pain management and buprenorphine - chi st. gabriel's health · 2019. 12. 12. · acute pain...

Pain Management and Buprenorphine

Anne Pylkas, MDInternal Medicine and Addiction Medicine

HealthPartners, Sage Prairie

Objectives

• Acute Pain in Bup/Nx patients• Chronic Pain

• Central Sensitization• Relation to Addiction• Treatment

Acute Pain Management in Bup/Nx Patients

• Why is acute pain management difficult in buprenorphine patients?


• Should we stop the bup/nx?• If so, when?• If not, should we decrease it? And how much?• What type of analgesia regimen will even work with bup/nx?• Does patient preference play a role?• What about risk of relapse?


• Regions Hospital example:• “…I have never felt (acute) pain management has gone great no matter what

we do with the bup…I honestly think that the suboxone prescribing doc makes a big difference…feeling that they are heard and understood makes a difference.”

• “…I feel like the ones who stay on do better, though it is always a struggle. But, the ones who come off feel more unstable and anxious…”


• No high level evidence to support a unified pain management strategy

• June 2017, Anderson et al. Anesth, To Stop or Not to Stop, That Is the Question

• Reviews• 4 case reports that support DC• 1 case reports that suggest that pain management is difficult either way• 3 cohort studies that support continuation

• Recommendations:• Urgent/Minimal pain: Continue bup, no post op opioids• Urgent/Mod-Severe pain: DC bup, start PCA, traditional post op opioids post op


• Nov 2018, Quaye, et al. Pain Medicine, Perioperative Management of Buprenorphine: Solving the Conundrum

• Reviews• 4 Case reports supporting DC• 2 Case series, 1 secondary observational, one prospective matched cohort, 4

retrospective cohorts supporting continuation• Recommendation:

• “We feel that it is unnecessary and may be harmful to…completely stop”• “The evidence suggests that analgesic or moderate doses of bup combined with opioid

agonists can have additive effects…”


• Evidence that pain control is difficult with continuation • Case reports: McCormick Pain Med 2013, Huang Can J Anesth 2014, Brummet J

Opioid Manag 2009, Harrington Am Surg 2010, Gillmore Am J Em Med 2012• Evidence that it pain control is manageable when continued

• Cohorts: Hansen Arthoplasty 2016, Macintyre Anaesth Int Care 2013, Kornfield Am J Ther 2010

• Peri-partum, Cohorts: ASAM Recommends continuing bup before elective c-sxn to avoid NAS, Jones Am J Drug Alc Ab 2009, Meyer Eur J Pain 2010, Vilkins J Addict Med 2017

• Evidence that DC associated with increased rates of illicit opioid use• Ling Addiction 2009, Bentzley J Subst Abuse Treat 2015, Sen Curr Pain Headache Rep

2016, Sigmon JAMA Psych 2013, Breen Drug Alcohol Dep 2003


• Receptor Availability• Optimal dose range for additive analgesia rather than competition?• Estimated receptor availability (Greenwald Biol Psych 2007, Greenwald Drug

Alcohol Dep 2014)• 1mg: 71-85%• 2mg: 53-72%• 4mg: 36-55%• 8mg: 11-22%• 12mg: 13-24%• 16mg: 9-20%• 24mg: 4-15%• 32mg: 2-12%

85

72

55

24 22 2015 12

0102030405060708090

1 2 4 8 12 16 24 32

Rec Avail (%)


• Receptor Availability• Optimal time interval between bup and opioid agonists?

• Slow dissociation• 10 patients on 16mg bup, told to withhold dose (Greenwald Biol Psych 2007)

• Agonist symptoms produced by 24 mg hydromorphone were blocked at 4 hours, but recovered increasingly at 28, 52, and 76 hours

• Suggests about 50% binding is required to suppress WD symptoms

4hrs 28hrs 52hrs 76hrs

OR availability 30% 54% 66% 82%

WD Score 1.8 3.5 6.9 (sig diff) 6.6

Perioperative

>8mg

Mild Pain

Post OperativePre-Op: Expected Pain

Moderate to Severe Pain

Continue Home BupDose

Add Opioid Agonists if needed

8mg-16mg:Cont Until Day Before

>16mg: Decrease to goal of 16mg until Day Before

<8mg

Decrease to 8mg after, maintain until off post op opioids

Add Opioid Agonists if needed

Taper off opioid agonists and increase back to previous

dose

Nov 2018, Quaye, et al. Pain Medicine, Perioperative Management of Buprenorphine: Solving the Conundrum


• As the bup providers ALWAYS:• Shared decision making with risks and benefits• Pain management goals• Risk of relapse• Prior experiences• REASSURE patient that their pain will be well managed

• This is a very vulnerable time• They are scared of pain, but also of relapse• They want to know that you are on top of it


• Talk to the surgeon pre-op: What is time frame?• Give the patient a 1 week supply• See me 1 week post op• Expect higher dose or potency of opioids required• If it is not cutting it, increase dose or potency


• Back to Regions:• Low dose ketamine infusion (5mg/hr) during the case• Possibly ICU for Dexmedetomidine (Precedex) or ketamine 5-10mg IV q4h prn• PLUS

• Acetaminophen• Gabapentin• NSAIDs• Muscle relaxants

• Opioids• Higher doses needed, assume they will need more and increase all of the above if pain

not controlled


• Patient on 8mg TDD bup has complicated tooth extractions• Likely no opioids needed, d/w dentist• Can split to TID dosing or increase bup temporarily


• Patient on 12mg TDD bup has femur fracture, ORIF• Can decrease to 8mg (or stay on 12mg)• Maximize non opioids• Speak to surgeon, ask to given them 1 week of opioids and what is normal

time frame• 2-3 weeks

• 1st post op visit: Oxycodone 5 mg q3h in terrible pain. Change to hydromorphone 2mg q4h, call if problems, rtc 1 week

• 2nd visit: Pain well controlled, decrease to 2mg q6h, RTC 1 week• 3rd visit: decrease to 2mg q8h, RTC 1 week• 4th visit: 2mg q12h x3 days, 2mg at HS q3 days• Off within 27 days

• Increase back to previous dose, even in during taper


• Patient on 16mg TDD falls and hurts back, no acute pathology seen• No opioids needed• I would not split bup (do not encourage use of any opioid in acute flare of

chronic pain)• Muscle relaxants, NSAIDs, heat, activity


• Patient on 24mg has planned cervical fusion • Slowly decrease towards 16mg, or continue current dose• Day of surgery take 8-16mg (depending on if they can taper down)• Maximize non opioids• Speak to surgeon, ask to given them 1 week of opioids and what is normal time

frame• 4-6 weeks

• 1st post op visit: Oxycodone 15 mg q3h in terrible pain. Change to hydromorphone 6mg q4h, RTC 1 week

• 2nd visit: Pain well controlled, decrease to 4mg q6h, RTC 1 week• 3rd visit: decrease to 4mg q8h, RTC 1 week• 4th visit: 2mg q8h x3 days, 2mg q12h x 3 days, 2mg at HS q3 days• Off within 30 days

• Increase back to previous dose when cravings occur, even if during taper


• Bup was DCd by outside provider?• Taper off post op opioids as fast as possible for pain

• Days - Weeks• Manage risk

• Length of the taper• Frequency• Relapse

• After off opioids, re-induct

Chronic Pain

• Categories of chronic pain • Inflammatory• Focal/structural• Neuropathic• “Central Pain”

• Pain localized to CNS Without a peripheral source Central sensitization

• Not mutually exclusive

Chronic Pain

General pain categories overlap with central pain a component in eachRA = Inflammatory synovitis, structural knee damage, pain response modified centrally

Chronic Pain

• Chronic Widespread Pain = Central Sensitization• Amplification of neural signaling in CNS • Allodynia and Hyperalgesia• Coexisting symptoms

• Fatigue • Sleep disturbances • Mood disturbances • Cognitive disturbances • Catastrophizing • Neuropathic symptoms

Central Sensitization• Chronification of Pain

• Changes occur in• 2) Transmission (Going up)• 3) Inhibition (Coming down) • 4) Interpretation (What does it all mean?)

1) Sensation

2) Transmission

3) Inhibition

4) Interpretation

https://www.change-pain.com/cms/cda/file/cp_com_content_pain_basics.jpg?fileID=310600089&cacheFix=1456495926000&__k=db9f24c77ea86cc78296d38ba1b4c126

Central Sensitization

2)Going Up

3)Coming Down

Descending pain modulation systems integrate body and environmental information with affective state and behaviors

Woolf, C. J. (2011). Central sensitization: implications for the diagnosis and treatment of pain. Pain, 152(3), S2-S15.

Central Sensitization• 3) What does it all mean?

• Hyperactive Amygdala• Emotional memory• Fear responses:

• Defensive behavior- Freeze or Flight• Autonomic nervous system responses: HR, BP

changes• Neuroendocrine responses

• Hypoactive Pre-Frontal Cortex• Decision making• Social behavior• Orchestrate thoughts and actions in accordance with

internal goals


• 3) What does it all mean?• Mesolimbic reward center

• Acute pain: Actives DA in mesolimbic DA reward center

• Prolonged pain: Prolonged activation of DA in mesolimbic reward center

• Decrease DA receptor availability in mesolimbic areas


• Clinically: • Hyperactive Amygdala

• Fear conditioning, activation of SNS, strong emotional/fear memories, cortisol release

• Anxiety, palpitations, nightmares, stress• Hypoactive Prefrontal Cortex

• Decreased ability to plan, think, control behavior

• Low DA in Mesolimbic Pathways• Anhedonia, apathy• Depression

The CS-Addiction Connection Common Neurobiological Mechanisms:• Prolonged exposure to drugs of

abuse also• Decrease DA receptor availability in

mesolimbic reward pathways• Hypoactive prefrontal cortex• Hyperactive amygdala

The CS-Addiction Connection

• But why/how does this happen?• Addiction: Continual use of a substance• Chronic Pain: Prolonged pain• BOTH:

• Sometimes childhood stresses/trauma creates an easy route to these pathways or low baseline dopamine receptor levels

• Concurrent stresses reinforce these pathways

The CS-Addiction Connection

Adverse childhood events

Poor sleep

Trauma

More Pain Sensitive/Higher Risk of AddictionLess sensitive/Lower Risk of Addiction

Deconditioning

Fatigue

Coping skills

Self-careSocial support

Physical Conditioning

Mogil JS. PNAS, 1999;96(14):7744-51. 2. Amaya et. al. J Neuroscience 2006;26(50):12852-60. 3. Tegeder et.al., NatMed. 2006;12(11):1269-77. 4. Diatchenko et. al. HumMolGenet. 2005;14(1):135-43

Opioid Induced Hypersensitivity

• Tolerance: Lower sensitivity to opioids• Desensitization of antinociceptive mechanisms• Opioid receptor down regulation

• OIH: Hyperalgesia and Allodynia• Sensitization of pronociceptive mechanisms

• Spinal dynorphin (k agonist) increases in OIH• Chronic opioid use induces down regulation of SC glu transporters, increases glu in the

SC, increases NMDA receptor activity, causes spinal neuron sensitization

CS-Addiction-OIH: The Triple Threat

Opioid Induced Hyperalgesia


Addiction

Treatment of The Triple Threat

• Treatments• OIH: Remove the offending agents• Addiction: Remove the offending agents, support with addiction

treatment/MAT• CS: The Hard Part

Treatment of CS: The Hard Part

• Calm the hyperactive amygdala• EMDR, Somatic Experiencing, Somatosensory therapies, Hypnosis,

Biofeedback, Yoga, Breathing, Acupuncture, Mindfulness, Meditation, Tai Chi, Qi Gong

• Medications that decrease SNS activation• Propranolol, prazosin, clonidine

• Medications that support serotonin system• SSRIs, duloxetine

• Medications that support gaba system• Gabapentin, pregabalin, avoid benzos

Treatment of CS: The Hard Part

• Retrain the hypoactive prefrontal cortex

• CBT, DBT, learning from activities

• Give the mesolimbic DA pathways the ability to regenerate DA receptors

• Time away from the offending agent

• Support with natural reinforcers: nutrition, exercise, time outside/nature, family

Buprenorphine = OIH?

• Ok, but what about buprenorphine?• Isn’t it just continued overstimulation of the DA reward pathways?• Differences between opioids used for chronic pain or addiction and

buprenorphine• Very long acting• No unlimited tolerance• No dysregulation of HPA axis • Pharmacology

• Mu partial agonist• Kappa antagonist- spinal dynorphin (k agonist) increases in OIH• NMDA antagonist- NMDA agonism in OID

Buprenorphine = OIH?

• Buprenorphine = OIH?• J Nat Sci 2017• 20 Pts with OIH transitioned to bup• Those on higher doses (>100MME)

• Decreased pain sensitivity• Improved FMS survey scores• Fewer neuropathic features• Less catastrophizing• Fewer depressive symptoms• Improved functioning• Return toward baseline at 6 months

For Questions or Sources:

[email protected]

pain management and buprenorphine - chi st. gabriel's health · 2019. 12. 12. · acute pain...

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