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When Cancer Pain Breaks Through, What Can You Do?

When Cancer Pain Breaks Through, What Can You Do?

ABSTRACT: Click here to link to the CME post-test for this article.

Abstract: Breakthrough pain in cancer patients can be very difficult to manage, primarily because of its heterogeneous and fleeting nature, so careful assessment is imperative to finding an adequate treatment regimen. Only a paucity of good research exists to support current interventions, and additional viable options need to be discovered. Oncology nurses must play an integral role in improving the treatment of breakthrough pain—one patient, one in-service for colleagues, and one clinical research study at a time.

Pain. Cancer pain. Breakthrough pain. What do you associate with those words? What do they mean to you? Will Rogers once said, “pain is such an uncomfortable feeling that even a tiny amount is enough to ruin every enjoyment.”

Pain is often the worst and most prevalent symptom caused by cancer—around 70%–90% of patients with advanced disease have pain.[1] Even when patients’ baseline or background pain is adequately controlled, often with a variety of medications and strategies, a large percentage (50%–89%) of cancer patients will have intermittent bouts of usually brief but severe pain, also known as breakthrough pain.[2] As an oncology nurse or advanced practice nurse, whether you are working in an inpatient or outpatient setting, you are more than likely involved in the management of breakthrough pain in some manner. This article will help to equip you with the basic knowledge to do so effectively.

There is no universally accepted definition of, or even term for, breakthrough pain.[3–6] There is even some disagreement about what constitutes breakthrough pain. The two widely identified and accepted categories of breakthrough pain are incident (or precipitated) pain and spontaneous (or idiopathic) pain, but a variety of authors assert that the third category, end-of-dose failure or end-of-dose pain (occurring regularly prior to the next scheduled long-acting analgesic dose), should not be included as a category of breakthrough pain because the baseline pain is not controlled.[3,4]

Incident pain is reported to occur in 32%–94% of patients and can be divided into further subcategories, namely volitional incident pain caused by predictable/voluntary factors (eg, movement) and nonvolitional incident pain caused by unpredictable/involuntary factors (eg, coughing).[3] A third potential subcategory is procedural pain caused by an intervention (eg, wound care).[4]

Spontaneous pain, reported to occur in 28%–45% of patients, can be especially difficult to manage due to its unpredictable nature and because it is without any apparent precipitating factors.[3]

NURSING ASSESSMENT OF CANCER BREAKTHROUGH PAIN
Before discussing the management of cancer-related breakthrough pain, one cannot forget that thorough assessment is usually crucial in helping to determine the proper treatment for all pain, including breakthrough pain. You will find that taking the time to do a comprehensive patient assessment is going to be worthwhile—whether you are, for example, an inpatient oncology nurse, a nurse in an oncology clinic, or an advanced practice nurse in either type of setting—to improve the quality of life for your patients.

Breakthrough vs Uncontrolled Baseline Pain
The most important aspect of the patient’s pain to assess is the type of pain: Are you truly treating breakthrough pain or are you instead treating pain resulting from undertreated baseline pain? If it is the latter, the next step is to determine whether this baseline pain has been ongoing (ie, chronic) or if there is a new (possibly undiagnosed and reversible) component. An important concept one must acknowledge is that cancer pain is frequently changing. In either case, is further workup (eg, x-rays vs magnetic resonance imaging [MRI], venous Doppler ultrasound tests), consultation (eg, radiation oncology for palliative radiation, interventional radiology for kyphoplasty), or immediate intervention (eg, paracentesis, intra-articular joint injection, treatment of herpes zoster) indicated? The intervention could even be as simple as treating constipation.[3] Does the dose of the patient’s long-acting opioid pain regimen need to be increased to reduce the frequency, and possibly also the intensity, of breakthrough pain? Is there an adjuvant medication that can treat an aspect of the pain that is not being optimally targeted by the patient’s current regimen (eg, steroid vs nonsteroidal anti-inflammatory drug vs bisphosphonate for pain related to bone metastasis, a tricyclic antidepressant to treat a neuropathic pain component)?

Breaking Down Breakthrough Pain
If you establish that you are, in fact, treating breakthrough pain, it is helpful to determine whether the pain is incident vs spontaneous breakthrough pain, and to further subcategorize any incident pain. If the pain is incident-related, what triggers it? You should ask the patient about time of onset, duration, and location of pain compared with baseline pain.[7] Are there any aggravating or relieving factors? Is the pain new or diff erent from that previously described by the patient? How has the pain responded to analgesics/other medications and nonpharmacologic interventions? How does this breakthrough pain aff ect the patient’s overall quality of life and level of functioning together with his/her overall physical, psychosocial, and possibly even spiritual health?[7] Not surprisingly, breakthrough pain has been found to have a signifi cant impact on patients’ functional levels, and thus their quality, and possibly even quantity, of life as a poor prognostic indicator, as well as their mental and social health.[4] Cancer patients with breakthrough pain also appear to incur more direct medical costs, in terms of pain-related hospitalizations and emergency department and physician office visits.[8]

Barriers to Effective Breakthrough Pain Management
The final aspect of breakthrough-pain assessment involves determining whether there are any apparent barriers to managing a patient’s breakthrough pain, and attempting to overcome them. A publication by the American Pain Foundation lists a variety of barriers that often prevent cancer patients from receiving adequate management of breakthrough pain.[9] Oncology nurses can be instrumental in helping to break down some of these barriers by attempting to identify them during their breakthrough pain assessment and then addressing any issues identifi ed with patients, their families, and, in some cases, other healthcare providers.

• An overt or perceived message that pain is simply a common aspect of life during/after cancer treatment that has to be endured, and that bringing attention to it marks one as a “difficult patient.”[9]

– Educate patients and their families that they should not have to suffer in silence.

– If not in a position to treat the pain yourself, encourage patients to ask their providers(s) to address their breakthrough pain more proactively (or, if feasible, act as their advocate and do so for them).

• Difficulty paying for pain medications and the care associated with pain management.[9]

– Search for financially appropriate alternatives to current pain medications.

– Offer assistance with applications for patients to receive medications from the manufacturer.

– Obtain assistance from a social worker to help find means of paying for medications/medical care in general.

• A paucity of good options to provide ongoing management of chronic treatment-related breakthrough pain after cancer treatment has ended.[9]

– Be aware of which options do exist and help to initiate referral.

– Help to develop a way to provide this continued care within your work setting.

• No uniform language exists to describe breakthrough pain, and this may prevent providers, patients with breakthrough pain, and the public from communicating effectively about this problem.[9]

– Lead/participate in research to develop standardized language associated with breakthrough pain.

– Help to develop a standardized assessment tool in your workplace that patients can use to relay the most important information about their breakthrough pain. Consider incorporating the clinical domains of breakthrough pain that were utilized to develop the Alberta Breakthrough Pain Assessment Tool: location, intensity, quality, frequency, and predictability of breakthrough pain, plus its response to medications and relationship to baseline pain.[10]

• Inadequate research data about best treatments for cancer breakthrough pain, especially for cancer survivors with chronic treatment-related pain.[9]

– Develop, initiate, or explore opportunities to participate in research.

– Educate yourself about the research that does exist, so that you can provide the best evidence-based care possible (eg, read original research articles and review articles on breakthrough pain).

• Inadequate training for providers in the management of cancer breakthrough pain.[9]

– Continue to educate yourself and then teach your peers/other providers in your work setting and beyond—become an expert and share your knowledge!

• Finally, another major barrier to pain management in general that needs to be mentioned is the stigma associated with use of opioids. This barrier is experienced by patients and families, and it is often associated with the fear of becoming addicted. Many healthcare providers hesitate to prescribe opioids because of the potential for their abuse.

– Educate patients, families, and other providers to help reduce the stigma.

TREATMENT OF CANCER BREAKTHROUGH PAIN
Th e highly variable nature of breakthrough pain underscores the critical importance of thorough pain assessment and the reason that treatment regimens often need to be tailored very specifi cally to the individual patient. Th ere is no standard approach to management and, as is the case with any pain treatment, one patient may respond very diff erently from another. A task group reviewing the literature on cancer-related breakthrough pain was unable to recommend individual interventions.[ 4] Th erefore, fi nding the right combination of pharmacologic and nonpharmacologic therapies can be very challenging, but you can once again play a major role.

Nonpharmacologic Interventions

Pharmacologic Interventions

Oral short-acting opioids have limited use for treating breakthrough pain, owing to their generally slow onset and peak effect (around 1 hour for most immediate-release opioids).[12] By the time most oral immediate-release opioids are peaking, the average episode of breakthrough pain will have ended (about 30 minutes after onset).[13] A 2006 Cochrane review examining use of opioids for breakthrough pain concluded that oral transmucosal fentanyl citrate (OTFC), absorbed through the buccal mucosa via lozenge primarily, was the only oral short-acting opioid with adequate evidence to support its use for breakthrough pain.[14] If breakthrough pain occurs during any prolonged period of increased activity, taking an oral short-acting opioid besides OTFC (eg, oxycodone, morphine, or hydromorphone) 30–60 minutes prior to activity as preemptive analgesia can help to prevent breakthrough pain, or reduce its severity.

For patients receiving continuous intrathecal medications via a programmable intrathecal pump and who also have a personal therapy manager device, an as-needed bolus of approximately 10% of the daily dose can be given and is usually delivered over a period of 10–45 minutes. IV and SC opioids have a much faster onset and peak effect compared with oral immediate-release opioids and are therefore more likely to be able to provide the rapid pain relief needed to treat breakthrough pain effectively.[12] They can be especially effective when delivered via a patient-controlled analgesia (PCA) pump (in both the inpatient setting and at home) for immediate administration of medication without delay.

You may be in a position to start or suggest initiation of a PCA and then monitor a patient’s response to this intervention (followed by dosing adjustments based on how well the breakthrough pain is controlled). If you are a bedside oncology nurse, it is crucial to administer doses of as-needed intravenous opioid as quickly as possible when patients have episodes of breakthrough pain. In a 2010 study, both IV morphine and OTFC breakthrough doses, given at a strength based on patients’ baseline opioid use, provided significant relief (> 50% reduction in pain intensity) in more than 90% of all cases of breakthrough cancer pain.[15]

Finally, intranasal fentanyl spray has been found to be effective in treating cancer breakthrough pain and is approved for use in Europe.[16,17] Sublingual tablets of fentanyl achieved clinically significant reduction in breakthrough pain in a European randomized phase II study.[18] It may be difficult for both of these formulations to gain US Food and Drug Administration (FDA) approval in the United States, owing to their high potential for abuse.

CASE STUDY

She has recently started experiencing severe episodes of breakthrough pain, up to 9/10, whenever she gets out of bed or performs any activity.

BW is not a candidate for surgery, kyphoplasty/vertebroplasty, or further radiation treatment. She has mild chronic kidney disease, with a baseline serum creatinine level of 1.7 mg/dL that has recently risen to 3.5 mg/dL. Even without the pain, she is no longer able to ambulate very much and has an ECOG (Eastern Cooperative Oncology Group) performance status of 3. She does enjoy getting up to use her rocking chair as much as possible and may sit in it most of the day. She has started experiencing occasional myoclonic jerking of her extremities.

For this worsening breakthrough pain, she has been taking escalating doses of oral immediate-release morphine 30–60 minutes prior to getting out of bed. Although the morphine helps to reduce her pain when she is able to take a dose at the right time in advance, she has started experiencing increased sedation for an hour or two after the pain subsides, as well as apparent worsening of her myoclonus.

Points to Consider

• What are some other options to treat her breakthrough pain more efficiently (and which, it is hoped, she will tolerate without side effects)?

• Would you consider changing her long-acting pain regimen? If so, what opioids would you consider foremost, and why?

• How would you consider changing her (baseline/breakthrough) pain regimen if she starts declining more acutely 6 weeks later and becomes less responsive to the point of no longer being able to swallow?

Recommendations
•Some form of fentanyl, taken transmucosally, intravenously, or subcutaneously, should provide the fastest relief without staying in her system as long and may be safest in light of her renal impairment.

• Changing her long-acting regimen is appropriate given her renal impairment and side effects that appear to be caused by the resulting morphine metabolite accumulation. Some options to consider are oxycontin at 150 mg every 12 hours, a fentanyl patch, at a dosage of 100 μg/hr every 3 days, oxymorphone at 50 mg orally every 12 hours, or methadone at 10 mg orally every 8 hours (dosages decreased approximately 25% for potential incomplete cross-tolerance after switching from a regimen that was adequately controlling her baseline pain).

Some points to consider are that methadone should be used carefully by experienced practitioners, given its higher risk for QT prolongation, potential drug–drug interactions, variable half-life with potential for delayed accumulation (and therefore also delayed peak effect compared with other opioids) over the course of several days, and resulting higher risk for respiratory depression. Fentanyl patches also do not achieve steady state until approximately 12–18 hours after application.

Switching to or continuing the fentanyl patch as her long-acting agent is probably the best option for BW if she is unable to swallow. Some form of short-acting fentanyl, or any intravenous/subcutaneous opioid, would be best for managing episodes of breakthrough pain. Because BW is likely now enrolled in hospice, however, cost considerations may result in at least a trial of highly concentrated liquid oxycodone at 20 mg/mL or even morphine at 20 mg/mL orally for breakthrough pain.

This may be very appropriate since the primary inciting factor of her breakthrough pain, activity, has been removed—she will probably have significantly fewer episodes of unpredictable breakthrough pain that cannot be controlled with pre-emptive analgesia.

She should therefore also require much less frequent dosing of breakthrough medicine, with lower doses needed, and she is now also much less likely to have myoclonus, since she is no longer on long-acting morphine. Sedation should also not be an issue any longer, owing to her new baseline level of unresponsiveness and likely lower dose of breakthrough medicine required.

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

References

1. Haugen DF, Hjermstad MJ, Hagen N, et al: Assessment and classification of cancer breakthrough pain: A systematic literature review. Pain 149(3):476–482, 2010.

2. Hwang SS, Chang, VT, Kasimis B: Cancer breakthrough pain and responses to treatment at a VA medical center. Pain 101(1–2):55–64, 2003.

3. Zeppetella G: Impact and management of breakthrough pain in cancer. Curr Opin Support Palliat Care 3(1):1–6, 2009.

4. Davies AN, Dickman A, Reid C, et al: The management of cancer-related breakthrough pain: Recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain 13(4):331–338, 2009.

5. Portenoy, RK, Payne D, Jacobsen P: Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain 81(1–2):129–134, 1999.

6. Lasheen W, Walsh D, Sarhill N, et al: Intermittent cancer pain: Clinical importance and an updated cancer pain classification. Am J Hosp Palliat Care 27(3):182–186, 2010.

7. McMillan C: Breakthrough pain: Assessment and management in cancer patients. Br J Nurs 10(13):860–866, 2001.

8. Fortner BV, Okon TA, Portenoy RK: A survey of pain-related hospitalizations, emergency department visits, and physician office visits reported by cancer patients with and without history of breakthrough pain. J Pain 3(1):38–44, 2002.

9. American Pain Foundation: Breakthrough Cancer Pain: A Break in the Continuum of Care. Baltimore, American Pain Foundation, 2010.

10. Hagen N, Stiles C, Nekolaichuk C, et al: The Alberta Breakthrough Pain Assessment Tool for cancer patients: A validation study using a delphi process and patient think-aloud interviews. J Pain Symptom Manage 35(2):136–152, 2008.

11. Arnold R, Verrico P, Davidson S: Opioid Use in Renal Failure. Fast Facts and Concepts, August 2006 p. 161. Available at: http://www.eperc.mcw.edu/fastfact/ff_161.htm. Accessed on July 31, 2010.

12. Divvela S, Williams A, Meives C, et al: Opioid analgesics: Comparison of pharmacokinetics and equianalgesic doses. Hosp Pharm 42(11):1130–1135, 2006.

13. Zeppetella G, Ribeiro MD: The pharmacotherapy of cancer-related episodic pain. Expert Opin Pharmacother 4(4):493–502, 2003.

14. Zeppetella G, Ribeiro MD: Opioids for the management of breakthrough (episodic) pain in cancer patients. Cochrane Database Syst Rev 1:CD004311, 2006.

15. Mercadante S, Villari P, Ferrera P, et al: The use of opioids for breakthrough pain in acute palliative care units by using doses proportional to opioid basal regimen. Clin J Pain 26(4):306–309, 2010.

16. Mercadante S, Radbruch L, Davies A, et al: A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: An open-label, randomised, crossover trial. Curr Med Res Opin 25(11):2805–2815, 2009.

17. Kaasa S, Moksnes K, Nolte T, et al: Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain. J Opioid Manag 6(1):17–26, 2010.

18. Lennernäs B, Frank-Lissbrant I, Lennernäs H, et al: Sublingual administration of fentanyl to cancer patients in an effective treatment for breakthrough pain: Results from a randomized phase II study. Palliat Med 24(3):286–293, 2010.

19. Perazella MA, Markowitz GS: Bisphosphonate nephrotoxicity. Kidney Int 74(11):1385–1393, 2008.

 
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