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Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaConflictsThe Opioid Crisis:Addiction and Anesthesia NoneRachael Rzasa Lynn, MDDepartment of AnesthesiologyUniversity of Colorado School of MedicineAddiction Chronic disease of reward, motivation andmemory Biological, psychological, social and spiritualmanifestations Characterized by:––––Inability to abstain from useLoss of control of use of the substanceCompulsion and craving for the substancePersistent use of the substance despite possibleharmful consequences Cycles of relapse and remissionEvaluation of Patient for OUDCAGE-AID (Adapted to Include Drugs):1. In the last three months, have you felt you shouldcut down or stop drinking or using drugs?2. In the last three months, has anyone annoyed youor gotten on your nerves by telling you to cutdown or stop drinking or using drugs?3. In the last three months, have you felt guilty orbad about how much you drink or use drugs?4. In the last three months, have you been waking upwanting to have an alcoholic drink or use drugs?Pseudoaddiction? The idea that drug‐seeking behaviors typicallyassociated with addiction may reflect undertreatedpain rather than addiction Defined based upon the patient’s motivation in seeking opioid:pain relief (pseudo‐) vs euphoria (addiction)– No evidence to support this phenomenon– Pain and addiction co‐exist! Pain is one of the most common symptoms of opioid withdrawal Chronic pain is associated with more opioid craving amongpatients on opioid maintenance for OUD However, tolerance is a well‐described and researchedphenomenon and must be treated adequatelyDSM‐5 Diagnosis ofOpioid Use Disorder (OUD)2 or more of the following within 12 months: Using larger amounts of opioidsor over longer time than intended Persistent desire to cut down orfailure to control use Inordinate time spent obtaining,using, or recovering from use Craving, or a strong desire or urgeto use substance Failure to fulfill major roleobligations at work, school, orhome due to recurrent opioid use Continued use despite recurrentor persistent social orinterpersonal problems caused orexacerbated by opioid use Giving up or reducing social,occupational, or recreationalactivities due to opioid use Recurrent opioid use in physicallyhazardous situations Continued opioid use despitephysical or psychologicalproblems caused or exacerbatedby its use *Tolerance (marked increase inamount; marked decrease ineffect) *Withdrawal syndrome withcessation of opioids or use ofopioids (or related substance) torelieve or avoid w/d symptoms.

Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaEvaluation of Patient with OUD Obtain a comprehensive history– Establish trust and effective communication to obtainan honest history; remain non‐judgmental DosageFrequencyTime of last doseIllicit drug useWhen possible, verify dosing regimen with opioidmaintenance provider– Consider urine drug screen (UDS) If negative, patient may be diverting medication False positives possible, time consuming to verify Will not give any information about past misuseFactors for Opioid Addiction or Abuse Risk Factors among adults on 90days of COT– Not being married (population ofveterans)– Younger age– Current Mental Health Disorder– Current painful physical disorder High level of pain if receiving 4 rx’sChronic pain dx in patients onmethadone therapyBack painHeadache– High levels of health care visits or “poorhealth”– History of opioid abuse– Current non‐opioid use disorder– Having an rx for 211‐day supply in 12months– High doses of opioid (esp 120mg MED)– Treatment with short‐acting opioid– Having an rx for sedatives or hypnotics Additional Risk Factors Protective Factors– Genetics ––––Certain mutations in genes for the μ‐, κ,or δ‐opioid receptorsPositive well‐beingBeing employedHaving health insuranceAmong adults on 90 days of COT: Long‐acting opioid onlyLower prescribed dosageSmaller prescribed supplySen S, Arulkumar S, Cornett EM, Gayle JA, Flower RR, Fox CJ, et al. New Pain Management Options for theSurgical Patient on Methadone and Buprenorphine. Curr Pain Headache Rep. 2016;20(3):16.Identifying Who Is at RiskSOAPP‐1.0 SF (Short Form) Scale 0 Never, 1 Seldom, 2 Sometimes, 3 Often, 4 Very Often Screening– Self report Questionnaires Assess risk of abuse with chronic opioid therapy Urine Drug Screening Check the state Prescription Drug MonitoringProgramOpioid Risk Tool Score of 3 low risk forfuture opioidabuse Score of 4 to 7 moderaterisk for opioidabuse Score of 8 high risk foropioid abuse1. How often do you have mood swings?2. How often do you smoke a cigarette within an hour afteryou wake up3. How often have you taken medication other than theway that it was prescribed?4. How often have you used illegal drugs (for example,marijuana, cocaine, etc.) in the past five years?5. How often, in your lifetime, have you had legal problemsor been arrested? Score 4 is Positive (86% sensitivity, 67% specificity;69% PPV and 85% NPV)Importance of Perioperative PainManagement More than 80% of surgical patients experiencepostoperative pain, and 86% of these patientsrated the pain as moderate, severe or extreme– Untreated pain risks persistent post‐operative pain Supported by both retrospective (recall bias) andprospective studies– Patients who attribute pain to trauma or surgeryexperience more emotional distress and higher painthan those whose pain was not associated with acuteevent

Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaCDC Guideline for Prescribing Opioidsfor Chronic Pain — United States, 2016 Regarding Acute Pain:– “Long‐term opioid use often begins with treatment ofacute pain. When opioids are used for acute pain,clinicians should prescribe the lowest effective dose ofimmediate‐release opioids and should prescribe nogreater quantity than needed for the expected durationof pain severe enough to require opioids. Three days orless will often be sufficient; more than seven days willrarely be needed (recommendation category: A, evidencetype: 4).”CDC Guideline for Prescribing Opioidsfor Chronic Pain — United States, 2016 Regarding Acute Pain:– “a greater amount of early opioid exposure is associated with greaterrisk for long‐term use (KQ5).”– “limiting days of opioids prescribed also should minimize the need totaper”– “each day of unnecessary opioid use increases likelihood of physicaldependence without adding benefit”– “when opioids are needed for acute pain, clinicians should prescribeopioids at the lowest effective dose and for no longer than theexpected duration of pain severe enough to require opioids”– “in most cases of acute pain not related to surgery or trauma, a 3days’ supply of opioids will be sufficient.”– “Acute pain can often be managed without opioids.”– “Given longer half‐lives and longer duration of effects (e.g., respiratorydepression) with ER/LA opioids, clinicians should not prescribe ER/LAopioids for the treatment of acute pain.”Reducing Long‐Term Use Use of opioid for acute pain associated with long‐term use Higher initial exposure (dose, duration/dayssupplied) also associated with long‐term use Not all acute pain requires treatment withopioids! Why do we care what our patients do for painlong‐term?CDC Guideline for Prescribing Opioidsfor Chronic Pain — United States, 2016 Regarding Acute Pain:– “a greater amount of early opioid exposure is associated with greaterrisk for long‐term use (KQ5).”– “limiting days of opioids prescribed also should minimize the need totaper”– “each day of unnecessary opioid use increases likelihood of physicaldependence without adding benefit”– “when opioids are needed for acute pain, clinicians should prescribeopioids at the lowest effective dose and for no longer than theexpected duration of pain severe enough to require opioids”– “in most cases of acute pain not related to surgery or trauma, a 3days’ supply of opioids will be sufficient.”– “Acute pain can often be managed without opioids.”– “Given longer half‐lives and longer duration of effects (e.g., respiratorydepression) with ER/LA opioids, clinicians should not prescribe ER/LAopioids for the treatment of acute pain.”Opioid Crisis:Role of Prescription Opioids In 2013, 1.9 million people abused or dependentupon prescription opioid (DSM‐IV dx criteria) Having a history of opioid analgesic rxincreases risk for overdose and OUD– 1/550 patients died from opioid‐related overdoseat median of 2.6 yrs from first opioid rx 1/32 patients on 200 MME died from opioid overdoseRisk Factors for OUD The use of prescription opioids for chronicnon‐cancer pain was a strong risk factor forOUD– BUT duration of therapy was a greaterdeterminant of OUD development than daily dose 0.2% on low‐dose/acute opioids vs 6% on highdose/chronic 120mg MED/ 90 days

Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaDo Chronic Pain andOpioid Use Disorder Coexist?Relationship between opioiddependence and addiction Estimates of OUD prevalence among patients onCOT for chronic pain vary– Several studies have quoted 1‐5%– A large meta‐analysis concluded that addiction waspresent in 8‐12% of patients on COT for chronic pain– Still others have estimated the prevalence of OUD at20‐35% Far more people use these drugs for intendedmedical purposes than misuse/abuse them!Opioids Change the Brain!Opioids Change the Brain! One month ofmorphine for chronicpain led tomorpholoigic changeson MRI that were notseen with placebotreatment One month ofmorphine for chronicpain led tomorpholoigic changeson MRI that were notseen with placebotreatment– amygdala, medialorbital gyrus,hypothalamus, mid‐cingulate, inferiorfrontal gyrus, ventralposterior cingulate,caudal pons, anddorsal posteriorcingulate– amygdala, medialorbital gyrus,hypothalamus, mid‐cingulate, inferiorfrontal gyrus, ventralposterior cingulate,caudal pons, anddorsal posteriorcingulate These changespersisted severalmonths aftermorphine was tapered These changespersisted severalmonths aftermorphine was taperedNon‐PharmacologicInterventions for Pain Expectations– What is patient’s pre‐operative pain baseline?– What is patient’s target number? 0/10 is not a reasonable goal! Focus on function (ambulation, PT, sleep) rather than # Interventions– Most low cost, few if any adverse effects Aromatherapy– Lavender for post‐operative pain Music therapy– Procedural pain, post‐operative pain, obstetric Relaxation breathing Acupressure– Joint Commission Standards Effective January 1, 2018 Non‐PharmacologicInterventions for Pain TENS– 80‐150 Hz– Meta‐analysis foundTENS reduced opioidconsumption vs placeboat 12, 24 and 48‐hoursafter TKA– Associated with lowerVAS at all 3 time points– Minimal side effects Acupuncture– May increase time untilfirst opioid dose afterTKA and reduce pain No impact on post‐operative opioid dose– May reduce pain in first2 days after TKA andTHA

Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaNon‐PharmacologicInterventions for Pain Structured attentivebehavior self hypnosis– Attentive, encouraging,provision of sense of control,neutraldescriptors/avoidance ofnegative suggestions scriptfor breathing, self‐guidedimagery– Stable rating of painthroughout procedure inhypnosis group vs linearincrease w/ time in others– Shorter procedure time forhypnosis than standard– Less PCA (0.5mg midaz/25μgfentanyl per demand) use inattention and hypnosisgroups: 1.9 units vs 0.8 and0.9 units, respectivelyThe Impact of Intra‐Operative Opioids In animal model ofspinal nerve injury,exposure to morphineafter trauma leads tosensitization, allodynia– Lower threshold formechanical stimulationof paws– May be via immuneactivation of glial cellsHyperalgesiaHyperalgesia Natural phenomenon after injury that servesto facilitate healing Central sensitization may lead to pathologicalpersistent pain hyperalgesia In human studies, techniques that are opioid‐sparing (multimodal) associated with lesspost‐operative pain and opioid use– Increased CNS hyperexcitability to stimuliDo Non‐Opioid Adjuncts ImpactLong‐Term Pain or Opioid Outcomes? Gabapentinoids– Single pre‐operative pregabalin dose or continuedadministration peri‐operatively can reduce post‐operative pain scores– Randomized, placebo‐controlled trial of 240 patientsgiven pregabalin pre‐op and for 14 days after surgery Lower post‐operative opioid consumption than placeboEarlier achievement of hospital discharge criteria ( 9 hrs)Greater active ROM (functional)Lower incidence of neuropathic pain at 3 and 6 monthspost‐op– 0% vs 8.7 and 5.2%– Avoidance of intra‐operative opioid with use ofbeta‐blocker infusion results in lower post‐op painscores and opioid use– In some studies, even results in less chronicneuropathic painDo Non‐Opioid Adjuncts ImpactLong‐Term Pain or Opioid Outcomes? Gabapentinoids– Gabapentin has similarly been shown to reducepain at 6 months after orthopedic, ENT, breast andabdominal/pelvic surgery– In a recent RCT, gabapentin did not acceleratecessation of post‐operative pain, but increasedprobability of opioid cessation after surgery (by24%) and reduced duration of opioid therapy(mean 25 days vs 32 days for placebo)

Rachael Rzasa Lynn, MDThe Opiod Crisis: Addiction and AnesthesiaDo Non‐Opioid Adjuncts ImpactLong‐Term Pain or Opioid Outcomes? Local Anesthetic Techniques Unfortunately, 2 recent database reviews suggests thatuse of regional anesthetic techniques for TKA andShoulder Arthroplasty is not associated with lower riskof chronic post‐surgical opioid useManagement of Patient with OUD No RCTs of acute pain management in patientson maintenance therapy for OUD– No evidence that exposure to opioids for acutepain increases relapse risk Suggested that the stress of uncontrolled pain maytrigger relapseSen S, Arulkumar S, Cornett EM, Gayle JA, Flower RR, Fox CJ, et al. New Pain Management Options forthe Surgical Patient on Methadone and Buprenorphine. Curr Pain Headache Rep. 2016;20(3):16.Management of Patient with OUD Has not been studied in opioid‐tolerant patients– Still WIDELY recommended to use a multi‐modalapproach in such patients where opioids may beineffective (tolerance, OIH, etc.) regional anesthesiaNSAIDs or COX‐2 InhibitorsacetaminophenNMDA antagonistsα2 agonistsanti‐convulsantsSen S, Arulkumar S, Cornett EM, Gayle JA, Flower RR, Fox CJ, et al. New Pain Management Options forthe Surgical Patient on Methadone and Buprenorphine. Curr Pain Headache Rep. 2016;20(3):16.

Addiction and Anesthesia Rachael RzasaLynn, MD Department of Anesthesiology University of Colorado School of Medicine Conflicts None Addiction Chronic disease of reward, motivation and memory Biological, painpsychological, social and spiritual manifestations Characterized by: - Inability to abstain from use