FOCUS v1n6 painmgmt

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Volume 1, Number 6

Pain Management inTerminal DiseaseRobert V. Brody, MD

In the past two decades, dramatic progress has been madein the successful treatment of pain in patients with terminaldiseases. The sources of these advances include researchlaboratories which are sorting out the mechanisms of pain, andthe consumer-based hospice movement, which has insisted thathealth professionals pay as much attention to symptommanagement as they do to disease management. In addition,pharmaceutical companies have made available new prep­arations of analgesic agents, and anesthesiologists and neuro­surgeons have attempted to define the role of invasive pro­cedures for pain control.

As the AIDS epidemic has grown, care strategies developedfor other terminal patients have been successfully adopted forthose with manifestations of the new syndrome. This isespecially true for plans of care for cancer patients, individualswho often show the same protracted downhill course withincreasing debility and dependence over time as seen in AIDSpatients. Thus, approaches to pain management in AIDS havegrown out of approaches to pain management in cancer, and itis these that I will discuss.

The Experience of Pain in AIDSBonica has estimated the prevalence of pain in cancer

patients as 40% in those with intermediate disease and 60-90%in those with advanced disease. No such proportion has beendetermined for AIDS patients, but the intensity and prevalenceof pain in AIDS is probably less than with cancer 0. Martin,Hospice of San Francisco, personal communication). In fact, othersymptoms in AIDS patients are often more debilitating anddifficult to control than pain, especially behavioral changes anddiarrhea. This latter devastating symptom actually makestreatment of pain easier because the patient can tolerate highdoses of narcotics without the otherwise universal constipation.Nevertheless, pain does occur in AIDS patients; and when itdoes, it must be addressed in a comprehensive and aggressivemanner.

Pain is always more than a distressing sensation, oreven theperception of a distressing sensation. It is useful to think of painas a person's emotional experience of a distressing sensation;thus, morale and mood can be as important as the intensity ofthe feeling itself in determining the degree of pain. This intensityof feeling is relatively constant, whereas the intensity required toelicit spontaneous complaints is highly variable.

Factors which can decrease the threshold of suffering paininclude any type of discomfort, such as insomnia. fatigue,anxiety, fear, anger, sadness, depression, and especially the

A REVIEW OFAIDS RESEARCH

May 1986

memory and expectation of pain. On the other hand, thethreshold can be raised by the relief of other symptoms,especially depression and anxiety. In addition, sleep, rest,sympathy, understanding. diversion, and analgesic agents canhave a beneficial effect. This broader view is especially importantin controlling the chronic pain of terminal disease, since chronicpain does not serve the protective or warning function of acutepain.

Treatment ApproachesHow, then, should one approach a patient in pain? As with

other medical compaints, a careful history and physicalexamination are indicated. Assessment instruments have beendeveloped to help the physician or nurse gather necessaryinformation, which falls into several dimensions:

(a) Pain location, intensity (perhaps objectified on a linearscale of one to ten), quality, onset. and duration all describe thesensory dimension.

(b) The physiological dimension can be described withlaboratory or radiological data.

"Pain is always more than a distressingsensation. It is useful to think ofpain as aperson's emotional experience ofadistressing sensation; thus, morale andmood can be as impotant as the intensityof the feeling itself in determining thedegree ofpain."

(c) The affective dimension notes the presence or absence ofanxiety or depression or other alterations in mood.

(d) Aggravating or ameliorating factors are importantbehavioral data.

(e) The cognitive dimension describes the meaning which thepatient attributes to the pain or the diagnosis.

Assessment must include past experiences with pain, andexperiences with both effective and ineffective therapies shouldbe documented. The functional status of the patient is alsoimportant. Physical examination should use the dues gained inhistory-taking to search for as specific a cause for the pain as canbe defined.

What is the cause of pain in terminal disease? Pain mayresult from the disease process, the therapy for the disease, or itcan be unrelated to the underlying disease. Thus a tumor mayinvade bone, compress a nerve, infiltrate a blood vessel, obstructa hollow organ, or cause swelling in a structure with a tight

continued on page 2

Alb~sHEALTHPROJECT

A Publication of the AIDS Health Project, University of California San FranciscoFOCUS is a monthly publication of the AIDS Health Project, an organization concerned with AJDS Prevention and Health Promotion. Fundedby a grant from the state Department of Health Services to the San Francisco Department of Public Health, FOCUS presents AIDS researchinfonnation relevant to health care and service providers. The AIDS Health Project is affiliated with the University of Califomia san Franciscoand the Department of Public Health.

Editor: Michael Helquist; Medical Adviser. Stephen Follansbee, MD; Administrative Assistant: Joseph Wilson.Director, AIDS Health Project: James W. Dilley. MD.

Pain Management ...conUnued from cover

capsule. In addition, surgical, chemotherapeutic, or irradiationmanipulations may result in pain. Finally, the patient dying ofcancer or AIDS may have a heart attack or broken boneunrelated to the terminal disease.

It is best to attempt local, specific therapy for the processcausing pain before relying on systemic analgesia. For instance,a boney metastasis may be irradiated for pain control, while atthe same time a non-steroidal anti-inflammatory drug may beadministered to antagonize the prostaglandins released at theperiphery of the lesion. (Prostaglandins are a group of fatty acidderivatives present in many tissues).

Tumors or other space-occupying lesions in the head mayproduce severe headache for which prednisone or otheradrenocorticosteroid may be used; these agents are also usefulfor pain caused by nerve infiltration. The potential deletriouschanges in the immune system induced by steroids are faroutweighed by the relief from suffering the patientexperiences.

There comes a point for many terminal patients when localtherapy will not control pain, and systemic analgesia is needed. Ithink it is important to remember that not all terminal patients inpain require narcotics. Aspirin, acetaminophen, non-steroidalagents - all are perfectly appropriate to use and are preferredfor their lower side effect and abuse potential. However, these,like all analgesics, must be used on the proper schedule. Nochronic pain syndrome should be treated with medication on ap.r.n. (as circumstances require) or as-necessary basis; thisdosing requires the patient to suffer pain before the next dose isadministered. Rather, the drugs should be administeredaround-the-clock to abolish the memory and expectation ofpain and therefore raise the pain threshold.

Behavioral therapy for pain in terminal disease can be veryhelpful for selected patients. Among the methods in commonuse are hypnosis, biofeedback, and psychotherapy. Othermodalities include accupuncture, physical therapy, heat, ice,massage, and transcutaneous electrical nerve stimulation(affecting the nerves that provide sensory pathways for stimulito the skin).

Narcotic InterventionsIf behavioral therapy and conventional analgesics,

including codeine and oxycodone or Percodan, are insufficientto control pain, then a shift to the narcotic analgesics isindicated. That these agents are under-utilized is welldocumented. Some physicians are afraid of the sedation andrespiratory depression induced by morphine and other nar­cotics. However, if the amount of the drug is carefully titratedagainst the pain in increasing doses, this central nervous systemdepression is minimal, especially after the first 48-72 hours. -

Professionals, patients, families, partners, or friends mayfear that the patient may become addicted to morphine.Certainly persons taking more than a minimal amount ofnarcotic for more than ten days are likely to show an abstinencesyndrome upon withdrawal of the drug, but the drug-seekingbehavior that marks the true addict is never seen in terminalpatients who take the narcotic to allow themselves to function asnormally as possible in the world. Finally, some observers worrythat patients will use narcotics to commit suicide. However,hospice workers report that if care-givers successfully addressthe two fears of dying people, the fear of abandonment and thefear of suffering, then suicide ceases to be an issue.

Morphine is the most useful narcotic for the severe chronicpain of terminal disease. Demerol is rarely used because of itsshort duration of action. Dilaudid is useful for those who find thesmall pills easier to take than the sometimes nauseatingmorphine elixir, and it is available in rectal suppository form iforal dosing is not possible for a short period. Heroin andmorphine are equally potent when proper doses are compared,

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and the only advantage of heroin seems to be its increasedsolubility so that a smaller volume can be used for intramuscularinjection. Oral preparations of the narcotics are preferred as theyare effective and are easy for patients and others to administer.Morphine should be given in an oral dose about two times theintramuscular, intravenous, or subcutaneous dose. Caregiversshould note the duration of relief to ensure the abolition of thememory and expectation of pain. With the introduction oflong-acting preparations of morphine which can be admin­istered every eight or even every twelve hours, nighttime dosingcan be eliminated. Methadone is less useful because of itspropensity to accumulate in the body. The concentrated oralsolution of morphine is useful in patients no longer able to takenormal amounts of fluid by mouth.

"Behavioral therapy for pain in terminaldisease can be very helpful for selectedpatients. Among the methods in commonuse are hypnosis, biofeedback, andpsychotherapy. Other modalities includeaccupuncture, physicial therapy, heat,ice, massage, and transcutaneouselectrical nerve stimulation (affecting thenerves that provide sensory pathways forstimuli to the skin). "

Side effects of narcotics can be anticipated and aggressivelymanaged. Nausea may be handled with pre-treatment with aphenothiazine, like Compazine and others; sedation, asmentioned, resolves after several days. The side effect usuallymost troublesome, and which must be anticipated with anadequate therapeutic regimen, is constipation, but for manyAIDS patients even morphine cannot slow the constant diarrhea.

Adjunctive pharmacological analgesia is useful whentreating with narcotics. The non-steroidal agents may allow theuse of lower narcotic doses with fewer side effects. Tricyclicagents, especially imipramine, amitriptyline, and doxepin, blockserotonin uptake and have an analgesic effect which occursearlier and at a lower dose than that seen when treatingdepression. Finally, anxiolytic or antidepressant medications arehelpful as analgesics when anxiety and depression lower thepain threshold.

In those very few patients for whom oral or other systemicnarcotics cannot control pain, nerve blocks, narcotics to affectthe intrathecal (within the spinal canal) or epidural (the areaabove the membrane covering the spinal cord) areas, or evenneurosurgical procedures may be considered. The indicationsfor these must be individualised.

In summary. the aims of pain control in dying patients are(a) to identify and address the cause of pain, (b) to preventchronic pain, (c) to erase the memory of pain in order to diminishanxiety, (d) to allow the patient to remain alert, (e) to allow thepatient to function as normally as possible, (f) to permit thepatient to have a normal affect, to have feelings, and to expressthem, and (g) to do this with greatest ease for the staff andfamily caring for the patient.

Robert V. Brody, MD is an Assistant Clinical Professor ofMedicine at UCSF and the Assistant ChiefofMedical Clinics atSan Francisco General Hospital. He is a memberof the Board ofDirectors of VNA of San Francisco, the parent organization ofHospice ofSan Francisco, and he serves as chair of the HospiceCommittee and Program Committee for the new Coming HomeHospice Residence.

Diagnosis/TreatmentHemophilia and AIDSMichael Helquist

People with hemophilia speak of their disbelief and dis­illusionment when the serious impact of AIDS upon theircommunity became apparent in 1982'. Many adults with theblood disorder had achieved a certain normality in their dailylives; they were able to control their bleeding problems withinfusions at home of Factor VIII or Factor IX, both blood clottingcomponents developed in the late 19605. Reconstructiveorthopedic surgery to correct the arthritis that often results fromthe disorder had become available, and many hemophiliacscould anticipate a nearly normal life-span.

When AIDS was first linked to blood clotting products, therecently-attained degree of autonomy, well-being, and stabilityof health among hemophiliacs was threatened. People withAIDS and hemophilia reported that once again they en­countered the misunderstanding, prejudice, and ostracism ofsociety that they had long endured as a result of their blooddisorder. Now they faced renewed discrimination plus a newlife-threatening illness.

A Blood DisorderHemophilia is the medical term applied to congenital

disorders that disrupt coagulation of the blood. These disordersleave hemophiliacs susceptible to bleeding that cannot bestopped without special treatments. The treatments essentiallyreplace the proteins that are deficient in the different types ofhemophilia. Thus, people with hemophilia A have a deficiency ofthe protein Factor VIII and must use manufactured treatments ofFactor VIII to control their bleeding. Those with hemophilia Black the protein Factor IX and must replace it with Factor IXproducts. 80th types of hemophilia are sex-linked disorders,transmitted from asymptomatic mothers to sons; thus bothhemophilia A and 8 are found in males only. The disorder isusually diagnosed either at birth due to family history or duringthe first year of life.

Symptoms of hemophilia can range from the mild to thesevere. Unlike the popular conception, hemophiliacs do not riskbleeding to death due to a minor cut. Instead, the major problemresults from intemal bleeding into the joints, muscles, andorgans. Often pain is a constant companion as a result of thearthritis and crippling that may develop after bleeding intojoints.

Hemophila and AIDS in the U.S.The Centers for Disease Control (CDC) notes a total of 156

cases of AIDS among hemophiliacs in the United States as ofApril 7, 1986. (San Francisco has had only two reported cases ofpersons with hemophilia and AIDS). The individuals have alldeveloped the disease as a result of receiving clotting factorconcentrates contaminated with the AIDS virus. The incidencerate of AIDS is higher in persons with hemophilia A, although afew individuals with hemophilia 8 have also developed AIDS2.

People with hemophilia A are more likely to have a severedeficiency of the blood clotting factor and thus receive moreclotting concentrate than those with hemophilia B. Thisdifference likely places the former group at a much greater riskfor exposure to viral agents, including the AIDS virus. Inaddition, people with severe clotting deficiences are at a greaterrisk than those with mild to moderate deficiencies.

An estimated 75 to 80% of the heavily-treated Factor VIIIpatients in the United States are seropositive to the AIDS virus.Health workers estimate that there are 1700 seropositivehemophiliacs in Califomia and more than 20,000 in the UnitedStates.

Heat treabnent of the clotting factor components has been

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shown to kill the AIDS virus. The process was initially developedin hopes of decreasing the risk of contamination with non-Anon -B hepatitis virus present in some blood products, but heattreatment apparently has no effect on this additional threat.

Retrospective studies of AIDS among hemophiliacs indicateinitial exposure in 1979 with greater rates of exposure occurringin 1981 and 1982.

The natural history of AIDS infection among hemophiliacsremains unknown. Pneumocystis carinii pneumonia is the mostcommon AIDS-related infection among hemophiliacs in theUnited States; few cases of hemophiliacs with Kaposi's sarcomahave been reported. The CDC also notes the incidence of AIDSRelated Conditions in hemophiliacs, with cases of Iymph­adenopathr, thrombocytopenic purpura, and Burkitt'slymphoma.

Psychosocial IssuesHealth care professionals who work with hemophiliacs.

have reported that several clients continue to fear using theclotting factors; some have discontinued their self-treatments,risking the pain and disability that may result from uncontrolledbleeding episodes.

Although hemophiliacs diagnosed with AIDS experiencethe same complex set of emotions that confront others withAIDS, the diagnosis also leads to unique problems. People withhemophilia fear further misunderstanding and isolation from apublic that still does not understand their bleeding disorder.Many are quite angry about their exposure to AIDS, feeling thatit could have been prevented. Those who also have AIDS areoften troubled with the popular association of AIDS withhomosexual activities and with I.v. drug use. This concem hasled many to "become invisible" about their medical and physicalstatus.

Some hemophiliacs view themselves as outcasts in light ofthe more stringent precautions taken by the health careproviders who work with them. Many are frustrated thatprotocols for AIDS experimental drug trials often excludepatients with complicating health problems like hemophilia.There is confusion about the risk of transmitting AIDS to sexualpartners, and some resentment exists about the lack ofeducational materials developed specifically to address theconcems of the hemophilia community.

On the other hand, public officials and funding agencies arefinding that the hemophiliac community is becoming morepolitically adept and more committed to obtaining funds fortheir own education needs. Several individuals with hemophiliahave assumed positions of leadership to help guide their friends,families, and communities through this most recent challenge.

Although heat-treating processes and use of the AIDSantibody test to screen blood appear to have greatly reduced therisk of further spread of AIDS among hemohiliacs, the highproportion of seropositivity in this risk group will inevitably leadto rising numbers of cases of AIDS. The need for risk reductioninformation, education about hemophilia, counseling, naturalhistory studies, and experimental therapies will only increase asAIDS continues to affect the hemophilia community.Note: The Hemophilia Council of Califomia is a non-profit organizationfunctioning as a consortium of local hemophilia foundations and chapters in thestate. The Council has established a statewide hemophilia AIDS Pro;ect to provideinformation, education, and psychosodal services related to the AIDS epidemic tomembers of the hemophilia CDfTlmunity. The Pro;ect Coordinatorcan be contactedat the following address and phone number: 2206 K Street. Suite 4; Saaamento.CA; (916) 448-7444. The coordinator for the San Francisco and Monterey BayAreas is Paul Murray. LCSW He can be contacted at 2712 Telegraph Avenue.Berkeley. CA 94701. Telephone: (415) 548-8357

References

1. Testimony delivered at Public Hearing on AIDS. Los Angeles City/County TaskForce on AIDS; January 30, 1986.

2. "The Inddence Rate of Acquired Immunodeficiency Syndrome in SelectedPopulations," Hardy AM, Allen JR, Morgan M. and Curran JW lAMA 1985. 253.2: 215-220.

3. "Update: AIDS Among Patients with Hemophilia - United States, .. MMWR1983; 32: 613-15.

"oncVI

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Treatment Update: AZTAzido-deoxythymidine, or AZT, is the latest of several

potentially effective antiviral drugs to be used as an. AIDStreatment. First called Compound S, AZT was tested with 19AIDS and ARC patients by researchers at the National CancerInstitute. Their report, published in The Lancet (March 15,1986), outlined the apparent benefits of the drug. Significantly,AZT was able to penetrate the cerebrospinal fluid - and thuspass the blood-brain barrier - an important function given theevidence that the AIDS virus is capable of infecting the nervoussystem. . . .

The study involved 8 subjects With ARC including personswith symptoms of candidiasis, fevers, lymphadenopathy, nightsweats, and weight loss. The other 11 subjects included 5 withKaposi's sarcoma and 6 who had recovered from a bout ofPneumocystis pneumonia. One of the 19 subjects was female.AZT was given intravenously for 2 weeks, then orally for 4 weeksat twice the intravenous dose. Side effects included headachesand depression of white blood cells.

Of the 19 patients, 15 had increases in their numbers ofcirculating helper-inducer T cells during therapy; 6 who wereanergic (unable to mount an immune response) at entry showedpositive skin test reactions; 2 had clearance of chronic fungalnailbed infections without specific anti-fungal therapy; and 6others had evidence of clinical improvement. The groups as awhole experienced a weight gain of 2.2 kg. The researchers alsoreported that with the highest dose regimen cultures ofperipheral blood mononuclear cells for HTLV-3 becamenegative. . .

The scientists cautioned that based on their study It cannotbe determined "whether AZT can be tolerated over a long time,whether immunological improvements will be sustained,whether viral drug resistance will develop, or ultimately whetherAZT will affect disease progression or survival in patients withHTLV-3 induced disease." They concluded that these questionscan only be answered by appropriately controlled long-termstudies.

The Burroughs Wellcome Company, manufacturers of AlT,have begun a large multi-center trial of the experimental drug.Company representatives report that the logistical demands ofthe trials limit use of the drug to the major cities with AIDS. Theyfurther comment that the study design does not make it practicalto follow patients away from the parent institution involved intrials, and the company has declined many requests to havepatients followed at outside hospitals. (Private correspondenceforwarded to FOCUS, February 1986). The spokesperson, JoanDrucker, MD, medical adviser to the company's infectiousdisease unit, observed that there is great interest in a nationaltrial of AZT with asymptomatic, antibody positive persons, butsuch an effort would have to await further experience with thedrug.

Experimental trials with AZT began in late March in SanFrancisco. Protocols have established a trial with 20 subjectswho have had pneumocystis pneumonia within the last 120days or who have a combination of ARC symptoms (a 10%weight loss in three months, documented culture of thrush, plusother conditions related to AIDS viral infection).

The trials are being conducted at San Francisco GeneralHospital; protocols manager is Doug Beardslee. People withprevious cases of pneumocystis pneumonia have been givenpreference in this initial trial. Beardslee explained to FOCUS t~at

additional trials with AZT are expected thiS summer. People WithARC and those with Kaposi's sarcoma will be eligibile for theselater trials. While news of the increased trials provide hope tomany people with AIDS and ARC, local physicians and mentalhealth professionals have observed that such news reports alsocause anxiety for patients who worry that they won't beincluded in the upcoming trial programs.

Those with questions about the current and future AIr trials in San Franciscoshould contact Beardslee by calling (415) 821-5531.

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BRIEFSRECENT REPORTS

The Impact of AIDS on Medical Residency Training. AIDS hashad a profound effect on the workload, education, and day-to­day emotions of medical residents in major urban centers, ac­cording to Robert M. Wachter, MD of the University ofCalifornia San Francisco. In a report published in the New Eng­land Journal of Medicine (Jan. 16, 1986), Wachter noted thatresidents find care of AIDS patients labor intensive due to theoften exhaustive and invasive workups required to exclude atreatable infectious cause. In addition, residents find that a largeproportion of teaching rounds, conferences, and Grand Roundsis devoted to the care of AIDS patients.

Residents must cope with their own fears of transmission,their frustrations with the limits of current therapies, and some­times their discomfort with the lifestyles of patients with AIDS.Wachter observes, "For house officers involvement in this tragicscenario must exact a substantial psychological toll."

The author does acknowledge that the care of patients withAIDS provides the resident with rewarding personal and profes­sional opportunities, including involvement with a new infec­tious disease that promises to reveal many of the mysteries ofthe human immune system. Wachter concludes that the resi­dents' involvement with AIDS care will be "an indispensableattribute of a well-trained internist for the foreseeable future."

The amount of research information now appearing in themedical and lay press staggers most AIDS health care andservice proViders. This newsletter represents an attempt to placemuch of the data and press reports in a context that will provemeaningfuland useful to its readers. Suggestions andcommentsare welcome and encouraged. Please address correspondenceto Editor, AIDS Health Proiect; 333 Valencia Street, 4th Floor;San Francisco, CA 94103. For information about other AIDSHealth Proiectprograrns, call (415) 626-6637.

NEXT MONTH

The public and the media remain alert to each newreport about the incidence and possible spread of AIDS tothe heterosexual population. Questions abound: Whatrelevance does the high ratio of AIDS among Africanheterosexuals have for Americans? Do prostitutes repre­sent a high-risk group? Do natural history studies of menat risk for AIDS provide applicable information for womenat risk?

In the June issue of FOCUS, Nancy Padian, MS,MPH, epidemiologist and project director of the Cali­fornia Partners Study, will outline the incidence of AIDSand ARC among women in the United states andthroughout the world. Padian will also consider the riskfor women of exposure to AIDS via sexual activities,artificial insemination, and needle-sharing I.V. drug use.

In addition, Paul Shearer, MSVV, LCSW and LeonMcKusick, PhD will discuss the impact on survivors oflosing a Joved one to AIDS. The grief experienced byfamilies and lovers is often complicated by the specialsocial context of AIDS. Shearer and McKusick will suggestapproaches counselors might take to assist survivors copewith their loss.