Opioid Prescribing in Acute Pain Management

Opioid Prescribing in Acute Pain Management

Opioid Prescribing in Acute Pain Management Amy Klopp, APRN, CNS, CNP Objectives Describe the principles of opioid therapy in acute pain management Identify strategies for identifying and managing common side effects of opioid therapy Identify best practice for opioid prescribing with comorbid conditions of chronic opioid therapy (COT) and substance abuse disorder (SUD). Identify strategies for safe opioid prescribing

Acute Pain Usually underlying pathology Trajectory of improvement with healing of underlying injury Trauma, surgery, labor, medical procedures, and acute disease states Nociceptive - Ongoing activation of A- and C-nociceptors in response to a noxious stimulus.

Visceral - Arising from visceral organs Somatic - Arising from tissues such as skin, muscle, joint capsules, and bone. Neuropathic Arising from one or more peripheral nerves, ganglion, plexus or CNS disease/injury. Biological Factors Disease Brain function Inflammation Transduction Biological

Factors Psychological Factors Mood Stress Coping Catastrophizing Social Factors Social Factors

Pai n Psychologi cal factors Culture Environment Social Support Economic factors Fillingim R. B. (2017). Individual differences in pain: understanding the mosaic that makes pain personal. Pain, 158 Suppl 1(Suppl 1), S11S18. Multimodal Therapy Benefits of multiple medication effects and greater pain control without relying on any 1 class of medication. Mitigation of risk profile of each medication, while

allowing for synergistic pain control from different classes of medication. Multimodal Analgesia Rational Polypharmacy Mechanism specific treating many targets Peripheral Sensitization (Na+ Channels) Brain Descendi ng Inhibition (NE, 5HT) TCA SNRI Tramadol

Opioids Central Sensitization (Ca2+ channels, NMDA receptors) Spinal Cord PNS NSAIDs Opioids TCA Lidocaine TCA Gabapenti n Opioids

Ketamine Assessment -HPI What happened? Get the story, keep a differential diagnosis even if diagnosis already made. OLDCARTS for chronic pain Tell me about what you live with

every day? Onset when did pain begin? Location where is pain, where does it go? Duration How long does it last? Characteristics What does it feel like? Assess for function Assess for severity How do you get through hard days? How many days a week do you spend in bed?

Engage in what works at home in addition to the plan you will make here. Aggravation factors What makes it worse? Relieving factors What makes it better? Treatments What have you tried? How does it work?

Severity-Numeric scale, change in function Assessment Medical/Surgical Family/Social Medications Anxiety/Depression/PTSD Alcohol use Insomnia Illicit drug use How many a day? Sleep apnea did you bring your CPAP? Use of medications not prescribed to

you How many at a time? COPD or other chronic lung disease Family history of chemical dependency Gastric Bypass / Gastric Ulcer Hx physical/sexual/emotional abuse Constipation Current life stressors Urinary retention Mental health - stable or flared/shaky

Renal disease Liver disease Recent or planned surgery Clotting disorder or on anticoagulation therapy Allergies what is the reaction? Reinforcers of pain- compensation or litigation issues Opioids- Medication Contract? PMP What has worked in the past? Allergies vs adverse effects Oral Morphine Equivalents Tramadol 50 mg = Morphine 10 mg ( 1:5 ratio) Oxycodone 20 mg = Morphine 30 mg Hydrocodone 20 mg = Morphine 30 mg Hydromorphone 7.5mg = Morphine 30

mg Codeine 200 mg = Morphine 30 mg (1:8) Methadone 1 mg = Morphine 6 mg (nonlinear) Dose50-80% when 10 rotating Buprenorphine mg/hr =opioids Morphineto 24 account for incomplete cross tolerance. Mr. Nigheve is a 66 year old insurance salesman. He is s/p R TKA this morning for DJD. PMHx: Anxiety, Depression, Obesity BMI 31, Sleep Apnea, GERD, HTN, Seizure Disorder, Current smoker - 20pack yr hx, Denies alcohol use or illicit drug use. Home medications: Lisinopril, Duloxetine, Carbamazepine, Acetaminophen PRN, Lorazepam PRN.

PMP: Lorazepam 0.5mg tabs #90/30 days, same prescriber, regular refills OR: EBL 50cc, 1mg IV hydromorphone, 150mcg IV Fentanyl. Femoral nerve block. PACU: 1mg hydromorphone, 50mcg Fentanyl You are asked to see him on the Orthopedic unit with complaints of uncontrolled pain. He denies nausea and is advancing diet. Pain is in R knee, sharp and throbbing. VS are WNL. He is mildly anxious but otherwise exam is unremarkable. He asks, Can you please order Dilaudid? Oxycodone doesnt work for me. The surgeon has ordered Oxycodone 5-10mg Q 3 hours PRN What post-op opioid regime is indicated? a. Oxycodone 10-15mg Q 3 hours PRN He is a large man and will need more than a normal weight patient. b. Hydromorphone 2-4mg Q 3 hours PRN Patient may have a genetic factor that affects his metabolism of oxycodone. c. Tramadol 25-50mg Q 6 hours PRN Tramadol has a safer side effect profile. d. Oxycodone 5-10mg Q 3 hours PRN The current order is adequate. His request for a specific opioid is concerning for undiagnosed substance abuse disorder. You proceed with the CAGE-Aid screening tool. a. Oxycodone 10-15mg Q 3 hours PRN

He is a large man and will need more than a normal weight patient. Opioids dosed by tolerance not weight Tolerance to opioids >/= 30mg Oral Morphine Equivalents x 1week Alcohol use? Both dopaminergic reward pathways. Naloxone to treat alcoholism. Go back to your questions: Have you ever had to take more than prescribed to get your pain controlled? b. Hydromorphone 2-4mg Q 3 hours PRN Patient may have a genetic factor that effects his metabolism of oxycodone. Pharmacogenetics make a difference! Genes encode isoenzymes integral in absorption, metabolism and excretion of drugs Cytochrome P450 isoenzyme CYP2D6 (tramadol, hydrocodone, codeine and oxycodone) Poor metabolizer (0.1% U.S. Population) Intermediate Metabolizer (6% Caucasian, 13% African, 6% Asian, 9% Native) Extensive Metabolizer (89% Caucasian, 77% African, 87% Asian, 89% Native)

Ultra. Rapid Metabolizer (5% Caucasian, 9% African, 6.5% Asian, 3% c. Tramadol 25-50mg Q 6 hours PRN Tramadol has a safer side effect profile. Tramadol is an opioid. Tramadol 50 mg = Morphine 10 mg ( 1:5 ratio) When Tramadol is given with known CYP 2D6 inhibitors there is a clinically relevant decrease in efficacy. ( Duloxetine for this patient) Tramadol inhibits the reuptake of serotonin and norepinephrine Serotonin syndrome may occur with concurrent use of serotonergic agents Tramadol lowers seizure threshold, especially for patients with d. Oxycodone 5-10mg Q 3 hours PRN The current order is adequate. His request for a specific opioid is concerning for undiagnosed substance abuse disorder. You proceed with the CAGE-Aid screening tool. Opioid Risk Tool (ORT) Female Male Score (Mr Nigheve)

Alcohol 1 3 0 Illegal drugs 2 3 0 Rx drugs 4 4

0 Alcohol 3 3 0 Illegal drugs 4 4 0 Rx drugs 5 5

0 Age between 16-45 1 1 0 Hx of preadolescent sexual abuse 3 0 0 ADD, OCD, bipolar, schizophrenia 2

2 0 Depression 1 1 1 Family history of substance abuse Personal history of substance abuse Score <3 = low risk Score 4-7 = moderate risk Score >8 = high risk Psycological disease

Scoring total: 1 Webster LR, Webster R. Predicting aberrant behaviors in Opioidtreated patients: preliminary validation of the Opioid risk too. Pain Med. Mr. Nigheve is a 66 year old insurance salesman. He is s/p R TKA this morning for DJD. PMHx: Anxiety, Depression, Obesity BMI 31, Obstructive Sleep Apnea, GERD, HTN, Seizure Disorder, Current smoker - 20pack yr hx, Denies alcohol use or illicit drug use. Home medications: Lisinopril, Acetaminophen PRN, Lorazepam PRN, Duloxetine, Carbamazepine. PMP: Lorazepam 0.5mg tabs #90/30 days, same prescriber, regular refills OR: EBL 50cc, 1mg IV hydromorphone (Dilaudid), 150mcg IV Fentanyl. Femoral nerve block. PACU: 1mg hydromorphone, 50mcg Fentanyl hat risk factors does this patient have for opioid related harm a. Obstructive Sleep Apnea b. Age c. Anxiety and Depression d. Smoking History

e. Concurrent sedating medications f. Obesity Mr. Nigheve is a 66 year old insurance salesman. He is s/p R TKA this morning for DJD. PMHx:Anxiety, Depression, Obesity BMI 31, Obstructive Sleep Apnea, GERD, HTN, Seizure Disorder, Current smoker - 20pack yr hx, Denies alcohol use or illicit drug use. Home medications: Lisinopril, Acetaminophen PRN, Lorazepam PRN, Duloxetine, Carbamazepine. PMP: Lorazepam 0.5mg tabs #90/30 days, same prescriber, regular refills OR: EBL 50cc, 1mg IV hydromorphone (Dilaudid), 150mcg IV Fentanyl. Femoral nerve block. PACU: 1mg hydromorphone, 50mcg Fentanyl hat risk factors does this patient have for opioid related harm a. Obstructive Sleep Apnea b. Age c. Anxiety and Depression d. Smoking History e. Concurrent sedating medications

f. Obesity Sleep Disordered Breathing Obstructive Sleep Apnea Central Sleep Apnea Obesity Hypoventilation Syndrome Opioids effect respiration by: Diminish hypercapnia and hypoxic responses Decrease phalangeal dilator and reflexes to collapsing airway Diminish arousal/awakening response Nobuo Sasaki, N., Meyer, M.J., Eikermann, M. (2013) Postoperative Respiratory Muscle Dysfunction: Pathophysiology and Preventive Strategies. Anesthesiology. 118:96178. STOP BANG Questionnaire Overnight oximetry Screen for OSA Not diagnostic but is ok for screening Average oxygen level over the night <93%

Oxygen desaturation events > 29/hr. More than 7% of the night at less than 90% saturated S Snoring T Tiredness / sleepiness / fatigue O Observed apnea P BP (>140/90) Rx or no Rx B BMI >35 A Age >50 N Neck circumference >40 cm G Gender male SCORING: 3 / 8 positive for OSA Chung et al. Anesthesiology 2008; 108:1-10 If patient meets any of these criteria, they are 2.2 times more likely to experience a post-op complication. Chung F, Liao P, Elsaid H, Islam S, Shapiro CM, Sun Y. Oxygen desaturation index from

nocturnal oximetry: a sensitive and specific tool Risk Factors for Opioid Related Harms Sleep disordered breathing Pregnancy Renal or hepatic insufficiency Age =/>65yrs Anxiety, depression or PTSD Concurrent substance use disorder Prior nonfatal overdose

Rotating to new opioid Lung disease Smoking > 40mg OME / day Obesity Concurrent use of benzodiazepines or other Risk Management Screen for and acknowledge risk, discuss with patient Wear home BiPAP / CPAP / Oral appliance Capnography or oximetry if capnography unavailable for at least first 24 hours after initiating opioid therapy Maximize opioid sparing multimodal analgesia Start with lowest dose in range dose order. Consider alternatives to benzodiazepines, i.e. tizanidine vs diazepam *Is a muscle relaxer indicated or just ordered? Naloxone The next morning Mr. Nigheve tells you his pain is better controlled with

Hydromorphone and multimodal therapy. He is glad you had his wife bring in his CPAP from home, he slept well and participated in therapy earlier in the morning. He has new complaints of abdominal boating and has not yet passed gas, although he feels constipated, he tells you having his morning coffee should do the trick. You note on his MAR he has refused to take Senna prescribed BID post-operatively. What do you recommend? a. Agree that coffee stimulates colonic motor activity and tell him he should also increase his fiber intake. b. Order a fleets enema PRN to be given prior to discharge if he has not yet had a BM. c. Order Methylnaltrexone SQ every other day PRN. d. Discuss his reason for refusing Senna a stimulant laxative and educate about its role in opioid induced constipation with or without a softener What do you recommend? a. Agree that coffee stimulates colonic motor activity and tell him he should also increase his fiber intake. b. Order Docusate Sodium 100mg twice daily. c. Order Methylnaltrexone SQ every other day PRN. d. Discuss his reason for refusing Senna a stimulant laxative and educate about its role in opioid induced constipation with or without a softener

or osmotic laxative. Incidence 40-60% in non-cancer patients Opioid receptors in GI tract Unlikely coffee or fiber laxative alone will benefit Docusate sodium alone - not demonstrated effectiveness against placebo. Methylnaltrexone Peripherally acting opioid antagonist, it does not cross blood brain barrier protecting opioids action centrally. Costly - approx 50$ per dose Should only be used in refractory cases. Sizar O, Gupta M. Opioid Induced Constipation. [Updated 2019 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Contraindicated in known or suspected partial or complete bowel As you are leaving, his wife pulls you aside and states, He is itching terribly all over from these sheets, he has always had sensitive skin. Doesnt this hospital use hypoallergenic detergents? You return and examine his

back, trunk and limbs and find intact skin without erythema. What do you recommend? a. Ask the bedside nurse about changing his sheets. b. Order Benadryl 25-50mg every 6 hours as needed for itch. c. Rotate to a new opioid d. Order naloxone 0.4mg IV x 1 What do you recommend? a. Ask the bedside nurse about changing his sheets. b. Order Diphenhydramine 25-50mg every 6 hours as needed for itch. c. Rotate to a new opioid d. Order naloxone 0.4mg IV x 1 Incidence of Pruritis 2-10% systemic opioids Up to 100% epidurally or spinally Occasionally with topical histamine flare response Mechanism of itch is unclear. Opioids like morphine may directly release histamine from mast cells. May be evoked by direct activation of mu receptors in the skin. Histamine receptor antagonists May cause drowsiness (Beers list)

Not effective for neuraxial opioid induced pruritis. Naloxone and Naltrexone can be effective but reduce analgesia Conflicting data on Serotonin (5HT3) receptor antagonists, propofol Topical moisturizers? Menthol? Camphor? Reich, A. and Szepietowski, J. C. (2010), Opioidinduced pruritus: an update. Clinical and Experimental Dermatology, 35: 2-6. Discharge Planning and Safety Intranasal Naloxone for any patient with >40mg OME and risk factors. Referral for sleep study, include copy of overnight oximetry if you have. Educate about multimodal therapy, medicine and non-medicine Opioid side effects and management, safe storage and disposal locations How many tablets to prescribe? MN Health Collaborative (ICSI) - 25th Percentile MME MAX = 25% of patients who received an opioid received that MME or less for a given procedure. #50 tabs oxycodone 5mg tabs Reducing number of opioids prescribed and pre- operative opioid education has been shown to reduce post-operative consumption. Farley Mrs. Sundown is 79y.o. retired teacher who lives alone in independent living senior apartment. Medical Hx: DMII diet controlled and CKD III.

She presents to the ED via ambulance after her neighbor heard a crash, checked in to find her on the floor unable to get up. She was found to have a right hip fracture and is now POD#2 R THA. You arrive to find her confused and hollering out in pain. Her daughter is at her side distraught with her mothers suffering. VS WNL, WBC 7.0, Hgb 10.4, CrCl 46 MAR: 1-2mg IV morphine q 3 hours PRN (8mg in past 24 hours = 24mg OME), Tylenol ordered but not administered, patient and family refused. Exam: Somnolent but wakes easily, restless when awake, oriented to self only, follows commands. LS CTA, S1 S2 RRR, Abdomen mildly distended, BS+, tender to any light palpation. Patient calls out in pain with abdominal Her daughter states, The morphine only makes her sleep. It doesnt seem to make the pain any better. Can you try another drug? What do you order? Select all that apply. a.Rotate opioid to hydromorphone 0.2mg IV every 6 hours PRN b.Schedule Tylenol add option for rectal administration c.Diclofenac gel 3% to right hip TID d.Lidocaine patch to right hip Q HS e.Gabapentin 100mg Q HS f. Bladder scan

g.Dulcolax suppository if no BM every other day PRN h.Seroquel 12.5mg BID PRN Her daughter states, The morphine only makes her sleep. It doesnt seem to make the pain any better. Can you try another drug? What do you order? Select all that apply. a.Rotate opioid to hydromorphone 0.2mg IV every 6 hours PRN b.Schedule Tylenol add option for rectal administration c.Diclofenac gel 3% to right hip TID d.Lidocaine patch to right hip Q HS e.Gabapentin 100mg Q HS f. Bladder scan g.Dulcolax suppository if no BM every other day PRN h.Seroquel 12.5mg BID PRN Diagnosis: Delirium, multifactorial Opioid induced, constipation, pain, urinary retention, underlying infection?, undiagnosed pre-existing mild dementia? a. Rotate opioid to hydromorphone 0.1-0.2mg IV every 6 hours PRN Morphine metabolized in liver to metabolites morphine-3,6glucuronide which can cause neurotoxicity. Metabolites

excreted renally. Avoid morphine in patients with reduced renal clearance, age> 65, underlying dementia. Diagnosis: Delirium, multifactorial Opioid induced, constipation, pain, urinary retention, underlying infection?, undiagnosed pre-existing mild dementia? b. Schedule Tylenol add option for rectal administration c. Diclofenac gel 3% to right hip TID d. Lidocaine patch to right hip Q HS e. Gabapentin 100mg Q HS Multimodal analgesia is opioid sparing Topical diclofenac bioavailability systemically has been reported at 1% or oral Gabapentin renally dosed, may enhance sleep, Diagnosis: Delirium, multifactorial Opioid induced, constipation, pain, urinary retention, hypoxia, underlying infection?, undiagnosed pre-existing mild dementia? f. Bladder scan g. Dulcolax suppository if no BM every other day PRN Reversible causes

Urinary retention Up to 10%, straight cath PRN, likely to resolve with reduced opioid/ discontinuation of opioid. Constipation Oxygen PRN, monitor capnography/oximetry Monitor for infection Diagnosis: Delirium, multifactorial Opioid induced, constipation, pain, urinary retention, hypoxia, underlying infection?, undiagnosed pre-existing mild dementia? h. Seroquel 12.5mg BID PRN Or other antipsychotic per preference or institution delirium protocol Include non medicine intervention Mr. Talus is a 40y.o. construction laborer and army veteran who you are seeing on observation unit. He initially presented to ED yesterday afternoon after a fall from a ladder on to his R foot now complaining of R ankle pain and inability to bear weight. He is found to have an ankle fracture which is splinted with plans to follow up with orthopedic surgery in a few days when swelling is reduced for possible surgery or casting. Medical HX: Chronic low back pain, chronic opioid therapy, PTSD, Depression.

Social History: Denies illicit drug use or abuse of prescription medications. Drinks alcohol socially only. Home medications: Oxycodone 10mg every 6 hours as needed for pain. Sertraline 200mg daily. PMP: Oxycodone 10mg tabs #90/30 days Consistently from same prescriber. Inpatient medications: Is the current opioid, Percocet 5/325mg 1-2 tabs q 4 hours PRN a good choice? Medical Hx Chronic back pain lives at 8/10 every day. Copes by pushing through it and working, keeping busy Family history: alcoholism in his father who is deceased Mental Health : shaky Psychologist recently moved away and needs to establish care. Denies suicidal ideation. Social Hx: living with his brother while in between jobs, he has been at new job for only 2 weeks Drinking Socially means to a case of beer every Saturday and Sunday. I never drink during the week. Never been through treatment, never experienced withdrawal. PMP would suggest #3 tabs 10mg Oxycodone/day = 30mg Oxycodone/day = 45mg OME Patient reports, I never use my Percocet when I drink. He reports taking 10mg

Oxycodone in AM and 20mg at night, So I can sleep. approx. 40mg oxycodone a day (tabs not used on weekends) = 60mg OME Is the current opioid, Percocet 5/325mg 1-2 tabs q 4 hours PRN a good choice? Multimodal therapy Tylenol 650mg TID- unless he is actively drinking (Max 2000mg /day in liver disease if not using alcohol) Topicals when able NSAIDS Gabapentin mood stabilization, reduction of sensitization, also used to treat alcoholism. Opioid tolerant >/= 30mg Oral Morphine Equivalents x 1week a. Add Oxycodone ER 20mg BID b. Oxycodone 15mg q 4 hours PRN Max daily dose 90mg oxycodone = 150mg OME c. Oxycodone 20mg Q 4 hours PRN d. Rotate Opioids to Hydromorphone 2-4mg Q 4 hours PRN Is the current opioid, Percocet 5/325mg 1-2 tabs q 4 hours PRN a good choice? Opioid tolerant >/= 30mg Oral Morphine Equivalents x

1week a. Add Oxycodone ER 20mg BID Not best option given pain trajectory, known use and concern for abuse. b. Oxycodone 15mg q 4 hours PRN Max daily dose 90mg oxycodone = 150mg OME c. Oxycodone 20mg Q 4 hours PRN d. Rotate Opioids to Hydromorphone 2-4mg Q 4 hours PRN Benefit of using lower dose due to incomplete cross tolerance. Discharge Planning and Safety Have a frank discussion with patient about his current behavior concerning for SUD, Cage Aid and risk of cross addiction. Who can support you? Brother, lifelong abstinence from alcohol due to fathers abuse. Pull the brother into conversation. Refer to Chemical Dependency treatment. Make a plan for AA, start today. Assist with re-establishing Mental Health support. Naloxone prescription, teach brother in use. Multimodal therapy!! No need to prescribe more opioids. He should have #60 tabs oxycodone 10mg left at home. Discharge instruction to change

how he takes them. Schedule plan to follow up with surgery team and primary prescriber, communicate directly. Scheduled taper to baseline? Or off altogether? Regular short prescriptions, 3 days at a time. Acute Pain Management for patients on Medication Assisted Therapy (MAT) Methadone Daily dosing for addiction, pain usually TID Chronic doses for pain or addiction will NOT be helpful for acute pain Verify dosing with treatment center, Will not be on PMP if through treatment center. Do not attempt to convert to equal analgesic dose, as it is non-linear. Must be certified to treat for addiction but allowed to continue outpatient plan of care. Continue chronic dosing and treat as opioid tolerant patient with another opioid. Multimodal therapy! Risk for prolonged QTc and sudden death due to Torsades de pointes, avoid medications with similar risk profile, i.e. Ondansetron. Metabolized in liver by CYP450 group of enzymes.

Acute Pain Management for patients on Medication Assisted Therapy (MAT) Buprenorphine and Naloxone (Suboxone) Buprenorphine Partial mu agonist with high affinity. Probable reduced risk of opioid related respiratory depression, ceiling effect. unless with benzodiazepine. Used to treat Opioid use disorder but also certain patients with coexisting chronic pain. Naloxone is an abuse deterrent only. Prescribers must obtain waiver to prescribe Buprenorphine and Naloxone (Suboxone) If patient is continuing dose, may need higher dose of full opioid agonist to overcome affinity of buprenorphine. High risk of adverse event if discontinued while on opioids for acute pain. If possible, stick with the plan or lack of plan patient presented with. If patient has discontinued, will still need opioid tolerant doses. Risk for SUD relapse while off. Restarting after acute pain treatment can precipitate withdrawal if done incorrectly. Patients often come with

plan in place from prescriber to restart 24-48 hours after discontinuation of short acting opioids for acute pain. Acute Pain Management for Patients on Medication Assisted Therapy (MAT) Naltrexone IM Depot (Vivitrol) Pure opioid antagonist dosed every 4 weeks for alcohol or opioid use disorder Discontinue at least 30 days prior to surgery, oral naltrexone may be used temporarily and stopped 72 hours prior For emergency pain management, opioids will not be effective. Use multimodal pain management including regional and general anesthesia Discharge for patients on MAT Safety measures as with any patient discharging in setting of substance abuse disorder Connect with addiction specialist for transition from acute pain management Challenging for discharge to facilities References Fillingim R. B. (2017). Individual differences in pain: understanding the mosaic that makes pain personal. Pain, 158 Suppl 1(Suppl 1), S11S18. Nobuo Sasaki, N., Meyer, M.J., Eikermann, M. (2013) Postoperative Respiratory Muscle Dysfunction: Pathophysiology and Preventive Strategies. Anesthesiology. 118:961-78.

Chung F et al. Br J Anaesth 2012, 108:76875 Chung F, Liao P, Elsaid H, Islam S, Shapiro CM, Sun Y. Oxygen desaturation index from nocturnal oximetry: a sensitive and specific tool to detect sleep disordered breathing in surgical patients Anesthesia and analgesia.2012;114(5). Centers for Disease Control and Prevention. 2018 Annual Surveillance Report of Drug-Related Risks and Outcomes United States. Surveillance Special Report 2pdf icon. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. Published August 31, 2018. Gomes, T., Juurlink, D. N., Antoniou, T., Mamdani, M. M., Paterson, J. M., & van den Brink, W. (2017). Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS medicine, 14(10), e1002396. Sizar O, Gupta M. Opioid Induced Constipation. [Updated 2019 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. MN Health Collaborative. Call to action: Adult Opioid Post-Operative Prescribing. MN Health Collaborative, ICSI. September 2019. Farley KX, Anastasio AT, Kumar A, Premkumar A, Gottschalk MB, Xerogeanes J. Association Between Quantity of Opioids Prescribed After Surgery or Preoperative Opioid Use Education With Opioid Consumption. JAMA. 2019;321(24):24652467. Maureen V. Hill, Ryland S. Stucke, Sarah E. Billmeier, Julia L. Kelly, Richard J. Barth, Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical Procedures, Journal of the American College of Surgeons, Volume 226, Issue 6, 2018, Pages 996-1003. Reich, A. and Szepietowski, J. C. (2010), Opioidinduced pruritus: an update. Clinical and Experimental Dermatology, 35: 2-6. Verhamme, K.M.C., Sturkenboom, M.C.J.M., Stricker, B.H.C. et al. Drug-Safety (2008) 31: 373. Tung1, A., Wong, C., Fairbairn, N. (2018), Perioperative management of opioid use disorder patients on buprenorphine/naloxone.

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