/PDFforms/MaterialRiskNotice.pdfConsider a behavioral agreementOutline goalsOutline other treatment: pharmacotherapy, otherConsult with other providers if neededDocument that the medication will be stopped if no meaningful responseConsider urine toxicology
An excellent guideline: Canadian Guideline for Safe and Effective Use of Opioids For Chronic Non-Cancer Pain. http://nationalpaincentre.mcmaster.ca/opioid/index.htmlFurlan AD, et al. CMAJ. 2010 June 15; 182(9): 923–930
A couple of details
Your friend: The DEA = Drug Enforcement Agency, they don’t approve, they regulateSchedule II: potent opioids. No refills.Schedule III: opioids with something else attached. Refills allowed.
http://www.justice.gov/dea/pubs/scheduling.html
You must have a DEA registration, specific for your state.PLUS: your state has a host of additional rules, guidelines and suggestions for you
Drug Selection, my version
Chronic Opioid Analgesic TherapyTwo options:
Intermittent, as needed.Tally the useConsider conversion to long actingStay with short acting if dose is low or truly intermittent
Start with time contingent dosing of sustained release opioid.
Low doseAdjust
The Opioid Agonists
Short actingPure opioids: oxycodone, hydromorphone, morphine, oxymorphone, codeine, fentanylMixed: hydrocodone/apap, codeine/apap, etc
Long actingMethadoneOxycodone, hydromorphone, TD fentanyl, morphine, oxymorphone
Orphan drug: levorphanolOpioid +: tapentadol, tramadolAbuse‐deterrant formulations: Embeda® (morphine and naltrexone)
Selecting an Opioid
No “best” opioidFentanyl: generic patch, buccal tablet, film, and oraletSustained release hydromorphone, oxymorphoneSeveral morphine preparationsOffice based addiction treatment: Suboxone(buprenorphine and naloxone)Methadone: a leading cause of opioid death in my home stateHydrocodone most likely to be divertedTapentadol: norepinephrine and opioid actionsTramadol: not scheduled, many interactions
Route
Oral: least expensive, most options, usually the first choiceTransdermal: a reasonable alternativeIV: rarely appropriate for chronic nonmalignant painBuccal: rarely appropriate for chronic nonmalignant pain, high diversion/abuse potential
Long Acting Opioid starting doses
Methadone: “special” 2.5 mg BID. Warn patients about long ½ life. Must be stable for many days before adjusting.Oxycodone SR: 10 mg BIDMorphine SR: 15 mg BID or 20 mg QDFentanyl patch: 12 mcg/hrHydromorphone SR: 8 mg/dayOxymorphone: not suggested as first, second, or third choice
Methadone
Variable elimination half life: 8 to 60 hoursLiver function critical
Half life much longer than analgesic half‐lifeBeyond the mu receptor: norepinephrine and serotonin reuptake inhibition, NMDA antagonistMay produce
Less toleranceBetter analgesia in neuropathyLess constipation
Other special features: QT prolongation, very dependent on liver metabolism, A LEADING CAUSE OF OPIOID‐RELATED DEATH, especially in the first week of use
Modesto-Lowe V, Brooks D, Petry N. J Gen Intern Med. 2010 Apr;25(4):305-9.
Morphine
Available in many formsActive metabolitesStandard starting opioid for intrathecaldelivery “morphine pump”Spinal and supraspinal actionsHistamine release primarily with rapid IV administrationEmbeda® (morphine and naltrexone): when to use it?
Morphine CR v. Oxycodone CR
Few head‐to‐head studiesOxycodone may produce less need for rescueMore nausea & vomiting with morphineCaveat: many morphine preparations
Lauretti GR. BJ Cancer 2003;89:2027-30
Duragesic® fentanyl patch
Generics are differentPossibly less constipationSlow onsetNOT FOR ACUTE PAINDuration 72 hours for most but not allSkin condition and temperature influence deliveryAbuse not easyTD fentanyl: no effect on balance, driving performance, cognition Menefee LA. et al Pain Medicine2004
Cornick CA. Drug Safety 2003;26:951-73
Meperidine
Mainly μ‐agonist; moderate affinity for κ and δreceptors.Weak local anesthetic activity (alter nerve conduction).Greater antishivering effect than other opioids by unclear mechanisms. Effectively terminates or attenuates shivering from diverse causes: general and epidural anesthesia, fever, cold, and transfusion reactions.Accumulation of normeperidine produces signs of CNS excitation (seizures).
TramadolStructurally related to codeine and morphine.Consists of two enantiomers:
(+)‐Tramadol and the metabolite (+)‐O‐desmethyl‐tramadol (M1) are agonists of the μ‐ opioid receptor.(+)‐Tramadol inhibits serotonin reuptake and (‐)‐Tramadol inhibits norepinephrine reuptake.
After oral administration, tramadol is rapidly and almost completely absorbed. Plasma protein binding is about 20%. The mean elimination half‐life is about 6 hours. It’s considered a weak opioid: analgesic potency is about 10% of that of morphine. Appears to produce less constipation and dependence than equianalgesic doses of strong opioids.Serotonin syndrome
Results from excessive activation of serotonin receptors in the nervous system, on the surface of platelets, and on the vascular endothelium. The clinical manifestations are a triad of altered conscious state, autonomic dysfunction, and neuromuscular excitability. Meperidine, tramadol, methadone, dextromethorphan and propoxyphene appear to be weak serotonin re‐uptake inhibitors and have all been involved in serotonin toxicity reactions with MAOIs and serotoninergic antidepressants.
Sustained release, combination, short acting forms available
OxymorphoneSemi‐synthetic opioid derived from thebaineApproximately 6–8 times more potent than morphine (or 3 times more potent?)Endo Pharmaceuticals markets oxymorphone in the United States as Opanaand Opana EROpana is available as 5 mg and 10 mg tablets; Opana ER, an extended‐release form, is available as tablets in strengths of 5 mg, 10 mg, 20 mg, and 40 mg.Food Effect Two studies examined the effect of food on the bioavailability of single doses of 20 and 40 mg of OPANA ER in healthy volunteers. In both studies, after the administration of OPANA ER, the Cmax was increased by approximately 50% in fed subjects compared to fasted subjects. A similar increase in Cmax was also observed with oxymorphone solution.
Tapentadol vs Oxycodone
Tapentadol: opioid agonist and norepinephrinereuptake inhibition, CIILBP randomly assigned to tapentadol 50 or 100 q4‐6 hr or oxycodone 10 or 15 mg q 4‐6 hr, 90 days
Low completion rates: 57.6% vs 50.6%Nausea, vomiting, constipation: 44.2% vs 63.5%Pain relief, nervous system side effects similar
Hale M, et al. Curr Med Res Opin. 25(5):1095-104, 2009 May.
Opioid Adverse Effects
Respiratory depression: variable, additive with other sedatives, tolerance developsConstipation: persists. New treatments: opioidantagonists (separate or combined with opioid)Sedation/mental status changes: variable, tolerance may develop.Sleep: emerging evidence of abnormal sleep, increased sleep apneaTolerance, physical dependence, abuse/addictionNo organ damage: renal, hepatic, hematopoetic, coagulation systems.Persistent pain, increased pain, hyperalgesia
Endocrine System
2005 Volume 1, Issue 9www.painmanagementrounds.orgNathaniel Katz, MD
Opioid Tolerance
Can occur quickly with all opioidsCan persist after opioid tapered and stoppedMechanisms still not understood
NMDA Receptor Uncoupling Internalizing ReceptorNO
Tx: opioid rotation, ketamine, nitroglycerine, alternative analgesicsKieffer & Evans Cell 108 2002; Lauretti et al J Clin Anesth 14 2002
Risk assessment
Two ways of looking at thisIdentify patients who won’t have improved pain control or functionIdentify patients at risk for misuseBOTH important
Risk for ongoing pain, low level of function:High levels of pain, ill defined goals, pre‐pain mental illness, limited coping, legal issues, severely compromised function, cigarette use, limited social support, DUI, other drug abuse history, multiple pain sites, etc
Risk assessment for misuse
Likely increase risk of inappropriate use: Alcohol, illicit drug, or cigarette abuse; uncontrolled anxiety or depression; younger; previous drug or DUI conviction; doctor shopping, family history of substance abuse
Concerning history:Unauthorized dose escalation, minimal responsiveness to dose adjustment, more than one source, focus on meds, marginal compliance, early refills, helps with stress or sleep, etc
Women and men different: women more likely to misuse related to mood, men for legal/behavioral reasons1
1. Jamison RN, et al. Journal of Pain. 11(4):312-20, 2010 Apr.
“It’s just a little marijuana…"
Recent review of literature looking at cannabis and opioids1
cannabis use among patients prescribed chronic opioid therapy in these studies ranged from 6.2% to 39%, compared with 5.8% in the general United States populationstatistically significant associations with present and future aberrant opioid‐related behaviors.
Plus: still against federal law
1. Reisfield GM, et al. Pain Medicine. 10(8):1434-41, 2009 Nov.
After first prescriptionAssess: compliance, response, adverse effects, mood, participation in treatment, aberrant behaviorsDocument: ongoing care, all of the above, exact prescription detailsDiscuss driving, other activity, functionSee the patient regularlyReview treatment goalsPerform history & physical exam on a regular basisConsider urine toxicology testingOnly adjust dose with a visit and re‐assessmentNo unscheduled refillsUtilize adjuvant treatmentsDiscuss inconsistenciesStop futile therapy!
Ongoing Treatment
Canadian Guideline for Safe and Effective Use of Opioids For Chronic Non‐Cancer Pain. http://nationalpaincentre.mcmaster.ca/opioid/index.htmlFurlan AD, et al. CMAJ. 2010 June 15; 182(9): 923–930
The Four A’s
Analgesia: does the patient have effective pain relief?Adverse effects: are they severe, limiting, or are they controlled?Activity: evidence of increased function with opioids? meeting activity goals?Aberrant Behavior: screen/monitor
Stopping Opioid Therapy
Compliant patient with flat dose response curve or intolerable side effects or pain improved by other means
Taper slowlyDocument
Noncompliant therapyDocumentOffer resources Either stop abruptly or quick taperNotify others involved in patient care
Factors Favoring Prescription Drug AbuseCharacteristics desired in drug of abuse
Rapid onsetBrief durationHigh lipophilicitySolubility or vaporization potential“Feel it work”
PROTOYPE: heroin
Prescriber practices that might favor abuse
Symptom contingency (prn)“Pseudoaddiction” (inadequate treatment, leading to further efforts to procure effective treatment)Poor patient selection and/or monitoringPoor documentationNot questioning
Urine Tox Screens
Often suggested by review articles/expertsTurn up “abnormal” up to 45% of the time
Prescribed medication absentIllegal substancesExtra prescribed medicationsAltered sample
Michna E et al. Clin J Pain 2007
Should be random, quantitative, done the same way every timeBaseline before first prescription?Point of care vs lab?Know in advance what you will do with the results
Standbridge JB, et al. Am Fam Physician. 2010 Mar 1;81(5):635‐40.
Barriers to good practicePhysicians and other prescribers:
Not enough time to assess patients fully, reimbursementNo easy system to assess patients fullyNot aware of alternatives to opioids, how to use them effectively; inadequate use of mental health, rehabilitation servicesNot assessing contributing and risk factorsShort horizon for assessing effect of treatmentEducational deficitsInadequate treatment of acute pain to prevent development of chronic pain
Patients:Insurance barriers to effective alternative treatmentsDesire for “quick fix”ETC
Barriers to good practice
No clear guidelines of what to do with problematic patients
Misuse to treat distress– how to manageAddiction problem– deficient resourcesDrug trafficking– what does a provider, pharmacist do?Prescription fraud– what does a provider, pharmacist do?Doctor shopping– how to stop this inefficient use of resources?
Acute PainTrauma, surgery, injuriesFamiliar to all Can serve a purpose Tends to resolve Cause often obviousTreatments may be curativeRest often helpful
Every Surgical Procedure
Cuts nervesCuts tissuesInduces the injury responseAlters peripheral and central nervous system pain processingCan cause chronic pain
In general: severity of postop pain correlates with risks of chronic pain
Postoperative Pain:Patients’ PerspectiveNational surveys of surgical patients:
70 ‐80%: moderate to extreme postop pain75%: continued pain after medicationMore with pain AFTER discharge25%: medication side effectsWarfield & Kahn, Anesthesiology 1995 Apfelbaum JL et al Anesth & Analg 2003
Patients willing to pay for better pain control, esp if they experienced poor pain control previously
Badner, Can J Anaesth 1997; van den Bosch JE et al, Anesthesiology 2006
Pain lasts for weeks to months and impacts recoveryVanDenKerkhof EG, Pain Res Manag 2006
Adapted from Siddal, Cousins. In: Cousins, Bridenbaugh, eds. Neural Blockade. 1998:675
Peripheral SensitizationTissue damage Inflammation Sympathetic
terminals
Decreased threshold of nociceptorsEctopic dischargesAbnormal accumulation of Na+ channels
SENSITIZING “SOUP”Hydrogen ions Histamine Purines LeukotrienesNoradrenaline Potassium ions Cytokines Nerve growth factorBradykinin Prostaglandins 5-HT Neuropeptides
Hyperalgesia Predicts Chronic Pain
Eisenach JC RAPM 2006
Persistent Postoperative Pain: 10‐50% of surgery patients with severe pain in 2‐10%
Thoracotomy 30‐60%*
Inguinal Hernia Repair: 6‐11%1,2
Extremity AmputationsCardiac Surgery
Breast Surgery, especially with dissectionSpinal SurgeryOrthopaedic Surgery Abdominal SurgeryHysterectomy
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. May 13 2006;367(9522):1618-1625.*Maguire MF, Ravenscroft A, Beggs D, Duffy JP. A questionnaire study investigating the prevalence of the neuropathic component of chronic pain after thoracic surgery. European Journal of Cardio-Thoracic Surgery. May 2006;29(5):800-805. 1. Aasvang EK. Bay-Nielsen M. Kehlet H. Pain and functional impairment 6 years after inguinal herniorrhaphy.Hernia. 10(4):316-21, 2006 Aug 2. Nienhuijs S, et al. Chronic Pain after Mesh Repair: a systemic review. The American Journal of Surgery 194 (2007) 394–400
Prospective Study
625 patients, mixed surgical procedure.Many variables collectedAt 6 months, patients with high levels of pain on postop day #4 and surgery longer than 3 hours:
More painMore functional restrictionsPoor “global recovery”Worse quality of life
Peters ML. Sommer M. de Rijke JM. Kessels F. Heineman E. Patijn J. Marcus MA. Vlaeyen JW. van Kleef M. Somatic and psychologic predictors of long‐term unfavorable outcome after surgical intervention. Annals of Surgery. 245(3):487‐94, 2007
Chronic pain starts as acute pain
Some of these same mechanisms have been identified in chronic pain patientsPoorly controlled postop pain is an identified risk factor for chronic painDoes better postop pain control lead to less chronic pain?
Enlightened Acute Pain Treatment
Goal is to decrease pain and adverse physiology associated with traumaMultimodal treatment initiated early is most likely to be successfulRequires a collaborative effort, continuous assessment, planningMust be individualized
Patient assessment
Chronic Pain ‐‐ Increased opioid requirements & painOpioid Tolerance – more pain and opioids PatanwalaAE et al. Pharmacotherapy. 28(12):1453‐60, 2008. Swenson JD et al. Anesthesiol Clin North America. 23(1):37‐48, 2005 Mar.
Anxiety, depression, catastrophizing ‐‐Increased pain Granot M & Ferber SG Clin J Pain 2005, Jamison Behv Res Ther 1987, Heath BJA 1995, Pavlin DJ et al Clin J Pain 2005; Gerbershagen HJ et al Eur J Pain. 13(8):853‐60, 2009
Substance abuse ‐‐ increased opioid requirements Stacey Anesth 1990
Background Stress ‐‐ Delayed recovery, increased pain, increased morbidity Liu Anaesthesia 1994
Neuropathic Pain ‐‐May be resistant to opioidsSleep Apnea – Increased risk for resp depression Blake DW, et al. Anaesth Intensive Care. 36(3):379‐84, 2008 May
Postoperative pain predictors
Knee surgery: preoperative experimental pain associated with postop pain with movement Werner MU et al Anesthesiology 2004
Abd surgery postop pain risks: preop pain, depression, anxiety, severity of illness, lack of multimodal tx Caumo W et al Acta Anaesthesiol Scan 2002
Gyn surgery: psychosocial factors associated with postop pain and morphine dosage. Preop pressure pain correlates with postop pain Cohen L et al J Psychosom Res2005; Hsu YW et al Anesthesiology 2005
Patients who predict more pain have more pain and opioid use. Logan DE & Rose JB J Pediatr Psychol 2005
Predictors, continued
Breast surgery: ANXIETY, being younger, single, and extent of surgery. Katz J et al Pain 2005
Cholecystectomy: acute postop pain predicts chronic pain (~10% 1 yr later) Bisgaard T et al Scand J Gastroenterol 2005
Hernia repair with mesh: postop pain, younger age, and numbness associated with chronic pain. 43% had pain, 14.5% severe Nienjuijs SW et al J Am Coll Surg 2005
Spine surgery: altered HPA axis and cytokines associated with ongoing pain Geiss A et al Pain 2005
Perioperative Multimodal Analgesia
Minimally invasive surgery along with:Neural Blockade or other local anesthetic
NSAID/COX‐2 Inhibitor/Acetaminophen/Steroid
Gabapentin/Pregabalin
NMDA antagonist
Clonidine
Recovery/rehabilitation plan
Together, these interventions can reduce immediate postop pain, facilitate recovery, and possibly reduce chronic pain
Reuben SS, Buvanendran A. Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques. Journal of Bone & Joint Surgery - American Volume. Jun 2007;89(6):1343-1358. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. May 13 2006;367(9522):1618-1625. Straube S, et al. Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies. ActaAnaesthesiologica Scandinavica. May 2005;49(5):601-613. Tiippana EM, et al. Do surgical patients benefit from perioperativegabapentin/pregabalin? A systematic review of efficacy and safety. Anesthesia & Analgesia. of contents, 2007 Jun 2007;104(6):1545-1556
One option for reducing opioid prescriptions
“Multimodal analgesia” for surgery and trauma:
Regional anesthesia, continued after surgeryAnti‐inflammatoriesAnesthetic adjuvant medicationsIf possible, minimally invasive surgery
This approach decreases pain, decreases chronic pain, decreases opioid need
Another option for reducing opioid prescriptions
Comprehensive Pain TreatmentPhysical therapy, exerciseCoping skills, relaxationAddress work, health issues that impact painPain relieving proceduresNonopioid medication (an example, a nonopioidjust approved for chronic musculoskeletal pain)Re‐assess utility of opioid prescriptions
What I really do/believe
I advocate aggressive multimodal analgesia for postop pain to promote recovery, avoid chronic pain, and minimize opioidsI use opioids in a minority of chronic pain patientsI focus on treating the baseline painI work on strategies to reduce distressI rarely focus on pharmacological treatment onlyMy pharmacological approach is polypharmacy, not reliance on opioids aloneI minimize use of short acting medications and medications with “street” appealI believe that higher doses of opioids are associated with less good outcomes, more adverse effects, therefore I focus on strategies to avoid tolerance and dose escalation
Thank you!