Prophylaxis of opioid-induced nausea in helicopter emergency medical service: a prospective quasi-experimental study

Prophylaxis of opioid-induced nausea in helicopter emergency medical service: a prospective quasi-experimental study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prophylaxis of opioid-induced nausea in helicopter emergency medical service: a prospective quasi-experimental study Jürgen Knapp, Robin Strohm, Markus Huber, Roland Albrecht, Urs Pietsch This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8582728/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objective In prehospital emergency medicine, opioids are usually used to treat acute traumatic pain. A common side effect of opioids is nausea. To prevent this, the prophylactic administration of 5-HT 3 antagonists such as ondansetron has become established in clinical practice, even though there is currently no evidence to support its use. Aromatherapy is also used as an alternative non-pharmacological method for the treatment of nausea. We therefore investigated whether the prophylactic administration of ondansetron or prophylactic aromatherapy after opioid administration is beneficial to the patient. Methods Patients over the age of 16 who received opioid therapy due to acute traumatic pain by the crews of a total of six HEMS bases between February 2024 and April 2025 were prospectively included. Nausea prophylaxis after opioid-based pain therapy was performed according to a fixed rotating 7-day schedule: no nausea prophylaxis, medication-based nausea prophylaxis with ondansetron 4 mg intravenously, and aromatherapy-based nausea prophylaxis by inhalation of isopropanol. A nausea score was evaluated at the time of opioid administration and upon handover at the destination hospital, using a numeric rating scale (NRS) between 0 (no nausea) and 10 (maximum nausea). Primary endpoint was the change in NRS between the time before opioid administration and the time of patient handover at the emergency department. Secondary endpoints were incidence of moderate and severe nausea (defined as an NRS > 3), the incidence of vomiting during prehospital patient care and need of rescue medication (ondansetron for therapeutic use). Results A total of 205 patients were included in the analysis. Eighty-six in the “no prophylaxis” group, 64 in the ondansetron group, and 55 in the aromatherapy group. There was no difference between the groups in terms of changes in nausea before opioid administration compared to the time of hospital admission as well as in the incidence of moderate and severe nausea. Therapeutic administration of ondansetron was necessary in 4 patients in the “no prophylaxis” group and in one patient in the aromatherapy group. None of the patients experienced any improvement in nausea as a result, three of these patients from the “no prophylaxis” group vomited after ondansetron administration. Conclusion Neither the prophylactic administration of ondansetron nor aromatherapy seem to be beneficial for the prevention of opioid-induced nausea in unselected patients in the setting of prehospital emergency medicine. Larger randomized controlled trials are needed to clarify whether certain subgroups may benefit. Trial registration: not applicable prehospital emergency medicine HEMS nausea prophylaxis pain management opioids Figures Figure 1 Background The use of opioids is widespread in prehospital emergency medicine to provide adequate analgesia. 1 – 3 Previous studies have shown an incidence of opioid-induced nausea in emergency department patients between 2 and 20%. 4 Nausea not only significantly impairs patient comfort, but can also lead to tachycardia and blood pressure fluctuations or vomiting, with the risk of aspiration or delays of rescue process and thus a clinical safety hazard to the patient. The prophylactic administration of antiemetics (especially 5-HT 3 antagonists as ondansetron) in the context of pain therapy with opioids has become widely established in prehospital emergency medicine. However, this indication is an off-label use with no evidence of its effectiveness in this setting and was simply transferred from recommendations for in-hospital anesthesia for prophylaxis of postoperative nausea and vomiting (PONV) after general anesthesia. On the other hand, there is evidence from randomized controlled trials and a meta-analysis that aromatherapy through inhalation of isopropyl alcohol is superior in relief of nausea especially in the postoperative and emergency department setting compared to 5-HT 3 antagonists. 5 – 7 This method is extremely cost-effective and easily available, as the patient simply has to sniff a disinfectant swab, and has no known side effects. So, some colleagues have adopted this method in their daily practice, even though data on its effectiveness for prophylactic use is still lacking. We therefore conducted a prospective quasi-experimental study to determine whether any of these prophylactic measures are effective in preventing opioid-induced nausea in the setting of helicopter emergency medicine service (HEMS). Methods Study design and participants The study was conducted at three HEMS bases of Swiss Air Rescue Rega between February 2024 and April 2025 and between June 2024 and April 2025 at three additional bases. Adult patients over the age of 16 who received opioid therapy due to acute traumatic pain were included. Exclusion criteria were life-threatening conditions, head injuries with neurological impairment, allergies to the prophylactic medications, and the patient's refusal to use disinfectant swabs for prophylactic aromatherapy. A nausea score between 0 and 10 was evaluated immediately before opioid administration and upon handover at the destination hospital, with 0 corresponding to no nausea and 10 to maximum nausea, subjectively assessed using a numeric rating scale (NRS). Procedures The following three procedures were applied after opioid-based pain therapy according to a fixed rotating 7-day schedule: no nausea prophylaxis in week one, medication-based nausea prophylaxis with ondansetron 4 mg intravenously in week two, and aromatherapy-based nausea prophylaxis by inhalation of isopropanol in week three. The patients in the aromatherapy group sniffed a disinfectant swab (SOFTA Swabs Reinigungstupfer, B. Braun, Melsungen, Germany), containing 80% isopropanol. They were instructed to take 3–5 deep breaths at a distance of 1–2 cm from the nose, repeated as needed after 10 minutes. Therapeutic administration of ondansetron was permitted at any time in the aromatherapy as well as in the “no prophylaxis” group if the patient complained of increasing or severe nausea after receiving opioids, according to the assessment of the treating team. All interventions, severity of nausea (NRS), vomiting, and need of rescue medication were documented prospectively in accordance with the study protocol and reviewed monthly by an external evaluator. All data and patient details were extracted from the corresponding mission logs in the Rega database in a fully de-identified, anonymized, and non-traceable format. Outcomes The primary endpoint was the change in NRS between the time before opioid administration and the time of patient handover at the emergency department. Secondary endpoints were incidence of moderate and severe nausea (defined as an NRS > 3) at the time of patient handover, the incidence of vomiting during prehospital patient care and need of rescue medication (ondansetron for therapeutic use). Ethics The study was approved by the EKOS Ethics Committee (EKOS23/220). Statistical analysis We estimated a sample size of 40 patients per group based on a previous randomized controlled trial on the therapeutic use of ondansetron and aromatherapy in an emergency department setting. 6 In terms of descriptive statistics, categorical variables were summarized with counts und frequencies and numerical variables with medians and interquartile ranges. Unadjusted group comparisons were based on standard statistical tests: chi-square tests or Fisher’s exacts test for categorical variables and Kruskal-Wallis tests for numerical variables. The dichotomous outcome discriminating between patients with an increase in their nausea score (NRS hospital arrival - NRS before opioids >0) and those whose nausea score remained unchanged or improved (NRS hospital arrival - NRS before opioids ≤0) was examined by means of logistic regression model with treatment, age, sex and ketamine administration as covariates. Given the exploratory nature of the secondary outcomes, no P -value adjustment for multiple comparisons was performed. All computations were performed with R version 4.4.2. Results A total of 205 participants were included in the analysis (“no prophylaxis” group n = 86, ondansetron group n = 64, aromatherapy group n = 55). The groups did not differ with respect to age, sex, or baseline nausea scores ( Table 1 ). Table 1 Demographics, numeric rating scale (NRS) of nausea, primary outcome and secondary outcomes. All Aromatherapy No prophylaxis Ondansetron P n = 205 n = 55 n = 85 n = 65 Demographics Age (years) 51 [33;61] 47 [34;59] 54 [38;62] 49 [30;61] 0.404 Sex (female) 98 (47.8%) 29 (52.7%) 36 (42.4%) 33 (50.8%) 0.412 Mono-trauma (Yes) 192 (93.7%) 53 (96.4%) 81 (95.3%) 58 (89.2%) 0.255 Ketamine (Yes): 29 (14.1%) 12 (21.8%) 10 (11.8%) 7 (10.8%) 0.159 NRS NRS before opioids NRS (original scale) 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.502 NRS > 0 38 (18.5%) 12 (21.8%) 13 (15.3%) 13 (20.0%) 0.584 NRS hospital arrival NRS (original scale) 0.0 [0.0;1.0] 0.0 [0.0;1.5] 0.0 [0.0;0.0] 0.0 [0.0;2.0] 0.851 NRS > 0 57 (27.8%) 17 (30.9%) 21 (24.7%) 19 (29.2%) 0.692 NRS > 3 25 (12.2%) 6 (10.9%) 12 (14.1%) 7 (10.8%) 0.778 Primary outcome Change in NRS NRS (original scale) 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.0 [0.0;0.0] 0.217 NRS (categorical scale) 0.969 Δ (NRS hospital arrival - NRS before opioids ) ≤ 0 175 (85.4%) 47 (85.5%) 72 (84.7%) 56 (86.2%) Δ (NRS hospital arrival - NRS before opioids ) > 0 30 (14.6%) 8 (14.5%) 13 (15.3%) 9 (13.8%) Secondary outcomes Rescue (Yes): 5 (2.4%) 1 (1.8%) 4 (4.7%) n.a. 0.179 Vomitus (Yes): 4 (2.0%) 0 (0.0%) 3 (3.5%) 1 (1.5%) 0.467 NRS: numeric rating scale There was no difference between the groups in terms of a worsening of nausea scores or unchanged or improved nausea scores before opioid administration compared to the time of hospital admission (Table 1 and Fig. 1 ). Incidence of moderate and severe nausea (NRS > 3) on hospital admission was 12% (14% in female patients, 10% in male patients). An increase of NRS after opioid administration was observed in 20% of female patients and 10% of male patients. Therapeutic administration of ondansetron (in the sense of a “rescue medication”) was necessary in 4 patients in the “no prophylaxis” group and in one patient in the aromatherapy group. None of the patients experienced any improvement in nausea afterwards, three of these patients from the “no prophylaxis” group vomited after “rescue” ondansetron administration. Logistic regression analysis is shown in Table 2 . Neither type of prophylactic treatment, nor sex or administration of ketamine appear to have any influence on outcome. Only with regard to age do younger patients appear to have a higher odds ratio for a deterioration in nausea scores. Table 2 Logistic regression analysis of unchanged or improved nausea score (NRS hospital arrival - NRS before opiods ≤0) with treatment, age, sex and ketamine administration as covariates. Unadjusted Adjusted Characteristic OR 95% CI P OR 95% CI P Treatment Aroma — — — — No prophylaxis 0.94 0.35, 2.41 > 0.9 0.98 0.35, 2.61 > 0.9 Ondansetron 1.06 0.37, 2.98 > 0.9 1.05 0.36, 3.05 > 0.9 Age (Years) 0.97 0.95, 1.0 0.023 Sex (Male vs. Female) 1.98 0.89, 4.59 0.10 Ketamine (Yes vs. No) 1.08 0.37, 3.96 0.9 CI = Confidence Interval, OR = Odds Ratio Discussion To our knowledge, this is the first study to evaluate the effectiveness of different prophylactic strategies for opioid-induced nausea in the setting of prehospital emergency medicine. Overall incidence of nausea and was high in our group of patients receiving prehospital opioid-based pain therapy for mainly mono-trauma. One reason for the higher incidence than in the emergency room could be the additional effect of motion sickness caused by the typically backward, reclining transport in the helicopter, without the possibility of looking outside, which typically reduces motion sickness. Our findings demonstrated no significant benefit from either pharmacologic prophylaxis or aromatherapy. In concordance to our results, previous studies also found that prophylactic intravenous antiemetics do not make a significant difference in decreasing opioid-induced nausea and vomiting in the setting of emergency departments. 4 , 8 Also, the therapeutic use of ondansetron for opioid-induced nausea and vomiting was found to be ineffective compared to placebo. 9 This corresponds with our findings that none of the five patients who received ondansetron for therapeutic purposes after complaining about increasing or severe nausea experienced a reduction in nausea, and three of these patients even had to vomit later on. No data is currently available on the prophylactic use of aromatherapy to prevent opioid-induced nausea. According to our findings, aromatherapy does not appear to be beneficial in this regard. Existing data on the therapeutic use of aromatherapy for PONV is inconsistent. In ambulatory surgery patients one study found no difference in the rate of PONV with aromatherapy, whereas another study showed a significant reduction. 10 , 11 The results for female patients after gynecological surgery (proofing a benefit from aromatherapy) are similarly contradictory when compared to female patients after general surgery (where no benefit could be demonstrated). 12 , 13 Although, according to the regression analysis, gender does not appear to be a significant influencing factor, given the magnitude of a possible effect between males and females – despite its large uncertainty – warrants further investigation. Numerous studies have shown that women are more likely to experience nausea and vomiting when given opioids. 14 – 17 Therefore, further studies should investigate whether female patients in particular may benefit from nausea prophylaxis in the context of opioid administration. According to existing data, also the subgroup of patients with known motion sickness and known history nausea after opioid use, may benefit from administration of prophylactic antiemetics when being treated with parenteral opioids. 8 Our findings regarding age also correspond with in-hospital experience regarding PONV, which young adults suffer from more frequently than older people. 15 – 17 The placebo effect may play a significant role in the treatment of nausea and PONV. 10 We informed patients receiving both drug prophylaxis and aromatherapy that the aim of this measure was to prevent opioid-induced nausea. However, despite this possible placebo effect in the ondansetron and aromatherapy group, we saw no advantage over the group without prophylaxis. Limitations The study has several limitations. For example, we could not rule out the influence of certain confounding factors, such as the susceptibility to motion sickness, the type of injury, the duration of transport, and the transport position (lying down facing backwards or sitting facing forwards). We also did not document how reliably the patients actually used the aromatherapy and inhaled deeply with the disinfectant swab directly in front of the nose. On the other hand, this reflects the practicality of the prophylactic aromatherapy in a real prehospital setting. Conclusion Based on our evaluation, neither the prophylactic administration of ondansetron nor aromatherapy were beneficial for the prevention of opioid-induced nausea in unselected patients in the setting of prehospital emergency medicine. Routine nausea prophylaxis with parenteral administration of opioids therefore does not appear to be indicated. Larger randomized controlled trials are needed to clarify whether certain subgroups may benefit. Declarations Ethics approval and consent to participate The study was approved by the EKOS Ethics Committee (EKOS23/220). Consent to participate was waived due to a retrospective, anonymized evaluation of the data. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests Funding None References Pietsch U, Strapazzon G, Ambuhl D, Lischke V, Rauch S, Knapp J. Challenges of helicopter mountain rescue missions by human external cargo: need for physicians onsite and comprehensive training. Scand J Trauma Resusc Emerg Med. 2019;27:17. Scharonow O, Vilcane S, Weilbach C, Scharonow M. Analgesic Therapy with the Opioids Fentanyl and Morphine by Ambulance Personnel in Rural Areas: An Observational Study Over 7 Years. J Pain Res. 2024;17:345–55. Thomas SH, Shewakramani S. Prehospital trauma analgesia. J Emerg Med. 2008;35:47–57. Culver MA, Richards EC, Jarrell DH, Edwards CJ. Use of Prophylactic Ondansetron with Intravenous Opioids in Emergency Department Patients: A Prospective Observational Pilot Study. J Emerg Med. 2017;53:629–34. Kimber JS, Kovoor JG, Glynatsis JM et al. Isopropyl alcohol inhalation versus 5-HT(3) antagonists for treatment of nausea: a meta-analysis of randomised controlled trials. Eur J Clin Pharmacol 2023. April MD, Oliver JJ, Davis WT, et al. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial. Ann Emerg Med. 2018;72:184–93. Hines S, Steels E, Chang A, Gibbons K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2018;3:CD007598. Rowland KD, Fuehrer J, Motov SM, Vilke G, Rosenbaum SB, Quenzer F. Should Antiemetics be Given Prophylactically with Intravenous Opioids While Treating Acute Pain in the Emergency Department? Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee. J Emerg Med. 2020;58:706–9. Ishihara M, Ikesue H, Matsunaga H, et al. A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction. Clin J Pain. 2012;28:373–81. Anderson LA, Gross JB. Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea. J Perianesth Nurs. 2004;19:29–35. Merritt BA, Okyere CP, Jasinski DM. Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting. Nurs Res. 2002;51:125–8. Ferruggiari L, Ragione B, Rich ER, Lock K. The effect of aromatherapy on postoperative nausea in women undergoing surgical procedures. J Perianesth Nurs. 2012;27:246–51. Tate S. Peppermint oil: a treatment for postoperative nausea. J Adv Nurs. 1997;26:543–9. Simensen R, Fjose LO, Thorsen K et al. Comparison of inhalational methoxyflurane, intranasal fentanyl, and intravenous morphine for treatment of prehospital acute pain in Norway (PreMeFen): a randomised, non-inferiority, three-arm, phase 3 trial. Lancet 2025. Apfel CC, Greim CA, Goepfert C, et al. [Postoperative vomiting. A score for prediction of vomiting risk following inhalation anesthesia]. Anaesthesist. 1998;47:732–40. Apfel CC, Greim CA, Haubitz I, et al. The discriminating power of a risk score for postoperative vomiting in adults undergoing various types of surgery. Acta Anaesthesiol Scand. 1998;42:502–9. Gan TJ, Jin Z, Ayad S et al. Fifth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting: Executive Summary. Anesth Analg 2025. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 06 Mar, 2026 Reviews received at journal 06 Mar, 2026 Reviews received at journal 02 Mar, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers invited by journal 19 Jan, 2026 Editor assigned by journal 12 Jan, 2026 Submission checks completed at journal 12 Jan, 2026 First submitted to journal 12 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8582728","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":576909706,"identity":"c1203979-e09a-49d6-a1c3-32a82541e0bf","order_by":0,"name":"Jürgen 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1","display":"","copyAsset":false,"role":"figure","size":332300,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in numeric rating scale of nausea between the timepoint immediately before opioid administration compared to the time of hospital admission in the group treated with ondansetron prophylactically, no nausea prophylaxis and “aromatherapy” for nausea prophylaxis. No differences between the groups.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8582728/v1/239ffb48f95bc598fc2b0ff8.png"},{"id":102397352,"identity":"3cf8ed99-f804-493e-8a86-186951c69f60","added_by":"auto","created_at":"2026-02-11 10:15:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":988392,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8582728/v1/6867d607-dbd3-4005-8f5d-84d3354830cd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prophylaxis of opioid-induced nausea in helicopter emergency medical service: a prospective quasi-experimental study","fulltext":[{"header":"Background","content":"\u003cp\u003eThe use of opioids is widespread in prehospital emergency medicine to provide adequate analgesia.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Previous studies have shown an incidence of opioid-induced nausea in emergency department patients between 2 and 20%.\u003csup\u003e4\u003c/sup\u003e Nausea not only significantly impairs patient comfort, but can also lead to tachycardia and blood pressure fluctuations or vomiting, with the risk of aspiration or delays of rescue process and thus a clinical safety hazard to the patient.\u003c/p\u003e \u003cp\u003eThe prophylactic administration of antiemetics (especially 5-HT\u003csub\u003e3\u003c/sub\u003e antagonists as ondansetron) in the context of pain therapy with opioids has become widely established in prehospital emergency medicine. However, this indication is an off-label use with no evidence of its effectiveness in this setting and was simply transferred from recommendations for in-hospital anesthesia for prophylaxis of postoperative nausea and vomiting (PONV) after general anesthesia. On the other hand, there is evidence from randomized controlled trials and a meta-analysis that aromatherapy through inhalation of isopropyl alcohol is superior in relief of nausea especially in the postoperative and emergency department setting compared to 5-HT\u003csub\u003e3\u003c/sub\u003e antagonists.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e This method is extremely cost-effective and easily available, as the patient simply has to sniff a disinfectant swab, and has no known side effects. So, some colleagues have adopted this method in their daily practice, even though data on its effectiveness for prophylactic use is still lacking.\u003c/p\u003e \u003cp\u003eWe therefore conducted a prospective quasi-experimental study to determine whether any of these prophylactic measures are effective in preventing opioid-induced nausea in the setting of helicopter emergency medicine service (HEMS).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThe study was conducted at three HEMS bases of Swiss Air Rescue Rega between February 2024 and April 2025 and between June 2024 and April 2025 at three additional bases. Adult patients over the age of 16 who received opioid therapy due to acute traumatic pain were included. Exclusion criteria were life-threatening conditions, head injuries with neurological impairment, allergies to the prophylactic medications, and the patient's refusal to use disinfectant swabs for prophylactic aromatherapy. A nausea score between 0 and 10 was evaluated immediately before opioid administration and upon handover at the destination hospital, with 0 corresponding to no nausea and 10 to maximum nausea, subjectively assessed using a numeric rating scale (NRS).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eThe following three procedures were applied after opioid-based pain therapy according to a fixed rotating 7-day schedule: no nausea prophylaxis in week one, medication-based nausea prophylaxis with ondansetron 4 mg intravenously in week two, and aromatherapy-based nausea prophylaxis by inhalation of isopropanol in week three. The patients in the aromatherapy group sniffed a disinfectant swab (SOFTA Swabs Reinigungstupfer, B. Braun, Melsungen, Germany), containing 80% isopropanol. They were instructed to take 3\u0026ndash;5 deep breaths at a distance of 1\u0026ndash;2 cm from the nose, repeated as needed after 10 minutes.\u003c/p\u003e \u003cp\u003eTherapeutic administration of ondansetron was permitted at any time in the aromatherapy as well as in the \u0026ldquo;no prophylaxis\u0026rdquo; group if the patient complained of increasing or severe nausea after receiving opioids, according to the assessment of the treating team.\u003c/p\u003e \u003cp\u003eAll interventions, severity of nausea (NRS), vomiting, and need of rescue medication were documented prospectively in accordance with the study protocol and reviewed monthly by an external evaluator. All data and patient details were extracted from the corresponding mission logs in the Rega database in a fully de-identified, anonymized, and non-traceable format.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was the change in NRS between the time before opioid administration and the time of patient handover at the emergency department. Secondary endpoints were incidence of moderate and severe nausea (defined as an NRS\u0026thinsp;\u0026gt;\u0026thinsp;3) at the time of patient handover, the incidence of vomiting during prehospital patient care and need of rescue medication (ondansetron for therapeutic use).\u003c/p\u003e\n\u003ch3\u003eEthics\u003c/h3\u003e\n\u003cp\u003e The study was approved by the EKOS Ethics Committee (EKOS23/220).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eWe estimated a sample size of 40 patients per group based on a previous randomized controlled trial on the therapeutic use of ondansetron and aromatherapy in an emergency department setting.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn terms of descriptive statistics, categorical variables were summarized with counts und frequencies and numerical variables with medians and interquartile ranges. Unadjusted group comparisons were based on standard statistical tests: chi-square tests or Fisher\u0026rsquo;s exacts test for categorical variables and Kruskal-Wallis tests for numerical variables. The dichotomous outcome discriminating between patients with an increase in their nausea score (NRS\u003csub\u003ehospital arrival\u003c/sub\u003e - NRS\u003csub\u003ebefore opioids\u003c/sub\u003e \u0026gt;0) and those whose nausea score remained unchanged or improved (NRS\u003csub\u003ehospital arrival\u003c/sub\u003e - NRS\u003csub\u003ebefore opioids\u003c/sub\u003e \u0026le;0) was examined by means of logistic regression model with treatment, age, sex and ketamine administration as covariates.\u003c/p\u003e \u003cp\u003eGiven the exploratory nature of the secondary outcomes, no \u003cem\u003eP\u003c/em\u003e-value adjustment for multiple comparisons was performed. All computations were performed with R version 4.4.2.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 205 participants were included in the analysis (\u0026ldquo;no prophylaxis\u0026rdquo; group n\u0026thinsp;=\u0026thinsp;86, ondansetron group n\u0026thinsp;=\u0026thinsp;64, aromatherapy group n\u0026thinsp;=\u0026thinsp;55). The groups did not differ with respect to age, sex, or baseline nausea scores \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics, numeric rating scale (NRS) of nausea, primary outcome and secondary outcomes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAromatherapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo prophylaxis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOndansetron\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;205\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;55\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;85\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;65\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDemographics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 [33;61]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 [34;59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 [38;62]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49 [30;61]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e (female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98 (47.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (52.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (50.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMono-trauma\u003c/b\u003e (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192 (93.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (96.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81 (95.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58 (89.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKetamine\u003c/b\u003e (Yes):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.159\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNRS\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNRS before opioids\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS (original scale)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.584\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNRS hospital arrival\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS (original scale)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0 [0.0;1.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 [0.0;1.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 [0.0;2.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (27.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (30.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (24.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (29.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.692\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS\u0026thinsp;\u0026gt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePrimary outcome\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in NRS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS (original scale)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 [0.0;0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS (categorical scale)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔ (NRS\u003csub\u003ehospital arrival\u003c/sub\u003e - NRS\u003csub\u003ebefore opioids\u003c/sub\u003e)\u0026thinsp;\u0026le;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175 (85.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (84.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56 (86.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔ (NRS\u003csub\u003ehospital arrival\u003c/sub\u003e - NRS\u003csub\u003ebefore opioids\u003c/sub\u003e)\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSecondary outcomes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRescue\u003c/b\u003e (Yes):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVomitus\u003c/b\u003e (Yes):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.467\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNRS: numeric rating scale\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere was no difference between the groups in terms of a worsening of nausea scores or unchanged or improved nausea scores before opioid administration compared to the time of hospital admission (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Incidence of moderate and severe nausea (NRS\u0026thinsp;\u0026gt;\u0026thinsp;3) on hospital admission was 12% (14% in female patients, 10% in male patients). An increase of NRS after opioid administration was observed in 20% of female patients and 10% of male patients.\u003c/p\u003e \u003cp\u003eTherapeutic administration of ondansetron (in the sense of a \u0026ldquo;rescue medication\u0026rdquo;) was necessary in 4 patients in the \u0026ldquo;no prophylaxis\u0026rdquo; group and in one patient in the aromatherapy group. None of the patients experienced any improvement in nausea afterwards, three of these patients from the \u0026ldquo;no prophylaxis\u0026rdquo; group vomited after \u0026ldquo;rescue\u0026rdquo; ondansetron administration.\u003c/p\u003e \u003cp\u003eLogistic regression analysis is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Neither type of prophylactic treatment, nor sex or administration of ketamine appear to have any influence on outcome. Only with regard to age do younger patients appear to have a higher odds ratio for a deterioration in nausea scores.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression analysis of unchanged or improved nausea score (NRS\u003csub\u003ehospital arrival\u003c/sub\u003e - NRS\u003csub\u003ebefore opiods\u003c/sub\u003e \u0026le;0) with treatment, age, sex and ketamine administration as covariates.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnadjusted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAdjusted\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAroma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo prophylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35, 2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.35, 2.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOndansetron\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37, 2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.36, 3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (Years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95, 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e (Male vs. Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.89, 4.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKetamine\u003c/b\u003e (Yes vs. No)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.37, 3.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCI\u0026thinsp;=\u0026thinsp;Confidence Interval, OR\u0026thinsp;=\u0026thinsp;Odds Ratio\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study to evaluate the effectiveness of different prophylactic strategies for opioid-induced nausea in the setting of prehospital emergency medicine. Overall incidence of nausea and was high in our group of patients receiving prehospital opioid-based pain therapy for mainly mono-trauma. One reason for the higher incidence than in the emergency room could be the additional effect of motion sickness caused by the typically backward, reclining transport in the helicopter, without the possibility of looking outside, which typically reduces motion sickness.\u003c/p\u003e \u003cp\u003eOur findings demonstrated no significant benefit from either pharmacologic prophylaxis or aromatherapy. In concordance to our results, previous studies also found that \u003cem\u003eprophylactic\u003c/em\u003e intravenous antiemetics do not make a significant difference in decreasing opioid-induced nausea and vomiting in the setting of emergency departments.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Also, the \u003cem\u003etherapeutic\u003c/em\u003e use of ondansetron for opioid-induced nausea and vomiting was found to be ineffective compared to placebo.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e This corresponds with our findings that none of the five patients who received ondansetron for therapeutic purposes after complaining about increasing or severe nausea experienced a reduction in nausea, and three of these patients even had to vomit later on.\u003c/p\u003e \u003cp\u003eNo data is currently available on the \u003cem\u003eprophylactic\u003c/em\u003e use of aromatherapy to prevent opioid-induced nausea. According to our findings, aromatherapy does not appear to be beneficial in this regard. Existing data on the \u003cem\u003etherapeutic\u003c/em\u003e use of aromatherapy for PONV is inconsistent. In ambulatory surgery patients one study found no difference in the rate of PONV with aromatherapy, whereas another study showed a significant reduction.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The results for female patients after gynecological surgery (proofing a benefit from aromatherapy) are similarly contradictory when compared to female patients after general surgery (where no benefit could be demonstrated).\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough, according to the regression analysis, gender does not appear to be a significant influencing factor, given the magnitude of a possible effect between males and females \u0026ndash; despite its large uncertainty \u0026ndash; warrants further investigation. Numerous studies have shown that women are more likely to experience nausea and vomiting when given opioids.\u003csup\u003e\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Therefore, further studies should investigate whether female patients in particular may benefit from nausea prophylaxis in the context of opioid administration. According to existing data, also the subgroup of patients with known motion sickness and known history nausea after opioid use, may benefit from administration of prophylactic antiemetics when being treated with parenteral opioids.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Our findings regarding age also correspond with in-hospital experience regarding PONV, which young adults suffer from more frequently than older people.\u003csup\u003e\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe placebo effect may play a significant role in the treatment of nausea and PONV.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e We informed patients receiving both drug prophylaxis and aromatherapy that the aim of this measure was to prevent opioid-induced nausea. However, despite this possible placebo effect in the ondansetron and aromatherapy group, we saw no advantage over the group without prophylaxis.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThe study has several limitations. For example, we could not rule out the influence of certain confounding factors, such as the susceptibility to motion sickness, the type of injury, the duration of transport, and the transport position (lying down facing backwards or sitting facing forwards). We also did not document how reliably the patients actually used the aromatherapy and inhaled deeply with the disinfectant swab directly in front of the nose. On the other hand, this reflects the practicality of the prophylactic aromatherapy in a real prehospital setting.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBased on our evaluation, neither the prophylactic administration of ondansetron nor aromatherapy were beneficial for the prevention of opioid-induced nausea in unselected patients in the setting of prehospital emergency medicine. Routine nausea prophylaxis with parenteral administration of opioids therefore does not appear to be indicated. Larger randomized controlled trials are needed to clarify whether certain subgroups may benefit.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the EKOS Ethics Committee (EKOS23/220). Consent to participate was waived due to a retrospective, anonymized evaluation of the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePietsch U, Strapazzon G, Ambuhl D, Lischke V, Rauch S, Knapp J. Challenges of helicopter mountain rescue missions by human external cargo: need for physicians onsite and comprehensive training. Scand J Trauma Resusc Emerg Med. 2019;27:17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScharonow O, Vilcane S, Weilbach C, Scharonow M. Analgesic Therapy with the Opioids Fentanyl and Morphine by Ambulance Personnel in Rural Areas: An Observational Study Over 7 Years. J Pain Res. 2024;17:345\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas SH, Shewakramani S. Prehospital trauma analgesia. J Emerg Med. 2008;35:47\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCulver MA, Richards EC, Jarrell DH, Edwards CJ. Use of Prophylactic Ondansetron with Intravenous Opioids in Emergency Department Patients: A Prospective Observational Pilot Study. J Emerg Med. 2017;53:629\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKimber JS, Kovoor JG, Glynatsis JM et al. Isopropyl alcohol inhalation versus 5-HT(3) antagonists for treatment of nausea: a meta-analysis of randomised controlled trials. Eur J Clin Pharmacol 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApril MD, Oliver JJ, Davis WT, et al. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial. Ann Emerg Med. 2018;72:184\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHines S, Steels E, Chang A, Gibbons K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2018;3:CD007598.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRowland KD, Fuehrer J, Motov SM, Vilke G, Rosenbaum SB, Quenzer F. Should Antiemetics be Given Prophylactically with Intravenous Opioids While Treating Acute Pain in the Emergency Department? Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee. J Emerg Med. 2020;58:706\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshihara M, Ikesue H, Matsunaga H, et al. A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction. Clin J Pain. 2012;28:373\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnderson LA, Gross JB. Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea. J Perianesth Nurs. 2004;19:29\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerritt BA, Okyere CP, Jasinski DM. Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting. Nurs Res. 2002;51:125\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerruggiari L, Ragione B, Rich ER, Lock K. The effect of aromatherapy on postoperative nausea in women undergoing surgical procedures. J Perianesth Nurs. 2012;27:246\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTate S. Peppermint oil: a treatment for postoperative nausea. J Adv Nurs. 1997;26:543\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimensen R, Fjose LO, Thorsen K et al. Comparison of inhalational methoxyflurane, intranasal fentanyl, and intravenous morphine for treatment of prehospital acute pain in Norway (PreMeFen): a randomised, non-inferiority, three-arm, phase 3 trial. Lancet 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApfel CC, Greim CA, Goepfert C, et al. [Postoperative vomiting. A score for prediction of vomiting risk following inhalation anesthesia]. Anaesthesist. 1998;47:732\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApfel CC, Greim CA, Haubitz I, et al. The discriminating power of a risk score for postoperative vomiting in adults undergoing various types of surgery. Acta Anaesthesiol Scand. 1998;42:502\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGan TJ, Jin Z, Ayad S et al. Fifth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting: Executive Summary. Anesth Analg 2025.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scandinavian-journal-of-trauma-resuscitation-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"stre","sideBox":"Learn more about [Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine](http://sjtrem.biomedcentral.com)","snPcode":"13049","submissionUrl":"https://submission.nature.com/new-submission/13049/3","title":"Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine","twitterHandle":"@SJTREM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"prehospital emergency medicine, HEMS, nausea prophylaxis, pain management, opioids","lastPublishedDoi":"10.21203/rs.3.rs-8582728/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8582728/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eIn prehospital emergency medicine, opioids are usually used to treat acute traumatic pain. A common side effect of opioids is nausea. To prevent this, the prophylactic administration of 5-HT\u003csub\u003e3\u003c/sub\u003e antagonists such as ondansetron has become established in clinical practice, even though there is currently no evidence to support its use. Aromatherapy is also used as an alternative non-pharmacological method for the treatment of nausea. We therefore investigated whether the prophylactic administration of ondansetron or prophylactic aromatherapy after opioid administration is beneficial to the patient.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients over the age of 16 who received opioid therapy due to acute traumatic pain by the crews of a total of six HEMS bases between February 2024 and April 2025 were prospectively included. Nausea prophylaxis after opioid-based pain therapy was performed according to a fixed rotating 7-day schedule: no nausea prophylaxis, medication-based nausea prophylaxis with ondansetron 4 mg intravenously, and aromatherapy-based nausea prophylaxis by inhalation of isopropanol. A nausea score was evaluated at the time of opioid administration and upon handover at the destination hospital, using a numeric rating scale (NRS) between 0 (no nausea) and 10 (maximum nausea). Primary endpoint was the change in NRS between the time before opioid administration and the time of patient handover at the emergency department. Secondary endpoints were incidence of moderate and severe nausea (defined as an NRS\u0026thinsp;\u0026gt;\u0026thinsp;3), the incidence of vomiting during prehospital patient care and need of rescue medication (ondansetron for therapeutic use).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 205 patients were included in the analysis. Eighty-six in the \u0026ldquo;no prophylaxis\u0026rdquo; group, 64 in the ondansetron group, and 55 in the aromatherapy group. There was no difference between the groups in terms of changes in nausea before opioid administration compared to the time of hospital admission as well as in the incidence of moderate and severe nausea. Therapeutic administration of ondansetron was necessary in 4 patients in the \u0026ldquo;no prophylaxis\u0026rdquo; group and in one patient in the aromatherapy group. None of the patients experienced any improvement in nausea as a result, three of these patients from the \u0026ldquo;no prophylaxis\u0026rdquo; group vomited after ondansetron administration.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eNeither the prophylactic administration of ondansetron nor aromatherapy seem to be beneficial for the prevention of opioid-induced nausea in unselected patients in the setting of prehospital emergency medicine. Larger randomized controlled trials are needed to clarify whether certain subgroups may benefit.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003enot applicable\u003c/p\u003e","manuscriptTitle":"Prophylaxis of opioid-induced nausea in helicopter emergency medical service: a prospective quasi-experimental study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 07:15:04","doi":"10.21203/rs.3.rs-8582728/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-06T11:24:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-06T10:58:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-02T14:59:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19605173019869430125074359132358162930","date":"2026-02-09T08:38:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97411685529543377171802011719292875661","date":"2026-02-06T12:07:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-19T14:09:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-13T00:22:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T00:21:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine","date":"2026-01-12T14:01:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scandinavian-journal-of-trauma-resuscitation-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"stre","sideBox":"Learn more about [Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine](http://sjtrem.biomedcentral.com)","snPcode":"13049","submissionUrl":"https://submission.nature.com/new-submission/13049/3","title":"Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine","twitterHandle":"@SJTREM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ee7bb866-b9b9-4869-8eb4-b4b9a1965a46","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-01T14:53:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 07:15:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8582728","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8582728","identity":"rs-8582728","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}