data sources: control in palliative c are

Seminars in Ontology Nursing, Vol 14, No 2 (May), 1998: pp 95-109 9 5

OBJECTIVES:

To describe management of com-

mon physical problems that oc-

cur in patients with advanced

cancer.

DATA SOURCES:

PROMOTING

SYMPTOM Research and review articles.

book chapters, and published

guidelines. CONTROL IN CONCLUSIONS:

Effective symptom control for pa-

tients wi th advanced cancer re-

quires the coordinated efforts of a

multidisciplinary team. Excellent

palliation can be achieved in pa-

tients suffering f rom pain. as well

as f rom gastrointestinal, respira-

tory, or dermatologic disorders.

IMPLICATIONS FOR

NURSING PRACTICE:

Nursing is the cornerstone of ef-

fective palliative care. Through

accurate assessments and exper-

tise in delivering pharmacologic

and nonpharmacologic treat-

ments, nurses ensure optimal

palliation of physical symptoms.

PALLIATIVE C ARE

JANET L. ABRAHM

p ROVIDING physical comfort is the corners tone to the relief of suffering in cancer patients. Pain and a number of o ther distressing disorders occur fre- quent ly in this pat ient populat ion 1 and contr ibute significantly to pat ient discomfort. Satisfactory con-

trol of many of these problems can be aeh ievedf and pain can be controlled in over 90% of patients. 3-s This article reviews pharmacologic and nonpharmaeologie t rea tment strategies used to reverse the most co m m o n problems encounte red by patients with cancer.

PAIN

From the University of Pennsylvania School of Medieine. Philadelphia.

Janet L. Abrahm. MD. FACP: Associate Professor of Medicine, University of Penn- sylvania School of Medicine, Philadelphia.

Supported in part by the Project on Death in America, Soros Faculty Scholars Pro- gram.

Address reprint requests to Janet Abrahm. MD. FACP. Philadelphia VAMC (111H), University and Woodland Avenues. Philadelphia, PA 19104.

Copyright © 1998 by W.B. Saunders Company 0749-2081/98/1402-0003,g8.00/0

p ain is usually classified as somatic, visceral, or neuropathie. 6 Determining the type of pain can help elucidate its cause and

indicate the type of pharmacologic therapy(ies) likely to be effective. 7 A comprehens ive pain assessment is required both to choose initial therapy and to measure its effectiveness. 7-12 The oneology patients ' exper ience of pain is often exacerbated by the psyehosoeia113-1s and spiritual a6,17 stresses of their disease ls,19.

In cancer patients, 62%-78% of pain is due to tumor involvement, 19%-25% is due to t r ea tment of the cancer, and 3%-10% is due to an unrela ted condition. 2° Every effort should be made to eliminate the cause of the discomfort. However, while the cause is being determined, while the pat ient is receiving cancer-di rected therapy, or when definitive therapy is no longer possible, the patient 's symptoms can often be relieved. 7

Pharmacologic therapy is the mainstay of cancer pain reliefel; nonster0idal ant i - inf lammatory drugs (NSAIDs), opioids, and adjuvant analgesics all have a role to play. 8,22,23

96 J A N E T L. A B R A H M

Nonsteroidal Anti-inflammatory Drugs The World Health Organization analgesic ladder

(Fig 1) indicates that NSAIDs are useful alone for mild pain, and, along with opioids, for moderate and severe pain. 24 Nonsteroidal anti-inflammatory drugs inhibit prostaglandin synthesis; therefore, they both decrease pain intensity and minimize the inflammation associated with bone or tissue injury that is mediated by prostaglandins. 25,26 Commonly used NSAIDs can be found in Table 1.

Both acetaminophen and aspirin have a "ceiling effect"; 1,000 mg is the ceiling dose for both agents. 27,2s Patients will not get more pain relief from a dose of 1,500 mg of aspirin or acetaminophen than they will from a dose of 1,000 mg. In cancer patients, however, the NSAIDs aspirin, acetaminophen, and ibuprofen are rarely used alone. Instead, combination preparations that include one of these NSAIDs along with an opioid (especially oxyeodone) are usually preferred for patients with mild to moderate somatic or visceral pain. Ketorolac, an NSAID, can be used alone, has the pain-relieving potency of an opioid 29 and is indicated for patients with severe pain.

Contraindications and side effects of NSAIDs. The NSAID-induced inhibition of prostaglandin synthesis can cause serious abnormalities in platelet 3° and kidney function, in the gastrointestinal tract, and in the lungs. Patients receiving these agents are therefore at risk of developing bleeding, a variety of renal and gastrointestinal disorders, and asthma. 31 Most NSAIDs are contraindicated in patients with low platelet counts or who are receiving anticoagulants. Prostaglandin inhibition

S E V E R E

M I L D

NSAID _+ Adjuvant

M O D E R A T E

OXYCODONE CODEINE

NSAID _+ Adjuvant

MORPHINE OXYCODONE DILAUDID FENTANYL METHADONE LEVODROMERAN

NSAID -+ Adjuvant

S T E P 1 S T E P 2 S T E P 3

FIGURE 1. World Health Organization analgesic ladder. 24 If pain persists, advance to next step.

is one of a number of mechanisms by which NSAIDs cause renal toxicity. 32 Renal function therefore must be assessed during the first weeks of NSAID use, especially in elderly patients. 33,34 Patients most likely to develop gastrointestinal bleeding are those older than 60 years; those with a history of previous ulcer disease, NSAID-induced bleeding, or cardio- vascular disease; and those with concomitant use of steroids or anticoagulants or receiving multiple NSAIDs. 35 Nonsteroidal anti-inflammatory drugs are also used with caution in asthmatic patients. 2s

The side effects described above occur with therapeutic doses of NSAIDs. 36 Patients who increase their dose of aspirin above 6,000 mg/d, however, often develop salieylate toxicity, mani- fested by tinnitus, ataxia, hyperventilation, delirium, and coma. 37 Aspirin also can be "hidden" in a combination agent, and overdose can unwit- tingly occur. Aeetaminophen excess from a similar increase in dose of combination medications can induce liver dysfunction, especially in patients who also ingest alcohol, as

Opioid Analgesics While NSAIDs are useful, opioids are needed to

relieve the pain of the vast majority of cancer patients. 21 General guidelines for the use of these agents can be found in Table 2.

Step 2 and 3 agents from the World Health Organization analgesic ladder (Pig 1) are listed in Table 3, along with recommended initial dosing, frequency of administration, adjustment for renal or hepatic failure, and available preparations. Be alert both to the differences between the oral and parenteral potency of the various agents and to the dosing equivalencies between agents, s For example, 1.5 mg of parenteral hydromorphone is equivalent in potency to 7.5 mg orally, a fivefold difference. Dosing equivalent charts are readily available for reference, s

Codeine. In cancer patients, using the step 2 agent codeine is problematic because it is nauseat- ing, dysphoric, and ineffective in those patients who lack a specific hepatic enzyme that converts it to morphine 41 or who are taking drugs that inhibit the enzyme's function, such as eimetidine. 42

Oxycodone. Oxycodone is listed both with the step 2 and step 3 agents because oxycodone is available both in a low-dose combination agent, effective only for moderate pain (step 2), and as pure oxyeodone, for severe pain (step 3). Both short-acting oxycodone and a 12-hour continuous- release preparation are available. 43

S Y M P T O M C O N T R O L 97

T A B L E 1. Nonsteroidal Antiinflammatory Drugs a

Chemical Class Generic Name Interval Initial Dose* Maximum 24-hr Dose

p-aminophenol Acetaminophen EveJ Salicylates Aspirint Ever

Choline magnesium salicylate Ever Salsalate Ever Diflunisol Ever, 12 hr

Propionic acids Ibuprofen Ever t 6 hr Fenoprofen Ever, 6 hr Ketoprofen Ever, 6 hr Naproxent Ever r 12 hr Flurbiprofen Ever, 12 hr

Acetic acids Indomethacin? Ever ~ 8 hr Tolmetin Every 8 hr Diciofenac Every 8 hr

r 4-6 hr 650 mg 6,000 mg r 4-6 hr 650 mg 6,000 mg v 12 hr 750-1,000 mg 4,500 mg t 12 hr 500-1,000 mg 4,000 mg

500 mg NA 400 mg 4,200 mg 200 mg 3,200 mg 25 mg 300 mg 250 mg 1,500 mg t00 mg 300 mg 25 mg 200 mg 200 mg 2,000 mg 25 mg 200 mg

Sutindac Every 12 hr 150 mg 400 mg Ketorotac Every 6 hr 30-60 mg IM load 150 mg d 1

15-30 mg IM every 6 hr 120 mg day 2-7 (orally: 10 mg every 6 hr) (orally: 40 mg)

Abbreviations: IM, intramuscularly NA, not available. *in the elderly and in patients with renal insufficiency start at half to two thirds of these doses. tAvailab e n suppository form McGuire, Yarbro Ferrell: Cancer Pain Management. © 1995 Boston: Jones and Bartlett Publishers. Reprinted with permission.

Morphine. Morphine is available in both sustained-release and immediate-release preparations. Patients commonly receive both a sustained- release agent every 12 or 24 hours 44 to eontrol their baseline pain and a short-acting agent as needed every 2 hours to eontrol unexpeeted exacerbations of pain. For those unable to swallow a pill, the drug pellets contained in the Kadian capsule (Zeneea, Wilmington, DE), if sprinkled on food or put in tube feedings with water, provide 24-hour relief. 44

Meperidine. Meperidine is not recommended for patients with cancer painS,2S; its metabolite, normeperidine, often eauses seizures. 4s

Transdermalfentanyl. Transdermal fentanyl patches are composed of a drug reservoir lined on the bottom with a rate-limiting membrane, which itself is attached to a backing that adheres to the patient's skin. The lipophilic opioid fentanyl, in the pateh's drug reservoir, diffuses into the fat in the skin and is absorbed into the blood stream.

At least 12 hours are needed before there is enough fentanyl in the skin depot to establish an adequate blood level. 46 By 14 to 20 hours, an effective plasma concentration is reached46; steady state is reached by 48 hours, and in most patients is maintained for 72 hours. 4r The patch is not the ideal choice for someone with acute, severe or excruciating pain because of this lag time; it is also problematic in febrile, medically unstable patients because drug absorption from the skin can increase, eausing toxicity. If the patient develops an overdose, a low-dose naloxone drip may be needed for 12 to 24 hours or more to maintain respiration until the drug remaining in the skin reservoir (after the patch is removed) is metabo- lized.3, 4s

9 8 J A N E T L. A B R A H M

TABLE 3. Commonly Used Opioids: Preparations Available s,z~'4°'43,44,49 . _ _ _ _

initial Dose (mg)*

Name Oral IM/IV Dose Interval (hr) Dose Adjustments Needed Preparations Avai[ablet

Morphine 30 10 3-4 Renal failure IM/IV/SQ, R, recta, qu d L q Conc Morphine, SR 60 NA 8-12 Renal/hepatic failure SR Morphine. SR 120 NA 24 Hydromorphone 6 1.5 3-4 Oxycodone, combo 10 NA 3-4 Oxycodone 20 NA 3-4 Oxycodone, SR 60 NA 12 Fentanyl NA 50 pg/h r 72 Fentanyl 200 mg NA 2 Methadone 20 10 6-8 Levorphanol 4 2 6-8

Renal/hepatic failure Renal/hepatic failure

Renal/hepatic failure SR Hepatic failure M/lV/SQ, IR, rectal Renal failure Combo Renal failure IR, liquid Rena/hepatic failure SR Hepatic failure TransdermaJ

Oral transmucosal IM/IV/SQ, IR, liquid IM/IV, IR

Oxymorphone NA 1 3-4 Renal failure IM/IV/SQ, rectal Demerol:l: N/R 100 3 Rena fa ure M/V, tR Tramadol§ 100 NA 4 Renal/hepatic failure IR

Abbreviations: IM, intramuscular y; V, intravenously SR, sustained re ease; NA, not available; N/R, not recommended. *For patients weighing over 110 b who nave moderate to severe pain (from Agency for Health Care Po cy and Research

94-0593: Management of Cancer Pain: Adu ts). t iM/V parenteral, suitable for intravenous or intramuscular use SQ: subcutaneous; R: oral immediately release, SR: oral, sustained re ease; L q Conc: concentrated liquid solution; Combo: oral combination preparation with an NSA D (acetaminophen,

asp r n, ibu profen, etc). :[:Not recommended for use other than for a limited time (see text). §Nonnarcotic, but binds to opioid receptors.

Oral transmncosal fentanyl citrate. Early reports demonstrate the safety and efficacy of a truly immediate-release form of pain relief: transmucosal fentanyl citrate in a palatable solid matrix. 49 Two thirds of pain relief is achieved 15 minutes after initiation of the drug.

Rectal morphine. Administration of sustained- release morphine tablets into the rectal vault or into colostomies has not been approved by the Food and Drug Administration, but it has been extensively studied and found to be safe and effective. 4°

Subcutaneous/intravenous infusions. Some patients will not be able to tolerate oral medication and will not respond to fentanyl patches. Most of these will benefit from subcutaneous infusions 3 of either morphine or hydromorphone. Subcutane- ous methadone is not as well tolerated. 5° Very high opioid doses can be delivered using hydromorphone preparations. 51 Three milliliters per hour of this solution delivers 30 mg/hr of hydromorphone (the equivalent of 200 mg/hr of morphine). If necessary, intravenous infusions can be given through an implanted vascular access device already in place or via a peripherally inserted central venous catheter. 52 Patient-controlled anal-

gesia is available for both the intravenous and subcutaneous routes, s3

Spinal opioids (epidural, subarachnoid). Spinal delivery of opioids produces pain relief because the exogenous opioids bind to receptors for natural opioids (enkephalins) that are already present in the spinal cord. s4,ss Because they are being delivered locally, epidural opioids are effective at one tenth the systemic doses, s6 Morphine is the agent most commonly used in epidural and intratheeal infusions, but fentanyl and its relatives also are used. sr

Spinal opioids benefit those few patients with bilateral or midline pain below the umbilicus whose deep somatic or neuropathic pain syndrome is not responding to systemic opioids, s'ss's9 They can be used alone or with anesthetics or ~-adrenergie agents to improve their efficacy or minimize the opioid-indueed side effects. 5961 Spi- nal opioids/anestheties can be delivered via either temporary epidural catheters or permanent epidural or subarachnoid catheters, s9'6° Patient-controlled epidura] analgesia is available for either temporary or permanent infusions. 62

Temporary catheters are used in some patients to enable them to regain sensitivity to lower doses

SYMPTOM CONTROL 99

of systemic opioids, but they also can be used to determine whether a patient will benefit from a permanent infusion. Patients with bilateral severe neuropathie pelvic pain from recurrent eoloreetal, bladder, or gynecologic cancers involving the lumbosaeral and perineal nerve plexi, for example, have temporary eatheter placement to determine whether the epidural route ean provide effective pain relief.

Cancer patients, who usually are not opioid naive, rarely develop side effects from spinal infusions. If they do, small doses of naloxone can reverse them without eliminating analgesia, s9 The most common complications of spinal infusions arise during implantation (bleeding, perforation of an abdominal or retroperitoneal viscus or lung, pump pocket seromas) 63 or from the catheters themselves (they become dislodged, kink, tear, and cause epidural fibrosis and infection).6°, 63

Adjuvant Analgesic Medications Drugs that are used primarily for other indica-

tions can be analgesic as well. They are given orally, parenterally, or rectally, 64 and are of particular value for patients with bone or neuropathic pain. Adjuvants useful for bone pain are listed in Table 4. Adjuvants useful for neuropathic pain are found in Table 5.

Steroids. Steroids are effective both in patients with malignant bone pain and in those with neuropathic pain, such as that caused by brain metastases, compression of the spinal cord, or infiltration of the brachial or lumbar plexus. 6s They can be given epidurally, intravenously, or orally. Steroids alone have been shown to decrease the acute pain associated with herpes zoster infections, but there is no long-term benefit. 66 Oral steroids also increase patients' appetites and sense of well-being, but results of controlled studies of their efficacy have been conflicting. 67

Side effects of steroids can be a problem.

Misoprostol (200 ~g two to three times per day) is often used to prevent peptie ulcers for patients reeeiving both steroids and NSAIDs. 6s Oral and esophageal eandidiasis can be treated either by low-dose ketoeonazole (200 mg twice a day) or, for patients with the acquired immunodefieiency syndrome or those taking antacids, flueonazole (100 mg a day). Topical oral antifungals such as clotrimazole troehes given three times a day help treat oral lesions but do not prevent esophageal eandidiasis. Steroid-indueed delirium responds to haloperidol (Table 6). 69 Glucose intolerance is easily managed with insulin, but proximal muscle weakness ean be refractory to therapy.

Anticonvulsants. Phenytoin, carbamazepine, and donazepam are used in patients with neuropathic pain that is described as "sharp," "cutting," or "like an electric shock. ''7° Opioids alone can relieve this neuropathie pain, but high doses are often required and the side effects of these doses are often difficult to tolerate.

Baclofen. Baelofen is normally used to relax spastic limbs, but it also relieves trigeminal neuralgia pain. 71 It therefore may help those patients with cancer of the head and neck who develop a neuropathie pain syndrome similar to that of trigeminal neuralgia.

Antidepressants. The trieyclie antidepressants are the best studied in patients with nonmalignant chronic pain, and they also are very useful for many cancer patients with continuous neuropathic pain,7°, 71 and laneinating neuropathie pain. 72 The pain-relieving effects of these agents are independent of their ability to reverse depression and can appear much more quickly (in 4 to 7 days). 72

All antidepressants cause significant side effects: anticholinergie, sedation, orthostatie hypotension, and cardiac arrythmias. Amitriptyline is therefore used with caution in the elderly, in

Drug

Pamidronate Calcitonin

Strontium chloride (Sr 89)

T A B L E 4. Adjuvants for Bone Pain 21

Dose Comments

90-120 mg IV over 4 hr, every 3-6 wk Effective for several months with repeated dosing 100-200 IU SQ twice daily Often effective for weeks to a few months; can cause

symptomatic hypocalcemia Induces signif cant cytopen as; can be used only once

Abbreviations: IV, intravenous; SQ, subcutaneous y. Also see text and tables for discussions of NSAIDS (Tab e 1 ) and steroids (Table 5).


TABLE 5. Adjuvants for Neuropathic Pain 3,s4"66,7°'73

Class Agent Dose Comments

Steroids e5 Prednisone 40-60 mg in div ded doses; taper to Add acylovir for acute herpes every other day as tolerate& zoster (see text) 66

Side effects: gastrointestinal disorders, candidiasis, euphoria, depression, delirium, hypergly- cemia

10-100 mg bolus; 6 mg orally/intravenously four times a day taper as tolerated

Dexamethasone

Anti-convulsants 7° Phenytoin

Carbamazepine 200 mg ora y, at bedt me, ncrease Suspension available for rectal every 3 days administration ~

Do not exceed 1,200 mg/24 hr Clonazepam 0.5 mg three t mes da ly; ncrease Rarely used for neuropathic pain

by 0 5 mg every 3 days Do not exceed 20 mg in 24 hr

Tdcyctic antidepressantsrO, 72

Benzodiazepines 7a Alprazolam

Amitriptyline, imipramine, Begin at 10-25 mg orally, at bed- Side effects: anticholinergic, seda- doxepin, clom pramine time; increase t-o therapeutic tion, cardiac a~hmias, ortho- des pram ne nor[dptyline dose (50-150 mg in divided static hypotension

doses) Amitdptyline: mos t sedating Desipramine: teast sedating,

minima card otoxicity; may need 150-300 mg for therapeutic effect

Nortriptyline: least orthostatic hypotension, minima]sedation

May be given sublingually 0 25-2 mg era ly three to four times a day

patients with a high risk of angle-closure glau- coma, or in patients with bladder Outlet obstruction, arrythmias, or other cardiac conduction problems. 7° Imipramine, desipramine, and nortriptyline are less sedating and have fewer other side effects than amitriptyline, 21 but their efficacy has been less well established. The benzodiazepine antidepressant, alprazolam, may relieve neuropathic pain, 73 but fluoxetine does not. 7°

Opioid-Induced Side Effects and Management Constipation. Constipation is the most com-

mon side effect of opioid therapy3; it usually does not diminish with time. For a brief discussion of constipation, refer to the Gastrointestinal Prob- lems section below.

Sedation. Sedation can be an important dose- limiting side effect in patients taking opioids and can make it difficult for a patient to achieve a satisfactory degree of pain control. Sedation is most prominent when the patient first begins taking opioids, it lessens within a few days, even if

the dose is kept the same. 74 Sustained-release preparations minimize sedation by providing a steady level of pain relief without excessive peak blood levels of opioid. 46,7s,76 If sedation persists beyond the first few weeks, another eause is usually sought (eg, an eleetrolyte imbalance, hyperealeemia, or other sedating medications).

If the opioid is responsible for the sedation, a different opioid may be substituted. If the sedation still persists, a psyehostimulant such as methylphenidate may be added. 77 Amphetamines have been shown to reduce the dose of opioid needed for pain relief by half, to reduce drowsiness, and to enhance mood. 77 A list of effective psyehostimulants and their usual starting doses is given in Table 7.

Respiratory depression. Respiratory depression is an unusual side effect of opioids given to treat cancer pain, so long as the opioid dose is titrated to the degree of pain and the patient's renal and hepatic function remain stable31 Opioid


T A B L E 6. Delirium 64,69

Drug Dose Comment

Halepeddol 0.5-5 mg oratly, IM, SQ, IV*; Do not exceed 20 mg in 24 hr repeat every 2-12 hr as needed. Maintain the patient on the effective dose (divided into a twice-

daily dose) for 3 to 4 d, then taper over 1 wk, as tolerated. Lorazepam 0.5-2 mg every 1-4 hr

Diazepam 10-30 rng Clonazepam 0.5-6 mg three times a day

Methotdmeprazine 12.5-50 mg every 4-8 hr orally, IV, SQ Midazolam 30 to 100 mg over 24 hr

Add to ha operido/for patients with agitated delirium tablets can be used PR for terminal delirium

Useful PR for patients unable to take oral medications. 64 Tablets have been used PR for terminal delirium64; do not

exceed 20 mg/24 hr Do not exceed 30 mg/24 hr Intravenous drip or subcutaneous infusion for terminal delirium

In delirious patients, first attempt to identify the underlying cause and begin to correct it as you give the agents listed; make the patient's surroundings as familiar as possible and have a family member or friend sit with the patient. Abbreviations: IM, intramuscularly; SQ, subcutaneously; IV, intravenously; PR, per rectum . . . . *Oral doses are half as potent as parenteral doses.

sensitivity leading to hypoventilation may occur in some hypothyroid patients, asthmatic patients, or patients with chronic obstructive pulmonary disease and patients taking sustained-release preparations can develop respiratory depression if the absorption or metabolism of the opioid suddenly changes. In all these conditions, the patient will appear sedated. If the patient is anxious or agitated, something other than opioid must be sought as a cause for the respiratory depression.

Laxatives, oral or intravenous motility agents, and enemas are used to help the patient rapidly eliminate remaining drug. If the patient is breathing normally, further opioid doses are withheld; if significant respiratory depression has occurred, a diluted solution of the opioid antagonist naloxone either as a slow intravenous "push" (1 mL [0.4 mg] naloxone in 10 mL normal saline) or a continuous

infusion is indicated. 7s The rate is adjusted to permit re-establishment of normal respirations but to not wake the patient suddenly. A severe withdrawal syndrome may occur if an undiluted injeetion of naloxone is administered.

Delirium. Delirium can be a frightening side effect both for the patients experiencing it and for their families. It manifests with hallucinations, paranoid ideation, disordered thinking and perception, delusions, and labile mood; patients may either appear withdrawn, lying in a fetal position, or agitated, exhibiting what is termed "psychomo- tor behavior. ''69 A number of organic problems cause delirium. Opioids alone are rarely responsible, but a number of other drugs are often implicated; these include psyehostimulants, steroids, short-acting benzodiazepines, and combina- tions of drugs with anticholinergie side effeets. 69

Treatment can begin while the cause is being sought. In some patients, lowering the opioid dose or stopping any other responsible agent will resolve the problem. Having a friend or family member sit with the patient, moving him to a well-known room, leaving the light on, and having a clock, a calendar, and favorite, familiar objects within sight may help the delirious patient. 69 When these measures are not effective, pharmacologic therapy (usually haloperidol) is used 69 (Table 6).

GASTROINTESTINAL PROBLEMS

Oral Oral discomfort in patients with eaneer arises

from poor oral hygiene, mueositis, eandida infee-

102 JANET L. ABRAHM

tions, or dry mouth caused by mouth breathing, previous radiation therapy, or medications. Gen- eral measures for oral comfort include presenting food at moderate temperatures; avoiding dry, aeidie, or highly spiced foods; and minimizing alcohol and tobacco use. 79-81

Oral hygiene should not be neglected. Patients should continue daily brushing using a soft-bristle brush, flossing (with unwaxed floss), and rinsing with an antibacterial mouth wash (that does not contain alcohol) or a solution of bicarbonate in water (eg, 1 tsp in a cup of water), sl They should be monitored closely for the development of mueositis, infection, and xerostomia, and treated promptly, s2

Mueositis due to chemotherapy often responds to granulocyte eolony-stimulating factorS3; sueralfate also has been used to treat chemotherapy- and radiation therapy-induced mucositis, but trials are contradictory concerning its benefit, s4,ss Capsa- iein also may be of benefit, s6 Patient-eontrolled analgesia may be needed for pain relief.

Candida infection presents as a burning tongue or pain when eating or swallowing; white plaques (which are easily wiped off, but bleed) along the sides of the tongue or cheeks, on the gums, or on the roof of the mouth; angular chelitis; or, in denture wearers, red, edematous areas. Mueositis from eandida can be effectively treated with flueonazole or topical antifungal agents, such as clotrimazole troches. 79

Xerostomia should be addressed, as saliva is important to oral health. It is a lubricant, helps control plaque, protects teeth from dissolution and the mouth from bacterial, fungal, or viral infection, and enhances taste and the ability to swallow food. sl Mild xerostomia may respond to sugar-free sour lemon drops or other sugar-free hard candy. For those without cardiac contraindieations, pilo- earpine can be given an hour before meals; it is

especially helpful for patients who have undergone radiation to the oral cavity or neck. sr,ss

In the last weeks of life, dry mouth may be caused by dehydration or opioids used to relieve pain. It is not necessary, however, to reverse the dehydration to relieve this symptom; in fact, no controlled studies have shown that rehydration is effective, sl Moistening the mouth with gauze soaked in ice water and offering sips of water, ice chips, or fruit-flavored ice pops are usually all that is needed, sl

Ascites Aseites occurs most often in patients with

ovarian or breast cancer, but also occurs in patients with genitourinary, lung, and gastrointes- final cancers, s9 For patients whose ascites is refractory to the usual diuretic measures (aldaetone _+ oral furosemide) and who have 1 month or less to live, repeated paracentesis may be the most appropriate therapy, s9 However, for those with a reasonable life expectancy, a perito- neal-venous shunt may provide prolonged syrup- tomatie relief. 9°,91

Constipation Increased water intake, increased activity, fiber

therapies, or disodium disueeinyl doeusate are usually ineffective for patients receiving opioids and may even exacerbate the problem. 21,92 Daily laxatives are therefore indieated in any patient receiving opioid therapy. 92,93 Agents that stimulate the myenterie nerve plexus and osmotic agents are the most effective. 92,94 These are listed in Table 8. For an impaction, glycerine suppositories or olive oil enemas may be required.

D i a r r h e a

Diarrhea may be due to newly acquired lactose intolerance (eg, after chemotherapy), drug side effects, intermittent bowel obstruction, fecal impae-

T A B L E 8 . Laxatives 21

Drug Mechanism In tial Dosage

Senna Myenteric r)lexus simulant 2 tablets orally twice daily B sacody Myenter c p exus s mu ant 5-10 mg ora y or 10 rng per rectum dai y Milk of Magnesia Osmotic 30-60 mL orally three times daily Lactulose Osmotic 15-30 mL orally, at bedtime Go ytely Osmotic 1 cup ora y two to three times da y (routine use for parapleg cs) Milk of Magnesia + mineral oil Osmotic 30-60 mL Milk of Magnesia + 15-30 mL mineral oil every day or

twice daily

SYMPTOM CONTROL 103

tion, sphincter incompetence, chronic radiation enteritis, infection, or products of rare neuroendo- erine tumors, such as carcinoid.

Specific treatment, including octreotide, is often effective. 95 Symptomatic treatment includes lop- eramide or tincture of opium and oral rehydration. 95 To replace potassium, patients can be encouraged to eat bananas. To avoid exacerbating the diarrhea or inducing a recurrence immediately after it resolves, lactose-containing foods should be avoided. Similarly, highly spiced and fatty foods are discouraged. Potatoes, rice, and macaroni are usually well-tolerated.

Nausea and Vomiting Nausea and vomiting are often amenable to

therapy in patients with advanced cancer. Com- mon etiologies in this population include pain, opioids, constipation, gastritis or gastric ulcer disease, gastric outlet or bowel obstruction, hyper- caleemia, hyponatremia, hepatic or renal failure, or disease of the central nervous system. 96 Fre- quent, small feedings of cold foods that have little odor, acupuncture, 97 and hypnosis 9s may alleviate the nausea. Pharmacologic therapies for nausea and vomiting and for bowel obstruction that cannot be treated surgically are reviewed in Table 9.99,100

Anorexia and Nutritional Replacement Anorexia. Anorexia is often distressing both

to patients and to their family members because those who have prepared the food may feel that they, not the food, is what is being rejected. 1°1 The

patient should be evaluated for xerostomia and depression, as both are reversible causes of decreased appetite. In patients with advanced cancer, however, often no clear etiology is appar- ent. Symptomatic treatment includes enhancing the taste of favorite foods and paying careful attention to the patient's likes and dislikes, sueh as avoiding foods with disturbing odors or tastes. 1°1

Unlike anabolic steroids, hydrazine sulfate, and cyproheptidine, the corticosteroids, 6s megestrol acetate, 1°2 and medroxyprogesterone acetate 1°3 have been demonstrated to improve appetite in these patients and may prevent continued weight loss. With prolonged use, however, megestrol acetate may induce adrenal suppression, and the risk of adrenal insuffieiency if the agent is stopped abruptly. TM Dronabinol has proved efficacious in reversing anorexia and weight loss in patients with AIDS, 1°5 but has been less well studied in patients with advanced cancer. 1°6

Parenteral/enteralfeeding. Parenteral or en- teral feeding is most useful early in the course of the illness, while the patient is undergoing surgery, chemotherapy, or radiation therapy. It is more difficult to determine its benefit in the patient with advanced cancer. Parenteral nutrition does not lead to a marked increase in strength or energy in these patients. 1°7 If they are hungry, but cannot eat, a feeding jejnnostomy or gastrostomy may be indicated. Most, however, do not complain of hunger or thirst, l°s Rather than asking them to undergo this invasive procedure, therefore, con-

T A B L E 9. Antiemetics 21,9~.10°

Etiology of nausea . . . . Dose

Initiation of opioid therapy Prochlorperazine 10 mg orally or 25 mg PR two or three times daily Stimulation of chemoreceptor trigger zone Halopeddol 1.5-5 mg orally three to four times daily; 2-10 mg IM

two to three times dally Prochlorperazine . . . . orally or 25 mg PR two to three times daily

Delayed gastric emptying Vertigo

Bowel obstruction*

Methotrimeprazine Metoclopramide Hycosine (scopolamine) Meclizine Octreotide

Multiple causes, refractory Ondansetron

2-6.25 mg IM three times daily or 6-25 mg over 24 hr 10-20 mg two to four times daily or 1-3 mg/hr IV 0.3 mg three times daily orally or SQ 50 mg orally three times daily or 25-50 mg IM 50-100 pg SQ two to three times daily or 300 #g over

24 hr SQ 4-8 mg orally two to three times daily

or nausea, initial steps should be (1) treat cause if identified; (2) consider changing to a different opioid agent (see text); and (3) use adjuvants to decrease opioid dose. *For symptomatic therapy when surgery is not possible. Abbreviations: PR, per rectum; IM, intramuscularly; IV, intravenously; SQ, subcutaneously.


sider helping the family to unders tand why a feeding tube would not be of benefit.

RESPIRATORY PROBLEMS

Dyspnea Dyspnea is frightening to patients and their

families; it creates significant problems in approximately 40% of these patients 1°9 and occurs in as many as 70% at some time during their last 6 weeks of life. 11° The most common etiologies are pu lmonary or cardiac pathology, superior vena cava syndrome, ascites, and anemia. These are reversed when possible and appropriate.

For those with anxiety, relaxation techniques or formal hypnot ic imagery may help. 111 For those in an uncontrol led panic due to a perceived inability to breathe, midazolam, morphine ( intravenous or by nebulizer), or chlorpromazine may be required. 1°9

Pleural effusions often can be symptomatical ly controlled with oxygen and/or morphine in seden- tary patients. Drainage through a chest tube with instillation of a selerosing agent 112,113 may be required. In patients whose lung cannot be adequately drained or in whom the lung does not re-expand, and who have a reasonable life expectancy, open pleurodesis 114 or a pleuroperi toneal shunt 115,116 may be considered.

For the 25% of patients in whom no specific cause is identified, use of a fan blowing air softly onto the face 117 or medicat ions by nebulizer can be helpful. Nebulized morphine or hydromorphone often combined with dexamethasone are given every 4 hours as needed. The opioid dose is increased until dyspnea is relieved. 1°9,117 If wheez- ing is present , albuterol can be added. The mixture is also given by a nebulizer using room air or oxygen at 5 to 6 L/rain through an open face mask. 109

Cough Cough, which is present in approximately 40%

of pat ients with advanced cancer, 1°9 is caused by postnasal drip, infection, hear t failure, as thma/ chronic obstructive pu lmonary disease or esophageal reflux, angiotensin-eonvert ing enzyme inhibi- tors, obstruct ion of the airway, and disorders of swallowing. Nonspeeific therapy includes oral opioids, sweet elixirs containing dext rometho- rphan, or one of the opioids used for mild pain; methadone syrup, if available, can be very effective. 1°9 For more resistant coughs, higher doses of oral or nebulized opioids may be needed. 1°9 In

addition, nebulized anesthet ics can be given up to three times a day. 1°9A18 For patients who cough from tenacious mucous, nebulized saline, albuterol, or terbutal ine have been helpfu1119; expec- torants and mueolyt ies have not. 1°9 Since ipatro- pr ium worsens this problem, 1°9 it is discontinued when possible.

Hiccups Hiccups are embarrassing and exhausting, and

interfere with a patient 's ability to eat, drink, and sleep. They are most commonly caused by gastric compression, injury to vagus or phrenie nerves, uremia, hyponatremia, hypocaleemia, benzodiazepines, barbiturates, intravenous eortieosteroids, or, rarely, ear infections, pharyngitis, esophagitis, or pneumonia . 12° If the underlying cause cannot be reversed, metoclopramide is usually effective. 121 Chlorpromazine is also effective, but causes significant postural hypotension. Baelofen and haloperidol are probably equally effective and safer in older patients. 121 If none of these work and sedation is not a concern, methot r imepraz ine or midazolam are often administered.121,122

SKIN PROBLEMS

Fungating Lesions Fungating lesions from cancers growing out

through the skin can cause a profound loss of self-esteem and lead to pat ient isolation. They occur in patients with pr imary skin cancers, cancers of the head and neck that are refractory to chemothe rapy and radiation, metastat ic breast cancer, renal cancer, and, rarely, o ther cancers. 123 Surgery, chemotherapy , and radiation are all considered when the metastases first appear. 124 Symptomat ic t reatment , however, is often needed. A number of skin care protocols are included in the literature. 125,126 Impor tant principles of care are listed in Table 10.123'125"128

Pressure Sores General t rea tment principles include prevent

contaminat ion and minimize shear forees~ eliminate or control infection and debride (see Table 10), and protect the wound and promote healing. If infected or necrotic , use normal saline irrigation and enzymat ic agents to remove eschar. Use hydroeolloid dressings and alginate dressings as indicated in Table 10.129-132

Pruritis Pain and pruritis is caused by dry skin, allergic

reactions to drugs, uremia, obstructive liver


disease, skin involvement with cancer, or factors produced by the cancer, such as the pruritis found in Hodgkirl's disease. 133 For pruritis from biliary obstruction, internal stenting or radiation to obstructing nodes in the porta hepatis often relieves the pruritis. If this is not possible, naloxone, TM ondansetron, 13s methyltestosterone, or cholestipol powder are used. 136

Oral antihistamines are probably the best nonspecific relievers of pruritis, but they may eause excessive daytime sedation. The skin should be kept moist, the fingernails cut short, and all bath products that eontain perfumes or deodor- ants avoided. The baths themselves should be lukewarm. Menthol-containing creams, calamine lotion, or a eombination of calamine lotion and diphenhydramine can provide symptomatic relief.

NONPHARMACOLOGIC THERAPIES FOR

SYMPTOM CONTROL

W~n ile they do not replace drug therapies, onpharmacologic techniques are valuable

adjunets and ean be effectively ineorporated into symptom management strategies. Although these therapies are most commonly used to manage pain, 137 they are also helpful adjunets in eontrol- ling nausea, vomiting, and dyspnea. They require skilled practitioners. Because many of the techniques can be performed by properly trained lay

persons, the practitioners often serve both as therapist and teacher.

Physical techniques inelude cutaneous interventions, such as heat and cold, 9,138,139 massage, 9,139,14° acupuneture/aurieulotherapy, 141 and transeutaneous electrical nerve stimulation, 141 as well as positioning and exercise.142

Cognitive-behavioral interventions are effective in ameliorating a wide range of symptoms, especially pain, 13 anxiety, depression, mild delirium, anorexia, nausea, and dyspnea. Education and reassuranee of patients and families relieves a great deal of fear and corrects potentially harmful misconceptions. 143 Diversion of attention with music, videos, or visitors, 139 progressive muscle relaxation and imagery, 144 and hypnosis help patients to escape the problem or to think about it in alternative ways. 145 Biofeedback teaches patients techniques to relieve their own pain by modifying certain physiologic functions. 146 Music therapy offers diversion, distraction, and en- hanced relaxation. 13s Psychological counseling and cognitive behavioral training offer support, education, and help in developing coping skills, and diminishes the anxiety, depression, or delirium that may exacerbate the symptoms. 13,144 Spiritual counseling relieves hidden eoneerrls, reestablishes hope and meaning, and, in the terminal setting, enables patients to resolve issues that may prevent a peaceful death. 26,147

Of the cognitive-behavioral therapies, the efficacy of relaxation,23,144 hypnosis, 145 and psychological counseling 13 are well established. The physical transeutaneous electrical nerve stimulation tech- nique 141 has documented utility in nonmalignant pain syndromes, but its effectiveness has not been demonstrated in patients with eaneer pain. In addition, there is much less data that support the efficacy of the other nonpharmaeologie therapies in relieving cancer pain. Mueh of the data that are available, such as that on acupuncture and biofeedback, are contradictory, m Alternative therapies have had increased attention and the reader is referred elsewhere for this discussion. 14s

CONCLUSION

p atients with advanced cancer commonly experience a number of distressing physical symp-

toms that can interfere with their ability to achieve their final goals. Using a eombination of pharmacologic and nonpharmaeologic techniques, many of these problems can be ameliorated and, in

106 JANET L. ABRAHM

s o m e e a s e s , e v e n r e s o l v e d . A t e a m a p p r o a e h e a n

h e l p e n s u r e t h a t al l t h e p a t i e n t ' s p r o b l e m s a r e

i d e n t i f i e d a n d a d e q u a t e l y m a n a g e d . H o s p i e e se r -

v i e e s p r o v i d e s u c h a n a p p r o a c h w i t h m e d i e a l ,

n u r s i n g , p s y c h o s o e i a l , a n d s p i r i t u a l a s s e s s m e n t s

a n d t h e r a p i e s to p a t i e n t s a n d t h e i r f a m i l i e s , as w e l l as b e r e a v e m e n t c a r e . 149,1s°

W h i l e a g r e a t d e a l h a s b e e n l e a r n e d a b o u t h o w to

a s s e s s a n d m a n a g e a v a r i e t y of d i s t r e s s i n g s y m p -

t o m s , m u e h r e m a i n s to be d o n e . S t a n d a r d ,

v a l i d a t e d a s s e s s m e n t too l s fo r p a i n a n d o t h e r

s y m p t o m s , s u c h as t h e M e m o r i a l S y m p t o m A s s e s s -

m e n t Sea l e , 151 n e e d to b e a d o p t e d b y h e a l t h e a r e

s y s t e m s a n d i n c o r p o r a t e d i n t o r o u t i n e m o n i t o r i n g

a n d d o c u m e n t a t i o n . In a d d i t i o n , m o r e r e s e a r c h is

n e e d e d to d e t e r m i n e t h e b e s t p a l l i a t i v e i n t e r v e n -

t i o n s if w e a r e to e n a b l e t h e m to f i n i s h t h e w o r k

t h e y w i s h to c o m p l e t e in t h e i r l a s t days .

R E F E R E N C E S

1. Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998

2. MaeDonald N: The interface between oneology and palliative medicine, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 11-17

3. Coyle N, Cherny N, Portenoy RK: Pharmacologic management of cancer pain, in MeGuire DB, Yarbro CH, Ferrell BR (eds): Caneer Pain Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 89-130

4. Jaeox A, Carr DB, Payne R: New elinical-praetiee guidelines for the management of pain in patients with cancer. N l~ngl J Med 330:651-655, 1994

5. Sehug SA, Zech D, Dorr U: Cancer pain management according to WHO analgesie guidelines. J Pain Symptom Manage 5:27-32, 1990

6. Payne R, Gonzales G: Pathophysiology of pain in eaneer and other terminal diseases, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 299-309

7. Foley K/VI: Pain assessment and caneer pain syndromes, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 310-330

8. Jaeox A, Carr DB, Payne R, et al: Management of Cancer Pain: Clinical Practice Guideline No 9. US Public Health Service, Agency for Health Care Policy and Research. AHCPR Pub No. 94-0592, 1994

9. MeCaffery M, Beebe A: Pain: A Clinical Manual for Nursing Practice. St Louis, MO, Mosby, 1989

10. Wallenstein SL: Measurement of pain and analgesia in cancer patients. Cancer 53:2217-2238, 1984

11. Daut RL, Cleeland CS, Flanery RC: The development of the Wisconsin Brief Pain Questionnaire to assess pain in caneer and other diseases. Pain 17:197-210, 1983

12. Graham C, Bond SS, Gerkovich MM, et al: Use of the MeGill Pain Questionnaire in the assessment of cancer pain: Replicability and consistency. Pain 8:377-387, 1980

13. Breitbart W, Passik SD: Psychiatrie approaches to eaneer pain management, in Breitbart W, Holland JC (eds): Psyehiat- rie Aspects of Symptom Management in Cancer Patients. Washington, DC, American Psyehiatrie Press, 1993, pp 49-86

14. Rhiner M, Coluzzi PH: Family issues influencing management of cancer pain, in MeGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 207-230

15. Fink RS, Gates R: Cultural diversity and cancer pain, in MeGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain

Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 19-39

16. Cosh R: Spiritual care of the dying, in Corliss IB, Germino BB, Pittman MA (eds): A Challenge for Living: Dying, Death and Bereavement. Boston, MA, Jones and Bartlett, 1995, pp 131-143

17. Taylor EJ, Ersek M: Ethieal and spiritual dimensions of cancer pain management, in McGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 41-60

18. Doyle D, Hanks G, MacDonald N: Introduetion, in Doyle D, Hanks G, MaeDonald N (eds): Oxford Textbook of Palliative Medicine. Oxford, UK, Oxford University Press, 1998, pp 3-8

19. McGuire DB: The multiple dimensions of cancer pain: A framework for assessment and management, in MeGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 1-17

20. Foley KM: Pain syndromes in patients with cancer. Med Clin North Am 71:169-184, 1987

21. Levy MH: Pharmacologic treatment of cancer pain. N t~ngl J Med 335:1124-1132, 1996

22. Ad Hoe Committee on Cancer Pain, American Society of Clinical Oneology: Cancer pain assessment and treatment curriculum guidelines. J Clin Oneol 10:1976-1982, 1992

23. Ameriean Pain Society: Principles of analgesic use in the treatment of acute pain and cancer pain. Skokie, IL, American Pain Society, 1992

24. Cancer Pain Relief and Palliative Care: Report of a WHO expert committee. "vVHO Teeh Rep Ser 804:1-73, 1990

25. Rawlins MD: Non-opioid analgesies, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 355-360

26. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 231:232- 235, 1971

27. Wallenstein SL: Analgesic studies of aspirin in cancer patients. Proceedings of the Aspirin Symposium. London, UK, Aspirin Foundation, 1975, pp 5-10

28. Sunshine A, Olson NZ: Non-narcotic analgesics, in Wall PD, Melzaek R (eds): Textbook of Pain (ed 2). New York, NY, ChurehiU Livingstone, 1989, pp 670-685

29. Buckley MM, Brogden RN: Ketorolae: A review of its pharmaeodynamic and pharmaeokinetie properties and therapeutic potential. Drugs 39:86-109, 1990

30. Stuart M J, Murphy SM, Oski FA, et al: Platelet function in recipients of platelets from donors ingesting aspirin. N Engl J Med 287:1105-1109, 1972

31. Eisenberg E, Berkey CS, Carr DB, et al: Efficacy and safety of non-steroidal anti-inflammatory drugs for cancer pain: A recta-analysis. J Clin Oneol 12:2756-2765, 1994

SYMPTOM CONTROL 107

32. Sehlondorff D: Renal complications of nonsteroidal anti-inflammatory drugs. Kidney Int 44:643-653, 1993

33. Ferrell BA: Pain evaluation and management in the nursing home. Ann Intern Med 123:681-687, 1995

34. Gloth FM: Concerns with ehronie analgesic therapy in elderly patients. Am J Med 101:19-24, 1996 (suppl 1)

35. Seheiman JM: NSAIDs, gastrointestinal injury, and cytoproteetion. Gastroenterol Clin North Am 25:279-298, 1996

36. Strom BL: Adverse reactions to over-the-counter analgesics taken for therapeutic purposes. JAMA 272:1866-1867, 1994

37. Roth SH: Merits and liabilities of NSAID therapy. Rheum Dis Clin North Am 15:479-498, 1989

38. V~rhiteomb DC, Block GD: Association of aeetaminophen hepatotoxicity with fasting and ethanol use. JAMA 272:1845- 1850, 1994

39. Westerling D, bindahl S, Anderson RE, et al: Absorption and bioavailability of rectally administered morphine in women. Eur J Clin Pharmaeo123:59-64, 1982

40. De Conno F, Ripamonti C, Saiti L, et al: Role of rectal route in treating cancer pain: A randomized crossover clinical trial of oral versus rectal morphine administration in opioid- naive cancer patients with pain. J Clin Oneol 13:1004-1008, 1995

41. Desmeules J, Gascon M-P, Dayer P, et al: Impact of environmental and genetie factors on oodeine analgesia. Eur J Clin Pharmaeo141:23-26, 1991

42. Sindrup SH, Arendt-Nielson L, Rosen K, et al: The effect of quinidine on the analgesic effect of codeine. Eur J Clin Pharmaco142:587-591, 1992

43. Kaiko R, Laeouture P, Hopf K, et al: Analgesic onset and potency of oral controlled-release (CR) oxyeodone and CR morphine. Clin Pharmaeol Ther 59:130, 1996 (abstr)

44. Broomhead A, West R, Knox K, et al: Morphine bioavailability and pharmacokinetie eomparison of Kadian (sustained release morphine sulfate) capsules and pellets ("sprinkling") in human volunteers under fasted or fed conditions. Proe Am Soe Clin Oncol 16:61, 1997 (abstr)

45. Kaiko RF, Foley KM, Grabinski PY, et al: Central nervous system exeitatory effeets of meperidine in cancer patients. Ann Neuro113:180-185, 1983

46. Varvel dR, Sharer SL, Hwang SS, et al: Absorption characteristics of transdermally administered fentanyl. Anes- thesiology 70:928-934, 1989

47. Portenoy RK, Southam MA, Gupta SK, et al: Transdermal fentanyl for eaneer pain: Repeated dose pharmaeokineties. Anesthesiology 78:36-43, 1993

48. Goldfrank L, Weisman RS, Erriek JR, et al: A nomogram for eontinuous intravenous naloxone. Ann t~merg Med 15:566- 570, 1986

49. Simmonds MA: Oral transmucosal fentanyl citrate produces pain relief faster than medieation typically used for breakthrough pain in eaneer patients. Proe Am Soe Clin Oneol 16:52, 1977 (abstr)

50. Bruera E, Fainsinger R, Moore M, et al: Local toxicity with subcutaneous methadone: Experience of two centers. Pain 45:141-145, 1991

51. Coyle N, Cherny NI, Portenoy RK: Subcutaneous opioid infusions in the home. Oneology 8:21-27, 1994

52. Portenoy RK, Moulin DE, Rogers A, et al: IV infusion of opioids for cancer pain: Clinical review and guidelines for use. Cancer Treat Rep 70:575-581, 1986

53. Citron ML, Kaira J-M, Seltzer VL, et al: Patient-

eontrolled analgesia for cancer pain: A long-term study of inpatient and outpatient use. Cancer Invest 10:335-341, 1992

54. Kitahata LM, Collins JG: Spinal aetion of nareotic analgesics. Anesthesiology 54:153-163, 1981

55. Johnson SM, Duggan AW: Evidenee that opiate receptors at the substantia gelatinosa contribute to the depression by intravenous morphine of the spinal transmission of impulses in the unmyelinated primary afferents. Brain Res 207:223-228, 1981

56. Du Pen S, Williams A: The clinical dilemma of systemic to epidural morphine eonversion: Development of a conversion tool for cancer pain patients. Pain 56:113-118, 1994

57. Paiee JA, Magolan JM: Intraspinal drug therapy. Nurs Clin North Am 26:477-498, 1991

58. Ferrante FM, Bedder M, Caplan RA, et al: Practice Guidelines for Cancer Pain Management: A report by the American Society of Anesthesiologists Task Force on Pain Management, Cancer Pain Section. Anesthesiology 84:1243- 1257, 1996

59. Swarm RA, Cousins MJ: Anaesthetic techniques for pain control, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medieine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 390-413

60. Paiee JA, Williams AR: Intraspinal drugs for pain, in MeGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain Management (ed 2). Boston, MA, Jones and Bartlett, 1995, pp 131-158

61. Du Pen SL, Kharaseh ED, Williams A, et al: Chronic epidural bupivaeaine-opioid infusion in intractable cancer pain. Pain 49:293-300, 1992

62. Marlowe S, Engstrom R, White PF: Epidural patient- controlled analgesia (PCA): An alternative to continuous epidural infusions. Pain 37:97-101, 1989

63. Krames ES: Intraspinal opioid therapy for chronic nonmalignant pain: Current practice and clinical guidelines, d Pain Symptom Manage 11:333-352, 1996

64. Warren DE: Practical use of rectal medications in palliative oare. d Pain Symptom Manage 11:378-387, 1996

65. Watanabe S, Bruera E: Cortieosteroids as adjuvant analgesics, d Pain Symptom Manage 9:442-445, 1994

66. Wood MJ, Johnson RW, MeKendriek MW, et al: A randomized trial of aeyelovir for 7 days or 21 days with and without prednisolone for t reatment of acute herpes zoster. N Engl J Med 330:896-900, 1994

67. Bruera E, Fainsinger t/L: Clinical management of eaehexia and anorexia, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 548-556

68. Graham DY, Agrawal NM, Roth SH: Prevention of NSAID-induced gastrie ulcer with misoprostol: A multieentre, double-blind, plaeebo-eontrolled trial. Lancet 2:1277-1280, 1988

69. Breitbart W, Passik SD: Psychiatric aspects of palliative care, in Doyle D, Hanks G, MaeDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 933-954

70. Portenoy RK: Adjuvant analgesies in pain management, in Doyle D, Hanks G, MaeDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 361-389

71. Fromm GH, Terrenee CF, Chattha AS: Baelofen in the t reatment of trigeminal neuralgia: Double-blind study and long-term follow-up. Ann Neurol 15:240-244, 1984

72. Max MB, Culnane M, Sehafer 8C, et al: Amitriptyline

1 0 8 J A N E T L. A B R A H M

relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 37:589-596, 1987

73. Fernandez F, Adams F, Holmes VF: Analgesic effect of alprazolam in patients with chronic, organic pain of malignant origin. J Clin Psychopharmacol 3:167-169, 1987

74. Vainio A, Ollila J, Matikainen E, et al: Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 346:667-670, 1995

75. Kaplan R, Parris W, Citron M, et al: Decrease in opioid-related adverse events during chronic therapy with controlled-release oxycodone in cancer patients. Proe Am Pain Soe A-146, 1995 (abstr)

76. Savarese J J, Goldenheim PD, Thomas GB, et al: Steady-state pharmaeokinetics of controlled release oral morphine sulphate in healthy subjects. Clin Pharmacokinet 11:505-510, 1986

77. Bruera E, Brenneis C, Paterson AH, et al: Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. J Pain Symptom Manage 4:3-6, 1989

78. Hanks G, Cherny N: Opioid analgesic therapy, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 166-181

79. Waller A, Caroline NL: Oral complications and mouth care, in Waller A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 113-122

80. Toth BB, Chambers MS, Fleming T J, et al: Minimizing oral complications of cancer treatment. Ontology 9:851-858, 1995

81. Ventafridda V, Ripamonti C, Sbanotto A, et al: Mouth care, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 691-708

82. Regnard C, Fitton S: Mouth eare: A flow diagram. Palliat Med 3:67-69, 1989

83. Chi K-H, Chen C-H, Chan W-K, et al: Effect of granulocyte colony stimulating factor on oral mucositis in head and neck eancer patients after cisplatin, fluorouraeil and leucovorin chemotherapy. J Clin Oneol 13:2620-2628, 1995

84. Loprinzi CL, Ghosh C, Camoriano J, et al: Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluoruraeil-based chemotherapy. J Clin Oneol 15:1235-1238, 1997

85. Allison RR, Vongtama V, Vaughan J, et al: Symptomatic acute mucositis ean be minimized or prophylaxed by the combination of sueralfate and fluconazole. Cancer Invest 13:16-22, 1995

86. Berger AM, Bartoshuk LM, Duffy VB, et al: Capsaicin for the treatment of oral mucositis pain. PPO Updates 9:1-11, 1995

87. Johnson JT, Perretti GA, Nethery WJ, et al: Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med 329:390-395, 1993

88. Iwamoto RR: A nursing perspective on radiation-induced xerostomia. Oneology 10:12-15, 1996

89. Bain VG: Jaundice, ascites, and hepatic eneephalopathy, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 557-572

90. Soderland C: Denver peritoneovenous shunting for malignant or cirrhotic aseites: A prospective consecutive ease series. Stand J Gastroentero121:1167-1172, 1986

91. Faught W, Kirkpatriek JR, Kreport GV, et al: Peritoneove-

nous shunt for gyneeologic malignant aseites. J Am Coll Surg 180:472-474, 1995

92. Billings JA: Constipation, diarrhea, and other GI problems, in Billings JA: Outpatient Management of Advanced Cancer: Symptom Control, Support, and Hospice-in-the-Home. London, UK, Lippineott, 1986, pp 69-76

93. Bruera E, Suarez-Almazor M, Velasco A, et al: The assessment of constipation in terminal cancer patients admit- ted to a palliative care unit: A retrospective review. J Pain Symptom Manage 9:515-519, 1994

94. Twycross RG, Harcourt JMV: The use of laxatives at a palliative eare center. Palliat Med 5:27, 1991

95. Waller A, Caroline NL: Diarrhea and rectal diseharge, in Waller A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 189-194

96. Billings JA: Nausea and vomiting, in Billings JA (ed): Outpatient Management of Advanced Cancer: Symptom Con- trol, Support, and Hospice-in-the-Home. London, UK, Lippin- eott, 1986, pp 46-56

97. Dundee JW, Yang J: Prolongation of the anti-emetic aetion of P6 acupuncture by acupressure in patients having cancer chemotherapy. J Royal Soc Med 83:360-362, 1983

98. Hammond DC (ed): Handbook of Hypnotic Suggestion and Metaphors. New York, NY, Norton, 1990

99. Baines M: Nausea and vomiting in the patient with advanced cancer. J Pain Symptom Manage 3:81-85, 1988

100. Currow DC, Coughlan M, Fardell B, et al: Use of ondansetron in palliative medicine. J Pain Symptom Manage 13:302-307, 1997

101. Billings JA: Anorexia and nutritional care, in Billings JA (ed): Outpatient Management of Advaneed Cancer: Symptom Control, Support, and Hospice-in-the-Home. London, UK, Lippincott, 1986, pp 58-69

102. Loprinzi CL, Miehalak JC, Schaiad D J, et al: Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or caehexia. J Clin Oncol 11:762-767, 1993

103. Simons JP-FHA, Aaronson NK, Vansteenkiste JF, et al: Effeets of medroxyprogesterone acetate on appetite, weight, and quality of life in advaneed-stage non-hormone-sensit ive eaneer: A placebo-controlled multieenter study. J Clin Oneol 14:1077-1084, 1996

104. Leinung MC, Liporace R, Miller CH: Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med 122:843-845, 1995

105. Beal JE, Olson R, Laubenstein L, et al: Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10:89-97, 1995

106. Wadleigh R, Spanlding M, Lembersky B, et al: Dronabi- nol enhancement of appetite and cancer patients. Proc Am Soe Clin Oneol 9:331, 1990 (abstr)

107. Bruera E, Fainsinger RL: Clinical management of cachexia and anorexia, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 534-547

108. McCann RM, Hall WJ, Groth-Junker A: Comfort care for terminally ill patients: The appropriate use of nutrition and hydration. JAMA 272:1263-1266, 1994

109. Ahmedzai A: Palliation of respiratory symptoms, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine (ed 2). Oxford, UK, Oxford University Press, 1998, pp 583-616

110. Ripamonti C, Bruera E: Dyspnea: Pathophysiology and assessment. J Pain Symptom Manage 13:220-232, 1997

SYMPTOM CONTROL 1 0 9

111. Corner J, Plant H, Hern RA, et al: Non-pharmacological intervention for breathlessness in lung cancer. Palliative Med 10:299-305, 1996

112. Moffett MJ, Ruekdesehel JC: Bleomycin and tetracy- cline in malignant pleural effusions: A review. Semin Oneol 19:59-63, 1992 (suppl 2)

113. Morales M, del Carmen Exposito M: Control of malignant effusions with intrapleural mitoxantrone. 8upp Cancer Care 3:147-149, 1995

114. Petrou M, Kaplan D, Goldstraw P: Management of recurrent malignant pleural effusions: The complementary role of tale pleurodesis and pleuroperitoneal shunting. Cancer 75:801-805, 1995

115. Ponn RB, Blancaflor J, D'Agostino RS, et al: Pleuroperi- toneal shunting for intractable pleural effusions. Ann Thorae Surg 51:605-609, 1991

116. Tsang V, Fernando HC, Goldstraw P: Pleuroperitoneal shunt for recurrent malignant pleural effusions. Thorax 45:369-372, 1990

117. Waller A, Caroline NL: Dyspnea, in Waller A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 203-207

118. Trochtenberg S: Nebulized lidocaine in the t reatment of refractory cough. Chest 105:1592-1593, 1994

119. Sutton P, Gemmell HG, Innes N, et al: Use of nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. Thorax 43:57-60, 1988

120. Waller A, Caroline NL: Hiccups, in Waller A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 135-142

121. Twyeross RG: Dysphagia, dyspepsia and hiccup, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine fed 2). Oxford, UK, Oxford University Press, 1998, pp 499-512

122. Wileock A, %wcross R: Midazolam for intractable hiccup. J Pain Symptom Manage 12:59-61, 1996

123. Wailer A, Caroline NL: Smelly tumors, in Waller A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 69-72

124. Wood DK: The draining malignant ulceration: Palliative management in advanced cancer. JAMA 224:820-822, 1980

125. Miller CM, O'Neill A, Mortimer PS: SMn problems in palliative care: Nursing aspects, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine. Oxford, UK, Oxford University Press, 1993, pp 395-407

126. Foltz AT: Nursing care of ulcerating metastatic lesions. Oncol Nurs Forum 7:8-13, 1980

127. Brennan S, Leaper D: Antiseptics and wound healing. Br d Surg 72:780-782, 1985

128. Beckett R, Coombes TH, Frost MR, et al: Charcoal cloth and malodorous wounds. Lancet 2:594, 1980

129. Clinical Practice Guidelines: Pressure ulcers in adults: Prediction and prevention. Silver Spring, MD, AHCPR Publica- tions Clearing House, 1992

130. DeConno F, Ventafridda V, Saita L: SMn problems in advanced and terminal cancer patients. J Pain Symptom Manage 6:247-256, 1991

131. Seller W, Stahelin H: Deeubitus ulcers: Treatment through five therapeutic principles. Geriatrics 40:39-44, 1985

132. Waller A, Caroline NL: Pressure sores, in Wailer A, Caroline NL (eds): Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 73-80

133. Goldman BD, Koh HK: Pruritis and malignancy, in Bernard JD fed): Mechanisms and Management of Pruritis. New York, NY, McGraw Hill, 1994

134. Bergasa NV, Talbot TL, Ailing DW, et al: A controlled trial of naloxone infusions for the pruritus of chronic cholestasis. Gastroenterol 102:544-549, 1992

135. Raderer M, Muller C, Scheithauer W: Ondansetron for pruritis due to cholestasis. N Engl J Med 330:1540, 1994 (letter)

136. Waller A, Caroline NL: Pruritis, in Waller A, Caroline NL (eds) Handbook of Palliative Care in Cancer. Boston, MA, Butterworth-Heineman, 1996, pp 97-104

137. McCaffery M: Nursing approaches to nonpharmaeologi- eal pain control. Int J Nurs Stud 27:1-5, 1990

138. Spross JA, Burke MW: Nonpharmaeological management of cancer pain, in McGuire DB, Yarbro CH, Ferrell BR (eds): Cancer Pain Management fed 2). Boston, MA, Jones and Bartlett, 1995, pp 159-205

139. Rhiner M, Perrell BR, Ferrell BA, et al: A structured nondrug intervention program for cancer pain. Cancer Prat t 1:137-143, 1993

140. Ferrell-Torry A, Gliek O: The use of therapeutic massage as a nursing intervention to modify anxiety and the perception of cancer pain. Cancer Nurs 16:93-101, 1993

141. Thompson JW, Filshie J: Transcutaneous electrical nerve stimulation (TENS) and acupuncture, in Doyle D, Hanks G, MacDonald N (eds): Oxford Textbook of Palliative Medicine. Oxford, UK, Oxford University Press, 1993, pp 229-244

142. MeCaffery M, Wolff M: Pain relief using cutaneous modalities, positioning, and movement. Hospice J 8:121-154, 1992

143. Devine EC, Westlake SK: The effects of psyehoeduca- tional care provided to adults with cancer: Meta-analysis of 116 studies. Oncol Nurs Forum 2:1369-1379, 1995

144. Syrjala KL, Donaldson GW, Davis MW, et al: Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: A Controlled clinical trial. Pain 63:189-198, 1995

145. Syrjala Kb, Roth-Roemer SL: Hypnosis and suggestion for managing cancer pain, in Barber J fed): Hypnosis and Suggestion in the Treatment of Pain. New York, NY, Norton, 1996, pp 121-157

146. Cleeland CS: Nonpharmaeologic management of cancer pain. J Pain Symptom Manage 2:523-528, 1987

147. Attig T: Respecting the spirituality of the dying and the bereaved, in Corless IB, Germino BB, Pittman MA (eds): A Challenge for Living: Dying, Death and Bereavement. Boston, MA, Jones and Bartlett, 1995, pp 117-130

148. Cassileth BR, Chapman CC: Alternative cancer medicine: A ten-year update. Cancer Invest 14:396-404, 1996

149. Abrahm JL, Callahan J, Rossetti K, et al: The impact of a hospice consultation team on the care of veterans with advanced cancer. J Pain Symptom Manage 11:1-9, 1996

150. Abrahm JL, Cooley ME, Ricaeho L: Efficacy of an educational bereavement program for families of veterans with cancer. J Cancer Edue 10:207-212, 1995

151. Portenoy RK, Thaler HT, Kornblith AB, et al: The Memorial Sysmptom Assessment Scale: An instrument for the evaluation of symptom prevalence, characteristics, and dis- tress. Eur J Cancer 30:1326-1336, 1994

data sources: control in palliative c are

Documents