N AUSEA AND VOMITING, often accompa- nied by anorexia, are among the most fre-
quent symptoms associated with cancer and cancer treatment. It is estimated that nausea and vomiting occur in most patients receiving chemotherapy and by the majority of patients receiving radiation to the brain and/or total body. ~,2 Other etiologies in- clude fluid and electrolyte imbalances, uremia, in- testinal obstruction, brain and hepatic metastases, infections, septicemia, and the side effects of medications such as steroids and analgesics. 3 Mul- tiple causes are likely to be present in most pa- tients.
Anorexia, which includes appetite depression and decreased food intake, also occurs in response to multiple factors. 4 Factors associated with de- creases in appetite and the ability to eat include gastrointestinal pathology, metabolic distur- bances, and the occurrence of distressing symp- toms such as pain, psychologic stress, and changes in the diet and the environment, s
Recent trends reveal a multidisciplinary ap- proach to the identification of related physiologic and behavioral mechanisms and the development and testing of pharmacologic and nonpharmacolo- gic interventions. This paper reviews the def- initions, causes, and consequences of nausea, vomiting, and anorexia, and discusses current rec- ommendations for nursing assessment and man- agement.
DEFINITIONS AND CAUSES
Nausea
Nausea is a very disagreeable feeling experi- enced in the back of the throat, the epigastrium, and generally culminating in vomiting. It may be accompanied by pallor, cold clammy skin, in- creased salivation, faintness, tachycardia, and di- arrhea. It is often associated with decreased gastric functioning such as hypotonicity, hypoperistalsis, and hyposecretion. 6
Nausea is caused by numerous factors. Acute drug-related nausea is experienced by many pa- tients receiving chemotherapy, steroids, analge- sics, and many other medications. 7 Acute radia- tion-related nausea is experienced by patients whose treatment field includes the brain, stomach, and/or small intestine, z Gastrointestinal causes in-
clude pyloric and intestinal obstructions and pan- creatic disease. Nausea is associated with preg- nancy and with motion sickness and other disorders involving the inner ear. Stimuli such as unpleasant odors and tastes, fear and anxiety, un- pleasant visual stimulation, and intense pain cause conditioned nausea. 8 In many cancer patients sev- eral of these factors occur simultaneously.
Vomiting
Vomiting is an involuntary reflex causing the forceful explusion of the contents of the stomach and the intestine. Vomiting is immediately pre- ceded by widespread autonomic stimulation re- sulting in tachypnea, copious salivation, dilation of the pupils, sweating, pallor," and rapid heart- beat.6, 9
Vomiting has a variety of types and causes. Acute vomiting occurs in many patients soon after administration of chemotherapy.1 Intensity varies with the kind and dosage of chemotherapy (Table 1). Delayed or persistent vomiting is defined as that which occurs 24 hours or more after adminis- tration of chemotherapy. ~6 Anticipatory nausea and vomiting (ANV) is a learned phenomenon stimulated by something that occurs in association with the true stimulant. 8A7 The learned stimuli in- clude thoughts, sights, tastes, and odors related to treatment. 18 Occurrence of ANV increases with each successive cycle of chemotherapy. Other cir- culating chemicals associated with vomiting in- clude analgesics, steroids, circulating toxins such as bacterial toxins, and high levels of urea, uric acid, and ammonia. 3.7,t9
Vomiting also occurs in patients undergoing ra- diation treatment of the brain and/or the gastroin- testinal tract. 2 Obstructions, infections, and in-
From the City of Hope National Medical Center, Duarte, CA.
Supported in part by grants from the American Cancer Soci- ety, Doctoral Program in Cancer NursbTg, and National Re- search Sen'ice Award #NU05572 from Division of Nursing, BHPr, HRSA, Public Heahh Service.
Address reprint requests to Marcia Grant, RN, MSN, City of Hope National Medical Center, 1500 East Duarte Rd, Duarte, CA 91010.
* High dose. Data from Geffner, 10 AHFS, 1~ Lasley and lgnoffo, lz Knobf et al, 13 Brager and Yasko, ~4 and Penta et aL TM
flammations of the gastrointestinal tract are frequently accompanied by vomiting. 19 No n - cancer-related causes include pregnancy and mo- tion sickness.
Anorexia
Anorexia is defined as a decreased appetite as- sociated with a decrease in spontaneous food in- take. 4 Physiologic causes include anorexigenic substances secreted by tumor cells, 2° distressing symptoms, early satiety, taste and smell changes, and oral-gustatory problems. 21 Psychologic and sociocultural factors lead to anorexia as well. 22,23
Interactions
Relationships among nausea, vomiting, and an- orexia are fairly complex. Each symptom may occur alone, any two can occur together, or all three can occur simultaneously or follow one an- other in various sequences. Nausea generally pre- cedes vomiting. Anorexia may be related solely to the occurrence of nausea and vomiting and cease when they are alleviated. Examination of the mechanisms influencing the occurrence of nausea, vomiting, and anorexia canprovide an under- standing of these complex relationships.
PHYSIOLOGIC AND BEHAVIORAL MECHANISMS
Nausea and Vomiting
Nausea and vomiting result from stimulation of a complex reflex coordinated by the vomiting center located in the medullary lateral reticular formation, z4 Neurologic stimulation arrives via several pathways (Fig 1). Afferent stimuli come from (1) the chemoreceptor trigger zone (CTZ) lo- cated in the floor of the fourth ventricle and re- sponding to levels of chemical substances in the blood and cerebral spinal fluid, (2) vagal visceral afferents (VV) responding to inflammation, isch- emia, and irritation in the gastrointestinal tract, (3) sympathetic visceral afferents (SV) responding to inflammation, ischemia, irritation, and obstruction of hollow organs including the gastrointestinal organs, (4) vesticulocerebellar afferents (VC) coming from the labyrinth of the inner ear in re- sponse to l~ody motion, and (5) the cerebral cortex (CC) and limbic system in response to stimulation from the senses, anxiety, pain, and increases in intracranial pressure. 17,24,25 While all pathways appear to converge on the vomiting center, differ- ent neurotransmitters may mediate incoming stim- uli. 25 The effectiveness of different antiemetic
NAUSEA, VOMITING, AND ANOREXIA 279
N E U
CTZ • 0 T
VV • R A
SV ' N S
VC t, M I
CC - T. T E R S
Fig 1. Pathways involved in nausea and vomiting. Abbre- viations: CTZ, chemoreceptor trigger zone; W , vagal visceral afferents; SV, sympathetic visceral afferents; VC, vest ibu lo- cerebel lar afferents; CC, cerebral cortex and Iimbic system; EC, emetic center.
agents may be dependent on which pathways and/ or neurotransmitters within the vomiting reflex arc are blocked. 25 Neurotransmitters include acetyl- choline, dopamine, serotonin, histamine, gluta- mine, and norepinephrine. The development of new antiemetics reflects attempts to chemically block many of these neurotransmitters.
Anorexia
Current theories on normal behavior postulate central and peripheral stimuli for feeding. When combined, these theories reveal a multifactor, re- dundant system with no hierarchy of stimuli iden- tified. In the central nervous system, the hypothal- mic contains two centers: the feeding center, which activates feeding and the satiety center, which inhibits feeding behavior. 26 Peripheral stim- uli arise from taste and smell sensors in the orona- sal region, volumetric, and chemical sensors in the upper gastrointestinal tract and the liver respon- sive to gastrointestinal pressure and serum levels of metabolites and hormones. 5
In cancer patients physiologic, psychologic, and/or sociocultural factors interfere with the mechanisms of normal food intake. 5 Neurologic pathways between these factors and the eating or satiety centers in the hypothalamus have not been fully described. One pathway may involve direct stimulation of the satiety center by anorexigenic factors that are secreted by tumors and travel via the circulatory system. 2~
CONSEQUENCES OF NAUSEA, VOMITING, AND ANOREXIA
The significance of nausea, vomiting, and an- orexia in cancer patients is related to the impact on
morbidity and quality of life. Interruption or alter- ation of symptoms before the occurrence of these consequences is of particular significance.
Nutritional consequences include weight loss and nutritional depletion from the decrease in food intake below metabolic need and/or alterations in host metabolism. 27,28 Weight loss is an important clinical indicator; a weight loss of more than 5% in four weeks or more than 10% in 6 months is considered severe. 29 While an isolated severe weight loss may not be dangerous, when coupled with major stress, such as trauma, surgery, or in- fection, weight loss may lead to life-threatening complications. Weight loss is accompanied by a depressed immune status, which results in de- creased macrophage mobilization, depressed lym- phocyte function, and impaired phagocytosis. 3° In surgical patients, decreased wound healing may result. Other paiients may suffer from the complex syndrome of cachexia, a profound systemic abnor- mality in host metabolism characterized by weak- ness, wasting, depletion, redistribution of host components, hormonal aberrations, and a progres- sive failure in vital function. 31 Another conse- quence is a decreased tolerance to treatment and delay or withdrawal from treatment when the nau- sea and vomiting reaches intolerable levels. 14,32
Nausea, vomiting, and anorexia also impact on the patient's quality of life. In one report, 40% of the patients surveyed reported that nausea and vomiting interrupted ability to perform daily activ- ities; 23% of the patients found the symptoms so debilitating that they went to bed. These results confirm the distress associated with these symp- toms and underscore the need to initiate interven- tions to alleviate the symptoms and/or the dis- tress. 32
ASSESSMENT OF NAUSEA, VOMITING, AND ANOREXIA
Assessment of nausea, vomiting, and anorexia in cancer patients is conducted for clinical man- agement and for research on the occurrence, dis- tress, and effectiveness of interventions for allevi- ation of these symptoms. Clinical assessment of nausea, vomiting, and anorexia begins with a de- scription of the occurrence and severity of these symptoms so that patterns and potential causes may be determined, z4 Assessment continues with the consequence of these symptoms. As the pa- tient moves from a potential for nausea, vomiting,
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and anorexia to the occurrence of severe symp- toms, the nature of the assessment increases in complexity, aa The Outcome Standards for Cancer Nursing Practice on information, coping, comfort, and nutrition are helpfld in organizing needed as- sessment parameters, a4
ASSESSING THE PATIENT WITH A POTENTIAL FOR NAUSEA, VOMITING, AND ANOREXIA
Within the information standard, assessment in- cludes interviewing both the patient and the family to determine learning needs about the disease and treatment modality as they relate to the occurrence of nausea, vomiting, and anorexia. The nurse needs to determine whether the patient and family expect these symptoms and what their occurrence means to the patient and family, a5 Myths may need clarification. For example, some patients think that the chemotherapeutic agents are not working adequately unless symptoms occur. Others feel that such symptoms indicate treatment failure. Clarification of such misconceptions is needed.
Within the coping standard, assessment in- cludes determining what stressors are present, and whether these may impact on the patient's and family's ability to manage toxicities. Previously successful coping strategies should be identified. Within the comfort standard, assessment includes the ability to obtain adequate rest and sleep, and the occurrence and patterns of pain. 36,37
Assessment in relation to nutrition should in- clude weight and height, both present and histori- cal; vital signs; and anthropometric measurements such as triceps skinfold, midarm muscle circum- ference, and hand grip strength. Laboratory tests may include albumin, total protein, transferrin, complete blood count with differential, electro- lytes, iron, and total iron binding capacity. A di- etary history should include common eating pat- t e rns , f a v o r i t e f o o d s , and s o c i o c u l t u r a l preferences. Finally, assessment should include other signs and symptoms that may precipitate or exacerbate nausea, vomiting, and anorexia, such as mouth and throat problems and fatigue, as
ASSESSING THE PATIENT WITH MODERATE NAUSEA, VOMITING, AND ANOREXIA
Assessment of moderate nausea, vomiting, and/ or anorexia should include the order, severity, and duration of symptoms. Information on successful
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interventions used in the past should be obtained. Nutritional assessments include weekly weights and laboratory work, daily monitoring of intake and output, and periodic evaluation of caloric and protein intake, as,39 The effectiveness of prescribed antiemetics must be evaluated carefully. These medications may correctly alleviate one symptom without alleviating the others. Assessment should focus on one symptom at a time, looking for pat- terns of occurrence that will be of assistance in designing individualized antiemetic regimens. 3a
ASSESSING THE PATIENT WITH SEVERE NAUSEA, VOMITING, AND ANOREXIA
The patient with severe symptoms should be monitored daily for caloric and protein intake via oral, enteral and parenteral sources. Fluid balance parameters such as skin turgor, presence of pe- ripheral edema, and respiratory congestion should be assessed. The patient should be monitored care- fully for the beginning signs of infection and any change in mental state. 39
MEASUREMENT OF NAUSEA, VOMITING, AND ANOREXIA FOR RESEARCH
A recent increase in intervention studies on nausea, vomiting, and anorexia has produced a number of instruments to measure these symp- toms. no Vomiting is objectively measured by the number of episodes in a specified period of time, and the amount of vomitus. Nausea as well as dis- tress related to nausea and vomiting needs to be fated by the patient since each is a subjective phe- nomenon. The Duke Descriptive Scale (DDS) in- cludes ratings of I to 4 on the intensity and severi- ty of nausea and vomiting and the impairment in patient activity levels, n° With the Morrow scale, information is obtained on onset, intensity, severi- ty, and duration of nausea and vomiting, nl Likert ratings by patients are obtained. The Rhodes Index of Nausea and Vomiting (INV) is a self-report in- strument that describes symptom occurrence and symptom distress of nausea and vomiting. The INV is the only rating scale that measures symp- tom distress of nausea and vomiting. Scale devel- opment on 42 subjects included a validity compar- ison of the INV with the Adapted Symptom Distress Scale (ASDS). 4z Reliability estimates re- vealed alphas of 0.80 to 0.97. Concurrent validity, established through correlations of patient and family ratings, revealed alphas of 0.87 and 0.83
NAUSEA, VOMITING, AND ANOREXIA 281
over two separate time periods and across two dif- ferent chemotherapy administrations. Construct validity was established (l) by comparing results of well individuals with chemotherapy patients, (2) by correlations with comparable items on the ASDS, and (3) by comparing patients' and nurses' evaluations of the amount and frequency of emesis. Results indicate acceptable reliability and validity.
Scales to measure anorexia are far less devel- oped and include two aspects of anorexia: the sub- jective experience of appetite loss and the objec- tive decrease in food intake. Loss of appetite is generally measured by having cancer patients state whether this has occurred. 43,44 Some investigators instruct patients to rate appetite on a 100-mm lin- ear analogue scale or a 5-point Likert scale. 42.45"47 One instrument consists of 22 items divided into 5 subscales: appetite/hunger, general symptoms, oral problems, psychologic state, and sociocultur- al influence. 47 Reliabilifies of 0.65 to 0.92 alpha coefficients have been reported. Overall reliability of 0.69 was reported in a study of 51 head and neck cancer patients undergoing radiation therapy.
Dietary intake measurements include tracking what subjects eat and quantifying the intake in re- lation to calories, protein, fat, carbohydrate, and other factors. 48 Patients may keep three-day di- etary histories that are analyzed for food values. As more studies on anorexia are conducted, an in- crease in tools for measurement of anorexia is ex- pected.
INTERVENTIONS FOR NAUSEA AND VOMITING
Pharmacologic Pharmacologic interventions include a variety
of medications that have been used to reduce both nausea and vomiting, and the distress associated with each of these. Prior to the 1960s, clinical trials of antiemetics were rare. As use of potent chemotherapeutic agents increased, effective anti- emetic regimens were needed. Clinical trials are now so frequent that a summary of results to date is beyond the scope of this article.
Different classes of antiemetics appear to inter- rupt different mechanisms involved in nausea and vomiting. Is.ag-s3 In Table 2, the action of each drug group, its side effects, and commonly pre- scribed drugs are delineated. Multidrug therapy combines antiemetics from several categories. 54 Efficacy of these combinations continues to be
tested in a variety of patient populations and che- motherapeutic regimens.
A major nursing responsibility is to administer the antiemetics on time for hospitalized patients and to teach patients when and how the medica- tions should be administered at home. Most regi- mens should be started prior to the administration of either radiation therapy or chemotherapy. Spe- cific written instructions should be available for the nonhospitalized patient. Teaching should in- clude specific signs and symptoms to report to the nurse and/or physician. 54 In addition, the nurse should assess the effectiveness of the medication in relation to the occurrence of side effects.
Nonphannacologic Interventions
Dietary interventions and behavioral interven- tions have been helpful in alleviating nausea and vomiting. Dietary interventions involve coaching patients regarding both timing of food intake and changes in the types of foods eaten. 55 Recommen- dations for dieting adjustments are based predomi- nantly on clinical experience, since formal testing of the values of specific foods has not been con- ducted. Foods reported by chemotherapy patients to relieve nausea and vomiting include soda crackers, soda pop, [apaya enzyme, salty food, fresh fruit, juices, broth, soft foods, and nonsweet foods . 32 TO maintain adequate calories and pro- tein, useful approaches include using bland pro- tein foods such as poultry and fish, and boiled or baked meats, rather than flied foods. Smaller, more frequent meals are appropriate, and should be timed to coincide when symptoms are minimal. Nutritional supplements are used to increase calor- ic and protein intake (Table 3). 56 Patients should be encouraged to eat in a pleasant setting with good company, and to avoid cooking or the smell of foods cooking if those circumstances lead to nausea.
For patients with moderate to severe nausea and vomiting that persists over time, food intake must be evaluated in order to prevent nutritional com- plications. With severe vomiting, the patient can lose gastrointestinal secretions, leading to electro- lyte and acid-base imbalances. Supportive care via enteral or parenteral nutrition may be necessary.
Behavioral interventions have been used to de- crease nausea and vomiting and the associated dis- tress. Distraction is used intuitively by many nurses. Distraction techniques include various vi-
282 MARCIA GRANT
Table 2. Antiemetics Used for Nausea and Vomiting in Cancer Patients
Examples (including Pharmacologic Side Effects routes and common
Effects and Toxicities Comments dosages)
Anticholinergics Depresses vestibular stimuli Suppresses emetic center
Extrapyramidal effects such as anxiety, restlessness, dystonia
Side effects decreased in patients under 40
Side effects partly controlled with diphenhydramine
Dexamethazone PO 4 - I 0 mg; IM, IV 10-20 mg
Methyl prednisone IV 250 mg
Metoclopramide IV 1-3 mg/kg
sual and auditory stimuli aimed at overriding the nausea and vomiting stimuli (ie, television, radio), and allowing the patient to concentrate on some- thing other than the symptoms and associated dis- tress. Relaxation techniques include guided imag- ery, progressive muscle relaxation, and hypnosis. Techniques that are effective are frequently specif- ic to the individual's previous approaches to stress reduction. Children are particularly open to the use of relaxation techniques.
Several studies have been done to test the effec- tiveness of these techniques, s7-62 In one study, 60 patients were randomly assigned to an experimen- tal group taught progressive muscle relaxation, a placebo control group with a therapist present, or a control group receiving no interventions. 63 Al- though antiemetic drug intake was not reported, results showed that the experimental group had significantly less vomiting and maintained signifi- cantly greater caloric intake. These techniques are without side effects, are within the control of the individual patient, are relatively easy to learn, and can be used at home as well as in the hospital. 57
Presently, a variety of approaches, pharmaco- logic and nonpharmacologic, are used to help pa- tients maintain control over cancer or cancer treat- ment induced symptoms of nausea and vomiting. Studies have provided beginning evidence of suc- cessful use of many of these approaches, and have pointed to the need for further testing so that inter- ventions can be matched with specific patients.
INTERVENTIONS FOR ANOREXIA
Pharmacologic interventions for anorexia in- clude steroids, trace elements, and analgesics.
Trace metals, such as copper and zinc, may play a part in taste and smell sensations, both of which are important in maintaining an appetite. 2t Anti- emetics and analgesics may improve appetite by relieving symptoms. Mood elevators and/or tran- quilizers may relieve depression and anxiety lead- ing to an increase in appetite and food intake.
Nonpharmacologic interventions include dietary counseling, symptom management, psychosocial support, and nutritional support. Dietary counsel- ing provides the patient and the family with infor- mation on daily caloric and protein requirements, and food selection. 35 The value of dietary counsel- ing was tested by Daly et al in a study of head and neck cancer patients undergoing radiation therapy. 64 Results revealed that the tube-fed group had better maintenance of weight during radiation therapy when compared with the oral feeding group. There was no difference between groups in response to radiation therapy, and no difference in patient survival.
Patients with early satiety should make the ear- lier meals in the day the biggest, since satiety in- creases throughout the day. Written materials on the nutritional needs of cancer patients are abun- dant, usually free, and specific to the type of treat- ment the patient is receiving. When given to pa- tients, time should be planned to review and discuss the materials with both the patient and the family.
Psychosocial support includes environmental manipulations and specific relaxation techniques. The environment should be conducive to promo- tion of a good appetite. Pleasant surroundings and companions frequently help patients maintain an adequate intake. Favorite foods should be encour-
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aged but may need to be adapted to maintain ca- loric intake and reduce distress.
In a study by Dixon, cancer patients at risk for nutritional depletion were randomly assigned to one of four groups: (1) nutritional supplementa- tion, (2) relaxation training, (3) both supplementa- tion and relaxation, and (4) neither supplementa- t ionnor relaxation. 65 Patients were evaluated over a four-month period with groups 1 through 3 visit- ed biweekly by a nurse. The greatest gain in weight, arm muscle circumference, and functional status occurred in the relaxation group, and the most severe losses occurred in the control group.
When oral intake is no longer adequate to main- tain weight, nutritional support may be needed. Prior to enteral or parenteral nutrition, nutritional supplements can be tried (Table 3). Taste tests are needed since compliance with supplements in- creases when they are palatable. 66 Artificial feed- ing via tube is the most invasive of feeding inter- ventions. In this approach, food intake is reduced to the provision of nutrients only, with few psy- chologic, social, or cultural values being met. Ar- tificial feeding carries with it a variety of physio- logic and psychologic side effects. 17 Nursing approaches for patients on artificial feeding in-
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volve education of the patient and family, provi- sion of oral care, and relief of tube associated dis- comforts and distresses. Provision of support and encouragement is needed from nursing staff, med- ical staff, and the patient's family.
A major issue involved in nutrition support is when to stop the feeding for patients who are no longer under active treatment or who have a termi- nal status. Since these measures may be life-pro- longing, the issues of patient and family prefer- ence, cost, and comfort should be addressed. Controversies in this area persist and require con- tinued examination by members of the health team, patients, and the public in order to examine and understand the personal, social, and medical values of artificial feeding. 67
SUMMARY
Nausea, vomiting, and anorexia are persistent symptoms in the cancer patient. Studies have re- vealed a beginning understanding of the mecha- nisms involved, the assessments needed, and the effectiveness of pharmacologic and nonpharmaco- logic interventions. Continued work is needed to refine clinical approaches and improve the impact on morbidity and quality of life.
Table 3. Common Nutritional Supplements
Protein Water Category P roduc t Manufacturer Cal,'cc (g,'L) (mosm,Icg) Flavors Form
Complete milk- Carnation Carnation, 1.0 53.8 677-715 Varied Powder based formula instant Inc
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