Alternatives to Pharmacological Treatment of Nausea and Vomiting: A Systematic Review

Abstract

Despite the progress made with antiemetics, nausea and vomiting still affect a great percent of our population. Hence, the objective of this review was to gather, compare, and contrast existing scientific data about alternative non-pharmacological therapies for the management of nausea and vomiting in three different scenarios: post-operative nausea and vomiting (PONV), chemotherapy-induced nausea, and nausea in patients presenting to the emergency department. MEDLINE complete Elton B. Stephens Co (EBSCO) database was searched for journal articles related to the use of alternative therapies and/or aromatherapy for nausea and vomiting. Only articles using English language were included. Eligible articles included randomized controlled clinical trials and original research. Ten articles met the inclusion criteria with a total of 835 participants. Although there were contradictory results, aromatherapy appears to be effective a non-pharmacological alternative for the management of nausea and vomiting. Other alternative therapies such as controlled breathing, acupuncture, and chewing gum were also proven to be effective. Given the limitations and mixed results of this review, it is difficult to reach a concrete conclusion. However, there is strong evidence that safe, quick, and inexpensive therapies such as aromatherapy, massage, controlled breathing, acupuncture, and chewing gum, may have potential benefits in alleviating nausea and vomiting. Therefore, it is suggested that whenever the symptoms are not severe or life threatening, alternatives like the ones discussed in this paper should be implemented. If they are found to be ineffective, routine treatment with antiemetics should be sought.

Key words: Nausea, vomiting, aromatherapy, breathing, acupuncture, gum, ginger, antiemetics, alternative therapies, chemotherapy, post-operative, emergency department.

Introduction

Nausea and vomiting are frequently encountered symptoms with a long list of potential causes. Nausea is often described as an “unpleasant painless subjective feeling that one will imminently vomit.”¹ The underlying pathophysiology of nausea and vomiting, although complex, has been well studied and is widely understood. The nucleus tractus solitarious in the medulla oblongata receives stimulus from the cerebellum, cerebral cortex, limbic system, and area prostema, which provokes physiological changes resulting in the sensation of nausea, with or without vomiting.¹

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 Common pharmacological treatments for nausea and vomiting are divided into two categories: antiemetics such as ondansetron (Zofran), which act centrally, and prokinetics such as metoclopramide, which control gastrointestinal motility.¹ However, there are several adverse effects linked to antiemetic use, such as alterations in blood pressure, possible adverse cardiac events, and sedation.² There are several other pharmacological treatments that have been shown to be effective in the management of nausea and vomiting, which will not be discussed in this paper.

Despite the progress made with antiemetics such as ondansetron, nausea and vomiting are still very common presenting symptoms in our population, especially among postoperative patients and chemotherapy recipients. In fact, people in these groups reported an incidence of nausea and vomiting of over 50%.³ The high incidence, combined with longer hospital stays, unplanned admissions, and the increased use of staff and supplies, results in an economic burden which is hard to estimate given the subjective nature of this complaint. However, it has been suggested that nausea and vomiting cost about $4-16 billion to the United States economy.¹ Furthermore, vomiting is associated with negative outcomes such as suture dehiscence, pneumothorax, pulmonary aspiration, esophageal rupture, and subcutaneous emphysema.² Therefore, it is essential that we find safer and inexpensive alternatives to the traditional pharmacological treatment of nausea and vomiting.

Recent scientific studies aiming to determine the efficacy of alternative therapies have been developed. The results of these clinical trials vary depending on the scenario and etiology of the complaint. As such, the objective of this systematic review is to compare and contrast alternative therapies to pharmacological treatment of nausea and vomiting in three different scenarios: post-operative nausea and vomiting, chemotherapy-induced nausea, and nausea in patients presenting to the emergency department.

Methods

Despite the progress made with antiemetics, nausea and vomiting still affect a great percent of our population. Controlled randomized trials comparing alternative therapies such as aromatherapy, chewing gum, controlled breathing, massage, and acupuncture, to placebo and/or traditional pharmacological management have been developed. Results vary depending on the setting and etiology of nausea and vomiting. For this systemic review, the researcher sought to identify randomized controlled trials and review articles involving alternatives therapies to pharmacological treatment of nausea and vomiting.

On September 16^th, 2018 MEDLINE complete (EBSCO) was searched for journal articles with “nausea and vomiting,” “alternative,” and “aromatherapy,” which yielded 173 articles. Four additional relevant articles were identified from other sources. Thirteen articles were eliminated because full text was not available. Seventy articles were then excluded because they were not published within the past ten years. Nine articles were then excluded for not using human subjects. Zero articles were excluded for not being published in English. After reviewing the remaining articles, 74 were excluded for not being relevant to the topic or unavailable for download. Therefore, 11 articles of studies were included in this systematic review.

Results

All reviewed articles are summarized in Table 1. The search identified eight clinical trials and three review articles involving a total of 835 participants.  All the articles used for this review explored different alternatives for pharmacological management of nausea and vomiting and are categorized based in three different scenarios: post-operative nausea and vomiting (PONV), chemotherapy-induced nausea, and nausea in patients presenting to the emergency department.

Postoperative

The studies in this category share the same study design as they are all randomized controlled trials with the same population sample (postoperative patients). In all four studies, participants were randomly divided into control and experimental groups, and neither study reports concerns during the randomization process. Blinding strategies differ amongst the studies: Sites et al. and Kiberd et al. used a single-blinded approach in which the researchers knew the treatments they are administering, but the participants did not.^2,5 Moeen used a double-blinded approach where both the researches and the participants were unaware of the experimental treatments.⁶ On the other hand, Darvall et al. chose to conduct a nonblinded study, where both the researches and the participants were aware of the treatments.⁷ The outcome evaluated in all four studies was postoperative nausea and vomiting (PONV).

All four studies reported using different alternative therapies and/or control groups. Sites et al. explored the use of controlled breathing alone (control group) versus controlled breathing plus peppermint aromatherapy (experimental group).² Kiberd et al. on the other hand, compared the efficacy of aromatherapy (lavender, ginger, mint, and spearmint) to a placebo group (normal saline).⁵ Moeen opted to compare sham acupuncture plus dexamethasone (control group), to bilateral acupuncture at P6 (wrist) and CV13 (upper abdomen) plus normal saline (experimental group).⁶ Lastly, Darvall et al. chose to compare the use of ondansetron (control) to chewing gum (experimental) for postoperative nausea and vomiting.⁷ Common to all four studies was the use of prophylactic ondansetron or dexamethasone prior to surgery.  

Sample size, sex, and age of participants also varied significantly amongst studies.  Sites et al. and Moeenhad larger sample sizes of 196 and 120 respectively.^2,6 Darvall et al. used 94 participants for his study.⁷ Kiberd et al. on the other hand, had the smallest sample size in this category with 39 participants.⁵ All participants were evaluated after undergoing surgeries of different types. The age of the participants ranged from 2-65 years of age and included both females and males.

Results in the postoperative setting were contradictory. Sites et al. concluded that controlled breathing, with or without peppermint aromatherapy, should be initiated without delay in postoperative patients, as it proved to be an effective first line of defense in the treatment of postoperative nausea and vomiting.² Likewise, Moeen concluded that there was no difference in the incidence of nausea and vomiting between the group that received acupuncture and the group that received dexamethasone for the treatment of PONV.⁶ Similarly, Darvall et al. concluded that chewing gum and ondansetron had similar effectiveness in the treatment of postoperative nausea.⁷ On the other hand, Kiberd et al. concluded that aromatherapy had very little efficacy in treating postoperative nausea and vomiting compared with control.⁵

Chemotherapy induced

Both studies in this category were randomized controlled trials with different blinding strategies. Zorba and Ozdemir designed their study as a quasi-randomized trial, whereas Evans et al. set up their study as a double-blind randomized controlled trial.^{8, 9} Distribution of participants also differed between studies. Evans et al. used three different groups: the  no treatment control group, the no treatment-placebo group, and the intervention group.⁹ Alternatively, Zorba and Ozdemir used a massage-only group, an inhalation-only group, and a control group.⁸ The main outcome evaluated in both studies was chemotherapy-induced nausea and vomiting.

Both studies in this category used aromatherapy as the alternative therapy. However, Zorba and Ozdemiradded an experimental group that received a 20-minute foot massage. The second experimental group received a combination of inhaled peppermint, bergamot, and cardamom in sweet almond oil, while his control group received routine treatment and care.⁸ Evans et al.used inhalation of a non-fragrant substance (water) for his no treatment group, inhalation of a nontherapeutic fragrant (Johnson’s® baby shampoo) for his no treatment placebo group, and inhalation of essential oil of ginger for his intervention group.⁹

Sample size, sex, and age of participants varied significantly between studies. Zorba and Ozdemir’s study had a sample size of 75 breast cancer patients with no exclusion criteria.⁸ Evans et al. used a sample size of 49 oncology patients aged 8-21 years and excludes asthmatic patients.⁹ 

Results in this category were contradictory. While Zorba and Ozdemirwere able to conclude that massage and inhalation aromatherapy significantly reduces nausea and vomiting in this population,⁸ Evans et al. concluded that ginger aromatherapy did not significantly decrease chemotherapy-induced nausea and vomiting.⁹

Emergency Department

Both Beadle et al. and April et al. designed their studies as double-blinded randomized controlled trials.^10,11 Beadle et al. randomized the participants into two different groups,¹⁰ whereas April et al. randomized the participants into three different groups.¹¹ The outcome evaluated in both studies was nausea and/or vomiting of any etiology.

Although both Beadle et al. and April et al. used Isopropyl alcohol as the alternative therapy,^10,11 the group distribution and interventions differed between studies. Beadle et al.separated the participants into two groups: the experimental group, in which participants inhaled isopropyl alcohol, and the control group in which they inhale normal saline.¹⁰ April et al. divided the participants into three groups: in the first group, the participants received inhaled isopropyl alcohol and 4mg of oral ondansetron, while participants from the second group inhaled isopropyl alcohol and received oral placebo; those in the third group inhaled saline solution placebo and received 4mg of oral ondansetron.¹¹

All of the participants included in both studies were adults (>18yo) presenting to the emergency department with chief complaints of nausea and vomiting. The sample size in the study by  Beadle et al. was 80 and it excluded patients who were allergic to isopropyl alcohol and those unable to inhale through the nares.¹⁰ On the other hand, April et al. had a sample size of 120 and it excluded participants requiring intravenous access, allergy to isopropyl alcohol, altered mental status, inability to inhale through the nares.¹¹

The studies in this category yield very similar results. Both Beadle et al. and April et al. were able to conclude that inhaled isopropyl alcohol is an effective first line therapy for patients complaining of nausea and vomiting in the emergency department.^10,11

Discussion

Study outcomes

Although there were contradictory results, aromatherapy appears to be an effective alternative for the treatment of nausea and vomiting as evidenced by findings in studies from the three different scenarios included in this review. Sites et al., Beadle et al., April et al, and Zorba and Ozdemir, all concluded that aromatherapy with different fragrances, was an effective therapy for the management of nausea and vomiting of different etiologies.^{2, 8, 10, 11} On the other hand, Kiberd et al. and Evans et al., found that aromatherapy had little effect in decreasing nausea and vomiting in their respective populations.^{5, 9} One possible explanation for their failure to prove the efficacy of aromatherapy is their sample sizes of less than 50 (n=<50), which is a less than ideal sample size for randomized controlled trials. Their studies also used participants that were younger than 21, which differentiates them from the other studies that used aromatherapy as their main alternative. This is significant because it is possible that the physiology of nausea and vomiting, as well as the response to treatment varies with age. Other therapies such as acupuncture and chewing gum also proved to be effective in the management of nausea and vomiting as evidenced by the studies by Moeen and Darvall.^6,7

Limitations

Despite the positive findings of this review, there are several limitations that need to be addressed. First, the sample size of the studies reviewed range from 39 to 196. Not only is 39 a rather small sample size, but the wide range makes it difficult to find consistency and accuracy in the results. Second, although most of the articles included in this study were randomized controlled trials, the blinding strategies differ from one another. Furthermore, some of the studies were designed as pilot studies (Kiberd et al.,Darvall et al.,Zorba and Ozdemir) and there was at least one quasi-experiment (Zorba and Ozdemir).^5,7,8 This variability among study designs and blinding strategies is significant because the accuracy and validity of the results can be compromised by researcher bias or the placebo effect. Third, although the articles were categorized by scenarios, the studies in each setting differed in many aspects. For instance, in the postoperative setting, participants underwent completely different surgeries, which means that they might have been exposed to different procedures/medications prior to surgery. Similarly, the participants in the two chemotherapy-induced studies conducted by Zorba and Ozdemirand Evans et al.,were receiving treatment for different types of cancers.^8,9 This discrepancy in the underlying diagnosis could potentially affect the accuracy of the results, as different cancers may affect the physiology of nausea and vomiting in different ways.  Lastly, although a detailed and systematic research strategy was used, it is difficult to ensure that all relevant trials were included.

Conclusion

Given the limitations and mixed results of this review, it is difficult to reach a concrete conclusion. However, there is strong evidence that safe, quick, and inexpensive therapies such as aromatherapy, massage, controlled breathing, acupuncture, and chewing gum may have potential benefits in alleviating nausea and vomiting. Therefore, it is suggested that whenever patients present with mild symptoms that are not life threatening, alternatives like the ones discussed in this paper should be implemented. If they are deemed to be ineffective, routine treatment with antiemetics should be sought. It is also recommended to replicate studies of this nature with improved methods and larger sample sizes for more accurate results. It could also be of benefit to develop studies in the postoperative setting, using therapies that were effective in the emergency department and/or in the chemotherapy induced scenario, and vice versa.

References

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