palliative pain management part 2-beyond the basics

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Palliative Pain Management

Part 2-Beyond The Basics

Presenter: Robert A. Friedman, MD FAAFP FAAHPM HMDC

Chief Medical Officer Hospice Austin

President Central Texas Palliative Care Associates

[email protected]

33rd Annual Convention of the

Texas & New Mexico Hospice Organization AND

Texas Academy of Palliative Medicine

February 25-28, 2016

Disclosures

No financial or other conflicts of interest

There will be off-label discussion

Objectives

Explain the use of methadone in pain management in the HPM setting

Identify and discuss other non-opioid pain medication choices including Ketamine

Lidocaine

Identify and discuss interventional pain management modalities

Discuss palliative radiation therapy

Discuss palliative chemotherapy

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Opioid use terminology

Misuse, non-medical use

Abuse

Addiction

Physical dependence

Tolerance

Pseudo-addiction

Diversion

Opioid

Iatrogenic

Tolerance A state of adaption in which the physiologic changes

from drug exposure over time lead to diminished drug effect

Is uncommon with stable disease

Tolerance to adverse effects, (sedation, nausea), is beneficial

An opioid tolerant patient is someone who has been on the following for at least one week 60 mg/day oral morphine

25 mcg/hr transdermal fentanyl

30 mg/day oral oxycodone

8 mg/day oral hydromorphone

25 mg/day oral oxymorphone

An equinanalgesic dose of another opioid

-ER/LA Opioid REMS Education, www.core-rems.org

Pseudo-addiction

An iatrogenic condition where patients

display aberrant drug-seeking behaviors

mimicking opioid use disorder, but driven

by intense need for pain relief.

Resolves with adequate pain relief

Can present as

Drug hoarding

Unsanctioned dose escalation

Doctor shopping aggressive demands for more

drug

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What is addiction? A primary, chronic, neurobiologic disease with genetic,

psychosocial, and environmental factors influencing its development and manifestations. Continued use despite harm and drug craving

5 characteristics* Inability to consistently abstain

Impairment in behavioral control

Craving or increased “hunger” for drug or reward experiences

Diminished recognition of significant problems with one’s behaviors and interpersonal relationships

A dysfunctional emotional response

Much confusion due to DSM-4 and earlier classifications/definitions.

With DSM-5 there is a new single diagnosis category of ‘substance use disorder’.

* American Society of Addiction Medicine

FP

57 y.o. female on hospice with dx of breast

cancer, metastatic to bone. Is on Morphine

ER 240 mg q12hrs, with BTP dose of MSIR

45 mg q1hr prn. She is taking the MSIR 4-5

times in a 24hr period. Her pain level is 5 on

the average. She would like a level of 3.

You recommend a conversion to methadone

and she is very agreeable, in part because it

also comes in a liquid form.

Routes of Administration

Advantages

Disadvantages

EKG?-

Methadone

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Analgesic onset 30-60 minutes

Analgesic peak 2.5 - 4 hours

Oral bioavailability >80%

Highly lipophilic

Metabolized in the liver to inactive metabolites (unlike morphine)

Metabolites are excreted by the kidneys

Very long and variable plasma half-life (13-120 hours)

Methadone Pharmacokinetics

Methadone conversion methods

Multiple methods

Morely Makin

Toombs

Friedman

Direct

And others

When converting to methadone, what is the

maximum allowable dose?

One methadone equianalgesic table

Steady state, chronic

Oral MEDD

Approx. conversion ratio

(morphine : methadone)

<30mg 2:1

31-99mg 4:1

100-299mg 8:1

300-499mg 12:1

500-999mg 15:1

1000-1200mg 20:1

>1200mg Consider consult

Reference AAHPM Primer equianalgesic guide MEDD stands for “Morphine Equivalent Daily Dose.” There are a number of such equianalgesic

charts. This one is fairly conservative.

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FP

MSER/24hrs = 480 mg

MSIR/24hrs = 180 mg

MEDD = 640 mg

Conversion ratio 15:1 = 43 mg

25% = 10.75 mg

10% = 4.3 mg

You start her on methadone 5 mg q12hrs

PRN BTP dose of MSIR 60 mg q1hr prn

TC

47 y.o. female with metastatic pancreatic cancer, with bone mets to thoracic and lumbar spine and a para-spinal mass which may be causing nerve compression. She has a hx of debilitating pain from her cancer, but has been fairly well controlled as of late. She now has intractable nausea and vomiting and she agrees to be admitted to the IPU for management. She is presently taking: Oxycodone ER 200 mg q12hrs

Oxycodone 40 mg q1hr prn pain, 3 doses in last 24 hours

TC

You decide to:

Treat the nausea with IV medication?

Convert to an IV opioid?

Try IV meds for nausea, but continue the PO

oxycodone?

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TC

You start her on

IV haloperidol

Convert her to IV hydromorphone

TC

You start her on hydromorphone Oxycodone ER = 400 mg

Oxycodone IR = 120 mg

520 mg oxycodone – 780 mg MEDD

780 mg/20 = 36, reduce by 33% = 24 mg

24 mg/24 hrs = 1.0 mg/hr

What is the prn breakthrough dose? O.4 mg q10 min, (10% of 24hr dose/6, given q10 min)

2.4 mg q30-60 min, (10% of 24hr dose q30-60 min

1.0 mg q15 min, (dosing hourly rate q15 min)

She does well with this conversion

TC

She goes home from the IPU and she can swallow. She is agreeable to conversion to oral meds

She is started on methadone 60 mg q8hrs

The conversion was calculated without using the BTP dosing

This is what was used 20 mg HM x 24 hours = 480 mg HM

480 mg = 9600 MEDD

9600 mg/20 = 480 mg methadone

480 mg x 37.5% = 180 mg, 180 mg/3 =

60 mg q8hrs, with HM 15 mg IV q15 min prn

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Opioid side effects

Sedation

Nausea

Hives/itching

Constipation

Respiratory depression

Opioid-induced neurotoxicity

Urinary retention

TC

Her NP checks on her 36 hours after the

methadone conversion and she is pain-free


With opioids, start low and go slow to avoid excessive rise in pCO2

If patient can be awakened and can hold a conversation, then the patient is not over-sedated

Long before patients stop breathing, they develop altered mental status

Consider writing parameters for nurses/caregivers Call immediately for RR <6-8/min

What about the actively dying patient?

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If opioid tolerant Do not completely reverse!

Complete reversal Triggers acute withdrawal syndrome

Completely “uncovers” all pain

Diluted naloxone

0.4 mg diluted with NS in a 10 mL syringe

Administer 0.25 to 1 mL aliquots q2-3 min

Titrate respiratory rate to 8-10 per min

Awakening the patient is not necessary/desirable

TC

What do you do?

Admit to hospital?

Hold methadone?

When should resume the methadone and at

what dose?

BTP medication?

Alcohol effects on opioids

In combination with opioids

May increase the risk of respiratory

depression during opioid titration or rescue

dosing with morphine

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Constipation

Opioids cause colonic slowing

Routine use of stimulant laxative plus stool softener when starting opioids (sennosides + docusate sodium), 2 po qpm or 1 tab po bid (up to 10/day) or Just a stimulant laxative

Consider other treatment choices if constipation persists

For opioid-induced constipation in patients with advanced illness, receiving palliative care, with insufficient response to laxative therapy-Relistor (methylnaltrexone bromide), Naloxegol, Lubiprostone Contraindicated in patients with mechanical bowel

obstruction

High Dose / Prolonged Use

Renal Insufficiency

Excitation Agitation / Myoclonus / Cognitive impairment /

Hallucinations / Delirium / Seizures / Hyperalgesia / Allodynia / Bad Dreams

Sedation / Coma

Treatment Hydration / Dose Reduction (by 20%) / Opioid Rotation

Opioid-induced Neurotoxicity

GG

41 y.o. male with colorectal adenocarcinoma, metastatic to lung, liver, peritoneum, s/p segmental sigmoid colon resection and multiple cycles of chemotherapy. His pain is abdominal and he has low back pain which radiates around to the abdomen. He also has anxiety. Has been on Oxycodone ER and steroids, methadone 70 mg q6hrs and Nucynta 2-3 x/day for BTP prn and scheduled at hs. He was converted to IV hydromorphone with initial good response, but ultimately complains of poorly controlled pain on what ended up being high-dose IV hydromorphone.

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GG

He is admitted to the IPU and treated with SC

Ketamine per your IPU protocol

SC ketamine

Is an anesthetic agent with analgesic

properties

Provides safe and, theoretically, effective

analgesia as a low dose infusion

May cause some sedation

May be used as separate infusion alongside

other opioids

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GG

GG has favorable response to SC ketamine initially

In spite of following the protocol, he, ultimately, has no improvement in pain control with the ketamine

Why?

Largest RCT to date shows no benefit with a dose escalating regimen “Ketamine does not have net clinical benefit when used as

an adjunct to opioids and standard coanalgesics in cancer pain.”

Prior evidence for use was extrapolated from other settings

Primary support prior to this study comes from case series and uncontrolled studies

GG

So let’s try IV Lidocaine

IV/SC Lidocaine

Indications-after less invasive methods have failed Intractable neuropathic pain or visceral pain due to malignancy.

Pain relief is superior and reduced analgesic requirement post-infusion are better than placebo in multiple clinical settings

Is inexpensive (24 hours supply can cost < $5).

One recent study found 71% positive response rate and 49% had a major positive response

Has analgesic, anti-inflammatory, and anti-hyperalgesic properties Suppresses spontaneous impulses generated from injured nerve

fibers and the proximal dorsal root ganglion

Blocks neural transmission at site of tissue injury

Interferes with the inflammatory process, suppressing peripheral and central sensitization, resulting in an anti-hyperalgesic effect

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IV/SC lidocaine

Many protocols require a 12 lead EKG prior to

initiating infusion

Continuous or intermittent infusions

Recent study (retrospective case series between 2003

and 2013) and companion protocol only obtains EKG

if

Male and older than 65 years

Female older than 55 years

And/or known or suspected of having cardiac problems

Infusion requires close nursing supervision, as in PCU, IPU,

ore residential hospices, possibly in the patient’s home

IV/SC lidocaine

Contraindications Absolute: allergies to “caine” anesthetics

Relative: cardiac failure, cardiac dysrhythmias, Prolonged PR interval on ECG, hepatic and renal dysfunction

Adverse effects/Toxicity Peri-oral tingling/numbness, metallic taste, light

headedness, irritability/excitability, visual disturbances, mm twitching, confusion/sedation

Good news Side-effect profile is predictable and has wide safety margin

Short half-life = transient/easily reversible side-effects

IV/SC lidocaine

Thorough pre-infusion assessment Medical hx, medication hx, pain hx/assessment

Consider a lidocaine challenge

Protocol sample-email

When/how to discontinue

Once pain is controlled Can result in significantly reduced opioid need

Can be tried on gabapentin or other adjuvants

If successful, can wean off the lidocaine

If not, can be maintained on lidocaine for weeks to months

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GG

The lidocaine is ineffective.

What next?

Interventional Pain Management

Or??

GG

MEDD ended up at 40 grams

Converted to methadone and ultimately went

home on methadone 30 mg q8hrs and

hydromorphone 30 mg q1hr prn, using up to

5 doses/24hrs, with good pain control

How was this accomplished?

Non-pharmacologic management of

pain Physical modalities

Heat, ice, elevation

Complementary techniques Massage,

acupuncture/pressure, manipulation, therapeutic touch

Music

Art

Aromatherapy

Guided imagery

Meditation/prayer

Biofeedback

Distraction Humor

Pet Therapy

Trans-epidural Nerve Stimulator Unit

Education about illness

Hypnosis

Cognitive and Behavioral Therapy

Better history

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DJ

60 y.o. male with dx of adenocarcinoma of the lung with mets to bone, liver, adrenal, bilateral kidneys, right vastus medialis muscle (necrotic lesion),lymph nodes in hilum and right chest.

His attending, a palliative care physician, is requesting an epidural pain pump for right leg pain secondary to metastatic disease and significant lymphedema.

What do you do?

Interventional pain management and the

nervous system

Spinal chord

Nerve roots

Nerves

Plexuses

Ganglia

Interventional pain management in cancer

patients 10-15% of cancer patients have intractable cancer

pain poorly responsive to analgesics

Neurolytic techniques Chemical, thermal, surgical

Employed for ablation of Individual nerve fibers

Plexuses

Intrathecal neurolysis

For patients with resistant pain and short life-expectancy

Neuromodulation Modulates or alters the pain perception

Neuraxial administration of drugs

Spinal cord stimulation

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Interventional pain management in cancer

patients General contraindications

Patient refusal

Local or systemic infection

Uncorrected coagulopathy (INR > 1.5, plts < 50,000)

Lack of technical expertise

Uncertainty regarding the dx

Uncooperative patient

Patient with opioid addiction or drug-seeking behavior

Allergy to the drugs to be used

Relative contraindications Antiblastic chemotherapy and neutropenia

Document neurological deficits prior to procedure

Interventions

Head and neck cancer

Nerve blocks

Trigeminal

Glossopharyngeal

Occipital

Vagal

Sphenopalatine ganglion

Cervical plexus

Interventions

Intractable thoracic/chest wall cancer pain Intercostal block

Neurolysis

Pulsed radiofrequency

Intrathecal pump implantation

Upper abdominal cancer pain Neurolytic celiac plexus block

Better for visceral and somatic pain, than neuropathic pain

Consider early in course of illness, where the plexus is free and no contraindication, such as approach

Splanchnic nerve block

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Interventions

Cancer-associated pelvic and perineal

visceral pain

Neurolytic superior hypogastric plexus block

Neurolytic inferior hypogastric plexus block

Ganglion impar block and neurolysis

Neurolysis of lower sacral roots (neurolytic

saddle block)

Interventions

Intraspinal techniques Epidural infusion of drugs

76-100% effective

Clinical data support intrathecal catheter use for more than 3 weeks

Epidural requires greater dosages, larger volumes and more frequent refills

Therefore, the cost is higher as are infection rates

Also increased risk of side effects Dislocation/obstruction

Nausea

Vomiting

Drowsiness

Constipation

Dural fibrosis

Interventions

Intrathecal Less complications than epidural

Trial of intraspinal analgesia should be considered before permanent implantation to assess Pain

Function

Mood

Adverse effects

Meds Opioids, ziconotide, clonidine, baclofen

Most frequently used = morphine (FDA approved), fentanyl, bupivacaine, ropivacaine, and clonidine

Morphine oral 300 mg = 100 mg IV/SC = 10 mg epidural = 1 mg intrathecal

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Interventions

Vertebroplasty and Kyphoplasty Boney metastases are common in cancer

30-80% involve vertebrae

Primary sources Lung

Breast

Prostate

Vertebroplasty Stabilization of pathological fractures via injection of bone cement

polymethylmetacrylate

Kyphoplasty Percutaneous placement of intravertebral balloon, with inflation

restoring vertebral height and reducing kyphotic angulation

Is more costly

Interventions

Role of early intervention in cancer pain

Neurolytic blocks can

Provide prolonged pain relief

Avoid or reduce distressing opioid-induced side-effects

When to avoid

Multiple sites

Multiple types

Dynamic pain

Poor performance status

DJ

Next steps?

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Radiation & Chemotherapy Therapy

Will the patient live long enough to benefit

from the therapy

PPS score

ECOG (Eastern Cooperative Oncology

Group) Performance Score

ECOG Performance Status

0 – Asymptomatic (Fully active, able to carry on all prediseaseactivities without restriction)

1 – Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)

2 – Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)

3 – Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours) (KPS 30-40%)

4 – Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair) (KPS 10-20%)

5 – Death (KPS 0)

Radiation therapy-decision making

Choosing Wisely HPM

Choosing Wisely Oncology

ASCO Guidelines (American Society of Clinical Oncology) http://www.asco.org/quality-guidelines/asco-institute-

quality-iq

inPractice® - Oncology On line and as an app

http://www.inpractice.com/Textbooks/Oncology.aspx

Your local oncologists

http://www.asco.org/quality-guidelines/asco-institute-quality-iq



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Choosing WiselyAn initiative of the ABIM Foundation

Choosing Wisely aims to promote conversations between clinicians and patients by helping patients choose care that is:

Supported by evidence

Not duplicative of other tests or procedures already received

Free from harm

Truly necessary

http://www.choosingwisely.org/about-us/

Choosing Wisely and Radiation Therapy

AAHPM Don’t recommend more than a single fraction of

palliative radiation for an uncomplicated painful bone metastasis.

American Society of Radiation Oncology Don’t routinely use extended fractionation schemes

(>10 fractions) for palliation of bone metastases. Studies suggest equivalent pain relief following 30 Gy in 10

fractions, 20 Gy in 5 fractions, or a single 8 Gy fraction.

A single treatment is more convenient but may be associated with a slightly higher rate of retreatment to the same site.

Strong consideration should be given to a single 8 Gy fraction for patients with a limited prognosis or with transportation difficulties.

Radiation therapy

?benefit if multiple mets

?value in brain mets

Whole Brain versus Stereotactic Radio Surgery

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Chemotherapy

Is the treatment palliative?

Is the treatment medically beneficial?

Is the patient likely to live long enough to benefit from the therapy

What is the impact of the therapy on QOL and might it hasten demise

Is the treatment likely to prolong survival?

Are there other more medically appropriate measures available?

What if the patient declines the alternative measures?

Chemotherapy

Breast cancer and multiple myeloma are two

malignancies for which treatment beyond 2

regimens of chemotherapy may be beneficial

Palliative treatment and chemotherapy

combination regimens

Chemotherapy-decision making

ASCO Guidelines (American Society of

Clinical Oncology)

http://www.asco.org/quality-guidelines/asco-

institute-quality-iq

inPractice® - Oncology

On line and as an app

http://www.inpractice.com/Textbooks/Oncology.as

px

Your local oncologists

http://www.asco.org/quality-guidelines/asco-institute-quality-iq



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And in the end….

Always have an exit strategy

Questions?

References and Resources

Watson, Lucas, Hoy, and Back. Oxford Handbook of Palliative Care. New York, USA: Oxford University Press, Inc; 2005.

Woodruff. Palliative Medicine. Victoria, Australia: Oxford University Press, 4th ed, reprinted in 2005.

Fast Facts and Concepts #089: Pain management in nursing homes: Analgesics Prescribing Tips, 2nd ed, Palliative Care Network of Wisconsin; April 2009.

Fast Facts and Concepts #181: Oral Oxymorphone, Palliative Care Network of Wisconsin; June 2007.

Fast Facts and Concepts #221: Treatment of Pain in Patients taking Buprenorphine for Opioid Addiction, Palliative Care Network of Wisconsin; November 2009.

Fast Facts and Concepts #228: Tapentadol, Palliative Care Network of Wisconsin; March 2010.

Quill, Holloway, Stevens Shah, Caprio, Storey. Primer of Palliative Care, 4th edition. © 2007 American Academy of Hospice and Palliative Medicine.

Collaboration for REMS Education, ER/LA Opioid REMS Education, www.core-rems.org

Opioid Intolerance Decision Algorithm: Pharmacist’s Letter, Therapeutic Research Center; © 2006

Butrans Patch: Official FDA information, Drug Information Online, Drugs.com

References and Resources Prescription Opioids: Risk Management and Strategies for Safe Use.

NetCE, CME for Physicians 2015

Bhatnager, Gupta. Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain. Indian Journal of Palliative Care. 2015 May-Aug;(21(2):137-147.

Weinberg, Inturrisi, Reidenberg, Moulin, Wallenstein, Houde, Foley. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther. 1988 Sep; 44(3):335-42

Salpeter, J Buckley, N Buckley, Bruera. The Use of Very-Low Dose Methadone and Haloperidol for Pain Control in the Hospital Setting: A Prelminary Report. Journal of Palliative Medicine. 2015;Volume 18,Number 2:114-119

Peixoto, Hawley. Intravenous Lidocaine for Cancer Pain without Electrocardiographic Monitoring: A Retrospective Review. Journal of Palliative Medicine. 2015;Volume 18, Number 4:373-377

Lidocaine and Ketamine Infusions for Intractable Cancer Pain. Presentation at Advanced Clinical Hospice and Palliative Care Workshop. October 23, 2014

http://www.core-rems.org/

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Ferrini, Paice. How to Initiate and Monitor Infusional Lidocaine for Severe and/or Neuropathic Pain. The Journal of Supportive Oncology. 2004;2:90-94

Hardy, Quinn, Fazekas, Plummer, Eckermann, Agar, Spruyt, Rowett, Currow. Randomized, Double-Blind, Placebo-Controlled Study to Asses the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain. J Clin Onco. 30:3611-3617

Fast Facts and Concepts #166: Once Daily Oral Morphine Formulations, CAPC; re-edited April 2009

Spaner. Effectiveness of the Buccal Mucosa Route for Methadone Administration at the End of Life. Journal of Palliative Medicine. 2014;Volume 17,Number 11:1262-5

Toombs, Kral. Methadone Treatment for Pain States. American Family Physician. 2005;71:1353-8

UK Hospice Model (Morley JS, Makin MK. The use of methadone in cancer pain poorly responsive to other opioids. Pain Rev. 1998;5:51-8.)


Coluzzzi. Sublingual Morphine: Efficacy Reviewed. J Pain Symptom Manage. 1998;16:184–192

Fast Facts and Concepts #36: Calculating Opioid Dose Conversions, Palliative Care Network of Wisconsin; re-edited March 2009.

Fast Facts and Concepts #161: Opioid Use in Renal Failure, Palliative Care Network of Wisconsin; re-edited April 2009, page updated 12/20/2011

McPherson. Demystifying Opioid Conversion Calculations: A Guide for Effective Conversion Calculations, Chapter 5-Transdermal and Parenteral Fentanyl Dosage Calculations and Conversions. Published by ASHP, 2009.

Primer of Palliative Care. 6th edition Published by AAHPM.

Gilron, Bailey, Tu, Holden, Weaver, Houlden. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005,352: 1324-1334

Fast Facts and Concepts #295: Opioid-induced Constipation Part II: Newer Therapies, Palliative Care Network of Wisconsin; April 2015

palliative pain management part 2-beyond the basics

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