Prof. Eric Buchser, MD, DEAAHead of Anaesthesia Pain Management ServicesNeuromodulation CentreMorges and Lausanne, Switzerland

Interventional treatments for the management of pain

Non-opioid + Adjuvant 1

Opioids for mild to moderate pain+ Non-opioids

+ Adjuvant2

Opiate for moderate to severe pain

+ Non-opioid+ Adjuvant

3

When the ladder is too short

When should interventional techniques be used?

Which interventional procedures?Which interventional procedures?

Nerve blocks Reversible

Local anaesthetics Anti-inflammatory drugs - steroids

Non-reversible Neurolysis

– Chemical• Alcohol• Phenol• Hypertonic saline

– Thermal (radiofrequency)

Intrathecal drug delivery

Benefits and risks of neurolytic blocksBenefits and risks of neurolytic blocks

Benefits

– One-time, long-lasting, highly effective Decreased Side effects & cost Increased quality of life & cognitive abilities

Risks

– Potential serious complications Neurological deficits Denervation pain and disaesthesia

– Do not last for ever (usually less than 1 year)

– Require highly experienced physicians

Efficacy and safety of NCPBEfficacy and safety of NCPB Eisenberg E. et al. Neurolytic celiac plexus block for treatment of cancer pain:a meta-analysis.Anesth Analg 1995;80:290-25.

Side effectsLocal pain 96%Diarrhoea 44%Hypotension 38%Others (alcohol intoxication)

Complications 2%ParaplegiaIntestinal infarction

Good to excellent pain relief

– in 89% of patients At 2 weeks At 3 months (survivors)

– In 70-90% until death

(even if >3 months)

24 studies 21 retrospective 1 prospective 2 RCT

1145 patientsPancreatic carcinoma 63%

Others 37%

Does NCPB improved survival ?Does NCPB improved survival ? Pain is a predictor of poor outcome

Survival is improved after chemical splanchniectomy

RCT NCPB vs optimal medical treatment

– NCPB improves pain (p<0.001)

– NCPB does not improve QOL Survival

Overall mortality unchanged

Pat

ient

su

rviv

al (

%)

Survival after NCPBBrown DL et al, Anesth Analg 1987;66:869-73

Kelsen DP et al, Surgery:122(1);53-59 (1997)

Wong GY et al, JAMA:291(9);1092-1099 (2004)

Lillemoe KD et al, Annals of Surgery: 217;447-457 (1993)

Spinal drug administration - Why at all ?Spinal drug administration - Why at all ?

Administration of drugs that cannot be used otherwiseLocal anaestheticsBaclofen (?)Clonidine (?)Peptides

• Decreased side effects (opiates)

Increased effectLess drug for same or better effect

(opiates, baclofen)

100

30

5

1

Oral

Im/Iv

Epidural

IntrathecalMorphine (mg) equianalgesic potency

IT morphine first reported in the late sixties Only opiate approved for long-term IT administration

Mixed results– 38% of patients fail IT morphine

20% side effects 80% lack of efficacy

Spinal drug administrationSpinal drug administration

84%16% Nonmalignant PainMalignant Pain

Hassenbusch SJ, Portenoy RK. J Pain Symptom Manage 2000;20:S4-S11.

84%

20%80%Side

Effects

Lack ofEfficacy

38%62%

The Cancer Pain TrialThe Cancer Pain Trial Thomas J. Smith, M.D.,

Richmond, Virginia Peter S. Staats, M.D.,

Baltimore, MD

Timothy Deer, M.D., Charleston, West Virginia

Lisa J. Stearns, M.D., Phoenix, Arizona

Richard L. Rauck, M.D., Winston-Salem, N.C

Richard L. Boortz-Marx, M.S. M.D., Minneapolis, MN

Eric Buchser, M.D., Morges, Switzerland

Elena Català MD, Barcelona, Spain

David A. Bryce, MD, Marshfield, Wisconsin

Patrick J. Coyne, RN, MSN, Richmond, Virginia

Michael Cousins, MD, Sidney, Australia

George Pool, MPH, Minneapolis, MN

Journal of Clinical Oncology 20(19):4040-4049 (2002)

Annals of Oncology 16(5):825-833 (2005)

Patient Disposition at 1 MonthPatient Disposition at 1 Month

202 Randomized

99 CMM 101 IDDS

16 Died6 Withdrew consent1 Lost to follow-up

7 Died

8 Withdrew consent

76 at 4-week follow-up 86 at 4-week follow-up

5 CMMImplanted

71 CMMNot implanted

62 IDDSImplanted

24 IDDSNot implanted

1 Protocol deviation1 Withdrew consent

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

RandomizationRandomization

CROSSOVER: was allowed 1 month after¨enrolment in either arm

INTENTION TO TREAT analysis

Trial

Pass

Yes

ITTherapy

Implanted pump(SynchromedTM) Comprehensive

Medical Management

(CMM)

No

CMM

Eligible

Randomize

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

Types of Patient PainTypes of Patient Pain

0%

10%

20%

30%

40%

50%

60%

70%

Neuropathic Nociceptive Mixed

CMMCMM + IT

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

Pain ReliefPain Relief Mean Reduction in VAS at 1 month

Error bars are +/- 2 standard errors

0

1

2

3

4

5

6

VA

S:

Me

an C

han

ge

CMM(n=72)

IDDS(n=71)

Intention to Treat(as randomised)

IDDS As Treated(adjusted)

Non-Implanted

(n=22)

Implanted

(n=49)

0

1

2

3

4

5

6

CMM as Treated(adjusted)

Non-Implanted

(n=89)

Implanted

(n=54)

1

2

3

4

5

6

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

Pain Relief - “As Treated” AnalysisPain Relief - “As Treated” AnalysisMean reduction in VAS at 1 and 12 months

Smith TJ et al Annals of Oncology 16(5):825-833 (2005)

VA

S:

Me

an C

han

ge

CMM(n=89)

IDDS implanted(n=54)

1 month

0

1

2

3

4

5

6

7

8

9

10

IDDS implanted(n=68)

CMM(n=35)

12 months

0

1

2

3

4

5

6

7

8

9

10P=0.002 P=0.23

Mean Reduction in Toxicity at 1 Month

Error bars are +/- 2 standard errors

ToxicityToxicity

0

1

2

3

4

5

6

Dru

g T

oxi

city

: M

ean

Ch

ang

e

CMM(n=75)

IDDS(n=73)

Intention to Treat(as randomized)

CMM as Treated(adjusted)

Non-Implanted

(n=92Implanted

(n=56)

1

2

3

4

5

6

IDDS as Treated(adjusted)

Non-Implanted

(n=22)Implanted

(n=51)

1

2

3

4

5

6

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

Reduced libido

Urticaria

Pruritus

Weight loss

Vomiting

Nausea

Dehydration

Constipation

Anorexia

Personality

Memory loss

Reduced level of consciousness

Confusion

Fatigue

Impotence

Reduction in Mean Severity-.8 -.7 -.6 0-.1.2-.3-.4-.5 .1 .2 .3

  CMM

  IDDS

Reduction in side effects

* Statistically significant (p<0.05) *

*

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

SurvivalSurvival

CMM 6.6% 24.6% 33.9% 34.8% 39.5% 45.5%

Percentage of patients implanted (%)

IDDS 72.1% 78.6% 79.0% 84.0% 83.7% 83.3%

p=0.06

0%

20%

40%

60%

80%

100%

30 60 90 120 150 180

Days

Su

rviv

al (

%)

Conventional Medical Management: 37.2%

CMM + IT drug delivery: 53.9%

Crossover(if patient whished)

Smith TJ et al Journal of Clinical Oncology 20(19):4040-4049 (2002)

ConclusionConclusion Interventional pain management

Should be considered when therapy unsatisfactory Neurolytic nerve blocks

Never on a peripheral sensory nerveCoeliac/splanchnic blockade are effectiveNever permanent

Intrathecal drug deliveryHas theoretical advantagesAllows the administration of drugs that cannot be

delivered by systemic routesSuffers from the lack of controlled studies

Thank you for your attention