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Constipation and diarrhea: The neglected symptoms
Constipation and Diarrhea: The Neglected Symptoms Penelope S.
W r i g h t and Sara L. T h o m a s
Objective: To review the symptom experience of cons t i ~ diarrhea related to cancer and its treatment. Data sources: Published articles and book chapters relating to constipation and diarrhea in patients with cancer. Conclusions: Constipation and diarrhea often represent a major concern and source of discomfort for the cancer patient. Research is needed to establish preven-
tion and treatment protocols for patients at risk for constipation or diarrhea. Implications for nursing practice: Oncology nurses are in an excellent position to recognize individuals who are at high risk for constipation and diarrhea. Preventive strategies and treatment protocols are of utmost importance. Copyright © 1995 by W.B. Saunders Company
N THE UNITED STATES, constipation affects 4.53 million individuals. 1 Untold millions of dollars are spent for over-the counter medications, prescription medications, and other medically related services to manage this disorder. 2 Although many health care professionals dismiss constipation as a relatively trivial problem that is easily managed, Triozzi, Goldstein, and Laszio 3 indicated that the pain, nausea, vomiting, and lethargy resulting from constipation and diarrhea are distressing to the patient with cancer. Like pain, constipation and diarrhea are defined differently by different individuals. Constipation may imply that stools are too small, too hard, too difficult to expel, too infrequent, or that the patient has a feeling of incomplete evacuation after defecation. Diarrhea may imply that stools are too large, looser than usual, or too frequent. Normality of bowel evacuation should be evaluated in terms of the patient's perception of well-being and usual elimination pattern rather than " w h a t most people d o . " Donatelle 2 defines constipation as a "chronic (longer than six weeks) gastrointestinal disorder consisting of hard stools, fewer than three stools per week or the inability to expel stool, whether hard or soft." Weinrich et al 4 define it as too few stools per day or week, too little stool passed, stools too hard, difficult defecation, or no sense of relief after defecation. Diarrhea has been defined as an increase in defecation frequency, an increase in fluid and volume of fecal material, 5 and the passage of more than 200 g of stool per day for 3 weeks. 6 Cultural beliefs and practices influence the definitions, which may vary from individual to individual. Constipation and diarrhea are symptoms, not diseases, and thus they are difficult to quantify.
Popular opinion holds that constipation is a problem of the elderly. Elderly individuals do report problems with constipation five times more often than younger persons; however, constipation is not necessarily a part of the normal aging process, and it does not affect a majority of the well elderly. It is a common dysfunction among all age groups, in both sexes, and at all educational and socioeconomic levels. 2 Constipation is classified as either primary, secondary, or iatrogenic. 7-9 Primary constipation results from extrinsic factors, such as decreased activity, inadequate privacy or time for defecation, or a low-fiber diet. 9 Constipation may be secondary to bowel obstruction, spinal cord compression at a level that affects bowel function (T8-L3), and the metabolic effects of hypercalcemia, hypokalemia, and hypothyroidism. 6 Iatrogenically induced constipation follows the use of pharmacological agents: analgesic opioids, c h e m o t h e r a p e u t i c agents, anticonvulsants, and certain psychotropic medications, l° Individuals with cancer may evidence any of these types of constipation although iatrogenically induced constipation is probably the most common. Diarrhea may be classified as either large vol-
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From the School of Nursing, University of Alabama at Birmingham, Birmingham, AL. Penelope S. Wright, PhD, RN: Associate Professor, School of Nursing, University of Alabama at Birmingham; Sara L. Thomas, BSN, RN: Master's Student, School of Nursing, University of Alabama at Birmingham. Address reprint requests to Penelope S. Wright, PhD, RN, School of Nursing, University of Alabama at Birmingham, Birmingham, AL 35294-1210. Copyright © 1995 by W.B. Saunders Company 0749-2081/95/1104-001055.00/0
Seminars in Oncology Nursing, Vol 11, No 4 (November), 1995: pp 289-297
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ume or small volume. Large-volume diarrhea resuits from a larger-than-usual amount of water, intestinal secretion, or both in the intestine. Smallvolume diarrhea most often results from excessive intestinal motility. Diarrhea may be acute or chronic, depending on the underlying pathology. 5 GASTROINTESTINAL PHYSIOLOGY
To understand the pathophysiology of constipation and diarrhea, the anatomy and physiology of the large bowel (Fig 1) will be reviewed. The colon is 1.5 m long, extending from the ileocecal sphincter to the anus. Its functions include elimination of waste products, production of mucous to lubricate the feces, storage of feces, absorption of fluid and electrolytes, and synthesis of vitamins B and K by bacterial flora.ll The coordinated interaction of three separate processes is required for bowel evacuation: motility, defecation, and continence. Motility refers to the transfer of fecal material through the colon to the rectum. Peristalsis is the colonic mechanism for movement of fecal material. Four factors affect colonic motility: myogenic activity, neural mechanisms, neurohormonal actions, and the local effects of intraluminal contents. 4 Defecation and continence are closely related functions. Weinrich et al 4 state that defecation is "transient overriding of continence." Maintaining continence is primarily unconscious until there is a conscious desire to defecate, which is triggered by the presence of fecal contents in the rectum. An intact nervous system stimulates both the internal and external anal sphincters, causing them to re-
Fig 1. The anatomy and physiology of the colon. (Reprinted with permission. 11)
lax. This process is enhanced as the diaphragm, abdominal, and levator ani muscles contract and the glottis closes. If the stimulus is acted on, the feces move into the rectum, the internal and external sphincters relax, and stool is passed, emptying the bowel from midtransverse colon to the anus. 7 The urge to defecate is felt when the rectal ampulla is approximately one-fourth full. If the urge to defecate is overridden at this point, sensory nerves in the rectum may be desensitized to fullness and may not initiate the reflex activity necessary for evacuation. CONSTIPATION
Weinrich et al 4 listed five poorly understood pathophysiological mechanisms for constipation: (1) segmental contractions that are too vigorous and impede the flow of colonic contents; (2) propulsive contractions that are too weak; (3) insufficient colonic muscle tone; (4) decreased sensitivity to distention in the anorectal area; and (5) incompletely relaxed internal sphincter. Other authors indentify mechanical problems, neurogenic problems, metabolic and endocrine disorders, diet, lack of activity, and medications as causing constipation. 12,12a Most causes of constipation are mechanical and arise from habitual neglect of afferent impulses and failure to initiate defecation. This results in an accumulation of large, dry fecal masses in the rectum. Other mechanical causes included anomalies of the myenteric plexi, functional outlet obstruction during defecation from incomplete sphincter relaxation, excessive contraction of the external sphincter, reduced anorectal angle, absence of rectosigmoid myoelectric and pressure responses, volvulus of the sigmoid colon, tumors, diverticulitis, intussusception, and hernias. Hemorrhoids, anal fissures, fistulas, perineal abscesses, and rectal strictures may prevent easy and adequate stool evacuation.]2'12a Muscle weakness or pain caused by abdominal surgery may also impair defecation by interfering with the generation of adequate intra-abdominal pressure. An additional mechanical cause is nerve damage resulting from stretch injury in women who have experienced multiple pregnancies and/or vaginal delivery of large infants. 5 Neurogenic problems that cause constipation most often involve absent or degenerated neural pathways. Diabetes mellitus may affect colonic
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motor function by damaging the extrinsic innervatio. Abuse of laxatives may alter colonic myenteric plexus function. 2 Other neurological disorders include spinal cord injuries, multiple sclerosis, cerebral palsy, senility, cerebral vascular accident, and acquired megacolon. 5'12'12a Metabolic and endocrine disorders that may cause constipation include hypothyroidism and hyperthyroidism, Addison's disease, Cushing's syndrome, lead poisoning, hypercalcemia, hypokalemia, and other electrolyte imbalances. 5 Studies have shown diet to be strongly related to constipation. A low-residue diet decreases the volume and number of stools, leading to constipation. Colonic motility increases with ingestion of fats, fluids, spices, and soluble and insoluble fibers; however, gastrointestinal motility may decrease as a late response to ingestion of lipids and amino acids. 5 Level of activity and mental status contribute to colonic motility. Sedentary life-style and lack of exercise have been shown to be frequent causes of constipation. 12'12a Depressed patients are at increased risk because of their tendency to be sedentary and lack of motivation to adhere to a healthy diet. The problem is compounded by treatment of depression using anticholinergic medications, which block parasympathetic impulses in the gastrointestinal tract. 12,12a Other medications that affect colonic motility include minerals often ingested in the form of antacids containing aluminum or iron and calcium supplements. Nonsteroidal anti-inflammatory drugs, antihypertensive drugs, opioids, certain chemotherapeutic agents (eg, vinca alkaloids), and antiemetics must also be considered as causative factors for the patient on therapy.2 It must always be remembered that constipation is usually a result of a combination of causes rather than the result of a single factor. In individuals with cancer, constipation can be caused by the tumor itself, the disability associated with advanced cancer, or the side effects of cancer treatment. When the tumor blocks or compresses the bowel, easy passage of stool is prevented. 13 Alternatively, the tumor may involve the nerves supplying the colon, interfering with passage of impulses and slowing gastric motility. 11 When constipation is associated with debility in patients with cancer, it is usually the result of weakness, poor muscle tone, suppression of stim-
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ulus to defecate and lack of energy to defecate. Patients with advanced cancer are more likely to have decreased activity levels and tolerance as well as poor food and fluid intake. In addition, confusion, inability to reach the toilet when the urge to defecate occurs, and lack of privacy must be considered as risks for the debilitated cancer patient. 11 Iatrogenically induced constipation may result from administration of chemotherapeutic agents, especially the vinca alkaloids, opioid analgesics administered for pain relief, or antiemetic medications. Gebbia et a114 administered vinorelbine plus cisplatin to 30 cancer patients with non-small cell lung cancer. Grade 1 (mild) constipation was noted in 20% of the sample and grade 2 in 27% of the sample. 14 Giaccone et a115 studied the pharmacokinetics of a 5-day continuous infusion of vinblastine in 26 patients with refractory advanced breast cancer. Neurotoxicity in the form of severe constipation developed in 14% of the subjects, with frank ileus in 4 subjects. They also evaluated the administration of divided-dose vinblastine to 92 evaluable patients with advanced cancer. The main side effects included neurotoxicity and myelosuppression. Twenty-six subjects had constipation, 4 with frank ileus; vinblastine dose was reduced in 3 patients because of severe constipation or neurotoxicity. ~6 Rambaldi et al ~7 administered interferon-[3 intraperitoneally to 8 patients with advanced ovarian carcinoma that was resistant to conventional chemotherapy. The investigators reported that therapy was tolerated relatively well, with abdominal pain, fever and constipation as the side effects. 17 Mitomycin C and vinblastine were administered to 44 subjects with refractory breast cancer. Only one subject developed constipation. 18 Agostara et a119 evaluated mitomycin C and vinorelbine as second line treatment in 40 subjects with anthracycline-pretreated metastatic breast cancer. Reversible transient mild to moderate constipation was noted in 45% of the sample. Vinorelbine was administered to 67 previously treated subjects with metastatic breast cancer. Sixteen subjects reported grade 2 or 3 constipation; 4 subjects refused further treatment because of chronic constipation or peripheral neuropathy and asthenia. z° Clavel et a121 reported the results of a study of cisplatin, methotrexate, bleomycin, and vincristine (CABO) versus methotrexate, bleomycin, and vincristine (ABO) for the treatment of patients with advanced inoperable head and neck squamous
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cell carcinoma. Constipation was reported in 24% of subjects in the CABO arm and in 26% of subjects in the ABO arm. 2~ Within these reported studies, discussion centered around the efficacy of the treatment regimen in terms of response rate, decrease of tumor size, and subject tolerance of the regimen. The investigators of each study catalogued all treatment side effects; however, there was no discussion of methods to treat or pretreat patients for prevention of side effects. Antiemetic medication, especially the serotonin (5-HT3) receptor antagonists (ondansetron, granisetron, tropisetron) given for control of side effects of other chemotherapeutic agents, have been evaluated for their efficacy. Aapro 22 analyzed the resuits of a series of rigorously designed experimental studies confirming that this group of medications is highly effective in controlling acute chemotherapy-induced nausea and vomiting without the extrapyramidal manifestations associated with other antiemetics. However, one of their side effects is constipation. Cubeddu et a123 found that ondansetron greatly reduced the intensity of nausea resulting from cyclophosphamide-based therapy; constipation, the most commonly reported gastrointestinal side effect, was reported by 0%. 2%, 4%. and 6% of subjects who received placebo. 1 mg, 4 mg, and 8 mg of the antiemetic, respectively. 23 Beck et a124 reported similar results with constipation. Harvey et a125 reported the results of 25 subjects who received 58 courses of ondansetron for relief of carboplatin-induced vomitmg refractory to standard antiemetic therapy. Although excellent control of nausea and vomiting was shown, constipation was found in 13 subjects (54%). Another study26 compared dexamethasone and ondansetron with dexamethasone and alizapride in preventing cisplatin-induced emesis in 36 randomly assigned patients. Mild constipation was frequently reported by subjects on both regimens. Tabona 27 noted that although granisetron was effective as an antiemetic, constipation was a common side effect that was thought to be related to higher doses of the medication and subsided spontaneously. Others have reported the incidence of constipation related to granisetron administration as less than 10% to 15%. 27 Although these investigators recognized the problem of constipation as a side effect of antiemetic therapy, ways to prevent constipation or decrease its impact were not discussed. Opioid analgesia is typically used for pain con-
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trol in patients with cancer. Surgery, chemotherapy, and/or radiation therapy may also account for pain in cancer patients. 29 A plethora of studies report the efficacy of opioid analgesics with variations of route of administration and amount and frequency of dosing. Several studies examined the virtues of long-acting versus intermediate-release morphine sulfate. 3°-35 All of these studies recognized constipation as a negative side effect of the medication. Brooks et a135 reported the loss of one subject because of nausea and constipation. Drexel et a136 reported a study of continuous, low-dose subcutaneous morphine to control severe cancer pain. In this study, a statistically significant increase in pain control was obtained with this delivery method; fewer instances of negative side effects were noted, including constipation, than those associated with pulse administration of analgesia. This was the single study that indicated that treatment with laxatives to control the side effect of constipation was highly effective. Glare and Walsh 37 found that mild side effects, including constipation, occurred in 59% of the subjects treated with oxycodone for chronic pain from advanced cancer. Transderrnal fentanyl was administered to 20 terminally ill cancer patients with excellent pain relief, patient compliance, and patient acceptance. Oral dryness and constipation were the main complaints of subjects, and these were believed to be minor in severity. Despite large doses of opioid analgesia, pain in 25% of individuals with cancer is inadequately managed. 38 The addition of heterocyclic antidepressant agents (HCAs) to pain control regimens may result in decreased narcotic doses, fewer adverse affects, such as constipation, and better pain control. However, there are insufficient data to draw conclusions about the usefulness of HCAs without rigorously designed experimental studi e s . 39
DIARRHEA
There are three major mechanisms of diarrhea: (1) osmotic. (2) secretory and (3) motile. 5 In the patient with osmotic diarrhea, unabsorbable substances in the intestine draw water into the intestinal lumen by osmosis, increasing the weight and volume of the stool. One example of osmotic diarrhea is lactase deficiency. Secretory diarrhea is caused by excessive mucosal secretion of fluid and electrolytes by the intestinal mucosa. This form is
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usually caused by bacteria such as Escherichia coli or Clostridium difficile or by cholera. Hormoneproducing neoplasms, such as thyroid cancer, may also cause this form of diarrhea. Motile diarrhea is caused by an inflammatory disorder of the bowel, such as Crohn's disease. In this form, bowel inflammation results in cramping, pain, and urgency and frequency of defecation. Patients to be evaluated for diarrhea include those who present with a history of weight loss; fever with or without cramping abdominal pain; bloody stools; abdominal radiation; intestinal resection; treatment with antibiotics, chemotherapeutic agents, diuretics, or antihypertensive or laxative medications; steatorrhea; constipation; or a clinical picture of dehydration or electrolyte imbalance. 12,12a Large-volume, iatrogenically induced diarrhea is the type most often experienced by cancer patients. It may result from administration of chemotherapeutic agents, especially the fluoropyramidines alone or in combination with other agents, 4°-68 antiemetic agents, 69-72 combination chemotherapy and radiation therapy, 73-77 treatment for anemia in cancer patients with human erythropoietin, 78 and antibiotic therapy in neutropenic cancer patients. 79 SYMPTOM MANAGEMENT
Evidence to date indicates that individuals with cancer are at risk for constipation or diarrhea as an immediate side effect of their treatment, as a side effect of medication intended to reduce other undesirable side effects, or as a side effect of pain relief medications. It is surprising then, with such widespread recognition of the frequency of occurrence and high degree of discomfort incurred, that the literature on the management of these problems in patients with cancer is extremely scant. Perhaps this may result in part from vague definitions that lack physiological parameters. Additionally, health care providers seem more intent on monitoring the direct effects rather than secondary effects of treatment. The frequency and degree of discomfort from constipation or diarrhea may be highly important to the patient. The financial and emotional cost of hospitalization for treatment of fluid and electrolyte imbalance caused by diarrhea must also be considered. Health care providers seem to consider constipation a rather trivial problem, possibly because
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treatment methods are well known (Table 1). 11 Also, the devastating effects of ineffectively treated cancer or the ineffective management of pain, nausea, or vomiting may have a more profound effect on an individual's health and life than constipation. The same statement cannot be made for diarrhea. Loss of fluid and electrolyte imbalance can profoundly affect the individual's physiological response to chemotherapy or radiation therapy. Literature supports two methods of management for treatment-induced diarrhea in cancer patients: sucralfate and octreotide. Sucralfate has been highly effective in patients receiving radiation therapy for localized prostate and urinary bladder cancer, s° Vails et al concluded that although their subjects needed adjunctive support, sucralfate effectively increased enteric tolerance of pelvic radiation therapy, sl Cascinu et al s2 found that 19 of 21 patients receiving octreotide and 3 of 20 patients receiving loperamide tolerated fluorouracil therapy combined with leucovorin or interferon without requiring hospitalization for fluid and electrolyte correction secondary to diarrhea. This group also reported that for control of cisplatin-induced diarrhea, patients receiving octreotide had significantly less diarrhea (p = .01) than those receiving placebo. Similarly, in a group of 40 patients randomly assigned to treatment with octreotide or loperamide, 80% of the octreotide group and 30% of the loperamide group had a reduction in chemotherapy-induced diarrhea.83 In another study, Gebbia et al v° found a statistically significant difference (p < .001) in the length of time necessary to achieve remission of diarrhea. NURSING IMPLICATIONS
Nurses are in an excellent position tO recognize individuals who by virtue of their treatment regiTable 1. Medications for Treating Constipation Type Bulk forming
Stimulant laxatives
Osmotic laxatives Rectally administered laxatives
Action Retain fluid, thus increasing the fecal mass and stimulating peristalsis; effective within a few days Increase intestinal motility and stimulate large bowel to produce a soft stool Attract and retain fluid in bowel to form a soft stool Lubricate and soften feces or irritate bowel to produce stool
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mens are at high risk for constipation and diarrhea. The goal for all patients should be prevention. This can be accomplished by using the nursing process and an established protocol. A recent integrative review and meta-analysis of patient-related cancer nursing research published between 1981 and 1990 found no nursing research on the subject of nursing management of constipation or diarrhea. 84 Considering the problems these symptoms cause in the cancer patient, there seems to be a serious lack of attention to an important area of nursing research. Constipation can be assessed using an eight-item instrument designed by McMillan and Williams. 7 Alternatively, M c C o r k l e ' s Symptom Distress Scale 85 or Rhodes Adapted Symptom Distress Scale 86 can be used. All of these instruments have acceptable psychometric data. Individuals who by virtue of their treatment regimens are at high risk for constipation must be observed closely and frequently for indications of constipation. Nursing actions that can be implemented at the initiation of treatment include patient education as to the side effects of treatment, including constipation or diarrhea, and methods of preventing these complications. Cameron 1 recommends dietary counseling regarding sufficient intake of dietary fiber and gradually increasing ingestion of fluid until the total is at least eight glasses daily. An inexpensive recipe that can be prepared and kept in the refrigerator or freezer and used for constipation is shown in Table 2. Although there are no data supporting exercise as preventing constipation, Cameron I argues that improved tone of the muscles important in defecation could likely play an important part in prevention. Furthermore, discussion with the patient to establish a daily bowel routine is essential. When constipation cannot be prevented, interventions designed to alleviate the problem must be undertaken. The physician or
Table 2. An Inexpensive Recipe to Relieve Constipation 12 oz each prunes, raisins, dates, and figs 2 o z powdered Senna Grind fruits and add powered Senna. Mix well and pat into a 9 x 13-inch pan. Cut into 11/2 × 11/2-inch squares. Refrigerate or freeze for later use. The usual dose is 1 square. This size portion equals one fruit exchange for patients on American Dietetic Association diets.
nurse practitioner responsible must be kept appraised of the quality and quantity of each individual's elimination state and deviation from the usual pattern. Orders for laxatives or enemas should be carried out in a timely manner, and results should be reported such that necessary modifications in the treatment regimen can be made. Because cancer treatment can result in diarrhea, the oncology nurse must be aware of the side effects of treatment and monitor patients accordingly. Assessment of the frequency and amount of diarrhea must be performed at each visit. Initiation of antidiarrhea therapy could begin at the initiation of the cancer therapy known to result in diarrhea. Oncology nurses can make significant contributions by engaging in research designed to establish prevention and treatment protocols for individuals at risk for constipation or diarrhea. The World Health Organization has developed a three-step "analgesic ladder" for analgesics in which each medication is classified as either a nonopioid, a weak opioid, or a strong opioid. 87 A similar approach could be taken to classify chemotherapeutic and antiemetic medications for the degree of constipation each usually produces in patients and to classify chemotherapeutic and radiation therapy regimens for the degree of diarrhea each usually produces in patients. Using a rigorous doubleblind, crossover design, preventive regimens for each level of increasing difficulty could be evaluated.
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the prevention of emesis induced by cisplatin-containing chemotherapies for urological cancers. Eur Urol 23:450-456, 1993 27. Tabona MV: An overview on the use of granisetron in the treatment of emesis associated with cytostatic chemotherapy. Eur J Cancer 26:$37-$41, 1990 (Suppl) 28. Plosker GL, Goa KL: Granisetron: A review of its pharmacological properties and therapeutic use as an antiemetic. Drug 42:805-824, 1991 29. Levy MH, Rosen SM, Ottery FD, et al: Supportive care in oncology. Curr Probl Cancer 16:329-418, 1992 30. Hammack JE, Lorprinzi CL: Use of orally administered opioids for cancer related pain. Mayo Clin Proc 69:384-390, 1994 31. Meed SD, Kleinman PM, Kantor TG, et al: Management of cancer pain with oral controlled-release morphine sulfate. Clin Res 27:155-161, 1987 32. Vijayaram S, Ramamani PV, Chandrashekhar NS, et al: Continuing care for cancer pain relief with oral morphine solution: One-year experience in a regional cancer center. Cancer 66:1590-1595, 1990 33. Walsh TD, MacDonald N, Bruera E, et al: A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer. Am J Clin Oncol 15:268-272, 1992 34. Terman GW, Loeser JD: A case of opiate-insensitive pain: Malignant treatment of benign pain. Clin J Pain 8:255259, 1992 35. Brooks I, DeJager R, Blumenreich M, et al: Principles of cancer pain management use of long-acting oral morphine. J Fam Pract 28:275-280, 1989 36. Drexel H, Dzien A, Spiegel R, et al: Treatment of severe cancer pain by low-dose continuous subcutaneous morphine. Pain 36:169-176, 1989 37. Glare PA, Walsh TD: Dose-ranging study of oxycodone for chronic pain in advanced cancer. J Clin Oncol 11:973-978, 1993 38. Zech DFJ, Grond SUA, Lynch J, et al: Transderrnal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain: A pilot study with 20 terminally ill cancer patients. Pain 50:293-301, 1992 39. Egbunike IG, Chaffee B J: Antidepressants in the managemem of chronic pain syndromes. Pharmacotherapy 10:262270, 1990 40. Fulton J: Chemotherapeutic treatment of colorectal cancer: Rationale, trends, and nursing care. J Wound Ostomy Continence Nurs 21:12-21, 1994 41. Raschko J, Akman S, Leong L, et al: Phase I study of 5-day continuous infusion fluorodeoxyuridine and high-dose folinic acid with oral hydroxyurea. Cancer Chemother Pharmacol 35:161-164, 1994 42. Conti F, Kemeny N, Saltz L, et al: Continuous infusion fluorouracil/leucovorin and bolus mitomycin-C as a salvage regimen for patients with advanced colorectal cancer. Cancer 73:769-774, 1995 43. Minsky B, Cohen A, Enkar W, et al: Pre-operative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer. Cancer 73:273-280, 1994 44. Vanhoefer U, Wilke H, Weh H, et al: Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer. Annals of Oncol 5:850-851, 1994 45. Zaniboni A, Meriggi F, Arcangeli G, et al: L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: A phase II study. Ann Oncol 4:41-43, 1993 (Suppl)
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46. Stein B, Petrelli N, Douglass H, et al: Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer 75:1-17, 1995 47. Repetto L, Miglietta L, Gardin G, et al: Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer. Breast Cancer Res Treat 30:i33-137, 1994 48. Pratt C, Meyer W, Howlett N, et al: Phase II study of 5-fluorouracil/leucovorin for pediatric patients with malignant solid tumors. Cancer 74:2593-2598, 1994 49. DeCaprio J, Mayer R, Gonin R, et al: Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: Results of a phase II trial. J Clin Oncol 9:2128-2133, 1991 50. Valcone F, Gandara D, Luce J, et al: Phase I trial of a 5-day infusion of L-leucovorin plus daily bolus 5-fluorouracil in patients with advanced gastrointestinal malignancies. Cancer Chemother Pharmacol 32:215-220, 1993 51. Falcone A, Pfanner E, Ricci S, et al: Oral doxifluridine in elderly patients with metastatic colorectal cancer: A multicenter phase II study. Ann Oncol 5:760-762, 1994 52. Abigerges D, Chabot G, Armand J, et al: Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 13:210-221, 1995 53. deForni M, Bugat R, Chabot G, et al: Phase I and pharmacokinetic study of the camptothecin derivative irinotecan administered on a weekly schedule in cancer patients. Cancer Res 54:4347-4354, 1994 54. Stoger H, Bauemhofer T, Schmid M, et al: A phase I/II study of 4'-otetrahydropyranyl-doxoruhicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients. Cancer Chemother Pharmacol 35:174178, 1994 55. Yamaguchi A, Maeda A, Hachisuka K, et al: Study of 5'-DFUR treatment as postoperative adjuvant chemotherapy for stomach and colorectal cancer: Tokai GATS Group. Jpn J Cancer Chemother 21:621-626, 1994 56. Francis P, Schmeider J, Harm L, et al: Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer. J Clin Oncol 12:2301-2308, 1994 57. Schifeling D, Konski A, Howard J, et al: Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas: A phase I study. Int J Pancreatol 12: 239-243, 1992 58. Minsky B, Cohen A, Kemeny N, et al: Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol 10:7984, 1992 59. Minsky B, Cohen A, Kemeny N, et al: Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer. Int J Radiat Oncol Biol Phys 25:821-827, 1993 60. Minsky B, Cohen A, Enker W, et al: Phase I trial of postoperative 5-FU, radiation therapy, and high dose leucovorin for resectable rectal cancer. Int J Radiat Oncol Biol Phys 23:130-145, 1992 61. Levi F, Misset J, Brienza S, et al: A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable
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pump: High antitumor effectiveness against metastatic colorectal cancer. Cancer 69:893-900, 1992 62. Fountzilas G, Kosmidis P, Makrantonakis P, et al: Carboplatin, continuous infusion fluorouracil and mid-cycle highdose methotrexate as initial treatment in patients with locally advanced head and neck cancer. Tumori 77:426-431, 1991 63. Gebbia V, Carreca I, Testa A, et al: Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy. Anticancer Drugs 4:443-445, 1993 64. Lovett D, Kelsen D, Eisenberger M, et al: A phase II trial of carboplatin and vinblastine in the treatment of advanced squamous cell carcinoma of the esophagus. Cancer 67:354-356, 1991 65. Siegert W, Beyer J, Strohscheer I, et al: High-dose treatmerit with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: A phase I/II study. J Clin Oncol 12:12231231, 1994 66. Gasparini G, Carlo O, Bami S, et al: Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: A phase II study. J Clin Oncol 12:2094-2101, 1994 67. Chiara S, Conte P, Franzone P, et al: High-risk earlystage ovarian cancer: Randomized clinical trial comparing cisplatin plus cyclophosphamide versus whole abdominal radiotherapy. Am J Clin Oncol 17:72-78, 1994 68. Vermoren J, Gundersen S, Clavel M, et al: Randomized phase II trial of iproplafin and carboplatin in advanced breast cancer. Annals of Oncol 4:303-306, 1993 69. Or R, Drakos P, Nagler A, et al: The antiemetic efficacy and tolerability of tropisetron in patients conditioned with highdose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation. Support Care Cancer 2: 245-248, 1994 70. Gebbia V, Gebbia N, Russo A, et al: Hydroxyurea modulates 5-fluorouracil antineoplastic activity in advanced head and neck carcinoma pretreated with chemotherapy. Anticancer Drugs 3:347-349, 1992 71. Rusthoven J, Pater J, Kaizer L, et al: A randomized, double-blinded study comparing six doses of batanopride (BMY-25801) with methylprednisolone in patients receiving moderately emetogenic chemotherapy. Ann Oncol 2:681-686, 1991 72. Kim H, Rosenberg S, Steinberg S, et al: A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2. J Immunother Emphasis Tumor Immunol 16:60-65, 1994 73. Resbeut M, Cowen D, Viens P, et al: Concomitant chemoradiation prior to surgery in the treatment of advanced cervical carcinoma. Gynecol Oncol 54:68-75, 1994 74. Resbeut M, Noirclerc M, Viens P, et al: Simultaneous radiotherapy and chemotherapy in the treatment of advanced cancer of the cervix uteri. Bull Cancer 80:984-993, 1993 75. Cevek J, Cufer T, Kragelj B, et al: Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: Initial report. Int J Radiat Oncol Biol Phys 25:777-782, 1993 76. Malviya V, Han I, Deppe G, et al: High-dose-rate aftefloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix. Gynecol Oncol 42:233-238, 1991
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77. Coia L, Hoffman J, Scher R, et al: Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum. Int J Radiat Oncol Biol Phys 30:161-167, 1994 78. Case D, Burkowski R, Carey R, et al: Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. J Natl Cancer Inst 85:801-806, 1993 79. Feliu J, Artal A, Gonzales B, et al: Comparison of two antibiotic regimens (piperacillin plus amikacin versus ceftazidime plus amikacin) as empiric therapy for febrile neutropenic patients with cancer. Antimicrob Agents Chemother 36:28162820, 1992 80. Henrikasson R, Franzen L, Littbrand B: Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer. J Clin Oncol 10:969-975, 1992 81. Valls A, Algara M, Domenech M, et al: Efficacy of sucralfate in the prophylaxis of diarrhea secondary to acute radiation-induced enteritis: Preliminary results of a doubleblind randomized trial. Medsicina Clinica 96:449-452, 1991 82. Cascinu S, Fedeli A, Fedeli S, et al: Octreotide versus
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loperamide in the treatment of fluorouracil-induced diarrhea: A randomized trial. J Clin Oncol 11:148-151, 1993 83. Cascinu S, Fedeli A, Fedeli S, et al: Control of chemotherapy induced diarrhea with octreotide: A randomized trial with placebo in patients receiving cisplatin. Oncology 51:7073, 1994 84. Wright PS: Review of a decade of patient-related oncology nursing research: Physiologic variables, in Proceedings of the American Cancer Society Third National Conference on Cancer Nursing Research. Atlanta, GA, American Cancer Society, 1994 85. McCorkle R, Young K: Development of a symptom distress scale. Cancer Nurs 1:373-378, 1978 86. Simms SG, Rhodes VA, Madsen RW: Comparison of prochlorperazine and lorazepam antiemetic regimens in the control of postchemotherapy symptoms. Nurs Res 42:234-239, 1993 87. Gond S, Diefenbach C, Zech D, et al: Validation of World Health Organization guidelines for pain relief in head and neck cancer. Ann Otol RhinoI Laryngol 102:342-348, 1993
W r i g h t and Sara L. T h o m a s
Objective: To review the symptom experience of cons t i ~ diarrhea related to cancer and its treatment. Data sources: Published articles and book chapters relating to constipation and diarrhea in patients with cancer. Conclusions: Constipation and diarrhea often represent a major concern and source of discomfort for the cancer patient. Research is needed to establish preven-
tion and treatment protocols for patients at risk for constipation or diarrhea. Implications for nursing practice: Oncology nurses are in an excellent position to recognize individuals who are at high risk for constipation and diarrhea. Preventive strategies and treatment protocols are of utmost importance. Copyright © 1995 by W.B. Saunders Company
N THE UNITED STATES, constipation affects 4.53 million individuals. 1 Untold millions of dollars are spent for over-the counter medications, prescription medications, and other medically related services to manage this disorder. 2 Although many health care professionals dismiss constipation as a relatively trivial problem that is easily managed, Triozzi, Goldstein, and Laszio 3 indicated that the pain, nausea, vomiting, and lethargy resulting from constipation and diarrhea are distressing to the patient with cancer. Like pain, constipation and diarrhea are defined differently by different individuals. Constipation may imply that stools are too small, too hard, too difficult to expel, too infrequent, or that the patient has a feeling of incomplete evacuation after defecation. Diarrhea may imply that stools are too large, looser than usual, or too frequent. Normality of bowel evacuation should be evaluated in terms of the patient's perception of well-being and usual elimination pattern rather than " w h a t most people d o . " Donatelle 2 defines constipation as a "chronic (longer than six weeks) gastrointestinal disorder consisting of hard stools, fewer than three stools per week or the inability to expel stool, whether hard or soft." Weinrich et al 4 define it as too few stools per day or week, too little stool passed, stools too hard, difficult defecation, or no sense of relief after defecation. Diarrhea has been defined as an increase in defecation frequency, an increase in fluid and volume of fecal material, 5 and the passage of more than 200 g of stool per day for 3 weeks. 6 Cultural beliefs and practices influence the definitions, which may vary from individual to individual. Constipation and diarrhea are symptoms, not diseases, and thus they are difficult to quantify.
Popular opinion holds that constipation is a problem of the elderly. Elderly individuals do report problems with constipation five times more often than younger persons; however, constipation is not necessarily a part of the normal aging process, and it does not affect a majority of the well elderly. It is a common dysfunction among all age groups, in both sexes, and at all educational and socioeconomic levels. 2 Constipation is classified as either primary, secondary, or iatrogenic. 7-9 Primary constipation results from extrinsic factors, such as decreased activity, inadequate privacy or time for defecation, or a low-fiber diet. 9 Constipation may be secondary to bowel obstruction, spinal cord compression at a level that affects bowel function (T8-L3), and the metabolic effects of hypercalcemia, hypokalemia, and hypothyroidism. 6 Iatrogenically induced constipation follows the use of pharmacological agents: analgesic opioids, c h e m o t h e r a p e u t i c agents, anticonvulsants, and certain psychotropic medications, l° Individuals with cancer may evidence any of these types of constipation although iatrogenically induced constipation is probably the most common. Diarrhea may be classified as either large vol-
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From the School of Nursing, University of Alabama at Birmingham, Birmingham, AL. Penelope S. Wright, PhD, RN: Associate Professor, School of Nursing, University of Alabama at Birmingham; Sara L. Thomas, BSN, RN: Master's Student, School of Nursing, University of Alabama at Birmingham. Address reprint requests to Penelope S. Wright, PhD, RN, School of Nursing, University of Alabama at Birmingham, Birmingham, AL 35294-1210. Copyright © 1995 by W.B. Saunders Company 0749-2081/95/1104-001055.00/0
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ume or small volume. Large-volume diarrhea resuits from a larger-than-usual amount of water, intestinal secretion, or both in the intestine. Smallvolume diarrhea most often results from excessive intestinal motility. Diarrhea may be acute or chronic, depending on the underlying pathology. 5 GASTROINTESTINAL PHYSIOLOGY
To understand the pathophysiology of constipation and diarrhea, the anatomy and physiology of the large bowel (Fig 1) will be reviewed. The colon is 1.5 m long, extending from the ileocecal sphincter to the anus. Its functions include elimination of waste products, production of mucous to lubricate the feces, storage of feces, absorption of fluid and electrolytes, and synthesis of vitamins B and K by bacterial flora.ll The coordinated interaction of three separate processes is required for bowel evacuation: motility, defecation, and continence. Motility refers to the transfer of fecal material through the colon to the rectum. Peristalsis is the colonic mechanism for movement of fecal material. Four factors affect colonic motility: myogenic activity, neural mechanisms, neurohormonal actions, and the local effects of intraluminal contents. 4 Defecation and continence are closely related functions. Weinrich et al 4 state that defecation is "transient overriding of continence." Maintaining continence is primarily unconscious until there is a conscious desire to defecate, which is triggered by the presence of fecal contents in the rectum. An intact nervous system stimulates both the internal and external anal sphincters, causing them to re-
Fig 1. The anatomy and physiology of the colon. (Reprinted with permission. 11)
lax. This process is enhanced as the diaphragm, abdominal, and levator ani muscles contract and the glottis closes. If the stimulus is acted on, the feces move into the rectum, the internal and external sphincters relax, and stool is passed, emptying the bowel from midtransverse colon to the anus. 7 The urge to defecate is felt when the rectal ampulla is approximately one-fourth full. If the urge to defecate is overridden at this point, sensory nerves in the rectum may be desensitized to fullness and may not initiate the reflex activity necessary for evacuation. CONSTIPATION
Weinrich et al 4 listed five poorly understood pathophysiological mechanisms for constipation: (1) segmental contractions that are too vigorous and impede the flow of colonic contents; (2) propulsive contractions that are too weak; (3) insufficient colonic muscle tone; (4) decreased sensitivity to distention in the anorectal area; and (5) incompletely relaxed internal sphincter. Other authors indentify mechanical problems, neurogenic problems, metabolic and endocrine disorders, diet, lack of activity, and medications as causing constipation. 12,12a Most causes of constipation are mechanical and arise from habitual neglect of afferent impulses and failure to initiate defecation. This results in an accumulation of large, dry fecal masses in the rectum. Other mechanical causes included anomalies of the myenteric plexi, functional outlet obstruction during defecation from incomplete sphincter relaxation, excessive contraction of the external sphincter, reduced anorectal angle, absence of rectosigmoid myoelectric and pressure responses, volvulus of the sigmoid colon, tumors, diverticulitis, intussusception, and hernias. Hemorrhoids, anal fissures, fistulas, perineal abscesses, and rectal strictures may prevent easy and adequate stool evacuation.]2'12a Muscle weakness or pain caused by abdominal surgery may also impair defecation by interfering with the generation of adequate intra-abdominal pressure. An additional mechanical cause is nerve damage resulting from stretch injury in women who have experienced multiple pregnancies and/or vaginal delivery of large infants. 5 Neurogenic problems that cause constipation most often involve absent or degenerated neural pathways. Diabetes mellitus may affect colonic
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motor function by damaging the extrinsic innervatio. Abuse of laxatives may alter colonic myenteric plexus function. 2 Other neurological disorders include spinal cord injuries, multiple sclerosis, cerebral palsy, senility, cerebral vascular accident, and acquired megacolon. 5'12'12a Metabolic and endocrine disorders that may cause constipation include hypothyroidism and hyperthyroidism, Addison's disease, Cushing's syndrome, lead poisoning, hypercalcemia, hypokalemia, and other electrolyte imbalances. 5 Studies have shown diet to be strongly related to constipation. A low-residue diet decreases the volume and number of stools, leading to constipation. Colonic motility increases with ingestion of fats, fluids, spices, and soluble and insoluble fibers; however, gastrointestinal motility may decrease as a late response to ingestion of lipids and amino acids. 5 Level of activity and mental status contribute to colonic motility. Sedentary life-style and lack of exercise have been shown to be frequent causes of constipation. 12'12a Depressed patients are at increased risk because of their tendency to be sedentary and lack of motivation to adhere to a healthy diet. The problem is compounded by treatment of depression using anticholinergic medications, which block parasympathetic impulses in the gastrointestinal tract. 12,12a Other medications that affect colonic motility include minerals often ingested in the form of antacids containing aluminum or iron and calcium supplements. Nonsteroidal anti-inflammatory drugs, antihypertensive drugs, opioids, certain chemotherapeutic agents (eg, vinca alkaloids), and antiemetics must also be considered as causative factors for the patient on therapy.2 It must always be remembered that constipation is usually a result of a combination of causes rather than the result of a single factor. In individuals with cancer, constipation can be caused by the tumor itself, the disability associated with advanced cancer, or the side effects of cancer treatment. When the tumor blocks or compresses the bowel, easy passage of stool is prevented. 13 Alternatively, the tumor may involve the nerves supplying the colon, interfering with passage of impulses and slowing gastric motility. 11 When constipation is associated with debility in patients with cancer, it is usually the result of weakness, poor muscle tone, suppression of stim-
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ulus to defecate and lack of energy to defecate. Patients with advanced cancer are more likely to have decreased activity levels and tolerance as well as poor food and fluid intake. In addition, confusion, inability to reach the toilet when the urge to defecate occurs, and lack of privacy must be considered as risks for the debilitated cancer patient. 11 Iatrogenically induced constipation may result from administration of chemotherapeutic agents, especially the vinca alkaloids, opioid analgesics administered for pain relief, or antiemetic medications. Gebbia et a114 administered vinorelbine plus cisplatin to 30 cancer patients with non-small cell lung cancer. Grade 1 (mild) constipation was noted in 20% of the sample and grade 2 in 27% of the sample. 14 Giaccone et a115 studied the pharmacokinetics of a 5-day continuous infusion of vinblastine in 26 patients with refractory advanced breast cancer. Neurotoxicity in the form of severe constipation developed in 14% of the subjects, with frank ileus in 4 subjects. They also evaluated the administration of divided-dose vinblastine to 92 evaluable patients with advanced cancer. The main side effects included neurotoxicity and myelosuppression. Twenty-six subjects had constipation, 4 with frank ileus; vinblastine dose was reduced in 3 patients because of severe constipation or neurotoxicity. ~6 Rambaldi et al ~7 administered interferon-[3 intraperitoneally to 8 patients with advanced ovarian carcinoma that was resistant to conventional chemotherapy. The investigators reported that therapy was tolerated relatively well, with abdominal pain, fever and constipation as the side effects. 17 Mitomycin C and vinblastine were administered to 44 subjects with refractory breast cancer. Only one subject developed constipation. 18 Agostara et a119 evaluated mitomycin C and vinorelbine as second line treatment in 40 subjects with anthracycline-pretreated metastatic breast cancer. Reversible transient mild to moderate constipation was noted in 45% of the sample. Vinorelbine was administered to 67 previously treated subjects with metastatic breast cancer. Sixteen subjects reported grade 2 or 3 constipation; 4 subjects refused further treatment because of chronic constipation or peripheral neuropathy and asthenia. z° Clavel et a121 reported the results of a study of cisplatin, methotrexate, bleomycin, and vincristine (CABO) versus methotrexate, bleomycin, and vincristine (ABO) for the treatment of patients with advanced inoperable head and neck squamous
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cell carcinoma. Constipation was reported in 24% of subjects in the CABO arm and in 26% of subjects in the ABO arm. 2~ Within these reported studies, discussion centered around the efficacy of the treatment regimen in terms of response rate, decrease of tumor size, and subject tolerance of the regimen. The investigators of each study catalogued all treatment side effects; however, there was no discussion of methods to treat or pretreat patients for prevention of side effects. Antiemetic medication, especially the serotonin (5-HT3) receptor antagonists (ondansetron, granisetron, tropisetron) given for control of side effects of other chemotherapeutic agents, have been evaluated for their efficacy. Aapro 22 analyzed the resuits of a series of rigorously designed experimental studies confirming that this group of medications is highly effective in controlling acute chemotherapy-induced nausea and vomiting without the extrapyramidal manifestations associated with other antiemetics. However, one of their side effects is constipation. Cubeddu et a123 found that ondansetron greatly reduced the intensity of nausea resulting from cyclophosphamide-based therapy; constipation, the most commonly reported gastrointestinal side effect, was reported by 0%. 2%, 4%. and 6% of subjects who received placebo. 1 mg, 4 mg, and 8 mg of the antiemetic, respectively. 23 Beck et a124 reported similar results with constipation. Harvey et a125 reported the results of 25 subjects who received 58 courses of ondansetron for relief of carboplatin-induced vomitmg refractory to standard antiemetic therapy. Although excellent control of nausea and vomiting was shown, constipation was found in 13 subjects (54%). Another study26 compared dexamethasone and ondansetron with dexamethasone and alizapride in preventing cisplatin-induced emesis in 36 randomly assigned patients. Mild constipation was frequently reported by subjects on both regimens. Tabona 27 noted that although granisetron was effective as an antiemetic, constipation was a common side effect that was thought to be related to higher doses of the medication and subsided spontaneously. Others have reported the incidence of constipation related to granisetron administration as less than 10% to 15%. 27 Although these investigators recognized the problem of constipation as a side effect of antiemetic therapy, ways to prevent constipation or decrease its impact were not discussed. Opioid analgesia is typically used for pain con-
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trol in patients with cancer. Surgery, chemotherapy, and/or radiation therapy may also account for pain in cancer patients. 29 A plethora of studies report the efficacy of opioid analgesics with variations of route of administration and amount and frequency of dosing. Several studies examined the virtues of long-acting versus intermediate-release morphine sulfate. 3°-35 All of these studies recognized constipation as a negative side effect of the medication. Brooks et a135 reported the loss of one subject because of nausea and constipation. Drexel et a136 reported a study of continuous, low-dose subcutaneous morphine to control severe cancer pain. In this study, a statistically significant increase in pain control was obtained with this delivery method; fewer instances of negative side effects were noted, including constipation, than those associated with pulse administration of analgesia. This was the single study that indicated that treatment with laxatives to control the side effect of constipation was highly effective. Glare and Walsh 37 found that mild side effects, including constipation, occurred in 59% of the subjects treated with oxycodone for chronic pain from advanced cancer. Transderrnal fentanyl was administered to 20 terminally ill cancer patients with excellent pain relief, patient compliance, and patient acceptance. Oral dryness and constipation were the main complaints of subjects, and these were believed to be minor in severity. Despite large doses of opioid analgesia, pain in 25% of individuals with cancer is inadequately managed. 38 The addition of heterocyclic antidepressant agents (HCAs) to pain control regimens may result in decreased narcotic doses, fewer adverse affects, such as constipation, and better pain control. However, there are insufficient data to draw conclusions about the usefulness of HCAs without rigorously designed experimental studi e s . 39
DIARRHEA
There are three major mechanisms of diarrhea: (1) osmotic. (2) secretory and (3) motile. 5 In the patient with osmotic diarrhea, unabsorbable substances in the intestine draw water into the intestinal lumen by osmosis, increasing the weight and volume of the stool. One example of osmotic diarrhea is lactase deficiency. Secretory diarrhea is caused by excessive mucosal secretion of fluid and electrolytes by the intestinal mucosa. This form is
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usually caused by bacteria such as Escherichia coli or Clostridium difficile or by cholera. Hormoneproducing neoplasms, such as thyroid cancer, may also cause this form of diarrhea. Motile diarrhea is caused by an inflammatory disorder of the bowel, such as Crohn's disease. In this form, bowel inflammation results in cramping, pain, and urgency and frequency of defecation. Patients to be evaluated for diarrhea include those who present with a history of weight loss; fever with or without cramping abdominal pain; bloody stools; abdominal radiation; intestinal resection; treatment with antibiotics, chemotherapeutic agents, diuretics, or antihypertensive or laxative medications; steatorrhea; constipation; or a clinical picture of dehydration or electrolyte imbalance. 12,12a Large-volume, iatrogenically induced diarrhea is the type most often experienced by cancer patients. It may result from administration of chemotherapeutic agents, especially the fluoropyramidines alone or in combination with other agents, 4°-68 antiemetic agents, 69-72 combination chemotherapy and radiation therapy, 73-77 treatment for anemia in cancer patients with human erythropoietin, 78 and antibiotic therapy in neutropenic cancer patients. 79 SYMPTOM MANAGEMENT
Evidence to date indicates that individuals with cancer are at risk for constipation or diarrhea as an immediate side effect of their treatment, as a side effect of medication intended to reduce other undesirable side effects, or as a side effect of pain relief medications. It is surprising then, with such widespread recognition of the frequency of occurrence and high degree of discomfort incurred, that the literature on the management of these problems in patients with cancer is extremely scant. Perhaps this may result in part from vague definitions that lack physiological parameters. Additionally, health care providers seem more intent on monitoring the direct effects rather than secondary effects of treatment. The frequency and degree of discomfort from constipation or diarrhea may be highly important to the patient. The financial and emotional cost of hospitalization for treatment of fluid and electrolyte imbalance caused by diarrhea must also be considered. Health care providers seem to consider constipation a rather trivial problem, possibly because
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treatment methods are well known (Table 1). 11 Also, the devastating effects of ineffectively treated cancer or the ineffective management of pain, nausea, or vomiting may have a more profound effect on an individual's health and life than constipation. The same statement cannot be made for diarrhea. Loss of fluid and electrolyte imbalance can profoundly affect the individual's physiological response to chemotherapy or radiation therapy. Literature supports two methods of management for treatment-induced diarrhea in cancer patients: sucralfate and octreotide. Sucralfate has been highly effective in patients receiving radiation therapy for localized prostate and urinary bladder cancer, s° Vails et al concluded that although their subjects needed adjunctive support, sucralfate effectively increased enteric tolerance of pelvic radiation therapy, sl Cascinu et al s2 found that 19 of 21 patients receiving octreotide and 3 of 20 patients receiving loperamide tolerated fluorouracil therapy combined with leucovorin or interferon without requiring hospitalization for fluid and electrolyte correction secondary to diarrhea. This group also reported that for control of cisplatin-induced diarrhea, patients receiving octreotide had significantly less diarrhea (p = .01) than those receiving placebo. Similarly, in a group of 40 patients randomly assigned to treatment with octreotide or loperamide, 80% of the octreotide group and 30% of the loperamide group had a reduction in chemotherapy-induced diarrhea.83 In another study, Gebbia et al v° found a statistically significant difference (p < .001) in the length of time necessary to achieve remission of diarrhea. NURSING IMPLICATIONS
Nurses are in an excellent position tO recognize individuals who by virtue of their treatment regiTable 1. Medications for Treating Constipation Type Bulk forming
Stimulant laxatives
Osmotic laxatives Rectally administered laxatives
Action Retain fluid, thus increasing the fecal mass and stimulating peristalsis; effective within a few days Increase intestinal motility and stimulate large bowel to produce a soft stool Attract and retain fluid in bowel to form a soft stool Lubricate and soften feces or irritate bowel to produce stool
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mens are at high risk for constipation and diarrhea. The goal for all patients should be prevention. This can be accomplished by using the nursing process and an established protocol. A recent integrative review and meta-analysis of patient-related cancer nursing research published between 1981 and 1990 found no nursing research on the subject of nursing management of constipation or diarrhea. 84 Considering the problems these symptoms cause in the cancer patient, there seems to be a serious lack of attention to an important area of nursing research. Constipation can be assessed using an eight-item instrument designed by McMillan and Williams. 7 Alternatively, M c C o r k l e ' s Symptom Distress Scale 85 or Rhodes Adapted Symptom Distress Scale 86 can be used. All of these instruments have acceptable psychometric data. Individuals who by virtue of their treatment regimens are at high risk for constipation must be observed closely and frequently for indications of constipation. Nursing actions that can be implemented at the initiation of treatment include patient education as to the side effects of treatment, including constipation or diarrhea, and methods of preventing these complications. Cameron 1 recommends dietary counseling regarding sufficient intake of dietary fiber and gradually increasing ingestion of fluid until the total is at least eight glasses daily. An inexpensive recipe that can be prepared and kept in the refrigerator or freezer and used for constipation is shown in Table 2. Although there are no data supporting exercise as preventing constipation, Cameron I argues that improved tone of the muscles important in defecation could likely play an important part in prevention. Furthermore, discussion with the patient to establish a daily bowel routine is essential. When constipation cannot be prevented, interventions designed to alleviate the problem must be undertaken. The physician or
Table 2. An Inexpensive Recipe to Relieve Constipation 12 oz each prunes, raisins, dates, and figs 2 o z powdered Senna Grind fruits and add powered Senna. Mix well and pat into a 9 x 13-inch pan. Cut into 11/2 × 11/2-inch squares. Refrigerate or freeze for later use. The usual dose is 1 square. This size portion equals one fruit exchange for patients on American Dietetic Association diets.
nurse practitioner responsible must be kept appraised of the quality and quantity of each individual's elimination state and deviation from the usual pattern. Orders for laxatives or enemas should be carried out in a timely manner, and results should be reported such that necessary modifications in the treatment regimen can be made. Because cancer treatment can result in diarrhea, the oncology nurse must be aware of the side effects of treatment and monitor patients accordingly. Assessment of the frequency and amount of diarrhea must be performed at each visit. Initiation of antidiarrhea therapy could begin at the initiation of the cancer therapy known to result in diarrhea. Oncology nurses can make significant contributions by engaging in research designed to establish prevention and treatment protocols for individuals at risk for constipation or diarrhea. The World Health Organization has developed a three-step "analgesic ladder" for analgesics in which each medication is classified as either a nonopioid, a weak opioid, or a strong opioid. 87 A similar approach could be taken to classify chemotherapeutic and antiemetic medications for the degree of constipation each usually produces in patients and to classify chemotherapeutic and radiation therapy regimens for the degree of diarrhea each usually produces in patients. Using a rigorous doubleblind, crossover design, preventive regimens for each level of increasing difficulty could be evaluated.
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