Archives of Academic Emergency Medicine. 2022; 10(1): e87 BR I E F RE P O RT Aromatherapy with Isopropyl Alcohol versus Intravenous Ondansetron in Management of Mild Brain Trauma Nau- sea and Vomiting; a Randomized Clinical Trial Behrang Rezvani Kakhki1∗, Tahereh Ghasemi1, Elnaz Vafadar Moradi1, Zahra Abbasi Shaye2, Seyed Mohammad Mousavi1 1. Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Clinical research development center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Received: August 2022; Accepted: September 2022; Published online: 31 October 2022 Abstract: Introduction: Nausea and vomiting are common complaints among patients who refer to the emergency de- partment with head trauma. This study aimed to compare the effect of aromatherapy with isopropyl alcohol versus intravenous ondansetron in management of mild head trauma nausea and vomiting. Methods: This randomized clinical trial was conducted on patients with isolated mild head trauma complaining of nausea and vomiting who were referred to emergency department during a 6-month period. Patients were randomly divided into control (IV ondansetron + aromatherapy with saline) and intervention (IV saline + aromatherapy with iso- propyl alcohol) groups. The frequency of vomiting and the severity of nausea (from 0 to 100 with the verbal scaling) were written before, and 10 and 30 minutes after intervention and compared between groups. Results: A total of 210 patients (105 patients in each group) with a median age of 38 years were included in the study, 112 (54.3%) of which were male. Ten minutes after aromatherapy, no significant difference was observed in nausea and vomiting between the two groups (p >0.05). Nausea score after 30 minutes (p = 0.015) was significantly lower in the intervention group compared to the control group, but vomiting after 30 minutes (p <0.001) was higher in the intervention group. Conclusion: Aromatherapy using isopropyl alcohol significantly reduced nausea of patients with mild isolate head trauma after 30 minutes. Regarding vomiting, no favorable result was observed in this study. However, the frequency of vomiting was reduced in both control and intervention groups. Keywords: Aromatherapy; Odorants; Head Injuries, Closed; Brain Injuries, Traumatic; 2-Propanol Cite this article as: Rezvani Kakhki B, Ghasemi T, Vafadar Moradi E, Abbasi Shaye Z, Mousavi SM. Aromatherapy with Isopropyl Alcohol versus Intravenous Ondansetron in Management of Mild Brain Trauma Nausea and Vomiting; a Randomized Clinical Trial. Arch Acad Emerg Med. 2022; 10(1): e87. https://doi.org/10.22037/aaem.v10i1.1792. 1. Introduction One of the main causes of mortality and disability in persons between the ages of 1 and 45 is a traumatic brain injury (TBI). The most frequent triggers of TBI are trauma, falls, car acci- dents, and sports-related injuries (1, 2). Driving accidents are the most significant and frequent cause of head injuries in Iran and Asia (3, 4). Since the number of patients with head trauma complaints in the emergency room is high and nau- sea and vomiting are common complaints among these pa- ∗Corresponding Author: Behrang Rezvani Kakhki; Department of Emer- gency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. E-mail: rezvanikb@mums.ac.ir, Tel: +989153114371, ORCID: https://orcid.org/0000-0003-3715-6618. tients (5), finding a safe, fast and effective treatment solution in the emergency room is needed and many medications are presented in literature for nausea control, while evidence on post-head trauma nausea is less available (6-9). Aromather- apy is a safe, low-cost, and non-invasive solution, which can complement existing therapeutic strategies. Aromatherapy aims to use scents and aromatic oils by inhalation or even with massage and sometimes orally to eliminate various un- pleasant conditions such as nausea, vomiting, pain, stress, mental restlessness, insomnia, and reaching the desired state (10). Numerous tests have shown that isopropyl alcohol is effective in treating nausea and vomiting after surgery (10). Several animal models have shown the safety of isopropyl al- cohol (11, 12). Human studies have not been conducted after inhalation of isopropyl alcohol (10). In a meta-analysis con- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem B. Rezvani Kakhki et al. 2 ducted by Gong et al. with the aim of evaluating the effect of aromatherapy on anxiety in patients, the results showed that aromatherapy with different essential oils can significantly reduce anxiety regardless of the cause of anxiety. However, the proper dosage of essential oils needs more re- search (13). Since anti-nausea injection treatments have their own concerns, such as lack or absence of drugs, and drug allergies, finding another solution to get rid of these symptoms is useful. In addition, with aromatherapy, the pa- tient can control the symptoms of nausea and vomiting by him/herself, and there is no need for a nurse to be constantly present at the patient’s bedside in the emergency room. Aro- matherapy has been used to control nausea and vomiting for various reasons (14) but no article has been published about the control of nausea and vomiting caused by mild head trauma by aromatherapy, yet. This study aimed to com- pare the effect of aromatherapy with isopropyl alcohol ver- sus intravenous ondansetron in management of nausea and vomiting following mild isolated head trauma. 2. Methods 2.1. Study design and setting The present study is a randomized, single-blind clinical trial that was conducted on patients with nausea and vomiting following isolated mild head trauma, who were referred to the emergency department of Shahid Hashminejad Hospi- tal, Mashhad, Iran, during a 6-month period from December 2019 to June 2020. Before entering the patients in this study, the research pro- cess was explained and informed consent was obtained from them. In all stages of the study, the researchers adhered to the ethical principles of Helsinki Declaration and the confi- dentiality of patient information. All the costs of this project were covered by the researchers and no additional costs were incurred by the patients. This study was approved by the Ethics Committee of Mashhad University of Medical Sciences under the ethical code "IR.MUMS.MEDICAL.REC.1398.840" and registered in the Clinical Trial Center of Iran with the code "IRCT20161226031577N3" 2.2. Participants Patients referring to the emergency room due to isolated head trauma who were complaining from nausea (with severity level 1) and/or vomiting were selected for inclusion. Isolated head trauma could be due to reasons such as an ac- cident where only the patient suffered head trauma, acci- dents at work, or head trauma with a hard object. Patient non-cooperation; Glasgow coma scale (GCS) <13; the pres- ence of neurological defects; patient dissatisfaction; age be- low 14 years; the presence of olfactory defects before the trauma; prescribing medicine to the patient that causes nau- sea or vomiting (such as prescribing narcotics for the pa- tient’s headache); the period of reduced level of conscious- ness less than 30 minutes; any forgetfulness of events be- fore or after the accident (less than 24 hours after the ac- cident); any change in the mental state at the scene of the accident (feeling lost, lack of awareness of time or place or person, confusion); were among the exclusion criteria. In addition, all subjects with missing data were excluded from the study and sampling was continued until reaching the re- quired sample size. 2.3. Intervention Patients were divided into two groups, A and B, based on the table of random numbers. In group A (control), on- dansetron was given intravenously and saline as aromather- apy, and in group B (intervention) saline was administered intravenously and isopropyl alcohol was applied for aro- matherapy with 3 cc sprinkled on a gauze pad, which the pa- tient used to inhale. 2.4. Data gathering All demographic variables of the patient, vital signs of the patient at the time of visit, and the initial outcome after re- ceiving ondansetron or isopropyl alcohol were recorded in a checklist. First, the frequency of vomiting and the severity of nausea was scored from 0 to 100 using Verbal scaling criteria, and then the presence of vomiting and the degree of nausea were evaluated and scored from 0 to 100 using Verbal scaling criteria on 2 other occasions, 10 and 30 minutes later. The difference in the score given by the patient showed the re- sponse to the treatment. The checklist included items such as age and gender of the patients, their medication history, the patient’s vital signs on arrival (O2 Saturation (SAT) and pulse rate (PR) measured by Fingertip Pulse Oximeter, Contec Company, China; Res- piratory rate per minute; and blood pressure measured by OMRON Blood Pressure Monitor, made in Japan), the feeling of nausea before intervention based on Verbal Scaling (from zero to 100, zero showing no feeling of nausea and 100 in- dicating the worst nausea that the person can imagine), and the presence or absence of vomiting before intervention. Vi- tal signs and nausea were measured before and 10 minutes after intervention; presence or absence of nausea and vom- iting were asked at 10 and 30 minutes after intervention. No further follow-ups were conducted after 30 minutes from in- tervention. 2.5. Statistical analysis Based on April et al.’s study (15) that reported mean nausea score of 16±19 in the aromatherapy group and 29±25 in the ondansetron group after intervention based on Visual Ana- logue Scale (VAS), and considering alpha 0.05 and power of This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e87 Table 1: Baseline characteristics of studied participants at the time of admission to emergency department Variable Total Intervention Control P Age (year) Median (Q1-Q3) 38 (25.75-53.25) 35 (25-50) 41 (27-56) 0.122 Gender Male 112 (53.3) 55 (52.4) 57 (54.3) 0.782 Female 98 (46.7) 50 (47.6) 48 (45.7) Vital sign Pulse rate (/min) 70 (64-84) 67 (61.78) 75 (64-86) 0.026 Respiratory rate (/min) 20 (18-24) 22 (18-24) 20 (16-23) 0.003 Oxygen saturation (%) 98 (97-100) 98 (97-100) 98 (97-99) 0.756 SBP (mmHg) 130 (110-140) 130 (110-145) 130 (112-140) 0.312 Nausea score Median (Q1-Q3) 40 (30-60) 50 (30-60) 40 (30-70) 0.916 Vomiting Yes 86 (40.95) 50 (47.6) 36 (34.3) 0.049 No 124 (59.05) 55 (52.4) 69 (65.7) Data are presented as median (interquartile range; IQR) or frequency (%). SBP: Systolic blood pressure. Table 2: Comparison of patients’ studied outcomes between the two groups 10 and 30 minutes after the intervention Outcomes Intervention Control P value Vomiting 10 min Yes 45 (42.9) 32 (30.5) 0.63 No 60 (57.1) 73 (69.5) Vomiting 30 min Yes 40 (38.1) 6 (5.7) 0.001 No 65 (61.9) 99 (94.3) Nausea score 10 min Median (IQR) 40 (20-60) 30 (0-70) 0.95 Nausea score 30 min Median (IQR) 10 (0-30) 20 (0-65) 0.015 Data are presented as median (inter quartile range; IQR) or frequency (%). Min: minutes. 80% in the formula for estimating the mean in two indepen- dent communities, the required sample size was estimated to be 96 people in each group and considering 10% attrition, 105 people were included in each group (Figure 1). After collecting the data, they were entered into SPSS version 22 software and described using appropriate tables, graphs, and indices, and then the chi-square or Fisher test was used to compare qualitative variables in the two groups, if nec- essary. Mann-Whitney test was used to compare quantita- tive variables (according to variable distribution). The signif- icance level in all tests was considered less than 0.05. 3. Results 3.1. Baseline characteristics of studied cases In total, 210 patients were included in the study, 112 (54.3%) were male and the rest were female with a mean age of 38 (IQR=27.5) years. Baseline characteristics of all the study samples are provided in table 1. The vomiting rate had a lower incidence among the controls than among interven- tion group (p = 0.049). Respiratory rate was lower in controls than in intervention group (p = 0.003) and the pulse rate was higher in the control group (p = 0.026). 3.2. Comparing the studied outcomes Nausea after 30 minutes (p = 0.015) in the intervention group was significantly less than = the control group. But vomit- ing after 30 minutes in the intervention group was more than the control group (p < 0.001). While 10 minutes after inter- vention, no significant differences were observed in case of vomiting rate or nausea score (p > 0.05). 32.38% (95% CI: 22.09 - 42.68) of patients experienced vomit- ing after 30 minutes under aromatherapy that they would not have under ondansetron. Based on the number needed to harm (NNH), for every 3.1 (95% CI: 2.3, 4.5) patients treated with aromatherapy, 1 vomiting after 30 minutes will occur beyond those that would have happened under ondansetron. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem B. Rezvani Kakhki et al. 4 Figure 1: The study flowchart. 4. Discussion The present study was conducted in order to investigate the effect of aromatherapy using isopropyl alcohol in compari- son with intravenous ondansetron in controlling nausea and vomiting caused by mild head trauma in patients who re- ferred to the emergency room with isolated head trauma. The results of our study showed that the rate of nausea of the patients, which was similar between the two groups at the be- ginning of the study, was significantly lower in the interven- tion group than in the control group after 30 minutes, and the aromatherapy performed in this group using isopropyl alco- hol had significantly reduced nausea. Of course, this reduc- tion of nausea in the intervention group was not observed af- ter 10 minutes, and probably more than 10 minutes was nec- essary for isopropyl alcohol inhalation to show its effect. Regarding vomiting, as mentioned, the amount of vomiting at the beginning of the study and before aromatherapy or ondansetron administration was higher in the intervention group than in the control group. After 30 minutes of the study, this difference still existed between the two groups. However, the vomiting of the patients was reduced in both the intervention group and the control group; but in the con- trol group, this decrease in the incidence of vomiting was more obvious (from 34% to 5.7%). Apparently, in this study, isopropyl alcohol was not as effective as ondansetron in re- ducing vomiting. Since we did not have a third group (a group without medication) in this study, it is not possible to comment on whether the use of isopropyl alcohol has an ef- fect on reducing vomiting or not. There are similar studies that have shown that isopropyl alcohol has been effective in reducing vomiting, which will be discussed below. Inhalation aromatherapy’s effect has been investigated for nausea control in different settings, ncluding the stem cell transplantation (15), stroke (16), and coronary bypass (17); This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2022; 10(1): e87 but most shreds of evidence are based on the trials of post- operative assessments (10). The literature review did not reveal any study with similar aromatherapy treatment for traumatic brain injury patients. In the case of traumatic brain injury, evidence was limited to some experimental animal models (18). On the other hand, clinical studies on aromatherapy in the emergency room have not separated different causes of nausea. Isopropyl al- cohol has been evaluated as the aromatherapy agent in some studies. In another study conducted in 2018 by Lindblad et al. (19) in Canada, the authors examined 122 adult patients presenting to the emergency department who complained of mild to moderate nausea and vomiting. In most patients, nausea and vomiting were caused by gastroenteritis. The re- sults obtained from this study showed that on a scale of 1 to 100, the rate of nausea after 30 minutes from the start of treatment was 20 in the group of patients who inhaled iso- propyl alcohol and 44 in the group of ondansetron patients. However, there was no significant difference between the two groups in the amount of vomiting and the length of hospital stay among the patients. No harmful side effects were ob- served in any of the groups. The results obtained in this study regarding the nausea of pa- tients were similar to our study and showed the significant effect of isopropyl alcohol in reducing nausea of patients re- ferred to the emergency room. Of course, it is possible that the small sample size in Lindblad et al.’s study has reduced the accuracy of their results. A clinical trial conducted by Candemir et al. (20) showed fas- cinating results, the average score of nausea and vomiting in the intervention group after 2 minutes was significantly lower than the control group. Also, the amount of nausea of the pa- tients in the intervention group was reduced in each of the measured times compared to the previous time. In general, the results obtained from this study were similar to our study and indicate the significant effect of isopropyl al- cohol in reducing nausea among emergency patients. How- ever, the difference between the two studies is that in our study, more time was needed for the anti-nausea effects of isopropyl alcohol to develop. The reason for the difference in the results of the two studies may be related to the differ- ence in the patients included in the study, because in Can- demir’s study, all patients referring to the emergency room with complaints of nausea and vomiting were included in the study, but in our study, only patients with head trauma were included in the study and the trauma patients included in our study may have delayed the use of gauzes impregnated with isopropyl alcohol to deal with the trauma situation by a few minutes, and this issue has led to the delayed appearance of nausea reduction results. In another study conducted in 2018 by April et al. in the United States, the authors divided 122 patients who referred to the emergency room with complaints of nausea and vom- iting into three groups, which included oral ondansetron and inhaled isopropyl alcohol, oral placebo and inhaled isopropyl alcohol, and oral ondansetron and inhaled placebo. The ob- tained results showed that the average reduction of nausea after 30 minutes in patients of three groups (on a 100-point scale) was 30, 32 and 9 units, respectively. Also, in the men- tioned groups, 27.5%, 25% and 45% of patients needed to re- ceive additional medicine to reduce nausea. In April et al. study, as in our study, the positive effect of using isopropyl alcohol to reduce nausea in emergency patients has been re- ported. However, this study did not measure the vomiting rate of the patients. Also, in this study, similar to our study, the nausea of the patients decreased after 30 minutes. Our study had a larger sample size than this study (21). In a 2016 study in the United States, Beadle et al. (22) in- vestigated the effects of inhaled isopropyl alcohol on nausea and vomiting in emergency room patients. In this study, iso- propyl alcohol was used as a placebo in one group of patients, and normal saline was used as a placebo in another group, and their nausea was checked after 10 minutes. 80 patients were included in the final analysis of the study. Median nau- sea among the patients of the isopropyl alcohol group was lower than that of the patients in the placebo group. Also, in- tervention group patients reported more satisfaction. In general, the results of this study were consistent with our study and showed the positive effect of isopropyl alcohol in reducing nausea in patients. Also, considering that in this study, unlike our study, ondansetron was not prescribed for any of the two groups, we can be sure that the effects of re- ducing nausea observed in the intervention group were due to the inhalation of isopropyl alcohol. 5. Limitation This study faced some limitations. First of all, there is a need for a placebo aromatherapy like a device with no essential oils and no effect on humidity for a double blinded method of RCT. Second, this was a single center study the results of which should be generalized to clinic after further larger studies with feasibility studies on implanting aromatherapy devices in emergency department. Third, this study’s sample size was powered for nausea and vomiting that might have affected the results of vital signs assessment. Also, we only followed patients for 30 minutes, which does not seem suffi- cient. 6. Conclusion Aromatherapy using isopropyl alcohol significantly reduced nausea of patients with mild isolate head trauma after 30 minutes. Regarding vomiting, no favorable result was ob- served in this study. However, the frequency of vomiting was This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem B. Rezvani Kakhki et al. 6 reduced in both control and intervention groups. 7. Declarations 7.1. Acknowledgments None. 7.2. Authors’ contributions Mohd Idzwan and Tan Maw Pin designed the protocol on methodology, ethical approval, writing, review and editing the manuscript. Mohd Idzwan also supervised the comple- tion of the manuscript. Nor Hadila was involved in research literature review, gaining ethical approval, sample collection, data analysis, writing and editing the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript. 7.3. Authors’ contribution BRK has designed the study. BRK, TG, and EVM planned the study protocols, samplings, and the interventions. ZAS and SMM collected the data. BRK and TG analyzed data. BRK, EVM, ZAS, and SMM provided the drafts of manuscript. All authors have contributed to revisions and have confirmed fi- nal version. 7.4. Conflict of interest None declared. 7.5. Sources of funding This work is funded by Mashhad University of Medical Sci- ences under the code IR.MUMS.MEDICAL.REC.1398.840; however, the funder has not interfered in any stage of this project. References 1. Werner C, Engelhard K. Pathophysiology of trau- matic brain injury. Brit J of Anest, 2007;99(1):4-9. doi: 10.1093/bja/aem131. 2. Tsang KK, Whitfield PC. Traumatic brain injury: review of current management strategies. Brit J of Oral and Max- illofacl Surg. 2012 Jun 1;50(4):298-308. 3. Khan M, Yaqoob U, Hassan Z, Uddin MM. Emergency Department Referral Profile of Traumatic Brain In- jury Records at a Tertiary Care Hospital of Pakistan. Updat in Emerg Med, 2021, 1(1), 21–27. Retrieved from http://uiemjournal.com/index.php/main/article/view/5. 4. Aghakhani K, Eslami SH, Khara A, Bijandi M. Epidemio- logic study of fall-related head injury in Iran and its com- parison with other countries. Teh Uni Med J TUMS Pub. 2018 Oct 10;76(7):437-45. http://tumj.tums.ac.ir/article- 1-9108-en.html. 5. Sturm JJ, Simon HK, Khan NS, Hirsh DA. The use of ondansetron for nausea and vomiting after head injury and its effect on return rates from the pediatric ED. The Amerc J of Emerg Med. 2013 Jan 1;31(1):166-72. doi: 10.1016/j.ajem.2012.07.002. 6. Ghasemloo, H., Sadeghi, S., Jarineshin, H., Jarineshin, H., Rastgarian, A., Taheri, L., Rasekh Jahromi, A., Mogharab, F., Kalani, N., Roostaei, D., Hatami, N., Vatankhah, M. Control of nausea and vomiting in women un- dergoing cesarean section with spinal anesthesia: A narrative review study on the role of drugs. Iran J of Obs, Gync and Infert, 2021; 24(7): 98-107. doi: 10.22038/ijogi.2021.18990. 7. Malekshoar M, Jarineshin H, Kalani N, Vatankhah M. Comparing the effect of metoclopramide and promethazine on preventing nausea and vomiting after laparoscopic cholecystectomy: A double-blind clinical trial. Koomesh 2021; 23 (2) :203-210 URL: http://koomeshjournal.semums.ac.ir/article-1-6188- fa.html. 8. Kalani N, Damshenas M H, Vagharfard J, Sadeghi S E, Hatami N, Zabetian H. Comparison of the ef- fect of adding dexmedetomidine and fentanyl to bupivacaine on nausea and vomiting in patients undergoing lower extremity orthopedic surgery with spinal anesthesia: A double-blind randomized clinical trial. Koomesh 2022; 24 (3) :313-319 URL: http://koomeshjournal.semums.ac.ir/article-1-7233- fa.html. 9. Jarineshin, H., Sadeghi, S., Malekshoar, M., Sanie Jahromi, M., Rahmanian, F., Hatami, N., Kalani, N. Non- pharmacological methods of controlling nausea and vomiting during pregnancy in Iran: A narrative review study. Iran J of Obs, Gync and Infert, 2022; 24(12): 110- 123. doi: 10.22038/ijogi.2022.19765. 10. Hines S, Steels E, Chang A, Gibbons K. Aromather- apy for treatment of postoperative nausea and vom- iting. Coch data of sys rev. 2018;3(3):Cd007598. doi: 10.1002/14651858.CD007598.pub3. 11. Gill MW, Burleigh-Flayer HD, Strother DE, Masten LW, McKee RH, Tyler TR, Gardiner TH. Isopropanol: acute va- por inhalation neurotoxicity study in rats. J of App Toxi- col. 1995 Mar;15(2):77-84. doi: 10.1002/jat.2550150204. 12. Ohashi Y, Nakai Y, Ikeoka H, Koshimo H, Esaki Y, Horiguchi S, et al. An experimental study on the res- piratory toxicity of isopropyl alcohol. J App Toxicol, 1988;8(1):67-71. doi: 10.1002/jat.2550080111. 13. Gong M, Dong H, Tang Y, Huang W, Lu F. Effects of aromatherapy on anxiety: A meta-analysis of ran- domized controlled trials. Journal of affective disorders. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 7 Archives of Academic Emergency Medicine. 2022; 10(1): e87 2020;274:1028-40. doi: 10.1016/j.jad.2020.05.118. 14. Hunt R, Dienemann J, Norton HJ, Hartley W, Hud- gens A, Stern T, et al. Aromatherapy as treat- ment for postoperative nausea: a randomized trial. Anest and Analg. 2013;117(3):597-604. doi: 10.1213/ANE.0b013e31824a0b1c. Epub 2012 Mar 5. 15. Izgu N, Yayla EM, Ozdemir L, Gemalmaz A. Inhala- tion aromatherapy on nausea, vomiting and anxiety during autologous hematopoietic stem cell transplan- tation: An open-label randomized controlled trial. Europ J of Integ Med. 2020 Apr 1;35:101091. DOI: 10.1016/j.eujim.2020.101091. 16. Contrada M, Cerasa A, Tonin P, Bagetta G, Scuteri D. Aro- matherapy in stroke patients: is it time to begin?. Front in Behav Neurosci. 2021 Dec 8;15:749353. Doi: 10.3389/fn- beh.2021.749353. 17. Bikmoradi, A., Seifi, Z., Poorolajal, J., Araghchian, M., Safiaryan, R. and Oshvandi, K., 2015. Effect of inhala- tion aromatherapy with lavender essential oil on stress and vital signs in patients undergoing coronary artery bypass surgery: A single-blinded randomized clinical trial. Comp Therap in Med, 23(3), pp.331-338. doi: 10.1016/j.ctim.2014.12.001. 18. Abbasloo E, Dehghan F, Khaksari M, Najafipour H, Vahidi R, Dabiri S, Sepehri G, Asadikaram G. The anti- inflammatory properties of Satureja khuzistanica Jamzad essential oil attenuate the effects of traumatic brain injuries in rats. Sci Rep. 2016 Aug 18;6(1):1-2. Doi: 10.1038/srep31866. 19. Lindblad AJ, Ting R, Harris K. Inhaled isopropyl alco- hol for nausea and vomiting in the emergency depart- ment. Can Fam Physician. 2018;64(8):580. Retrieved from https://www.ncbi.nlm.nih.gov/ pubmed/30108075. 20. Candemir H, Akoglu H, Sanri E, Onur O, Denizbasi A. Iso- propyl alcohol nasal inhalation for nausea in the triage of an adult emergency department. Amerc J of Emerg Med. 2021;41:9-13. doi: 10.1016/j.ajem.2020.12.052. 21. April MD, Oliver JJ, Davis WT, Ong D, Simon EM, Ng PC, Hunter CJ. Aromatherapy versus oral on- dansetron for antiemetic therapy among adult emer- gency department patients: a randomized controlled trial. Ann Emerg Med. 2018 Aug 1;72(2):184-93. doi: 10.1016/j.annemergmed.2018.01.016. Epub 2018 Feb 17. 22. Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ. Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Con- trolled Trial. Ann Emerg Med. 2016;68(1):1-9.e1. doi: 10.1016/j.annemergmed.2015.09.031. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Limitation Conclusion Declarations References