Am Fam Physician. 2000;61(3):755-764
End-of-life care can be a challenge requiring the full range of a family physician's skills. Significant pain is common but is often undertreated despite available medications and technology. Starting with an appropriate assessment and following recommended guidelines on the use of analgesics, family physicians can achieve successful pain relief in nearly 90 percent of dying patients. Physicians must overcome their own fears about using narcotics and allay similar fears in patients, families and communities. Drugs such as corticosteroids, antidepressants and anticonvulsants can also help to alleviate pain. Anticonvulsants can be especially useful in relieving neuropathic pain. Side effects of pain medications should be anticipated and treated promptly, but good pain control should be maintained. The physical, psychologic, social and spiritual needs of dying patients are best managed with a team approach. Home visits can provide comfort and facilitate the doctor-patient relationship at the end of life.
Family physicians are uniquely qualified to manage end-of-life care. Proper end-of-life care requires an intimate knowledge of the dying patient and experience with a wide range of treatment modalities. Although the provision of this care can be demanding, it can also be fulfilling.
This article addresses the topic of pain management in dying patients. Pain in cancer patients is often used as an example, but the principles of pain management are applicable to a multitude of painful conditions that patients experience at the end of life.
Types of Pain
The patient who is near death may suffer in a variety of ways. Physical pain is common and is often most feared by cancer patients. Other physical causes of suffering can include dyspnea or stiffness resulting from immobility. In addition to physical pain, dying patients often experience social isolation, psychologic stress and spiritual crises.
Because of the multiple causes of suffering, treating only the physical symptoms can result in an unsatisfactory experience for both physician and patient. Assessing all aspects of suffering and providing appropriate care is best done using a team approach.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage—or described in terms of such damage.1 From another perspective, pain is always subjective. Perhaps a better operating definition would be that pain is what the patient says it is, regardless of actual or potential tissue damage.
Physical pain can have visceral, somatic and neuropathic origins. Visceral pain is poorly localized and is either cramping (usually from a hollow viscus) or sharp or achy (from an encapsulated organ). Somatic pain is usually well localized and can be described as sharp, achy, throbbing or pressure-like. Neuropathic pain is often radiating and is generally characterized as burning or stabbing.2
Studies indicate that 30 to 40 percent of cancer patients complain of moderate to severe pain at the time of diagnosis, with up to 90 percent experiencing significant pain sometime during the course of their disease.3,4 One study of cancer patients reported that 35 percent of the pain was somatic in origin, 17 percent was visceral, 9 percent was neuropathic and the remainder was of mixed origin.4
Assessment of Pain
A proper assessment is critical to identifying the type, characteristics and severity of a dying patient's pain. The patient's description of pain intensity should be accepted as accurate. Although elaborate pain assessment tools have been created,5 simple instruments can be used for initial screening and follow-up (Figure 1).
The physician should assess the intensity of the patient's pain, the characteristics of the pain, the patient's emotional response to the pain and the effect of the pain on the patient's ability to function.6 Accurate diagnosis of a patient's pain requires historical information about each type of pain, a thorough physical examination that includes the neurologic system, and appropriate diagnostic tests.
Pain should be assessed at the first meeting with the patient, during a follow-up visit after pain treatment has been initiated and at any time that the patient's pain changes. Assessments performed by hospice nurses between physician visits allow the patient's concerns to be addressed promptly.
Principles of Pain Management
The choice of analgesic drug should be based on the type of pain (Tables 1 through 4).7–9
Patients with chronic or frequently recurring pain should receive medications around the clock according to the recommended dosing schedules. This allows attainment of a steady state of medication, which minimizes side effects and avoids periods of subtherapeutic treatment.
Episodic or breakthrough pain should be anticipated and treated with as-needed pain relief in addition to the regularly scheduled analgesics. When opioids are used, the available daily breakthrough dosage should be equal to the regularly scheduled analgesic dosage. For example, if a patient is receiving 30 mg of sustained-release morphine (MS-Contin) every 12 hours, the breakthrough morphine dosage would be 10 mg administered every 4 hours. (Both approaches result in a dosage of 60 mg per 24 hours.) If large amounts of breakthrough medications are required, consideration should be given to raising the dosage of the regularly scheduled analgesic. In general, only-as-needed prescribing should be avoided.
Medication dosages should be titrated promptly to achieve effective pain control. For most medications, dosage adjustments can be made every 24 to 48 hours. Dosages of morphine and other strong opioids can be safely increased by 50 percent every 24 hours until a satisfactory response is obtained.8
Conversely, opioid dosages can be decreased by 50 to 75 percent every 24 hours without causing withdrawal symptoms.7–9
|Type of pain or associated condition||Medications and starting dosages|
|Amitriptyline (Elavil), 10 mg three times daily|
|Imipramine (Tofranil), 10 mg three times daily|
|Carbamazepine (Tegretol), 200 mg twice daily|
|Gabapentin (Neurontin), 100 mg per day*|
|Divalproex (Depakote), 125 mg once or twice daily|
|Phenytoin (Dilantin), 100 mg three times daily|
|Mexiletine (Mexitil), 150 mg three times daily|
|Capsaicin (Zostrix) applied to affected area three times daily|
|Clonidine (Catapres), 0.1 mg per day|
|Baclofen (Lioresal), 5 mg three times daily, with the dosage increased every third day until symptoms resolve|
|Dexamethasone (Decadron), 16 mg per day in divided doses|
|Methylprednisolone (Medrol), 120 mg per day in divided doses|
|Nonsteroidal medications (see Table 2)|
|Lorazepam (Ativan), 0.5 mg three times daily|
|Diazepam (Valium), 5 mg three times daily|
|Hydroxyzine (Atarax), 25 mg three times daily|
|Diphenhydramine (Benadryl), 25 mg three times daily|
|Bone metastasis||Pamidronate (Aredia), 90 mg once a month, administered in an infusion over 2 to 4 hours|
|Calcitonin (Calcimar), 100 IU per day administered subcutaneously or intramuscularly|
|Muscle spasms||Baclofen, 5 mg three times daily, with the dosage increased every third day until symptoms resolve|
|Lorazepam, 0.5 mg three times daily|
|Diazepam, 5 mg three times daily|
|Generalized chronic pain||Antidepressants|
|Amitriptyline, 10 mg three times daily|
|Imipramine, 10 mg three times daily|
|Dexamethasone, 16 mg per day in divided doses|
|Methylprednisolone, 120 mg per day in divided doses|
|Drug||Usual starting dosage||Maximum dosage||Cost||Comments|
|Acetaminophen||10 to 15 mg per kg||3 to 4 g per day||Low||Potential liver toxicity, available over the counter|
|Aspirin||10 to 15 mg per kg||3 to 4 g per day||Low||High dosages not recommended for elderly patients, available over the counter|
|Celecoxib (Celebrex)||100 mg twice daily||200 mg three times daily||Very high||Useful in those at risk for upper gastrointestinal tract bleeding|
|Fenoprofen (Nalfon)||200 mg four times daily||800 mg four times daily||Low|
|Flurbiprofen (Ansaid)||50 to 100 mg twice daily||100 mg three times daily||Medium|
|Ibuprofen||400 mg every 6 to 8 hours||800 mg four times daily||Low||Available over the counter|
|Indomethacin (Indocin)||25 mg three times daily||50 mg four times daily||Low||High dosages not recommended for elderly patients|
|Ketoprofen (Orudis)||50 mg every 12 hours||75 mg four times daily||Medium||Higher than average renal excretion, available over the counter|
|Ketorolac (Toradol)||10 mg every 6 hours||10 mg every six hours||High||Not indicated for long-term use|
|Nabumetone (Relafen)||1 g per day||2 g per day||High||Can be used once a day|
|Naproxen (Anaprox)||275 mg every 12 hours||550 mg twice daily||Low||Available over the counter|
|Rofecoxib (Vioxx)||12.5 mg per day||50 mg per day||Very high||Useful in patients at risk for upper gastrointestinal tract bleeding|
|Drug||Equivalent dose||Usual starting dosage||Maximum daily dosage|
|Tramadol (Ultram)||20 mg||1 tablet (50 mg) four times daily||400 mg (8 tablets) given in divided doses every 6 hours|
|Aspirin with codeine no. 3 (Empirin W Codeine)||325 mg/30 mg||1 tablet four times daily||3,900 mg/360 mg (12 tablets) given in divided doses every 4 to 6 hours|
|Acetaminophen with codeine no. 3 (Tylenol W Codeine)||325 mg/30 mg||1 tablet four times daily||3,900 mg/360 mg (12 tablets) given in divided doses every 4 to 6 hours|
|Acetaminophen with oxycodone (Percocet)||325 mg/5 mg||1 tablet four times daily||3,900 mg/60 mg (12 tablets) given in divided doses every 6 hours|
|Aspirin with oxycodone (Percodan)||325 mg/4.9 mg||1 tablet four times daily||3,900 mg/59 mg (12 tablets) given in divided doses every 6 hours|
|Acetaminophen with hydrocodone (Vicodin)||500 mg/5 mg||1 tablet four times daily||4,000 mg/40 mg (8 tablets) given in divided doses every 6 hours|
|Morphine||5 mg||1 tablet every 4 hours||No maximum dosage|
|Propoxyphene (Darvon)*||65 mg||1 tablet four times daily||600 mg (9 tablets) given in divided doses every 6 hours|
|Acetaminophen with propoxyphene (Darvocet)*||325 mg/50 mg||1 tablet four times daily||3,900 mg/600 mg (12 tablets) given in divided doses every 6 hours|
|Opioid drug||Equianalgesic dosage||Initial oral dosage||Comments|
|Oral dosage||Parenteral dosage|
|Morphine||30 mg every 3 to 4 hours||10 mg||30 mg every 4 hours||Available in a long-acting preparation|
|Codeine||180 mg every 3 to 4 hours||NA||60 mg every 3 to 4 hours||Higher incidence of side effects than morphine|
|Oxycodone (Roxicodone)||30 mg every 3 to 4 hours||10 mg||10 mg every 3 to 4 hours||Available in a long-acting preparation|
|Hydromorphone (Dilaudid)||7.5 mg every 3 to 4 hours||1.5 mg||6 mg every 3 to 4 hours||Lower incidence of side effects than morphine|
|Levorphanol (Levo-Dromoran)||4 mg every 6 to 8 hours||2 mg||4 mg every 6 to 8 hours||Higher incidence of side effects than morphine|
|Methadone||20 mg every 6 to 8 hours||10 mg||20 mg every 6 to 8 hours||Lower incidence of side effects than morphine|
|Conversion to methadone at higher dosages may require only 3 to 5 mg per 30 mg of morphine|
|Oxymorphone (Numorphan)||NA||1 mg every 3 to 4 hours||NA|
|Tramadol (Ultram)||100 mg four times daily||80 mg||50 mg every 6 hours||Maximum of 8 tablets per day|
|Fentanyl (Duragesic)||24-hour dose of any of the above is equivalent to 50 μg per hour of transdermal fentanyl||25 μg per hour patch||Lower incidence of side effects than morphine|
Best used in patients with stable pain because the patch is applied only every three days
|Meperidine (Demerol)*||300 mg every 3 to 4 hours||75 mg||NR||Possible accumulation of toxic metabolites|
|Butorphanol (Stadol)*||NA||2 mg||NA||Can cause withdrawal symptoms in opioid-dependent patients|
|Nalbuphine (Nubain)*||NA||10 mg||NA||Can cause withdrawal symptoms in opioid-dependent patients|
|Pentazocine (Talwin)*||180 mg||60 mg||Can cause withdrawal symptoms in opioid-dependent patients|
|Buprenorphine (Buprenex)*||NA||0.3 mg||NA||Can cause withdrawal symptoms in opioid-dependent patients|
Sometimes patients may need to change from one opioid to another because of side effects or the need to alter the route of delivery. Changing opioids is best done using an equianalgesic chart (Tables 37–9 and 48,9 ). When a strong opioid is needed, it is common to start with morphine. The sustained-release form of morphine is equally effective and causes less nausea and sedation.11 Oxycodone (Roxicodone) and fentanyl (Duragesic) are also available in sustained-release preparations. These agents usually have fewer side effects than morphine, but they cost more.12,13 Although the oral route is usually preferred, patients with upper gastrointestinal tract disease or confusion may require rectal or transdermal administration of opioids. Intravenous administration is occasionally necessary when more conventional routes are unsuccessful. Referral for intrathecal administration is useful in rare instances, such as when pain is intractable to standard treatment.
Certain medicines routinely used in the treatment of acute pain are ill-suited for the management of ongoing pain, especially in debilitated patients. Meperidine (Demerol), propoxyphene (Darvon) and pentazocine (Talwin) have metabolites that can accumulate to toxic levels over time.8 Partial opioid antagonist analgesics should not be used, especially for breakthrough pain in a patient receiving a regularly scheduled opioid, because administration of these agents can cause an acute withdrawal reaction.8
USE OF OPIOIDS
Pseudoaddiction (drug-seeking behavior caused by inadequate analgesic medication prescribing) is more likely to be present in extremely ill patients. In pseudoaddiction, the drug-seeking behavior stops when adequate medication dosages are given. In true addiction, drug-seeking behavior continues to escalate.
Patients often believe that pain is inevitable and will become uncontrollable—a fatalistic view that is sometimes shared by inexperienced health professionals.17 Tolerance (the need for increasing dosages of a medicine over time to achieve the same result) is a normal physiologic occurrence in any person who takes opioids for more than a few days. Patients with stable pain sometimes need gradually increasing dosages. Because there is no therapeutic ceiling for morphine, extremely large dosages can be used safely and effectively if the drug is titrated properly.
Worsening pain is often a sign of worsening disease. Therefore, patients may tolerate increasing pain in order to deny their worsening condition. It is important to clarify whether each escalation of the opioid dosage is due to tolerance, worsening illness or inappropriate usage. Patients with a strong fear of opioid tolerance in the future have been found to have higher pain intensity in the present. Consequently, both their anxiety and their pain should be treated.18
Physicians also erect barriers to the effective use of opioid analgesics. They may subtly convey the idea that “good” patients do not complain or need narcotics. Hoping to please these physicians, some patients withhold complaints of pain. In addition, physicians may not anticipate predictable side effects of narcotics and may not educate their patients about them. Therefore, they may set up a situation in which patients choose pain relief with side effects or choose not to take the pain medication.
Physicians often separate curative care from palliative care. Consequently, they withhold adequate pain relief until curative attempts have failed. Because pain relief does not interfere with any accepted treatment for cancer or most other painful conditions, this approach adds unnecessarily to patient suffering.
Finally, some physicians withhold narcotics until death is imminent because they are concerned about running afoul of their state medical board or the U.S. Drug Enforcement Agency. These regulating bodies have rules about the proper use of narcotics. If followed, these rules should not interfere with the proper care of a dying patient or put physicians at significant risk.
STEPPED CARE IN PAIN RELIEF
Based on these guidelines, pain that is assessed as mild to moderate with no previous treatment should be treated with nonopioid analgesics, or step 1 drugs (Table 2).8 For previously treated pain, analgesic dosages should be optimized. Coanalgesic or adjuvant drugs should be added as appropriate, depending on the type of pain.
Moderate pain or pain that has not responded to previous treatment should be treated with weak opioids, or step 2 drugs (Table 3).7–9 In general, step 1 analgesics should be continued as step 2 analgesics are added. If not already started, appropriate adjuvant drugs should be used when step 2 drugs become needed.
Patients with initial severe pain or pain that does not respond to steps 1 and 2 drugs should be treated with strong opioids, or step 3 analgesics (Table 4).8,9 Step 1 drugs often should be continued into this stage, but step 2 analgesics are redundant and should be discontinued. Low dosages of step 3 drugs are much better tolerated than higher dosages of step 1 or 2 analgesics, because of the limited dosage ranges of step 1 and 2 medications and the lower incidence of side effects with the strong opioids.
When possible, drug side effects should be anticipated and prevented to lessen the patient's overall suffering. Most step 1 medications have the potential to cause dyspepsia, which can be prevented with misoprostol (Cytotec). Geriatric patients are at particular risk for gastrointestinal side effects from non-steroidal anti-inflammatory drugs. In addition, these patients probably cannot tolerate maximal dosages of acetaminophen because of liver toxicity. They can tolerate low dosages of step 3 drugs more safely than full dosages of step 1 or 2 drugs.10
Predictable side effects of opioids include nausea, constipation, sedation and, occasionally, myoclonus (Table 5).7,8 Nausea is common and most often occurs at the beginning of opioid therapy. This side effect should be treated quickly but judiciously, because antiemetics have their own side effects. Constipation is so common that a bowel regimen ought to be started as soon as opioid therapy is initiated. Mild sedation is usually tolerated fairly well, and significant sedation can be treated with psychostimulants.20 Myoclonus is a less common side effect and can be treated with clonazepam (Klonopin) or nifedipine (Procardia). Respiratory depression is very rare when opioids are used properly.
|Nausea||Metoclopramide (Reglan), in a dosage of 5 to 10 mg four times daily, or a phenothiazine (e.g., promethazine [Phenergen]) is usually better tolerated than an antihistamine.|
|Constipation||First-line therapy is increased hydration and bulk agents.|
|Second-line treatment is lactulose (Cephulac) or a mild stimulant such as senna (e.g., Senokot) or bisacodyl (Dulcolax).|
|The last option is to use castor oil or products that contain magnesium.|
|Sedation||Dextroamphetamine (Dexedrine), in a dosage of 2.5 to 5 mg twice daily, or methylphenidate (Ritalin), in a dosage of 2.5 to 5 mg twice daily|
|Myoclonus||Clonazepam (Klonopin), in a dosage of 0.5 mg three times daily, or nifedipine (Procardia), ina dosage of 10 mg three times daily|
|Respiratory depression||As long as patient is oxygenating, a temporary reduction in narcotic dosage should suffice; rarely, a diluted, slowly administered dose of naloxone (Narcan) can be used.|
Coanalgesic, or adjuvant, medication may be used as first-line therapy for atypical pain or may be added to any step of the treatment ladder to manage a specific type of pain (Table 1).7,8 For example, corticosteroids and antidepressants may be used to aid the treatment of a variety of pain types. Because neuropathic pain often responds poorly to opioids alone, it is usually necessary to add an anticonvulsant, mexiletine (Mexitil), clonidine (Catapres) or baclofen (Lioresal).7–9 Bone metastasis can be treated with pamidronate (Aredia), calcitonin (Calcitonin) or strontium 89.7,9
Additional procedures to assist in the relief of pain and suffering include topical agents, physical therapy, massage, transcutaneous electrical nerve stimulation (TENS), radiation therapy, chemotherapy, psychotherapy and pastoral care.
Topical agents can be useful in treating cutaneous and musculoskeletal pain. Physical therapy and massage are helpful for musculoskeletal pain. Radiation therapy is often used in a palliative manner but tends to be most successful in patients with mild to moderate neuropathic pain.21 TENS has been used in a variety of pain syndromes, although often with variable results.8
Psychologic illness is associated with poor pain relief. Consequently, relaxation techniques, positive imagery and cognitive behavioral therapy may be helpful in reducing pain directly or in reducing anxiety that aggravates pain. Consultation with clergy can often be valuable, in that spiritual crises can exacerbate pain.
Communication with the Family
In one study on end-of-life care, many patients reported having inadequate communication with their physicians, and several patients reported feeling abandoned.22 Bereaved family members indicated that improved communication and greater access to the physician were the two most important ways to improve end-of-life care.22 Many family members reported that their physicians left them uninformed and that the lack of information created uncertainty among these valuable members of the care team. Therefore, proper care of the dying patient requires communication with the patient's caregivers and attention to their needs.
The Home Visit
Many patients choose to spend their final days at home. The advantages of home care include patient and family privacy, a sense of security and familiarity, and enhanced patient autonomy. Family and friends are more likely to stay involved when a patient is receiving home care. Finally, with home care, there tends to be a reduced focus on illness and more attention to daily living.
The home visit is one of the physician's most powerful tools. This visit enhances communication and other aspects of the care of a dying patient. It allows the physician to provide support to the patient and family and to assess the interaction of patient, family members and other participants in the care team. The home visit uniquely enables the physician to see the role of the patient in the family and to better understand how to integrate this role into management strategies.
The home visit also provides a setting for the physician to meet with the patient, family members, hospice workers, other care providers and, hopefully, the person who holds power of attorney for the patient. Documents relating to a living will and advanced directives should be reviewed.
During the home visit, the physician should address the practical needs of the patient that interfere with pain management. For example, the patient may need assistance with various activities of daily living. The physician can discuss situations in which the family or patient should call the hospice nurse or 911. The question of financial help to pay for the patient's care can also be addressed. In the modern managed-care environment, it is reassuring to know that team-oriented palliative care is usually less expensive than traditional aggressive terminal care.23