1. Y V O N A G R I F F O , M D
P A I N & P A L L I A T I V E C A R E S E R V I C E
M E M O R I A L S L O A N K E T T E R I N G C A N C E R
C E N T E R
PAIN MANAGEMENT
The following material is intended for MSKCC internal medicine housestaff teaching
purposes only. The slides were updated for the LibGuide in 2012-2013.

2. 2
The International
Association for
the
Study of Pain:
An unpleasant
sensory or
emotional
experience
associated with
actual or potential
tissue damage or
described in terms
of such damage

3. BASIC APPROACH
1. ETIOLOGY of PAIN
2. CLASSIFICATION of PAIN
3. ASSESEMENT of PAIN
4. TREATMENT of PAIN

4. ETIOLOGY
 PAIN CAUSED BY CANCER
 Infiltration of Bone, Viscera, Soft tissue, Muscles
 Infiltration of Spinal Cord, Roots ,Plexus or Peripheral
Nerves
 Occlusion of Blood Vessels
 PAIN AS SEQUELAE OF CANCER
TREATMENT
 PAIN DUE TO FRAILTY
 PAIN UNRELATED TO CANCER

5. ETIOLOGY-Treatment related
POST-SURGICAL - Phantom Pain
- Neuroma
- Adhesions
- Post-Thoracotomy, Mastectomy
CHEMOTHERAPY -Peripheral Neuropathy
-Mucositis
RADIOTHERAPY -Radiation Dermatitis
-Radiation Neuritis

6. Mixed Type
Caused by a
combination of both
primary injury or
secondary effects
CLASSIFICATION of PAIN
Nociceptive
Pain
Caused by activity in
neural pathways in
response to potentially
tissue-damaging stimuli
Neuropathic
Pain
Initiated or caused by
primary lesion or
dysfunction in the
nervous system
Postoperative
pain
Mechanical
low back pain
Sickle cell
crisis
Arthritis
Postherpetic
neuralgia
Neuropathic
low back pain
CRPS*
Sports/exercise
injuries
*Complex regional pain syndrome
Central post-
stroke pain, spine
Trigeminal
neuralgia
Distal
polyneuropathy
(eg, diabetic, HIV)

7. CANCER PAIN
 INITIAL ASSESMENT and DIAGNOSIS of
Underlying cause
 TREATMENT OF ACUTE UNDERLYING CAUSE
 SPECIFIC ANTI-TUMOR THERAPY
-Surgery
-Radiation
-Chemotherapy
 PAIN MANAGEMENT-ANALGESICS
WHO LADDER Step 1-3

8. CLINICAL ASSESSMENT OF PAIN
8
Believe the patient’s self-report of pain
Take a careful history
—ONSET (temporal pattern) of pain
—LOCATION site of pain/widespread or localized/uni-bilateral
—DURATION of pain /constant or incidental/
—CHARACTER/quality and intensity of pain/
—AGGRAVATING/RELIEVING factors
—RESPONSE to analgesics
—DEGREE of intensity and interference with patient’s life
—ASSOCIATED signs and symptoms

9. ASSESSMENT of PAIN INTENSITY
No Mild Moderate Severe Very Worst
pain pain pain pain severe possible
pain pain
Verbal Pain Intensity Scale
No
pain
Visual Analog Scale
Faces Scale
0 1 2 3 4 5
0–10 Numeric Pain Intensity Scale
No Moderate Worst
pain pain possible pain
0 1 2 3 4 5 6 7 8 9 10
Worst
possible
pain
19

11. WHO –3 Steps ANALGESICS LADDER
 For mild pain, use non-opioid first
 When pain persists or increases, add an opioid
 If pain becomes more severe, increase the opioid
potency or dose
 Schedule doses on around-the-clock basis, with
additional PRN doses -rescues

12. ADJUVANT ANALGESICS
 Anticonvulsants
 Antidepressants
 Corticosteroids
 Neuroleptics
 Anxiolytics
 Muscle relaxants
 Anesthetics
 Antispasmodics

13. BASIC PAIN MANAGEMENT
 Believe Pt’s self report
 Assess factors affecting Pt’s pain report (medical,
psychological, spiritual, functional)
 Titrate analgesics to effectiveness and tolerance of
side effects
 If on ATC opioid must have PRN
 Treat Opioids side effects (bowel regimen)

14. STEP 1- WHO ANALGESICS
14
NON-OPIOID ANALGESICS
ACETAMINOPHEN
NASIDS -(COX -2 INHIBITORS,ASA, SALICYLIC ACID
DERIVATIVES)
Benefits:
NO TOLERANCE or PHYSICAL DEPENDENCE
ADDITIVE ANALGESIA when COMBINDED with an OPIOID
Caution:
CEILIING EFFECT for ANALGESIA
RISKS RELATED to PLATELET DYSFUNCTION, GASTRIC
ULCERATION and GI BLEEDING, CARDIOVASCULAR EVENTS,
HTN, RENAL INSUFFICIENCY or LIVER TOXICITY

15. STEP 2- WHO ANALGESICS
15
WEAK OPIOIDS
CODEINE
HYDROCODONE
OXYCODONE –(in combination with a non-
opioid)
TRAMADOL (mu-agonist, norepinephrine
and serotonin reuptake inhibitor)
TAPENTADOL (mu-agonist, norepinephrine
reuptake inhibitor)

16. STEP 3 – WHO ANALGESICS
STRONG OPIOIDS
MORPHINE
HYDROMORPHONE
FENTANYL
OXYCODONE
METHADONE
LEVORPHANOL
BUPRENORPHINE
OXYMORPHONE
MEPERIDINE

17. CHOOSING THE OPIOID ANALGESIC
17
Patient sensitivity and allergy
Prior opioid exposure
Current intensity of pain or pain crisis
Pain pathophysiology (nociceptive vs neuropathic)
Available route of administration
Requirements for rescue medications
Metabolic factors
Drug interactions
Cost/availability and formulary preparations
Street value

18. ROUTES of OPIOID ADMINISTRATION
 ORAL -tablets, elixirs
 RECTAL-suppository
 TRANSDERMAL, TRANSBUCCAL
 SUBCUTANEOUS
 INTRAVENOUS
 bolus, continuous infusion, PCA
 EPIDURAL
 INTRATHECAL

19. ALGORITHM for OPIOID THERAPY
Patient
Selection
Initial Patient
Assessment
Trial of Opioid
Therapy
Alternatives to
Opioid Therapy
Patient
Reassessment
Exit Strategy
Conversion to
Long-acting
Opioid
Opioid Rotation
Continue
Opioid Therapy Used with permission of Nathaniel P. Katz, MD
7

20. MONITORING OPIOID THERAPY
20
Continual monitoring and follow-ups are
essential to good opioid analgesic therapy –
during the trial and throughout chronic therapy
CRITICAL OUTCOMES = “4 A’s of Pain”
 Analgesia
 Adverse effects
 Activities of daily living
 Aberrant opioid-related behavior
Adjust and Manage therapy based on
outcomes
Document critical outcomes

21. 21
Short acting Opioids = (immediate release preparations)
– Morphine (MSIR ®, Roxanol ™, rectal suppositories
– Codeine (Tylenol with codeine, Soma)
– Hydrocodone (Vicodin ®, Zydone ® Lortab ®,
Vicoprofen ®, Norco®)
– Oxycodone (Roxicodone, Oxy IR ®, OxyFAST, Percocet
®, Percodan ®, Tylox ®)
– Hydromorphone (Dilaudid ®)
– Oxymorphone (Opana IR)
– Fentanyl (Actiq ®, Fentora ®,Onsolis)
CATEGORIES OF OPIOID ANALGESICS

22. CATEGORIES OF OPIOID ANALGESICS
LONG – ACTING OPIOIDS – EXTENDED RELEASE
PREPARATIONS
 Morphine sustained – release (MS Contin, Avinza, Kadian,
Oramorph)
 Oxycodone sustained – release (OxyContin)
 Oxymorphone – sustained release (Opana ER)
 Fentanyl – transdermal patches (Duragesic)
 Hydromorphone –(Exalgo)
LONG – HALF LIFE OPIOIDS
 Methadone
 Buprenorphine
 Levorphanol

23. 23
“GOLD STANDARD” – FOR TREATMENT of
MODERATE TO SEVERE PAIN”
Full mu-receptor agonist
Bioavailability – 30% (PO: IV dose is 3:1)
Easily available in wide range of preparations
– Immediate and sustained release
– Oral tablets, elixir, suspension, capsules
– Rectal suppositories
– Parenteral (IV, IM, SC, epidural, intrathecal)
Most widely used opioid analgesic
CAVEAT !!! – BID/TID medication
– Active morphine metabolites
MORPHINE-6-
GLUCURONIDE
MORPHINE-3-
GLUCURONIDE
MORPHINE

24. 24
Semisynthetic derivative of thebaine
Most utilized opioid worldwide
Full mu-receptor agonist, Kappa receptor agonist ??
Bioavailability – 50%
Oxycodone : morphine dose ration 1: 1.5-2
IR and ER preparations, oral only(tablets or elixir)
Sustained release preparation OXYCONTIN has 2
phase release (immediate and extended in the same
pill)
OXYCODONE

25. FENTANYL
25
Full- mu receptor agonist
High potency, short duration of action, rapid onset of action
Lipophilic – ideal drug for transdermal and transmucosal
administration
bioavailability – 50%
Parenteral, transdermal and transmucosal preparations
25 mcg/hour transdermal Fentanyl patch = 1mg/1 hour IV Morphine
Transdermal Fentanyl patch takes 12 hours to reach analgesic blood
levels on initiation (6 – 18h)
90 – 95% of transdermal Fentanyl reaches systemic circulation as
unchanged Fentanyl
Convenient to use (3 – day drug reservoir)
Ideal for children and uncooperative/impaired adults

28. FENTANYL PATCH
24-hour Oral Morphine Initial Fentanyl dose
30-59 mg 12 mcg
60-134 mg 25 mcg
135-224 mg 50 mcg
225-314 mg 75 mcg
315-404 mg 100 mcg

29. ACTIQ, FENTORA, SUBSYS,ABSTRAL
 Transbuccal Fentanyl -No direct
correlation with TD Fentanyl dose !!!
 NEVER use for opioid naïve patient !!!
 Keep away from children, pets
 Restricted distribution-TIRF-REMS

30. 30
Semisynthetic opioid, hydrogenated ketone analog of
morphine
Full, potent – mu – receptor agonist
Available for oral, parenteral and rectal use PO:IV
dose is 5:1
Oral hydromorphone : morphine dose ration is 1: 4
Parenteral hydromorphone : morphine dose ratio is
1:7
Short duration of action : 3-4 hours
HYDROMORPHONE

31. 31
Synthetic opioid - mu- receptor agonist
- NMDA receptor antagonist
- serotonin reuptake inhibitor
Unique pharmacology - variable and long half-life (8 – 80 hours)
- steady-state plasma concentration up to 10 days
- potency greater then expected
Good oral bioavailability – 60 – 95% PO:IV dose is 2:1
Inexpensive and effective – oral( tablets or elixir) or parenteral
But requires special knowledge
- how to initiate and titrate the dose
- monitor for cardiac toxicity (QT prolongation )
No active metabolites ! Clearance not influenced by hepatic or renal
impairment
METHADONE

32. METHADONE
32
ACUTE USE: 1 MG IV MORPHINE = 1 MG IV
METHADONE
CHRONIC USE: 10 MG IV MORPHINE = 1MG IV
METHADONE
30 – 90 mg daily PO Morphine 4 : 1
90 – 300 mg daily PO Morphine 6-8 : 1
>300 mg daily PO Morphine 10-12 : 1
1960-s – in single dose studies morphine and methadone
doses are equal (Raymond Houde, Equianalgesic
conversion tables)

33. OPIOID EQUIANALGESIC DOSES
Opioid parenteral oral conversion duration
(mg) (mg) (IV to PO) (hours)
Morphine 10 30 3 3 - 4
Methadone 10 20 2 4 - 8
Hydromorphone 1.5 7.5 5 2 - 3
Meperidine 75 300 4 2 - 3
Levorphanol 2 4 2 4- 6
Oxycodone - 20 - 3 - 5
Oxymorphone 1 5 5 3 - 4
Fentanyl 0.25 - 1 1- 2

34. OPIOID CONVERSIONS
 Calculate 24 hrs IV or PO requirement
 Multiply by IV or ORAL conversion factor
 Divide in multiple dosages or hourly rate depending
on medication to be used
 If using SR preparation, add 10-15% of 24 hrs dose
in IR form for breakthrough pain PRN

35. OPIOID CONVERSION
 Example: Opioid equianalgesic values for:
Morphine 10 mg IV= morphine 30 mg PO
=hydromorphone 1.5 mg IV = hydromorphone 7.5 PO
=Fentanyl 250 mcg IV = Methadone 1mg IV
 Example: Same drug, changed route
Change 90 mg q12 MS Contin PO to IV continuous
infusion
Calculate 24-h current dose: 180 mg MS/24 h
Look up equianalgesic ratio: PO/IV= 3
Calculated new dose using ratios: 180/3=
60 mg IV/24 hours =2.5 mg/h continuous infusion
61

36. 36
OPIOID THERAPY
ASSESMENT
ANALGESI
A
+ - -
ADVERSE
EFFECTS - + +
   
-
CONTINUE
CURRENT
OPIOID
INCREASE
DOSE OF
OPIOID
IMPROVE
MANAGEMENT
OF SIDE EFFECTS
OPIOID
ROTATION
+

37. OPIOID SIDE EFFECTS
37
COMMON
– CONSTIPATION
– NAUSEA and VOMITING
– COGNITIVE IMPAIRMENT
• sedation
• confusion
• hallucinations
• agitation/myoclonus
– MIOSIS
– RESPIRATORY DEPR.
– COUGH SUPPRESSION
LESS COMMON
– URINARY RETENTION
– ENDOCRINE
DYSFUNCTION
– ITCHING (HISTAMINE
RELEASE)
– SWEATING
– HEADACHE
– DELIRUM
– BILIARY SPASM/GASTRIC STASIS
– DRY MOUTH
– SEIZURES
– HYPEALGESIA/ALLODYNIA
– TOLERANCE, PHYSICAL DEPENDENCE,
ADDICTION

38. MANAGEMENT OF OPIOIDS SIDE EFFECTS
38
NALOXONE
ANTIEMETICS
LAXATIVES
ANTICHOLINERGICS
PSYCHOSTIMULANTS
ANTIPSYCHOTICS
POLYPHARMACY

39. NALOXONE (Narcan)
 Opioid Antagonist
 Used to reverse opioid-induced respiratory
depression
 May precipitate severe withdrawal symptoms and
pain
 Onset of action 1-2 min
 Short duration of action- 45 min

40. NALOXONE DOSAGE
 RESPIRATORY DEPRESSION RR < 8/min
 DILUTE !!! 1 ml in 9 ml normal saline
 0.04 mg IV push over 15 sec every 1-3 min PRN
 RESPIRATORY ARREST
 1 ml UNDILUTED !!! = 0.4 mg IV push over 15 sec
 follow by 0.4 mg every 1- 3 min PRN

41. OPIOID naïve ADULTS
 Avoid starting long acting opioid !!!
 Start small doses short acting (Oxycodone 5 mg q3h
prn, MSIR 15 mg q3h prn, Dilaudid 2mg q3h prn)
 Acute severe pain- Morphine 5-10 mg IV, Dilaudid
0.5-2 mg IV, Toradol 15-30 mg IV
 IV-PCA- AVOID BASAL for first several hours and
 CAVEAT- Pts with respiratory disease, sleep apnea

42. IV –PCA Patient Controlled Analgesia
If pain is not controlled:
3 choices
- increase basal hourly rate
- increase rescue doses
- increase both (most common approach)
Mild-moderate pain- increase dose by 25%
Severe pain- increase dose by 50%
Or increase basal rate based on # of rescues taken in
the last 12-24 hours

43. RESCUE-PRN dose
 IV rescue- ½ of IV hourly basal dose
 IV rescue can be given every 10- 15-20 min
 PO rescue- 10-20 % of TOTAL daily opioid dose
given every 2-3 hours PRN

44. IV- PCA
 Do not prescribe rescue doses in delirious patients !!!
 Family members can not operate PCA !
 CAB= Clinician activated bolus, given by nurse/MD.
Used for pain crisis, prior to tests or PT
 Methadone and Fentanyl require separate IV line

45. SWITCH from FENTANYL PATCH to
IV-PCA
 Determine target IV PCA setting
 Remove patches (in most cases)
 Start with 0 basal (in most cases)
 6h after patch removal increase basal to 50% of
target dose
 12h after patch removal increase basal to full target

46. SWITCH from IV PCA to FENTANYL PATCH
 Determine patch dose
 6h after patch placement decrease PCA basal by 50
%
 12h after patch placement D/C basal and continue
rescues overnight
 D/C PCA in AM and start oral PRN rescues

47. OPIOIDS RESTRICTED to Pain Services at
MSKCC
 Fentanyl PCA- for basal and rescues at and above 50
mcg/h
 Dilaudid PCA- for basal and rescues at and above 0.4
mg/h
 IV Methadone
 IV Oxymorphone
MORPHINE PCA IS UNRESTRICTED!!!

48. TAPERING OF OPIOIDS
 Literature- Pts can tolerate 75% decrease without
withdrawal symptoms
 Clinical experience- many Pts need slow taper- 25-
50% or less every 2-3 days
 Educate Pts on withdrawal symptoms and how to
manage it

49. PRINCIPLES OF PAIN MANAGEMENT
- SUMMARY -
 Cancer pain can - and must be - treated
 Establish underlying diagnosis of pain
 Use analgesics AROUND THE CLOCK and PRN !!!
 WHO-3-step analgesic ladder approach, non-
opioids and opioid mu- agonists
 Prophylactic bowel regimen
 Add adjuvant analgesics when indicated
 Continued supervision and dose adjustments

50. Thank You