Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy 1

ABSTRACT Objective: to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. Method: integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. Results: only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. Conclusion: this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes.


Introduction
The incidence of nausea during chemotherapy ranges from 37 to 70% (1) . This incidence is mainly related to the emetogenic potential of chemotherapeutic drugs associated with the individual variations of each patient. Being aware of a drug's emetogenic potential and the characteristics of this adverse event in terms of peak and interval of occurrence is key and essential for the practice of oncologic nursing (2) .
The ability to control vomiting during chemotherapy has improved considerably in recent years, essentially with regard to drug management, with the development and use of new and modern antiemetic drugs. Controlling nausea, however, seems to be a challenge (3) , and yet the healthcare staff and patients themselves have neglected this symptom.

Some of the likely reasons chemotherapy-induced
nausea is difficult to control include: the subjectivity of the symptom, lack of focus when assessing it, lack of validated instruments, limited understanding of physiopathology, inefficient record of this event on the part of patients, and failure on the part of nurses to assess its impact in the lives of patients, especially quality of life (4) .
The impact of nausea on the patients' nutritional status and quality of life become evident few days after chemotherapy. Because in most cases the treatment is administered in an outpatient clinic, this symptom that requires careful assessment is neglected, hindering specific clinical management and nutritional interventions, in addition to the combination of pharmacological and non-pharmacological therapies (5) .
The identification and planning of nursing care concerning the nursing diagnosis (ND) nausea values the work of nurses in the Oncology field and improves the quality of care provided to patients. For this reason, investigating the factors related to this diagnosis is key.
Factors related to the ND nausea can favor management and allow the nursing staff to devise a care plan that enables the implementation of efficacious and immediate actions to solve problems (6) .
Given the previous discussion, this study's objective was to identify the factors related to the nursing diagnosis nausea among cancer patients during chemotherapy through an integrative review.

Method
An integrative review involves six steps (7)(8) : It is important to note that there were variations, especially with regard to non-controlled descriptors in the different databases, as shown in Figure 1. CINAHL did not present non-controlled descriptors. The Boolean operator AND was used with controlled descriptors and OR was used for non-controlled descriptors; NOT was also used for radiotherapy, surgery, metastasis and chemotherapy.  After the study authors reached a consensus regarding relevant information in each study, data were synthesized. Thus, all papers in the sample were read, aiming to explore the texts and extract data using an instrument (9) addressing the following items: identification of studies, introduction, objectives, methodological characteristics, results and conclusions.
The instrument was completed for all the papers, which were cataloged in ascending order according to year of publication.
All data concerning the characteristics of each study, as well as information regarding nausea-related factors among cancer patients undergoing chemotherapy were grouped in tables and analyzed descriptively.
The studies' level of evidence was classified according to Melnyk and Fineout-Overholt (10) , following

Results
The final sample comprised 30 studies  , 29 of which were indexed in PUBMED and one in EMBASE;29 were published in English and one in Spanish.     Prior experience with chemotherapy 2 (6.7) Nausea in previous cycles 2 (6.7) Performance status 2 (6.7) Weight loss 2 (6.7) Severity of nausea in previous cycle 2 (6.7) Toxins (non specified) 2 (6.7) To the treatment Family support/conflicts 3 (10) Expectation of response after treatment 2 (6.7)
One study aimed to assess the predictive power of personal characteristics related to the development of chemotherapy-induced nausea and vomiting (CINV) in a heterogeneous sample of 991 patients with different types of cancer, concluding that the key variables that characterized antecedents for nausea included: not using antiemetic medication according to international guidelines, being young, experiencing nausea before chemotherapy, and inappropriate response to CINV in previous cycle (43) .
Motion sickness causes discomfort when movement disturbs the organs responsible for balance. It refers to a combination of autonomic and cognitive signs and symptoms induced when exposed to certain types of movement and may include nausea, vomiting, paleness, cold sweats, hyper salivation, and headache.
The control and prevention of these symptoms include pharmacological, behavioral and complementary therapies (44)(45) .
The Aurélio dictionary emphasizes, in its definition of nausea, that motion sickness is an "unpleasant sensation, well described by familiar expressions, such as having a gag reflex and upset stomach. Associated to feeling nauseated when travelling, especially on water." (46) A prospective observational study conducted with 213 women with gynecological cancer, which aimed to investigate risk factors for CINV, revealed that being young, motion sickness and the high emetogenic potential of chemotherapy are associated with late nausea (47) .
Another individual factor was the patient's sex.
The incidence of more frequent nausea and vomiting among women may be explained by the frequent use of protocols with higher emetogenic potential and a low consumption of alcohol (48) .
Data also reported by a study investigating risk factors show that female patients are significantly more likely to experience CIVN. Additionally, the following risk factors stand out in the acute phase: being a woman, younger than 55 years of age, and non-habitual consumption of alcohol. In the late phase, only being a woman is a risk factor for CIVN (49) .
Some factors that triggered CINV are related to the treatment, including the antiemetic regimen adopted, the specific agent, dose of chemotherapy, route and speed of administration. Short intravenous infusions more frequently induce vomiting than prolonged infusions or oral medications (48) .
Patients treated with highly emetogenic antineoplastic chemotherapy were 5.61 times more likely to experience chemotherapy-induced nausea and vomiting in the first cycle than when treated with moderately emetogenic protocols (41) . The occurrence of anticipatory nausea was also significantly associated with the high emetogenic potential of chemotherapy (50) .
Being a woman and moderate to highly emetogenic chemotherapy stood out among the risk factors that trigger nausea (51) .
Some anxiety symptoms, such as fear of death, fear for the worse, inability to relax, hot or cold sweats, nervousness, weakness, and numbness were identified as potential indicators of chemotherapy-induced nausea and vomiting (52) . Similarly, the level of pre-treatment anxiety and expectation of nausea and vomiting were strongly associated with the development of severe symptoms (53) .
A study conducted with 94 women with gynecological cancer, which employed the State-Trait Anxiety Inventory and a self-report questionnaire, reported that being young and anxiety levels are associated with a high risk of experiencing CINV (54) .  (55) . Conditioned stimuli were reported in nine studies (11)(12)(13)(14)16,(19)(20)27,34) as being a factor related to chemotherapy-induced nausea.
After experiencing repetitive cycles in which stimuli are paired with subsequent nausea, cycles acquire the ability to trigger nausea and vomiting even before chemotherapy is administered (56) .
Expecting nausea after the treatment was reported in seven studies (13,23,(26)(27)30,33,35) included in the integrative review. Patients classified as having a high expectation of experiencing nausea presented the highest mean of occurrence of nausea when compared to those classified as having low expectation (57) .

Conclusion
The most frequent factors related to the ND nausea presented by patients undergoing antineoplastic chemotherapy were: being young, being a woman, motion sickness, the emetogenic potential of chemotherapy, anxiety, conditioned stimulus, and expectation that nausea will be experienced after the treatment. Of these, only motion sickness and anxiety are factors related to the ND Nausea containing in the North American Nursing Diagnosis Association-International (NANDA-I Inc), which shows an important difference between evidence found and that used by NANDA-I Inc.
This analysis shows that, although the current definition of nausea presented by NANDA-I Inc. is appropriate to patients undergoing chemotherapy, this definition does not include among its related factors "chemotherapy" or "antineoplastic chemotherapy", despite the various studies addressing this topic, using different designs and presenting different objectives and outcomes Given this review's findings and the incidence of nausea among cancer patients undergoing chemotherapy, it is crucial to include the term "chemotherapy" or "antineoplastic chemotherapy" among the factors related to the ND Nausea presented by NANDA International, Inc.