Comparison of Administration of Midazolam via Intravenous Infusion with Nasal Atomizer in an Office-based Vasectomy Procedure Clinic

Comparison of Administration of Midazolam via Intravenous Infusion with Nasal Atomizer in an Office-based Vasectomy Procedure Clinic | 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 Comparison of Administration of Midazolam via Intravenous Infusion with Nasal Atomizer in an Office-based Vasectomy Procedure Clinic Taylor Wright, Shaunta' Chamberlin, Robert E. Heidel, G. Anthony Wilson This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7216627/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: This study compared administration of midazolam via intravenous route with nasal atomizer route for moderate sedation in an office-based vasectomy clinic. Methods: Patients were randomly assigned to one of two groups: midazolam given via traditional intravenous route or with a nasal atomizer. Outcomes were patient perception of anxiety with the drug deliver method, discomfort with administration, pain during the procedure, length of sedation effects. Medical personnel rated ease of use, efficacy, time to sedation and time to transport after procedure. Results: Patient surveys showed no significant differences between the administration groups for being anxious when seeing the delivery device, experiencing discomfort when the medication was given, length of sedation effects, and overall pain level experienced during the procedure. Nurses felt that patients experienced significantly more discomfort with drug delivery via the Nasal Atomizer, and that IV method of delivery provided significantly better sedation for the vasectomy procedure. The nurses did not rate the two delivery methods differently for ease of use, and there were no differences in the amount of Versed administered, the amount of time from the patient being brought the procedure room to the beginning of the procedure, or the amount of time until transport was called. Surgeon’s rating of delivery method efficacy showed no difference between the groups. Conclusion: Midazolam administered with a nasal atomizer device showed similar perceptions of sedation on patient and surgeon survey. Midazolam administration via nasal atomizer is an acceptable alternative for moderate sedation in an office-based vasectomy procedure for patients who desire a method that does not require an IV. Trial Registration: This study was registered at clinicaltrials.gov (clinical trial # NCT06449365). Vasectomy anesthesia nasal atomizer Figures Figure 1 Figure 2 Background Intranasal delivery of pharmacologically active substances has been utilized for centuries, both for recreational purposes and in medical settings. (1) Nasal pharmaceuticals were used primarily for local effect until recently. (2) Nasal delivery of medications is effective, as the nasal mucosa provides excellent absorption (3) and avoid first pass effect. (2) Midazolam is frequently used for mild to moderate sedation for office-based procedures. Midazolam intravenous solution given intranasally has been studied in other clinical settings. (4) Methods Midazolam has been used for moderate sedation in our clinic for the no-scalpel vasectomy procedure, administered intravenously. We utilized a nasal atomizer device (MAD300 Nasal Intranasal Mucosal Atomization Device) already approved for administration of midazolam and sought to determine if midazolam given via nasal atomizer provided comparable sedation and perception of pain control as compared to midazolam given intravenously. We also analyzed time burden between the two methods. Patients were invited to take part in the study at the pre-operative evaluation and consent for the study was signed at that time if they chose to participate. Upon arrival to their surgery appointment, the patients were randomized via a randomization table to receive midazolam intravenously or via nasal atomizer. Nursing staff and the surgeon filled out a questionnaire after the conclusion of each procedure (Figure 1). The patient was called two to three weeks later and answered questions over the phone (Figure 2). In our office, two surgeons share the patient load for no-scalpel vasectomy, with or without resident or medical student assistance or observation. Three nurses were assigned to assist with the procedure during the study period. Other than the midazolam delivery method, the procedure was the same between the two groups. Statistical Methods The two randomized drug delivery method groups were compared on the Likert-type ratings for each survey question using Mann-Whitney U tests. Medians (Mdn) and interquartile ranges (IQR) were reported and interpreted for the Mann-Whitney U comparisons. Statistical significance was assumed at an alpha value of 0.05 and all analyses were performed using SPSS Version 29 (Armonk, NY: IBM Corp.). Results For the patient questionnaire, there were no significant differences between the administration groups for being anxious when seeing the delivery device, p = 0.33, experiencing discomfort when the medication was given, p = 0.13, experience pain during the procedure, p = 0.56, length of sedation effects, p = 0.66, and pain level experienced during the procedure, p = 0.88. See Table 1 for the medians and interquartile ranges associated with the patient questionnaire survey questions. Table 1. Patient Questionnaire Survey Question IV Midazolam ( n =16) Nasal Atomizer Midazolam ( n =19) p -value Before your procedure, were you worried that the procedure might be painful? (1=not at all worried → 5=extremely worried) 1 (1-2) 3 (2-4) 0.052 When you saw the delivery device, did you become anxious? (1=not at all anxious → 5=extremely anxious) 1 (1-2) 1 (1-1) 0.33 Did you experience discomfort when the sedating medication was given? (1=no discomfort → 5=extremely uncomfortable) 2 (1-2) 3 (2-4) 0.13 Did you experience pain during the vasectomy? (1=no pain at all → 5=extremely painful) 2 (1-2) 1 (1-3) 0.56 How long did the sedation effects last? (2-4 hours; 4-6 hours; 6-8 hours; 8-10 hours; >10 hours) 1 (1-1) 1 (1-1) 0.66 On a scale of 1-10 with 1 being no pain and 10 being the worst pain you can imagine, where would you rate the pain you experienced during the procedure? 2 (2-3) 2 (2-3) 0.88 The nurses that were surveyed felt that patients experienced significantly more discomfort with drug delivery via the Nasal Atomizer, p = 0.002. They also felt that the IV method of delivery provided significantly better sedation for the vasectomy procedure, p = 0.02. The nurses did not rate the two delivery methods differently for ease of use, p = 0.36. There were no differences in the amount of Versed administered, p = 0.38, the amount of time from the patient being brought the procedure room to the beginning of the procedure, p = 0.52, or the amount of time until transport was called, p = 0.31. See Table 2 for the descriptive statistics for the nursing survey. Table 2. Nursing Questionnaire Survey Question IV Midazolam ( n =16) Nasal Atomizer Midazolam ( n =19) p -value Was the sedation method easy to use? (1=very difficult to use → 5=very easy to use) 5 (5-5) 5 (5-5) 0.36 Did the patient experience discomfort with the sedation delivery method? (1=no discomfort → 5=extremely uncomfortable) 1 (1-2) 2 (2-2) 0.002 Did the method of sedation provide adequate sedation for the no-scalpel vasectomy procedure? (1=very poor sedation → 5=excellent sedation) 5 (4-5) 4 (4-4) 0.02 How much Versed did you administer to the patient? (mg) 5 (5-5) 5 (5-5) 0.38 How many minutes from the time that the nurse brought the patient back until the patient was ready for the doctor? (mins) 12 (10-15) 15 (10-15) 0.52 How many minutes after the procedure did you call transport? (mins) 5 (2-15) 10 (5-15) 0.31 The surgeon was asked one question related to adequate sedation between the two delivery methods. The surgeon rated the IV drug delivery method higher, but not significantly higher, p = 0.09. See Table 3 for the surgeon ratings for the two drug delivery methods. Table 3. Surgeon Questionnaire Survey Question IV Midazolam ( n =16) Nasal Atomizer Midazolam ( n =19) p -value Did the method of sedation delivery provide adequate sedation for the no-scalpel vasectomy procedure? (1=very poor sedation → 5=excellent sedation) 5 (4-5) 4 (3-5) 0.09 Discussion The patients who answered the questions did not rate their experiences significantly differently between the two methods of midazolam delivery. The response rate was not high due to difficulty contacting patients by phone within the allotted time frame. Nurses did rate the efficacy of the IV preparation as giving significantly better sedation as compared to the intranasal atomizer group, but the surgeons did not rate the sedation as significantly different between the two groups. Time burden was not rated as significantly different between the two groups. A weakness of the study included dependence on the principle investigators calling the patients within an allotted period of time and asking the questions over the phone. Response rate could be improved by utilizing an emailed survey that the patient can complete on a computer or mobile device. Further studies could utilize a previously validated sedation scoring system to more accurately quantify the level of sedation attained. Conclusion Delivery of intravenous preparation of midazolam via a nasal atomizer is a reasonable alternative for sedation for no-scalpel vasectomy procedure depending on patient preference. This method of midazolam delivery could be studied in the setting of other in-office procedures. Declarations Ethics approval and consent to participate: Our study received human ethics Institutional Review Board (IRB) approval through the University of Tennessee Graduate School of Medicine and University of Tennessee Health Science Center. Consent for publication: Not applicable. Availability of data and materials: All data generated or analysed during this study are included in this published article Competing interests: The authors declare that they have no competing interests. Funding : There was no funding from outside the department for this study. Authors' contributions: TW, SC and AW wrote the protocol. TW and AW performed the study. EH Analyzed data. All authors wrote the main manuscript text. SC and AW figures/tables. All authors reviewed the manuscript Acknowledgements: Not applicable References Ghori M, Mahdi M, Smith A, Conway B. Nasal Drug Delivery Systems: An Overview. American Journal of Pharmacological Sciences, 2015, Vol. 3 No. 5, 110-119. Sheth N, Mistry R. A Review: Nasal Drug Delivery System. Research J. Pharm. And Tech. 4(3); March 2011; Page 349-355. Fortuna A, Schindowski K, Sonvico Editorial: Intranasal Drug Delivery: Challenges and Opportunities. Front. Pharmacol. March 2022, 13:868986. Chung S, Petters J, Detyniecki K, Tatum W, Rabinowicz A, Carrazana E. The nose has it: Opportunities and challenges for intranasal drug administration for neurologic conditions including Seizure clusters. Epilepsy and Behavior Reports , https://doi.org/10.1016/j.ebr.2022.100581. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 22 Jan, 2026 Editor assigned by journal 30 Jul, 2025 Submission checks completed at journal 30 Jul, 2025 First submitted to journal 25 Jul, 2025 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7216627","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":579694957,"identity":"83c6009f-c125-48b2-a16c-9046d725cef5","order_by":0,"name":"Taylor Wright","email":"","orcid":"","institution":"University of Tennessee Health Science Center College of Medicine Knoxville","correspondingAuthor":false,"prefix":"","firstName":"Taylor","middleName":"","lastName":"Wright","suffix":""},{"id":579694958,"identity":"b30f4b74-5d65-400e-bc6b-1e8c1f8416de","order_by":1,"name":"Shaunta' Chamberlin","email":"","orcid":"","institution":"University of Tennessee Health Science Center College of Medicine Knoxville","correspondingAuthor":false,"prefix":"","firstName":"Shaunta'","middleName":"","lastName":"Chamberlin","suffix":""},{"id":579694959,"identity":"dee88c9e-4d61-429c-85a7-8f42c27970d2","order_by":2,"name":"Robert E. 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Anthony Wilson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYFACxsYDQFIOzGyAYIJaGkBajBnYiNfCwADSkthAtBb5iOSGgz8q7qRvuN+d+HEGg43shgMEtBjeSGw4zHPmWe6GY7ybJTcwpBkT1jIbqIWx7TBIyzbGBwyHE4nScvBn2+F0A4iW/4S1yEsnNhzgbTucANaygeEAYS0G8g9BfjlsOPNY7mbJGQbJxjMJ2tJz/OHDHxWH5fkOn934safCTraPoC2oCgwIKAfb0kCEolEwCkbBKBjhAAA8bE+lrsEJNQAAAABJRU5ErkJggg==","orcid":"","institution":"University of Tennessee Health Science Center College of Medicine Knoxville","correspondingAuthor":true,"prefix":"","firstName":"G.","middleName":"Anthony","lastName":"Wilson","suffix":""}],"badges":[],"createdAt":"2025-07-25 18:23:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7216627/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7216627/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101362509,"identity":"98bf6211-11f5-403c-9ba9-9d62274b6ca8","added_by":"auto","created_at":"2026-01-29 00:29:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84950,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Legend not included with this version.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7216627/v1/4dc2106b475367ed91b1e8a6.png"},{"id":101362510,"identity":"ee9b066f-7da6-4216-9f8e-8b74b9ce7487","added_by":"auto","created_at":"2026-01-29 00:29:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85783,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Legend not included with this version.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7216627/v1/1165d89fb794435c0407a918.png"},{"id":101398416,"identity":"6a51d7ed-7758-41c1-8818-55ae99c01595","added_by":"auto","created_at":"2026-01-29 09:41:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":555353,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7216627/v1/04e7ea51-1192-4f04-842f-8855c8ac7057.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Administration of Midazolam via Intravenous Infusion with Nasal Atomizer in an Office-based Vasectomy Procedure Clinic","fulltext":[{"header":"Background","content":"\u003cp\u003eIntranasal delivery of pharmacologically active substances has been utilized for centuries, both for recreational purposes and in medical settings.\u003csup\u003e(1)\u003c/sup\u003e Nasal pharmaceuticals were used primarily for local effect until recently. \u003csup\u003e(2)\u003c/sup\u003e Nasal delivery of medications is effective, as the nasal mucosa provides excellent absorption\u003csup\u003e(3)\u003c/sup\u003e and avoid first pass effect.\u003csup\u003e(2)\u003c/sup\u003e Midazolam is frequently used for mild to moderate sedation for office-based procedures. Midazolam intravenous solution given intranasally has been studied in other clinical settings.\u003csup\u003e(4)\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eMidazolam has been used for moderate sedation in our clinic for the no-scalpel vasectomy procedure, administered intravenously. \u0026nbsp; We utilized a nasal atomizer device (MAD300 Nasal Intranasal Mucosal Atomization Device) already approved for administration of midazolam and sought to determine if midazolam given via nasal atomizer provided comparable sedation and perception of pain control as compared to midazolam given intravenously. We also analyzed time burden between the two methods.\u003c/p\u003e\n\u003cp\u003ePatients were invited to take part in the study at the pre-operative evaluation and consent for the study was signed at that time if they chose to participate. Upon arrival to their surgery appointment, the patients were randomized via a randomization table to receive midazolam intravenously or via nasal atomizer. Nursing staff and the surgeon filled out a questionnaire after the conclusion of each procedure (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient was called two to three weeks later and answered questions over the phone (Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our office, two surgeons share the patient load for no-scalpel vasectomy, with or without resident or medical student assistance or observation. Three nurses were assigned to assist with the procedure during the study period. Other than the midazolam delivery method, the procedure was the same between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe two randomized drug delivery method groups were compared on the Likert-type ratings for each survey question using Mann-Whitney U tests. Medians (Mdn) and interquartile ranges (IQR) were reported and interpreted for the Mann-Whitney U comparisons. Statistical significance was assumed at an alpha value of 0.05 and all analyses were performed using SPSS Version 29 (Armonk, NY: IBM Corp.).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFor the patient questionnaire, there were no significant differences between the administration groups for being anxious when seeing the delivery device, p = 0.33, experiencing discomfort when the medication was given, p = 0.13, experience pain during the procedure, p = 0.56, length of sedation effects, p = 0.66, and pain level experienced during the procedure, p = 0.88. See Table 1 for the medians and interquartile ranges associated with the patient questionnaire survey questions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003ePatient Questionnaire\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eSurvey Question\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eIV Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eNasal Atomizer Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eBefore your procedure, were you worried that the procedure might be painful?\u003c/p\u003e\n \u003cp\u003e(1=not at all worried → 5=extremely worried)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e3 (2-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eWhen you saw the delivery device, did you become anxious?\u003c/p\u003e\n \u003cp\u003e(1=not at all anxious → 5=extremely anxious)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eDid you experience discomfort when the sedating medication was given?\u003c/p\u003e\n \u003cp\u003e(1=no discomfort → 5=extremely uncomfortable)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e3 (2-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eDid you experience pain during the vasectomy?\u003c/p\u003e\n \u003cp\u003e(1=no pain at all → 5=extremely painful)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e1 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHow long did the sedation effects last?\u003c/p\u003e\n \u003cp\u003e(2-4 hours; 4-6 hours; 6-8 hours; 8-10 hours; \u0026gt;10 hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eOn a scale of 1-10 with 1 being no pain and 10 being the worst pain you can imagine, where would you rate the pain you experienced during the procedure?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe nurses that were surveyed felt that patients experienced significantly more discomfort with drug delivery via the Nasal Atomizer, p = 0.002. They also felt that the IV method of delivery provided significantly better sedation for the vasectomy procedure, p = 0.02. The nurses did not rate the two delivery methods differently for ease of use, p = 0.36. There were no differences in the amount of Versed administered, p = 0.38, the amount of time from the patient being brought the procedure room to the beginning of the procedure, p = 0.52, or the amount of time until transport was called, p = 0.31. See Table 2 for the descriptive statistics for the nursing survey.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eNursing Questionnaire\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eSurvey Question\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eIV Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003eNasal Atomizer Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eWas the sedation method easy to use?\u003c/p\u003e\n \u003cp\u003e(1=very difficult to use\u0026nbsp;→ \u0026nbsp;5=very easy to use)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eDid the patient experience discomfort with the sedation delivery method?\u003c/p\u003e\n \u003cp\u003e(1=no discomfort\u0026nbsp;→ \u0026nbsp;5=extremely uncomfortable)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2 (2-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eDid the method of sedation provide adequate sedation for the no-scalpel vasectomy procedure?\u003c/p\u003e\n \u003cp\u003e(1=very poor sedation\u0026nbsp;→ \u0026nbsp;5=excellent sedation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (4-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4 (4-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eHow much Versed did you administer to the patient? (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eHow many minutes from the time that the nurse brought the patient back until the patient was ready for the doctor? (mins)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e12 (10-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e15 (10-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eHow many minutes after the procedure did you call transport? (mins)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (2-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e10 (5-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe surgeon was asked one question related to adequate sedation between the two delivery methods. The surgeon rated the IV drug delivery method higher, but not significantly higher, p = 0.09. See Table 3 for the surgeon ratings for the two drug delivery methods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eSurgeon Questionnaire\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eSurvey Question\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eIV Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eNasal Atomizer Midazolam\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en\u003c/em\u003e=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eDid the method of sedation delivery provide adequate sedation for the no-scalpel vasectomy procedure?\u003c/p\u003e\n \u003cp\u003e(1=very poor sedation\u0026nbsp;→ \u0026nbsp;5=excellent sedation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e5 (4-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e4 (3-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe patients who answered the questions did not rate their experiences significantly differently between the two methods of midazolam delivery. The response rate was not high due to difficulty contacting patients by phone within the allotted time frame. Nurses did rate the efficacy of the IV preparation as giving significantly better sedation as compared to the intranasal atomizer group, but the surgeons did not rate the sedation as significantly different between the two groups. Time burden was not rated as significantly different between the two groups.\u003c/p\u003e\n\u003cp\u003eA weakness of the study included dependence on the principle investigators calling the patients within an allotted period of time and asking the questions over the phone. Response rate could be improved by utilizing an emailed survey that the patient can complete on a computer or mobile device. Further studies could utilize a previously validated sedation scoring system to more accurately quantify the level of sedation attained.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDelivery of intravenous preparation of midazolam via a nasal atomizer is a reasonable alternative for sedation for no-scalpel vasectomy procedure depending on patient preference. This \u0026nbsp;method of midazolam delivery could be studied in the setting of other in-office procedures.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate: \u003c/strong\u003eOur study received human ethics Institutional Review Board (IRB) approval through the University of Tennessee Graduate School of Medicine and University of Tennessee Health Science Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials: \u003c/strong\u003eAll data generated or analysed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: There was no funding from outside the department for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e TW, SC and AW wrote the protocol. TW and AW performed the study. EH Analyzed data. All authors wrote the main manuscript text. SC and AW figures/tables. All authors reviewed the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements: \u003c/strong\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGhori M, Mahdi M, Smith A, Conway B. Nasal Drug Delivery Systems: An Overview. \u003cem\u003eAmerican Journal of Pharmacological Sciences, 2015, Vol. 3 No. 5, 110-119.\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003eSheth N, Mistry R. A Review: Nasal Drug Delivery System. \u003cem\u003eResearch J. Pharm. And Tech. 4(3); March 2011; Page 349-355.\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003eFortuna A, Schindowski K, Sonvico Editorial: Intranasal Drug Delivery: Challenges and Opportunities. Front. Pharmacol. March 2022, 13:868986.\u003c/li\u003e\n \u003cli\u003eChung S, Petters J, Detyniecki K, Tatum W, Rabinowicz A, Carrazana E. The nose has it: Opportunities and challenges for intranasal drug administration for neurologic conditions including Seizure clusters. \u003cem\u003eEpilepsy and Behavior Reports\u003c/em\u003e, https://doi.org/10.1016/j.ebr.2022.100581.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"contraception-and-reproductive-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"carm","sideBox":"Learn more about [Contraception and Reproductive Medicine](http://contraceptionmedicine.biomedcentral.com)","snPcode":"40834","submissionUrl":"https://submission.nature.com/new-submission/40834/3","title":"Contraception and Reproductive Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Vasectomy, anesthesia, nasal atomizer","lastPublishedDoi":"10.21203/rs.3.rs-7216627/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7216627/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThis study compared administration of midazolam via intravenous route with nasal atomizer route for moderate sedation in an office-based vasectomy clinic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePatients were randomly assigned to one of two groups: midazolam given via traditional intravenous route or with a nasal atomizer. Outcomes were patient perception of anxiety with the drug deliver method, discomfort with administration, pain during the procedure, length of sedation effects. Medical personnel rated ease of use, efficacy, time to sedation and time to transport after procedure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient surveys showed no significant differences between the administration groups for being anxious when seeing the delivery device, experiencing discomfort when the medication was given, \u0026nbsp;length of sedation effects, and overall pain level experienced during the procedure. Nurses felt that patients experienced significantly more discomfort with drug delivery via the Nasal Atomizer, and that IV method of delivery provided significantly better sedation for the vasectomy procedure. The nurses did not rate the two delivery methods differently for ease of use, and there were no differences in the amount of Versed administered, the amount of time from the patient being brought the procedure room to the beginning of the procedure, or the amount of time until transport was called. Surgeon’s rating of delivery method efficacy showed no difference between the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eMidazolam administered with a nasal atomizer device showed similar perceptions of sedation on patient and surgeon survey. Midazolam administration via nasal atomizer is an acceptable alternative for moderate sedation in an office-based vasectomy procedure for patients who desire a method that does not require an IV.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration: \u003c/strong\u003eThis study was registered at clinicaltrials.gov (clinical trial # NCT06449365).\u003c/p\u003e","manuscriptTitle":"Comparison of Administration of Midazolam via Intravenous Infusion with Nasal Atomizer in an Office-based Vasectomy Procedure Clinic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 00:29:47","doi":"10.21203/rs.3.rs-7216627/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-01-22T05:46:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-31T00:52:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-31T00:51:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Contraception and Reproductive Medicine","date":"2025-07-25T18:07:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"contraception-and-reproductive-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"carm","sideBox":"Learn more about [Contraception and Reproductive Medicine](http://contraceptionmedicine.biomedcentral.com)","snPcode":"40834","submissionUrl":"https://submission.nature.com/new-submission/40834/3","title":"Contraception and Reproductive Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7df4233d-f2f5-4816-bed8-bca374e41ac1","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-29T00:29:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 00:29:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7216627","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7216627","identity":"rs-7216627","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}