April 2008, Volume 12, Number 2

 

Article

Putting Evidence Into Practice®: Evidence-Based Interventions for the Prevention and Management of Constipation in Patients With Cancer

Myra Woolery, MN, RN, CPON®, Annette Bisanz, MPH, BSN, RN, Hannah F. Lyons, MSN, RN, BC, AOCN®, Lindsay Gaido, MSN, RN, Mary Yenulevich, BSN, RN, OCN®, Stephanie Fulton, MS, and Susan C. McMillan, PhD, ARNP, FAAN

 

 

Constipation is a major source of distress for patients with cancer, significantly affecting quality of life. It can be secondary to disease sequelae, side effects of treatment, or preexisting conditions. It often is unrecognized, underassessed, and ineffectively managed. Nurses play a key role in the prevention and management of constipation and need evidence-based interventions. This article summarizes the existing research evidence for constipation interventions and identifies gaps. Many of the strategies have been evaluated in nononcology populations; researchers should evaluate their effectiveness in oncology populations.

 

At a Glance

 

·         Many expert opinions are available on the prevention and management of constipation in patients with cancer, but no high-level evidence supports the recommendations.

·         Strategies likely to be effective in patients with cancer include instituting a prophylactic bowel regimen, switching from oral morphine to fentanyl (transdermal) or methadone, and using osmotic laxatives such as polyethylene glycol.

·         Further research is needed to determine optimal strategies for preventing and managing constipation.

 

Constipation is a common issue in patients with cancer and a source of major distress. Although the exact incidence in the adult oncology population is not known, it has been reported as ranging from 50%–95%, with the highest incidence observed in patients receiving opioids (Cimprich, 1985; McShane & McLane, 1985; Smith, 2001). Among patients with cancer at the end of life, the prevalence of constipation may be as high as 60% and increases to 87% in such patients taking opioids (Wirz & Klaschik, 2005). Constipation is not unique to oncology. In nononcology populations, constipation is one of the most common digestive complaints in the United States and the primary reason for approximately 2.7 million ambulatory care visits annually. The total cost to the healthcare system is $235 million annually, and about 55% of costs are incurred from inpatient hospitalization (Martin, Barghout & Cerulli, 2006).

 

Patients with cancer can experience constipation for a variety of reasons. Five common causes have been identified: (a) the cancer itself, which can obstruct the bowel, affect the autonomic nervous system, or cause spinal cord compression; (b) disease effects from illness such as dehydration, spinal cord compression, immobility, or changes in normal bowel habits; (c) previous laxative abuse; (d) cancer therapies such as the vinca alkaloids; and (e) interventions for symptom management such as opioids or tricyclic antidepressants (Wilkes & Barton-Burke, 2006). Figure 1 summarizes potential causes of constipation in the oncology population, underscoring the complexity of the issue.

Management of constipation can be complex and challenging because it often has more than one etiology in patients with cancer. The prevention and management of constipation should be essential components of oncology nursing practice and should include evidence-based interventions. If constipation is not managed proactively, patients can experience negative consequences, such as anorexia, nausea, bowel impaction, or bowel perforation, all of which can have an impact on quality of life. Furthermore, primary tumor burden in the abdomen, metastatic disease in the liver, and peritoneal or mesenteric spread increase the risk and potential for discomfort as well as complications associated with constipation. A variety of pharmacologic and nonpharmacologic interventions are used for the management of this distressing symptom. The purpose of this article is to identify evidence-based interventions for the prevention and management of constipation in patients with cancer.

 

Methods

 

An initial step in the Oncology Nursing Society (ONS) Putting Evidence Into Practice® (PEP) process was identifying a definition for constipation. A review of the literature revealed no consistently accepted definition. The most developed definitions were related to chronic constipation. After carefully critiquing the literature, the researchers adopted a definition for constipation and used it to guide the literature search. For purposes of this project, constipation was defined as a decrease in the passage of formed stool characterized by stools that are hard and difficult to pass. Patients with constipation typically have fewer than two to three stools per week and may strain to have a bowel movement. Constipation can be accompanied by abdominal pain, nausea, vomiting, abdominal distention, loss of appetite, headache, and dry, hard stools (Bisanz, 2005; Cope, 2001; Petticrew, Rodgers, & Booth, 2001; Thompson, Boyd-Carson, Trainor, & Boyd, 2003). The various pharmaceutical and nonpharmaceutical interventions used in the prevention and treatment of constipation also were defined. Figure 2 includes some of the definitions used for this project. The full table of definitions may be found at http://ons.org/outcomes/volume2/constipation.shtml.

 

Search Strategy

 

In consultation with a medical librarian, the researchers conducted computerized searches of a variety of databases in July 2006 to identify meta-analyses, systematic reviews, research studies, and practice guidelines for interventions related to the prevention and management of constipation. The search was limited to English publications. Databases searched included Wiley’s Cochrane Database of Systematic Reviews, Ovid’s MEDLINE® (1966-July 2006), the National Guideline Clearinghouse, the National Cancer Institute’s PDQ®, the National Comprehensive Cancer Network, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL®) (1982–July 2006). To identify randomized, controlled trials (RCTs) in MEDLINE, the researchers used Cochrane’s Highly Sensitive Search. In addition, a search for critically appraised topics was conducted in Ovid’s Clinical Evidence and the American College of Physician’s Information and Education Resource. Search terms included constipation, defecation, fecal incontinence, bowel function, colonic transit, stool impaction, colonic inertia, and cancer, neoplasms, oncology. Additional search terms included specific pharmacologic (e.g., laxatives, polyethylene glycol [PEG], senna) and nonpharmacologic (e.g., diet changes, biofeedback) interventions related to constipation.

 

The search then was refined and expanded to include specific interventions, using the term constipation combined with vinca alkaloids, fluids, biotherapy, biofeedback, or acupuncture. Additional searches were conducted through October of 2006 in the Cochrane Library; MEDLINE (1966–September Week 2 2006); CINAHL (1982–September 4, 2006) SCOPUS, and International Pharmaceutical Abstracts. The Institute of Scientific Information’s Science Citation Index (1975 to present) also was used for cited references from key references and references in reviewed articles.

Abstracts of the literature search were reviewed to determine whether articles met the inclusion criteria. Articles were retrieved and critiqued if they included constipation as an outcome variable or contained guidelines for the prevention and management of constipation.

 

Additional data sources were identified from manual searches in article bibliographies. Published references before October 2006 were retrieved. An updated literature search was conducted in June 2007 for this article and found an American Society of Clinical Oncology (ASCO) abstract reporting the findings of two phase III RCTs of methylnaltrexone and an updated version of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHN) guidelines.

 

Synthesis and Evaluation

 

Two dyads of advanced practice nurses (APNs) and staff nurses extracted data in a systematic way from the selected publications as related to the prevention and management of constipation. An APN in the researcher role and a nurse researcher provided guidance in data extraction. Information was collected in a standardized format according to the type of publication (i.e., meta-analysis, systematic review, individual research study, guideline, or expert opinion). Data were extracted and a level of evidence was assigned for each category of intervention (e.g., stool softeners, osmotic laxatives). Most of the meta-analyses, systematic reviews, literature reviews, and guidelines contained information on a variety of interventions. Individual studies were rated and assigned an ONS level of evidence based on their type and quality (Ropka & Spencer-Cisek, 2001) (see Table 1). Studies then were grouped by intervention. The strength of evidence supporting each intervention was weighted based on seven categories of evidence identified by ONS, ranging from recommended for practice to not recommended for practice. The final category, expert opinion, included consensus panel reviews and publications by clinicians addressing bowel management in oncology and nononcology populations. A description of each of the weighted evidence categories is described in Table 1.

 

Most of the research identified was not conducted specifically in the oncology population. Because little to no evidence was found for interventions commonly used in practice and because patients with cancer can have comorbid reasons for constipation, the project team decided to review the research related to constipation in the nononcology population. For interventions studied only in nononcology populations, the highest level of categorization assigned based on the strength of the evidence was likely to be effective. All of the summarized data were documented in standardized tables and reviewed for accuracy by the project team, by a second PEP project team, and by outside reviewers. Revisions were made based on feedback. In addition, the PEP short resource card and detailed card were reviewed by outside reviewers and revised based on feedback. The resources are available at www.ons.org/outcomes/constipation/shtml.

 

Highlights of Reviewed Literature: Constipation in Adult Patients With Cancer

 

Only eight studies were found that examined the management of constipation in patients with cancer. Two studies addressed nonopioid–induced constipation; one was a descriptive study looking at vincristine-induced constipation (Harris & Jackson, 1977), and the second was a poorly controlled trial examining the use of dietary fiber after radical hysterectomy (Griffenberg, Morris, Atkinson, & Levenback, 1997). The remaining six studies, which addressed opioid-induced constipation (OIC), were of mixed quality and evaluated different questions related to the management of the side effect. They were an RCT comparing senna and lactulose (Agra et al., 1998); two studies evaluating the efficacy of opioid rotation from morphine to fentanyl (Ahmedzai & Brooks, 1997; Radbruch et al., 2000); one small, controlled study examining the use of oral naloxone (Meissner, Schmidt, Hartmann, Kath, & Reinhart, 2000); and two small, descriptive studies: one examining the relationship between opioid dose, bowel function, and activity and the other examining the use of fresh baker’s yeast (Wenk et al., 2000). A summary of the studies can be found in Tables 2 and 3.

 

Recommended for Practice

 

As of September 30, 2006, the literature revealed no interventions that could be recommended for nursing practice in the oncology population. “Interventions which are recommended for practice are those for which effectiveness has been demonstrated by strong evidence from rigorously conducted studies, meta-analysis, or systematic reviews and for which expectation of harms is small compared with the benefits” (ONS, n.d.).

 

Likely to Be Effective

 

Several interventions for the prevention and management of constipation in patients with cancer were considered likely to be effective based on less well-established evidence. Examples include a well-conducted RCT, “consistent supportive evidence from well-designed controlled trials using small samples,” or guidelines developed by a consensus panel of experts (ONS, n.d.) such as Guideline for the Management of Cancer Pain in Adults and Children (Miaskowski et al., 2005) and Clinical Practice Guidelines in Oncology: Palliative Care (National Comprehensive Cancer Network [NCCN], 2006a). The interventions considered likely to be effective include strategies for addressing OIC and those for managing refractory constipation in adult patients with cancer.

 

Opioid–induced constipation: OIC also is referred to as opioid bowel dysfunction and opioid–induced bowel dysfunction. Opioids bind to the mu receptors of the gastrointestinal tract, delaying gastric emptying and causing symptoms of constipation (Friedman & Dello Buono, 2001; Tamayo & Diaz-Zuluaga, 2004). In addition to the symptoms associated with constipation, OIC is thought to include abdominal cramping, bloating, and gastrointestinal reflux (Pappagallo, 2001). OIC is the most commonly occurring gastrointestinal side effect of chronic opioid use. About 41% of patients with cancer and more than 50% of all opioid–treated patients experience symptoms associated with OIC (Kalso, Edwards, Moore, & McQuay, 2004; McNicol et al., 2003; Tamayo & Diaz-Zuluaga). Strong evidence and expert opinion support the initiation of a prophylactic bowel management regimen and monitoring when opioids are prescribed (Bisanz, 2005; Kalso et al.; McNicol et al.; Miaskowski et al., 2005; National Cancer Institute, 2006; NCCN, 2006a; Robinson et al., 2000). However, the literature has a paucity of research indicating the most effective regimen to prevent OIC.

 

Opioid rotation is another strategy thought to decrease the incidence of constipation. Opioid rotation takes advantage of the different properties of opioids to maximize analgesia and minimize adverse effects (McNicol et al., 2003). Several researchers have studied whether switching opioids can decrease the constipating side effects associated with opioid administration in oncology and nononcology populations. Research, including three crossover studies rotating sustained-released oral morphine to fentanyl transdermal patch, demonstrated a significant decline in laxative use or episodes of constipation after the switch to fentanyl (Ahmedzai & Brooks, 1997; Allan et al., 2001; McNicol et al.; Miaskowski et al., 2005; Radbruch et al., 2000).

 

Persistent constipation: Polyethylene glycol 3350 (PEG 3350), an iso-osmotic laxative without electrolytes (Miralax®, Schering-Plough), is recommended as a treatment option for persistent constipation by the NCCN (2006a). It is used frequently in the oncology population, although no published meta-analyses, systematic reviews, or RCTs were found to support its use in that population. The categorization of PEG 3350 as likely to be effective is further supported by a high level of evidence concerning its safety and efficacy in nononcology populations.

 

Stimulant or osmotic laxatives also are likely to be effective in improving bowel function in patients with cancer who have persistent constipation at the end of life. In addition, some patients may need both types of laxatives to achieve optimal results (Agra et al., 1998; NCCN, 2006a). Although the NCCN recommends the use of senna and docusate, this review of the literature did not identify any trials to recommend the use of a specific stimulant laxative with or without the addition of a stool softener in the management of constipation in any population. One RCT of patients with terminal cancer (N = 91) comparing senna to lactulose found no significant difference in efficacy or tolerability (Agra et al.).

 

Benefits Balanced With Harms

 

The benefits balanced with harms category is designated for interventions “for which clinicians and patients should weigh the beneficial and harmful effects according to individual circumstances and priorities” (ONS, n.d.). The current review identified one intervention in this category.

 

Naloxone, an opioid receptor antagonist, has shown mixed efficacy and inconsistent reliability in reversing OIC. With naloxone, benefits must be balanced with potential harms. Its effects on central and peripheral opioid receptors can cause loss of analgesia and withdrawal symptoms such as nausea, sweating, restlessness, and abdominal cramps (Freidman & Dello Buono, 2001; McNicol et al., 2003). Multiple dosing and titration schedules have been studied (Choi & Billings, 2002; Friedman & Dello Buono; McNicol et al.; Meissner et al., 2000; Miaskowski et al., 2005).

 

Effectiveness Not Established

 

The pharmacologic and nonpharmacologic interventions classified as effectiveness not established are used commonly in the oncology population to prevent or treat constipation. They were not associated with any clear indication of harm; however, the data related to their efficacy were conflicting or of insufficient quality (i.e., inadequate power, limited sample sizes, or major flaws in study design or procedure) (ONS, n.d.). See Figure 3 for pharmacologic and nonpharmacologic interventions categorized as effectiveness not established. In addition, two promising investigational agents for the management of OIC are categorized under effectiveness not established because they have not been approved by the U.S. Food and Drug Administration (FDA): methylnaltrexone and alvimopan. Finally, many nonpharmacologic interventions, such as dietary fiber, physical activity, aromatherapy, massage, and biofeedback, are discussed in the literature addressing chronic constipation; however, they lack significant study using RCTs.

 

Pharmacologic interventions: Psyllium, a bulk laxative, often is prescribed to patients with cancer despite a lack of research evaluating its efficacy in the population. Evidence for its use in chronic constipation is conflicting (Brandt et al., 2005; Frizelle & Barclay, 2005; Ramkumar & Rao, 2005). Of the three systematic reviews that examined data related to psyllium, one concluded, “based on low-intermediate quality RCTs, psyllium appears to improve stool frequency and consistency” (Brandt et al.); one concluded that moderate evidence supports its use (Ramkumar & Rao); and another reported finding numerous RCTs of mixed quality (Frizelle & Barclay). Several publications have identified potential harms associated with psyllium, which may have implications for the oncology population. To prevent adverse events, patients must have good functional status, such as engaging in physical activity (Brandt et al.; Frizelle & Barclay; Petticrew et al., 2001; Ramkumar & Rao) and being able to consume adequate fluids (Miaskowski et al., 2005). For adults, psyllium should be taken with at least 200–300 ml of water (Miaskowski et al.; Sykes, 1994). Expert opinion recommends an additional 200–300 ml of water to prevent adverse events. Psyllium should not be administered in large amounts because it has been associated with increased flatulence, abdominal distension, bloating, mechanical obstruction of the esophagus and colon, and anaphylactic reactions (Brandt et al.; Frizelle & Barclay). Therefore, the intervention should be used with caution in patients with severe constipation (Petticrew et al.) and, according to expert opinion, in patients with advanced cancer (Klaschik, Nauck, & Ostgathe, 2003; Mancini & Bruera, 1998) because its use may worsen symptoms.

 

Osmotic laxatives, such as lactulose and sorbitol, are associated with significant improvements in stool consistency, fecal impaction, straining of stool, and other symptoms of chronic constipation (Brandt et al., 2005; Kot & Pettit-Young, 1992; Petticrew et al., 2001). The two osmotic laxatives contain the same main ingredients but are manufactured by different pharmaceutical companies, with lactulose costing more than sorbitol (Agra et al., 1998). Several RCTs support their use for constipation management in nononcology patients. Systematic reviews have found mixed-quality studies indicating no significant differences in efficacy between sorbitol and lactulose (Kot & Pettit-Young; Lederle, Busch, Mattox, West, & Aske, 1990), between senna and lactulose (Agra et al.), and between lacticol (not available in the United States) and lactulose (Frizelle & Barclay, 2005). Of note, the cited adverse effects of lactulose are cramping and flatus, which may be considered harmful in the oncology population (Kot & Pettit-Young; Petticrew et al.; Ramkumar & Rao, 2005).

PEG 3350 was mentioned previously in relation to persistent constipation. In the United States, standard-dose PEG with electrolytes is known as Golytely® (PEG-3350 and electrolytes for oral solution, Braintree Laboratories, Inc.) and Colytely® (Schwartz Pharma, Inc.). Low-dose PEG 3350 is available in the United States without electrolytes, marketed as Miralax, and with or without electrolytes in the United Kingdom and the Netherlands. Of note, PEG with electrolytes should be avoided in patients with renal compromise. Because of the lack of high-quality evidence supporting its use in the management of other forms of constipation in patients with cancer, all forms of PEG are categorized as effectiveness not established, excluding PEG 3350 for persistent constipation. In nononcology populations, evidence supports the use of all forms of PEG in patients with idiopathic chronic constipation. Four systematic reviews, including seven RCTs, two with populations of more than 100 participants, found that PEG (in various forms) has significant effects on stool frequency and consistency over placebo and lactulose (Brandt et al., 2005; Frizelle & Barclay, 2005; Petticrew et al., 2001; Ramkumar & Rao, 2005).

 

Tegaserod (Zelnorm®, Novartis) has not been investigated in patients with cancer, so its efficacy has not been established. However, it was approved by the FDA for the treatment of irritable bowel syndrome with constipation in women and for the treatment of chronic constipation in men and women younger than 65 (Brandt et al., 2005). On March 30, 2007, the FDA notified healthcare professionals and patients that Novartis had agreed to discontinue marketing tegaserod for the short–term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years of age with chronic constipation. FDA analysis of safety data pooled from 29 clinical trials involving more than 18,000 patients showed an excess number of serious cardiovascular adverse events, including angina, heart attacks, and strokes, in patients taking tegaserod compared to patients taking placebo (FDA, 2007; Novartis, 2007). In July 2007, the FDA approved restricted use of tegaserod for patients for whom other treatment options were considered unsafe or ineffective. Use is now limited by strict criteria to patients without heart disease. Each individual patient is evaluated by Novartis under FDA supervision to ensure that he or she meets the criteria for treatment. In addition, patients who receive tegaserod are fully informed of the potential risks and benefits of using tegaserod. Updated information can be found at www.fda.gov/bbs/topics/NEWS/2007/NEW01673.html.

 

Investigational agents: Alvimopan and methylnaltrexone, two peripherally selective mu opioid receptor antagonists, are under investigation for FDA approval. The drugs are promising in the prevention and treatment of OIC because they do not cross the blood-brain barrier and therefore do not inhibit the desired analgesic effects of opioids or cause symptoms of withdrawal.

 

Alvimopan compared to placebo has shown significant improvements in stool frequency in nononcology chronic opioid users (Webster et al., 2006) and in earlier return of bowel function and food tolerance in patients after abdominal surgery (Neary & Delaney, 2005). Side effects noted during the phase III trial of alvimopan include nausea, vomiting, and hypotension (Neary & Delaney). In June 2007, the FDA suspended the approval of alvimopan pending complete analysis of safety data (GlaxoSmithKline, 2007). In February 2008, the FDA extended the new drug application for alvimopan to May 2008 pending evaluation of the revised Risk Management Program.

 

Three phase III trials comparing parenteral MTNX with placebo for OIC had been completed as of June 2006. One RCT (N = 154) comparing two dosages of MTNX in patients with advanced illness (80% with cancer) found a significant decrease in time to laxation (60% within one hour); no significant difference was found between the two doses, but both were significantly more effective than placebo (p < 0.0001) (Yuan & Israel, 2006). Two phase III trials (N = 124 and N =78) in patients with cancer found that laxation occurred within the first 24 hours of administration without increased pain or opioid withdrawal symptoms (Karver, Slatkin, Thomas, Israel, 2007). Cramping was the most common adverse event discussed in the literature (Choi & Billings, 2002; Yuan & Israel); flatulence, nausea, and dizziness were reported with higher doses (Yuan & Israel).

 

Nonpharmacologic interventions: Although dietary fiber often is recommended for the prevention and management of constipation, the research evidence is inconclusive. A synthesis of empirical research studies found mixed-quality studies and conflicting findings, primarily in subjects with chronic constipation (Brandt et al., 2005; Muller-Lissner, 1988; Ramkumar & Rao, 2005; Richmond & Wright, 2004). Of note, fiber is not recommended in patients with advanced disease or those with inadequate fluid intake (NCCN, 2006a). A small, poorly controlled RCT of women with cervical cancer (N = 35) who had radical hysterectomies (type II or III) compared a high-fiber diet and dietary instruction (treatment group) versus regular diet (control group); women in the treatment group reported less abdominal cramping and positive bowel function changes compared to those on a regular diet. Limitations of the study included lack of regulation of the amount of fiber intake in the control group (Griffenberg et al., 1997). Further research is needed.

 

Increased activity and exercise have been considered beneficial in preventing and managing constipation by increasing blood flow to the digestive organs, leading to improved motility (Richmond & Wright, 2004). However, research findings are conflicting and few RCTs have supported the hypothesis (Frizelle & Barclay, 2005). A small, descriptive, prospective study (N = 50) examining factors influencing constipation in patients with advanced oncology found no relationship between bowel scores and physical functioning (Bennett & Cresswell, 2003).

 

One small study suggested a potential benefit in using fresh baker’s yeast (FBY) in patients with cancer; however, the intervention was not well tolerated and storage is an issue (Wenk et al., 2000). Furthermore, FBY is a fungus and would not be recommended for use in neutropenic patients with cancer.

 

Aromatherapy is the use of essential oils that produce odors thought to affect physiologic functions. A Cochrane review looked at the effects of aromatherapy with or without massage. The findings of the systematic review yielded eight RCTs of aromatherapy and/or massage in 357 patients with cancer and found no data to support their use in the management of constipation in the oncology population (Fellowes, Barnes, & Wilkinson, 2004).

 

Biofeedback is a mechanism used to train the body and mind to change a particular bodily function, bowel management for example. The majority of biofeedback RCTs included patients with pelvic floor dysenergia and excluded those with cancer. The findings of most of the studies were inconclusive; further research is needed to determine whether biofeedback is an effective intervention (Brandt et al., 2005; Coulter et al., 2002; Frizelle & Barclay, 2005).

 

Not Recommended for Practice

 

The category not recommended for practice describes “interventions for which lack of effectiveness or harmfulness has been demonstrated by strong evidence from rigorously conducted studies, meta-analyses, or systematic reviews or interventions for which the costs, burdens, or harms associated with the intervention exceed anticipated benefit” (ONS, n.d.).

 

Nalmefene and naltrexone, two opioid receptor antagonist medications similar to naloxone but with longer half-lives, have been studied for the management of OIC and were found to have harms that outweigh their benefits. The drugs are lipid soluble and cross the blood-brain barrier, acting on the central and peripheral opioid receptors. As a result, they have a propensity to inhibit the desired effect of analgesia as well as decrease the constipating effects of opiates (Choi & Billings, 2002). Because of that finding, few studies of nalmefene have been conducted in humans. Furthermore, naltrexone is not recommended for use in the oncology population because of reports of psychological dependence and dose-related elevations in serum transaminase levels, resulting in discontinuation of the drug (Choi & Billings).

 

Cisapride and DantronTM (Hexal Pharma) are not recommended for practice in the management of constipation in adult patients, not specific to opioids. Cisapride, a prokinetic drug known to increase gastrointestinal motility, has been effective in managing constipation (Ramkumar & Rao, 2005). However, access to cisapride is restricted in some countries because of adverse cardiac effects and was taken off the market in the United States in 2000 by the FDA (Coggrave, Wiesel, & Norton, 2006). Dantron, a stimulant laxative, has not been approved by the FDA for use in the United States because it has been associated with rodent cancer.

 

Expert Opinion

 

Numerous articles and guidelines from experts have addressed the management of constipation in oncology and nononcology populations. A proactive approach to preventing constipation is recommended strongly in at-risk patients with cancer, particularly those receiving medications such as vinca alkaloids, which slow colonic transit times, or opioids (Bisanz, 2005; Harris & Jackson, 1977; NCCN, 2006a; NCI, 2006; Smith, 2001; Tamayo & Diaz-Zuluaga, 2004). Thorough assessment, including normal bowel pattern, medication history including use of laxatives, and a physical examination, also is widely recommended (Bisanz; Coggrave et al., 2006; Cope, 2001; Klaschik et al., 2003; Mancini & Bruera, 1998; NCCN, 2006a; NCI; Richmond & Wright, 2004; Sykes, 1994). Bisanz stressed the importance of normalizing the bowel (i.e., clearing the build-up of stool or impaction) before instituting a maintenance bowel regimen, as well as the importance of establishing goals for the frequency of bowel movements. She also recommended an interdisciplinary approach, including a nutrition consultation, in developing the plan of care. The importance of teaching patients about bowel function and involving them in the development of a bowel regimen also is stressed in the adult oncology literature (Bisanz; McCallum, Walsh, & Nelson, 2002).

 

Several general recommendations related to optimizing bowel function were noted in the literature. Expert opinion recommends a good bowel management program that includes increasing fluids and fiber and decreasing constipating medications or providing medications to offset constipating side effects of medications (Bisanz, 2005; Cope, 2001; NCCN, 2006a; NCI, 2006). Other recommendations include the following.

 

·         Provide a comfortable, quiet, private environment for defecating (Folden, 2002; NCI, 2006; Smith, 2001; Sykes, 1994).

·         Provide a toilet, bedside commode, and any necessary assistive devices and avoid the use of a bedpan whenever possible (Folden, 2002; NCI, 2006).

·         Encourage adequate fluid intake (eight 8 oz glasses of fluid per day). Warm or hot liquids may be of some benefit (Consortium for Spinal Cord Medicine, 1998; NCI, 2006).

·         Perform valsalva maneuver in patients with neurogenic problems (Consortium for Spinal Cord Medicine, 1998).

·         Use mealtimes for bowel routines to capitalize on the gastrocolic reflex (Day, 2001).

·         Maintain a diary of bowel movements (NCI, 2006).

 

After three days without a bowel movement, a patient should initiate a bowel management program (Bisanz, 2005; NCI, 2006). Insufficient high-quality evidence exists to recommend a systematic approach in the titration of a bowel program in patients with long-term effects of constipation. A systematic review, including 10 RCTs of patients with neurologic diseases (Coggrave et al., 2006) and expert opinion (NCCN, 2006a; NCI, 2006; Robinson et al., 2000), recommended an individualized approach based on outcomes to reach the desired goal for bowel management. Because insufficient evidence exists to guide a bowel management program, a trial-and-error approach with nursing guidance is common. The NCCN recommends titrating prophylactic medications, including a stimulant laxative plus a stool softener, to achieve one nonforced bowel movement every one or two days; increasing fluid intake; increasing dietary fiber if a patient has an adequate fluid intake and physical activity; and increasing exercise if appropriate. Although the NCCN recommends the use of senna and docusate, this review of the literature did not identify any adequately powered trials to recommend the use of a specific stimulant laxative in the prevention of constipation.

 

Experts have identified several agents that are not recommended for practice or that should be used with caution.

 

Castor oil is not recommended because it causes severe cramping (Mancini & Bruera, 1998).

Prokinetic medications such as metoclopramide should be reserved for use in individuals with severe constipation and those resistant to bowel programs (Mancini & Bruera, 1998; NCCN, 2006a; Consortium for Spinal Cord Medicine, 1998). In addition, prokinetic agents should be avoided in patients with large abdominal tumors or bowel obstruction (Wilkes & Barton-Burke, 2006).

Oral mineral oil is effective for hard stool but should not be used for routine prevention of constipation because it may interfere with absorption of some nutrients; it should not be used in patients at risk for aspiration (Bisanz, 2005; Mancini & Bruera, 1998).

 

In myelosuppressed patients, rectal agents and manipulation (i.e., rectal examinations, suppositories, and enemas) are discouraged because they can lead to development of bleeding, anal fissures, or abscesses, which are portals for infection. In addition, the stoma of a neutropenic patient should not be manipulated (NCI, 2006).

 

Lastly, patients with impactions should be evaluated to determine whether impaction is high or low. With high impactions, stool remains in the ascending and transverse colon, causing nausea and vomiting, loss of appetite, abdominal distention, and cramping. In some cases, liquid stool oozing around an impaction can appear to be diarrhea but can be a sign of high impaction (Bisanz, 2005). High impactions are relieved comfortably with low-volume (less than 300 ml) milk and molasses enemas given high (12 inches) as many as four times per day along with an oral laxative (Bisanz; Thorpe, 2001). The recipe for a molasses enema is described in Figure 2. With low impactions, stool is detected by digital examination in the rectum. Patients with low impactions have the urge to defecate but are unable to expel stool. Patients may describe it as, “I can’t sit because I feel like I’m sitting on something.” For low impactions, oil retention enemas soften hard stool. In non-myelosuppressed patients, stool can be disimpacted manually followed by enemas of choice (Bisanz).

 

Highlights of Reviewed Literature: Pediatric Constipation

 

Constipation in the general pediatric population is predominantly functional constipation, also known as idiopathic constipation, functional fecal retention, and fecal withholding. The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) (2006) described the evolution of functional constipation from painful defecation related to such things as toilet training, changes in routine, and stressful events to the development of retentive behavior and accompanying symptoms of constipation. Normal bowel function (stool frequency) in children is dependent on age, with a gradual decline in mean stools per day until about 4 years of age (NASPGHN, 2006).

 

Only a small percentage of children have a pathologic cause of constipation. Children with cancer may have comorbid or coexisting etiologies, and one may exacerbate the other. The only literature that specifically addressed pediatric constipation in the oncology population was the NCCN Clinical Practice Guidelines: Pediatric Cancer Pain (NCCN, 2006b), which review interventions for the management of OIC. The guidelines are supported by uniform NCCN expert panel consensus based on lower-level evidence, including clinical experience. Numerous guidelines, research studies, and expert opinions addressing a variety of interventions for constipation and encopresis (voluntary or involuntary passage of stools causing soiling of clothes) in children without a diagnosis of cancer were found, and many of the interventions are used in pediatric oncology. However, because of the lack of any data in the pediatric oncology population, interventions were categorized under effectiveness not established or expert opinion. Interventions described in this article address constipation in children, with only a few recommendations for infants. The NASPGHN guidelines for constipation in infants and children referenced in the original project (Baker et al., 1999) were updated and available online after September 2006, the last search date for the PEP constipation project. The updated guidelines (NASPGHN, 2006) are endorsed by the American Academy of Pediatrics. Because no significant changes were found in recommendations between the older and revised versions, the newer version is referenced. The complete NASPGHN guidelines are available online at www.naspghn.org.

 

As of September 30, 2006, no interventions found in the literature could be categorized as recommended for practice, likely to be effective, or benefits balanced with harms for pediatric oncology.

 

Effectiveness Not Established

 

Pharmacologic interventions: Although studies have not been conducted in the oncology population, a high level of evidence was found for the safety, effectiveness, and tolerability of PEG 3350 in pediatric patients for the short-term and long-term management of chronic or functional constipation as well as fecal impaction (Arora & Srinivasan, 2005; NASPGHN, 2006). PEG 3350 was associated with fewer side effects and better laxation outcomes in at least four RCTs as well as numerous lower-level studies (Arora & Srinivasan; Bell & Wall, 2004; Kinservik & Friedhoff, 2004). A number of the studies found that compliance with PEG 3350 was better than with other laxatives such as lactulose and magnesium hydroxide (milk of magnesia) (Arora & Srinivasan). Additional RCTs are needed to determine the optimal dosing and most effective form of PEG 3350 in children as well as its role in constipation management in pediatric oncology.

 

The other pharmacologic intervention categorized as effectiveness not established is stimulant laxatives; their use in the general pediatric population is not supported by a high level of evidence (Bell & Wall, 2004; NASPGHN, 2006; Rubin, 2004). NASPGHN recommended only short-term use of stimulant laxatives as rescue therapy in selected patients to prevent fecal impaction or in patients who are difficult to manage with mineral oil, magnesium hydroxide, lactulose, or sorbitol. NASPGHN did not recommend the use of stimulant laxatives for maintenance therapy in the general pediatric population.

 

Nonpharmacologic interventions: Support for the use of dietary fiber in the management of pediatric constipation is mixed and requires additional investigation (Bell & Wall, 2004; NASPGHN, 2006; Rubin, 2004). The evidence supporting the use of biofeedback in children with defecation disorders, including encopresis, is inconsistent (Brazzelli & Griffiths, 2006; Coulter et al., 2002; Rubin).

 

Not Recommended for Practice

 

The use of cisapride as an effective laxative in the pediatric population was supported by high levels of evidence from several systematic reviews (Baker et al., 1999; Rubin, 2004). However, as previously noted, cisapride was taken off of the market and therefore is not recommended for practice. In addition, soap suds, tap water, and magnesium enemas are not recommended for rectal disimpaction in children because of their potential toxicity, and enemas are not recommended for use in infants (Bell & Wall, 2004; NASPGHN, 2006). Lastly, information is conflicting related to the use of corn syrup as a stool softener based on concerns that it is not sterilized when packaged and may be a source of Clostridium botulinum spores (Bell & Wall). The spores have been isolated in samples of corn syrup; however, since changes in corn syrup processing were initiated, no further spores have been identified (Risko, 2006). The NASPGHN (2006) guidelines state that “light and dark corn syrup are not considered to be potential sources of Clostridium botulinum spores” (p. E11) and thus can be used as stool softeners in infants and children. Any pasteurized corn syrup is considered safe for use in infants and children. Corn syrup was categorized under not recommended for practice on the constipation PEP cards, based on the 2004 article by Bell and Wall citing the potential risk of Clostridium botulinum, because the pediatric cancer population often is immunocompromised.

 

Expert Opinion

 

In the literature addressing constipation in children without cancer, many strategies for prevention and management were the same as for adults. The importance of providing education and counseling for parents and children regarding the etiology of constipation and the need for a consistent and positive approach to the issue was stressed by the NASPGHN in its 2006 guidelines. Consistent with expert opinion regarding adults, the guidelines also support the need to disimpact children before initiation of a maintenance bowel regimen. Pharmacologic interventions for disimpaction include oral and rectal medications, such as enemas when age appropriate. No high-level evidence has clarified which route is more effective, and clinicians should consider each case individually when determining the choice of treatment. Disimpaction with the oral administration of high-dose PEG, mineral oil, or both has been found to be effective in the clinical setting. Phosphate soda, saline, and mineral oil enemas are considered acceptable rectal therapies, and bisacodyl suppositories for children and glycerin suppositories for infants younger than one year also may be used (Bell & Wall, 2004; NASPGHN).

 

Maintenance therapy aimed at preventing recurrence includes dietary and behavior modifications as well as laxatives. The evidence related to dietary fiber is conflicting; however, numerous experts support increasing whole grains, fruits, and vegetables as part of the treatment for constipation (Bell & Wall, 2004; NASPGHN, 2006; NCCN, 2006b; Rubin 2004). In addition, Baker et al. (1999) noted that sorbitol found in some juices (prune, pear, and apple juices) can cause an increase in frequency and water content of stool. In addition, modifying behaviors and establishing routine toilet habits are important adjuncts in the treatment of pediatric constipation (Bell & Wall; NASPGHN). For children one year of age or older, mineral oil, magnesium hydroxide, PEG, lactulose, sorbitol, or a combination may be used for maintenance bowel regimens (Bell & Wall; NASPGHN; Rubin). For children, mineral oil may be more effective than senna-based laxatives but less effective than osmotic laxatives (Brandt et al., 2005). As noted previously, stimulant laxatives are not recommended for maintenance therapy but can be used for acute constipation, for patients who have failed other protocols, and for children receiving opioids (Bell & Wall; NASPGHN; NCCN, 2006b).

 

Implications for Practice and Research

 

Nurses are in a unique position to impact the quality of life of patients with cancer through the assessment, prevention, and management of constipation. Clinicians should understand individual characteristics that predispose patients to developing constipation and guidelines that are effective for managing it in the oncology population. Constipation is a common gastrointestinal symptom, and the lack high-quality evidence to support the pharmacologic and nonpharmacologic interventions often recommended in the literature is surprising. Most interventions identified were categorized as effectiveness not established because the interventions were not studied in patients with cancer. Expert opinion forms the foundation of current practice because of the lack of evidence. When implementing evidence-based practice for the management of constipation, consider the strength of the evidence, clinical expertise, and patient preferences (Melnyk & Fineout-Overholt, 2005).

A limitation in synthesizing findings for this project was the lack of consistent definitions used to describe the issue, the interventions, and the measurement of outcomes across studies.

 

Researchers must define study variables clearly and, when possible, build on existing definitions so that a standardized definition can be established. This will facilitate the ability to synthesize research findings in the future. Nurse scientists in collaboration with clinical experts can contribute to evidence-based practice by identifying areas for research and developing research protocols to study this phenomenon. Some authors propose the use of mixed-methods research, combining qualitative, experiential, and intuitive aspects of nursing knowledge with the quantitative methods of RCTs to broaden the base for evidence-based practice (Flemming, 2007). Answering high-priority clinical questions using the PICO format is advised. The process identifies: (a) the patient population of interest, (b) the intervention to be evaluated, (c) the comparison intervention, and (d) the outcomes of the study (Melnyk & Fineout-Overholt, 2005). Combining clinical expertise and patient input in the research design will produce clinically relevant research outcomes. When studying pharmaceutical agents, researchers should determine whether observed side effects are attributable to the drug or the disease process. Figure 4 contains a list of suggested research areas based on the gaps identified.

 

Conclusions

 

Constipation continues to be overlooked and under-reported. When not addressed proactively in patients with cancer, it often results in increased discomfort and negative consequences, some of which can be life threatening (e.g., impaction, bowel perforation). Oncology nurses should identify patients at risk and implement evidence-based interventions. The goal for managing constipation should be prevention, accomplished through patient education and proactive treatment to decrease associated discomfort. Selection of interventions should be individualized for patients according to history, disease process, and plan of care. Despite the variety of interventions used commonly for the prevention and management of constipation, a surprising lack of research has evaluated the effectiveness of interventions in the oncology population. Although a breadth of research exists in some areas related to constipation in nononcology populations, many gaps in the evidence remain. As a result, the prevention and management of constipation in patients with cancer is based on tradition, theoretical considerations, clinical practice experience, and findings extrapolated from nononcology populations. Further studies are needed in patients with cancer and should include controls, larger samples, and clearer explanations of outcomes measured. As research evolves, oncology nurses should synthesize the information and update the evidence underlying various interventions.

 

The authors gratefully acknowledge the many contributions of ONS staff members, including Linda Eaton, MSN, RN, AOCN®, Gail Mallory, PhD, RN, CNAA, and Kelly Egnotovich; the outcomes project field reviewers; and the reviewers of this article.

 

References

 

Agra, Y., Sacristan, A., Gonzalez, M., Ferrari, M., Portugues, A., & Calvo, M.J. (1998). Efficacy of senna versus lactulose in terminal cancer patients treated with opioids. Journal of Pain and Symptom Management, 15(1), 1–7. [CrossRef]

 

Ahmedzai, S., & Brooks, D. (1997). Transdermal fentanyl versus sustained-release oral morphine in cancer pain: Preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. Journal of Pain and Symptom Management, 13(5), 254–261. [CrossRef]

 

Allan, L., Hays, H., Jensen, N.H., de Waroux, B.L., Bolt, M., Donald, R., et al. (2001). Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ, 322(7295), 1154–1158. [CrossRef]

 

Arora, R., & Srinivasan, R. (2005). Is polyethylene glycol safe and effective for chronic constipation in children? Archives of Disease in Childhood, 90(6), 643–646. [CrossRef]

 

Avila, J.G. (2004). Pharmacologic treatment of constipation in cancer patients. Cancer Control, 11(3, Suppl), 10–18.

 

Baker, S.S., Liptak, G.S., Colletti, R.B., Croffie, J.M., Di Lorenzo, C., Ector, W., et al. (1999). Constipation in infants and children: Evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 29(5), 612–626. [CrossRef]

 

Bell, E.A., & Wall, G.C. (2004). Pediatric constipation therapy using guidelines and polyethylene glycol 3350. Annals of Pharmacotherapy, 38(4), 686–693. [CrossRef]

 

Bennett, M., & Cresswell, H. (2003). Factors influencing constipation in advanced cancer patients: A prospective study of opioid dose, dantron dose, and physical functioning. Palliative Medicine, 17(5), 418–422. [CrossRef]

 

Bisanz, A. (2005). Bowel management in patients with cancer. In J.A. Ajani (Ed.), Gastrointestional cancer (pp. 313–345). New York: Springer. [CrossRef]

 

Brandt, L.J., Prather, C.M., Quigley, E.M., Schiller, L.R., Schoenfeld, P., & Talley, N.J. (2005). Systematic review on the management of chronic constipation in North America. American Journal of Gastroenterology, 100(Suppl. 1), S5–S21. [CrossRef]

 

Brazzelli, M., & Griffiths, P. (2006). Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database of Systematic Reviews, 2, CD002240.

 

Choi, Y.S., & Billings, J.A. (2002). Opioid antagonists: A review of their role in palliative care, focusing on use in opioid-related constipation. Journal of Pain and Symptom Management, 24(1), 71–90. [CrossRef]

 

Cimprich, B. (1985). Symptom management: Constipation. Cancer Nursing, 8(Suppl. 1), 39–43. [CrossRef]

 

Coggrave, M., Wiesel, P.H., & Norton, C. (2006). Management of faecal incontinence and constipation in adults with central neurological diseases. Cochrane Database of Systematic Reviews, 2, CD002115.

 

Consortium for Spinal Cord Medicine. (1998). Neurogenic bowel management in adults with spinal cord injury. Washington, DC: Paralyzed Veterans of America.

 

Cope, D.G. (2001). Management of chemotherapy-induced diarrhea and constipation. Nursing Clinics of North America, 36(4), 695–707.

 

Coulter, I.D., Favreau, J.T., Hardy, M.L., Morton, S.C., Roth, E.A., & Shekelle, P. (2002). Biofeedback interventions for gastrointestinal conditions: A systematic review. Alternative Therapies in Health and Medicine, 8(3), 76–83.

 

Day, A. (2001). The nurse’s role in managing constipation. Nursing Standard, 16(8), 41–44.

Fellowes, D., Barnes, K., & Wilkinson, S. (2004). Aromatherapy and massage for symptom relief in patients with cancer. Cochrane Database of Systematic Reviews, 3, CD002287.

 

Flemming, K. (2007). The knowledge base for evidence-based nursing: A role for mixed methods research? Advances in Nursing Science, 30(1), 41–51.

 

Folden, S.L. (2002). Practice guidelines for the management of constipation in adults. Rehabilitation Nursing, 27(5), 169–175.

 

Friedman, J.D., & Dello Buono, F.A. (2001). Opioid antagonists in the treatment of opioid-induced constipation and pruritus. Annals of Pharmacotherapy, 35(1), 85–91. [CrossRef]

 

Frizelle, F., & Barclay, M. (2005, December). Constipation in adults. Clinical Evidence, 14, 557–556.

 

GlaxoSmithKline. (2007). GlaxoSmithKline and Adolor update alvimopan (Entereg/Entrareg) development programme. Retrieved February 18, 2008, from http://us.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=1101#

 

Griffenberg, L., Morris, M., Atkinson, N., & Levenback, C. (1997). The effect of dietary fiber on bowel function following radical hysterectomy: A randomized trial. Gynecologic Oncology, 66(3), 417–424. [CrossRef]

 

Harris, A.C., & Jackson, J.M. (1977). Lactulose in vincristine-induced constipation. Medical Journal of Australia, 2(17), 573–574.

 

Kalso, E., Edwards, J.E., Moore, R.A., & McQuay, H.J. (2004). Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain, 112(3), 372–380. [CrossRef]

 

Karver, S.B., Slatkin, N.E., Thomas, J., & Israel, R.J. (2007). Methylnaltrexone treatment of opioid-induced constipation in cancer patients [Abstract]. 2007 ASCO Annual Meeting Proceedings Part I. Journal of Clinical Oncology, 25(18, Suppl.), 9081.

 

Kinservik, M.A., & Friedhoff, M.M. (2004). The efficacy and safety of polyethylene glycol 3350 in the treatment of constipation in children. Pediatric Nursing, 30(3), 232–237.

 

Klaschik, E., Nauck, F., & Ostgathe, C. (2003). Constipation—Modern laxative therapy. Supportive Care in Cancer, 11(11), 679–685. [CrossRef]

 

Kot, T.V., & Pettit-Young, N.A. (1992). Lactulose in the management of constipation: A current review. Annals of Pharmacotherapy, 26(10), 1277–1282.

 

Lederle, F.A., Busch, D.L., Mattox, K.M., West, M.J., & Aske, D.M. (1990). Cost-effective treatment of constipation in the elderly: A randomized double-blind comparison of sorbitol and lactulose. American Journal of Medicine, 89(5), 597–601. [CrossRef]

 

Locke, G.R., III, Pemberton, J.H., & Phillips, S.F. (2000) American Gastrological Association medical position statement: Guidelines on constipation. Gastroenterology, 119(6), 1761–1778. [CrossRef]

 

Mancini, I., & Bruera, E. (1998). Constipation in advanced cancer patients. Supportive Care in Cancer, 6(4), 356–364. [CrossRef]

 

Martin, B.C., Barghout, V., & Cerulli, A., (2006). Direct medical costs of constipation in the United States. Managed Care Interface, 19(12), 43–49.

 

McCallum, P., Walsh, D., & Nelson, K.A. (2002). Can a soft diet prevent bowel obstruction in advanced pancreatic cancer? Supportive Care in Cancer, 10(2), 174–175. [CrossRef]

 

McEligot, A.J., Gilpin, E.A., Rock, C.L., Newman, V., Hollenbach, K.A., Thomson, C.A., et al. (2002). Research and professional briefs. High dietary fiber consumption is not associated with gastrointestinal discomfort in a diet intervention trial. Journal of the American Dietetic Association, 102(4), 549–551. [CrossRef]

 

McMillan, S.C. (2004). Assessing and managing opiate-induced constipation in adults with cancer. Cancer Control, 11(3 Suppl.), 3–9.

 

McNicol, E., Horowicz-Mehler, N., Fisk, R.A., Bennett, K., Gialeli-Goudas, M., Chew, P.W., et al. (2003). Management of opioid side effects in cancer-related and chronic noncancer pain: A systematic review. Journal of Pain, 4(5), 231–256. [CrossRef]

 

McShane, R.E., & McLane, A.M. (1985). Constipation. Consensual and empirical validation. Nursing Clinics of North America, 20(4), 801–808.

 

Meissner, W., Schmidt, U., Hartmann, M., Kath, R., & Reinhart, K. (2000). Oral naloxone reverses opioid-associated constipation. Pain, 84(1), 105–109. [CrossRef]

 

Melnyk, B.M., & Fineout-Overholt, E. (2005). Making the case for evidence-based practice. In B.M. Melnyk & E. Fineout-Overholt (Eds.), Evidence-based practice in nursing and healthcare: A guide to best practice (pp. 3–24). Philadelphia: Lippincott Williams and Wilkins.

 

Miaskowski, C., Cleary, J., Burney, R., Coyne, P., Finley, R., Foster, R., et al. (2005). Guideline for the management of cancer pain in adults and children. Glenview, IL: American Pain Society.

 

Mitchell, S.A., & Friese, C.R. (n.d.). ONS PEP (Putting Evidence Into Practice) weight of evidence classification schema. Decision rules for summative evaluation of a body of evidence. Retrieved February 18, 2008, from http://www.ons.org/outcomes/volume2/constipation/constipation_woe.shtml

 

Muller-Lissner, S.A. (1988). Effect of wheat bran on weight of stool and gastrointestinal transit time: A meta analysis. British Medical Journal Clinical Research Edition, 296(6622), 615–617.

 

National Cancer Institute. (2006). Gastrointestional complications. Health professional version. Retrieved November 9, 2006, from http://www.cancer.gov/cancertopics/pdq/supportivecare/gastrointestinalcomplications/healthprofessional

 

National Comprehensive Cancer Network. (2006a). NCCN Clinical Practice Guidelines in OncologyTM: Palliative care [v.1.2006]. Retrieved November 13, 2006, from http://www.nccn.org/professionals/physician_gls/PDF/palliative.pdf

 

National Comprehensive Cancer Network. (2006b). NCCN Clinical Practice Guidelines in OncologyTM: Pediatric cancer pain [v.1.2006]. Retrieved November 13, 2006, from http://www.nccn.org/professionals/physician_gls/PDF/pediatric_pain.pdf

 

Neary, P., & Delaney, C.P. (2005). Alvimopan. Expert Opinion on Investigational Drugs, 14(4), 479–488. [CrossRef]

 

North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. (2006). Clinical practice guideline—Evaluation and treatment of constipation in infants and children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 43(3), E1–E13.

 

Novartis. (2007). Novartis suspends US marketing and sales of Zelnorm® in response to request from FDA. Retrieved March 17, 2008, from http://www.novartis.com

 

Oncology Nursing Society. (n.d.). Constipation. Retrieved March 17, 2008, from http://www.ons.org/outcomes/volume2/constipation.shtml

 

Pappagallo, M. (2001). Incidence, prevalence, and management of opioid bowel dysfunction. American Journal of Surgery, 182(5A, Suppl.), 11S–18S.

 

Petticrew, M., Rodgers, M., & Booth, A. (2001). Effectiveness of laxatives in adults. Quality in Health Care, 10(4), 268–273. [CrossRef]

 

Radbruch, L., Sabatowski, R., Loick, G., Kulbe, C., Kasper, M., Grond, S., et al. (2000). Constipation and the use of laxatives: A comparison between transdermal fentanyl and oral morphine. Palliative Medicine, 14(2), 111–119. [CrossRef]

 

Ramkumar, D., & Rao, S.S. (2005). Efficacy and safety of traditional medical therapies for chronic constipation: Systematic review. American Journal of Gastroenterology, 100(4), 936–971. [CrossRef]

 

Richmond, J.P., & Wright, M.E. (2004). Review of the literature on constipation to enable development of a constipation risk assessment scale. Clinical Effectiveness in Nursing, 8(1), 11–25. [CrossRef]

 

Risko, W. (2006). Infant botulism. Pediatrics in Review, 127(1), 36. [CrossRef]

 

Robinson, C.B., Fritch, M., Hullett, L., Petersen, M.A., Sikkema, S., Theuninck, L., et al. (2000). Development of a protocol to prevent opioid–induced constipation in patients with cancer: A research utilization project. Clinical Journal of Oncology Nursing, 4(2), 79–84.

 

Ropka, M.E., & Spencer-Cisek, P. (2001). PRISM: Priority Symptom Management Project. Phase I: Assessment. Oncology Nursing Forum, 28(10), 1585–1594.

 

Rubin, G. (2004, June). Constipation in children. Clinical Evidence, 11, 385–390.

 

Smith, S. (2001). Evidence-based management of constipation in the oncology patient. European Journal of Oncology Nursing, 5(1), 18–25. [CrossRef]

 

Sykes, N.P. (1994). Current approaches to the management of constipation. Cancer Surveys, 21, 137–146.

 

Tamayo, A.C., & Diaz-Zuluaga, P.A. (2004). Management of opioid-induced bowel dysfunction in cancer patients. Supportive Care in Cancer, 12(9), 613–618.

 

Thompson, M.J., Boyd-Carson, W., Trainor, B., & Boyd, K. (2003). Management of constipation. Nursing Standard, 18(14–16), 41–42.

 

Thorpe, D.M. (2001). Management of opioid-induced constipation. Current Pain and Headache Reports, 5(3), 237–240. [CrossRef]

 

U.S. Food and Drug Administration. (2007). FDA public health advisory: Tegaserod maleate (marketed as Zelnorm). Retrieved March 30, 2007, from http://www.fda.gov/cder/drug/advisory/tegaserod.htm

 

Webster, L., Jansen, J., Peppin, J., Lasko, B., Snidow, J., Pierce, A., et al. (2006). A randomized, double-blind, placebo-controlled, mutlicenter phase IIb study to evaluate the efficacy and safety of multiple alvimopan dosage regimens for the treatment of gastrointestional adverse events (GIAEs) associated with opioid use in subjects. Paper presented at the 25th Annual


Scientific Meeting of the American Pain Society. Abstract retrieved November 15, 2006, from http://www.ampainsoc.org/db2/abstract/2006/view?poster_id=2760#761

 

Wenk, R., Bertolino, M., Ochoa, J., Cullen, C., Bertucelli, N., & Bruera, E. (2000). Laxative effects of fresh baker’s yeast. Journal of Pain and Symptom Management, 19(3), 163–164. [CrossRef]

 

Wilkes, G.M., & Barton-Burke, M. (2006). 2007 oncology nursing drug handbook. Sudbury, MA: Jones and Bartlett.

 

Wirz, S., & Klaschik, E. (2005). Management of constipation in palliative care patients undergoing opioid therapy: Is polyethylene glycol an option? American Journal of Hospice and Palliative Care, 22(5), 375–381. [CrossRef]

 

Yuan, C.S., & Israel, R.J. (2006). Methylnaltrexone, a novel peripheral opioid receptor antagonist for the treatment of opioid side effects. Expert Opinion on Investigational Drugs, 15(5), 541–552. [CrossRef]

 

Myra Woolery, MN, RN, CPON®, is a pediatric clinical nurse specialist at the National Institutes of Health in Bethesda, MD, and a doctoral student in the School of Nursing at the University of Maryland in Baltimore; Annette Bisanz, MPH, BSN, RN, is a clinical nurse specialist at the University of Texas M.D. Anderson Cancer Center in Houston; Hannah F. Lyons, MSN, RN, BC, AOCN®, is an oncology clinical nurse specialist at Massachusetts General Hospital in Boston; Lindsay Gaido, MSN, RN, is a clinical nurse specialist at the University of Texas M.D. Anderson Cancer Center; Mary Yenulevich, BSN, RN, OCN®, is a charge nurse at Dana-Farber Cancer Institute in Boston; Stephanie Fulton, MS, is an assistant director of the research medical library at the University of Texas M.D. Anderson Cancer Center; and Susan C. McMillan, PhD, ARNP, FAAN, is a professor in the College of Nursing at the University of South Florida in Tampa. This work was supported, in part, by an American Cancer Society doctoral scholarship in nursing to Woolery (DSCN # 06-202-01). Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. (Submitted July 2007. Accepted for publication August 18, 2007.)

 

Author Contact: Myra Woolery, MN, RN, CPON®, can be reached at mwoolery@cc.nih.gov, with copy to editor at CJONEditor@ons.org.

 

Digital Object Identifier:10.1188/08.CJON.317-337