姑息治疗疼痛问题Miles J. Belgrade.Palliative Pain Issues.Current Clinical Oncology,2010(10)51-61

8 Palliative Pain Issues Miles J. Belgrade Abstract Pain often presents with a very complex mixture of medical, psychological, and social factors. Physicians frequently approach persistent pain with apprehension and biases. Patients and families often believe pain can be cured, while clinical medicine is still far from cure or even consistent success. This chapter outlines an approach that allows physicians to be dispassionate about the process of pain management, yet compassionate for their patients in pain. It presents a strategy and framework for understanding and approaching patients with advanced medical illness who have complex pain issues. Through a discussion of the overall goals of therapy relative to pain relief goals, this approach helps physicians and their patients determine the actual or inferred pathophysiology of pain, the contributing factors that impact the pain experience, and the numerous barriers that complicate pain assessments and treatment. Utilization of opioid analgesics, adjuvants, and nonpharmacologic are also incorporated into this model. Key Words: Opioid analgesics; Pain assessment; Pain treatment; Pathophysiology of pain; Pain management Ms. N is a 27-year-old female with systemic lupus erythematosis and renal osteodystrophy with a history of multiple fractures and mechanical abnormalities contributing to multire- gional joint, bone, and muscular pain. She is on chronic hemodialysis for end-stage renal disease. She has chronic pain in her shoulders, back, hips, and both legs in addition to daily headaches. She has severe hearing impairment and is blind in one eye from infection. She lives with her mother, sister, and niece and spends most of her time at home watching television. She receives social security disability income. Communication is also difficult because she is hostile toward the clinicians. She has been unreliable with adhering to physician recommendations in the past. From: Current Clinical Oncology: Palliative Care: A Case-based Guide, Edited by: J.E. Loitman et al. DOI: 10.1007/978-1-60761-590-3_8, © Springer Science + Business Media, LLC 2010 51 52 Belgrade Consider 1. A strategy and framework for understanding and approaching patients with advanced medical illness who have complex pain issues 2. An approach allowing physicians to be dispassionate about the process of pain manage- ment, yet compassionate for their patients in pain 3. A discussion related to overall goals of therapy relative to pain relief goals Key Points Pain often presents with a very complex mixture of medical, psychological, and social • factors. Physicians frequently approach persistent pain with apprehension and biases. Our training leaves us ill-prepared to deal with it. Patients and families often believe pain can be cured, while medical science is still far • from cure or even consistent success. Pain issues are similar regardless of the proximity to the end of life.• Determining the actual or inferred pathophysiology of pain directs treatment options.• Contributing factors impact the pain experience.• Numerous barriers complicate pain assessments and treatment.• sCenario 1: Goals of theraPy Ms. N’s primary physician prescribes hydrocodone/acetaminophen 5 mg/500 mg every 4 h as needed. She says she takes about six to eight tablets per day but it is not control- ling the pain. The physician suspects she is abusing opioids because of lost prescrip- tions and requests for early prescriptions and for “something stronger.” She uses doses of hydroxyzine for uncontrolled itching regularly. She had previously tried nonsteroidal antiinflammatory drugs (NSAIDs), antidepressants, and diazepam without relief. She tried biofeedback, chiropractic care, and counseling, but she is currently only utilizing medications. She has moderate lip reading ability and limited hearing. Her mother is present and appears to be an exhausted caregiver and advocate. Many elements above make managing her pain challenging. Frustration occurs when pain is widespread or communication is made difficult due to hearing loss and personality. Efforts to provide stable analgesia may be sabotaged by a loss of control over the prescription proc- ess or by a condition that may be progressive with an unpredictable, ill-defined timeline. Developing a pain management strategy begins with determining the goals of care regard- ing pain. The physician collaborates with the patient on the goals of care and the treatment strategy. The healthcare provider must provide an estimated prognosis to patients such that goals are concordant with planned therapies (Fig. 1). The choice of palliative vs. restorative treatment goals for persistent pain is influenced by disease burden, the level of responsibility a patient accepts, and what level of treatment-related risk is appropriate. The goals and treat- ments are different for a healthy patient with an ankle sprain than for a patient with uncon- trolled ankle pain due to Charcot joint with recurrent infection, underlying diabetes, and renal failure. Where does Ms. N fit on the chart in Fig. 1 below? fig. 1. Priority for pain management goals depends on the degree of disease burden. Chapter 8 / Palliative Pain Issues 53 sCenario 2: the PathoPhysioloGiC tyPes of Pain On physical examination, Ms. N presents as a young woman of short stature, her physi- cian has to repeat things over and over before she understands. She is completely blind in the right eye. Her skin is excoriated in places where she scratches. There are deformi- ties of the long bones at sites of healed old fractures. She has multiple tender points on the neck, back, and limbs. She can walk independently. She has peripheral neuropathy with a stocking distribution loss of pinprick and vibratory senses and absent deep tendon reflexes. Ms. N is not near the end of life, but her disease is disabling and life-limiting. Providing aggressive pain management, including opioid analgesics, should be balanced with structur- ing the treatment so that the prescribing process is more successful and less prone to failure. Her disease burden is high, dictating a treatment approach that is more palliative. Incorporating aggressive rehabilitation or physical reconditioning is more appropriate for patients with low disease burden. Establishing the level of disease burden helps guide the clinical approach. Pain science has advanced in the last two decades allowing identification of different pathophysiologic mechanisms for discrete types of pain. Nociceptive pain is due to activation of nociceptors either through mechanical compression or by inflammation. Neuropathic pain occurs with damage or dysfunction to the peripheral or central nervous system. Bone pain can be caused by osteoclast activity as in bone metastases; pain is maintained by activated glial cells in the spinal cord. Muscular pain has its own mechanisms that are distinct from the oth- ers. These four pain types respond to different therapeutic interventions by virtue of their distinct mechanisms. NSAIDs are used for inflammatory pain, whereas mechanical pain is generally treated with specific measures to decompress or stabilize involved structures. Nociceptive Muscle Neuropathic Muscle Bone fig. 2. Check off grid for noting physiologic types of pain. Type of pain Treatment strategies Nociceptive NSAID, corticosteroid, mechanical decompression/stabilization Neuropathic Anticonvulsants (gabapentin, pregabalin) antidepressants (Tricyclic, SNRIs) Muscle Physical therapies, muscle relaxants, trigger point injections Bone NSAID, corticosteroid, calcitonin, bisphosphonates Table 1 Physiological types of pain and their associated treatment strategies 54 Belgrade Examples include vertebroplasty in spinal compression fracture, bracing, debulking a mass, and draining an effusion. For neuropathic pain, hyperexcitable and sensitized neurons are targeted for pain therapies. Gabapentin, an anticonvulsant, regulates neuronal hyperactivity by modulating the voltage-gated calcium channels located on the nerves. Tricyclic antidepres- sants affect the descending modulation of pain through serotonin and norepinephrine reuptake inhibition in the brainstem. Muscular pain typically requires physical therapeutic approaches like stretching, range of motion, TENS, massage, aquatic therapy, and mobilization. Sometimes trigger point injection or botulinum toxin injections are used to break a cycle of muscle dysfunction. Bone pain responds to prostaglandin inhibitors or corticosteroids. On the basis of historical information, pain distribution, and physical findings, one can infer the pathophysiologic type of pain. Ms. N presents with three of the four cardinal pain types: bone pain, muscular pain, and nociceptive pain (Fig. 2). A history of multiple fractures underlying renal osteodystrophy and bone deformities points to bone pain as an important mechanism. Muscular pain is inferred from the tenderness on exam. Lupus predisposes her to inflammatory joint pain. The presence of neuropathy suggests neuropathic pain, but her symptoms do not correlate anatomically (e.g., no burning pain in a stocking distribution). With three inferred pain types, the next step in a pain management strategy is selecting medications and other treatments. An antiinflammatory drug would reduce nociceptive pain from lupus arthritis. NSAIDs would also help manage bone pain due to fracture and microfractures which may continue to occur. Muscle pain is generally managed with physical modalities that could include stretching, posture correction, exercise, local modalities like ultrasound, passive range of motion, trigger point injection, and muscle relaxants. Table 1 summarizes the pain types and some of the specific treatment strategies for those pain types. Chapter 8 / Palliative Pain Issues 55 sCenario 3: ContributinG faCtors and barriers Ms. N’s fragile bone status is an important primary cause of her pain. Ms. N may be avoiding activities that take her out of the house because pain is worse with standing or walking. Hearing and visual impairment are hampering communication with Ms. N. Her anger and lack of trust interferes with her receptivity toward recommended treatments and engenders a hands-off approach by many clinicians. Contributing factors amplify pain or perpetuate it but are not the original cause of pain. For example, pain from a simple rib fracture is amplified with coughing from bronchitis. Managing contributing factors will lessen pain. Treating the cough will reduce the amplified pain from a rib fracture. Other contributing factors include anxiety, depression, fever, poor positioning, weight-bearing on an unstable joint, edema in a painful limb, and vomiting in a patient with back or abdominal pain. Often, an improvement in pain control is achieved when contributing factors are modified, even when the underlying pain is intractable. Treatment of osteodystrophy and functional activities like walking and climbing stairs limit fracture risk and reduce pain exacerbation. Physical or occupational therapy evaluation can ameliorate pain in the hips and lower limbs by reducing weight-bearing forces with assistive devices like a cane or walker. Barriers neither cause nor amplify the pain, but do make assessment or management more difficult. Insurance noncoverage for effective pain treatments has become an increasingly important hinderance to pain control. Language, cultural, and other communication barriers limit the ability to fully assess pain. Patient-centered factors such as low motivation, poor compliance, and chemical dependency may also impede ideal pain management. Such bar- riers are important to identify to better understand successes and failures of pain manage- ment strategies. Recognizing barriers may prevent continued escalation of ineffective therapies in a futile attempt to obtain relief and putting the patient at greater risk. Some bar- riers, once identified, can be effectively managed, thereby allowing pain management to take place with greater success. Nonadherence with medication is an important barrier to providing aggressive pharma- cological treatment for pain. Recognizing this, as a barrier, improves clinical management. One strategy includes frequent visits every 1 or 2 weeks. This provides a structure for the scheduled medications, which reduces the risk of misuse. Additionally, patients may feel more comfortable that the clinician is providing a more aggressive pain medicine approach. sCenario 4: ManaGinG oPioids Because of Ms. N’s compelling burden of disease, her physician decides to utilize opioid analgesics. The concerns about which opioid to choose and in what formulation are considered. Opioid Dosages available Dosing interval (default underlined) Comments Morphine 15, 30, 50, 60, 100 mg Q 8, 12, 24 h Avoid in renal insufficiency Oxycodone 10, 15, 20, 30, 40, 80 mg Q 8, 12 h Fentanyl transdermal patch 12, 25, 50, 75, 100 mcg/h Q 48, 72 h Methadone 5, 10 mg Q 6, 8h, 12 Wait 3–5 days between dose increases. Watch for prolonged QT inter- val and other arrhyth- mias. Recommended for experienced prescribers only Oxymorphone 5, 7.5, 10, 15, 20, 30, 40 mg Q 12 h Table 2 Commonly used opioids with prolonged effects 56 Belgrade The five commonly used choices of opioids with prolonged effects are depicted in Table 2. All have both pros and cons: Morphine’s metabolite, morphine-3 glucuronide, accumulates with renal insufficiency and may produce toxicity in the form of sedation, confusion, or myoclonus. Many prepara- tions are inexpensive. Methadone acts as an opioid agonist and an N-methyl d-aspartate (NMDA) antagonist. The latter mechanism may provide advantages in neuropathic pain. Methadone is particularly inexpensive. The pace of titration is more gradual than other strong opioids due to its pro- longed terminal half-life but intermediate duration of analgesia. Fatal ventricular arrhythmias have occurred with methadone at high doses (such as greater than 300 mg/day), particularly when prescribed to patients with heart disease and metabolic disarray. Thus methadone pre- scribing should be reserved for clinicians with experience. Fentanyl transdermal patches are changed every 72 h or sometimes every 48 h. Febrile patients may have a more rapid and less predictable accumulation of drug in the subcutane- ous tissue. For patients requiring very high doses of opioids, it may be impractical to use transdermal fentanyl beyond a few hundred mcg per hour (i.e., three or four 100 mcg/h patches) which is equivalent to the potency of 300–400 mg/day of oxycodone. Sustained-release tablet formulations of oxycodone, morphine, or oxymorphone tablets must not be cut, crushed, or chewed because that violates the sustained-release structure of the tablets which leads to release of the entire dosage. Sustained-release morphine also comes in capsules containing time-release beads. The beads can be sprinkled on applesauce for ingestion, maintaining the extended release effects. Ms. N’s end-stage renal disease makes morphine a less desirable choice due to potential accumulation of metabolites. Her impulsive behavior and compliance barriers make metha- done, which must be titrated with great care, a poor choice. Sustained-release tablets would be a good choice if chewing or breaking is not anticipated. Fentanyl transdermal patches may also reduce impulsive use. Table 3 Opioid equivalences Drug Oral (mg) IV/SQ (mg except as noted) Morphine 30 10 Oxycodone 20 – Hydromorphone 7.5 1.5 Methadonea 5 2.5 Fentanylb – 20 mcg/h IV/TD Hydrocodone 30 – Oxymorphone 10 – Equivalence doses are based on opioid naïve patients aThe methadone conversion here is appropriate for moderate doses of opioids. See Walker et al (2008) for a detailed account of this drug’s complex dose-related conversions bUniversity of Minnesota Medical Center uses this fentanyl conversion which equates 20 mg of oral oxycodone per day to 20 mcg/h IV infusion or transdermal fentanyl Chapter 8 / Palliative Pain Issues 57 Opioid starting doses depend on prior opioid exposure. Ms. N has been taking six to eight hydrocodone 5 mg tablets per day which is equal to 30–40 mg hydrocodone per day. To determine the transdermal fentanyl dose that would be equipotent to her daily hydroco- done, refer to the opioid equivalence table (Table 3). Hydrocodone, 30 mg/day, is equivalent in analgesic potency to 20 mcg/h of transdermal fentanyl. So, hydrocodone, 40 mg/day, would be equivalent to about 27 mcg/h of transdermal fentanyl. When converting from one opioid to another, calculate the equivalent dose but undercut by at least 25–50% to account for incomplete cross tolerance. That is the tolerance that develops after a patient has previously been on one opioid that is not fully transferred to a new opioid exposure. Ms. N will start on a 25 mcg/h fentanyl transdermal patch changed every 72 h. She will continue to use hydrocodone/acetaminophen 5/500 mg up to four per day for breakthrough pain. To minimize risk with opioid prescribing, increase structure to the prescribing process by having prescriptions renewed weekly or every other week, at least initially. Once satisfactory and predictable dosing is achieved, the frequency of refills can change. This also helps the patient and physician build a relationship and communication. Ms. N’s mother might be asked to take on a medication dispensing role, but that may overburden an exhausted caregiver and the mother–daughter relationship. Ms. N’s Case Summary Pain assessment. Multiregional joint and bone pain due to renal osteodystrophy with fractures and associated muscle dysfunction. Contributing factors. Weight-bearing and anxiety. Barriers. Hearing and visual impairment limits communication and increases social iso- lation. Anger interferes with successful communication and care. Noncompliance negatively affects treatment. Treatment plan. Begin fentanyl transdermal patch 25 mcg/h every 72 h. Continue up to four hydrocodone/acetaminophen per day, but expect less need. Initiate a trial of a new NSAID and begin calcitonin nasal spray, one spray per day alternating nostrils. Refer to physical therapy for evaluation including possible assistive devices to facilitate increased 58 Belgrade function and mobility and a TENS trial for additional regional pain management. Follow-up in clinic for prescription refills weekly for the first month and then every 2 weeks. things to tell Ms. n I want to help you control your pain as much as possible. You have a serious pain prob- lem because of your kidney and bone disease. We will use strong pain medicines – even stronger than your Vicodin; but none of the pain medicines can do this alone. We have to attack the problem from different directions. We can start a fentanyl patch that is as strong as taking about six Vicodin per day. Each patch will last 3 days and will be working even when you are asleep. You may still use up to four Vicodin per day if you need to, but I think you will find that you do not need it so much. When you do take it, it will work better for you. Even though you tried the NSAID before, I think it is a good idea to try another one together with a nasal spray that strengthens your bones and may help bone pain. I want to make sure we get the medicines and other treatments correct and on track, so I am going to ask you to see me every week for a few weeks so we can make adjustments if we need to. I will send you to a physical therapist who will help you find ways to do more with less pain like walking and climbing stairs. She will also let you try a stimulator that you can use when your pain flares up in certain places. Even though th