Transcript Spinal Analgesia for Palliative Care

Opioids for chronic pain in the
prison population– good or bad?
Dr Lesley Colvin
Consultant/ Hon Reader in Anaesthesia & Pain
Medicine
University of Edinburgh
Opioids for severe chronic pain?
Opioids are
essential drugs
Patients must have
access to effective
treatment
Efficacy
Safety
Opioids may
have long-term
problems
• Evidence of efficacy?
• Other long term harms?
• Legal & social need to
stem diversion and
abuse
Access to specialist
services
E.g. pain and addiction
Pain and disability
“Great news Mr W – you’ll still
be able to play the harmonica!”
Evidence for opioid use in
chronic pain
Key recommendations


Strong opioids should be considered for chronic low
back pain or osteoarthritis, and only continued if
there is ongoing pain relief (B)
Specialist referral or advice if:

concerns about rapid-dose escalation with continued
unacceptable pain relief
or


>180 mg/day morphine equivalent dose is required (D)
…How do these apply in the context of
substance misuse and in the prison
population?
Opioids – long term adverse
effects
Central Nervous System – cognitive function
 Endocrine
 Immune function
 Fracture
 Cardiovascular
 Cancer biology
 Misuse and addiction

Long term harm from opioids?
No studies of long term outcomes (>1 year)
from opioid Rx compared to no opioid
 Increased risk of:

 Sexual
dysfunction [OR 1.45 (CI -1.87)]
 Fractures [OR 1.27 (CI 1.21-1.33)]
 Myocardial infarction [OR 1.28 (CI 1.19-1.37)]
 Abuse [wide range – up to 37%]
 Overdose [HR 5.2 (CI 2.1-12.5)]
 Motor vehicle accident [OR 1.24-1.42]
Opioid endocrinopathy
Hypothalamic-pituitary-adrenal axis
dysfunction
and/ or
 Hypothalamic-pituitary-gonadal axis
 Symptoms of hypogonadism, adrenal
dysfunction
 Coupled with such disorders as osteoporosis
and mood disturbances

Testosterone levels in men –
secondary hypogonadism with
reduced pituitary hormones
(LH, FSH)
• Dose related
• HADs higher
• Fatigue
• Poorer survival (OR of
death=2.87, p<0.001)
Mx of hypogonadism – necessary?
Discontinue opioid therapy
Switch opioid
Hormone supplementation
Opioids
Pain
Peripheral & Central Nervous System
response
Physiological
- analgesia
Pathological
- hyperalgesia
E.g. methadone
maintenance
Effect of opioids on “wind up”
HV = Healthy volunteers
OA = Opioid misuse
CNCP= Chronic nonmalignant pain
CP= Cancer pain
* p<0.0001
Implications for
Rxing pain?
➢ Opioid-associated sensory dysfunction
Bathgate et al, EFIC, Sept 2011
Opioids an the immune system:
Toll like receptors
Opioids
Intracellular
signaling pathways
Opioids and the immune system:
central effects
Opioid activity at TLRs elicit proinflammatory
reactivity (similar to endotoxin) from glia, the
immunocompetent cells of the central nervous
system
• Includes release of cytokines and chemokines and
associated disruption of glutamate homeostasis
➢elevated neuronal excitability
➢decreased opioid analgesic efficacy
➢heightened pain states
•
Hutchinson MR. Et al. Pharmacological Reviews. 63(3):772-810, 2011;
Wang X. et al, Proc Nat Acad Sci.109(16):6325-30, 2012
Opioid effects on cytokines
Cong D et al, SPaRC 2014
Opioids and cancer neurobiology
Colvin et al, BJA, August, 2012
Clinical Challenges in opioid
dependence
Pain
assessment
Response to opioids:
• Tolerance
• ?OIH
Previous
experience of
healthcare
Opioid misuse
•
•
Many studies exclude patients with a Hx of
misuse, definitions vary
Misuse often not reported – event rate of 0.27%
in Cochrane review (Noble, 2010)
Low risk
High risk
0.19%
3.27%
Adverse drug-related 0.59%
behaviour
11.5%
Addiction
(Fishbain, 2008)
•
Prediction: limited evidence for validated tools
or urine drug testing
Increasing Prescription Drug
Abuse
3000
120000
2500
100000
2000
80000
number of 1500
initiates (in
thousands) 1000
number 60000
500
20000
0
0
40000
1985
1991
1993
1995
1997
1999
National Household Survey
On Drug Use and Health
2001
1995 1996 1997 1998 1999 2000 2001 2002
Drug Abuse Warning
Network
Portenoy, Beth Israel, New York
Substance misuse – “pain relievers”
 5.1
million users of pain relievers
55% got the pain relievers from a friend or
relative for free
 11.4 % bought them from a friend or
relative (cf 8.9% from 2007-2008)
 4.8 % took them from a friend or relative
without asking.

SAMHSA, 2011
Opioid prescribing in Scotland 2003-2012
•
•
•
•
Total of ~3.7M in 2003
Increase to 5.9M total paid items in 2012
Increase of 63% in 10 years
In 2012 >4.8M weak & >1M strong opioid
prescriptions
• 18% of population had opioid script in 2012
Total Prescription (Paid) Items
6,000,000
5,000,000
4,000,000
WEAK
STRONG
3,000,000
2,000,000
1,000,000
0
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
OPIOIDS AND SCOTTISH INDEX OF MULTIPLE
DEPRIVATION (SIMD)
If in most deprived area 3.5 times more likely to be
prescribed a strong opioid
SIMD quintiles: 1= most deprived, 5=least deprived
WEAK OPIOIDS
STRONG OPIOIDS
10,000
35,000
DDDs per 1,000 population
DDDs per 1,000 population
9,000
8,000
7,000
6,000
5,000
4,000
3,000
30,000
25,000
20,000
15,000
10,000
2,000
5,000
1,000
0
0
1
2
3
SIMD 2012
4
5
1
2
3
SIMD 2012
4
5
Opioid related mortality
Questions?
Which opioid?
Methadone
 Buprenorphine

 Subutex
 Suboxone
(with naloxone)
 DHC (unlicensed use)

Avoid short acting if possible
Assessment – history:
pain and substance misuse




Pain

Is there likely to be a neuropathic component?
Substance misuse history
 Stable/ chaotic – prescription? Support?
 IVDA – Hep C/ HIV (BBV) status and Rx
 Alcohol; stimulants & / or benzos; cannabis; NPAs;
gabapentin…
Mental Health
Social history/ Child protection issues
Assessment – examination:
pain and substance misuse


Pain
 Sensory changes/ ? neuropathic
 Motor impairment/ impact on function
Substance misuse history
 Toxicology – urine / oral swab
 Track marks
 Intoxication
Management
 Early
assessment & explanation
 Non-pharmacological
– eg TENS (also
acupuncture)
 Nerve
blocks/ regional techniques
Management
 Pharmacological
Non-opioids – NSAIDs
 Avoid cyclizine
 ?Gabapentin / Pregabalin

 Strong
opioids if needed:
monitoring important
 split dose
 ? buprenorphine

Opioids and cancer neurobiology
•
•
•
Up regulation of MORs (non-small cell lung ca)
Rodent studies - MOR over expression increased tumour growth and metastases
Peripheral MOR antagonist, methylnaltrexone,
prevented tumour growth (similar to silencing
MOR expression )
Opioids and cancer
•
•
Population based study (n=42,000) of patients
undergoing colectomy ( 22% -epidural analgesia):
5 year survival better in epidural group cf
"traditional pain management”
Retrospective study (n=655) of colorectal cancer:
increased risk of death up to 5 years later in
patients receiving patient controlled analgesia cf
epidural analgesia, only in rectal, but not colon
cancer.
Cummings KC et al. Anesthesiology 2012; 116:797-806.
Gupta A et al. BJA 2011; 107:164-170
Assessment: The effect of patient
expectation?


Remifentanil – a potent opioid analgesic?
Constant dose – burn - manipulate expectation
Behavioural effects of the contextual modulation of
opioid analgesia
Bingel U et al. Sci Transl Med 2011;3:70ra14-70ra14
Cortical correlates of behaviour
VAS 6.6/10
VAS 5.5/10
VAS 3.9/10
VAS 6.4/10
Bingel U et al. Sci Transl Med 2011;3:70ra14-70ra14
Pain studies – design problems?
Overestimation of effect
Little difference from placebo
Endocrine effects of opioids

Hypogonadism
 Low
LH, oestradiol, testosterone (free and
total)

Symptoms
 Reduced
libido, irregular menses
 Low energy
 Depression
 Poor concentration
 Reduced physical performance