Future Webinar ConferencesMarch 24, 2010 12-1pm ET

Symptom Assessment and ManagementSteven Weisbord, MD

April 28, 2010 12-1pm ETIncorporating Palliative Care into the Dialysis Unit

Michael Germain MDMichael Germain, MD

To register contact:Samantha Dorr

1

Mid-Atlantic Renal Coalition804.794.3757

sdorr@nw5.esrd.net

For additional information, including resources for patients and families, p

visit www.kidneyeol.org

Advance care planning informationDo not resuscitate orders in the dialysis unitAccess to hospice

C t t th Kid E d f Lif C liti t

pClinician educational resources

2

Contact the Kidney End of Life Coalition atkidneyeol@nw5.esrd.net

Pain Assessment and Pain Assessment and Management in ESRD

Sara Davison3

Sara Davison

ObjectivesObjectives

Discuss the magnitude and impact of chronic Discuss the magnitude and impact of chronic pain in ESRDpain in ESRD

Discuss barriers to adequate pain assessment Discuss barriers to adequate pain assessment and management in ESRDand management in ESRDand management in ESRDand management in ESRD

Outline potential strategies to enhance painOutline potential strategies to enhance painOutline potential strategies to enhance pain Outline potential strategies to enhance pain assessment and management in ESRD assessment and management in ESRD

4

Symptom Burden in Dialysis Patients 507n = 507

80

60

70

80

tiredwell-being

40

50

60 gappetitepainitching

20

30

40 itchingdrowsyanxiousSOB

0

10

20 SOBnausea

5

0

Davison, et al KI 2006;69:1621

Severity of Pain: Brief Pain I t SInventory Scores

Severity Mild Moderate Severe Mean BPI y(n=103) (0-3) (4-5) (6-10) Score

WorstWorst 17.5%17.5% 27.2%27.2% 55.3% 7.037.03

LeastLeast 74 8%74 8% 16 5%16 5% 8 7% 3 073 07

82.5%82.5%LeastLeast 74.8%74.8% 16.5%16.5% 8.7% 3.073.07

Average Average 41.7%41.7% 30.1%30.1% 28.2% 5.615.6158.3%58.3%NowNow 44.7%44.7% 28.2%28.2% 27.2% 4.994.99

6Davison, AJKD 2003

Cause of pain is NOT predictive for severity of pain

The Impact of Pain and Overall S t B d f ESRD P ti tSymptom Burden for ESRD Patients

No – Mild Mod – Severe Odds Ratio PNo Mild pain

Mod Severe pain

Odds Ratio P

Depression 18% 34% 2.312.31 0.010.01p 3 %Insomnia 53% 75% 2.322.32 0.020.02

D i JPSM 2005

Symptom burden accounted for 29% of the impairment in physical HRQL and 39% of the impairment in mental HRQL

Davison JPSM 2005

physical HRQL and 39% of the impairment in mental HRQLDavison KI 2006

Change in symptom burden accounted for 34% of the change in

7

g y p gphysical HRQL and 46% of the change in mental HRQL.

Davison NDT 2006

Point Prevalence of Analgesic U DOPPS Use: DOPPS Bailie GR et al, KI 2004

Analgesic Number of PatientsAnalgesic Number of Patients1997

N = 29882000

N = 2476N = 2988 N = 2476Any analgesicAny analgesic 30.2%30.2% 24.3%24.3%Any narcoticAny narcotic 18 0%18 0% 14 9%14 9%Any narcoticAny narcotic 18.0%18.0% 14.9%14.9%Any NSAIDAny NSAID 6.4%6.4% 2.3%2.3%AnyAny 11 1%11 1% 6 3%6 3%Any Any acetaminophenacetaminophen

11.1%11.1% 6.3%6.3%

¾ f ti t ti d t t i8

¾ of patients reporting moderate to severe pain were not prescribed analgesics

Barriers to Effective Pain M i ESRD Management in ESRD Davison Adv CKD 2005

Complicated pharmacokinetics and pharmacodynamicsComplicated pharmacokinetics and pharmacodynamicsp p p yp p p yUremic symptoms may mimic opioid toxicityUremic symptoms may mimic opioid toxicityTreatment algorithms for cancer may not apply to ESRD Treatment algorithms for cancer may not apply to ESRD ElderlyElderlyyyLimb preservationLimb preservationPain is often experienced in the context of multiple, complex Pain is often experienced in the context of multiple, complex symptoms and EOL issues symptoms and EOL issues

Interfere markedly with psychological, social and physical coping Interfere markedly with psychological, social and physical coping skillsskills

Lack of recognition of the problemLack of recognition of the problem Weisbord SD. CJASN 2007

Therefore not a clinical or research focus Therefore not a clinical or research focus –– a unique body of a unique body of knowledge is required to integrate nephrology & PCknowledge is required to integrate nephrology & PCImplementation of a standardized symptom screening & assessmentImplementation of a standardized symptom screening & assessment

9

Implementation of a standardized symptom screening & assessment Implementation of a standardized symptom screening & assessment process may improve provider recognition & treatment of symptomsprocess may improve provider recognition & treatment of symptoms

Symptom Screening - ESAS

10

11

Dialysis Dialysis Symptom Index

12

13

14

Pain AssessmentPain history - Appropriate investigations and diagnosis

OnsetLocationDurationI t itIntensitySeverity – impact on HRQLTemporal characteristicse po a c a ac e s csTriggering/relieving factorsType (nociceptive, neuropathic)Psychological symptomsTreatment (duration, dosage, side-effects)Goals & expectations of treatment

15

Goals & expectations of treatment

Etiology of Pain Percentage (%)Musculoskeletal 63 1Musculoskeletal 63.1

Osteoarthritis 19.4Musculoskeletal: Not yet diagnosed 18.4Musculoskeletal: Not yet diagnosed 18.4Osteoporosis (resulting in spinal fractures)

9.7

Inflammatory Arthritis 6.8Renal Osteodystrophy 4.9Discitis/Osteomyelitis 1.9

Related to Dialysis Procedure 13.6P i h l P l th 12 6Peripheral Polyneuropathy 12.6Peripheral Vascular Disease 9.7Other (including trauma PCKD 20 3

16

Other (including trauma, PCKD, malignancy, calciphylaxis)

20.3

Davison, AJKD 2003

Calciphylaxis (calcific uremic arteriolopathy)

17

18

Osteitis Fibrosa

Bone and joint pain on exertion in skeletal sites that are subject to biomechanical stress.Frequently associated with calcium phosphate deposition in arteries, joints, soft tissues, and the viscera; may be associated with proximal myopathy, ruptured tendons,Adynamic Bone disease: bone and

19

with proximal myopathy, ruptured tendons, pseudogout, and calciphylaxis. joint pain (at rest and with exertion),

fractures, skeletal deformities

Pain Assessment

Pain history, appropriate investigations and diagnosisType of pain (nociceptive, neuropathic, or both) directs nociceptive, neuropathic, or both) directs

l i t tl i t tanalgesic strategyanalgesic strategyDN4

20

21

Bouhassira D et al. Pain 2005

Pain AssessmentPain Assessment

Pain history, appropriate investigations and diagnosisType of pain (nociceptive, neuropathic, or both) directs analgesic strategyanalgesic strategy

Regular assessment and recording of pain severity, effects g g p y,on functioning and HRQL, and adverse effects of current management

This can be largely protocol drivenThis can be largely protocol drivenPossible role for advanced nurse practitioner

22Pharmacologic and non-pharmacologic interventions

Principles of Pain Management

‘by mouth’‘by the clock’by the clock‘by the ladder’‘f th i di id l’

_

‘for the individual’‘attention to detail’

23

OPIOID FOR MODERATE

Freedom from painFreedom from pain

OPIOID FOR MODERATE TO SEVERE PAIN

± NON-OPIOID± ADJUVANT

3± ADJUVANT

Pain persisting or increasingPain persisting or increasing

WEAK OPIOID FOR MILD TO MODERATE PAIN

± NON-OPIOIDADJUVANT

2± ADJUVANT

Pain persisting or increasingPain persisting or increasing

NON-OPIOID ± ADJUVANT1

24

± ADJUVANT

PAINPAIN

Efficacy of the WHO Analgesic Ladder to Treat Pain in ESRDLadder to Treat Pain in ESRD

89

107.7 7.5

45 HD patients

678

Initial Pain Score (0-10) Post Treatment Pain Score (0-10)

45

1 8

Score (0 10)

123

1.41.8

25

1Neuropathic Pain Nociceptive Pain

Type of Pain Barakzoy, JASN 2006

WHO Analgesic Ladder: Step 1WHO Analgesic Ladder: Step 1WHO Analgesic Ladder: Step 1WHO Analgesic Ladder: Step 1

A t i hAcetaminophen

Does not require dose adjustment in ESRD

Non-narcotic of choice for mild-moderate pain in CKD/ESRD

26

WHO Analgesic Ladder: Step 1WHO Analgesic Ladder: Step 1g pg pNSAIDS

Can be used in conjunction with acetaminophenj p

Increased risk of bleeding with CKD/ESRD

Potential cardiovascular risks associated with COX- 2 inhibitors

Renal side effects: hypertension, hyponatremia, loss of RRF, hyperkalemia

Topical agents can be used effectively

27

More appropriate for specific acute indications e.g. gout v. chronic use

WHO Analgesic Ladder: Step 2WHO Analgesic Ladder: Step 2g pg p

TramadolN i id ith i il id ff t t i idNon-opioids with similar side effects to opioids

Should not be given to patients on SSRIsShould not be given to patients on SSRIs

Prolongation of ½ life in renal failure (metabolized g (in liver with renal excretion of active metabolites).

May be epileptogenic in conditions with loweredMay be epileptogenic in conditions with lowered seizure threshold such as ESRD

28

Maximum dose is 50mg BID

OpioidsOpioidsActive metabolites are renally excretedActive metabolites are renally excreted

Side Effects

ConstipationConstipationNausea and vomitingNausea and vomitingDecreased appetiteDecreased appetiteP iP iPruritusPruritusHypotensionHypotensionCNS d i t d iCNS d i t d i

29

CNS and respiratory depressionCNS and respiratory depression

WHO Analgesic Ladder: Step 2g p

CodeineWeak opioidWeak opioidpp

Elimination ½ life is significantlyElimination ½ life is significantlyElimination ½ life is significantly Elimination ½ life is significantly increased in dialysis patientsincreased in dialysis patients

Reports of neurotoxicityReports of neurotoxicityReports of neurotoxicityReports of neurotoxicityToxicity is unpredictableToxicity is unpredictable

30Should not be usedShould not be used

WHO Analgesic Ladder: Step 2Dextropropoxyphene

i iWeak opioid

Usually prescribed in combination with acetaminophenUsually prescribed in combination with acetaminophen

major active metabolite is norpropoxyphene:accumulates in CKDassociated with toxicity

Dextropropoxyphene is not recommended for use in patients with severe CKD

31It has been withdrawn from use in the UK.

WHO Analgesic Ladder: Step 3WHO Analgesic Ladder: Step 3

Oxycodone

Elimination significantly decreased in ESRDFibrillary GNGrowing popularity as a drug of abuse and is now considered one of the most desirable of prescription drugsof prescription drugs

Should be used with caution in ESRD

32

Should be used with caution in ESRD

WHO Analgesic Ladder: Step 3

Morphine

Active metabolite M6G is renally excreted and accumulates in ESRD: increased side effects and toxicityto c ty

No data regarding dose adjustments for sustained-release preparations of morphine

Should not be used for chronic pain management33

Should not be used for chronic pain management

WHO Analgesic Ladder: Step 3Hydromorphone

5-7 times more potent than morphine (when administered orally), shorter duration of action

Case reports of adverse effects

Published and clinical experience indicates that it may be administered safely in ESRD

May be particularly useful in patients who have intolerable side effects from other narcotics

34

May cause less pruritus, sedation, & nausea

Lee MA, Palliat Med 2001

Non-Compartmental Pharmacokinetics for Hydromorphone and H3G (n=12)

t1/2 AUC(Tau)

for Hydromorphone and H3G (n=12)

Phase (h) (ng.h/mL) RHydromorphone

Dialysis 3.2 ± 2.4 41.6 ± 20.3 1.8 ± 0.8

M l i D 5 9 4 4 33 9 27 3 2 7 1 6Multi-Dose 5.9 ± 4.4 33.9 ± 27.3 2.7 ± 1.6Hydromorphone-3-Glucuronide

Dialysis 3.3 ± 2.1 3243.9 ± 2768.0 1.8 ± 0.7

35

Multi-Dose 33.3 ± 41.8 4229.9 ± 2975.4 12.5 ±15.1

Davison, JOM 2008

Non Compartmental Non-Compartmental Pharmacodynamics (n=12)

Maximum Time to Max % time with

PhaseAnalgesia(% ± SD

Analgesia(hours ± SD)

analgesia(% ± SD)

Dialysis -68.8 ± 37.5 1.8 ( 0.5 - 4.0) -66.3 ± 40.1Multi-dose -65.5 ± 43.3 3.0 (0.5 - 4.0) -40.2 ± 21.8

36Davison, JOM 2008

WHO Analgesic Ladder: Step 3WHO Analgesic Ladder Step 3Methadone

Opioid commonly used for treatment of severe pain orOpioid commonly used for treatment of severe pain orOpioid commonly used for treatment of severe pain or Opioid commonly used for treatment of severe pain or withdrawal in opioid addictswithdrawal in opioid addicts

High oral bioavailability and a long ½ lifeHigh oral bioavailability and a long ½ lifeHigh oral bioavailability and a long ½ lifeHigh oral bioavailability and a long ½ life

Essentially no PK data in ESRD; single report Essentially no PK data in ESRD; single report ti l l l i ESRDti l l l i ESRDsuggesting normal levels in ESRDsuggesting normal levels in ESRD

Excreted mainly in the feces, with metabolism into Excreted mainly in the feces, with metabolism into pharmacologically inactive metabolites primarily in pharmacologically inactive metabolites primarily in the liver althoughthe liver although 20% is excreted unchanged in20% is excreted unchanged inthe liver, although the liver, although ∼∼20% is excreted unchanged in 20% is excreted unchanged in the urinethe urine

A d t l i t l ti l d f tA d t l i t l ti l d f t37

Anecdotal experience suggests a relatively good safety Anecdotal experience suggests a relatively good safety profile in ESRD if monitored carefully.profile in ESRD if monitored carefully.

WHO Analgesic Ladder: Step 3WHO Analgesic Ladder Step 3

Fentanyl (transdermal formulation)When patients are on a stable narcotic doseWhen patients are on a stable narcotic dose

Essentially no PK data of transdermal Essentially no PK data of transdermal yyformulation or effect of dialysis on levels (one formulation or effect of dialysis on levels (one report stated poor removal)report stated poor removal)

Toxicity has been reported but anecdotal Toxicity has been reported but anecdotal

38

experience suggests a reasonable safety profile experience suggests a reasonable safety profile in ESRD if monitored carefullyin ESRD if monitored carefully

WHO Analgesic Ladder: Step 3BuprenorphineSemisynthetic opioid with a long duration of action

30 - 60 x as potent as oral morphine when given SLMetabolized by the liver, little unchanged drug in the urineThe two major metabolites excreted in the urine

Buprenorphine-3-glucuronide (B3G): inactive Norbuprenorphine: is a less potent analgesic

Administered sublingually or via a transdermal patch. Given these properties and the minimal changes in kinetics in renal failure, it may be a potentially useful y yanalgesic for use in CKD

Might be difficult to antagonize with opioid antagonists

39

Care should be taken when used with benzodiazepines

WHO Analgesic Ladder: Step 3WHO Analgesic Ladder Step 3

Pethidine (Meperidine)

Active metabolite norpethidine accumulates in Active metabolite norpethidine accumulates in patients with renal impairment patients with renal impairment

neuroexcitatory effects and risk of neuroexcitatory effects and risk of convulsionsconvulsions

DO NOT use in CKDuse in CKD

40

Adjuvants: Neuropathic PainAdjuvants: Neuropathic PainAntidepressants p

Tricyclic antidepressants: synergistic with opioidsTricyclic antidepressants: synergistic with opioids

Anticholinergic effects: dry mouth; sedation, Anticholinergic effects: dry mouth; sedation, weight gain; caution in patients with cardiac weight gain; caution in patients with cardiac conduction abnormalitiesconduction abnormalitiesconduction abnormalitiesconduction abnormalities

minor adverse events occur in about oneminor adverse events occur in about one--third of third of patientspatientsDespiramine may have less side effects than Despiramine may have less side effects than amitriptylineamitriptylineSelective serotonin reSelective serotonin re--uptake inhibitors (SSRIs) uptake inhibitors (SSRIs)

41

p ( )p ( )appear to be less effective as adjuvant analgesics but appear to be less effective as adjuvant analgesics but have fewer adverse reactionshave fewer adverse reactions

AdjuvantsAnticonvulsants

Gabapentin: effective for neuropathic pain and restless legsSuppresses depolarization of afferent pain neurons by inhibiting calcium influxAccumulation with toxicity in ESRD – Max dose 300mg/dayg yPregabalin: identical mechanism of action as gabapentin for the tx of neuropathic pain.

Carbamazepine: neuropathic painDoes not require dose adjustment in ESRD

42

q jStart @ 200mg BID

43http://www.kidneyeol.org/painbrochure9.09.pdf.

44

45

46

47

48

49

50

Historical Use of Marijuana (Cannabis) Oldest known Neolithic Oldest known Neolithic

culture in China culture in China

An 1848 commentary in the An 1848 commentary in the British Pharmacopoeia British Pharmacopoeia outlined psychotropic, outlined psychotropic, antispasmodic and analgesicantispasmodic and analgesicantispasmodic and analgesic antispasmodic and analgesic effects of Cannabiseffects of Cannabis

51

Marijuana (Cannabis)Marijuana (Cannabis)Marijuana is a crude drug obtained from the Marijuana is a crude drug obtained from the C bi tiC bi ti l tl tCannabis sativa Cannabis sativa plantplant

Consists of approximately 460 activeConsists of approximately 460 activeConsists of approximately 460 active Consists of approximately 460 active componentscomponents

> 60 of these have the 21> 60 of these have the 21--carbon structure of carbon structure of typical cannabinoidstypical cannabinoids

∆9∆9 THCTHC∆9∆9--THCTHC11

Analgesic, muscle relaxant, antiemetic, Analgesic, muscle relaxant, antiemetic, appetite stimulant, psychoactive effectsappetite stimulant, psychoactive effects

52

pp , p ypp , p y

Cannabinoid ReceptorsCannabinoid Receptors

CB1 receptorCB1 receptorFound in the brain, spinal cord and peripheral nervous system.nervous system.

Also present in various peripheral tissues such as heart and vasculature

CB2 receptorFound on immune cells in peripheral tissues

More recently, found in the CNS

53(Davison JS et.al. Science 2006)

Endogenous CannabinoidsEndogenous CannabinoidsAnandamide (AEA): 1992 “internal bliss”( )

endogenous ligand of the CB1 receptor resembles THC structurally: similar

tiactions levels in the brain ~ to neurotransmitters such as dopamine and serotoninsuch as dopamine and serotonin .

2-arachidonyl glycerol (2-AG):y g y ( )Brain tissue concentrations ~ 200-fold higher than AEA

20 hi h th GABA54

~ 20 x higher than GABA

Putative Mechanism of Action of Endocannabinoids

URB597

Endocannabinoids

VDM11

55Christie and Vaughan, 2001

Cannabinoid Drugs Approved by FDA and Health Canada

Dronabinol: synthetic THC (Marinol)Anorexia/wasting in patients with HIVEmesis due to cancer chemotherapy

Nabilone: synthetic cannabinoid similar to THC (Cesamet)

THC:CBD Cannabis extract (Sativex)Adj ti t f thi i (MS)

56

Adjunctive tx for neuropathic pain (MS)Adjunctive tx for cancer pain

Cannabidiol (CBD)Cannabidiol (CBD)

Anti-inflammatoryAntioxidantAnti-seizureAnxiolytic o y cAntipsychotic properties.

Inflammatory and neuropathic pain

57

Cannabinoids v. OpioidsOpioids Cannabinoids

Nausea & Vomiting Increases DecreasesNausea & Vomiting Increases DecreasesAppetite Decreases IncreasesAgitation Increases DecreasesAgitation Increases DecreasesSleep Disturbs ImprovesPruritus Increases DecreasesPruritus Increases DecreasesHypotension ++ +Constipation ++ +/-Constipation ++ +/-Sense of well-being +/- IncreasesPsychosis/abuse + ++

58

Psychosis/abuse + ++

ConclusionsConclusionsChronic pain is common in ESRD and is ptypically severe

Chronic pain has a substantial negative impact on HRQL

Pain assessment tools for ESRD arePain assessment tools for ESRD are available (mESAS)

59Pain algorithms for ESRD are available

Questions?Q

60

For questions about pain management,e-mail Samantha Dorr

at sdorr@nw5 esrd netat sdorr@nw5.esrd.netand for information

about pain management resourcesabout pain management resources visit www.kidneyeol.org/

and click on Professional Resources

Contact the Kidney End of Life Coalition at

61

ykidneyeol@nw5.esrd.net

To Register for the Webinar To Register for the Webinar Conferences on March 24 and April 28April 28

ContactSamantha Dorr

Mid-Atlantic Renal CoalitionMid-Atlantic Renal Coalition804.794.3757

d @ 5 d62

sdorr@nw5.esrd.net