Chronic Non Cancer Pain (CNCP) - PowerPoint Presentation

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Chronic Non Cancer Pain (CNCP) - PPT Presentation

Feedback from the Oxford Advanced Pain and Symptom Management Course July 18 Anne Hounsell Speciality Doctor The Rowans Hospice 61218 Objectives The use of opioids in CNCPrisks and benefits ID: 933748

opioid pain opioids chronic pain opioid chronic opioids patients study ketamine effects cancer amp drug limb ischaemic group epidural

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Slide1

Chronic Non Cancer Pain (CNCP)Feedback from the Oxford Advanced Pain and Symptom Management Course –July 18

Anne Hounsell, Speciality Doctor, The Rowans Hospice

6/12/18

Slide2

ObjectivesThe use of opioids in CNCP-risks and benefits.Looking at alternative management options. An example of chronic non cancer pain –peripheral vascular disease.

As well as looking at the management of CLA (critical limb ischaemia)

Appendix 1- examples of chronic pain

Appendix 2 –Managing chronic pain

Appendix 3 –further information on CLA

Appendix 4 –some papers

Slide3

BackgroundDefinitionPain for > 3 months or after expected duration/recovery post injury. With a non malignant cause.

Pathophysiology

Tends to be that there was disease or damage to the somatosensory nervous system

However then there is an ongoing Inappropriate response of the pain signalling pathways

Pain continues despite healing with ongoing pain signalling

Who can get this pain?

Anyone really!

Many of our patients have co-morbidities and non cancer diagnoses.

Likely to increase as people live for longer.

Slide4

EXAMPLES YOU HAVE SEEN?

Slide5

Background ContinuedExamples include:1) Patients with non –cancer conditions

MND, Multisystem Atrophy, MS, Parkinson’s disease, Dementia, Cardiac failure, COPD.

Patients with co-morbidities

Arthritis, fibromyalgia, chronic back pain, chronic regional pain syndrome etc

(Also chronic constipation, pressure sores)

Further information in appendix 1

Slide6

The use of Analgesics for CNCPWe have tended to use the WHO analgesic ladder:

Slide7

HOWEVER…..This ladder was developed for cancer pain and has not been validated for non cancer pain.Research has found that opioids for CNCP are often not very helpful and can be harmful

Slide8

The Use of Opioids in GeneralStudies: Most of the patients on opioids in the UK have chronic non cancer pain. There is however no evidence for the use of opioids in these patients –no better than placebo.

Recent RCT –chronic back pain –pain intensity was actually worse in the opioid group.

Data looking at QOL with long term opioids is inconclusive.

No evidence relating to a) different dosing strategies 2) short versus long acting 3) continuous versus PRN 4) opioid rotation

Therefore in most patients the burdens and side effects outweigh the benefits

In most people we need to focus on opioid deprescribing

Slide9

The Effect of Opioids vs Non Opioid Medications in Pain Related Function in Patients with Chronic Back Pain or Hip/Knee Pain from OA. The SPACE RCT. Jama Journal, 18, Krebs et al.12-month trial ( 240 patients)

Compared the use of opioid vs non -opioid treatment for lower back pain and OA

Outcomes:

Pain related function

No improvement in pain-related function over 12 months

(3.4 vs 3.3 points on an 11-point scale at 12 months, respectively)

Pain intensity

Pain significantly better in the nonopioid group over 12 months

(mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the non-opioid group (difference, 0.5 [95% CI)

Medication related adverse symptoms

Significantly more SE’s common in the opioid group

over 12 months (overall P = 0.03)

Slide10

POTENTIAL PROBLEMS?

Slide11

Possible damage caused by opioid use in patients with CNCP1)Side effects and toxicity2)Potential for abuse and addiction

3)Potential for drug overdose and death

4) Potential drug interactions

5) Others

Risks of problems

Patient factors

mental heath problems, alcohol misuse/non-opioid drug misuse, opioid misuse

There is a strong association was demonstrated between long-term opioid use and the clustering of addictive behaviours.

Drug factors

High doses, multiple opioids, More potent drugs, Concurrent benzodiazepines/sedative drugs

Slide12

1)Possible Side Effects and ToxicityGastrointestinalNausea, vomiting, constipation

Neurological

Drowsiness, cognitive impairment (decreased attention), delirium, respiratory depression, seizures, hyperalgesia, myoclonus

Autonomic

Dry mouth, urinary retention, postural hypotension

Cutaneous

Itch, sweating

Slide13

1)Possible opioid side effects and toxicity continuedTestosterone deficiency –opioids suppress GNRH :

affects sexual function and mood

Can decrease bone density (and therefore risk of

fractures

Can contribute to obesity

Can decrease pain control and lead to hyperalgesia.

Increase risk of MI

Increased risk of osteoporosis

50% of men on opioids for non cancer chronic pain have osteopenia

Due to testosterone deficiency and

Via a direct effect on bones – inhibits osteoblast activity

Immunosuppression

Slide14

2) Potential for Abuse and AddictionOPIOID MISUSE Taking for wrong reason/not according to prescription, eg

using for sleep alone, or swigging from the bottle.

People with depression/other mental health problems, are more likely

be prescribed opioids as

pple

say it calms them.

ADDICTION

Continued use with experience of harm (

, impaired control over drug use, compulsive use, continued use despite harm, craving)

Sadly not much help

PAPER

Review rates on opioid misuse, abuse and addiction in chronic pain-a SR and data synthesis. Pain 15,Rowles

Problematic use ranged from < 1 – 81%

Misuse - 21 – 29%

Addiction - 8 – 12% (In another paper -up to 37%)

(Also noted is an increase in abuse from

gabapentinoids

)

Slide15

3) Potential for Drug Overdose and DeathCo-prescription of benzodiazepines with opioids increased the risk of overdose death 4 fold Concomitant gabapentin use (> 900mg per day) was associated with a 60% increase in the risk of opioid-related death Very high doses gabapentin associated with 2 fold increase

The office for national statistics 2016 – for those deaths from drug poisoning 54% involved opioids.

Overdose [HR 5.2]

An increase in deaths from fentanyl

Slide16

4) Drug interactionsCombined with the following can cause potential problem -EG:BenzodiazepinesZopiclone

Antidepressants (SSRIs)

Other opioids

Ciprofloxacin

Fluconazole

Antipsychotics

Methyphenidate

Anticonvulsants

And of course alcohol

Slide17

5) OthersLong term opioid use outcomes-Pain 06, Eriksen, Critical Issues on Opioids for Chronic Non Cancer Pain. Epidemiological study:-228 opioid users compared with 1,678 non-opioid users

-Opioids usage significantly associated with:

1)Reporting of severe pain

2)Poor self-rated health

3)Inactivity during leisure

4)Unemployment

5)Higher healthcare utilization

6) Poor health orientated quality of life

7)Motor vehicle accident [OR 1.24-1.42)

Slide18

Despite all this…….-There are a subset of patients that might benefit from opioids (though difficult to know who)-If you are going to trial it:

120mg morphine/day maximum (risk of harm substantially increases above this)

or use intermittently.

If no useful effect after 2-4 weeks –stop

Slide19

Opioid De-prescribingIf no useful effect after a trial of 2-4 weeks –stopIf you do wean/stop opioids -you must provide other supportOPIOID DEPENDANCE (physical) :

1)Therefore don’t stop suddenly -

opioid withdrawal syndrome

2)anxiety, irritability, alternating chills and hot sweats, ‘wetness’ ( salivation, lacrimation,

rhinorrhea

, sweating), sneezing, goose flesh.

3) At the peak of withdrawal –the patient can get nausea, vomiting, abdominal cramps, insomnia and occasionally myoclonus.

4) Suggestions are to

taper dose

by 10% per week –but no consensus! (Cochrane library)

Slide20

If we are trying to avoid opioids for CNCP–what other options are there?

Slide21

Managing CNCPCan be very difficult to manage (hence why often opioids are used)Its complex with variable interplay between biological, psychological and social factors.

Thinking of the pathophysiology of the particular pain is important. For example there may be neuropathic/inflammatory/muscle spasm components. This can help guide medication use.

Paying particular attention to non drug management is especially important. We need to help the patient

function

as well as possible despite the pain.

Other aspects include PT,OT, psychology (

chronic pain clinics)

It is important to look at function rather than pain scores.

See APPENDIX 2

Slide22

Slide23

An example of chronic non cancer pain Peripheral Vascular Disease and Ischaemic limb pain

Slide24

Peripheral Vascular DiseaseCommon (12% of adult population), especially those with other co-morbidities eg DM, CKD, IHD etc

Risk factors include smoking, raised cholesterol/triglycerides, diabetes, age

FEATURES:

1. Limb pain -worse at night and wakes them up

-can include phantom limb pain

2. Reduced functional status

3. +/- episodes of opioid toxicity (due to the pain being very complex to treat, as well as the patient having co-morbidities)

4. +/- episodes of delirium (due to the above and infections of ulcers)

Slide25

Non Reconstructable Critical Limb IschaemiaDefinition 1) Chronic rest pain/ulceration/gangrene

(ulcer DD)

2) Patient has proven arterial occlusive disease

Fontaine and Rutherford grades are used and ABPI (< 0.5)

( RG - stage 0- asymptomatic, 1-mild claudication, 2-moderate claudication, 3 –severe claudication, 4-rest pain, 5- ischaemic ulcers of toes, 6-severe ischaemic ulcers/frank gangrene)

3) Have had multiple surgical interventions (

revascularisation/ amputation) and been assessed by the vascular team -no option of further surgery/management

There is a 20% mortality rate within 6 months of diagnosis.

Major amputation required within 1

in 40% of patients

5 year mortality > colorectal/breast/prostate cancer, stroke, MI

Has a negative impact on QOL

The level of blood flow correlates with the severity of pain

reduced flow = increase pain

Slide26

Slide27

Treating Critical Limb Ischaemia Any experience??

Slide28

Treating Critical Limb Ischaemia1) Create goals eg pain management, reduction in ulcers, improving functional status and QOL, and survival

Unfortunately currently there is no effective medical therapy

A MDT holistic approach

is needed as well as attention to the co-morbidities

Further details of diagnosis, risk factors etc are in APPENDIX 3

Slide29

(Conservative) Management of Ischaemic Pain -1Little data - studies involving patient reported outcome measures do not exist!

Most research focuses on physician reported outcome measures (graft patency, survival, etc.)

Cannot recommend one medication over another.

There is a significant neuropathic element -distal axonopathy.

Slide30

Systematic Review of Pharmacological Therapies in the Management of Ischaemic Pain in Patients with Non–reconstructable Critical Limb Ischaemia.BMJ Supportive and Palliative Care, Aug 17, onlineLaoire et al

See appendix 4 for more detail

•5 RCTs, 1 observational study

IV LIDOCAINE

• IV Lidocaine vs IV morphine sulphate

• Effect: At 15 & 30 mins mean VAS

pain score lower in intervention group

• No adverse effects but only monitored for 30 mins post infusion

GABAPENTIN

• Gabapentin titrated from 300mg OD to 600mg TDS, no control

• Median

pain score significantly reduced

each of assessment days

• 15 patients -

improved night pain & perceived QOL

• No adverse effects

Poor quality study though

Slide31

Study continuedKETAMINEStudy 1RCT, N=35IV Ketamine vs N Saline over 4 hrs (b/g opioids + haloperidol)

Outcomes:

Greater pain relief

at 24 hrs & 5 days post ketamine infusion

improved general activity & enjoyment of life

33% “

more emotional

than usual” post ketamine, 6% post placebo

Study 2

RCT, N=8

IV Ketamine (3 different doses) vs IV Morphine (no prophylactic antipsychotic)

No stat. sign. difference at peak effect times

All had perceptual disturbances & psychotropic effects

Slide32

Study continuedBURPRENORPHINE AND EPIDURAL N=86Buprenorphine 35µg/hr patch + epidural morphine/ropivacaine Vs epidural alone

Outcome:

Signiﬁcantly lower pain scores

in intervention group

better sleep quality

3) More SEs (drowsiness, fatigue, constipation, nausea) in control group

Slide33

STUDY OUTCOMELidocaine - Promising BUT further studies neededGabapentin - poor study design, but widely used & well tolerated

Ketamine

remains controversial! **

Buprenorphine + epidural

- effective but poor quality studies - ?reproducible effect

Slide34

KETAMINEAnalgesic in subanaesthetic dosesAnti-inflammatory, Antidepressant, Anti-Noiceptive

, NMDA antagonist

But there are multiple SEs -CV, urine toxicity, cognition/psychiatric

Weak evidence for its use in CLI

Strong evidence for its use on acute/post op pain

Some evidence for use on chronic regional pain syndrome

No papers looking at subcutaneous ketamine

For chronic cancer pain -NNT 25, NNH 6

No standard regimen in dose, route, frequency of use

The current evidence is insufficient

to assess the benefits and harms of its use

Slide35

Managing Ischaemic Pain –Other optionsOthersPregabalin (no research)Methadone? But no studies

Midazolam -can help with neuropathic pain

Ketorolac -very end of life

Non pharmacological

Spinal cord stimulation

Lumbar sympathectomy -no studies

Epidural -effective but poor quality studies

GET EARLY INVOLVEMENT WITH THE SURGICAL TEAM SO THAT WE CAN SUPPORT THEM. MDT approach with vascular /chronic pain/pall care teams

Slide36

Summary of How to Manage Ischaemic Limb PainNo single recommendation of a pharmacological agent possibleTitrate (renally friendly) opioidAdd a neuropathic agent (gabapentin 1st

line)

Consider ketamine (though cannot be recommended on current level of evidence)

Slide37

SummaryThe use of opioids in CNCPNo evidence for benefit –can even increase the painRisk of multiple problems :

1) GI, neurological, autonomic, cutaneous, immune, cardiac and hormonal side effects

2) Opioid toxicity

3) Misuse, addiction, overdose, drug interactions

Other management options for CNCP

MultidiscipIinary

- including psychology, OT, PT

Non drug methods

Analgesics

An example of CNCP

Peripheral Vascular Disease

Managing ischaemic limb pain in critical limb ischaemia:

Evidence available.

Consider renally friendly opioid, gabapentin, ketamine -

Slide38

THANKYOU! ANY QUESTIONS?

Slide39

ReferencesOxford Handbook of Palliative MedicineGoogle scholar‘ Testosterone deficiency in non cancer opioid treated patients’ Coluzzi et al, Dec 18, Journal of endocrinological investigation

British Medical Association –chronic pain –supporting safer prescribing of analgesia

NICE, SIGN, Department of public health

Opioid overdose and deaths -

Kaplovitch

E et al. (2015)

PLoS

ONE 10(8)

-Gomes T et al. (2017)

PLoS

Med 14(10)

Faculty of pain medicine –the effectiveness of opioids for long term pain

-opioid aware website

Review rates on opioid misuse, abuse and addiction in chronic pain-a SR and data synthesis. Pain. 15,Rowles

Slide40

References continuedAddictive behaviours related to opioid use for chronic pain –a population based study. Pain 2013,Hojsted et al, 154:26Critical issues on opioids for chronic non cancer pain. Epidemiological study

Pain 06, Eriksen

The Effectiveness and Risks of Long Term Opioid Therapy for Chronic Pain: Systematic Review for a National institutes of Health Pathway to Prevention Workshop.

Annuals of Internal Medicine, 2015, 162, Chou

Wilsey

et al. Pain Med 2008; 9: 1107.

Gudin

et al. Postgrad Med 2013 125:115.

Fishbain

et al. Pain Med 2008; 9: 444.

Chou et al. Ann Int Med 2015; 162: 276

http://www.rcoa.ac.uk/faculty-of-pain-medicine/opioids-aware

-A resource for patients and HCP to support the prescribing of opioid medication for pain.

TASC 2 (transatlantic intersociety consolidation document on the Mx of PVD)

Systematic Review of Pharmacological Therapies in the Management of Ischaemic Pain in Patients with Non–

reconstructable

Critical Limb Ischaemia.

BMJ Supportive and Palliative Care, Aug 17, online.

Laoire

et al

Cochrane Library

Slide41

APPENDIX 1 -Non malignant conditionsMotor Neuron DiseaseUp to 73% of patients complain of pain.

Often musculoskeletal (loss of muscle, muscle contractures, joint stiffness)

Also pressure sores

Stroke

Musculoskeletal –contractures, pressure sores

18-23% have post stroke headaches

Up to 30% have shoulder hand syndrome (oedema, pain, trophic skin changes, muscle atrophy).

8% have central pain-especially if vascular lesion.

Slide42

Non malignant conditions continuedParkinsons diseasePain is common in end stage Parkinsons

’ disease

Stiffness, rigidity, dystonic spasms, posture

Constipation

Pressure sores

Dementia

Contractures, stiffness

Pressure sores

Slide43

Non malignant conditions continuedMultiple Sclerosis50-60% get pain Including spasticity, trigeminal neuralgia, spasms eg

in legs,

Lhermittes

sign (sudden pain on

neck flexion)

Headache

cluster, retro-orbital pain due to optic neuritis, trigeminal neuralgia

Dysaesthetic

pain (abnormal sensation)

Lower back pain

Visceral pain (constipation, bladder spasms, bladder distention)

Slide44

Non malignant conditions continuedRenal Failure> 50% of dialysis patients get severe painStudies have shown that the pain can be as severe as from peripheral vascular disease

Often mixture of nociceptive, neuropathic and ischaemic

Analgesic challenges as often elderly with co-morbidities

Examples of causes

1)-Often musculoskeletal –renal osteodystrophy (altered bone turnover), osteoporosis

2)-Calciphylaxis- calcification of small blood vessels –ischaemia –very painful skin lesions and ulcers

3)-Neuropathy with dopaminergic dysfunction -restless legs and crawling sensation

Slide45

Non malignant conditions continuedHeart FailureChest pain –refractory angina can be distressing and debilitatingCOPD and other respiratory conditionsChest wall pain –Musculoskeletal, effort of breathing

Slide46

APPENDIX 2 –Managing CNCPSIGN (Scottish Intercollegiate Guideline Networks)- General Principles -1Initial AssessmentPatient centred approach

Detailed pain and biopsychosocial assessment assessment(including function, mood and QOL)

Try and identify cause(s) and assess for neuropathic component

Watch out for red flags (

spinal cord compression etc)

Slide47

SIGN -2ManagementListen, validate, educateTreat underlying cause/ contributing factors where possible.

Encourage self help management

Encourage patient to stay at work

Encourage patient to stay active

Acupuncture, TENS, heat/cold

Physiotherapy, Occupational therapy

Focus of living despite the pain, function and quality of life

Psychological support –depression and anxiety common –viscous circle

(This includes CBT –psychoeducation, relaxation, distraction, cognitive restructuring)

Analgesia

Slide48

SIGN -3Management continuedAnalgesia –before prescribing:Offer non drug strategies

Agree goals –

increased function/increased mobility/increased QOL/reduction in pain.

Agree length of analgesic trial

Discuss side effects and significant risks

Discuss short term/long term benefits (

potential loss of analgesic effect with time)

Avoid too much co-prescribing.

Review after 2-4 weeks

Set scheduled follow up.

Slide49

Possible Analgesic agents for CNCPORAL ParacetamolNSAIDS –bone and inflammatory painSteroids

for pain due to tumour inflammation (affecting CNS/PNS)

rapidly tapering for shoulder hand syndrome in CVA

Antispasmodics

Smooth muscle –hyoscine

butylbromide

, nifedipine

skeletal – tizanidine, dantrolene, baclofen, clonidine, quinine, benzodiazepines, cannabinoids,

gabapentinoids

Anti-

anginals

ISMN, Nicorandil, Nifedipine

Dopamine agonists

L dopa, Sinemet(includes

methyphenidate

) –for stiffness and rigidity from PD.

Others

–

methadone

Slide50

Analgesic options other than opioidsORALNeuropathic agents Antidepressants eg

amitriptyline, duloxetine, mirtazapine

Anticonvulsants

gabapentin, pregabalin, lamotrigine, sodium valproate, carbamazepine

sodium channel blockers –

Lidocaine

Cholinergic (or acetylcholinesterase inhibitors) drugs -

neostigmine.

Benzodiazepines

clonazepam

Calcitonin (and for bone pain)

Prazosin,

Propanolol

phenoxubenzamine

Ketamine

Useful for neuropathic pain, including TGN, central CVA pain, diabetic neuropathy

Slide51

Analgesic options other than opioidsTOPICALLidocaine patch –localised neuropathic painCapscacin cream –localised neuropathic pain

Topical morphine in

intrasite

–pressure sores

INJECTION

Botulinum toxin –painful tonic spasms

in PD

OTHERS

Nerve blocks –refractory neuropathic pain

GTN -angina

Slide52

APPENDIX3Risk factorsforCLI

Slide53

Slide54

Treatments and Outcomes for CLI

Slide55

Differential Causes for Lower Limb Ulcers

Slide56

APPENDIX 4Paper 1Addictive behaviours related to opioid use for chronic pain –a population based study. Pain 2013,Hojsted et al, 154:26

Six potential addictive behaviours were investigated

Daily smoking, high alcohol intake, illicit drug use, obesity, long-term BZD (or related drug) use.

At least two behaviours found in:

1) 22.6 % long-term opioid users

2) 11.5 % chronic pain but not taking opioids

3) 8.9% individuals without chronic pain

Thus, a strong association was demonstrated between long-term opioid use and the clustering of addictive behaviours.

An intricate relationship between chronic pain, opioid use, and addictive

behaviors

was observed in this study

Slide57

Paper 2 Systematic Review of Pharmacological Therapies in the Management of Ischaemic Pain in Patients with Non–reconstructable Critical Limb Ischaemia.BMJ Supportive and Palliative Care, Aug 17, onlineLaoire et al

Aim

To identify & evaluate the effectiveness of pharmacological therapies to treat ischaemic pain secondary to non-

reconstructable

CLI

Method

Systematic review in accordance with PRISMA guidelines

All study designs apart from single case reports

CLI from any cause - experimentally induced ischaemic pain excluded

Surgical, revascularisation & invasive procedures excluded

From 792 screened, 6 suitable for inclusion; 5 RCTs, 1 observational study

4 interventions: ➢IV Lidocaine ➢Gabapentin ➢Ketamine ➢Transdermal buprenorphine + epidural morphine/ropivacaine

Slide58

Paper 2 continuedIV LIDOCAINE (VAHIDI 2015) • Double-blind parallel RCT, N=40• Lidocaine 2mg/kg IV Vs Morphine Sulphate 0.1mg/kg IV

• Effect: At 15 & 30 mins mean VAS pain score lower in intervention group (mean difference 1.25, CI 0.095-2.405, mean difference 2.25, CI 1.218-3.282)

• No adverse effects but only monitored for 30 mins post infusion

GABAPENTIN (MORRIS STIFF 2010)

• Prospective observational study (pilot study), N=20

• Gabapentin titrated from 300mg od to 600mg

tds

, no control

• Median pain score significantly reduced each of assessment days (p<.001)

• 15 patients - improved night pain & perceived QOL

• No adverse effects

KETAMINE (MITCHELL & FALLON 2002)

• Double-blind placebo controlled RCT, N=35

• IV Ketamine 0.6 mg/kg Vs 0.9% Saline over 4 hrs, b/g opioids + haloperidol