January 2007, Volume 11, Number 1
Putting Evidence Into Practice: Evidence-Based Interventions to Prevent, Manage, and Treat Chemotherapy-Induced Nausea and Vomiting
Janelle M. Tipton, MSN, RN, AOCN®,
Roxanne W. McDaniel, PhD, RN, Laurel Barbour, RN, MSN, AOCN®, Mary
Pat Johnston, RN, MS, AOCN®,
Marilyn Kayne, BSN, RN, OCN®, Patricia LeRoy, RN, BSN, OCN®, and Marita L. Ripple, RN, OCN®
Chemotherapy-induced nausea and vomiting (CINV) continues to have a considerable effect on the physical and psychological well-being of patients with cancer, despite significant advances in antiemetic drugs since the 1990s. This article reviews and summarizes past and current empirical evidence related to interventions for CINV. A resource that summarizes evidence-based interventions for CINV is critical for effective management of this distressing symptom. Pharmacologic and nonpharmacologic interventions are appraised. Finally, gaps in the literature and opportunities for research, education, and practice changes are discussed.
Nursing-sensitive patient outcomes are outcomes that are attained through or are significantly impacted by nursing interventions. The interventions must be within the scope of nursing practice and integral to the processes of nursing care.
Editor’s note. This article is the third in a series on Oncology Nursing Society’s Putting Evidence Into Practice project, in which best practices for patient care are presented.
Nausea and vomiting continue to be among the most distressing side effects of chemotherapy, despite the development of more efficacious antiemetic agents (Rhodes & McDaniel, 2001). Research has documented that the incidence of acute and delayed postchemotherapy nausea and vomiting is greater than 50% (Liau et al., 2005; Neymark & Crott, 2005), even after antiemetic prophylaxis.
Successful interventions to prevent, manage, and treat nausea and vomiting decrease the distress associated with the symptoms and promote well-being and quality of life for patients and their families (Bender et al., 2002). This article describes the process and results of an Oncology Nursing Society (ONS) initiative to examine and evaluate current evidence-based interventions to prevent, manage, and treat chemotherapy-induced nausea and vomiting (CINV) in adults. The ONS Putting Evidence Into Practice (PEP) project is a collaborative effort that demonstrates commitment to quality care in the development of resources regarding nursing-sensitive patient outcomes. The nausea team united researchers, advanced practice nurses, and staff nurses to develop the ONS PEP resources that provide evidence-based guidelines for CINV interventions.
The definitions of nausea and vomiting from the Oncology Nursing-Sensitive Patient Outcomes Measurement Summaries (ONS, n.d.) were used to guide the review of strategies to manage CINV. The purpose of the measurement summaries is to provide a centralized resource regarding the measurement of specific oncology nursing-sensitive patient outcomes. In addition to definitions, the summaries provide references to integrative reviews and meta-analyses, guidelines and standards of practice, tables of tools, outcome measurement instrument references, summaries of key evidence and gaps, recommendations, and links to current research. Nausea is defined as “an unpleasant feeling in the back of the throat and stomach that may or may not result in vomiting” (Rhodes & McDaniel, 2004, p. 1). Vomiting is defined as “a forceful contraction of the abdominal (stomach) muscles to cause stomach contents to come up through the mouth” (Rhodes & McDaniel, 2004, p. 1). Specific types of nausea are defined because some interventions are more effective for certain types of nausea. Anticipatory nausea occurs before patients receive their chemotherapy treatments. It is a conditioned response and can occur after a prior negative experience with chemotherapy. Prevention is key, especially early in therapy (National Comprehensive Cancer Network [NCCN], 2007). Acute nausea usually occurs within a few minutes to several hours after chemotherapy administration and often resolves in the first 24 hours (NCCN). Delayed nausea occurs more than 24 hours after chemotherapy administration. It often peaks 48–72 hours after chemotherapy and can last six to seven days (NCCN).
A systematic database search was conducted to identify research on interventions for nausea and vomiting. Computerized searches of CINAHL®, MEDLINE®, HealthSTAR, Biological Abstracts®, Dissertation Abstracts, ProQuest® Digital Dissertations and Theses, the Cochrane Collection, Database of Abstracts of Reviews of Effects, EMBASE, PsycINFO, and Health Source: Nursing/Academic Edition (via EBSCO) databases were performed using the search terms listed in Figure 1. Database searches were performed by the project team leader, researcher, and the ONS information resources supervisor, who is a medical librarian. At first, citations from 2000–2005 were searched and retrieved. But because data were limited for nonpharmacologic interventions, the search was expanded to cover publications from 1988–2005. The abstract of each study was reviewed, and those meeting the inclusion criteria were identified for further critique. The articles’ reference lists also supplied additional studies.
Studies were selected based on the following inclusion criteria: findings were published in English, the sample consisted of adult patients with cancer who were receiving or had received chemotherapy, the publication was a complete report of a study, nausea and/or vomiting were the dependent variable(s), nausea and/or vomiting were measured using an instrument designed to measure the variables or were a subscale of an instrument that was reported separately, and the publication contained guidelines for prevention, management, or treatment for nausea and/or vomiting.
Critical Review of the Evidence
Three subgroups of the project team, each which included an advanced practice nurse and a staff nurse, reviewed the articles using standardized worksheets to promote a systematic examination of each study. The subgroups had guidance from a nurse researcher experienced in CINV and an ONS Research Team member. The research nurse provided guidance and mentored the subgroups in review of the literature and in practical questions and applications. The subgroups prepared tables of evidence organized by intervention category or subcategory, including the following information: author and year, intervention characteristics (e.g., delivery method, dose), sample characteristics (e.g., size, age, gender, race, ethnicity, disease and treatment characteristics, treatment phase), setting (e.g., inpatient, outpatient, community; number of sites), study design, conceptual model, nausea and vomiting measures, results and conclusions, limitations, cautions or contraindications, special training to deliver the intervention and its cost, ONS levels of evidence rating, ONS PEP weight-of-evidence category rating (see Table 1), and comments or directions for future research.
Effective Interventions for Prevention and Treatment
Pharmacologic interventions to prevent, manage, and treat CINV were the only interventions that were supported by enough strong empirical evidence of effectiveness to allow them to be recommended for practice. The research on nonpharmacologic interventions lacked sufficient empirical evidence to be recommended for practice. However, several nonpharmacologic interventions were evaluated as likely to be effective for the prevention, management, and treatment of CINV when used in conjunction with pharmacologic interventions. Interventions that are likely to be effective are supported by evidence that is less well established than for those listed under recommended for practice. Examples include one well-conducted randomized, controlled trial with fewer than 100 patients or at one or more study sites and guidelines developed by consensus or expert opinion without synthesis or quality rating. Included in the likely to be effective interventions are acupuncture, acupressure, guided imagery, music therapy, progressive muscle relaxation, and psychoeducational support and information. Figures 2 and 3 summarize the interventions supported by empirical studies, or lack thereof, and by expert opinion.
Pharmacologic interventions for nausea and vomiting are recommended based on the type of nausea and/or vomiting and the emetogenicity of the chemotherapy. The NCCN (2007) Antiemesis Practice Guidelines and the results of the 2004 Perugia International Antiemesis Consensus Conference (Roila, Hesketh, & Herrstedt, 2006) support the use of benzodiazepines such as alprazolam and lorazepam for anticipatory nausea and vomiting.
A 5-HT3 receptor antagonist such as palonosetron, granisetron, ondansetron, or dolasetron; a corticosteroid such as dexamethasone; and aprepitant and a benzodiazepine are recommended for acute nausea and vomiting associated with moderately and highly emetogenic chemotherapy.
Acupuncture involves the insertion of wire-thin needles into acupoints along a specific meridian of the body. Acupuncture at the P6 point (see Figure 4) is used frequently to treat nausea and vomiting. The P6 acupoint is the most commonly investigated and accessible acupoint, located on the anterior surface of the forearm, approximately three finger widths from the wrist crease (Klein & Griffiths, 2004). A review of the literature that examined the effect of acupuncture on CINV found that P6 acupuncture plus antiemetics was more effective than antiemetics alone or antiemetics with placebo acupuncture (Mayer, 2000). Electroacupuncture with antiemetics was more effective in controlling emesis than placebo acupuncture with antiemetics or antiemetics alone in a randomized, controlled trial of 104 women receiving chemotherapy for breast cancer (Shen et al., 2000). A meta-analysis by Ezzo et al. (2005) found that acupuncture was effective in reducing the incidence of acute vomiting but not the severity of acute nausea. Three studies reviewed by Ezzo et al. evaluated delayed vomiting and did not support the intervention. The pooled results of 11 studies using acupuncture-point stimulation plus antiemetics for CINV showed significant reduction in acute vomiting and marginal statistical significance for reducing acute nausea.
Acupressure is the application of pressure to acupoints digitally or with acustimulation bands; again, the P6 point is used most commonly because of ease of access. Two controlled trials with a total of 482 adult subjects found that acupressure may decrease nausea in patients receiving chemotherapy (Klein & Griffiths, 2004). Acupressure was effective in Korean patients with gastric cancer receiving chemotherapy (Shin, Kim, Shin, & Juon, 2004). Additional work is needed before conclusively advising patients on the efficacy of acupressure in preventing and treating CINV.
A systematic review, a meta-analysis, and five randomized, controlled trials (Arakawa, 1997; Ezzone, Baker, Rosselet, & Terepka, 1998; Luebbert, Dahme, & Hasenbring, 2001; Molassiotis, Yung, Yam, Chan, & Mok, 2002; Redd, Montgomery, & DuHamel, 2001; Sahler, Hunter, & Liesveld, 2003; Troesch, Rodehaver, Delaney, & Yanes, 1993) found that guided imagery, music therapy, and progressive muscle relaxation reduce nausea and/or vomiting. The nonpharmacologic interventions may be useful in combination with antiemetics. Many of the strategies may be helpful interventions for the prevention and treatment of anticipatory nausea and vomiting. In many studies, at least two interventions were used together (e.g., guided imagery with music therapy).
The use of guided imagery was supported by a meta-analysis of 15 studies. Clinically significant reductions in nausea were found, but the effect on vomiting could not be analyzed because of the low incidence of vomiting in the studies that were reviewed (Luebbert et al., 2001). Molassiotis et al. (2002), in an experimental study of 71 Chinese women with breast cancer, found that 25 minutes of progressive muscle relaxation with 5 minutes of guided imagery was superior to standard antiemetic treatment alone in managing acute and delayed nausea and vomiting.
relaxation as a complementary therapy may be beneficial for preventing or
managing nausea and vomiting in patients receiving chemotherapy. Several
studies examined progressive muscle relaxation either alone or in combination
with other interventions. An experimental study of 71 patients with breast
Music therapy may be effective as an intervention for nausea and vomiting. A randomized study with 33 patients undergoing bone marrow transplantation found less nausea and fewer instances of vomiting in the group that received music therapy (Ezzone et al., 1998). A case-control study of bone marrow transplant recipients also demonstrated decreased nausea with music therapy (Sahler et al., 2003).
The use of psychoeducational support and information as an intervention may be effective in managing CINV. Informational audiotapes on self-care behaviors and the occurrence and intensity of common side effects were useful in managing side effects of chemotherapy in a study of 70 women with breast cancer (Williams & Schreier, 2004); however, the study did not use controls to obtain any additional information outside of the intervention. A meta-analysis of 116 intervention studies indicated that psychoeducational and psychosocial care have beneficial effects for nausea and vomiting in cancer (Devine & Westlake, 1995).
Virtual reality is an intervention for nausea and vomiting that may have benefit balanced with harms. It is a computer-simulated technique that allows individuals to hear and feel stimuli that correspond with a visual image. Individuals wear a headset that projects an image with an accompanying sound. Virtual reality is interactive, and it engages the senses simultaneously (Schneider, Prince-Paul, Allen, Silverman, & Talaba, 2004). Schneider et al. used a crossover design with 20 subjects who were randomly assigned to receive a virtual reality distraction intervention during one chemotherapy treatment and received no distraction intervention (control condition) during an alternate chemotherapy treatment. A significant decrease in symptom distress was noted immediately following chemotherapy treatments when women used the virtual reality intervention. Oyama, Kaneda, Katsumata, Akechi, and Ohsuga (2000) found a decrease in emesis three to five days after chemotherapy when patients received a virtual reality intervention. Although the intervention may be effective, it can cause motion sickness, which may increase nausea and vomiting. Also, use of the intervention may be limited because of the cost of the virtual reality system.
Exercise, hypnosis, massage and aromatherapy, acustimulation with wristband device, and consumption of ginger have been examined for use in nausea and vomiting but do not have established effectiveness. A randomized, controlled study of aerobic exercise in women with breast cancer showed marked improvement in nausea in the treatment group (Winningham & MacVicar, 1988). The study results suggest that moderate aerobic activity may be beneficial as an adjunct to antiemetic therapy in controlling CINV and in promoting physical well-being. To date, no other studies examining the effect of exercise on nausea and vomiting have been published.
Hypnosis was examined as an intervention for patients who experienced anticipatory nausea and vomiting. Fourteen of 16 patients experienced a complete remission of anticipatory nausea and vomiting following hypnotherapy (Marchioro et al., 2000).
Two randomized, controlled studies examined massage and aromatherapy as interventions for nausea. The massage groups experienced a significant decrease in nausea following the first massage and a significant reduction in nausea after massage overall. The effect of aromatherapy was more difficult to assess because different essential oils were used (Fellowes, Barnes, & Wilkinson, 2004).
The use of acustimulation with wristbands for prevention and management of nausea and vomiting has been examined in several studies with conflicting findings. Two studies had positive but inconclusive results with the use of the bands, and two other studies found no significant differences (Roscoe et al., 2003, 2005; Roscoe, Morrow, Matteson, Bushunow, & Tian, 2002; Treish et al., 2003). In a systematic review, Collins and Thomas (2004) found no benefit with the use of acustimulation bands.
Although anecdotal evidence supports the consumption of ginger to manage and treat CINV, the treatment is not supported by research. A systematic review on the effectiveness of ginger on various types of nausea and vomiting did not support the effectiveness of ginger in treating CINV in 40 patients with leukemia (Ernst & Pittler, 2000). In a randomized, crossover study with 40 patients being treated for gynecologic cancer, ginger was not found to be effective in treating acute nausea, nor was it significantly different from metoclopramide in delayed nausea (Manusirivithaya et al., 2004).
Only pharmacologic interventions are supported by sufficient strong empirical evidence of effectiveness to allow them to be recommended for practice. Evidence for nonpharmacologic interventions is limited. However, evidence does support several interventions as likely to be effective to prevent, manage, and treat CINV when used in conjunction with pharmacologic interventions.
Additional research on nonpharmacologic interventions for CINV needs to be conducted. Many nonpharmacologic interventions are inexpensive and require minimal patient teaching, such as exercise. Randomized clinical trials with large samples are needed for interventions that have the potential to prevent and manage nausea and vomiting. Studies are needed to include patients with different types of cancers, ethnic and cultural groups, and genders. Caucasian women with breast cancer were the subjects of many of the reviewed articles.
Herbal interventions such as ginger lack dose regulation. Treatments must be consistent across studies to allow for comparison. Anecdotal evidence supports the efficacy of lemon, peppermint, and chamomile, but no research has examined their use in CINV. With the increased attention on complementary and integrative therapies in cancer, additional studies are needed to validate the safety of herbal interventions as well as the combination with other traditional interventions to prevent, manage, and treat CINV.
Oncology nursing staff must be educated about evidence-based interventions and assessment of individual patient characteristics. For example, nurses should assess risk factors for nausea and vomiting, a patient’s physical and psychological capability of participating in or performing the interventions, and accessibility and cost of the interventions before developing plans of care. ONS PEP resources (pocket cards and the Outcomes Resource Area located at www.ons.org/outcomes), and discussion of the resources in a journal club format, are strategies that can be used in practice to educate nurses about evidence-based interventions for nausea and vomiting. Staff knowledge of an intervention, including the definition, and staff members’ ability to learn, perform, and teach the intervention should be assessed and developed when implementing evidence-based interventions.
Clinicians should continually work to improve the symptom experience for patients receiving chemotherapy. Nausea and vomiting, despite many improvements in treatment, still are feared by patients and still are a challenge for clinicians to overcome. Prevention of CINV is key, and evidence-based interventions can help to better control the problem. The current review shows the critical need for improvements in the gaps of knowledge and research. Oncology nurses are in an ideal situation to be leaders or “symptom experts” by asking critical questions in practice, identifying evidence-based interventions, applying the interventions in the clinical setting, and assessing the impact of the interventions. These steps would enable oncology nurses to demonstrate the impact of nursing interventions on patient outcomes.
The authors would like to acknowledge the many contributions of ONS staff members, including Mark Vrabel, MLS, AHIP, Gail Mallory, PhD, RN, CNAA, and Kelly Egnotovich, as well as the outcomes project field reviewers.
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Author Contact: Janelle M. Tipton, MSN, RN, AOCN®, can be reached at Janelle.Tipton@utoledo.edu, with copy to editor at
Digital Object Identifier: 10.1188/07.CJON.69-78