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Objectives

The following module was designed to supplement medical students’ learning in the clinic. Please take the time to read through each section by clicking the headings below. Information on prevalence, classification, syndromes, assessment of cancer pain along with principles of pain management is provided.By the end of the tutorial, the following objectives should be addressed:

  1. Describe the prevalence of pain in cancer patient
  2. Describe a general approach to pain management
  3. Classify and be able to characterize pain
  4. Describe common pain syndromes in patients with cancer
  5. Describe an approach to assessing pain
  6. Recognize the importance of patient education in pain management
  7. Utilize the WHO pain ladder to choose analgesic medication appropriate to pain level
  8. Understand the use of non-opioid analgesics in cancer pain control
  9. Understand the use of pharmacology and metabolism of opioid analgesics
  10. Describe factors to consider when selecting an opioid for pain management
  11. Convert between opioids while maintaining analgesia
  12. Understand the differences between immediate-release opioid preparations, extended-release opioid preparations, and breakthrough opioid preparation.
  13. Understand the use of adjuvant analgesic agents
  14. Acknowledge common adverse effects of analgesic agents
  15. Understand the different routes of administration for opioids
  16. Describe precautions during chronic opioid use
  17. Understand principle methods of interventional and other non-pharmacological approaches to pain management

Prevalence

Pain management is an important part of oncology care. Pain is a significant player in patient morbidity. Most patients with advanced cancer and up to 60% of patients with any stage of the disease experience significant pain. The World Health Organization estimates that 25% of all cancer patients die with unrelieved pain [1].

Approach

Below is an easy to follow general approach when considering cancer pain assessment and management [1].

The ABCDE system, developed by the Agency for Health Care Policy and Research, is another good tool [2].

Patient Education

Studies suggest that patient education can be highly effective in managing pain. For a cancer patient already taking opioid analgesics, education may be more effective than the addition of co-analgesic therapies such as gabapentin and paracetamol (reduction of about one point on a 0-10 scale) [3].

  • Patient education should occur in an appropriate setting with sufficient time allotted to discuss any patient concerns. It should be conducted when patient and preferably also the care giving is present.
  • Specific areas to address include dispelling misconceptions about pain and pain management, promoting user involvement through the provision of education about pain and its management, and the use of appropriate teaching materials especially when literacy is an issue [3].

Assessment

Classification

Physical pain can be largely classified as nociceptive or neuropathic. It is helpful to find out what kind of pain the patient is experiencing as it will guide the selection of medication and or procedures.

It is also important to realize patients’ total pain may have more than one cause or presentation.

TABLE 1: CLASSIFICATION OF PAIN [1], [2], [3]

Common Cancer Pain Syndromes

Common pain syndromes in patients with cancer: There are three major categories of pain syndromes [4].

1. Direct tumor involvement:

  • Tumor invasion of bone (e.g. metastases to the base of skull, jugular foramen syndrome, clivus metastases, sphenoid sinus metastases, metastases to vertebral bodies), tumor infiltration of nerve, plexus, meninges and spinal cord

2. Pain associated with cancer therapy:

  • Post surgical pain syndromes: post mastectomy pain syndrome, post thoractomy pain syndrome, post-radical neck syndromes, phantom limb and stump pain
  • Post chemotherapy pain syndromes: peripheral neuropathy, steroid pseudorheumatism, aseptic necrosis of bone, postherpetic neuralgia
  • Post radiation pain syndromes: radiation fibrosis of the brachial plexus, radiation myelopathy

3. Pain not related to cancer or cancer therapy: 

  • ‍Accurate diagnosis in this group of patients clearly alters both therapy and prognosis

The table below shows the percentages of cancer pain accounted for by each of the three etiologies.

TABLE 2: BREAKDOWN OF CANCER PAIN SYNDROMES

Assessment

1. History 

When managing pain, it is important to elicit a detailed and focused history. It is useful to inquire for the following [1], [5]:  (P,Q,R,S,T, AAA)

  • Precipitating factors
  • Quality: listen for typical features for nociceptive and neuropathic pain
  • Radiation
  • Severity: use pain scale out of 10
  • Timing: duration and if sporadic or continuous
  • Aggravating and alleviating factors: inquire response to past and current analgesic therapy and related adverse effects
  • Associated symptoms
  • Activities of daily living, any fear they have about analgesics
  • Other aspects that may contribute to total pain such as psychologic, social, and spiritual factors

2. Physical, psychological, laboratory and imaging assessments and tests

These coupled with a detailed pain history can be useful in identifying relevant pathophysiology underlying the pain. Determine whether the pain is directly or indirectly related to the cancer, associated with therapeutic interventions or unrelated. This may help elucidate the pathophysiology of the pain and direct therapy [1].

3. Pain assessment tools

Pain is a uniquely subjective experience. As practitioners, we need to trust our patients’ ratings of their pain. Verbal analogue scale is a simple and widely used tool. Ask the patient to quantify their pain on a scale of 0 to 10, 0 being no pain, 10 being the worst pain imaginable. It is sometimes helpful to conceptualize the numeric rating scale (5):

  • 0 = No Pain
  • 1-3 = Mild Pain (nagging, annoying, interfering little with ADLs)
  • 4–6 = Moderate Pain (interferes significantly with ADLs)
  • 7-10 = Severe Pain (disabling; unable to perform ADLs)

Analgesic Medication

Analgesic drugs remain key in managing cancer pain. A general principle is to match the severity of pain to the strength of the analgesic i.e. strong analgesics for severe pain [1].

The WHO has a 3-step model to guide analgesic choice based on this principle. It is not necessary to traverse each step sequentially, a patient with severe pain may need to have step 3 opioids right away.

WHO-pain-ladder-corrected1
FIGURE 1: WHO PAIN LADDER

Non-opioid Analgesics

Non-opioid analgesics – Acetaminophen and NSAIDS are effective WHO pain ladder step 1 analgesics and coanalgesics. They are usually used in full doses but have a ceiling effect to their analgesia and tolerable adverse effects.

NSAIDS:

NSAIDs work by inhibiting cyclo-oxygenase which is an enzyme that converts arachidonic acid to prostaglandins. NSAIDS have significant adverse effects but are variable between classes which may be attributed to their relative COX-2 selectivity. Adverse effects include gastropathy, renal failure, and inhibition of platelet aggregation. Gastric cytoprotection with misoprostol may be needed in patients with significant risk factors such as history of gastric ulcers or bleeding, current nausea/vomiting, or cachexia in the elderly. To minimize risk of renal failure, ensure adequate hydration and good urine output in all patients on NSAIDS. COX-2 selective inhibitors have less of these toxicities and may be indicated in high-risk patients.

Acetaminophen:

Acetaminophen’s site and mechanism of action are not known but is presumed to have a central mechanism. Chronic doses > 4.0 g/24 h or acute doses > 6.0 g/24 h are not recommended as they may cause hepatotoxicity. Hepatic disease or heavy alcohol use increases the risk further.

*For recommended dosages check in an updated CPS text.

Opioid Analgesics

Opioid analgesics are the first-line therapy for moderate to severe pain in nociceptive, neuropathic, and mixed-pain syndromes. However, for severe neuropathic pain, opioids alone are often insufficient [1] and must be combined with adjuvant analgesics (see later section).

Pharmacology and Metabolism:

It is important to understand the pharmacology and metabolism of opioid analgesics to prescribe them appropriately and safely.

TABLE 1: PHARMACOLOGY AND METABOLISM OF OPIOID ANALGESICS

Special Considerations:

When dehydration or renal failure impairs renal clearance, opioid doses should generally be lower than normal, with increased intervals between doses to avoid excessive accumulation of active drug.

If urine output is minimal (oliguria) or none (anuria), stop routine dosing and administer morphine only as needed. This is particularly important when patients are dying.

Opioid metabolism is not usually affected by extensive liver metastases. However, if hepatic function becomes severely impaired by hepatitis or there is clinical liver failure, increase the dosing interval or decrease the dose [1].

Opioid Selection:

There is no strong evidence that support the superiority of one opioid over another as comparative trials are very difficult to perform. However, considerations that guide the choice of opioids include combination formulation opioid, adverse effect, and available route of administration which will be discussed later in this module.

WHO pain ladder Step 2 opioid analgesics include tramadol and combination formulations of acetaminophen or aspirin with opioids. Commonly available opioids available as combination medications include codeine, oxycodone, and hydrocodone. The opioids combined with acetaminophen or aspirin are limited in dosage due to their nonopioid components. For example, combinations containing acetaminophen 500 mg would be limited to ≤8 tablets per day due to the risk of hepatotoxicity.

WHO pain ladder Step 3 opioids do not share this dosing limitation and in fact have no theoretical ceiling for efficacy. They are only limited by adverse effects. This group of opioids includes morphine, oxycodone, hydromorphone, levorphanol, fentanyl, and methadone [1].

Switching Between Opioids:

Sometimes, it becomes necessary to switch patients from one opioid to another. Because cross-tolerance among the opioid analgesics is incomplete, switching from one opioid drug to another is sometimes done by using half the equianalgesic dose and then titrating the patient up to effective pain control [3].

*For information on starting dosages and titrating dosages see an updated CPS text.

TABLE 2: OPIOID CONVERSION [2]

Opioid Dosing Preparations:

TABLE 3: OPIOID PREPARATIONS [1]

Route of Administration:

In general, the oral route is the least invasive and more convenient route of administration. However, selected patients may benefit from other routes of administration if oral intake is not possible (vomiting, dysphagia, obstruction) or causes uncontrollable adverse effects (nausea, drowsiness, confusion). For example, transdermal fentanyl or buprenorphine can be useful in patients with swallowing difficulties.

Alternative routes of administration include enteral, transmucosal, rectal, transdermal, parenteral, intravenous, and intraspinal [1].

Common Adverse Effects:

There is no clear evidence that adverse effects differ between opioid. However, anecdotal evidence suggests patient related individual differences in tolerating opioids. Hence it may be worthwhile to ask if a patient is known to be sensitive to a particular adverse effect and monitor patients for any new unexpected adverse effects. When a patient experiences an uncontrollable side effect or toxicity, it may be appropriate to switch them to different opioid [4].

Tolerance to analgesia is not a major clinical problem and can usually be managed by changing the dose or substituting another agent [5].

Aberrant drug-taking is not likely to occur in patients without a history of substance abuse [5].

TABLE 4: COMMON ADVERSE EFFECTS AND MANAGEMENT
TABLE 5: OTHER ADVERSE EFFECTS

Precautions for Chronic Opioid Therapy [5]:

  • Normeperidine is a toxic metabolite of meperidine that accumulates with repetitive dosing; thus, use of meperidine for chronic pain should be limited. Propoxyphene is also relatively contraindicated due to accumulation of norporpoxyphene.
  • Physical withdrawal symptoms can be avoided by tapering doses
  • A change in mental status should not be attributed to opioid therapy until medical and neurologic factors have been fully evaluated
  • Mixed agonist-antagonist drugs and partial agonist drugs are not recommended for cancer pain.

Adjuvant Therapy

Neuropathic pain may be less responsive to standard analgesics alone and adjuvant medications are often required to decrease pain. Major classes of adjuvant medication include steroids, antidepressants, anxiolytics, phenothiazines, anticonvulsants, amphetamines, and topical local anesthetics. They are helpful for particular indications and may be administered various routes.

The table below shows the therapeutic effects, indications, and adverse effects of various adjuvant medications.

*For dosage information refer to an updated CPS text.

TABLE 1: ADJUVANT MEDICATION

Non-Pharmacological Therapy

Besides pharmacologically, cancer pain can also be managed with various other approaches which will be briefly discussed below. Although the discussion here is brief, these may be very beneficial to some patients when used appropriately.

TABLE 1: OTHER MANAGEMENT OPTIONS

Summary

1.  Describe the prevalence of pain in cancer patients

Pain is a significant player in patient morbidity. Most patients with advanced cancer and up to 60% of patients with any stage of the disease experience significant pain. The World Health Organization estimates that 25% of all cancer patients die with unrelieved pain.

2.  Describe a general approach to pain management

  • Identify cancer pain and provide support
  • Treat underlying disease if possible
  • Qualify cancer pain
  • Start pharmacological therapy using WHO pain ladder as guide
  • Choose adjuvant appropriate to quality of pain as needed
  • Switch opioid if adverse reaction or if previous opioid is minimally effective

3.  Recognize the importance of patient education in pain management

Studies suggest that patient education can be highly effective in managing pain. For a cancer patient already taking opioid analgesics, education may be more effective than the addition of coanalgesic therapies such as gabapentin and paracetamol.

4.  Classify and be able to characterize pain

5.  Describe common pain syndromes in patients with cancer

6.  Describe an approach to assessing pain

  • History: PQRST AAA
  • Physical, psychological, lab, imaging assessments and tests: elucidate pathophysiology of pain
  • Pain assessment tools: Verbal and visual analogue pain scales 0-10

7.  Utilize the WHO pain ladder to choose analgesic medication appropriate to pain level

8.  Understand the use of non-opioid analgesics in cancer pain control

Acetaminophen and NSAIDS are effective WHO pain ladder step 1 analgesics and coanalgesics. They are usually used in full doses but have a ceiling effect to their analgesia and tolerable adverse effects.

NSAIDS adverse effects include gastropathy, renal failure, and inhibition of platelet aggregation.

Acetaminophen chronic doses > 4.0 g/24 h or acute doses > 6.0 g/24 h are not recommended as they may cause hepatotoxicity.

9.  Understand the use of pharmacology and metabolism of opioid analgesics

10.  Describe factors to consider when selecting an opioid for pain management

There is no strong evidence that support the superiority of one opioid over another as comparative trials are very difficult to perform. However, considerations that guide the choice of opioids include combination formulation opioid, adverse effect, and available route of administration which will be discussed later in this module.

11. Convert between opioids while maintaining analgesia

Table of Opioids

12. Understand the differences between immediate-release opioid preparations, extended-release opioid preparations, and breakthrough opioid preparation.

13. Understand the different routes of administration for opioids

In general, the oral route is the least invasive and more convenient route of administration. However, selected patients may benefit from other routes of administration if oral intake is not possible (vomiting, dysphagia, obstruction) or causes uncontrollable adverse effects (nausea, drowsiness, confusion). For example, transdermal fentanyl or buprenorphine can be useful in patients with swallowing difficulties.

Alternative routes of administration include enteral, transmucosal, rectal, transdermal, parenteral, intravenous, and intraspinal(2).

14. Acknowledge common adverse effects of opioid analgesic agents

15.  Describe precautions during chronic opioid use

Normeperidine is a toxic metabolite of meperidine that accumulates with repetitive dosing; thus, use of meperidine for chronic pain should be limited. Propoxyphene is also relatively contraindicated due to accumulation of norporpoxyphene.

Physical withdrawal symptoms can be avoided by tapering doses

A change in mental status should not be attributed to opioid therapy until medical and neurologic factors have been fully evaluated

Mixed agonist-antagonist drugs and partial agonist drugs are not recommended for cancer pain.

16.  Understand the use of adjuvant analgesic agents

17.  Understand principle methods of interventional and other non-pharmacological approaches to pain management

Virtual Patient Case

This case study was designed to supplement your knowledge on cancer pain management and test what you have learned after going through the pain management module. Use your mouse to click through the slides and answer each question in the text box provided.

Note: This case can be completed on an iPad. To do this download the (free) Articulate Mobile Player for the iPad by clicking here.

References

Prevalence

  1. Pazdur R, Coia LR, Hoskins WJ, Wagman LD. Cancer Management: A Multidisciplinary Approach 6th Edition. PRR, Melville, NY; 2002.

Approach

  1. Advisory Committee. BC Guidelines & Protocols: Pain and symptom management. 2011. Available at www.bcguidelines.ca/pdf/palliative2_pain.pdf. Accessed June 20th 2013.
  2. Bistros, BS. Advocating for Management of Cancer Pain. Journal of the American Osteopathic Association December 1, 2007 vol. 107 no. suppl 7 ES4-ES8.
  3. Bennett, Michael I, Flemming, Kate, Closs, Jose S. Education in cancer pain management. Current Opinion in Supportive & Palliative Care 2011; Vol 5, Issue 1, 20-24.

Assessment

  1. National Cancer Institute: Cancer Pain Management Module 2. Available at: http://www.cancer.gov/cancertopics/cancerlibrary/epeco/selfstudy/module-2/module-2-pdf. Accessed June 13th 2013.
  2. International Association for the Study of Pain: Taxonomy. Available at: http://www.iasp-pain.org/AM/Template.cfm?Section=Pain_Definitions. Accessed June 10th, 2013.
  3. International Association for Study of Pain: Clinical Updates Vol. XVIII, Issue 7. Diagnosis and Classifi cation of Neuropathic Pain. 2010. Available at http://www.iasp-pain.org/AM/Template.cfm?Section=Pain_Definitions&TEMPLATE=/CM/ContentDisplay.cfm&CONTENTID=15084. Accessed June 15th 2013.
  4. Holleb AI, Fink DJ, Murphy GP. American Cancer Society textbook of clinical oncology. 1st Edition. American Cancer Society, Atlanta, GA. 1991.
  5. University of Toronto: Pain Management. Available at: http://www.cme.utoronto.ca/endoflife/PAIN%20MANAGEMENT.pdf. Accessed June 13th 2013.
  6. National Institute of Health: Pain Intensity Instruments. 2003. Available at: http://painconsortium.nih.gov/pain_scales/NumericRatingScale.pdf. Accessed June 13th 2013.

Analgesic Medication

  1. National Cancer Institute: Cancer Pain Management Module 2. Available at: http://www.cancer.gov/cancertopics/cancerlibrary/epeco/selfstudy/module-2/module-2-pdf. Accessed June 13th 2013.

Non-opioid Analgesics

University of Toronto: Pain Management. Available at: http://www.cme.utoronto.ca/endoflife/PAIN%20MANAGEMENT.pdf. Accessed June 13th 2013.

Opioid Analgesics

  1. National Cancer Institute: Cancer Pain Management Module 2. Available at: http://www.cancer.gov/cancertopics/cancerlibrary/epeco/selfstudy/module-2/module-2-pdf. Accessed June 13th 2013.
  2. University of Toronto: Pain Management. Available at: http://www.cme.utoronto.ca/endoflife/PAIN%20MANAGEMENT.pdf. Accessed June 13th 2013.
  3. Holleb AI, Fink DJ, Murphy GP. American Cancer Society textbook of clinical oncology. 1st Edition. American Cancer Society, Atlanta, GA. 1991.
  4. Fallon M, Hanks G, Cherny N. ABC of palliative care: Principles of control of cancer pain. BMJ 2006; 332(7548): 1022-1024.
  5. Pazdur R, Coia LR, Hoskins WJ, Wagman LD. Cancer Management: A Multidisciplinary Approach 6th Edition. PRR, Melville, NY; 2002.

Adjuvant Therapy

Pazdur R, Coia LR, Hoskins WJ, Wagman LD. Cancer Management: A Multidisciplinary Approach 6th Edition. PRR, Melville, NY; 2002.

Non-Pharmacological Therapy

Pazdur R, Coia LR, Hoskins WJ, Wagman LD. Cancer Management: A Multidisciplinary Approach 6th Edition. PRR, Melville, NY; 2002.

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