NEUROPATHIC PAIN IN CANCER PATIENTS AUDIT · neuropathic pain in cancer patients audit may 1st 2014...

NEUROPATHIC PAIN IN

CANCER PATIENTS AUDIT

MAY 1ST 2014

DR ESRAA SULAIVANY, DR GRAHAM

LENG, DR KATE MARLEY, DR SÉAMUS

COYLE, DR GRACE TING, DR LAURA

MCGLYNN, STEVEN SIMPSON

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PRESENTATION JULY 2012

V1.0

AGENDA

• Literature Review

• Review of Standards

• Audit Results

• General Principles /

Guidelines

• Recommendations

• Discussion

NEUROPATHIC PAIN IN

CANCER

LITERATURE REVIEW

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QUESTIONS ASKED

1. What is the Definition and How do you diagnose NP?

2. What are the existing guidelines for the treatment of cancer NP?

3. Do Opioids have a role? – Are any particular opioids better than another?

4. What is the evidence for the use of the following agents in cancer related neuropathic pain? – Anti-depressants / Anticonvulsants / Other

Adjuvants e.g Steroids, clonazepam, capsaicin / lidocaine / tapentadol / other?

5. What is the evidence for non-pharmacological approaches to managing neuropathic pain? – e.g. TENS, acupuncture, hydrotherapy,

psychological interventions?

DEFINITION AND DIAGNOSIS

WHAT IS THE DEFINITION AND HOW DO YOU DIAGNOSE NP?

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• Neuropathic pain has is defined as “pain arising as a

direct consequence of a lesion or disease affecting the somatosensory system”

• There is no gold standard test used for the diagnosis of neuropathic pain

• Diagnosis is usually made from clinical history and examination finding

• Screening tools for example McGill Pain Questionnaire, S-LANSS, Neuropathic Pain Questionnaire have not been validated for the diagnosis of cancer related neuropathic pain

References

An international survey of cancer pain characteristics and syndromes. Author(s) Caraceni A., Portenoy R.K. Citation: Pain, September 1999, vol./is. 82/3(263-274), 0304-3959 (01 Sep 1999)

Diagnosing neuropathic pain in patients with cancer: comparative analysis of recommendations in national guidelines from European countries. Author(s) Piano V, Verhagen S, Schalkwijk A, Burgers J, Kress H, Treede RD, Hekster Y, Lanteri-Minet M, Engels Y, Vissers K Citation: Pain Practice, July 2013, vol./is. 13/6(433-9), 1530-7085;1533-2500

Neupsig criteria in neuropathic cancer pain (NCP). Author(s) Rayment C.S., Kurita G.P., Sjogren P., Bennett M.I. Citation: Palliative Medicine, June 2012, vol./is. 26/4(422), 0269-2163

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Pharmacological approaches

What is the evidence for the use

of the following agents in cancer

related neuropathic pain? Opioids / Anti-depressants /

Anticonvulsants / Other Adjuvants e.g

Steroids, clonazepam, capsaicin /

lidocaine / tapentadol / other?

IS THERE ANY EVIDENCE FOR

THE USE OF OPIOIDS IN CANCER

RELATED NEUROPATHIC PAIN?

DR ESRAA SULAIVANY

DR GRAHAM LENG

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RECOMMENDATION

• There is evidence to support

the use of opioids (tramadol,

morphine, oxycodone) in

neuropathic cancer pain

either as monotherapy or in

combination with adjuvant

analgesics (Grade B)

Arbaiza 2007 Level 1-

RCT / N = 36 Tramadol vs

placebo

Improvement in pain, less

adjuvant analgesia,

improved performance

status, ADLs, sleep

quality

Patarica-Huber

2011 Level 1-

RCT / N = 75 Gabapentin vs

G + Diclofenac vs

G + D + Morphine

Pain improved in all

groups but best in

group 3

Keskinbora

2007 Level 2+

RCT / Cohort

N = 75

Morphine vs

Morphine +

Gabapentin

Both groups improved

Li

2010 Level 2+

RCT / Cohort

N = 63

Oxycodone vs

Oxycodone +

Gabapentin

Both groups improved

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IS ANY OPIOID SUPERIOR

TO ANOTHER?

• There are no trials

comparing opioids in cancer

related neuropathic pain

EVIDENCE FOR USE OF

ANTICONVULSANTS IN

CANCER NEUROPATHIC PAIN.

GRACE TING & SÉAMUS COYLE

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TABLE SUMMARY OF LEVEL 1 TRIALS

Mishra 2012

Level 1++

RCT / N=120 Placebo vs

Amitriptyline vs

GBP vs

PG

All drugs have morphine sparing

effects

Pregablin greatest effect

clincally

Garassino 2013

Level 1+

RCT / N=75 Oxycodone +

PG vs

Oxycodone +PG

Control can be achieved with PG

without opioid dose

Arai 2010

Level 1-

RCT / N=52 GBP 200bd vs

GBP 400bd vs

Imipramine vs

GBP 200bd +

Imipramine

Low dose Imipramine significantly

total pain score and daily

paroxysmal pain episodes

Kesinbora 2007

Level 1+

RCT / N=63 Morphine vs

Morphine + GBP

GBP pain relief

Caraceni 2004

Level 1+

RCT / N=121 Opioid + Placebo

vs

Opioid +GBP

GBP improved analgesia in patients

already on opioids

Mercadante 2013

Level 1-

RCT / N=48 Morphine vs

Morphine + PG

No difference 2 groups

EVIDENCE FOR THE USE OF

ANTIDEPRESSANTS FOR THE

MANAGEMENT OF CANCER RELATED

NEUROPATHIC PAIN

STEVEN SIMPSON

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IN CANCER RELATED NP

• Some evidence for TCA

(Grade A)

– RCT Level 1++

• None for Duloxetine

– A case series in 2012 was

inconclusive

IS THERE ANY EVIDENCE FOR THE USE

OF STEROIDS IN CANCER

NEUROPATHIC PAIN MANAGEMENT?

DR ESRAA SULAIVANY

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ROLE OF STEROIDS

• ‘Corticosteroids may have a moderate analgesic effect in cancer patients but the evidence was graded as “very low”’

– Do Corticosteroids provide analgesic effects in cancer pain? A systematic review Paulsen et al

• The lack of RCTs means that the evidence is very weak.

(Grade C)

IS THERE ANY EVIDENCE FOR

THE USE OF CLONAZEPAM IN

NEUROPATHIC CANCER PAIN?

DR ESRAA SULAIVANY

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CONCLUSION

• There is weak evidence for the use of

clonazepam in cancer related

neuropathic pain (Grade D)

• Clonazepam as an adjuvant analgesic in patients with

cancer related neuropathic pain

Hugel H et al, Journal of pain and symptom management

,2003

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THERE IS NO EVIDENCE

FOR THE FOLLOWING IN

CANCER RELATED NP…

• Paracetamol

• Lidocaine (Topical / IV)

• Capsaicin (Topical)

• Tapentadol

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Non-Pharmacological

Approaches

What is the evidence for non-

pharmacological approaches to

managing neuropathic pain? e.g. TENS, acupuncture, hydrotherapy,

psychological interventions?

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Acupuncture for

Neuropathic pain

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COCHRANE REVIEW

• 3 RCTs (total 204 patients)

• One positive high quality study using auriculo-acupuncture

• Two lower quality studies also positive

• Conclusion – ‘There is insufficient evidence to judge whether acupuncture is effective in treating cancer pain in adults’

Paley CA, Johnson MI, Tashani OA, Bagnall AM. Acupuncture for cancer pain in adults.

Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD007753. DOI:

10.1002/14651858.CD007753.pub2.

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THERE IS NO EVIDENCE FOR

THE FOLLOWING IN CANCER

RELATED NP… • TENS

• Scrambler

• Hydrotherapy

• Psychological Interventions – "Although these interventions have not been

systematically studied in cancer patients specifically

for the treatment of neuropathic pain, recent work in

other patient populations experiencing chronic pain

suggests their promise"

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Current Pre-Existing

Guidelines

What are the existing guidelines

for the treatment of cancer NP?

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EVERYONE SAYS … ‘TREAT

WITH AN ANTIDEPRESSANT OR

ANTICONVULSANT’ • Treat with Non-Opioid and Opioid medication

– ESMO, SEOM

• Antidepressant or Anticonvulsant (IA) – ESMO, SEOM, NCCN

• XRT to bone mets (II,B) – ESMO

• Intraspinal techniques (II,B) – ESMO

• Coeliac Plexus Block in pancreatic cancer (II,B) – ESMO

• XRT if nerve compression – SEOM

• Steroids in Nerve Compression – NCCN, SEOM

• Topical Agents (Lidocaine, NSAID) – NCCN (IIA)

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A WORD ABOUT NICE NOV

2013

• Designed for non-specialists

• For all types of pain

including chronic non cancer

pain

• Its pharmacological

management

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RECOMMENDATIONS

‘WHAT’S NICE ABOUT NICE!’

All neuropathic pain (except trigeminal neuralgia)

• Offer a choice of amitriptyline, duloxetine, gabapentin or pregablin as initial treatment for neuropathic pain (except trigeminal neuralgia)

• If the initial treatment is not effective or is not tolerated, offer one of the remaining 3 drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated.

• Consider tramadol only if acute rescue therapy is needed.

• Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.

Treatments that should not be used

• Do not start the following to treat neuropathic pain in non-specialist settings, unless advised by a specialist to do so:

– cannabis sativa extract / capsaicin patch / Lacosamide / Lamotrigine / Levetiracetam / Morphine / Oxcarbazepine /Topiramate / tramadol (this is referring to long-term use; see recommendation 1.1.10 for short-term use) / venlafaxine.

REVIEW OF CURRENT

STANDARDS

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STANDARDS

• All patients with neuropathic pain should be monitored with a pain diary.

• Patients with poorly controlled neuropathic pain should have at least weekly follow-up if an outpatient, and 48 hourly reassessment if an in-patient.

• If neuropathic pain is escalating, an Anaesthetic Pain Specialist should be contacted for advice within 48 hours

AUDIT RESULTS

0

5

10

15

20

25

Locality

0

5

10

15

20

25

30

35

40

45

Grade/Profession

0

5

10

15

20

25

30

35

40

45

50

Hospice Community Hospital

49

32

26

Nu

mb

er

of

pat

ien

ts

Setting in which patient was seen

16

2

17

2 1 4

12

5

2

4

1

2

2

2 1

2 2

Site of Primary Tumour Breast

Ovarian

Lung

Gastric

Pancreas

Prostate

Colorectal

Head&Neck

Multiple Myeloma

Cervical

Oesophagus

Mesothelioma

Sarcoma

Melanoma

Renal

Bladder

Cerebral

18

4

2

4

1

5

3

18

18

3

1

3

4

3

1

3

2 1

2 1 3

Region of body affected by pain

Chest WallArmGroinHipHandAbdomenShoulderLegBackNeckJawPerineumFaceRectumPelvisHeadAxillaAll overSacrumEye

0

2

4

6

8

10

12

14

16

18

20

What regular opioids was the patient taking at the time of the initial assessment?

0

5

10

15

20

25

30

35

None Codeine Oramorph Oxynorm

What prn opiods was the patient taking at the time of the initial assessment?

0

5

10

15

20

25

30

What was done with the opioid medications at the initial assessment?

12%

13%

75%

Which drug was the patient switched to from morphine?

Alfentanil

Fentanyl

Oxycodone

0

2

4

6

8

10

12

14

16

18

What was done at the first assessment with non-opioid medications and adjuvants to manage the pain?

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

1

You stated that Ketamine was used. What kind of regime was used?

Oral Sublingual SC driver 'burst' regime SC driver other regime

23

52

Was a Pain Diary Used?

Yes

No

0

5

10

15

20

25

30

35

At 24 hours At 48 hours At or within 1week

At 2 weeks orbetween 1

and 2 weeks

At 3 weeks orwithin 2-3

weeks

More than 3weeks

32

4

27

9

3 1

How soon was the patient reviewed by Specialist Palliative Care after the initial assessment?

0

5

10

15

20

25

30

35

40

45

50

Yes pain resolvedmore or lesscompletely

Pain improved butnot controlled

completely

Pain no different Pain worsening

9

50

11

5

Did the patient's pain improve?

0

5

10

15

20

25

30

Referral alreadymade at 1stassessment

Referral made atsubsequent

review

Consideration ofanaesthetic

assessment notdocumented

Patient toounwell

Patient didn'twant

intervention

6

15

28

8 9

You stated that the patient's pain was not fully controlled despite modification of analgesia. Was referral for consideration of

Anaesthetic intervention considered at the subsequent review?

0

1

2

3

4

5

6

7

8

Within 24 hours Within 48 hours Within 1 week Within 2 weeks More than 2 weekslater

8

2

7

1

3

You stated that consideration had been made for an anaesthetic intervention. Tell us about the timing of this referral in relation to the time of the consultation where the referral was considered:

RECOMMENDATIONS

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General principles

• Neuropathic pain may be relieved in the majority of patients by multimodal management

• A careful history and examination are essential. Investigations such CT and MRI may be appropriate

• It is important to have a logical and rational approach to prescribing

• Chemotherapy or radiotherapy may be indicated if the tumour is chemosensitive or radiosensitive

• Non-pharmacological approaches should be considered including TENS, acupuncture, hydrotherapy and psychological interventions

• Interventional techniques may be indicated and should always be discussed at an early stage with the Anaesthetic Pain Specialist

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• Carry out regular clinical reviews to assess and monitor the effectiveness of

the treatment. Each review should include an assessment of:

– Pain control

– Impact on lifestyle, daily activities (including sleep disturbance) and

participation

– Physical and psychological wellbeing

– Adverse affects

– Continued need for treatment

• Consider referring to a specialist pain service and/or a condition- specific at

any stage, including at initial presentation and at the regular clinical reviews

if:

– They have severe pain OR

– Their pain significantly limits their lifestyle, daily activities (including sleep

disturbance) and participation

• (ref NICE guidelines)

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Guidelines

• The WHO analgesic ladder should be followed (level 2)

• Strong opioids should be titrated against response. Adjuvants and non-opioids should be used as appropriate (level 1)

• The endpoint of titration is pain relief or intolerable side effects. If dose limiting side effects occur despite the use of adjuvants or other interventions, a switch of opioid should be considered (level 3)

• Figure 28.1 features a flow diagram which may be a useful guide for adjuvant prescribing in neuropathic pain (level 1+)

• If nerve compression is suspected, a trial of corticosteroids could be considered (level 2+) but the evidence is weak e.g dexamethasone 8mg for 5 days (level 1). Pain relief following the use of corticosteroids often predicts a favourable response to radiotherapy

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• Anaesthetic techniques may be indicated. They should always be discussed

early with an Anaesthetic Pain Specialist whilst the patient remains fit

enough to tolerate any appropriate procedure (see Guidelines on

Interventional Pain techniques) (Level 3)

• If the pain is escalating despite the use of recommended guidelines, or if

urgent control is required, consider early referral for an Anaesthetic Pain

Specialist opinion (level 4)

• For anaesthetic approaches see MCCN Guidelines on Interventional Pain

Techniques

• Topical treatment with capsaicin cream may be of benefit In patients

intolerant of other treatments (level 1)

• In patients with symptoms that are difficult to control or who have severe

allodynia / hyperalgesia, consider admission to a specialist centre (level 4)

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Guidelines (cont) • Methadone is a potent mu agonist and acts as a non-competetive

antagonist at the NMDA receptor. It has also been shown to inhibit the re-uptake of serotonin and noradrenaline. Morphine, hydromorphone, fentanyl and oxycodone do not exhibit this additional action. Methadone is therefore often used as a broad-spectrum opioid in the treatment of resistant cancer related neuropathic pain, where there have been dose-limiting side effects and rapid development of tolerance to the previous opioid. Methadone should only be initiated in a specialist unit (see Guidelines on use of Methadone) (level 1)

• Ketamine may be given as an infusion prior to conversion to an oral preparation where appropriate. It should only be initiated under specialist supervision. It can be given IV (level 1) or SC. Various regimens have been described and the choice will depend on the preference of the specialist team (level 3)

• For treatment of resistant cancer-related neuropathic pain Methadone and or Ketamine could be considered in a specialist palliative setting (See MCCN Guidelines for Methadone and Ketamine use).

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Anaesthetic approaches (see

Guidelines on Interventional Pain

Techniques) • If the pain is escalating despite the use of recommended guidelines, or if

urgent control is required, consider early referral for an Anaesthetic Pain Specialist opinion (level 4) (MOVED into Guidelines)

• The use of peripheral nerve blocks using local anaesthetic and / or corticosteroids may be effective for the relief of pain in the distribution of one or more peripheral nerves (level 3)

• Neurolytic procedures such as a saddle block using phenol may relieve some painful sacral neuropathies. However this may cause significant problems with bladder and bowel function. Some experts favour epidural catheters as an alternative (level 4)

• Epidural steroids +/- bupivicaine may be of use in patients with neuropathic pain, particularly in patients with intractable radicular pain or where systemic opioids have caused severe side effects. However, they may cause significant problems with the bladder and bowel function

• If unilateral pain below the shoulder and prognosis between 3 months and 12 months, consider referral for percutaneous cordotomy (level 3)

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Fig 28.1 Approaches to the adjuvant analgesics in neuropathic pain (level 4)

Fig 28.1 Approaches to the adjuvant analgesics in neuropathic pain

Commence Antidepressant or Anticonvulsant of Choice

& TITRATE

NO RESPONSE PARTIAL RESPONSE

SWITCH DRUG Consider adding second different class of drug

NO / PARTIAL

RESPONSE

Consider: • Alternative Drugs /

Approaches • Refer for Intervention

assessment if patient well enough

Refer SPCT & Consider Pain intervention review

INSUFFICIENT RESPONSE

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Drug Name Initial Dose Titration Side Effects Notes

Amitriptyline

Level 1+

Level 1++

10-25mg nocte

10mg at night in

the elderly.

Median

preferred dose

of 75mg daily

Increase every

3 days as

tolerated

Occur in 33% of

patients. Include

drowsiness and

dry mouth

Speed of onset 1-7days.

May get improved sleep pattern

and mood.

Use with caution in the following:

cardiac disease; arrhythmias;

epilepsy; concurrent use of

SSRIs; angle closure glaucoma;

history of urinary retention

Capsaicin

0.075% cream

(Level 1-)

Apply topically 3

or 4 times daily

Skin burning and

redness

May take up to 10 day s to have

an effect.

Always wear gloves when

applying

Carbamazepine

(Level 1+)

200mg daily.

100mg daily in

elderly

Increase by

100mg-200mg

every 3 days.

Give in divided

doses.

Nausea,

drowsiness,

confusion and

ataxia.

Beware of drug interactions.

Clonazepam

(Level 3)

500 micrograms

nocte

Increase by

500mcg every

3 days.

Maximum dose

is 8mg

Sedation May be given subcutaneously via

a syringe driver. May adsorb to

PVC so use non PVC equipment

for infusions. A CSCI containing

clonazepam should only run for a

maximum of 12 hours as stability

of diluted clonazepam currently

only confirmed for 12 hours.

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Drug Name Initial dose Titration Side

effects

Notes

Dexamethaso

ne (Level 1-)

Level 4

8mg daily Give for 5 days.

Discontinue if no response

Reduce to lowest dose to

maintain effect (see

Guidelines on

Corticosteroids)

If good response then

may benefit from

radiotherapy.

Monitor blood sugar

levels.

Consider gastric

protection.

Gabapentin

(Level 1+)

(Level 1++)

300mg nocte.

100mg nocte

if elderly

Increase after 3 days to

300mg bd. Increase to

300mg tds after a further 3

days. Maximum dose is

2400mg.

Note: May need to use

slower titration regimen

e.g. start at 100mg od and

increase by 100mg every 2

days

Sedation

,

dizziness

.

Reduce dose in renal

failure / impairment.

Use in caution in patients

with CCF.

Diabetic patients may

need to adjust

hypoglycaemic treatment

as weight gain may

occur.

Lidocaine

patch

(Level 1-)

One strength.

Apply for 12

hours daily

over painful

area and then

remove.

Can use up to 3 patches at

any one time.

Skin

reaction

Current evidence is for

post herpetic neuropathic

pain. May be useful for

post thoracotomy pain.

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Drug

Name

Initial dose Titration Side effects Notes

Pregablin

(Level 1-)

(Level 1++)

Day 1: 25mg od

Day 2: 25mg bd

Increase every 2

days by 25mg

bd

150mg-600mg

daily in 2 divided

doses. Avoid tds

dosing.

Treatment costs

increase with no

benefit.

Sedation, dizziness Potential pharmacodynamic

interactions with all opioids and

sedatives.

Caution may be required in

patients with chronic heart

failure.

Diabetic patients may need to

adjust hypoglycaemic treatment

as weight gain may occur.

Sodium

Valproate

(Level 2-)

200mg nocte Increase by

200mg every 3

days. Maximum

dose is 1000mg

daily.

Nausea, ataxia.

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Revised Standards

• All patients with neuropathic pain should be

monitored with a pain diary.

• Patients with poorly controlled neuropathic pain

should have at least weekly follow-up if an

outpatient, and 4824 hourly reassessment if an in-

patient.

• If neuropathic pain is escalating (despite optimum

medical treatment), an Anaesthetic Pain Specialist

should be contacted for advice within 48 hours(?)

within 1 week where available

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Discussion

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• Any addition to Standards?

• Is it worth removing certain adjuvants (e.g

Carbamepine, Valproate)?

• What to recommend when the oral route is

not available?

• What to do when a local Anaesthetic pain

team is not available?

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NEUROPATHIC PAIN IN CANCER PATIENTS AUDIT · neuropathic pain in cancer patients audit may 1st 2014...

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