Kyle P. Edmonds, MD
Doris A. Howell Palliative Care Consult Service
UC San Diego Health System
Dr. Doris Howell, pediatric
oncologist.
 Multi-disciplinary team
 For those with life-threatening
disorders
 Complex C...
 Describe the concept of the pain ‘elevator.’
 List the principles for dosing constant and

breakthrough pain.
 Name th...
PAIN

International Association
for the Study of Pain ( IASP ):
“An unpleasant sensory
and emotional experience
associated...
5
 Transduction
 Transmission
 Perception

 Modulation
Disease
Mgmt
EOL
Worry

Physical

Pain
Practical

Spiritual

Psych

Social
7
8
9
 Opioid: anything that binds the

opioid receptor
 Opiate: derived from the opium

poppy (Papaver somniferum)
 Narcotic...
11
12
 Diagnosis
 Assessment
 Efficacy
 Safety / tolerability
 Ease of use
 Cost
3, Pain 7 – 10
Morphine

2, Pain 4 – 6

Hydromorphone
Fentanyl

Tramadol

Acetaminophen
NSAID’s

A / Hydrocodone

Methadon...
Uncommon

Common
 Constipation
 Dry mouth

 Nausea
 Sedation
 Sweats

 Bad dreams / hallucinations
 Delirium
 Myoc...
Plasma Concentration

Death
Bradypnea
Sedation
Awake &
in Pain

0

Time
17
18
Oral/Rectal

Analgesic

IV/SC/IM

15

Hydrocodone

--

15

Morphine

5

10

Oxycodone

--

3

Hydromorphone

1

19
20
 Don’t delay control
 Unmanaged pain

nervous system changes
 Treat underlying cause
22
First Order Kinetics
Plasma Concentration

When biological effect
follows plasma concentration

Absorption

0

Excretion

...
Maximum Concentration ( Cmax )

10

Plasma Concentration

20

= maximum concentration
during the dosage interval
Cmax

0

...
Time to Maximum
Concentration ( t Cmax )

10

Plasma Concentration

20

= time it takes to get to
maximum concentration
Cm...
10min

Plasma Concentration

IV
30min

Time to Maximum
Concentration ( t Cmax )
SC / IM

60min

0

PO / PR

Half-life (t1/...
Half-Life ( t ½ )

10

Plasma Concentration

20

= time it takes for the body
to excrete half the dose

Morphine
all route...
Dosing every half-life ( t ½ )
Plasma Concentration

Oral morphine = 4 hours

100%

97%
93.75%

87.5%
75%
50%

0

4

8

12...
Steady state after 5 half-lives
Plasma Concentration

Morphine ≈ 20 hours
Concentration
where side-effects
start to occur
...
31
32
Time to Drip Steady State
Plasma Concentration

Change GTT
Pain Control

100%

97%
93.75%

87.5%
75%
50%

0

4

8

12

16
...
Plasma Concentration

Steady state for
Morphine ≈ 20 hours

Concentration
where side-effects
start to occur
Concentration
...
35
Breakthrough Pain

Plasma Concentration

PO / PR
≈ 1 hr
Cmax

0

Time
37
38

XKCD.COM/1195/
39
 Persistent
 May have no obvious

cause
 Prolonged functional

impairment
 No sympathetic response
41
42
 Desperation over sxs
 Aggressively complaining
 Requesting specific drug
 Buying opioids on street
 Doctor shopping
...
 Tolerance
 Physiologic Dependence
 Drug Diversion
 Pseudo-addiction
 Addiction
 Continued use of drugs

in spite of harm
 Rare outcome of pain
management
46
47
 Metastatic colorectal CA
 Stable on OP regimen

 Here for tune-up prior to

AM procedure
Oral/Rectal

Analgesic

IV/SC/IM

15

Hydrocodone

--

15

Morphine

5

10

Oxycodone

--

3

Hydromorphone

1

49
 Medication choice is driven by severity and type of

pain.
 It takes 20 hours of constant dosing to reach steady

state...
Kyle P. Edmonds, MD
M: 928.853.1483
O: 619.471.9424
P: 619.290.1212
kpedmonds@ucsd.edu
Pain Pearls & Pet-Peeves
Upcoming SlideShare
Loading in …5
×

Pain Pearls & Pet-Peeves

499 views

Published on

An evidence-based review of the pharmacology of inpatient pain management with focus on opioid therapy. Geared towards advance medical students and housestaff.

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
499
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
3
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • Transdisciplinary team serving those with life-threatening disorders:Complex communicationExpert symptom managementClarifying patient & family goals of careCall the pain service forManaging chronic non-malignant painInterventional pain options
  • Pain is a frequent problem whether associated with advanced illness or other acute or chronic conditions,Weiss SC, Emanuel LL, Fairclough DL, Emanuel EJ. Understanding the experience of pain in terminally ill patients. Lancet. 2001;357(9265):1311-1315. PMID: 11343734.50% of 988 terminally ill patients reported pain. Of those patients experiencing moderate or severe pain,29% wanted more therapy, 61% wanted therapy to remain the same, 9% wanted less therapy or to stop their pain treatment altogether. Of these, 34% feared addiction, 31% were adverse to physical side effects (eg constipation), 33% averse to mental side effects (eg confusion) and 30% averse to additional pills or injections. Although the majority of patients had cancer, there was no association between disease and level of pain. We will briefly review the basic concepts important to understanding the physiology of pain This starts to build the common language we need when assessing and managing painWho in this room has experienced pain? Would you be willing to share you experience?
  • This is how the International Association for the Study of Pain has defined pain… recognizes that it is not only a sensory but also emotional experience Pain is the physical symptom that patients and families fear most
  • This reflects “normal” pain, a healthy nervous system doing what it is designed to do
  • Why is this applicable?
  • Narcotic, in the press & in law enforcement may refer to use of opioids, cannabinoids, cocainr, meth, benzos and even steroids (all subject to abuse).Opioid, includes endogenous and exogenous substancesMorphine is both an opioid and an opiate but fentanyl is only an opioid
  • There’s really no “peeve” here. We all learn how to treat pain the same way: we watch someone else and then copy their doses and choices! That’s how I learned…but let’s try to see if we can agree on some guiding principles to make smart choices for ourselves…
  • A 3-step model to guide analgesic choice depending on the severity of the patient’s painThis ladder can be used for nociceptive and neuropathic painDepending on the severity of the pain, start management at the corresponding stepFor mild pain (1–3/10 on a numerical analogue scale), start at step 1For moderate pain (4–6/10), start at step 2 For severe pain (7–10/10), start at step 3 It is not necessary to traverse each step sequentially; a patient with severe pain may need to have step 3 opioids right awayThe addition of adjuvant analgesics is often critical to achieving an excellent outcomeAs you move between steps and between medications, approaches have been developed to switch opioids while maintaining analgesiaAlthough not displayed on this ladder, nonpharmacologic approaches may significantly increase the relief achievedAsk the group which step contains the most dangerous medications[CLICK] Step 1ASAInhibits thromboxane-induced platelet aggregation, producing an irreversible effect on platelets and a reported increase in bleeding time for up to 7 days after the last doseHigh risk for GI toxicity AcetaminophenHepatic effectNSAIDSRenal effectPlatelet effectCardiovascular effectGI effect
  • How much of each drug, in each form, equals another.
  • This is not to say that there aren’t some who…Respond less to a certain med…Would benefit from rotating to another med.
  • First Order Kinetics are important for all members of the IDT to understandOpioids, codeine, hydrocodone, hydromorphone, morphine, oxycodone, etc., all follow first-order kinetics and pharmacologically behave very similarlyThis curve represents a single, oral dose As we look at the graph, we see that the plasma concentration changes over timeincreases to a point during the absorption phasedecreases during excretion phaseAt the bedside, we can relate this curve to the reported pain relief: pain decreases with taking a dose, plateaus and then increases back to baseline (without a repeated dose of analgesic)
  • The second important pharmacology principles is the maximum concentration or the CmaxThis represents the maximum concentration of the drug for the dose just given [CLICK]At the bedside, this is where we see the expected maximum pain relief from the dose just given The Cmax is the parameter that determines the breakthrough dosing interval
  • Opioids reach their peak plasma concentration (Cmax) approximately 60 to 90 minutes after oral (including enteral feeding tube) or rectal administration[CLICK]
  • The analgesia associated with each opioid has a half-life (t½) that depends on the rate of liver metabolism andits rate of renal clearanceMost of the opioids we use (codeine, hydrocodone, hydromorphone, morphine, oxycodone), and their metabolites have a half-life of approximately 3-4 hours when renal clearance is normal At the bedside, this would be the duration we would expect for pain relief from a single dose It is the half life that determines the routine dosing schedule
  • This graph demonstrates the plasma concentration increasing with routine dosing based on the half-life [CLICK]100%, or maximum plasma concentration is reached after 5 doses, when consistently given based on half lifeWhen dosed repeatedly, the plasma concentrations approach a steady state after 4 to 5 half-lives. Thus, steady-state plasma concentrations are usually attained within a day4 hr half life x  4 doses  = 16 hr4 hr half life x  5 doses  = 20 hour
  • We work towards the steady state of plasma concentration to provide pain relief[CLICK] We try to avoid too little medication (trough) that leads to increased pain, or too much medication (peak) that leads to unwanted side effects This curve represents optimal dosing with the trough and the peak both staying within the therapeutic rangeLow end of the therapeutic range would be the plasma concentration needed to control painHigh therapeutic range would be the plasma concentration where side effects start to occur
  • For the patient with CONSTANT pain, non-scheduled dosing leads to return of pain prior to effective concentration of next breakthrough dose[CLICK] with routine dosing, you can see that the steady state (represented by the line at the peak of the curves) results in each scheduled dose becoming effective before the prior dose is removed from the body.
  • Save yourself the overnight calls and schedule it!
  • Continuous opioid or benzodiazepine drips should not be titrated to symptoms (neither should long acting formulations such as fentanyl patch of extended-release morphine)Steady state not reached for 20 hours!!
  • Given this, I would like you to think about starting morphine drips. Often times, we will increase drips, we will titrate them up, when people have symptoms out of control.Can anyone think of a problem with this, knowing what we now know??When will that drip reach steady state…reach its maximum effect?
  • …or at least every 2 hours while in house.BTP dose = 10% of total 24-hour routine dose
  • Thoughts or questions?...
  • Persistent: usually > 3 to 6 months; does not resolve spontaneously May not be an obvious cause for the reported pain May be due to a chronic disease or conditionProlonged Impairment: both physical and psychologicalUsually no sympathetic responseMay not APPEAR to be in pain when looking at themmay exhibit insomnia, anorexia, irritability, depressionChronic pain is often more challenging to manage
  • For chronic, non-malignant pain (pain from a condition that does not threaten the patient’s life), the pain management service would be your experts.
  • Pharmacologic tolerance is the reduced effectiveness of a given dose of medication over time Clinical importance is rareTolerance to unwanted effects is observed commonly and is favorableTolerance to analgesia is rarely significant clinically when opioids are used routinely Doses may remain stable for long periods if the pain stimulus remains unchangedWhen increasing doses are required, suspect worsening disease rather than pharmacologic toleranceDependenceProcess of neuro-adaptationAbrupt cessation withdrawalTitrate down if stoppingAvoid antagonistsDiversionRegulationRecord keepingAccountabilityPseudo-addictionMost common cause of apparentdrug ‘ failure ’ is under-dosingBehavior LOOKS like drug seekingAddictionPsychological dependenceCompulsive useLoss of control over drugsLoss of interest in pleasurable activities
  • Its hallmark is psychological dependence on drugs and a behavioral syndrome characterized by compulsive drug use and continued use, despite harmAddiction is a rare outcome of pain management when there is no history of substance abuse
  • How much of each drug, in each form, equals another.
  • Pain Pearls & Pet-Peeves

    1. 1. Kyle P. Edmonds, MD Doris A. Howell Palliative Care Consult Service UC San Diego Health System
    2. 2. Dr. Doris Howell, pediatric oncologist.  Multi-disciplinary team  For those with life-threatening disorders  Complex Communication  Expert symptom mgmt  Clarifying goals of care 2
    3. 3.  Describe the concept of the pain ‘elevator.’  List the principles for dosing constant and breakthrough pain.  Name the most common unwanted effect of opioid therapy.  Describe the principle for titration of drips.
    4. 4. PAIN International Association for the Study of Pain ( IASP ): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage.”
    5. 5. 5
    6. 6.  Transduction  Transmission  Perception  Modulation
    7. 7. Disease Mgmt EOL Worry Physical Pain Practical Spiritual Psych Social 7
    8. 8. 8
    9. 9. 9
    10. 10.  Opioid: anything that binds the opioid receptor  Opiate: derived from the opium poppy (Papaver somniferum)  Narcotic: archaic term, associated with illicit use 10
    11. 11. 11
    12. 12. 12
    13. 13.  Diagnosis  Assessment  Efficacy  Safety / tolerability  Ease of use  Cost
    14. 14. 3, Pain 7 – 10 Morphine 2, Pain 4 – 6 Hydromorphone Fentanyl Tramadol Acetaminophen NSAID’s A / Hydrocodone Methadone A / Oxycodone 1, Pain 1 – 3 Oxycodone ± Adjuvants ± Adjuvants ± Adjuvants WHO. Geneva, 1996.
    15. 15. Uncommon Common  Constipation  Dry mouth  Nausea  Sedation  Sweats  Bad dreams / hallucinations  Delirium  Myoclonus / seizure  Pruritis / urticarial  Respiratory depression  Urinary retention
    16. 16. Plasma Concentration Death Bradypnea Sedation Awake & in Pain 0 Time
    17. 17. 17
    18. 18. 18
    19. 19. Oral/Rectal Analgesic IV/SC/IM 15 Hydrocodone -- 15 Morphine 5 10 Oxycodone -- 3 Hydromorphone 1 19
    20. 20. 20
    21. 21.  Don’t delay control  Unmanaged pain nervous system changes  Treat underlying cause
    22. 22. 22
    23. 23. First Order Kinetics Plasma Concentration When biological effect follows plasma concentration Absorption 0 Excretion Time
    24. 24. Maximum Concentration ( Cmax ) 10 Plasma Concentration 20 = maximum concentration during the dosage interval Cmax 0 Time ( hours )
    25. 25. Time to Maximum Concentration ( t Cmax ) 10 Plasma Concentration 20 = time it takes to get to maximum concentration Cmax 0 1 Morphine PO / PR Cmax = 1 hour Time ( hours )
    26. 26. 10min Plasma Concentration IV 30min Time to Maximum Concentration ( t Cmax ) SC / IM 60min 0 PO / PR Half-life (t1/2) Time
    27. 27. Half-Life ( t ½ ) 10 Plasma Concentration 20 = time it takes for the body to excrete half the dose Morphine all routes t ½ = 4 hours 0 4 Time ( hours )
    28. 28. Dosing every half-life ( t ½ ) Plasma Concentration Oral morphine = 4 hours 100% 97% 93.75% 87.5% 75% 50% 0 4 8 12 16 20 24 Time ( hours )
    29. 29. Steady state after 5 half-lives Plasma Concentration Morphine ≈ 20 hours Concentration where side-effects start to occur Peak Trough 0 Concentration needed to control pain Time
    30. 30. 31
    31. 31. 32
    32. 32. Time to Drip Steady State Plasma Concentration Change GTT Pain Control 100% 97% 93.75% 87.5% 75% 50% 0 4 8 12 16 20 24 Time ( hours )
    33. 33. Plasma Concentration Steady state for Morphine ≈ 20 hours Concentration where side-effects start to occur Concentration needed to control pain …20 Time
    34. 34. 35
    35. 35. Breakthrough Pain Plasma Concentration PO / PR ≈ 1 hr Cmax 0 Time
    36. 36. 37
    37. 37. 38 XKCD.COM/1195/
    38. 38. 39
    39. 39.  Persistent  May have no obvious cause  Prolonged functional impairment  No sympathetic response
    40. 40. 41
    41. 41. 42
    42. 42.  Desperation over sxs  Aggressively complaining  Requesting specific drug  Buying opioids on street  Doctor shopping  Prescription forgery Passik et al. JClinPain. 2006. 43
    43. 43.  Tolerance  Physiologic Dependence  Drug Diversion  Pseudo-addiction  Addiction
    44. 44.  Continued use of drugs in spite of harm  Rare outcome of pain management
    45. 45. 46
    46. 46. 47
    47. 47.  Metastatic colorectal CA  Stable on OP regimen  Here for tune-up prior to AM procedure
    48. 48. Oral/Rectal Analgesic IV/SC/IM 15 Hydrocodone -- 15 Morphine 5 10 Oxycodone -- 3 Hydromorphone 1 49
    49. 49.  Medication choice is driven by severity and type of pain.  It takes 20 hours of constant dosing to reach steady state.  Breakthrough pain dosing should occur on the Cmax.  Around-the-clock dosing should occur on the half- life.  Titrate drips to number and amount of bolus dosing; titrate bolus dosing to symptoms. 50
    50. 50. Kyle P. Edmonds, MD M: 928.853.1483 O: 619.471.9424 P: 619.290.1212 kpedmonds@ucsd.edu

    ×