Pain, 51 (1992) 153-161 153

0 1992 Elsevier Science Publishers B.V. All rights reserved 0304-3959/92/$05.00

PAIN 02131

Description of a mechanistic approach to pain management in advanced cancer. Preliminary report

Michael A. Ashby ‘, Beverley G. Fleming a*c, Mary Brooksbank ‘, Bruce Rounsefell b,c, William B. Runciman ‘, Kate Jackson d, Nell Muirden d and Michael Smith ’

’ Mary Potter Hospice, Calcary Hospital, North Adelaide, SA 5006 (Australia), ’ Pain Unit, Royal Adelaide Hospital, Adelaide (Australia),

’ Department of Anaesthesia and IntensiLle Care, University of Adelaide and Royal Adelaide Hospital, Adelaide (Australia), * Palliative Care Unit, Peter McCallum Cancer Institute, Melbourne, Victoria 3000 (Australia)

and ’ Silt%er Chain Nursing Association Hospice Care Sertice, Osborne Park, Western Australia 6017 (Australia)

(Received 19 December 1991, revision received 6 May 1992, accepted 20 May 1992)

Summary A mechanistic approach to advanced cancer pain management is proposed, based on the clinically perceived anatomical and pathophysiological mechanisms of pain generation. It is an extension of the World Health Organisation (WHO) analgesic ladder in which severity of pain is the principal determinant of analgesic choice. The mechanistic categories are: superficial somatic, deep somatic, visceral and neurogenic (mixed or pure, i.e., nociceptive component present or absent). Allocation of pain to the different categories is based on clinical history, physical findings and investigations to establish the site and extent of active primary or metastatic tumour deposits, and evidence of previous response to medication. Drug choice sequence is determined by the dominant pain mechanism judged to be present and not the severity of the pain.

In order to describe this approach, mechanisms of pain, disease distribution and drug treatment have been analysed in the first 20 consecutive patients who consented to enter a longitudinal pain description and evaluation study on admission to an inpatient hospice unit. Despite a high exclusion rate from research standard monitoring due to severity of illness and related factors, the majority of eligible patients approached to enter the study did so, and the pain scoring was well tolerated. The implications of this for future research and clinical practice are discussed.

In 6 patients only 1 pain mechanism was identified (visceral 4, deep somatic 2). Two mechanisms were present in 8 patients and 3 mechanisms in 6 patients. The deep somatic mechanism was identified in 15 patients, visceral mechanism in 13, neurogenic in 10 and superficial somatic in 2. The most common combination of mechanisms was neurogenic/visceral/deep somatic (5 patients) and neurogenic/deep somatic (4 patients). No patient had neuro- genie pain alone or superficial pain alone. To achieve optimal analgesia, a mean of 2.8 drug classes per patient was required (range: l-5). All 20 patients required an opioid, and in 2 patients with visceral pain only, morphine was the initial and sole analgesic used. None of the 15 patients with deep somatic pain achieved acceptable pain relief with an anti-inflammatory drug alone at conventional dose levels.

It is concluded that the approach is feasible, and prospective assessment and validation of the response of these proposed mechanism categories to specific drug classes is now underway. Assessment of the anti-inflammatory responsive component of nociceptive cancer pain has emerged as a priority for further investigation.

Key words: Hospice; Palliative care; Cancer pain classification

Introduction

Correspondence to: Dr. Michael Ashby, Calvary Hospital, P.O.

Box 231, North Adelaide, SA, 5006, Australia. Tel.: (61-8) 267-3144;

FAX: (61-8) 239-0478.

There have been considerable improvements in can- cer pain management, mainly since the advent of mod- ern pain clinics and hospice/palliative care pro-

TA

BL

E

I

ME

CH

AN

IST

IC

(‘IL

ASS

IFIC

‘AT

ION

O

F C

AN

CE

R

PAIN

Key

: 0

= op

ioid

: A

l =

anti-

infl

amm

ator

y;

AC

=

antic

onvu

lsan

t: A

D

= an

tidep

ress

ant:

S =

ster

oid;

L

A

= lo

cal

anae

sthe

tic:

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= an

tispa

smod

ic.

Noc

icep

tive

Supe

rfic

ial

som

atic

D

eep

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atic

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isce

ral

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gin

of s

timul

us

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in.

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utan

eous

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of m

outh

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ur

ethr

a,

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tend

ons.

lig

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ts

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rfic

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ph

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s

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an

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tone

um)

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. I.

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ell

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ned

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ca

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on

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amm

atio

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test

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eric

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lic

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l, ac

hing

aggr

avat

ed

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ovem

ent

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l de

fine

d

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be

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l

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p

Poor

ly

defi

ned

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be

May

be

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sea,

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miti

ng,

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ting,

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uton

omic

in

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ility

: w

arm

th,

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d pr

essu

re

and

hear

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ting,

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, cy

anos

is

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ges

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alis

ed

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e pa

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ay)

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ce

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cl

ass

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Al

0 M

ixed

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re

Al

AD

or

A

C

*’

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C

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orA

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cl

ass

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ass

4th

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ce

drug

cl

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er

mea

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s

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0 Hea

t or

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ld

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gatio

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erap

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erap

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AS

if c

olic

ky

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1 _ Pr

essu

re

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t

Rad

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erap

y

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roge

nic

I.

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(d

eaff

eren

tatio

n):

noci

cept

ive

elem

ent

abse

nt

2.

Mix

ed:

noci

cept

ive

elem

ent

pres

ent

due

to

tum

our

inva

sion

or

com

pres

sion

of

ner

ve

path

way

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: po

st-h

erpe

tic

neur

algi

a,

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-

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my

synd

rom

e,

phan

tom

pa

in

Mix

ed:

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hiai

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mho

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al

plex

us

or

ches

t w

all

inva

sion

, sp

inal

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rd

com

pres

sion

I.

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aest

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abno

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se

nsat

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d ne

edle

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rnin

g

pain

in

num

b ar

ea

2.

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a *’

3.

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cina

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tom

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ve

or

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atom

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stri

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n

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dura

l L

A

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roly

tic

proc

edur

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ock

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erap

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NS

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du

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a

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w

hich

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es

not

norm

ally

pr

ovok

e pa

in

(IA

SP).

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A

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firs

t if

ian

cina

ting

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ures

.

*’

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sion

an

d/or

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mpr

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on

are

pres

ent.

155

grammes. The World Health Organisation (WHO) analgesic ladder describes mild, moderate and severe pain categories for which non-opioids, weak opioids and strong opioids were indicated respectively, either sequentially or additively (World Health Organisation 1986). More recently, the WHO has adjusted steps 2 and 3 of the ladder to bring it into line with the recommendation that morphine be accepted as the opioid of choice for cancer pain (World Health Organi- sation 19901. This model evolved from the early work and teaching of the modern British hospice movement and has been the basis of a highly successful world-wide campaign to improve the management of cancer pain (Stjernsward and Teoh 1989). The ladder has stood the test of time, experience and validation studies (Takeda 1986; Ventafridda et al. 1987; Walker et al. 1988). The message is simple and effective and has established the principle of the use of the oral route as first line management and has demonstrated the safety of dose escalation of regular oral opioids (morphine or diamor- phine). The term ‘adjuvant’ has been adopted to de- scribe drugs which are thought to enhance analgesic response by diverse mechanisms.

However, a mechanistic approach to pain classifica- tion is now emerging (Artier and ArnCr 1985; Bruera et al. 1989; Payne 1989; Portenoy et al. 1990; Samuelsson and Hedner 1991; Ventafridda and Caraceni 1991). It seems to be generally agreed on the basis of anatomy, physiology and pharmacology that there are three prin- cipal categories of pain mechanisms: somatic, visceral and neurogenic (National Health and Medical Re- search Council 1989; Payne 1989; Ventafridda and Caraceni 1991) and that pathophysiological mecha- nisms appear to have significant therapeutic implica- tions. The pathophysiology of cancer pain is complex and poorly understood, particularly for visceral and neurogenic pain (Payne 1989; Ness and Gebhart 1991). It is universally agreed that patients with neurogenic cancer pain are difficult to treat effectively (Ventafridda and Caraceni 1991). It is also known that patients may have more than one pain, and hence more than one pain mechanism operative at any given time (Twycross and Fairfield 1982). The presence or absence of a somatic nociceptive (i.e., anti-inflamma- tory or opioid responsive) component in the neuro- genie group is sometimes difficult to determine without a therapeutic trial (Tasker 1987; Bowsher 1990). In addition, smooth or skeletal muscle spasm may also be present.

Hospice inpatient units tend to admit a subpopula- tion of very ill patients with complicated and unre- solved pain issues, and hence ‘polypharmacy’ is com- mon. There is a need to rationalise drug choice and improve pain control and side-effect profiles. The aims of this study were to apply a mechanistic approach to cancer pain management, to assess the application of

this approach coupled with research standard pain scoring in the hospice environment, and to establish a basis for the planning of future studies. Pain mecha- nisms, disease distribution and drug treatment were analysed in 20 patients entered into a longitudinal descriptive study of pain control in consenting patients admitted to the inpatient hospice component of a palliative care programme.

Methods

Patients Over a 4-month period 121 patients were admitted to Mary

Potter Hospice for symptom control, terminal care or respite. Of

these, I12 patients were assessed for admission to the pain study, but

78 were excluded due to one or more of the following criteria being

present: unwilling or too ill to participate (341, patient and/or

relative distress (11, diagnosis other than cancer (3). absence of pain

(17). and communication difficulties due to speech impairment,

impaired cognitive functioning, language barrier (23). A further 14

patients were subsequently excluded due to: patient distress (4I, pain

abatement and cessation of analgesics (31, unwillingness to continue

participation (41, and patient discharge or death resulting in insuffi-

cient data for analysis (3).

The remaining 20 consenting patients were entered into a pilot

study of pain description and evaluation on admission to the Mary

Potter Hospice. Some of these patients may have been known to the

palliative care team prior to this and may have had previous admis-

sions. The patients were cared for in the hospice by one of the

visiting medical officers or by the patients’ own general practitioner.

Pain mechanism categories The classification used in this study is adapted from the practice

of Moon and colleagues at the Peter MacCallum Cancer Institute in

Melbourne (Muirden et al. 1990a. b), and others (Paterson personal

communication). These are in turn based on the work of Lewis

(1942) and Ganado (Ganado 1945). The categories arc as follows:

superficial somatic; deep somatic; visceral; and neurogenic. Visceral

pain may or may not have a colicky component present, and neuro-

genie pain may be pure or mixed (i.e., with a nociceptive element

present), and may have either dysaesthesiae or lancination as the

most prominent clinical characteristic (Table II. This classification is

made on the basis of clinical characteristics, pharmacological re-

sponse, and also more tentatively upon possible neuroanatomical

and embryological principles. The major questions are: (a) is noci-

ceptive tumour present causing pain by compression, invasion or

oedema; tb) is there anatomical or physiological nerve pathway

interruption (partial or complete); and (c) is the pain mediated by

somatic or visceral nervous pathways? Knowledge of the natural

history, with particular regard to anatomical site and distribution of

primary tumour, local, regional and distant metastatic spread is

essential. Using this classification the principal determinant of drug

sequence is the perceived clinicopathological mechanism of pain

generation, rather than pain intensity. If a mechanism cannot be

ascribed to a patient’s pain experience, a trial of an anti-inflamma-

tory drug with opioid rescue available concurrently is initiated. If the

anti-inflammatory response is poor after 24-4X h, regular opioids are

commenced.

Drug class choice sequence is listed in Table I. Anti-inflammatory

drugs are regarded as first choice for superficial and deep somatic

pain. and mixed (nociceptive) neurogenic pain. Opioids are first

choice for visceral pain, second choice for deep somatic and neuro-

genie pain of mixed origin, and third choice for superficial somatic

IO

11

12

13

14

15

16

F

M

M

F

F F

F M

F

F

F

67

65

67

72

x2

85

86

64

Ade

noC

A

DM

Cer

vix

(Bon

e

Bra

in

Lun

g)

Ade

noC

a L

R

Rec

tum

D

M

(bon

e,

lung

, liv

er)

Mul

tiple

D

M

(bon

e,

My&

ma

pleu

ra)

Ade

noC

a L

R

PH

KIe

aS

DM

(l

iver

)

SCC

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in

LR

(fac

e)

DM

(b

one,

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k-ce

rvic

al

Dee

p so

mat

ic

-tho

raci

c N

euro

geni

c

-lum

bosa

cral

Hea

d

Upp

er

limbs

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er

limbs

Bac

k-lu

mbo

D

eep

som

atic

sacr

al

Vis

cera

l

Low

er

limbs

N

euro

geni

c

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k-ce

rvic

al

Dee

p so

mat

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-tho

raci

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isce

ral

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st

wal

l N

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omen

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eep

som

attc

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isce

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d an

d D

eep

scun

at~

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k V

isce

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paro

tid

glan

d)

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Ade

noC

a L

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omen

CO

lOIl

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noC

a L

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Abd

omen

C&

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(l

iver

) B

ack-

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cral

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lu

ng

LR

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hest

w

all

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noC

a L

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d an

d

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l/3

DM

(b

rain

) ne

ck

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opha

gus

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st-d

eep

NH

L

DM

(b

one)

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hest

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bs

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lvic

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cera

l

Vis

cera

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p

som

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p so

mat

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p so

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0 S 0 S AI

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0 AI

s AD

0 AI

AD

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0 S Al

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0 S 0 AC

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0 0 0 AI

Yes

Yes

Yes

YES

Yes

Yes

Yes

NO

Yes

Yes

Yes

NO

Yes

YC

S

YC

S

Yes

Yes

Ye5

Yes

Yes

Yes

Yes

YC

%

Yes

N

O

Yes

Yes

Yes

NO

25

25

88

30

30

105

8 8

46

15

15

44

13

13

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7 7

19

11

11

37

9 5

19

20

20

53

9 9

43

23

23

76

1 1 I 1 1 2 1 2 1 1 1

22

(88%

1)

9

23

(77%

) 11

3 (3

7%)

20

12

(80%

)

12

(92%

)

13 4

6 (8

5%)

9 (8

1%)

5 (1

00%

)

20

(100

%)

7 (7

7%)

6

21

(91%

)

57

20

8 3

1.03

+2.

03

(65%

) (2

3%

) (9

%)

(3%

)

41

53

8

(39%

) (5

0%)

(8%

)

3 1.

28f

1.71

(3%

)

7 4

24

11

4.89

f

2.53

(15%

) (9

%)

(52%

) (2

4%)

31

I

(70%

) (2

%)

21

2

(72%

) (7

%)

5 2.

29

* 3.

73

(11%

)

6 1.

78

+ 3

.32

(21%

)

12

(63%

)

22

(59%

)

0 14

(38%

)

3 1.

95+

2.89

(16%

)

0 1.

23f3

.5

13

5

(6R

R)

(26%

)

0 0.

73

f 1.

28

33

13

(62%

) (3

0%)

29

10

(67%

) (2

3%)

2 1.

08f

1.98

(4%

)

4 1.

23

f 2.

56

(9%

)

50

25

(65%

) (3

3%)

2

(5%

)

0 4

(21%

)

1

(3%

)

1

(5%

)

5

(9%

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0 0 1

0.54

f 1.

13

(1%

)

and pure neurogenic (deafferentation) pain. Steroids are indicated

for the reduction of tumour-related oedema, particularly where this

is thought to involve the nervous system. The relative merits of

steroidal and non-steroidal agents have yet to be evaluated for their

anti-inflammatory properties in cancer pain management. Anticon-

vulsants are tried first for neurogenic pain with lancinating features,

and tricyclic or tetracyclic antidepressants are used if the pain has a

burning dysaesthetic quality.

Allocation to pain mechanism category was done by the research

nurse at the time of the patient’s entry to the study. The mechanisms

and clinical data were subsequently retrospectively reviewed by two

investigators (M.A.A. and M.B.). The categories were assigned on

the basis of clinical history, examination, and investigations to deter-

mine the site(s) of disease activity and hence pain mechanism,

according to the principles set out in Table I. Key determinants

were: anatomical location of known tumour deposits, tender palpa-

ble tumour masses or bone metastases (for deep somatic pain) and

specific neurogenic features.

Pain scoring Pain scoring was by linear analogue scale (LAS) (Murphy et al.

198X) using a ruler designed by the Department of Biomedical

Engineering. Flinders Medical Centre, Bedford Park, South Aus-

tralia. A blank linear scale with no intervals. with the words ‘no pain’

at the left hand end and ‘worst pain imaginable’ on the right, was

shown to the patient. The patient then moved a sliding cursor to the

position of perceived pain. The patient’s score was then converted to

a number by reading off a lOO-mm scale on the reverse of the ruler.

This result was recorded on a chart which was not concealed from

the patient. Scores were obtained by the primary nurse caring for the

patient, supervised and validated by the research nurse. Scores were

obtained at 4-h intervals during waking hours, usually at the follow-

ing times: 08.00, 12.00, 16.00 and 20.00 h. Sleeping patients were not

woken. but a score was obtained if they woke and required break-

through medication. If the patient was unable to give a score the

nurse recorded a yes/no response of her or his impression as to

whether the patient was in pain.

Results

The clinical details are summarised in Table II. There were 6 men and 14 women (M/F ratio of 0.42: Il. The mean age was 67.6 years (range: 43-86). All patients had advanced incurable cancer, and all are now dead.

There were 30 admissions (mean: 1.5 SD. f 0.7/patient; range: l-31. The mean time in the study prior to death was 30 days (S.D. zt 25.7 days; range 7-1031. The mean number of days observed was 20.7 fS.D.rt. 15.5; range 7-57 days) with the mean number of observations/ patient was 83.5 (S.D. + 78.4; range: 19-2841. There are missing data as a result of dis- charges home, temporary absences from the unit, and because patients were too ill to cooperate or unable to give a score owing to impaired consciousness.

The mean pain scores for each patient varied from 0.26 rt 0.92 to 4.89 rt 2.53. Pain was arbitrarily divided into the following categories: no pain (LAS score 01, mild pain (LAS score 0.1-3.91, moderate pain (LAS score 4-6.91, severe pain (LAS score 7-10). As shown in Table ii the distribution of scores for all patients is

skewed towards the no pain or mild pain categories. AI1 of the mean scores were in the mild category, with the exception of one patient who scored in the moder- ate category. The majority of nights were pain free.

There were a total of 152 breakthrough events recorded, a mean of 7.6 (S.D. + 5.8, range: O-20) per patient. Pain scores were recorded in 85 (56%) of these events and were as follows: mild 8.2%, moderate 52%, severe 40%. Morphine was administered for all break- through events either subcutaneously, intramuscularly or orally, at 20-50% of the regular dose.

Of the 20 patients observed, there was 1 mechanism judged to be operative in 6. In the other 14, 8 patients had 2 mechanisms operating and 3 mechanisms were active in 6 patients. The deep somatic mechanism was identified in 15 patients, visceral mechanism in 13, neurogenic mechanism in 10 and superficial somatic mechanism in 2. The commonest combination was neu- rogenic/visceral/ deep somatic in 5 patients, and neu- rogenic/deep somatic in 4 patients. No patient had neurogenic pain alone or superficial pain alone. In the 6 patients who had one mechanism, it was judged to be visceral in 4 and deep somatic in 2.

A range of l-5 drug classes, a mean of 2.8 per patient, were required to achieve satisfactory pain con- trol during the period of observation. Five drug classes were used in 1 patient, 4 classes in 5 patients, 3 classes in 6 patients, 2 classes in 5 patients and 1 class in 3 patients.

@kids: All 20 patients received morphine and clini- cal evidence of opioid response was seen in all of them. In 7 patients this was administered orally, and in 18 it was given by subcutaneous infusion. Of the 7 patients receiving oral morphine, 2 remained on oral doses, 4 changed to subcutaneous infusion and 1 patient who started on subcutaneous infusion was changed to oral morphine and later returned to subcutaneous infusion. Oral morphine doses ranged from 2.5 mg to 90 mg 4 hourly, the mean maximum dose/patient used was 32 mg 4 hourly. Subcutaneous morphine doses ranged from 20 mg to 2000 mg in 24 h, the mean maximum dose/patient being 378 mg in 24 h. Morphine doses were escalated as required throughout the course of the study. Two patients with visceral pain as the sole identified operative mechanism achieved satisfactory control on morphine alone.

A~t~-i~~arnrn~t~~ drz.qjs. Anti-in~ammato~ drugs were used in 12 of 15 patients with deep somatic pain: aspirin alone in 3, non-steroidal anti-inflammatory drugs (NSAlDs) alone in 3 and steroids alone in 3. A combination of 2 or 3 of these drug groups was used in the remaining 6 patients. No patient with deep somatic pain achieved satisfactory pain relief on anti-inflamma- tory drugs alone.

159

Other drug classes. Antidepressants were used in 9 patients with evidence of response in 5. Anticonvul- sants were used in 2 patients with lancinating neuro- genie pain with 1 patient responding. An anxiolytic was used in 4 cases, with some impact on pain in 1 patient.

Discussion

Prospective pain measurement research has been limited in hospice work, as there is a natural reluctance on the part of carers and families to subject dying people to research methodologies. However, we found that the presence of a research nurse integrated into the hospice community was readily accepted by pa- tients, families and other staff, and is essential to the success of any such project. The high number of exclu- sions from the study confirms that this is a difficult area to research, owing to the fragile nature of the patients and the multiple confounding variables and events. The recruitment rate is low and the drop-out rate is high when using research standard methods of assessment, and all results need to be interpreted in the light of this. There is an inevitable selection bias in favour of patients in better general condition with well preserved communication skills. Missing data are com- mon. The difficulties should not deter much needed research efforts in this field. Scientific pain measure- ment and management need not conflict with the prin- ciples of hospice and palliative care, provided that researchers have experience in the area and desist when conflicts or dissatisfaction arise. The pain scoring methods used in this study have indeed now become an integral part of patient assessment and management in the hospice.

The hospice patient population is different from that seen in most pain clinic studies. All the patients in this study were very ill and either bedridden or mini- mally ambulant. They were all in the last few weeks of life when pain may become more severe due to disease progression, drug metabolism may be adversely af- fected by body system failure (particularly renal and hepatic impairment) and tolerance may be a real issue. Experiences such as total body pain and hyperaesthetic states are common but poorly understood. Psychologi- cal influences may also have a greater part to play as death approaches, and acute brain syndromes of multi- factorial aetiology are common. There is an under- standable intolerance of poorly controlled pain and, as time is short, there is an element of impatience on the part of patient, family and carers to achieve optimal pain relief as soon as possible. ‘Polypharmacy’ is there- fore a common practice, with inadequate time for therapeutic trials of differing drug classes on their own. This may expose patients to the risk of receiving drugs which are ineffective or give rise to unwanted side effects, or both.

The numbers in this preliminary study are too small to allow a correlation between pain mechanisms and level of pain control. There are also methodological difficulties in deciding what constitutes good or accept- able pain control. For patients with incurable cancer the pain experience has features of both acute and chronic pain. This longitudinal dimension to pain con- trol documentation represents a significant method- ological challenge. Such a description has to express the onset of new sites and mechanisms of pain, as well as fluctuating pain intensity. The variability between patients in pain perception and scoring makes compar- ison across patients difficult, and the trend of scores for individual patients may be the most valid way of assessing the effectiveness of pain control. In this study we have summarised the LAS scores and categorised them as no pain, mild, moderate or severe pain. In addition, the proportion of nights free of pain and the number of breakthrough pain events (Portenoy and Hagen 1990) have been recorded to give an overall picture of control, but no attempt has been made to derive a summarising score for all these parameters. All values are skewed towards the desirable end of the scale but may not necessarily indicate whether pain control was optimal for each patient.

The deep somatic category is the most frequently documented mechanism, due principally to the high incidence of malignant bone pain, followed by visceral and neurogenic pain. It is noteworthy that no patient with deep somatic pain obtained adequate relief with an anti-inflammatory drug alone, and that all patients required morphine to obtain adequate pain control. This suggests that there is a ceiling effect for anti-in- flammatory drugs in this context. The development of new anti-inflammatory agents with lower side-effect profiles and dose escalation studies might be poten- tially fruitful avenues of research to pursue. NSAIDs are effective and widely used in cancer pain, but rheumatological experience indicates that there is con- siderable individual variation in response and side-ef- fect profile with different members of this class (Graham 1987; Mannix and Rawlins 1987; Champion 1988; Brooks 1991). Although aspirin is an old drug, there remains much to be learnt about its kinetics and dynamics (Gunsberg et al. 1984; Mills 1991). Soluble aspirin in the high-dose range (6 g/day) previously used in acute rheumatic fever management is presently being evaluated as a first line test of anti-inflammatory response. It appears to be both reliable and effective. However there may be limitations to its longer term use because of issues of compliance and side effects (particularly gastro-intestinal). A prospective ran- domised trial will be required to address the relative role of aspirin (with dose escalation) and NSAIDs for cancer pain.

It is also noted that neurogenic pain was not identi-

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fied as the sole mechanism in any patient, there being a co-existent deep somatic and/or visceral component in most cases. It seems likely that management of such patients will inevitably entail the use of multiple drugs, with sequential therapeutic trials of opioids and anti- inflammatory drugs. It is difficult to quantify the noci- ceptive, anti-inflammatory sensitive, component of neurogenic pain per se, but this should be suspected wherever there are active tumour deposits invading the nervous system. Particular examples are invasion of the body wall, notably in the chest and pelvis, spinal nerve irritation due to vertebral bone metastases or collapse, brachial plexus invasion by breast or apical lung cancer and perineural spread of head and neck cancer. It has been suggested that nociceptive nerve pain should be differentiated from true neurogenic or deafferentation pain (Ventafridda and Caraceni 1991). This approach may assist in the selection of patients who should receive a trial of anti-inflammato~ drugs as it might be argued that patients with classical phantom pain or chronic established nerve damage after local tumour eradication are unlikely to respond to anti-inflamma- tory drugs (Arner and Meyerson 1988). There appears to be some evidence that opioid response may occur in both groups (Portenoy et al. 1990).

The notion of ‘adjuvant’ drugs is challenged, and it is suggested that drugs should simply be described in terms of their primary action. The term adjuvant is still widely used to describe drugs which have primarily non-analgesic properties but which also exert an anal- gesic effect by a poorly understood mechanism or interaction. Examples of these would include tricyclic and tetracyclic antidepressants, anticonvulsants, steroids and possibly anxiolytics and major tranquillis- ers. Centrally acting drugs also have important roles in the overall management of pain, where both psycholog- ical and somatic components are usually operative, and depression and anxiety require both pharmacoIogica1 and non-pharmacological intervention and support. Phenothiazines are commonly used, but there is no real evidence of a useful synergistic action with opi- oids.

Primary analgesics are those drugs which belong to an analgesic class and have analgesia as the main pharmacodynamic property. Examples of primary anal- gesics would be: opioids, salicylates, NSAIDs, and local anaesthetics. The term ‘weak’ opioid is also not used as this is not a discrete drug class, and the drugs which are normally included in this group are not included in our model, although opioids other than morphine may be useful in some patients who have intractable side effects with morphine. Oxycodone (which is not a ‘weak opioid), methadone and particularly fentanyl are occasionally indicated and tolerated where mor- phine is not, although it appears that for some patients nausea is a problem with several or all of the opioids.

Opioid administration route changes (oral to subcuta- neous or epidural) are also helpful. Where an opioid is indicated in hospice practice, morphine, the paradigm ‘strong’ opioid, is usually recommended. It is interest- ing to note that the relatively pejorative terms of ‘weak’ and ‘strong’ opioid have recently been dropped by the WHO. In our study 2 patients with visceral pain as the sole proposed operative mechanism achieved good pain relief on morphine alone, and this subgroup may repre- sent the most straightforward group to treat, although the pathophysiofo~ is complex and incompletely un- derstood (Ness and Gebhart 1990. Recent work indi- cates that opioids may also have a peripheral nocicep- tive action and that opioid receptors may be trans- ported to peripheral nociceptive sites (Basbaum and Levine 1991; Stein et al 1991).

The system of pain management described here is now undergoing prospective evaluation in our services. Having proposed that cancer pain be unravelled into its component mechanistic parts, some unifying con- cepts emerge. Firstly, it is clear that nearly all cancer pain is nociceptive and that trials of relative response to and sequence of use of anti-inflammato~ and opioid drugs are the central questions except for those few cancer patients with pure neurogenic (deafferentation) pain. Secondly, the majority of patients have multiple mechanisms operating either SynchronousIy or metachronously and may require several drug classes simultaneously or sequentially. More information on the mechanism profile of a larger number of patients is underway. The focus now is on evaluation of drug class response and sequence in the mechanistic categories and combinations described. Once response rates are established for given drug classes and mechanisms, randomised trials of drug sequence and different agents of the same class will be possible.

Although it is not always possible to confidently assign a mechanistic category to all pain, this is a clinical approach that is suitable to most situations encountered in hospice and palliative care practice. It seeks to provide a more reflective basis to modern cancer pain management by moving away from a model of a single chronic entity to one of an acute on chronic multi-mechanistic model which recognises that there is more to cancer pain than intensity.

Acknowledgements

We wish to acknowledge the pioneering work of Dr. Walter Moon, Founder and Director for many years of the Pain Clinics at the Austin Hospital and the Peter MacCallum Cancer Institute, Melbourne. His pain classification was the stimuius to several of us (K.J., N.M., M.A.A.) to pursue this approach. His original classification was: peripheral: superficial, intermediate,

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deep; central; and psychogenic (Moon unpublished). He started practising palliative care with a mechanistic classification of cancer pain long before either was fashionable. We would also like to thank Mrs. Lyn Earnshaw for typing the manuscript. We are grateful to Drs. Fraser, Massolino, Kain and Thomas; Elizabeth Keam (Clinical Nurse Consultant) and the nursing staff of the Mary Potter Hospice for allowing patients under their care to be studied. Beverley Fleming is funded by the Faculty of Medicine, University of Adelaide and the Mary Potter Foundation.

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