Recognition and Diagnosis of Breakthrough Pain

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1 Blackwell Publishing IncMalden, USAPMEPain Medicine American Academy of Pain Medicine? 20078S137Original ArticleRecognition and Diagnosis of Breakthrough PainPayne PAIN MEDICINE Volume 8 Number S Recognition and Diagnosis of Breakthrough Pain Richard Payne, MD Duke Institute on Care at the End of Life, Duke University Divinity School, Durham, North Carolina, USA ABSTRACT ABSTRACT Objective. To review major clinical issues related to recognition and diagnosis of breakthrough pain. Issues. Persistent pain and breakthrough pain (BTP) are distinct clinical entities that should be recognized, diagnosed, and treated individually. BTP is common in patients with cancer and a variety of other chronic diseases. Reported incidence of BTP varies widely from 16% to 95% of those with persistent pain syndromes. Such variability is likely due to lack of a clear consensus on the definition of BTP. It is most commonly defined as an abrupt, short-lived, and intense pain that breaks through the around-the-clock analgesia that controls persistent pain. The three subtypes of BTP are incident, idiopathic, and end-of-dose failure. BTP also is categorized as somatic, visceral, neuropathic, or mixed. Appropriate assessment of the patient takes into consideration source, severity, pattern, subtype, and cause of pain. Successful treatment is important because BTP has a profound impact on the patient s quality of life, as well as cost of health care. BTP is likely to be underdiagnosed and undertreated because of the lack of consensus on its definition and unwarranted concerns among health care professionals and patients about overmedicating. Additionally, and for reasons not entirely clear, many physicians and other health care providers place a low priority on pain management and underrecognize the occurrence of BTP in patients with persistent pain. Conclusion. Greater knowledge and awareness of BTP in cancer and nonmalignant conditions will lead to improved recognition and diagnosis of BTP and ultimately to more effective treatment and enhanced quality of life for these patients. Key Words. Pain; Analgesics; Opioid; Cancer; Palliative Care; Diagnosis Introduction B aseline persistent pain, defined as pain having a duration of 6 months or more, is a common reason why patients consult their primary care physicians [1]. Surveys of patients from 15 medical Reprint requests to: Richard Payne, MD, Esther Colliflower Director, Duke Institute on Care at the End of Life, Duke University Divinity School, 2 Chapel Drive, Westbrook Building, Room 0032, Durham, NC 27708, USA. Tel: ; Fax: ; rpayne@div.duke.edu. This manuscript is based on the content of the CME symposium The Scope of Breakthrough Pain in Clinical Practice held on February 24, 2006, in San Diego, CA, at the Annual Meeting of the American Academy of Pain Medicine. centers in 15 countries found that 22% of primary care patients reported having persistent pain [1]. Breakthrough pain (BTP) also is common, and data from several clinical trials suggest that it may occur in up to 93% of patients with persistent pain [2 6]. In contrast to persistent pain, BTP is abrupt in onset, intense, and short-lived. It breaks through the around-the-clock analgesia used to treat baseline persistent pain. The term was popularized by Portenoy and Hagen, who in 1990 described BTP as a transitory exacerbation of pain to greater than moderate intensity, which occurs on a baseline pain of moderate intensity or less in a patient receiving chronic opioid therapy [4]. The idea was that significant, baseline persistent pain had to be present before there could be BTP. Over time, other definitions have appeared American Academy of Pain Medicine /07/$15.00/S3 S3 S7

2 S4 Table 1 Year Evolution of definitions of breakthrough pain Definition 1990 Transitory increase in pain to greater than moderate intensity, which occurs on a baseline pain of moderate intensity or less, in a patient receiving chronic opioid therapy [4] Transitory exacerbation of pain experienced by the patient who has relatively stable and adequately controlled baseline pain [7] Transitory flare of pain superimposed on an otherwise stable pain pattern in patients treated with opiates [8] Transient exacerbation of pain that occurs in patients with otherwise stable baseline persistent pain [9] Moderate to excruciating acute pains that occur intermittently, often on a background of well-controlled chronic pain [10] Transitory increase in pain that occurs in addition to persistent pain [11]. in the literature (Table 1) [4,7 11], and controversy over the best definition persists. The time from onset of BTP to peak severity is usually within 3 5 minutes, the duration is approximately 30 minutes, and intensity is severe or excruciating [4,12]. Persistent pain and BTP are distinct clinical entities that should be addressed individually [4,7 9]. Any of the commonly accepted working definitions of BTP assume that the baseline persistent pain is controlled and stable [4]. However, frequent episodes of BTP probably indicate inadequately treated persistent pain, and more than four episodes of BTP per day may warrant a reassessment of the cause and/or the approach to the management of the baseline persistent pain [9]. Cancer-related BTP has a profound impact on both quality of life and health economics [3,13,14]. Uncontrolled or poorly controlled pain of any etiology is strongly associated with impairment of sleep, walking, daily activities, enjoyment of life, and relationships with others. It also is correlated with worsening of anxiety and depression, dissatisfaction with opioid therapy, and poor medical outcomes [1]. In addition, patients with cancer-related BTP or uncontrolled pain are likely to use more health care resources, have more pain-related hospitalizations and emergency department visits, and have greater direct and indirect treatment costs than those without BTP [3,13]. One study found that the total annual cost of cancer pain-related hospitalizations, emergency visits, and physician office visits was approximately five times greater for patients with BTP than for patients without BTP ($12,000/patient/year vs $2,400/patient/ year) [3]. Prevalence of BTP in Cancer and Nonmalignant Conditions Payne A review of 28 international epidemiological surveys of more than 62,000 patients with cancer found that pain (persistent and BTP) was common and occurred in 50% or more of the patients in almost half of the surveys [15]. During the course of cancer, the prevalence of BTP is estimated at between 24% and 95% [16]. A large, prospective, multicenter survey of pain specialists in 24 countries found that 65% of 1,095 cancer patients had BTP [6]. This type of pain is also commonly reported by patients with nonmalignant but terminal disease, such as end-stage multiple sclerosis, motorneuron disease, cardiac failure, or cerebrovascular accidents, and in one study, BTP was seen in 63% (27 of 43) of those admitted to a hospice [5]. However, it is likely that the most common nonmalignant cause of BTP is low back pain syndrome. The prevalence of persistent low back pain among all adults has been estimated at 17.8% in the United States, 32% in Greece, and 22% in the UK, and in German women, as high as 44.9% [17]. In a recent survey of 228 patients with noncancer pain, 74% had BTP, and the most common cause for their pain syndrome (the cause in 52% of cases) was low back pain [18]. Subtypes of BTP Based on the information obtained from medical history and physical examination, the BTP experienced by most patients can be categorized as one of three subtypes: incident, idiopathic or spontaneous, and end of dose (Table 2) [9,10]. The incident subtype is the most common, accounting for about half of BTP episodes. Incident BTP can be predictable and directly related to musculoskeletal movements, such as coughing or turning over in Table 2 Subtype Incident, predictable Subtypes of breakthrough pain Incident, unpredictable Idiopathic End of dose Characteristics Adapted with permission from Bennett D, et al. [9]. Consistent temporal relationship with a precipitating factor Inconsistent temporal relationship with precipitating factor Not induced by a readily identifiable cause; lasts longer then incident subtype Presents prior to a scheduled dose of an around-the-clock analgesic; onset is more gradual and duration is longer than either incident or idiopathic subtypes

3 Recognition and Diagnosis of Breakthrough Pain Table 3 Type of Pain Somatic Visceral Neuropathic Pain quality bed [4]. It also can result from contraction or spasm of visceral smooth muscle, such as with bowel or bladder spasms, and in that case, the occurrence of the pain can be unpredictable. The idiopathic subtype of BTP does not have a readily identifiable cause and usually lasts longer than the incident subtype, often more than 30 minutes [19]. The end-of-dose subtype occurs when patients experience a spike in their baseline persistent pain an hour or more before they are scheduled to receive their next dose of pain medication and usually signifies that either the dosing interval or the amount of pain medication is insufficient. The cause and anatomical site of BTP is often, but not always, the same as those of the baseline persistent pain [16]. The quality of the BTP is usually categorized as somatic, visceral, or neuropathic based in part on the anatomic location of the pain and on typical causes (Table 3) [7,8,10,20]. Somatic BTP is most often caused by low back muscle spasms, bone metastases, or osteoarthritis. Liver metastases, peritoneal carcinomatosis, irritable bowel syndrome, or angina pectoris are all potential causes of visceral BTP. This type of pain may be localized to the visceral site of origin or referred to distant body sites, as in the case of left neck and face pain resulting from angina pectoris [10]. Neuropathic pain is caused by lesions of, or dysfunction in, the central nervous system (e.g., brain, spinal cord) or peripheral nervous system (e.g., dorsal nerve roots, peripheral nerves). There may be common mechanisms and processes underlying BTP in both malignant and nonmalignant diseases, and the clinical features of BTP are therefore similar among patients with either form of disease [5,16]. Diagnosis of BTP Characteristics Data from Abrahm JL [10]. Skeletal involvement localized to area of lesion; constant throbbing, aching, increased by movement Arises from internal organs or lining of body cavities; often difficult to isolate origin; deep, cramping, twisting, tearing Structural changes to nerves stimulus-dependent or -independent; shooting, burning, tingling, electrical A consensus panel recommendation from 2005 suggested that BTP be defined as pain that is abrupt in onset, intense, short-lived, and breaks through the around-the-clock analgesia used to treat baseline persistent pain [9]. Creation of a standard definition of BTP was important because a large, prospective, multicenter survey of pain specialists in 24 countries found a great deal of variability in the way BTP was defined and diagnosed [6]. The consensus panel also found that it was important to differentiate BTP from persistent pain because a different treatment strategy is required for effective long-term management of each. The diagnosis of BTP usually is made based on multiple sources, but when patients have a normal mental status, their self-report is the best source of information about this type of pain [11]. In cases where mental status is altered, the diagnosis of BTP must rely on assessments by family members or other caregivers who have frequent contact with the patient. In cases where the patient does not understand the concept of BTP, physicians need to pose specific questions and ask about a recent episode of pain [9]. Details regarding the source, severity, pattern, subtype, and possible etiology of the pain episodes must be carefully documented [10]. The physical examination can help localize the pain and identify any inciting physical characteristics. Where appropriate, imaging studies such as spine radiographs, computed tomography, or magnetic resonance imaging can sometimes identify surgically correctable causes for BTP [11]. In addition to these relatively passive aspects of the initial evaluation, interactive patient assessment tools, either unidimensional or multidimensional, have become invaluable for the detailed characterization of pain [9]. Unidimensional instruments quantitatively assess a single dimension of pain severity; examples include the Numerical Rating Scale, a visual analog scale, and the Wong-Baker FACES Scale. These instruments are easy to use and quickly completed by most patients, and they do not require any input from the physician. The Wong-Baker FACES Scale is suitable across all cultures, as well as for patients with cognitive impairment. Multidimensional instruments, including the Brief Pain Inventory and the patient-completed pain diary, characterize pain more thoroughly than unidimensional instruments by providing both quantitative and qualitative information. However, they require considerably more time to complete and often require input from a physician or other health care provider. They cannot be completed by patients with significant cognitive S5

4 S6 Table 4 opioids Impediments to effective analgesic therapy with Impediments attributable to health care professionals Inadequate knowledge of pain management Inaccurate evaluation of the pain patient Legal issues for controlled substances Concerns about addiction Fears of respiratory depression Concerns about the patient becoming tolerant to opioids Impediments attributable to patients Underreporting of pain Fears that their disease is worsening Concern about not being a good patient Not wanting to distract their physician from treating the primary disease Not wanting to be considered an addict or fears about becoming addicted Worries about adverse events Impediments attributable to the health care system Low priority given to pain treatment Inadequate reimbursement Restrictive regulation of controlled substances Opioids unavailable in the patient s pharmacy Adapted with permission from National Cancer Institute [11]. impairments. Nonetheless, a detailed pain diary is usually the best account of the nature, duration, severity, and predictability of BTP episodes over a 24-hour period. Breakthrough pain is often undertreated, and patients with cancer or nonmalignant conditions suffer needlessly as a result. Undertreatment is attributed to a variety of barriers that have been well characterized in the literature as being related to the health care professional, the patient, or the health care system (Table 4) [11]. Unfortunately, these barriers often are the result of naïve or unsubstantiated social or legal beliefs, or medical opinions that are not evidence-based. An accurate determination of why a patient needs BTP medication can overcome some of these barriers [11]. Ongoing education of physicians and health care providers about the definitions, prevalence, impact, and importance of treating BTP and baseline persistent pain is essential. Treatment Considerations The initial treatment of BTP should begin with nonpharmacologic interventions unless the pain episodes are especially severe or frequent [21]. Examples include lifestyle changes to limit or pace physical activities, and routine exercise. Cognitive behavioral techniques (i.e., hypnosis and relaxation methods) or alternative medical therapies such as acupuncture may be very beneficial in some patients either alone or as adjuncts to opioid therapy [11,22]. While there are some advantages Payne to using nonpharmacologic interventions for BTP, including the potential empowerment of patients and the lack of adverse events, the disadvantages are that some of these interventions require a specialized staff to administer the treatments (e.g., acupuncture, hypnosis). For the pharmacologic treatment of BTP, the goals are to reduce the frequency and intensity of the BTP with a medication that has a rapid onset and relatively short duration of action. When prescribing a drug for BTP, the Four As of pain treatment should be considered: Analgesia, Activities of daily living, Adverse events, and Aberrant drug-taking behaviors [23]. Analgesic pain medication should be sufficient to optimize the patient s daily physical capabilities while minimizing adverse events and the possibility for abuse. A large variety of opioid and nonopioid medications are available for the treatment of BTP; pharmacokinetic and pharmacodynamic considerations play a key role in selecting the most effective medication for each patient [20]. The medication should have a short enough half-life to avoid toxicity from accumulation if frequent dosing is necessary, have minimal or manageable adverse events, have no interactions with the around-the-clock medication, and be easy to administer. Pharmacologic therapy for BTP is discussed in more detail in the next chapter of this supplement. Summary Breakthrough pain is a complex and clinically challenging condition defined as a transitory increase in pain to greater than moderate intensity, which occurs on a baseline pain of moderate intensity or less in a patient receiving chronic opioid therapy [4]. Episodes of BTP typically are rapid in onset and last for 30 minutes or more. In addition to severely impairing the patient s quality of life, BTP has been shown to lead to as much as a fivefold increase in the use of medical resources [3,13]. Appropriate assessment considers the source, severity, pattern, subtype, and cause of the pain; this information is best obtained from a pain diary. As part of individualizing treatment, general pain management strategies should focus on alleviating pain and on improving the quality of life of patients and their families. Currently, BTP is underdiagnosed and undertreated. Greater knowledge and awareness of BTP in cancer and nonmalignant conditions will lead to improved recognition and diagnosis, and ultimately to more effective treatment and enhanced quality of life for patients.

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