Pain and Symptom Management in End Stage Renal Disease

1
Pain and Symptom Management in End Stage Renal
Disease
CARING THROUGH THE END Palliative Care Along
the Continuum of CKD

• Sara Davison
• MD, MHSc (Bioethics)John Dosseter Health Ethics
  Centre, University of Alberta

2
Objectives

• Discuss the magnitude and scope of chronic pain
  and other symptoms in the ESRD population
• Prevalence, severity, etiology
• Discuss the impact of chronic pain in ESRD
  patients
• Global HRQOL
• Psychological distress, insomnia, functional
  status
• Discuss the potential barriers to adequate pain
  and symptom management
• Outline potential strategies to enhance pain and
  symptom management

3
ESRD Population

• The elderly represent a steadily increasing
  proportion of new patients
• 50 patients starting dialysis gt 65 years old
• Significant co-morbidity

4

• As the dialysis population ages and experiences
  multiple co-morbidities, it is increasingly
  important and challenging to maintain a
  reasonable HRQOL.
• Symptoms, especially pain, are important
  determinants of HRQOL
• Kimmel PL, AJKD 2003
• Effective pain management is an integral
  component of quality patient care

5
Burden of Symptoms in HD Patients
42.5
26.8
28.8
51.1
63.8
Davison, 2002
6
Most Common Symptoms Reported by Symptomatic HD
Patients
with Symptoms
Symptoms
Kimmel PL, AJKD 2003
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Pain in Hemodialysis Patients

• Although dialysis sustains life, underlying
  systemic disease persist
• Ischemic limbs, peripheral neuropathies
• Numerous painful syndromes unique to chronic
  kidney disease
• Calciphylaxis, renal bone disease
• Prospective cohort study of 205 HD patients (UAH)
• 103 (50) reported a current problem with pain
• 55 of these patients reported their pain as
  severe
• Causes of pain were diverse
• 18 had multiple causes for their pain

Davison, AJKD 2003
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Etiology of Pain
Davison, AJKD 2003
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Severity of Pain Brief Pain Inventory Scores
82.5
58.3
Davison, AJKD 2003
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Pain Management
11
Point Prevalence of Analgesic Use DOPPS
¾ of patients reporting moderate to severe pain
were not prescribed analgesics
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Impact of Pain on HRQOL
Total Score
Scales
Kimmel PL, AJKD 2003
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The Impact of Pain

• Symptoms, especially pain, are important
  determinants of HRQOL of patients with ESRD
• Symptoms may be more important than objective
  clinical assessments in determining HRQOL for
  these patients
• Pain is a multidimensional phenomenon with
  physical, psychological and social components
• Failure to treat pain adequately could be
  expected to lead to disruption in many aspects of
  life such as functional status, mood, sleep, and
  global HRQOL

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Brief Pain Inventory Interference Items
55.3
62.1
Davison, 2004
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The Impact of Pain Depression and Insomnia

• Prevalence of Depression (BDI)
• 18 in patients with no-mild pain v. 34 in
  patients with moderate-severe pain (OR 2.31,
  p0.01)
• Pain was the only significant predictor in
  multivariate analyses
• Prevalence of insomnia
• 53 in patients with no-mild pain v. 75 in
  patients with moderate-severe pain (OR 2.32,
  p0.02)
• Pain and younger age were the only significant
  predictors

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Impact of Pain on QOL, Depression and Sleep
Scores
Scales
Davison, 2004
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The Impact of Pain

• Pain contributed significantly to psychological
  distress anxiety, irritability, ability to cope
  with stress in addition to depression
• Pain had a significant adverse effect on
  recreational activities, relationships, physical
  functioning, emotional functioning (P lt 0.001),
  and sexual functioning (P 0.034) in patients with
  pain compared to those without pain
• Pain had a significant impact on all measured
  activities of daily living

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Spirituality

• The ways in which chronic pain patients cope or
  adjust to their illness is likely central to
  understanding the great variability across
  patients in their ability to function with their
  pain.
• Issues of spirituality and social support are
  likely very important for many patients in this
  equation although were not studied here.
• The concept of Total Pain (Cicely Saunders)
  emphasizes the contribution of psychological,
  spiritual and social factors to the experience of
  pain.
• These factors need to be taken into consideration
  when caring for our patients

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Consideration of Withdrawal from Dialysis

• Patients with more likely to have considered or
  be considering withdrawal of dialysis if they
  suffered from moderate-severe pain
• 59 patients with pain were considering stopping
  dialysis
• 46 of patients with moderate-severe pain
• 17 of patients with no-mild pain (P lt 0.001)
• Pain was NOT the most common reason for
  considering withdrawal of dialysis

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Reasons for Consideration of Withdrawal
Davison, 2004
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End-of-Life Pain Management

• Pain control is an essential component of EOL
  care, especially in patients with ESRD
• Adequate pain control is central to a patients
  perception of a high quality death
• Pain is present in 42 of patients discontinuing
  dialysis during the last 24 hrs of life (Cohen
  LM, Arch Int Med, 1995)
• Patients with cognitive impairment may have
  difficulty communicating pain

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Interim Conclusions

• Pain and other symptoms are common, often severe,
  and are suboptimally treated
• Pain is associated with depression, anxiety,
  insomnia, decreased functional status and
  decreased global HRQOL
• Need to focus more on pain and symptom management
  if we are to improve HRQOL
• Effective pain management will likely require
  attention to issues relating to psychological
  status, sleep, functional ability, spirituality
  and social support

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Barriers to Effective Pain Management

• Patient reluctance to report pain
• Lack of staff time and training in the basic
  principles of pain management

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Barriers to Effective Pain Management

• ESRD Specific
• Lack of recognition of the problem therefore not
  a clinical or research focus
• Lack of education, training and dedicated
  resources
• Complicated pharmacokinetics and pharmacodynamics
• Uremic symptoms may mimic opioid toxicity
• Treatment algorithms for cancer patients may not
  apply to ESRD patients
• Objective data on appropriate and effective
  management strategies for ESRD patients are still
  required

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Barriers to Effective Pain Management

• Limb preservation, defer high risk surgery
• Pain is often experienced in the context of
  multiple, complex symptoms and EOL issues which
  may interfere markedly with psychological, social
  and physical coping skills

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Barriers to Effective Pain Management

• ELDERLY
• More sensitive to the effects of many analgesics
• More susceptible to adverse effects
• Polypharmacy
• High number of comorbid conditions
• Pharmacokinetic and pharmacodynamic changes occur
  with aging
• Analgesics associated with falls in the elderly

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Pain Management

• Pharmacological and non-pharmacological
  interventions!
• Appropriate investigations and diagnosis re
  cause
• An understanding of the type of pain is useful in
  tailoring analgesic therapy
• Regular assessment and recording of pain
  severity, effects on functioning and HRQOL etc,
  and adverse effects of current management
• This can be largely protocol driven
• Possible role for advanced nurse practionner

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Freedom from pain
OPIOID FOR MODERATE TO SEVERE PAIN
NON-OPIOID ADJUVANT
3
Pain persisting or increasing
WEAK OPIOID FOR MILD TO MODERATE PAIN
NON-OPIOID ADJUVANT
2
Pain persisting or increasing
NON-OPIOID ADJUVANT
1
PAIN
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Non-Narcotic Analgesics

• Acetaminophen
• Does not require dose adjustment in ESRD
• Non-narcotic of choice for mild-moderate pain in
  CKD/ESRD
• Numerous OTC meds contain acetaminophen
  hepatotoxicity
• Potential cause of CKD/loss of GFR
• NSAIDS
• Can be used in conjunction with acetaminophen
• Increased risk of bleeding with CKD/ESRD
• Potential cardiovascular risks associated with
  COX-2 inhibitors
• Renal side effects hypertension, hyponatremia,
  loss of RRF, hyperkalemia (CKD)

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Narcotics

• Can be used in combination with non-narcotics or
  alone for moderate-severe pain
• Active metabolites are renally excreted
• Side Effects
• Constipation
• Nausea and vomiting
• Pruritus
• Hypotension
• CNS and respiratory depression

ESRD
Co-Morbidity
Prevention
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• Codeine
• Elimination ½ life is significantly increased in
  dialysis patients
• Reports of neurotoxicity
• Should be used with caution but tolerated
  relatively well if carefully monitored
• Oxycodone
• Elimination significantly increased in ESRD
• Fibrillary GN
• Growing popularity as a drug of abuse and is now
  considered one of the most desirable of
  prescription drugs
• Should be used with caution but tolerated
  relatively well if carefully monitored

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• Morphine
• Active metabolite M6G is renally excreted and
  accumulates in ESRD
• Increased side effects
• No data regarding dose adjustments for
  sustained-release preparations of morphine
• Hydromorphone
• 10 times more potent than morphine, shorter
  duration of action
• Case reports of adverse effects, essentially no
  PK data
• 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

Lee MA, Palliat Med 2001
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• Methadone
• Opioid commonly used for treatment of severe pain
  or withdrawal in narcotic addicts
• High oral bioavailability and a long ½ life
• Essentially no PK data in ESRD single report
  suggesting normal levels in ESRD
• Anecdotal experience suggests a relatively good
  safety profile
• Fentanyl
• Transdermal formulation
• When patients are on a stable narcotic dose
• Essentially no PK data of transdermal formulation
  or effect of dialysis on levels (one report
  stated poor removal)
• Toxicity has been reported but anecdotal
  experience suggests a reasonable safety profile
  if monitored carefully

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Propoxyphene

• Related to Methadone
• Active metabolite, norpropoxyphene is renally
  excreted
• Local anesthetic properties similar to quinidine
• Predispose patients to risk of cardiac conduction
  abnormalities
• Neither proppoxyphene or norpropoxyphene are
  removed with dialysis
• Cardiotoxicity cannot be reversed by naloxone
• Use with extreme caution
• Never use

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Adjuvants

• Anticonvulsants
• Gabapentin effective for neuropathic pain and
  restless legs
• Accumulation with toxicity in ESRD Max dose
  300mg/day
• Carbamazepine neuropathic pain
• Does not require dose adjustment in ESRD
• Less adverse effects start _at_ 200mg BID
• Antidepressants
• Tricyclic antidepressants neuropathic pain,
  synergistic with opioids
• Anticholinergic effects dry mouth sedation,
  weight gain caution in patients with cardiac
  conduction abnormalities
• Despiramine may have less side effects than
  amitriptyline

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Narcotic Drug Abuse Myths and Fears

• Tolerance the need for increasing doses of a
  drug in order to achieve the same pharmacological
  action
• Unwanted effects (nausea) desired pain relief
• Dose escalation may be required
• Incomplete cross tolerance to unwanted effects is
  the basis for switching from one opioid to
  another aim to maintain analgesia while reducing
  adverse effects
• Physical dependence characterized by withdrawal
  symptoms if treatment is stopped abruptly or an
  antagonist is given.
• Does not prevent dose reduction if pain is
  relieved
• Does not prevent the effective use of opioids

• Tolerance and physical dependence are expected
  consequences and should NOT lead to a reduction
  of therapy

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Narcotic Drug Abuse Myths and Fears

• Addiction (psychological dependence) a
  behavioral pattern characterized by craving for
  the drug and an overwhelming preoccupation with
  obtaining it
• Extensive clinical experience has shown that it
  occurs rarely in patients receiving opioids for
  pain relief!

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Dosing of Analgesics

• by mouth
• When ever possible, drugs should be given orally
  (transdermal)
• by the clock
• Drugs should be given regularly PRN
  breakthrough
• by the ladder
• Use the sequence of the WHO analgesic ladder
• for the individual
• There is no standard (ceiling) dose for strong
  opioids. The right dose is the dose that
  relieves pain without unacceptable side effects
• Every patient is different
• attention to detail
• Pain changes over time assessment and
  reassessment
• Actively prevent adverse effects

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Dosing

• Ineffective medications should be tapered and
  discontinued and REPLACED with another agent
• Clear communication ensure patients understand
  the regimen, the goals of therapy, adverse
  effects and what to do if control inadequate.
• Dosing should be as simple as possible

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Conclusions

• ESRD patients have a high burden of symptoms
  throughout their illness (not just at the EOL)
• Pain in ESRD is common, often severe and poorly
  managed
• Symptoms, especially pain, have a tremendous
  negative impact on all aspects of HRQOL
• Effective pain and symptom management is an
  integral component of quality ESRD patient care
• For management of pain to be effective, issues
  relating to psychological status, sleep,
  functional ability and HRQOL must be addressed
  along with the pain

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Conclusions

• Multidisciplinary nephrology teams must focus on
  pain and symptom management (clinical and
  research)
• Enhanced training for residents, CME for staff,
  training for nursing staff and allied HCP
• Culture of the dialysis unit must change to
  support this new focus on pain and symptom
  management
• Infrastructure must reflect these new priorities
  dedicated resources

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Conclusions

• Concerns about analgesics (especially opioids)
  has lead to a more cautious use of analgesics in
  ESRD patients and has resulted in potential under
  prescription
• Must optimize BOTH pharmacological and
  non-pharmacological interventions for effective
  pain management