holy cows! how do we manage opioid use disorder in the

10/18/2021

1

Holy COWS! How Do

We Manage Opioid

Use Disorder in the

Perioperative Setting?Delaware Association of Nurse

Anesthetists

Fall Conference

October 17, 2021

Lisa A. Wallace MSN, APRN, FNP-BC

Addiction Consult Liaison Service

No

Financial

Disclosures

1

2

10/18/2021

2

Objectives

• Provide at least one statistic that describes the breadth of the opioid crisis

• Name at least one neuro-biologic influence on the perception of pain in opioid users

• Name at least one general principle of perioperative pain management

• Provide at least two examples of multimodal pain management

• Briefly articulate the principles of perioperative pain management for those in remission on naltrexone, methadone, and buprenorphine

Some Sobering Statistics

3

4

10/18/2021

3

• From 1999-2019, 500,000 Americans died from an opioid overdose.

• In 2019 alone, 50,042 drug overdose deaths involved an opioid.

– That represents 70.6% of all drug overdose deaths in 2019.

– 72.9% of opioid-involved overdose deaths, involved synthetic opioids other than methadone.

• Economic Burden: cumulative cost each year approaches 1 trillion dollars

Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National

Center for Health Statistics; 2020. Available at http://wonder.cdc.gov.

Delaware Overdose Death

Rates

Year DE OD Death Rate

2017 250

2018 401

2019 431

2020 447

2021 258 as of 10/15/21 2147

Delaware Overdose Commission

5

6

10/18/2021

4

CDC ranks Delaware first

in the nation for high-

dose and long-

acting/extended-release

opioid prescribing.

7

8

10/18/2021

5

9

10

10/18/2021

6

The Moral of the Story

11

12

10/18/2021

7

Two Immediate Areas of Focus

1. Prevent Opioid Withdrawal 2. Control Pain

Goal: Avoid Separation and Surreptitious Use of Substance

Preventing Opioid Withdrawal

• Measure and record

COWS score

• Treat COWS > 5 with

opioids.

13

14

10/18/2021

8

OUD Influence

on the

Pain Experience

15

16

10/18/2021

9

Neuro-biologic Adaptations of OUD

• G coupled proteins: a family of proteins that act as molecular switches,

transmitting signals from outside the Mu Opioid Receptor (MOR) cell to its

interior.

• Changes in G Proteins:

– G Protein degradation

– G Protein synthesis

• The results is MOR desensitization and downregulation of the surface of the

MOR.

• This leads to:

– Tolerance

– Hyperalgesia

– Physical Dependence

DeAquino, J, Parida, S., and Sofuoglu, M. (2021). The Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder. Clinical Drug Investigation . 41; 425

436

Opioid Induced Hyperalgesia• Increased sensitivity to pain resulting from opioid administration and

characterized by increase in pain sensation to external stimuli over

time and spreading of pain to locations beyond the initial pain site

• Generalizes across:

– Nociceptive stimuli (thermal, chemical, electric)

– Opioid agent (heron, fentanyl, morphine)

– Route of administration (IV, SC, IT, and oral)

• Hyperalgesia is dose dependent:

– Cumulative dose

– Cumulative exposure

Intensifies with withdrawal and worsens with repeated withdrawal

episodes.

Miller, s. Fiellin, D. Rosenthal, R. and Saitz, R. (2019). Pain and Addiction. ASAM Principles of Addiction Medicine. Philadelphia: Wolters

Kluwer; pp.1484-1499.

17

18

10/18/2021

10

Measured:

Pain Threshold: time to first feel pain

Pain Intensity: visual analog scale, 1-100

Pain Tolerance: time to hand withdrawal

19

20

10/18/2021

11

Results Conclusions

• Pain Threshold

– 6.6 seconds v. 10.9

seconds p < 0.0001

• Pain Intensity

– 74 v. 55 p < 0.0001

• Pain Tolerance

– 31.7 seconds v. 56.4

seconds p = 0.001

• Evidence of

opioid induced

hyperalgesia in

the opioid-

using

population

21

22

10/18/2021

12

Measured:

Pain Intensity: visual analog scale, 1-100

Pain Tolerance: time to hand withdrawal

Pain Distress

Cue-Related Craving

Cue-Related Anxiety

Results Conclusions

• Those with a h/o OUD had less

pain tolerance than control

subjects

• There was no difference in pain

intensity

• Those with a h/o OUD had more

pain distress

• In the abstinent group, pain

sensitive subjects had more cue-

induced craving for opioid than

pain tolerant subjects

– Pain sensitivity was positively

correlated with experience of craving

• Supports the hypothesis that pain perception and SUD share similar neural pathways and are closely linked.

• Untreated or undertreated pain is a critical factor in relapse

23

24

10/18/2021

13

The Emotional Response to Pain• The “nociceptive amygdala”

• Robustly connected to the hippocampus, a center for memory

formation, storage and retrieval

– Processes memory and assigns emotional value to it

– Development of pain memory

– Previous life experiences (trauma, stressful life events) influence

pain memory, which then modifies perception of pain

– Contributes to a cyclic interaction where fear, anxiety, and

emotions amplify pain, which in turn creates anticipatory anxiety,

distress, and suffering.

• Amygdala:

– Reward center

– Highly Overactive Stress system

Miller, s. Fiellin, D. Rosenthal, R. and Saitz, R. (2019). Pain and Addiction. ASAM Principles of Addiction Medicine. Philadelphia: Wolters

Kluwer; pp.1484-1499.

General Principles of

Perioperative

Pain Management

25

26

10/18/2021

14

Goal: Prevent the Surgical Event

from Transitioning to OUD

• 50% of those with opioid use disorder began with prescription

opioids

• 80% of heroin/fentanyl users began with prescription opioids

• Avoid excessive post-operative prescribing

– Short term opioid prescription in the opioid naive can lead to persistent

opioid use

– The greater the initial prescription, the higher the incidence.

– Left over pills, source of diversion

“Just Enough, Not Just in Case”

27

28

10/18/2021

15

29

30

10/18/2021

16

Multimodal

Approach

Every Patient,

Every Presentation

• Cognitive Behavioral Therapy

• Meditation Mindfulness

• Aroma Therapy

• Music Therapy

• Exercise Therapy

• Heat/Cold

• Non-opioid adjuncts

• Multidisciplinary Approach

• Coordination with outpatient prescriber before discharge: warm handoff

Non-Opioid Adjuncts: Blocks

• Peripheral Nerve Blocks

• Neuraxial Anesthesia and

Analgesia

• Local Anesthetic Additives

31

32

10/18/2021

17

Non-Opioid Adjuncts: Parenteral

• Dexmedetomindine:

– Alpha 2 agonist with sedative and anxiolytic properties

– Central anti nociceptive activity

– Cochrane Review:

– 7 RCTs, 422 patients

– Decreased breakthrough opioid consumption in the first 24

hours

– No significant decrease in pain scores.

Kumar, K. , Kirksey, M. A. , Duong, S. & Wu, C. L. (2017). A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods

to Decrease Opioid Use Postoperatively. Anesthesia & Analgesia, 125 (5), 1749-1760. doi: 10.1213/ANE.0000000000002497.


• Ketamine:

– NMDA receptor antagonist

– Mechanism of Action:

• Decreases nociceptive and inflammatory pain transmission

• Exerts analgesic effects by interacting with MOR and Kappa opioid

receptors


– 39 RCTs, 2482 subjects

– Low dose IV ketamine provides 40% opioid sparing effect

Kumar, K. , Kirksey, M. A. , Duong, S. & Wu, C. L. (2017). A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods to

Decrease Opioid Use Postoperatively. Anesthesia & Analgesia, 125 (5), 1749-1760. doi: 10.1213/ANE.0000000000002497.

Brinck, E. C., Tiippana, E., Heesen, M., Bell, R. F., Straube, S., Moore, R. A., & Kontinen, V. (2018). Perioperative intravenous ketamine for acute

postoperative pain in adults. The Cochrane database of systematic reviews, 12(12), CD012033. https://doi.org/10.1002/14651858.CD012033.pub4

33

34

10/18/2021

18


• Lidocaine:

– Antiarrhythmic


• Decreases release of proinflammatory cytokines and nuclear factor

K-B

• Inhibits NMDA receptors



– Bolus of Lidocaine 100 mg or 1-3 mg/kg followed by an infusion

of 1-5 mg/kg/hour

– Significantly lowered pain scores at 1-4 hours and at 24 hours

– Decreases perioperative opioid requirements




• Esmolol

– Beta Blocker


• Blockade of excitability effects of pain signaling in the central and

peripheral nervous systems

• Modulation of central adrenergic activity



– Perioperative infusion of esmolol 5-500 mcg/kg/min

– Low post operative opioid consumption

– 69% decrease in post operative breakthrough opioid

requirement

– 61% decrease in post operative nausea and vomiting



35

36

10/18/2021

19

Non-Opioid Adjuncts: Oral• Acetaminophen

• NSAIDs

• Clonidine

• Tizanidine

• Gabapentinoids

• Dextromethorphan: NMDS receptor antagonist

– 21 RCTs

– Decreased pain from 1-24 hours post surgery

– Reduced morphine consumption 24-48 hours post op after a variety of

procedures

• Duloxetine and TCAs: limited and contradictory evidence

– Use not yet supported



Perioperative

Management

_________________

Specific Scenarios

37

38

10/18/2021

20

Perioperative Management:

Patient With Active OUD• Variety of Presentation:

– Trauma: Falls, MVA, GSW

• Likely to go to OR earlier, before withdrawal controlled

• Pain management challenging

• Aggressive treatment

• Discharge can be within days

– Osteomyelitis, Discitis, Epidural Abscess, Endocarditis

• Likely to receive treatment with IV antibiotic first

• Opportunity to address withdrawal and pain and taper

opiates prior to surgery

Complicating Factors

• Inadequate Pain Relief

• Anxiety affecting pain

perception

• Fear of being treated

unfairly

• Fear of being judged

• Mistrust of the Health Care

System

– “You don’t understand, I use

fentanyl”

• Poor social support systems

39

40

10/18/2021

21


Patient with Active OUD• Prevent Opioid Withdrawal

• Address Pain:

– Multimodal Approach

– Multidisciplinary Approach

– Maximize use of non-opioid adjuncts—Blocks, Ketamine

– Expect need for higher doses of opioid than customary, to manage pain

• Consider continuous infusion with or without demand dosing

• Capitalize on opportunity to engage the patient into Substance

Use Treatment—The Reachable Moment

– Consult Addiction Medicine and Project Engage

– Induct Medication Assisted Treatment Prior to Discharge

– Avoid discharging on a standard opioid regimen, if possible

– Discharge to community Addiction Medicine Provider/Opioid Treatment

Center


Patient in Remission, on MAT

RELAPSE

Reintroduction to Euphoria

Access to OpioidsPoor Pain Control

Missed Methadone Dosing

Missed Buprenorphine Dosing

Anxiety/Dysphoria

41

42

10/18/2021

22


Patient in Remission• Identify the situation as early as possible

• Involve multidisciplinary team:

– Surgery

– Anesthesia

– Addiction Medicine

– Patient

– Nursing Staff

– Outpatient Prescriber/Opioid Treatment Center

• Perioperatively:

– Regional Anesthesia

– Multimodal adjuncts

• At Discharge:

– Avoid opioid prescribing, especially if patient requests it

– Resume MAT if applicable, arrange follow up

– Discharge with Narcan

Perioperative Management:In Remission, Receiving Naltrexone• Naltrexone: full

opioid antagonist• Used for OUD and

AUD

• ReVia= Oral Naltrexone, usually 50 mg per day

• 3 day wash out period

• Vivitrol = Extended-Release Naltrexone, 380 mg IM monthly

• 4 week wash out period

This Photo by Unknown Author is licensed under CC BY-SA

43

44

10/18/2021

23

Laes, J, Weigand, T. Torniainen, C, and Malcho, J. (2019). When Your Patient on Opioid Agonist or Antagonist Therapy Gets Sick. ASAM 2019

Annual Scientific Conference: Innovations in Addiction Medicine and Science.

ER Naltrexone: Emergent Procedure

Expect extraordinary opioid needs

Multimodal Treatment, Imperative


In Remission, Receiving Naltrexone

• Preoperatively:

– Advanced planning with Vivitrol prescriber


– Watch for opioid sensitivity

– Maximize all nonopioid adjuncts

– Multimodal Approach

– Involve Addiction Medicine

• At Discharge:

– Avoid/limit opioids

– Warm hand off to Vivitrol prescriber

– Discharge with Narcan

45

46

10/18/2021

24

Perioperative Management:Patient Receiving Methadone

• Methadone: synthetic full MOR agonist and NMDA antagonist

• Confirm dose with Opioid Treatment Center and maintain

• Consider TID or four time per day dosing schedule

• If necessary, can administer IV (1/2 usual dose)


Perioperative Management:Patient Receiving Methadone

• Use additional short acting opiates

• Multimodal Pain Regimen

• Involve Addiction Medicine

• Involve Project Engage/social work to facilitate transition back to Opioid Treatment Center

• Cannot discharge on any other opiates

• Discharge with Narcan


47

48

10/18/2021

25

Perioperative Management:Patient Receiving Buprenorphine• Partial MOR receptor

agonist and kappa antagonist

• 30 times more potent than MS

• Unique Attributes:• Ceiling Effect:

High Safety Profile• Very High Affinity

for the MOR• Slow dissociation

form MOR therefore long duration of action

Perioperative Management:In Remission, Receiving Buprenorphine

• Preoperatively:

• Advanced planning with buprenorphine prescriber essential


• Maximize all nonopioid adjuncts

• Multimodal Approach

• Buprenorphine dose??????????

49

50

10/18/2021

26

Three Studies

Seven, Five, and Ten Heroin-Dependent Volunteers

Varying Doses of Buprenorphine

Varying Time to PET Scan Intervals

Study One• Volunteers were given buprenorphine SL:

– 0 mg, 2 mg, or16 mg x 4 days

• Double-blinded study

• PET scans were started at 4 hours after daily dose of

buprenorphine

• Brain areas of interest:

– Prefrontal Cortex

– Rostral division of the anterior cingulate cortex

– Caudate nucleus

– Thalamus

– Nucleus Acumbens

– Amygdala

51

52

10/18/2021

27

Study One• Results

• Buprenorphine plasma concentrations are dose-

proportional and peak 1 hour after daily SL

administration.

• Plasma concentration of principle metabolite

norbuprenorphine peaks at 1.5 hours after daily

administration

• Opioid withdrawal symptoms and opioid craving

scores exhibit significant inverse linear relationship

with buprenorphine dose paralleling MOR availability

Study Two• Wider maintenance doses: 0

mg, 2 mg, 16 mg, and 32 mg

• PET Scan at 16 hours

• Results:

• Buprenorphine dose

dependently decreased MOR

availability, reliably across all

participants and regions of brain

involvement.

53

54

10/18/2021

28

Greenwald, M. K., Comer, S. D., & Fiellin, D. A. (2014). Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder:

implications for clinical use and policy. Drug and alcohol dependence, 144, 1–11. https://doi.org/10.1016/j.drugalcdep.2014.07.035

Greenwald, M. K., Comer, S. D., & Fiellin, D. A. (2014). Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder:

implications for clinical use and policy. Drug and alcohol dependence, 144, 1–11. https://doi.org/10.1016/j.drugalcdep.2014.07.035

55

56

10/18/2021

29

Quaye, A. N., & Zhang, Y. (2019). Perioperative Management of Buprenorphine: Solving the Conundrum. Pain medicine (Malden, Mass.), 20(7), 1395–1408. https://doi.org/10.1093/pm/pny217

Harvard/ Massachusetts General

Protocol

. Qyaye, A, Potter, K, Roth, S, et.al. Buprenorphine at Low-Moderated Doses was Associated with Lower Postoperative Pain Scores and Decreased

outpatient Opioid dispensing Compared with Buprenorphine Discontinuation. Pain Medicine. 2020; 0(0): 1-6.

57

58

10/18/2021

30





59

60

10/18/2021

31

So…

What Can I

Do As an

Anesthetist?

Helpful Tips for Nurse Anesthetists

• Assess for signs and symptoms of opioid withdrawal and treat them, especially in the OR and PACU

• If you have a suspicion for opioid use, send Urine Psychiatric Drug Screen, BEFORE YOU ADMINISTER FENTENYL

• If you know of a scheduled case, be sure there has been clear communication with outpatient prescriber and patient.

• Have a plan going into the procedure. Include patient and outpatient prescriber in the planning process

• If the case is emergent, involve Addiction Medicine.

• Use multimodal pain management techniques

• Include blocks on the first trip to the OR

• Always have frank dialog with patients about risk of opioid use and attempt to engage into treatment

61

62

10/18/2021

32

Helpful Tips for Nurse Anesthetists

Addiction Medicine

Available 24/7

for

Questions and

Consultations

302-320-7099

63

64

10/18/2021

33

References1. Acampora GA, Nisavic M, Zhang Y. Perioperative buprenorphine continuous maintenance and administration simultaneous

with full opioid agonist: patient priority at the interface between medical disciplines. J Clin Psychiatry.

2020;81(1):19com12810.

2. Alalade, E., Bilinovic, J., Walch, A. G., Burrier, C., Mckee, C., & Tobias, J. (2020). Perioperative Pain Management for

Median Sternotomy in a Patient on Chronic Buprenorphine/Naloxone Maintenance Therapy: Avoiding Opioids in Patients at

Risk for Relapse. Journal of pain research, 13, 295–299. https://doi.org/10.2147/JPR.S222885

3. Alford, D. P., Compton, P., & Samet, J. H. (2006). Acute pain management for patients receiving maintenance methadone

or buprenorphine therapy. Annals of internal medicine, 144(2), 127–134. https://doi.org/10.7326/0003-4819-144-2-

200601170-00010

4. Brinck, E. C., Tiippana, E., Heesen, M., Bell, R. F., Straube, S., Moore, R. A., & Kontinen, V. (2018). Perioperative

intravenous ketamine for acute postoperative pain in adults. The Cochrane database of systematic reviews, 12(12),

CD012033. https://doi.org/10.1002/14651858.CD012033.pub4

5. Center for Substance Abuse Treatment Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid

Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD:

Substance Abuse and Metnal Health; 2004.

6. DeAquino, J, Parida, S., and Sofuoglu, M. (2021). The Pharmacology of Buprenorphine Microinduction for Opioid Use

Disorder. Clinical Drug Investigation . 41; 425-436

7. Goel, A., Azargive, S., Weissman, J. S., Shanthanna, H., Ladha, K. S., Lamba, W., Duggan, S., Hanlon, J. G., Di Renna, T.,

Peng, P., & Clarke, H. (2019). Perioperative Pain and Addiction Interdisciplinary Network (PAIN): protocol of a practice

advisory for the perioperative management of buprenorphine using a modified Delphi process. BMJ open, 9(5), e027374.

https://doi.org/10.1136/bmjopen-2018-027374

8. Greenwald, M. K., Comer, S. D., & Fiellin, D. A. (2014). Buprenorphine maintenance and mu-opioid receptor availability in

the treatment of opioid use disorder: implications for clinical use and policy. Drug and alcohol dependence, 144, 1–11.

https://doi.org/10.1016/j.drugalcdep.2014.07.035

References9. Kumar, K. , Kirksey, M. A. , Duong, S. & Wu, C. L. (2017). A Review of Opioid-Sparing Modalities in Perioperative Pain Management:

Methods to Decrease Opioid Use Postoperatively. Anesthesia & Analgesia, 125 (5), 1749-1760. doi: 10.1213/ANE.0000000000002497.

10. Laes, J, Weigand, T. Torniainen, C, and Malcho, J. (2019). When Your Patient on Opioid Agonist or Antagonist Therapy Gets Sick. ASAM

2019 Annual Scientific Conference: Innovations in Addiction Medicine and Science.

11. . Lembke, A., Ottestad, E., & Schmiesing, C. Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue

Buprenorphine Through the Perioperative Period. Pain medicine (Malden, Mass.), 20(3), 425–428. https://doi.org/10.1093/pm/pny019

12. Miller, s. Fiellin, D. Rosenthal, R. and Saitz, R. (2019). Pain and Addcition. ASAM Principles of Addiction Medicine. Phildaelphia: Wolters

Kluwer; pp.1484-1499.

12. Pud, D, Cohen, D, Lowental, E, and Eisenberg, E. (2006). Opioids and Abnormal Pain Perception: New Evidence from a Study of Chronic

Opioid Addicts. Drug and Alcohol Dependence, 2006; 82(3): 218-223

13.Quaye, A. N., & Zhang, Y. (2019). Perioperative Management of Buprenorphine: Solving the Conundrum. Pain medicine (Malden,

Mass.), 20(7), 1395–1408. https://doi.org/10.1093/pm/pny217

14. Qyaye, A, Potter, K, Roth, S, et.al. Buprenorphine at Low-Moderated Doses was Associated with Lower Postoperative Pain Scores and

Decreased outpatient Opioid dispensing Compared with Buprenorphine Discontinuation. Pain Medicine. 2020; 0(0): 1-6.

15. St Marie, B., & Broglio, K. (2020). Managing Pain in the Setting of Opioid Use Disorder. Pain management nursing : official journal of the

American Society of Pain Management Nurses, 21(1), 26–34. https://doi.org/10.1016/j.pmn.2019.08.003

16. 3. Wachholtz, A., Foster, S., & Cheatle, M. (2015). Psychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use

disorder. Drug and alcohol dependence, 146, 1–6. https://doi.org/10.1016/j.drugalcdep.2014.10.023

17. Wakeman SE, Larochelle MR, Ameli O, et al. Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder. JAMA

Netw Open. 2020;3(2):e1920622. doi:10.1001/jamanetworkopen.2019.20622

18. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2020. Available

at http://wonder.cdc.gov.

65

66

holy cows! how do we manage opioid use disorder in the

Documents