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Palliative Care and HIV, Part II: Systemic Manifestations and Late-Stage Issues

Last month in Palliative Care and HIV, Part I, Drs. Reiter and Kudler discussed opportunistic infections and cancers in relation to palliative care. Their review concludes this month with a focus on systemic manifestations, approaching death, and hospice reimbursement issues.

Systemic Manifestations of HIV

The final stages of HIV infection are characterized by a series of events leading to death. Antiretroviral resistance, rapid replication of the virus, and deterioration of organ systems all play a role in an acceleration toward death. This process is characterized by a constellation of debilitating symptoms; pain, gastrointestinal discomfort, and depression are almost universal. Palliation of the systemic manifestations should be addressed as aggressively as restorative and prophylactic therapies.

Somatic and Visceral Pain

Since its inception two years ago, the home care and hospice program at the San Francisco General AIDS Clinic has cared for approximately 200 people with disabling disease. Pain is the most frequent symptom, affecting more than 75% of patients. Palliation of pain is achieved with a wide range of agents.

It is essential to classify the type of pain experienced. People who are bedridden or are suffering from an inflammatory or infiltrative process are likely to suffer from somatic pain (e.g., arthralgias, decubiti) or visceral pain (e.g., gastrointestinal, pleural). Somatic and visceral pain are managed with the use of the analgesic stepladder, first promoted by the World Health Organization in 1986. For minor aches or low-intensity intermittent pain, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) may be adequate. Although most of these agents are relatively equivalent in their efficacy, some may cause dose-limiting side effects (Table 1). Step 2 of the ladder includes the lower-potency opiate derivatives, alone and in combination with a step 1 agent (Table 2). Further along the scale are the high-potency opiates (Table 3). As a general rule, medication should be given at a maximum tolerated dose before advancing to medications of greater potency.

An analgesic regimen should be administered around the clock (ATC) in the simplest possible way, in order to prevent anticipated pain. An ATC schedule should be augmented with use of short-acting medications as necessary to treat intermittent or breakthrough pain. For continual treatment of severe pain, useful agents include sustained-release morphine tablets and transdermal fentanyl patches. Medications for breakthrough pain range from step 1 agents such as NSAIDs to step 3 agents such as morphine elixir. Intravenous catheters are rarely necessary for the sole purpose of analgesia.

Many patients and their providers are concerned with the potential adverse effects of opiate agents in the treatment of severe pain. Sedation may be mitigated with the use of amphetamine derivatives such as methylphenidate or dextroamphetamine. These agents are useful for maintaining awareness and arousal and may act synergistically with opiates in analgesic effect. Though remarkably useful in maintaining alertness, stimulants are unlikely to counteract respiratory depression. Respiratory depression and consequent acceleration of death are risks of narcotic use in palliation, but their consideration should be seen as an opportunity to discuss the goals of care with a patient. Many patients would rather forgo pain, even with the incumbent risks of high-dose narcotic analgesia. Others prefer to negotiate between complete sedation and brief periods of consciousness that may be spent with loved ones, despite attendant pain.

Treatment of constipation caused by narcotics is straightforward. The concomitant use of stool softeners and senna when beginning narcotic analgesia often prevents constipation. If constipation occurs, magnesium-based laxatives should be used, followed by a daily regimen of senna and stool softeners.

Chronic Pain and Narcotic Abuse

A simple conversion to either sustained-release morphine sulfate or a transdermal fentanyl patch may be useful for home-bound, terminally ill patients who have been on methadone maintenance. Like any patient with chronic pain, those with a history of narcotic abuse are unlikely to develop addictive patterns when opiates are used for terminal care. Analgesic dosage requirements may be greater; however, as a patient's debilitation progresses, concerns about overuse and abuse become moot. Though prescribing narcotics for the treatment of narcotic withdrawal or addiction is not sanctioned, these patients will usually be suffering from pain and other symptoms at the end of life for which narcotics can legitimately be prescribed. It is the health care provider's duty to assess the patient's needs, and treat symptoms as indicated. Methadone and morphine sulfate are essentially equipotent; it is prudent to reduce the conversion dose by about one-third in order to avoid overdosage. Once a steady requirement is clarified with short-acting agents, an around-the-clock regimen can be developed for prevention of breakthrough pain or withdrawal symptoms.

View this table: [in a new window]   Table 1. Step 1 analgesic agents

 

View this table: [in a new window]   Table 2. Step 2 analgesic agents

 

View this table: [in a new window]   Table 3. Step 3 analgesic agents

 

Neuropathic Pain

Neuropathic pain is extremely common in HIV, affecting 30% to 40% of those seen in some settings. This type of pain can disable patients who are potentially ambulatory. The common causes of peripheral neuropathy in HIV-infected people include HIV-associated sensory polyneuropathy, acute and postherpetic neuralgia, and nucleoside (ddI, ddC, d4T) toxicity. This pain can be distinguished from visceral and somatic pain by its characteristic burning, tingling, and "electrical" sensations. Neuropathic pain is best treated with tricyclic antidepressants (TCAs) and antiepileptic agents (Table 4). Nonsteroidal anti-inflammatory agents are sometimes useful. Opiates are not effective as first-line agents, though they may be used as adjuvant therapy.

View this table: [in a new window]   Table 4. Agents used in the treatment of neuropathy

 

View this table: [in a new window]   Table 5. Antidepressants*

 

Tricyclic antidepressants should be used for initial treatment of peripheral neuropathy. Side-effect profiles of specific agents may aid in their selection. For example, amitriptyline and doxepin are particularly useful for patients with insomnia. Doxepin has the added benefit of being highly antihistaminic, making it ideal for patients with intractable pruritus. Desipramine and nortriptyline are less sedating and less anticholinergic than the former agents. If a patient does not respond to a specific agent in a class, they may respond to another in the same class, e.g., nortriptyline substituted for desipramine. A response should be appreciable within three to five days of administering a low-to-moderate dose, such as desipramine 50 mg a day.

Other antidepressants, such as trazodone and the selective serotonin reuptake inhibitors (SSRIs, such as fluoxetine, sertraline, and paroxetine), have no role in the treatment of neuropathic pain. Antiepileptic agents may be added to a tricyclic once a maximally tolerated dose is determined. Antiepileptic agents are generally started at the same doses as for seizure control. The principles of selection and titration parallel those for tricyclic agents.

Depression

Depression is common in people with HIV, affecting as many as 30% of infected individuals during the course of their illness. The SSRIs are very useful in treating depression, since they are taken once a day, are easily tolerated, tend to be effective, and may provide some needed "activation." Tricyclics remain viable choices in the treatment of depression, especially if they are already being employed for another indication. Combining an SSRI and a tricyclic may precipitate "serotonin syndrome," characterized by tachycardia, flushing, hypertension, diarrhea, muscle rigidity, and mental status changes.

Nausea and Vomiting

Nausea and vomiting are devastating symptoms that affect many who are dying of AIDS. Though nausea and vomiting are often related to opportunistic infections, neoplasms, and medications, the etiology is sometimes never fully clarified. Many antiemetics are effective (Table 6). The care of AIDS patients with nausea and vomiting is not the same as for cancer patients who have these symptoms on chemotherapy. The innumerable causes of discomfort make therapies difficult to generalize. It is usually best to start with one agent, typically prochlorperazine or trimethobenzamide, push to tolerance, and then add another agent of a different class. Concomitant use of three or four agents may be necessary to provide adequate relief.

Diarrhea

Diarrhea can usually be palliated effectively in end-stage AIDS without a diagnostic evaluation. Over-the-counter agents like loperamide and diphenoxylate-atropine are useful when titrated to effect. Both of these agents contain weak opioid derivatives that slow GI motility and affect water and electrolyte movement through the bowel. Deodorized tincture of opium, as well as other potent opiate agents, can be titrated with excellent results for those with intractable diarrhea. Bulk-forming and resin-binding agents should be used with caution due to the risk of fecal impaction from inadequate fluid intake. Octreotide, a synthetic somatostatin analogue with a variety of GI effects, has been shown to be effective in treating diarrhea 50% to 60% of the time. Its major disadvantages are high cost and the fact that it needs to be administered subcutaneously on a regular basis.

Approaching Death

Physicians and other health care providers tend to focus on the technical aspects of care when dealing with an overwhelming illness such as AIDS. The guidelines are important in prescribing adequate palliation, but, as patients approach death, the interpersonal relationship a health care provider develops with a patient and family is one of the best therapeutic tools available.

People with terminal diseases ask difficult questions of health care providers: "When will I die?" "What else can go wrong with me?" "Why do you think I'm ready for hospice now?" These are difficult for even the most experienced clinician to answer. Clinicians' discomfort with the deeply personal and unpredictable nature of these questions is one reason many physicians seek refuge in and emphasize the mechanistic elements of patient care. Yet, it is precisely the personal side of patient care that can make these complex issues more bearable for both patient and physician.

Once palliative care plans have been developed with the home-care team, physicians and other health care providers can concentrate on spending time with patients. It is valuable to take the time to talk with patients about things that might seem excessively time-consuming in usual patient visits. Encouraging patients to speak about their lives and current or past relationships brings up a host of issues and concerns which patients often want and need to revisit. Telling life stories is very healing for patients and families; it has become a technique used by many hospice organizations. Physical contact is important. Sitting by a patient, holding a hand, stroking the head, or rubbing the shoulders are soothing, deeply human methods of providing comfort.

Spiritual reflection often emerges as death approaches. In hospice care, the opportunity to discuss values and hopes can make for a rich and rewarding relationship for both patient and provider. As the decision is made to remain at home and restrict intervention to comfort measures, it is useful to review the situation with the patient. Questions such as: "Where do you think you are in the course of your disease?" and "Do you have any fears or anxieties about the future?" are helpful ways to open these essential discussions.

Often, peoples' connections to their religious traditions emerge or re-emerge after years of dormancy. At times it is helpful to encourage a patient to explore personal values and spiritual concepts. Most hospice programs are associated with clergy; arranging a clerical visit for a patient may be useful.

View this table: [in a new window]   Table 6. Antiemetics

 

View this table: [in a new window]   Table 7. Representative Medication Costs*

 

Hospice Reimbursement

Contemporary hospice care has evolved largely in response to the needs of patients with end-stage cancer. The hospice and palliative care needs of patients with AIDS are different from those of cancer patients in that the most appropriate palliation in AIDS is often achieved through standard restorative modalities. This paradigm shift in palliative care has been difficult for hospice administrators and insurance companies to appreciate, for two reasons: first, hospice providers and insurers have had to recognize the needs of patients with AIDS as different from those of cancer patients, and second, reimbursement mechanisms for hospice care are inadequate to pay for the medications that often provide the best palliation for patients with AIDS.

In western Massachusetts, the usual hospice reimbursement is $75 to $100 per patient, per day. This amount must cover the costs of medication, nursing, social services, and psychological and pastoral care, as well as the administrative staff necessary to support these services. Adding medications that may cost $50 to $1000 per week severely stretches the budget of most hospices (see Table 7). As an example, the weekly cost of IV ganciclovir is approximately $245. This would consume 35% to 46% of a patient's weekly hospice funds. IV foscarnet therapy would exceed the entire allotment.

Many communities cope with these financial constraints by relying on visiting nurse services, avoiding hospice referrals until the last day or two of a patient's life. The patient's insurer will continue to cover the cost of medications when hospice is circumvented in this way. The obvious problem with this approach is that the hospice staff members who are best equipped to help the patient and family in this terminal stage of the patient's illness are not involved with the patient until the final days of life. Once the last-minute hospice referral is made, the visiting nurses who have developed a relationship with the patient and family will not be present for the final days of the patient's life.

Private, state, and federal insurers are currently paying for care that is provided in this ad-hoc system. These insurers, in consultation with providers of HIV-related medical care, need to re-evaluate reimbursement mechanisms for AIDS patients in hospice so that excellent palliative care can be provided by those best trained and equipped to do so.

Conclusion

Palliation of HIV disease should be patient-centered. It should be predicated on patient preference, effectiveness in relieving symptoms, ease of administration, and minimization of side effects. Many restorative therapies are appropriate palliative therapies in end-stage AIDS. It is essential for hospice organizations and insurance providers to familiarize themselves with the special aspects of the palliation of AIDS, so that timely care can be appropriately rendered and compensated.

— Gary S. Reiter, MD, FACP, and Neil R. Kudler, MD

Dr. Reiter is assistant clinical professor at Tufts and medical director and associate director, respectively, of the River Valley HIV Clinic and Hospice LifeCare of Holyoke, Massachusetts. Dr. Kudler is clinical instructor at the University of California, San Francisco, and director of Home Care and Hospice at San Francisco General Hospital AIDS Clinic.

Published in Journal Watch HIV/AIDS Clinical Care April 1, 1996

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