1. Managing Pain (effectively!)
Alec Price-Forbes
Consultant Rheumatologist
March 21st 2012

2. Mrs W OA, Inflammatory arthritis April 2010 unwell anaemic, APR raised
July 2010 presumed osteomyelitis right ankle
September 2010 Staph sepsis
Cervical discitis
? SBE

3. Mrs W 3/12 IV antibiotics November 2010 - septic - CCU for inotropes
- drowsy
On fentanyl 175mcg/hr
What is PRN dose
What dose of diamorphine would you convert to?

4. Aims To consider general aspects of pain relief What is pain?
To consider issues around assessing and diagnosing pain
To understand the principles of choosing an analgesic
To understand the use of morphine and appropriate dose calculations

5. What is pain? How would you describe and define pain?
- please share thoughts with your neighbour

6. The background 6

7. What is pain?
Pain is perceived along a spectrum from peripheral pain receptors to the cerebral cortex and is modified at every step along its travel
Pain is an unpleasant, complex, sensory and emotional experience
Pain is a distressing experience for the patient
Pain is what the patient says it is

8. Causes of failure to relieve pain
Reasons
Belief that pain is inevitable
Inaccurate diagnosis of the cause
Lack of understanding of analgesics
Unrealistic objectives
Infrequent review
Insufficient attention to mood and morale
Consequences
Unnecessary pain
Inappropriate Rx
Use of inappropriate, insufficient or infrequent analgesics
Dissatisfaction with Rx
Rejection of Rx by patient
Lowered pain threshold
Adapted from Twycross Update 1972

9. Total Pain Spiritual Physical Total Pain Social Psychological
Saunders 1964

10. Chronic pain is different…

11. Ms. Unhappy
Why can’t you fix my back and fxxk off 11

12. Ms. Unhappy 33 year old woman, accident at work
“lifted something heavy and felt a click at the back”
MRI: unremarkable
Nociception 12

13. Ms. Unhappy
She felt so bad that she cannot sleep, cannot eat, and became irritable
Affect 13

14. Ms. Unhappy
She cannot work, cannot go out, cannot do housework, cannot….
Social 14

15. Ms. Unhappy
She insisted in using a walking aid, visited 4 doctors for the “right diagnosis”, alcohol to “knock me off the pain”
Behavior 15

16. Acute versus chronic pain
Acute (eg fracture)
Obviously in pain
Complains of pain
Understands why they have pain
Primarily affects patient
Chronic (eg neuralgia)
May only seem depressed
May only complain of discomfort
May see pain as never-ending/meaningless
Pain overflows to affect others

17. Definitions Nociception Pain threshold versus pain tolerance Allodynia
Analgesia
Dysasthesia

18. CLASSIFICATION OF PAIN
Nociceptive – associated with tissue distortion or injury
Caused by tissue damage injury – information carried to the brain via normal nerves

19. CLASSIFICATION OF PAIN
Neuropathic – associated with nerve compression or injury
The nerves carrying the information to the brain are abnormal and are associated with abnormal sensations
Nerve compression
Nerve crushing/destruction
Nerve being cut

20. Issues in assessing pain
Where is it?
What is it like?
How long has it been present?
How severe is it?
Does it spread anywhere else
How is it affecting functioning?
What are the goals for the pain?

21. Managing Pain Take a good history and examine the patient
Think about the cause or type of pain
Somatic
Visceral
Neuropathic
Establish patient’s expectations, priorities
Choose appropriate medication
Set realistic goals, negotiate a plan
3 Types
Can be acute or chronic
Can all occur together or alone and at different times
Somatic -activation of pain receptors in cutaneous or deep (muskuloskeletal) tissues (e.g. bone metastasis, post surgical incision pain) Dull/aching, localized for deep, sharper or prickling if superficial
Visceral -activation of pain receptors from stretching, compression, infiltration of viscera (e.g. pancreatic pain) Pressure, deep, squeezing, not well-localised
Neuropathic -compression, invasion or damage to nervous system Severe, burning, tingling

22. Problems in assessing pain
Think about TWO problems that could make
it difficult to assess someone’s pain?

23. Common mistakes in pain management
Forgetting there may be more than one pain
Reluctance to prescribe morphine
Failure to explore holistically
Failure to educate patient about dose, timing, side effects and deal with their fears
Reducing the interval instead of increasing the dose

24. Problems in assessing pain
The number of different pains (50% of patients have 3 or more different pains)
Not all pains respond to morphine
Patients underplaying their pain
Patients reacting markedly to their pain (usually anxiety, anger or depression are present)
Staff or partners assessing a patient’s pain
The patient with poor or absent communication

25. Help with assessing pain
Ask the patient highly accurate
Ask the partner subject to bias
Body chart involves patient
VAS some patients stuggle with the concept
Pain diary qualitative research
Pain questionnaire

26. Diagnosing Pain Bone metastases produce pain worsened with movement
Muscle pain produces pain on active movement
Chest infection causes pain worse on inspiration
Constipation causes pain at rest in the abdomen which is periodic
Neuropathic pain causes an unpleasant sensory change at rest, sometimes with pain on touching

27. Pain behaviours/signs where communication impaired
Expressive: grimacing, clenched teeth, shut eyes, wide open eyes
Adaptive: rubbing or holding area, keeping still, reduced or absent function
Distractive: rocking, pacing, biting, clenched fists
Postural: increased muscle tension, limping
Autonomic: sympathetic, parasympathetic

28. Analgesic Mantra By the Mouth By the Clock By the Ladder
Attention to detail and regular reassessment
By the Mouth
By the Clock
By the Ladder
Individualised Treatment
Attention to detail

29. Types of analgesic Primary Non-opioids eg paracetamol
Weak opioid agonists eg codeine, DF118
Strong opioid agonists eg morphine, diamorphine, fentanyl, oxycodone
Opioid partial agonist/antagonists eg buprenorphine
NSAIDs
NMDA antagonists eg ketamine, methadone
Nitrous oxide

30. Types of analgesic Secondary analgesics
Adrenergic pathway modifiers eg clonidine
Antibiotics
Anticonvulsants eg CMZ, gabapentin
Antidepressants eg amitriptyline
Antispasmodics eg hyoscine
Antispastics eg Baclofen
Corticosteroids
Membrane stabilising drugs eg flecanide, lidocaine
NSAIDs

31. WHO Pain Ladder Consider nerve block Structured yet flexible
Selection of analgesics guided by intensity of pain vs cause
Approx 80% gain relief from pain by adopting these basic principles
Adjuvants: Non analgesic drugs eg Amitriptylline for neuropathic pain
Psychotropic drugs eg sleeping tablets and antidepressants
Side effect drugs eg antiemetics and laxatives
Step 2 weak opioids and NSAIDS- ?need for step 2. Codeine metabolised to morphine via cytochrome enzymes. Codeine is much weaker agonist at mu receptors than morphine. Small proportion of Caucasians and smaller prop Asians are unable to metabolise, therefore poor responders. 8mg codeine plus paracetamol confers no benefit over paracetamol alone.
Tramadol is a weak opioid and SSRI. Max dose limits usefulness

32. WHO Analgesic staircase
Use non-opioids, weak opioids and strong opioids as the 3 steps
However, not all pain opioid responsive (eg colic, neuropathic pain)
Consider adjuvants for each patient
Different pains need different analgesics

33. Opioids
Agonists at opioid receptors (mu, kappa, delta) in spinal cord and brain
Differences between opioids relate to differences in receptor affinity
Morphine is the strong opioid of choice- cost, effectiveness, no ceiling effect

34. CASE SCENARIO
In groups of 3, work through the first 4 questions

35. Opioid choice Morphine given Orally Regularly Prevents pain
Haloperidol treats nausea
Injections are unnecessary
No addiction is seen and
Early use is best
Morphine is still the gold standard opioid:
It has more evidence for its use and safety
No evidence that other opioids are better
30 years use
Wide safety margin
Well tolerated in most people

36. ANSWER Q1 F never delay using if pain requires a strong opioid
T aim is not simply to treat pain, but prevent recurrence
F injection route more potent (less drug needed for same effect) but is not more effective
F morphine is converted to active metabolites so reduced liver function has little effect
T active metabolites are excreted via kidney

37. Starting Opioids
What concerns might patients have about starting morphine?

38. Dependence and Addiction
Dependence- state in which an abstinence syndrome may occur following abrupt opioid withdrawal or administration of opioid antagonist.
Addiction - characterised by psychological dependence

39. Morphine dose timing
For continuous pain analgesia should be continuous
Regular administration should enable good pain control and prevent it returning
Do not rely on PRN
PRN = ‘PAIN RELIEF NIL’

40. Indications for injections
Inability to tolerate other routes (eg nausea and vomiting)
But NOT because of poor pain control:
Giving injections means need less drug to have same effect
But it cannot be more effective because it’s the same drug

41. Metabolism
Morphine is absorbed from small bowel, metabolised in liver to active metabolite (morphine 6-glucuronide, M6G) which is renally excreted
Liver impairment has little effect; kidney impairment does affect handling
Other metabolites (eg M3G) also renally excreted and can accumulate

42. Strong Opioids
Immediate release (peak concentration after 1h, duration of action 1-4 hours)
Oramorph, Sevredol, OxyNorm
Modified release (peak concentration after 2-6 hours, duration 12-24h depending on formulation)
MST, MXL, Oxycontin
Oramorph 10mg/5ml and 20mg/ml strengths

43. Starting morphine
(5mg – 10mg) 4hrly + 30mins prn (& laxative) (2.5 mg 4hrly if previously on non-opioid)
4hrly dose plus prn dose over 24hrs=TDD (total daily dose)
TDD/2= 12 hourly (bd) dose
TDD/6= prn dose
Median dose for morphine is 100mg/day so PRN is 15mg 4-hrly
90% patients managed with morphine dose <500mg 43

44. Question 3
NO high dose would produce adverse effects and deter patient from continuing with an effective drug
NO usually any increase is done third day
NO useful rule is to increase by half (50%)
Yes increase by 50% of dose every third day

45. Calculate breakthrough dose for
MST 30mg bd
MST 60mg bd
MST 120 mg bd
MST 1500 mg bd
MST 3000 mg bd 45

46. Dose titration 12 hourly dose & total prn use= new TDD
New TDD/2= new 12 hourly dose
New TDD/6= new prn dose 46

47. Calculate new MST dose and breakthrough dose for
MST 10mg bd and 4 doses of oramorph 2.5 mg
MST 120 mg bd and 2 doses of oramorph 40mg
MST 600 mg and 6 doses of oramorph 200mg 47

48. Case scenario
Please do questions 5-7

49. Q5 Morphine worries
Feeling drugged is unlikely since tolerance to may side effects is rapid (effects wear off quickly)
Tolerance to analgesia is not seen (pain relief does not wear off with time)
Withdrawal symptoms are likely if morphine stopped abruptly but not if reduced slowly eg. over 5 days
Addiction to morphine is unlikely. Circumstances in which they take morphine does jot encourage addictive behaviour
Constipation is very likely
Hallucinations, confusion and nightmares very unlikely

50. Q6 True intolerance to opioids very unusual and allergy rare
REAL INTOLERANCE
Fear of opioids is commonest cause of intolerance but can be managed by explanation
Reduced drug clearance
Morphine and oxycodone accumulate in renal impairment; fentanyl, methadone little effect
Opposite for liver impairment
APPARENT INTOLERANCE
Dose too high
Titration too rapid
Conversion ratio incorrect
Other cause of confusion (biochemical, infections, other drugs)
Constipation

51. Changing the route of administration
po morphine > sc morphine
po morphine > sc diamorphine
po morphine > sc oxycodone
po oxycodone > sc oxycodone
1/2
1/3
1/4 51

52. STRONG OPIOIDS Morphine – global strong oral opioid of choice
Morphine – s/c if unable to take oral morphine (When changing to Morphine (s/c) from morphine (oral) give 1/2 of the PO morphine dose)
Fentanyl – transdermal patch or sublingual

53. Alternative Strong Opioids
Equivalent potency to oral morphine
Key points
Oxycodone
= 1/2 x oral morphine dose
(10mg oral oxycodone = 20mg oral morphine)
Patients experiencing toxicity with another opioid
Diamorphine
=1/3 oral morphine dose
(10mg diamorphine sc = 30mg oral morphine
More soluble than morphine, used in CSCI
Buprenorphine
BuTrans 7 day patch
20 micrograms/h = mg oral morphine
Transtec 3-4 day patch
35 micrograms/h = mg oral morphine
In practice main route used is transdermal
Useful in renal disease or when oral route not possible
For CONTROLLED pain
Methadone specialist use
Hydromorphone used less often as oral alternative in renal impairment or toxicity with alternative opioids
Alfentanil used in renal failure

54. Alternative Opioids Fentanyl Patches
Adhesive patch delivering a constant amount of fentanyl per unit time: e.g. 25 micrograms/hour
Less constipation, sedation and nausea
Preferable in serious renal impairment
Change every 72 hours
Takes up to 24 hours to start or stop acting
For controlled pain
Need to supply breakthrough morphine or oxycodone

55. Equivalent doses of fentanyl
Fentanyl patch dose
Approximate equivalent dose of oral morphine in 24 h
Breakthrough dose of morphine
12mcg/h
45mg
5-10mg
25 mcg/h
90mg
10-20mg
50mcg/h
180mg
20-35mg
75mcg/h
270mg
35-45mg

56. STRONG OPIOIDS continued
Hydromorphone – analogue of morphine with similar pharmacokinetics
Oxycodone – similar properties to morphine. Less SE’s in some patients
Methadone – needs to be started as inpatient

57. Starting Opioids Dorothy, 63y diagnosed with advanced ovarian cancer
Constant low abdominal pain
Bowels regular
Taking co-codamol 30/500, 2 tablets qds
What dose of morphine would you start?
How would you advise her to take it?
MR or IR titration, breakthrough analgesia, laxatives and anti-emetics

58. Name and address of the patient The name of the drug
The form and strength of the preparation
The total quantity of the preparation, or the number of dose units, in both words and figures
Dosing instructions
Dosing instructions (“prn”  “one prn” )
Prescription valid for 28 days
Quantity 30 days only (DH Guidance, 2006)

59. Nerve Damage Membrane stabilizing drugs Tricyclics
Anti-epileptic drugs eg. Carbamazepine
Gabapentin

60. Routes of administration
Oral : Tablets / Liquids
Rectal
Sublingual / Transdermal
Parenteral / Subcutaneous

61. Other forms of treatment
Physiotherapy
Hot / Warm
TENS stimulation
Acupuncture
Hypnosis
Complementary therapies
Relaxation therapies
Treating of underlying psychological, social, spiritual distress

62. Mrs W
Fentanyl 175
What is equivalent morphine/diamorphine dose?

63. Summary
Pain is a subjective “total” experience and assessment and management must take this into account
The WHO Ladder provides a framework for managing pain
There are a number of opioid medications, with morphine being the opioid of choice in most situations
Adjuvant drugs are an important part of pain management