Abstract
Background
Hemodialysis patients suffer from physical and mental symptoms for which aromatherapy might be useful. This study aimed to determine the effectiveness of Melissa officinalis L. (Lemon Balm) essential oil inhalation on anxiety and the burden of symptoms in hemodialysis patients.
Methods
This study is a randomized clinical trial with a pretest-posttest design. Sixty-eight hemodialysis patients were randomly divided into intervention (who underwent Melissa officinalis L. inhalation aromatherapy 3 times a week for one month) and control (who inhaled refined sweet almond oil) groups. The intervention in both groups was conducted during the hemodialysis session. The data were collected using the state-trait anxiety inventory and Dialysis Symptom Index. Data were analyzed through SPSS-25, using Mann-Whitney, Wilcoxon, t-tests and MANOVA.
Results
Before the intervention, both groups were similar in terms of anxiety and symptoms burden (P > 0.05). However, after the intervention, a significant difference was found between the groups in terms of state and trait anxiety, and severity of constipation, nausea, vomit, diarrhea, swelling in legs, muscle cramps and shortness, worry, nervousness and anxiety, and trouble staying asleep. Moreover, after the intervention, a significant difference was observed between the groups regarding the prevalence of symptoms burden such as feeling anxious and having a dry mouth (P < 0.05).
Conclusion
Melissa officinalis L. essential oil inhalation aromatherapy reduced the symptoms burden and anxiety in hemodialysis patients. Given the effectiveness of aromatherapy in hemodialysis patients, it is suggested that healthcare workers should use this complementary and integrative health to reduce the anxiety and symptoms burden in hemodialysis patients.
Trial registration RCT registry
Iranian Registry of Clinical Trials (IRCT) number: IRCT20191021045178N3; Registration date 27/04/2021.
Keywords: Aromatherapy, Melissa officinalis L., Anxiety, Symptom burden, Hemodialysis
Background
Chronic kidney disease (CKD) is a fast-growing chronic disease in the world [1, 2]. The prevalence of end-stage renal disease (ESRD) has increased significantly around the world [3], including the United States [4] and Iran [5, 6]. Hemodialysis is an effective treatment for patients with ESRD and can significantly improve their quality of life and prolong their survival [7].
Hemodialysis patients experience some degree of symptom burden. Painful physical and mental symptoms are important symptoms of ESRD. They experience fatigue, itching, irritability, anxiety, nausea and vomiting, headache, hypotension, muscle cramps, fever, and chills [8]. One study reported bone and joint pain (97.4%) and irritability (94.7%) as the most common symptoms of hemodialysis patients [9]. Other symptoms, such as weakness, exhaustion, muscle cramps, anorexia, nausea, changes in sexual function, sleep problems [10], changes in body image, anxiety, discomfort, and severe worry are also due to physiological problems and complications of hemodialysis [11]. Patients also experience issues, such as family problems, feelings of guilt, and fear of death due to dependence on the dialysis machine [12]. In fact, all aspects of a health-promoting lifestyle, including health responsibility, nutrition, spiritual development, interpersonal relationships and stress management, and especially the physical activity of hemodialysis patients, are negatively affected by this disease, its treatments, and complications [13]. Owing to exposure to numerous stressful factors, some of these patients suffer from psychiatric disorders like anxiety [14].
Anxiety is a common psychological symptom in patients with ESRD undergoing hemodialysis. The results of a study indicated that approximately 38% of these patients had anxiety disorders, and this rate varied from 12 to 52% [15]. During COVID-19 pandemic, it was reported that the mental health of hemodialysis patients has been severely affected and may have increased their anxiety and depression [16]. Issues such as the patient’s loneliness during hemodialysis, the alarm of the hemodialysis machine, insertion of the needle into the fistula, and central venous catheterization can cause anxiety in such patients [17].
Management of patients undergoing hemodialysis is significantly important in terms of increasing compatibility with dialysis and improving quality of life all of the time [12], especially in COVID-19 pandemic. During this period, professional healthcare workers, including nurses, who are at the forefront of the care and treatment of these patients, need to consider nursing care planning to overcome the process of COVID-19 with the least losses and reach healthy days [18], especially for hemodialysis patients. Both pharmacological and non-pharmacological methods can help manage these cases [12]. Complementary and integrative health (CIH) may be effective in managing and improving the patients’ physical, psychological, and social symptoms [19–22]. The use of CIH in chronic diseases has increased all over the world during the last two decades [23]. Researchers have used different types of CIH, music therapy [24], acupuncture [25], the use of herbal medicines [26], aromatherapy [27, 28], etc.
Aromatherapy is a form of CIH. It can be used in massage, cosmetics, and olfactory issues. Olfactory aromatherapy using the essential oil aroma sends the aroma into the brain limbic system through the sense of smell. Along with other treatment methods, aromatherapy may be an effective way to manage anxiety [12]. Different essential oils, such as bergamot orange essence, lemon, lavender, and Melissa officinalis L. essential oils are used in aromatherapy [19, 21, 29, 30].
Melissa officinalis L. (Lemon balm) essential oil is an aromatic herb from the mint family (Lamiaceae) [31]. It contains volatile components such as geranial, citral, citronellal, and geraniol ones [32]. It was reported that monoterpenes of the Lamiaceae family might have peripheral and central analgesic effects [33]. Moreover, Geraniol affects cancer and inflammatory diseases [34]. Citronellal has neuro-protective effect [35]. Review studies showed Melissa officinalis L. (Lemon balm) had antioxidant properties [31], antiviral effect [36], and cardiovascular disease protection.
In in-vivo studies in animals such as mice and rats, the anti-anxiety [37] and anti-inflammatory [38, 39] effects of Melissa officinalis L. (Lemon balm) were reported. In in-vivo studies on humans, it was indicated that Melissa officinalis L. was effective in mild and moderate depression [40]. Another in-vivo study on humans such as mothers of preterm infants admitted in intensive care units showed that Melissa officinalis L. (Lemon balm) aromatherapy improved the sleep quality in these mothers [41]. In addition, Melissa officinalis L. (Lemon balm) aromatherapy reduced anxiety and improved the quality of sleep in Iranian patients undergoing coronary artery bypass surgery [42]. A systematic review and meta-analysis on 302 patients showed that Melissa officinalis L. consumption reduced triglyceride and cholesterol [43]. Another systematic review and meta-analysis indicated that Melissa officinalis L. might be effective in reducing anxiety in acute situations [44]. As mentioned, these situations and diseases are acute, and patients’ anxiety and symptoms would be different from the chronic conditions. Results of a study on Iranian chronic conditions such as chronic stable angina showed using Melissa officinalis L. (Lemon balm) supplement reduced anxiety, depression, and sleep disturbance [30].
As mentioned, studies have pointed out the positive effects of Melissa officinalis L. (Lemon balm) in the form of aromatherapy and oral consumption, etc. in in-vivo conditions. However, a few studies used this aromatherapy in chronic diseases [30]. Moreover, the effect of Melissa officinalis L. (Lemon balm) aromatherapy on chronic diseases such as ESRD patients undergoing hemodialysis and their complications is unknown. In addition, the literature review could not answer the researchers’ question: Could Melissa officinalis L. (Lemon balm) essential oil aromatherapy reduce anxiety and the prevalence and severity of symptoms burden of ESRD undergoing hemodialysis? Therefore, conducting a study using Melissa officinalis L. (Lemon balm) aromatherapy on ESRD patients, as a chronic disease, would be a novel evidence-based practice. These novel findings would improve the evidence-based practice regarding the effectiveness of Melissa officinalis L. (Lemon balm) essential oil inhalation aromatherapy on anxiety and symptoms burden in hemodialysis patients. The hypotheses posed were as follows:
1) Melissa officinalis L. (Lemon balm) essential oil inhalation is effective in reducing state and trait anxiety in hemodialysis patients.
2) Melissa officinalis L. (Lemon balm) essential oil inhalation is effective in reducing the symptoms burden in hemodialysis patients.
Methods
Design
The present study is a randomized clinical trial with a pretest-posttest design and intervention and control groups. This study was registered in the Iranian Registry of Clinical Trials (IRCT) with the code number of IRCT20191021045178N3 in 27/04/2021.
Setting
The study was conducted on ESRD patients under treatment with hemodialysis in the Hemodialysis Center of Imam Reza Clinic and Nemazi Hospital affiliated with Shiraz University of Medical Sciences from July to September 2021.
Participants
The inclusion criteria for the participants were 18 years of age and older, the ability to understand and speak the Persian language, at least 6 months after the start of the current hemodialysis, and those under hemodialysis 3 times a week. Exclusion criteria included respiratory and allergic problems such as asthma, allergy to any smell, or obstruction to smell; history of allergy to plants; oral problems such as dry mouth, and parotitis; chronic mental illness; use of psychotropic medication; current or previous history of COVID-19; a known case of severe anxiety disorder based on their report; intolerance to essential oil during the intervention; any allergy to the aromatic oil used during the intervention; acute pain during the intervention; absence in more than two consecutive sessions during the intervention; and the patient’s unwillingness to continue cooperation with the researcher. It is necessary to explain that we were supposed to exclude the patients who were previously, currently, or during the study infected with COVID-19, but no patient had this condition. Figure 1 shows the distribution of the hemodialysis patients during the study.
Fig. 1.
Distribution of research participants
Sample size
The sample size was estimated at 27 based on the results of a similar study [12] and a comparison of two mean scores with a 5% type 1 error, and 90% power in two groups. To this end, 34 samples per group and 68 samples were considered to increase the accuracy according to a drop of 25%.
Randomization
Given the hemodialysis program for most of the patients was performed every other day, on odd and even days, we used the method of dropping a coin; even days were randomly allocated to the control group and odd days to the intervention group. This was conducted to prevent spreading the smell in the ward and its effect on the control group. The research participants were selected using the simple random sampling method. Therefore, a code was randomly assigned to each patient in the list of the patients who presented on even and odd days. Then, 68 patients (34 from even days and 34 from odd days) were randomly included in the study using a random number table.
Measurements
The patients’ anxiety and symptom burden were evaluated using the Spielberger state-trait anxiety inventory (STAI) and the Dialysis Symptoms Index (DSI) before the intervention. The participants completed the demographic information forms. The researcher assistant guided the literate participants to fill out the questionnaires. The questions were read for the illiterate participants and what they said was accurately written in the questionnaires. The demographic information form included information about age, gender, education level, marital status, underlying diseases, and number of years of hemodialysis.
STAI consisted of 40 questions scored using a 4-point Likert scale. The questionnaire measured state and trait anxiety. The scores ranged from 20 to 80, and higher scores indicated greater anxiety. The internal correlation of the questionnaire ranged from 0.86 to 0.95, and the reliability coefficients of the test-retest were also reported from 0.65 to 0.75 [45]. The validity and reliability of the Persian version of the questionnaire were previously confirmed, and the Cronbach’s alpha of state and trait anxiety was obtained at 0.87 and 0.90, respectively [18].
Weisbord et al. developed the Dialysis Symptom Index (DSI) in 2004. This questionnaire is used to evaluate the presence and severity of physical and mental symptoms in hemodialysis patients and includes 30 items scored based on a 5-point Likert scale. The total score of symptom severity ranges from 0 (if none of the 30 symptoms are present) to 150 (the most severe annoying state in each symptom). This questionnaire has high validity and reliability. Cronbach’s α ranged from 0.82 to 0.84, and the Kappa statistics ranged from 0.06 to 0.90 for all questionnaire items [46, 47]. The validity and reliability of the Persian version of the questionnaire were confirmed with a Cronbach’s alpha of 0.90 and a Kappa coefficient of 0.23 to 0.93 [48].
Intervention
The intervention group
In the intervention group, 200 µl of Melissa officinalis L. essential oil was poured on a cotton ball and attached to the patient’s clothes with a pin 20 cm from the patient’s nose; then, it was inhaled by the patient for 20 min. The intervention was carried out 3 times a week during hemodialysis (first 20 min of dialysis) for one month.
The pure Melissa officinalis L. (Lemon balm) essential oil was obtained from Adonis Gol Darou Pharmaceutical Company in Tehran, Iran. In this company, Lemon balm extract is obtained from the comminuted herb of Melissa officinalis L. by extraction with particular solvents. The appearance of this essential oil is yellowish.
The composition of this essential oil was analyzed using a gas chromatography-mass spectrometry (GC/MS) device. Gas chromatography/Mass spectroscopy (GC/MS) analysis was performed via an Agilent technologies (7890 A) gas chromatograph equipped with an HP-5MS capillary column (coated with phenyl methyl siloxane, 30 m × 0.25 mm i.d.) and connected to a mass detector (Agilent technologies model 5975 C). The flow rate of the carrier gas (Helium) was adjusted as 1 ml/min with a split ratio of 1:30. The mass spectrometer was acquired in EI mode (70 eV) with a mass range of 30–600 m/z. The injector and detector temperatures were adjusted at 250 and 280 °C, respectively. The column temperature was linearly programmed from 60 to 250 °C with a rate of 5 °C/min and subsequently held at 250 °C (10 min). The data from GC/MS were used to identify the constituents of the samples. This process compared the resulting Kovats indices (KI) calculated by using a homologous series of n-alkanes C8-C22 as well as mass spectra data of the components with those mentioned in the respective literature [49].
According to the GC/MS chromatogram, 95.37 of the components, mainly monoterpenes, were identified. Both major and minor identified volatile constituents were as below: Citronellal (4.5%), Citral (37.46%), Geranial (46.16%), thymol (0.5%), Trans-Geranic acid methyl ester (0.7%), Delta-Carene (1.49%), Trans-Caryophyllene (2.14%), and Caryophyllene oxide (2.42%). Figure 2 shows the Gas chromatography/Mass spectroscopy profile for Melissa officinalis L. essential oil.
Fig. 2.
Gas chromatography/Mass spectroscopy profile for Melissa officinalis L. essential oil
The control group
In the control group, the refined sweet almond oil prepared from Adonis Gol Darou Pharmaceutical Company in Tehran, Iran, was used as a placebo in the same method. Both control and intervention groups similarly received routine care. Owing to COVID-19 during the intervention, three-layer medical masks were used for all patients in the intervention and control groups to comply with health protocols.
Side effects and harms
Little information has been reported on the adverse effects of Melissa officinalis L. One study reported the occurrence of vomiting, dizziness, wheezing, restlessness, abdominal pain, nausea, and headache after consuming the Melissa officinalis L. extract (60 drops per day) [50]. Other reported side effects included higher appetite [51], redness, contact dermatitis, burning sensation, and skin irritation in topical use [50]. The side effects were explained to the participants, and they were asked to contact the third author in case of any complications. The trial was to be stopped in case of any side effects of aromatherapy; however, no significant side effects or complications were reported.
Outcomes
The symptom burden and anxiety questionnaires were re-completed by both groups after the intervention at the end of one month (12 hemodialysis sessions).
Blinding
One researcher, who was unaware of the classification of the groups, assisted us in performing data collection and completing the questionnaires due to the blind nature of the research. However, the differences in aromas on data collection days may lead to identification. Therefore, the only person who was effectively blinded was the statistical analyst who was unaware of the intervention and control groups.
Ethical consideration
The present study was approved by the Ethics Committee of Shiraz University of Medical Sciences (Code: IR.SUMS.REC.1400.065). The study was performed following the Declaration of Helsinki. All hemodialysis patients signed the informed consent form. The research participants were aware of the research objectives and method, confidentiality of information, side effects of the essential oil, and the right to withdraw from the study; they were assured that there would be no change in their treatment and care. Written informed consent was obtained from all participants.
Data analysis
In the present study, quantitative variables were shown with mean and standard deviation and qualitative variables with number and percentage. Independent t-tests and Mann-Whitney tests were used to measure inter-group relationships. In addition, chi-square and Fisher’s exact tests were used to measure the relationship between the two qualitative variables; also, Wilcoxon and paired t-tests were employed to measure intra-group relationships. Moreover, to determine how large the effect of the intervention was on the state and trait anxiety and symptoms burden, we used Multivariate analysis of variance (MANOVA) and partial Eta Square (η2). Based on the results, η2 = 0.01, 0.06, and 0.14 showed a small, medium, and large effect, respectively. P values < 0.05 were considered as the significance level, and SPSS 25 was used for data analysis.
Results
In the present study, the participants’ mean age was 49.79 (SD = 14.96) and 54.14 (SD = 16.07) in the intervention and control groups, respectively. Mann Whitney U test showed that both groups were similar in age (Z = 3.02, P = 0.41). Most of the participants were women (64.7%) in the intervention and control groups. Moreover, 70.6% of those in the intervention group and 67.6% in the control group were married. Half of the hemodialysis patients in the intervention group and 52.9% of them in the control group had primary and secondary school education. Approximately, one-third of the participants in both groups reported diabetes and coronary artery diseases. Most of the patients in the intervention group (70.6%) and control group (76.5%) had hypertension. The length of time they had undergone hemodialysis was 2.97 (SD = 3.41) and 3.64 (SD = 3.26) years in the intervention and control groups, respectively. Mann Whitney U test showed that both groups were similar regarding the length of time they had undergone hemodialysis (Z = 0.14, P = 0.39). Based on the results, the two groups were similar in terms of demographic characteristics, underlying diseases, and number of years of dialysis (P-value > 0.05) (Table 1).
Table 1.
The demographic and clinical characteristics of the Hemodialysis patients in the intervention and control groups
| Intervention n (%) |
Control n (%) |
Test P-value |
|
|---|---|---|---|
| Gender | |||
|
Male Female |
12 (35.3) 22 (64.7) |
12 (35.3) 22 (64.7) |
- P = 0.99 |
| Marital status | |||
|
Single Married Divorce Widow |
6 (17.6) 24 (70.6) 2 (5.9) 2 (5.9) |
3 (8.8) 23 (67.6) 2 (5.9) 6 (17.6) |
χ2 = 3.02 P = 0.41 |
| Educational levels | |||
|
Illiterate Primary school Secondary school High school Academic |
4 (11.8) 11 (32.4) 6 (17.6) 7 (20.6) 6 (17.6) |
5 (14.7) 13 (38.2) 5 (14.7) 8 (23.5) 3 (8.8) |
χ2 = 1.43 P = 0.87 |
| Having Diabetes | |||
|
Yes No |
11 (32.4) 23 (67.6) |
13 (38.2) 21 (61.8) |
χ2 = 0.25 P = 0.61 |
| Having hypertension | |||
|
Yes No |
24 (70.6) 10 (29.4) |
26 (76.5) 8 (23.5) |
χ2 = 0.30 P = 0.58 |
| Having coronary artery diseases | |||
|
Yes No |
10 (29.4) 24 (70.6) |
11 (32.4) 23 (67.6) |
χ2 = 0.06 P = 0.79 |
| Having hyperlipidemia | |||
|
Yes No |
8 (23.5) 26 (76.5) |
14 (41.2) 20 (58.8) |
χ2 = 2.41 P = 0.12 |
State anxiety
Based on the results of the independent t-test, the mean state anxiety was not significantly different in the intervention and control groups before the intervention (P-value = 0.91). However, there was a significant difference between the intervention and control groups in terms of the mean scores of state anxiety after the intervention based on the Mann-Whitney test (P-value = 0.01). Based on the partial Eta Square (η2) that was 0.1, a moderate effect size was estimated (Table 2).
Table 2.
Determination and comparison of the mean dialysis symptom index and state and trait anxiety between and within the intervention and control groups
| Variable | Group | Test, P-value between | Partial Eta Squared (η2) | Interpreting η2 | ||
|---|---|---|---|---|---|---|
| Intervention Mean (SD) |
Control Mean (SD) |
|||||
| Dialysis symptom index | Pre-intervention | 53.08 (22.18) | 49.38 (25.50) | ta=0.63, P = 0.52 | ||
| Post-intervention | 41.50 (21.32) | 49.50 (25.06) | ta=-1.41, P = 0.16 | 0.03 | Small | |
| Test, P-value within | t b =7.29, P < 0.001 | t b =-0.14, P = 0.88 | ||||
| State anxiety | Pre-intervention | 47.73 (4.53) | 47.85 (4.13) | t a =-0.11, P = 0.91 | ||
| Post-intervention | 45.88 (3.64) | 48.38 (3.63) | Z c =-2.41,P = 0.01 | 0.10 | Medium effect | |
| Test, P-value within | Z d =-3.15, P = 0.002 | Z d=-1.43, P = 0.15 | ||||
| Trait anxiety | Pre-intervention | 45.44 (5.60) | 46.35 (3.78) | Z c =-1.52, 0.12 | ||
| Post-intervention | 43.41 (3.59) | 45.70 (3.52) | Z c =-0.73,P = 0.006 | 0.09 | Medium effect | |
| Test, P-value within | Z d=-2.97, P = 0.003 | Z d=-3.66, P > 0.001 | ||||
a: Independent t-test; b: Paired t-test; c: Mann-Whitney test, d: Wilcoxon test
According to the Wilcoxon test results, there was a statistically significant difference between the mean scores of state anxiety in the intervention group before and after the intervention (P-value = 0.002), revealing the effect of the intervention and reducing state anxiety. However, there was no significant difference between the mean state anxiety scores in the control group before and after the intervention (P-value = 0.15), (Table 2).
Trait anxiety
According to the results of the Mann-Whitney test, the mean trait anxiety was not significantly different between the intervention and control groups before the intervention (P-value = 0.12). Nevertheless, there was a significant difference between both groups in the mean trait anxiety scores after the intervention (P-value = 0.006). Based on the partial Eta Square (η2) that was 0.09, a moderate effect size was estimated (Table 2).
The Wilcoxon test results showed a statistically significant difference between the trait anxiety mean scores in the intervention group before and after the intervention (P-value = 0.003), demonstrating the effect of the intervention and reduction of trait anxiety. Similarly, there was a significant difference between the mean trait anxiety scores in the control group before and after the intervention (P-value < 0.001) as the mean trait anxiety significantly decreased in the control group after the intervention compared to that before the intervention (Table 2).
Dialysis Symptom Index (DSI)
According to the independent t-test results, as shown in Table 2, the mean dialysis symptom index was not significantly different between the intervention and control groups before the intervention (P-value = 0.52). There was no significant difference between the mean dialysis symptom index of the intervention and control groups after the intervention (P-value = 0.16). Based on the partial Eta square (η2) which was 0.03, a small effect size was estimated.
According to the results of the paired t-test, as shown in Table 2, there was a significant difference between the mean dialysis symptom index in the intervention group before and after the intervention (P-value < 0.001), indicating the effect of the intervention and reduction of the dialysis symptom index. Nevertheless, the mean dialysis symptom index had no significant difference in the control group before and after the intervention according to the P-value = 0.88.
As Table 3 shows, no significant difference was found between the intervention and control groups in terms of the prevalence of symptoms burden before the intervention. Moreover, after it, no significant difference was observed between them in the prevalence of symptoms burden except for “feeling anxious” and “dry mouth”.
Table 3.
Comparison of the prevalence of the symptoms burden between the intervention and control groups
| Pre-intervention | Post-intervention | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Intervention | Control | χ2, P-value | Intervention | Control | χ2, P-value | |||||
| Yes n (%) |
No n (%) |
Yes n (%) |
No n (%) |
Yes n (%) |
No n (%) |
Yes n (%) |
No n (%) |
|||
| Constipation | 12 (35.3) | 22 (64.7) | 17 (50.0) | 17 (50.0) | 1.50, 0.22 | 14 (41.2) | 20 (58.8) | 15 (44.1) | 19 (55.9) | 0.06, 0.80 |
| Nausea | 15 (44.1) | 19 (55.9) | 15 (44.1) | 19 (55.9) | 0, > 0.99 | 12 (35.3) | 22 (64.7) | 17 (50.0) | 17 (50.0) | 1.50, 0.22 |
| Vomiting | 8 (23.5) | 26 (76.5) | 7 (20.0) | 27 (79.4) | 0.08, 0.77 | 2 (5.9) | 32 (94.1) | 6(17.6) | 28 (82.4) | 2.26, 0.13 |
| Diarrhea | 11 (32.4) | 23 (67.6) | 5 (14.7) | 29 (85.3) | 2.94, 0.08 | 7 (20.6) | 27 (79.4) | 5 (14.7) | 29 (85.3) | 0.40, 0.52 |
| Decreased appetite | 18 (52.9) | 16 (47.1) | 15 (44.1) | 19 (55.9) | 0.53, 0.46 | 19 (55.9) | 15 (44.1) | 16 (47.1) | 18 (52.9) | 0.53, 0.46 |
| Muscle cramps | 19 (55.9) | 15 944.1) | 16 (47.1) | 18 952.9) | 0.53, 0.46 | 19 (55.9) | 15 (44.1) | 14 (41.2) | 20 (58.8) | 1.47, 0.22 |
| Swelling in legs | 14 (41.2) | 20 (58.8) | 11 (32.4) | 23 (67.6) | 0.56, 0.45 | 14 (41.2) | 20 (58.8) | 11 (32.4) | 23 (67.6) | 0.56, 0.45 |
| Shortness of breath | 8 (23.5) | 26 (76.5) | 8 (23.5) | 26 (76.5) | 0, > 0.99 | 6 (17.6) | 28 (82.4) | 9 (26.5) | 25 (73.5) | 0.77, 0.38 |
| Lightheadedness or dizziness | 11 (32.4) | 23 (67.6) | 11 (32.4) | 23 (67.6) | 0, > 0.99 | 7 (20.6) | 27 (79.4) | 11 (32.4) | 23 (67.6) | 1.20, 0.27 |
| Restless legs | 12 (35.3) | 22 (64.7) | 12 (35.3) | 22 (64.7) | 0, > 0.99 | 10 (29.4) | 24 (70.6) | 11 (32.4) | 23 (67.6) | 0.06, 0.79 |
| Numbness or tingling in feet | 18 (52.9) | 16 (47.1) | 11 (32.4) | 23 (67.6) | 2.94, 0.08 | 18 (52.9) | 16 (47.1) | 13 (38.2) | 21 (61.8) | 1.48, 0.22 |
| Feeling tired or lack of energy | 31 (91.2) | 3 (8.8) | 27 (79.4) | 7 (20.6) | 1.87, 0.17 | 29 (85.3) | 5 (14.7) | 28 (82.4) | 6 (17.6) | 0.10, 0.74 |
| Cough | 11 (32.4) | 23 (67.6) | 10 (29.4) | 24 (70.6) | 0.06, 0.79 | 9 (26.5) | 25 (73.5) | 10 (29.4) | 24 (70.6) | 0.07, 0.78 |
| Dry mouth | 10 (29.4) | 24 (70.6) | 17 (50.0) | 17 (50.0) | 3.01, 0.08 | 9 (26.5) | 25 (73.5) | 17 (50.0) | 17 (50.0) | 3.98, 0.04* |
| Bone or joint pain | 17 (50.0) | 17 (50.0) | 19 (55.9) | 15 (44.1) | 0.23, 0.62 | 16 (47.1) | 18 (52.9) | 19 (55.9) | 15 (44.1) | 0.53, 0.46 |
| Chest pain | 11 (32.4) | 23 (67.6) | 8 (23.5) | 26 (76.5) | 0.65, 0.41 | 8 (23.5) | 26 (76.5) | 9 (26.5) | 25 (73.5) | 0.07, 0.77 |
| Headache | 15 (44.1) | 19 (55.9) | 11 (32.4) | 23 (67.6) | 0.99, 0.31 | 17 (50.0) | 17 (50.0) | 14 (41.2) | 20 (58.8) | 0.53, 0.46 |
| Muscle shortness | 14 (41.2) | 20 (58.8) | 15 (44.1) | 19 (55.9) | 0.06, 0.80 | 10 (29.4) | 24 (70.6) | 17 (50.0) | 17 (50.0) | 3.01, 0.08 |
| Difficulty concentrating | 17 (50.0) | 17 (50.0) | 20 (58.8) | 14 (41.2) | 0.53, 0.46 | 15 (44.1) | 19 (55.9) | 8 (23.5) | 26 (76.5) | 3.21, 0.07 |
| Dry skin | 17 (50.0) | 17 (50.0) | 20 (58.8) | 14 (41.2) | 0.53, 0.46 | 16 (47.1) | 18 (52.9) | 18 (52.9) | 16 (47.1) | 0.23, 0.62 |
| Itching | 21 (61.8) | 13 (38.2) | 15 (44.1) | 19 (55.9) | 2.12, 0.14 | 18 (52.9) | 16 (47.1) | 13 (38.2) | 21 (61.8) | 1.48, 0.22 |
| Worrying | 32 (94.1) | 2 (5.9) | 32 (94.1) | 2 (5.9) | 0, > 0.99 | 26 (76.5) | 8 (23.5) | 30 (88.2) | 4 (11.8) | 1.61, 0.20 |
| Feeling nervous | 22 (64.7) | 12 (35.3) | 23 (67.6) | 11 (32.4) | 0.06, 0.79 | 15 (44.1) | 19 (55.9) | 23 (67.6) | 11 (32.4) | 3.81, 0.05 |
| Trouble falling asleep | 23 (67.6) | 11 (32.4) | 23 (67.6) | 11 (32.4) | 0, > 0.99 | 21 (61.8) | 13 (38.2) | 24 (70.6) | 10 (29.4) | 0.59, 0.44 |
| Trouble staying asleep | 22 (64.7) | 12 (35.3) | 25 (73.5) | 9 (29.5) | 0.62, 0.43 | 21 (61.8) | 13 (38.2) | 26 (76.5) | 8 (23.5) | 1.72, 0.18 |
| Feeling irritable | 28 (82.4) | 6 (17.6) | 23 (67.6) | 11 (32.4) | 1.96, 0.16 | 24 (70.6) | 10 (29.4) | 23 (67.6) | 11 (32.4) | 0.06, 0.79 |
| Feeling sad | 26 (76.5) | 8 (23.5) | 20 (58.8) | 14 (41.2) | 2.41, 0.12 | 22 (64.7) | 12 (35.3) | 21 (61.8) | 13 (38.2) | 0.06, 0.80 |
| Feeling anxious | 30 (88.2) | 4 (11.8) | 26 (76.5) | 8 (23.5) | 1.61, 0.20 | 21 (61.7) | 13 (38.3) | 30 (88.2) | 4 (11.8) | 6.35, 0.01* |
| Decreased interest in sex | 30 (88.2) | 4 (11.8) | 26 (76.5) | 8 (23.5) | 1.61, 0.20 | 30 (88.2) | 4 (11.8) | 28 (82.4) | 6 (17.6) | 0.46, 0.49 |
| Difficulty becoming sexually aroused | 30 (88.2) | 4 (11.8) | 25 (73.5) | 9 (26.5) | 2.37, 0.12 | 30 (88.2) | 4 (11.8) | 28 (82.4) | 6 (17.6) | 0.46, 0.49 |
*significant
As displayed in Table 4, before the intervention, there was no significant difference between the groups regarding the severity of the burden of 30 symptoms except for “difficulty concentrating” in the hemodialysis patients. On the other hand, after the intervention, a significant difference was observed between the groups in the severity of constipation, nausea, vomiting, diarrhea, muscle cramps, swelling in the legs, muscle shortness, worrying, nervousness, anxiety, and trouble staying asleep. The burden of the other 19 symptoms was not different between the groups after the intervention.
Table 4.
Comparison of the severity of the symptoms burden between the intervention and control groups
| Pre-intervention | Post-intervention | |||||
|---|---|---|---|---|---|---|
| Intervention | Control | Test a, P-value | Intervention | Control | Test a, P-value | |
| Mean (SD) | Mean (SD) | Mean (SD) | Mean (SD) | |||
| Constipation | 1.0 (1.49) | 1.41 (1.57) | -1.17, 0.23 | 0.55 (1.0) | 1.41 (1.34) | -3.38, 0.001* |
| Nausea | 1.26 (1.54) | 1.41 (1.74) | -0.26, 0.79 | 0.41 (1.2) | 1.41 (1.30) | -3.29, 0.001* |
| Vomiting | 0.58 (1.31) | 0.52 (1.10) | -0.26, 0.79 | 0.11 (1.1) | 0.76 (1.2) | -2.32, 0.02* |
| Diarrhea | 0.76 (1.18) | 0.44 (1.10) | -1.47, 0.13 | 0.14 (0.60) | 0.79 (1.1) | -2.20, 0.03* |
| Decreased appetite | 1.64 (1.80) | 1.55 (1.90) | -0.31,0.75 | 1.35 (1.41) | 1.55 (1.81) | -0.61, 0.54 |
| Muscle cramps | 1.94 (1.87) | 1.61 (1.84) | -0.76, 0.44 | 0.84 (1.4) | 1.58 (1.60) | -2.00, 0.04* |
| Swelling in legs | 1.17 (1.67) | 0.82 (1.26) | -0.80, 0.42 | 0.44 (1.0) | 1.11 (1.50) | -2.16, 0.03* |
| Shortness of breath | 0.55 (1.10) | 0.70 (1.33) | -0.21, 0.83 | 0.44 (1.02) | 0.76 (1.34) | -0.99, 0.31 |
| Lightheadedness or dizziness | 0.79 (1.27) | 0.79 (1.20) | -0.12, 0.89 | 0.47 (0.96) | 0.73 (1.10) | -1.07, 0.28 |
| Restless legs | 0.91 (1.33) | 1.02 (1.46) | -0.28, 0.77 | 0.73 (1.23) | 0.91 (1.37) | -0.44, 0.65 |
| Numbness or tingling in feet | 1.70 (1.80) | 1.08 (1.65) | -1.42, 0.15 | 1.55 (1.61) | 1.11 (1.53) | -1.14, 0.25 |
| Feeling tired or lack of energy | 3.52 (1.44) | 2.97 (1.80) | -1.19, 0.23 | 2.73 (1.73) | 3.05 (1.68) | -1.27, 0.20 |
| Cough | 0.70 (1.08) | 0.76 (1.25) | -0.008, 0.99 | 0.64 (1.15) | 0.79 (1.29) | -0.42, 0.66 |
| Dry mouth | 1.00 (1.66) | 1.67 (1.88) | -1.64, 0.10 | 0.88 (1.59) | 1.64 (1.75) | -1.86, 0.06 |
| Bone or joint pain | 1.55 (1.76) | 2.05 (1.93) | -1.18, 0.23 | 1.38 (1.57) | 2.05 (1.93) | -1.63, 0.10 |
| Chest pain | 0.85 (1.28) | 0.61 (1.23) | -0.91, 0.35 | 0.55 (1.07) | 0.67 (1.24) | -0.25, 0.79 |
| Headache | 1.38 (1.65) | 1.05 (1.63) | -0.88, 0.37 | 1.32 (1.47) | 1.26 (1.63) | -0.30, 0.76 |
| Muscle shortness | 1.32 (1.73) | 1.35 (1.68) | -0.10, 0.91 | 0.79 (1.00) | 1.52 (1.80) | -2.06, 0.04* |
| Difficulty concentrating | 1.52 (1.69) | 0.52 (1.02) | -2.66, 0.008* | 1.26 (1.56) | 0.52 (1.02) | 2.27, 0.13 b |
| Dry skin | 1.67 (1.90) | 1.79 (1.71) | -0.35, 0.72 | 1.47 (1.82) | 1.67 (1.73) | -0.46, 0.64 |
| Itching | 1.91 (1.69) | 1.50 (1.89) | -1.06, 0.28 | 1.23 (1.32) | 1.20 (1.71) | -0.56, 0.57 |
| Worrying | 3.47 (1.37) | 3.41 (1.25) | -0.17, 0.85 | 2.67 (0.9) | 3.14 (1.0) | -2.03, 0.04* |
| Feeling nervous | 2.00 (1.74) | 2.11 (1.63) | -0.29, 0.77 | 1.26 (1.54) | 2.08 (1.63) | -2.10, 0.03* |
| Trouble falling asleep | 2.47 (1.94) | 2.58 (1.92) | -0.27, 0.78 | 1.91 (1.69) | 2.64 (1.87) | -1.85, 0.06 |
| Trouble staying asleep | 2.41 (1.97) | 2.79 (1.88) | -0.83, 0.40 | 1.26 (1.2) | 2.44 (2.90) | -2.19, 0.03* |
| Feeling irritable | 2.85 (1.61) | 2.41 (1.84) | -0.79, 0.42 | 2.05 (1.51) | 2.41 (1.86) | -1.12, 0.26 |
| Feeling sad | 2.64 (1.79) | 2.05 (1.98) | -1.24, 0.21 | 2.02 (1.69) | 2.14 (1.94) | -0.19, 0.84 |
| Feeling anxious | 3.32 (0.91) | 2.97 (1.42) | -0.78, 0.43 | 2.05 (1.32) | 2.94 (1.39) | -2.71, 0.007* |
| Decreased interest in sex | 3.05 (1.53) | 2.70 (1.80) | -0.67, 0.49 | 2.79 (1.37) | 2.94 (1.68) | -0.80, 0.42 |
| Difficulty becoming sexually aroused | 2.80 (1.69) | 1.50 (0.50) | -0.87, 0.38 | 2.82 (1.42) | 2.94 (1.68) | -0.60, 0.54 |
a Mann-Whitney tests, b ANCOVA and Difficulty concentrating pre-intervention as covariate, * Significant
Discussion
Based on the results of the present study, Melissa officinalis L. (Lemon Balm) essential oil inhalation aromatherapy decreased the state and trait anxiety and symptoms burden in hemodialysis patients. Moreover, using aromatherapy reduced the severity of constipation, nausea, vomiting, diarrhea, muscle cramps, swelling in legs, muscle shortness, worrying, nervousness, anxiety, and trouble staying asleep in ESRD patients undergoing hemodialysis. In addition, the prevalence of feeling anxious and dry mouth reduced after using Melissa officinalis L. (Lemon Balm) inhalation aromatherapy.
This study indicated that Melissa officinalis L. (Lemon Balm) essential oil inhalation aromatherapy reduced state anxiety, which happened in reaction to stressful situation. Moreover, Melissa officinalis L. (Lemon Balm) essential oil inhalation aromatherapy was effective in decreasing trait anxiety which is part of someone’s personality or method of viewing the world. Our findings also showed that the effect of Melissa officinalis L. essential oil inhalation aromatherapy on state and trait anxiety in ESRD patients undergoing hemodialysis was at a moderate level. In a study conducted by Lotfi et al., Melissa officinalis L. inhalation aromatherapy significantly decreased anxiety in hospitalized patients with acute coronary syndrome [52]. Another study indicated that drinking Melissa officinalis L. reduced anxiety in patients undergoing coronary artery bypass surgery [42]. Veiskaramian et al. reported that Melissa officinalis L. essential oil inhalation aromatherapy could decrease stress and regulate hemodynamic changes in patients with acute coronary syndrome in emergency and acute situations [53]. Melissa officinalis L. inhalation aromatherapy reduces anxiety, regulates the cardiovascular response, and reduces the symptoms in patients together with improvements in the balance of the autonomic nervous system in tissues, such as the heart and kidney tissues, and changes in the level of noradrenaline in the blood [53]. A review study reported that Melissa officinalis L. had a potentially wide range of effects on diseases, especially anxiety and central nervous system disorders [50].
Our findings showed that the mean trait anxiety significantly decreased in the control group (sweet al.mond oil inhalation aromatherapy) after the intervention compared to that before the intervention. In a study, it was stated that the anxiety change in the aromatherapy group with lavender (9.9), almond oil (5.3) and in the water group was 3.6 [54]. This suggests that the almond oil can reduce anxiety less than lavender but more than water. Another study indicated that foot massage using sweet al.monds decreased anxiety post-surgery [55]. It is possible that the sweet al.mond oil not only was absorbed through the skin but also entered the olfactory center through inhalation and led to the reduction of trait anxiety.
This study showed that Melissa officinalis L. inhalation aromatherapy was effective in reducing 11 symptoms burden in hemodialysis patients. Based on the literature review, no study has mentioned this finding, and it is a novel finding for hemodialysis patients. Our study indicated Melissa officinalis L. (Lemon Balm) inhalation aromatherapy reduced the prevalence of and severity of feeling anxious and severity of worrying and feeling nervous in hemodialysis patients. A review study reported that this herb was effective in mood, cognition, and memory. This study revealed that these effects were related to neurological effects such as simulation of the acetylcholine and GABAA receptors and inhibition of matrix metallo proteinase-2 [50].
Our study showed that Melissa officinalis L. (Lemon Balm) inhalation aromatherapy reduced the severity of gastrointestinal symptoms such as constipation, nausea, vomiting, and diarrhea in ESRD patients undergoing hemodialysis. A few studies reported the effect of Melissa officinalis L. inhalation on nausea, vomiting, and diarrhea [56]. It was reported that Melissa officinalis L. could be used in colic, diarrhea, and irritable bowel syndrome [56]. Based on our findings, it seems that aromatherapy with Melissa officinalis L. might have anti-inflammatory and antimicrobial effects on the gastrointestinal system. Chromatographic findings in our study showed that 46.16% of Melissa officinalis L. essential oil component was Geranial. This monoterpene has anti-inflammatory, antioxidant, and antimicrobial effects. Geranial stimulates apoptosis and cell cycle rest, regulates target molecules such as p53 and STAT3, triggers the activation of caspases, and controls inflammation [34].
This study revealed that Melissa officinalis L. (Lemon Balm) inhalation aromatherapy reduced the severity of symptoms burden such as trouble staying asleep in hemodialysis patients. Similarly, a study indicated that a combination of Melissa officinalis L. and Nepeta menthoides might improve insomnia [57]. Soltanpour et al. indicated that drinking Melissa officinalis L. improved the sleep quality in patients undergoing coronary artery bypass surgery [42]. By simulation of the acetylcholine and GABAA receptors [50], analgesic effect [33], and potentially calm and anti-spasmodic effects of Melissa officinalis L [38], it may reduce the severity of trouble staying asleep in hemodialysis patients.
This study showed Melissa officinalis L. (Lemon Balm) inhalation aromatherapy reduced the severity of muscle cramps, legs swelling, and muscle shortness in ESRD patients undergoing hemodialysis. It was shown that Melissa officinalis L. had anti-inflammatory effect [58]. Researchers indicated that oral Melissa officinalis L. supplement had anti-inflammatory effect, and C-reactive protein, as a biomarker of inflammation, was lower in chronic stable angina patients who administered this herb compared to the placebo group [58]. Studies indicated that Melissa officinalis L. relieved pain [59], led to calmness, and potentially had anti-spasmodic and anti-inflammatory effects [54]. It is an anti-spam, sedative, painkiller, and tonic inhibition herb [31]. As we reported, citronellal was one of the monoterpenes of Melissa officinalis L. Citronellal and linalool had energy affinity for “α-Synuclein, Adenosine Receptors, Monoamine Oxidase (MAO), and Dopamine D 1 receptor proteins” and reduced Parkinson disease symptoms [35]. It seems that with the mentioned effects, the severity of swelling of the leg, muscle cramps, and shortness of the muscle decreased in ESRD patients undergoing hemodialysis using Melissa officinalis L. (Lemon Balm) inhalation aromatherapy.
Despite the beneficial effects of Melissa officinalis L. (Lemon Balm) inhalation aromatherapy on various symptoms of hemodialysis patients, generalization of the results should be made with caution as there are few clinical studies on its effects on physical and mental dimensions in these patients. Determination of the exact dose and method of using the aroma is a challenge in the use of aromatherapy. Several studies have reported different amounts and methods of using the aroma; hence, more studies, particularly clinical trials with a much larger sample size, are needed to confirm the effects of Melissa officinalis L. (Lemon Balm) inhalation aromatherapy with more certainty.
This clinical trial study had some challenges including knowledge of the safety of Melissa officinalis L. essential oil, clinical protocols, selection of the product, and its administration. To tackle these challenges, an associate professor of Traditional Pharmacy who is a member of the Medicinal Plants Processing Research Center was a member of this research team. The product was prepared by an aromatherapy specialist who was familiar with Melissa officinalis L. and the extraction method in a reliable pharmaceutical company. To ensure the product safety the research assistant was present with the patients throughout the intervention and was ready to answer their phone calls about possible side effects. Given the challenges and findings of this study, using Melissa officinalis L. (Lemon Balm) might be effective in a hemodialysis setting as an implication of this study.
The research limitations included the short duration of the study (20 min in each time), patients’ visits in three separate four-hour cycles per day, fear and anxiety of the patients and the researcher about the COVID-19 pandemic, and quick and correct removal of cotton impregnated with essential oil to prevent the spread of aroma in the place after the intervention. Filling out the forms by the researcher’s assistant might cause bias. Therefore, it is suggested that in another study illiterate patients should be excluded from the study to reduce the risk of researcher bias.
The results of the present study showed that sweet almond oil reduced trait anxiety. To compare its effect on trait anxiety, it is suggested that three groups of almond oil, Melissa officinalis L. (Lemon Balm), and water inhalation aromatherapy should be compared in another study to determine the effect size of each aromatherapy.
Conclusion
The present study demonstrated that Melissa officinalis L. essential oil inhalation aromatherapy decreased the symptoms burden and anxiety in hemodialysis patients. Melissa officinalis L. essential oil inhalation aromatherapy reduced the severity of constipation, nausea, vomiting, diarrhea, swelling in legs, muscle shortness, worrying, and trouble staying asleep. Moreover, this intervention reduced the prevalence of feeling anxious and dry mouth. Thus, it is suggested that healthcare workers should use this intervention. As to evidence-based practice, it is recommended that more studies should evaluate the effect of Melissa officinalis L. aromatherapy on symptoms in ESRD patients undergoing hemodialysis.
Acknowledgements
The present study was extracted from a master’s thesis by Mansoureh Aghababaei at School of Nursing and Midwifery, Shiraz University of Medical Sciences, Iran (Code: 20701). We are deeply grateful to those patients who actively participated in the study, as well as the respected colleagues of the Hemodialysis Department of Imam Reza Clinic and Nemazi Hospital and all individuals who helped us conduct this study. The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and Center for Development of Clinical Research of Nemazee Hospital and Dr. Nasrin Shokrpour for English editorial assistance.
Author contributions
MR, NP, MA and MMZ wrote the main manuscript text. The management of the data analysis was conducted by MR, NP, and MA. MMZ prepared Fig. 2. All authors reviewed and approved the manuscript.
Funding
The study was funded by Vice-chancellor for Research and Technology of Shiraz University of Medical Sciences (Code: 20701).
Data availability
The datasets of this study is available from the first author on reasonable request.
Declarations
Ethics approval and consent to participate
The present study was approved by the Ethics Committee of Shiraz University of Medical Sciences (Code: IR.SUMS.REC.1400.065). The study was performed following the Declaration of Helsinki. All hemodialysis patients signed an informed consent form. The research participants were aware of the research objectives and method, confidentiality of information, side effects of the essential oil, and the right to withdraw from the study; they were assured that there would be no change in their treatment and care. Written and informed consent was obtained from all participants.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets of this study is available from the first author on reasonable request.