Drug Incompatibility in Emergency Departments: A Comparative Evaluation of Clinical Practices and Pharmaceutical Interaction Sources

Drug Incompatibility in Emergency Departments: A Comparative Evaluation of Clinical Practices and Pharmaceutical Interaction Sources | 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 Drug Incompatibility in Emergency Departments: A Comparative Evaluation of Clinical Practices and Pharmaceutical Interaction Sources Ahmet Özyürek This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9354196/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Intravenous (IV) drug incompatibility represents a significant patient safety concern in emergency departments, where multiple medications are frequently administered under time pressure. This study aimed to evaluate physicians’ real-world IV drug mixing practices and to assess the consistency of major IV compatibility databases with these practices. Material and Methods This nationwide, cross-sectional study was conducted using an anonymous online survey distributed to emergency department physicians across Türkiye. The survey collected data on drugs commonly mixed in clinical practice, drugs perceived as compatible, and information sources used for compatibility checks. All reported drug combinations were evaluated using four major IV compatibility databases. Analyses were limited to descriptive statistics and are presented as frequencies and percentages. Results A total of 34 physicians participated in the study. Clinical experience was the most frequently used source for assessing IV drug compatibility (n = 30, 88.2%). Significant discrepancies were observed between clinical practice and database information. Several commonly mixed drugs had no compatibility data available in any of the databases. Among evaluated combinations, some were classified inconsistently across sources, being reported as compatible, incompatible, or uncertain depending on the database. Overall, substantial gaps and inconsistencies in IV compatibility information were identified. Conclusion Emergency physicians predominantly rely on informal knowledge when mixing IV drugs, while available compatibility databases demonstrate notable data gaps and inter-database inconsistencies. These findings highlight the need for improved clinician education, expansion of compatibility database content—particularly for commonly used agents—and the development of practical decision-support tools to enhance medication safety in emergency settings. Clinical Pharmacology Drug Information Databases Emergency Medicine Intravenous Drug Incompatibility Medication Safety Figures Figure 1 INTRODUCTION Intravenous (IV) incompatibility is a significant and widespread problem in clinical settings where parenteral drugs are administered.( 1 ) While administering multiple medications via a single intravenous line or syringe can offer benefits such as reduced workload, time, and cost savings, particularly in busy departments like emergency medicine or intensive care units,( 2 , 3 ) clinicians may have a limited understanding of potential pharmaceutical interactions.( 4 , 5 ) Some drugs are co-administered via the same mixture, intravenous line, or syringe without sufficient supporting data on their miscibility in the literature. Numerous studies have shown that incompatibility is a major contributor to medication administration errors.( 6 ) Clinicians may also confuse pharmacokinetic and pharmacodynamic interactions with pharmaceutical incompatibilities. This is a significant issue because it is incorrect to use the interaction modules of resources like uptodate.com and drugs.com to evaluate IV incompatibility. While various sources are available for checking IV incompatibility, some discrepancies exist among them. Therefore, there is a need for a comparative study that includes current and most well-known sources to assist clinicians in their selection. Comparisons of IV compatibility sources are not as common as those performed for drug-drug interactions. A study in 2023 noted that factors such as a lack of knowledge contributing to incompatibilities have not been extensively examined.( 5 ) This observation is fully consistent with our hospital practice and a review of the literature. Therefore, in comparing sources, it is crucial to consider the drugs that clinicians are already mixing, as this approach can yield more practically meaningful results. Detecting incompatible mixtures, along with a firm grasp of the fundamental chemistry and pharmacology involved in compatibility assessment and a heightened awareness of the issue, will play a significant role in improving patient care. The purpose of this study is to investigate physicians' knowledge on this subject, acquire data to generate solutions for potential problems, and simplify the selection of resources by providing a comparison of the most current and well-known sources. METHODS This nationwide cross-sectional study was conducted between October and December 2024 in emergency departments across Türkiye. Ethical approval was obtained from the Ankara Bilkent City Hospital 1st Medical Research Scientific and Ethical Evaluation Board (TABED) (Decision No: TABED 1/606/2024, Date: 9 October 2024). Emergency department physicians actively practicing in Türkiye were eligible to participate. Participation was voluntary and anonymous, and no personal identifying information was collected. All responses obtained during the study period were included in the analysis. Data were collected using an online survey developed with Google Forms. The survey was distributed through digital communication channels, including social media platforms, in order to reach physicians working in emergency departments across multiple cities and regions. The questionnaire included both multiple-choice and open-ended questions addressing IV drug mixing practices, drugs perceived as compatible, information sources used for compatibility assessment, and physicians’ educational needs on this topic. Anonymity was ensured to encourage candid responses and to minimize social desirability bias. All drugs reported by physicians were evaluated using the IV compatibility tools of four major drug information databases: Clinical Pharmacology (CP), DynaMedex (DM), Lexidrug (LD), and Stabilis (Ss). Drug mixtures containing more than two agents were analysed as binary combinations, since compatibility data in these databases are reported for drug pairs. For combinations identified as incompatible or uncertain, the route of administration (Y-site, admixture, or in-syringe) was recorded. This detailed classification was not applied to combinations with no reported incompatibility. Statistical analyses were limited to descriptive statistics, and all analyses were performed using Microsoft Excel. Results are presented as frequencies and percentages. RESULTS Only 34 physicians responded to the survey. Of these, 25 were general practitioners, while 9 stated they were specialists or in specialist training. The most frequently chosen method for checking the suitability of drug mixtures was "what I learned from my professors/friends/my own clinical experience" (CE [Clinical Experience]) (n = 30, 88.2%). Of the four individuals who did not select this option, three chose online databases (ODB) and one chose “hospital protocols, algorithms, tables, brochures, or handbooks” (HP [hospital protocols]). Looking at the total numbers, 15 individuals selected ODB, and 9 selected HP. There were 15 physicians who selected only CE. When asked for details about the sources, “experience” was dominantly highlighted (including visual changes), while specific named sources included Medscape, Uptodate, Vademecum, Google, acilci.net, and WhatsApp. Other sources mentioned were drug leaflets, books, pharmacists, and internet searches. Three physicians stated that they did not check or research this information. The number of drugs in the mixtures varied (min: 2, max: 6). When organized as binary combinations, the most frequent mixtures they administered were pheniramine-dexamethasone (13%), diclofenac-thiocolchicoside (12%), and hyoscine butylbromide-metoclopramide (9.6%). Dexketoprofen and dexamethasone were the most frequently reported drugs in mixtures. When examining the drugs physicians knew to be compatible (PKCD) and the mixtures they actually administered (PMD), 14 physicians listed additional drugs in PKCD beyond those in PMD, while 14 physicians listed additional drugs in PMD beyond those in PKCD. The number of physicians common to both groups was 5. Furthermore, 13 physicians listed the exact same drugs for both PKCD and PMD. The survey question “Which drugs would you like to learn about their mixing compatibility?” generated a high number of requests for specific drug combinations (Table 1 ), and the responses to the question about additional questions and contributions revealed broader concerns and practical issues related to drug mixing (Table 2 ). Table 1 What drugs would you like to know can be mixed? Diclofenac-thiocolchicoside All of them All drugs used in the emergency department Pheniramine-dexamethasone, hyoscine butylbromide-metoclopramide, dexketoprofen-metoclopramide, dexketoprofen-thiocolchicoside, dexketoprofen-paracetamol, tramadol-paracetamol Diclofenac-dexamethasone Which drugs insulin can be mixed with Pheniramine Hyoscine butylbromide I would like a template on how the most frequently used drugs in the emergency department can be used Antiepileptics I had read that antibiotics cannot be mixed with any drug group. If there are any that can be mixed, I'd like to know None of them I would like to know about combinations with antibiotics and steroids Antibiotics and nonsteroidal anti-inflammatory drugs Whether all the drugs I mentioned are 100% miscible *Similar answers are listed only once in the table. Table 2 Responses to the question "Your additional questions and contributions regarding drugs administered in the same syringe or mixture" What are the duration parameters and metabolism in the mechanism of action? Which ones can be administered together? A reliable source is essential. As a general pharmacology principle, we should not mix any drugs, but we do so for practical reasons due to the high workload in emergency departments and the shortage of support staff. Is it more effective to administer them separately rather than as a single mixture? As new practitioners, many of my colleagues and I feel it is safer to apply simple treatments based on what we hear and learn from others. By 'simple treatments,' I mean avoiding a wide variety of orders in the emergency department. I am personally hesitant about mixing drugs myself. Simple, clear templates that could help us with this would be very useful. Ondansetron and pantoprazole cannot be mixed. Antibiotics should not be mixed. Mixing multiple drugs should be avoided as much as possible. We sometimes observe that pheniramine causes some drugs to deteriorate. Could you recommend a simple, practical app or website for this? 30 (88.2%) of the physicians thought they needed more information on this topic, while 2 (5.9%) stated they did not, and 2 (5.9%) were unsure. When the four sources were evaluated together, 15 of the PMD+PKCD were found to be compatible, 1 to be incompatible, and for 3 the results were mixed (uncertain). For the other mixtures, there was no data. There was no entry for pheniramine in any of the four sources, so no results were available for it. All details are provided in Fig. 1 . The acetaminophen-dexketoprofen mixture was found to be y-site incompatible in LD and in-syringe uncertain in Ss. While the pantoprazole-metoclopramide mixture was y-site uncertain in DM, CP, and LD, it was in-syringe incompatible in all four sources. The ceftriaxone-vitamin C mixture was y-site incompatible in DM, CP, and LD. For the ceftriaxone-metronidazole mixture, it was admix and y-site compatible in DM, admix uncertain but y-site compatible in CP, admix and y-site compatible in LD, and in-syringe uncertain in Ss. DISCUSSION Consistent with our clinical experience, the most frequently used source of information for physicians regarding drug mixtures was their colleagues. However, physicians also expressed a desire to learn the names of reliable sources they could use for this purpose. It would be beneficial for physicians to be aware of resources that specifically evaluate pharmaceutical incompatibilities, in addition to the databases they use for pharmacokinetic/pharmacodynamic interactions. The mention of sources like Uptodate.com and Medscape in the surveys was a predictable finding, consistent with our clinical experience and correspondence among physicians on this topic. The Uptodate interaction module attempts to prevent this confusion with a note stating, “NOTE: This tool does not address chemical compatibility related to I.V. drug preparation or administration.”; however, this warning may have been overlooked by some users. To address all these problems, more studies on this under-discussed topic are needed. There is a notable lack of studies evaluating IV compatibility databases. Some of these studies compare outdated or no longer used resources.( 7 ) This current work is the first of its kind to not only compare these sources but also survey emergency physicians directly on the subject. The scarcity of research on such a vital topic is consistent with the apparent lack of adequate interest among physicians regarding this issue. While one physician in the study used visual changes for compatibility assessment, this remains the most fundamental component of physical compatibility evaluation, although it is insufficient on its own.( 8 ) Physical compatibility is generally considered more critical than chemical compatibility.( 9 ) Differences were observed between the mixtures physicians actually administered (PMD) and the drugs they knew to be compatible (PKCD). Contributing factors may include the mixing of drugs based on empirical knowledge and the predominant use of different medications in various emergency departments. In fact, some physicians, when asked which drugs they would like to know can be mixed, listed the same drugs they had already reported administering. One physician reported administering a ceftriaxone-vitamin C mixture. This mixture was found to be y-site incompatible in three sources (with 4 references in each database). For admix or in-syringe administration, the result was 'No Data'. In Stabilis (Ss), there was no result at all. Furthermore, this physician specified the mixture as ceftriaxone + hyoscine butylbromide + metoclopramide + vitamin B complex + vitamin C + dexketoprofen. Since the B vitamin complex is yellow in color, it is difficult to visually assess the physical compatibility of this mixture. While the results for the acetaminophen-dexketoprofen and pantoprazole-metoclopramide mixtures showed differences, a potentially more significant problem was observed with the ceftriaxone-metronidazole mixture. Specifically, while it appeared compatible in DM and LD, it was found to be uncertain in CP and Ss. This serves as a good example of how relying on a single database can lead to negative outcomes. These databases are tertiary references, and it is crucial to evaluate and verify information from multiple tertiary sources.( 10 ) Pheniramine is not listed in any of the four sources. Therefore, it is not possible to assess the compatibility of pheniramine using these databases. This study should draw attention to this issue. It is observed that physicians, in the additional questions and contributions section of the survey, requested "robust," "simple," and "practical" resources. While the results are variable even for a drug that is available in the sources, the complete absence of some drugs is far from meeting this demand from physicians. Physicians working in the demanding conditions of an emergency department need to work with fewer resources and fewer confusing factors. The pheniramine-dexamethasone pair, which is frequently used in our emergency departments but for which compatibility data is insufficient, was the most common PMD in this study. In a previous study we conducted, this mixture was found to be physiochemically compatible.( 11 ) Furthermore, additional studies on pheniramine compatibility are still needed. A physician in this study stated that they have "witnessed pheniramine sometimes causing some drugs to deteriorate". Chlorpheniramine is available in DM, LD, and CP; however, from a chemical standpoint, its use as a substitute for pheniramine would not be appropriate. For the same reason, substituting ketoprofen for dexketoprofen was also not deemed appropriate. Indeed, when ketoprofen is selected instead of dexketoprofen in sources that do contain dexketoprofen, different results are observed. Ketoprofen is available in both DM and CP. Piracetam is another drug that continues to be frequently used in emergency departments, yet an entry for it is found only in LD. In contrast, there is no entry for another commonly used drug, thiocolchicoside, in LD. Although tenoxicam is not used as frequently, its absence from the free database Ss may be another potential drawback for physicians. This is also the case for the vitamin B complex, which is not found in Ss. Furthermore, even if the active ingredients of the preparations used for vitamin B complex are the same, the variation in excipients (auxiliary substances)( 12 , 13 ) indicates that checking a single database is not a definitive solution. Brousseau et al. indeed reported observing precipitation in a mixture when they used a new preparation with the same active ingredient from a different manufacturer.( 14 ) Updates addressing this excipient issue could be implemented in the databases. Differences in excipients (e.g., lidocaine content) may alter compatibility, requiring caution. The source used for IV compatibility in DM, CP, and LD is stated to be the Trissel’s 2 Clinical Pharmaceutics Database. Users might assume that because the source name is the same, the databases are identical in all aspects; however, this study has shown that this is not the case. Trissel’s has been regarded as a fundamental resource for drug information for many years,( 7 , 15 ) which suggests that ensuring consistency and standardization among the databases that use it would be beneficial for users. A study from 2009, for example, demonstrated that resources based on Trissel’s performed better than other incompatibility checkers.( 7 ) The positive aspects of Ss include its free nature and the fact that its authors draw on a wide variety of languages. The data obtained from these databases and the literature review, taking personal experiences into account, could be useful in preparing templates or guidelines; however, this is a short-term solution. All drugs mentioned by the physicians should be investigated, but particular attention should be paid to the drugs that physicians listed as "mixed" (PMD) but did not list as "known to be compatible" (PKCD). This suggests that physicians may be using these mixtures without being certain of their compatibility. This is further supported by physicians' requests in the additional questions and contributions section to "learn whether the drugs they mentioned can be mixed". This study can serve as a pilot study for larger and more advanced research that could be conducted with different surveys. The fact that some mixtures are listed as 'No Data' (ND) in the sources may be because certain drugs have never been tested due to their chemical structure. For example, pantoprazole is an acid-labile drug and can be affected by the pH of hyoscine butylbromide,( 16 ) while diclofenac sodium is alkaline.( 17 ) Mixtures that are ND in databases but have such theoretical chemical risks should be avoided if possible. While it was anticipated that the pantoprazole-hyoscine butylbromide mixture might be chemically incompatible, our laboratory study did not observe significant pH changes; however, incompatibility signals were seen in the optical density values.( 11 ) Considering that physicians reported using this mixture and that pantoprazole is one of the most common causes of incompatibility,( 1 , 18 ) this is highly significant. Three mixtures containing pantoprazole were reported in this study, and the results for all three were either ND or uncertain. Studies on intravenous incompatibility have been found to be insufficient. Garcia et al. noted that this limitation is particularly pronounced in the "national scenario".( 19 ) This statement is consistent with the findings of our study. Furthermore, while metamizole is frequently used in Brazil, compatibility studies on it are inadequate.( 20 ) In our country, metamizole use is also common, and physicians reported mixing it with some drugs. However, no data is available in the databases. During the analysis phase of this study, the names of the active ingredient salts from the commercial preparations specified by the physicians were used. For example, instead of methylprednisolone acetate, methylprednisolone sodium succinate salt was selected in the database. It is evident that healthcare professionals need more training on this topic. Almost all of the physicians in our study (n = 30) answered "yes" to the question of whether they needed more information. Notably, one of the two physicians who selected "I am not sure" was a specialist using Medscape for IV compatibility, while the other was a general practitioner who left most of the questions blank. Of the physicians who answered "no," one only mentioned the diclofenac-thiocolchicoside mixture. It can be inferred that this physician was not very interested in the topic or did not feel the need for more information. The other physician who answered "no," however, stated that although drugs should not be mixed, they do so due to high workload and a lack of personnel, which highlights the need for further discussion on this issue. Indeed, our study included physicians who reported being "hesitant about mixing drugs" and requested suggestions for simple, practical templates, apps, or websites. Although the sample size was limited, the participants were from many different cities. The consistency of their answers suggests that this list effectively captures the national practice. Regarding the analysis, we did not perform complex statistical tests. Since our goal was to simply map the current situation and the lack of database data, we chose to present the results with descriptive statistics only. Finally, while the survey structure might appear detailed, it was deliberately designed to be sufficient for the planned scope of this study, offering valuable insights into the gap between theoretical knowledge and clinical habits. Declarations Conflict of Interest: The author declares no conflict of interest. Financial Support: No financial or institutional support was received for this study. Author Contributions: Concept and design: AÖ; Data collection: AÖ; Analysis and interpretation: AÖ; Manuscript drafting and revision: AÖ; Final approval of the manuscript: AÖ References Sriram S, Aishwarya S, Moithu A, Sebastian A, Kumar A (2020) Intravenous Drug Incompatibilities in the Intensive Care Unit of a Tertiary Care Hospital in India: Are they Preventable? 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Eur J Clin Pharmacol 79(8):1081–1089. 10.1007/s00228-023-03509-0 Hecq J-D, Krämer I, Vigneron J (2019) European Databases on Stability and Compatibility of Injectable Medicinal Products in Europe. Pharmaceutical Technology in Hospital Pharmacy. De Gruyter 4(3–4):113–117. 10.1515/pthp-2019-0012 Smith WD, Karpinski JP, Timpe EM, Hatton RC (2009) Evaluation of seven i.v. drug compatibility references by using requests from a drug information center. Am J Health-System Pharm 66(15):1369–1375. 10.2146/ajhp080373 Vijayakumar A, Sharon EV, Teena J, Nobil S, Nazeer I (2014) A clinical study on drug-related problems associated with intravenous drug administration. J Basic Clin Pharm 5(2):49–53. 10.4103/0976-0105.134984 Hanifah S, Ball PA, Kennedy RA The influence of flushing on reducing precipitation of intravenous (IV) drug compatibility. JResPharm 26(7). 10.29228/jrp.339 Van Cuyk MP, Cooper JC, New JP (2019) Chapter 9 - Drug Information Services and Sources of Information. In: Thomas D (ed) Clinical Pharmacy Education, Practice and Research. Elsevier. DOI: 10.1016/B978-0-12-814276-9.00009-X Özyürek A, Yeşilyurt-Dirican ZE Physicochemical Compatibilities: Analyzing Aspects in Four Different Mixtures [Internet] Titck - Türkiye İlaç ve Tıbbi Cihaz Kurumu [cited 2025 Aug 12]. Available from: https://www.titck.gov.tr/kubkt Drugs.com [Internet] Vitamin B Complex: Package Insert / Prescribing Information [cited 2025 Aug 12]. Available from: https://www.drugs.com/pro/vitamin-b-complex.html Brousseau P, Nickerson J, Dobson G (2007) Dexamethasone and ondansetron incompatibility in polypropylene syringes. Can J Anesth 54(11):953–954. 10.1007/BF03026805 Fernández-Peña A, Katsumiti A, De Basagoiti A, Castaño M, Ros G, Sautua S et al (2021) Drug compatibility in neonatal intensive care units: gaps in knowledge and discordances. Eur J Pediatr 180(7):2305–2313. 10.1007/s00431-021-04028-9 Nasef AM, Gardouh AR, Ghorab MM (2017) Formulation and in-vitro evaluation of pantoprazole loaded pH-sensitive polymeric nanoparticles. Future J Pharm Sci 3(2):103–117. 10.1016/j.fjps.2017.04.004 Madhanagopal K, Balamurugan K (2024) Formulation and Evaluation of Diclofenac Sodium Injection. Cuestiones de Fisioterapia 53(03):5003–5009. 10.48047/t5701s80 Maison O, Tardy C, Cabelguenne D, Parat S, Ducastelle S, Piriou V et al (2019) Drug incompatibilities in intravenous therapy: evaluation and proposition of preventive tools in intensive care and hematology units. Eur J Clin Pharmacol 75(2):179–187. 10.1007/s00228-018-2602-6 Garcia JH, Crespo JCL, Handa AY, Padilha KG, Secoli SR (2021) In(compatibility) of intravenous drugs in critical units: adult cohort. Rev Bras Enferm FapUNIFESP (SciELO) 74(2). 10.1590/0034-7167-2020-0501 Leal KDB, Leopoldino RWD, Martins RR, Veríssimo LM (2016) Potential intravenous drug incompatibilities in a pediatric unit. einstein (São Paulo). Instituto Israelita de Ensino e Pesquisa Albert Einstein 14:185–189. https://doi.org/10.1590/S1679-45082016AO3723 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted 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-9354196","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":619491338,"identity":"8bca6845-4c57-4406-be53-6d1ef8b1dbbd","order_by":0,"name":"Ahmet Özyürek","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYDCCAwxsyDwbIMHcABImpMUAxktjYGBjJE3LYcJa+G4ffvboRsUfOfkZOWYfPpw5L2dwv7HxwYczDPL8Ytj1SZ5LMzfOOWNgzDgjx3jmjBu3jQ2OMTYbzrjBYDhzdgJWLQZnGMykc9sMEpslcoyZeT7cTtxwjLFNmucDQ4LBbVxa2L9J5/4zSGwDafnz4RwxWniAtjQYJPaAtDDcOADVcgO3FskzPGXSOceMjSV4nhUz9pxJNpY8lgj0yxkJnH7hO8O+TTqnRk5Ovj15M8OPY3ZyfIcPH3zw4ZiNPL80di0IIICqQIKAchDgP0CEolEwCkbBKBiRAADUyGQFLDYgPwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-8839-8444","institution":"General Directorate of Public Health","correspondingAuthor":true,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"Özyürek","suffix":""}],"badges":[],"createdAt":"2026-04-08 08:45:52","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9354196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9354196/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106543085,"identity":"1eb101ae-0136-40ab-b54e-9d2f8733cbcc","added_by":"auto","created_at":"2026-04-09 16:33:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":177226,"visible":true,"origin":"","legend":"\u003cp\u003eHeatmap displaying the compatibility status of drug mixtures across four major databases. Green indicates compatibility, red indicates incompatibility, yellow indicates uncertainty, and grey indicates no data available. *Drug pairs reported by physicians as known to be compatible but not reported as used.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9354196/v1/aa336c4ffad98dc523f85bb3.png"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eDrug Incompatibility in Emergency Departments: A Comparative Evaluation of Clinical Practices and Pharmaceutical Interaction Sources\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eIntravenous (IV) incompatibility is a significant and widespread problem in clinical settings where parenteral drugs are administered.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) While administering multiple medications via a single intravenous line or syringe can offer benefits such as reduced workload, time, and cost savings, particularly in busy departments like emergency medicine or intensive care units,(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) clinicians may have a limited understanding of potential pharmaceutical interactions.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Some drugs are co-administered via the same mixture, intravenous line, or syringe without sufficient supporting data on their miscibility in the literature. Numerous studies have shown that incompatibility is a major contributor to medication administration errors.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Clinicians may also confuse pharmacokinetic and pharmacodynamic interactions with pharmaceutical incompatibilities. This is a significant issue because it is incorrect to use the interaction modules of resources like uptodate.com and drugs.com to evaluate IV incompatibility. While various sources are available for checking IV incompatibility, some discrepancies exist among them. Therefore, there is a need for a comparative study that includes current and most well-known sources to assist clinicians in their selection. Comparisons of IV compatibility sources are not as common as those performed for drug-drug interactions. A study in 2023 noted that factors such as a lack of knowledge contributing to incompatibilities have not been extensively examined.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) This observation is fully consistent with our hospital practice and a review of the literature. Therefore, in comparing sources, it is crucial to consider the drugs that clinicians are already mixing, as this approach can yield more practically meaningful results. Detecting incompatible mixtures, along with a firm grasp of the fundamental chemistry and pharmacology involved in compatibility assessment and a heightened awareness of the issue, will play a significant role in improving patient care. The purpose of this study is to investigate physicians' knowledge on this subject, acquire data to generate solutions for potential problems, and simplify the selection of resources by providing a comparison of the most current and well-known sources.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis nationwide cross-sectional study was conducted between October and December 2024 in emergency departments across T\u0026uuml;rkiye. Ethical approval was obtained from the Ankara Bilkent City Hospital 1st Medical Research Scientific and Ethical Evaluation Board (TABED) (Decision No: TABED 1/606/2024, Date: 9 October 2024). Emergency department physicians actively practicing in T\u0026uuml;rkiye were eligible to participate. Participation was voluntary and anonymous, and no personal identifying information was collected. All responses obtained during the study period were included in the analysis.\u003c/p\u003e \u003cp\u003eData were collected using an online survey developed with Google Forms. The survey was distributed through digital communication channels, including social media platforms, in order to reach physicians working in emergency departments across multiple cities and regions. The questionnaire included both multiple-choice and open-ended questions addressing IV drug mixing practices, drugs perceived as compatible, information sources used for compatibility assessment, and physicians\u0026rsquo; educational needs on this topic. Anonymity was ensured to encourage candid responses and to minimize social desirability bias.\u003c/p\u003e \u003cp\u003eAll drugs reported by physicians were evaluated using the IV compatibility tools of four major drug information databases: Clinical Pharmacology (CP), DynaMedex (DM), Lexidrug (LD), and Stabilis (Ss). Drug mixtures containing more than two agents were analysed as binary combinations, since compatibility data in these databases are reported for drug pairs. For combinations identified as incompatible or uncertain, the route of administration (Y-site, admixture, or in-syringe) was recorded. This detailed classification was not applied to combinations with no reported incompatibility.\u003c/p\u003e \u003cp\u003eStatistical analyses were limited to descriptive statistics, and all analyses were performed using Microsoft Excel. Results are presented as frequencies and percentages.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOnly 34 physicians responded to the survey. Of these, 25 were general practitioners, while 9 stated they were specialists or in specialist training. The most frequently chosen method for checking the suitability of drug mixtures was \"what I learned from my professors/friends/my own clinical experience\" (CE [Clinical Experience]) (n\u0026thinsp;=\u0026thinsp;30, 88.2%). Of the four individuals who did not select this option, three chose online databases (ODB) and one chose \u0026ldquo;hospital protocols, algorithms, tables, brochures, or handbooks\u0026rdquo; (HP [hospital protocols]). Looking at the total numbers, 15 individuals selected ODB, and 9 selected HP. There were 15 physicians who selected only CE. When asked for details about the sources, \u0026ldquo;experience\u0026rdquo; was dominantly highlighted (including visual changes), while specific named sources included Medscape, Uptodate, Vademecum, Google, acilci.net, and WhatsApp. Other sources mentioned were drug leaflets, books, pharmacists, and internet searches. Three physicians stated that they did not check or research this information.\u003c/p\u003e \u003cp\u003eThe number of drugs in the mixtures varied (min: 2, max: 6). When organized as binary combinations, the most frequent mixtures they administered were pheniramine-dexamethasone (13%), diclofenac-thiocolchicoside (12%), and hyoscine butylbromide-metoclopramide (9.6%). Dexketoprofen and dexamethasone were the most frequently reported drugs in mixtures.\u003c/p\u003e \u003cp\u003eWhen examining the drugs physicians knew to be compatible (PKCD) and the mixtures they actually administered (PMD), 14 physicians listed additional drugs in PKCD beyond those in PMD, while 14 physicians listed additional drugs in PMD beyond those in PKCD. The number of physicians common to both groups was 5. Furthermore, 13 physicians listed the exact same drugs for both PKCD and PMD.\u003c/p\u003e \u003cp\u003eThe survey question \u0026ldquo;Which drugs would you like to learn about their mixing compatibility?\u0026rdquo; generated a high number of requests for specific drug combinations (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and the responses to the question about additional questions and contributions revealed broader concerns and practical issues related to drug mixing (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eWhat drugs would you like to know can be mixed?\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiclofenac-thiocolchicoside\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll of them\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll drugs used in the emergency department\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePheniramine-dexamethasone, hyoscine butylbromide-metoclopramide, dexketoprofen-metoclopramide, dexketoprofen-thiocolchicoside, dexketoprofen-paracetamol, tramadol-paracetamol\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiclofenac-dexamethasone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhich drugs insulin can be mixed with\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePheniramine\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyoscine butylbromide\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI would like a template on how the most frequently used drugs in the emergency department can be used\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiepileptics\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI had read that antibiotics cannot be mixed with any drug group. If there are any that can be mixed, I'd like to know\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone of them\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI would like to know about combinations with antibiotics and steroids\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics and nonsteroidal anti-inflammatory drugs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhether all the drugs I mentioned are 100% miscible\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"1\"\u003e*Similar answers are listed only once in the table.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eResponses to the question \"Your additional questions and contributions regarding drugs administered in the same syringe or mixture\"\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhat are the duration parameters and metabolism in the mechanism of action?\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhich ones can be administered together?\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA reliable source is essential.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAs a general pharmacology principle, we should not mix any drugs, but we do so for practical reasons due to the high workload in emergency departments and the shortage of support staff.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIs it more effective to administer them separately rather than as a single mixture?\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAs new practitioners, many of my colleagues and I feel it is safer to apply simple treatments based on what we hear and learn from others. By 'simple treatments,' I mean avoiding a wide variety of orders in the emergency department. I am personally hesitant about mixing drugs myself. Simple, clear templates that could help us with this would be very useful.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOndansetron and pantoprazole cannot be mixed. Antibiotics should not be mixed. Mixing multiple drugs should be avoided as much as possible.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWe sometimes observe that pheniramine causes some drugs to deteriorate.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCould you recommend a simple, practical app or website for this?\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\u003e30 (88.2%) of the physicians thought they needed more information on this topic, while 2 (5.9%) stated they did not, and 2 (5.9%) were unsure.\u003c/p\u003e \u003cp\u003eWhen the four sources were evaluated together, 15 of the PMD+PKCD were found to be compatible, 1 to be incompatible, and for 3 the results were mixed (uncertain). For the other mixtures, there was no data. There was no entry for pheniramine in any of the four sources, so no results were available for it. All details are provided in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe acetaminophen-dexketoprofen mixture was found to be y-site incompatible in LD and in-syringe uncertain in Ss. While the pantoprazole-metoclopramide mixture was y-site uncertain in DM, CP, and LD, it was in-syringe incompatible in all four sources. The ceftriaxone-vitamin C mixture was y-site incompatible in DM, CP, and LD. For the ceftriaxone-metronidazole mixture, it was admix and y-site compatible in DM, admix uncertain but y-site compatible in CP, admix and y-site compatible in LD, and in-syringe uncertain in Ss.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eConsistent with our clinical experience, the most frequently used source of information for physicians regarding drug mixtures was their colleagues. However, physicians also expressed a desire to learn the names of reliable sources they could use for this purpose. It would be beneficial for physicians to be aware of resources that specifically evaluate pharmaceutical incompatibilities, in addition to the databases they use for pharmacokinetic/pharmacodynamic interactions. The mention of sources like Uptodate.com and Medscape in the surveys was a predictable finding, consistent with our clinical experience and correspondence among physicians on this topic. The Uptodate interaction module attempts to prevent this confusion with a note stating, \u0026ldquo;NOTE: This tool does not address chemical compatibility related to I.V. drug preparation or administration.\u0026rdquo;; however, this warning may have been overlooked by some users. To address all these problems, more studies on this under-discussed topic are needed. There is a notable lack of studies evaluating IV compatibility databases. Some of these studies compare outdated or no longer used resources.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) This current work is the first of its kind to not only compare these sources but also survey emergency physicians directly on the subject. The scarcity of research on such a vital topic is consistent with the apparent lack of adequate interest among physicians regarding this issue. While one physician in the study used visual changes for compatibility assessment, this remains the most fundamental component of physical compatibility evaluation, although it is insufficient on its own.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Physical compatibility is generally considered more critical than chemical compatibility.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Differences were observed between the mixtures physicians actually administered (PMD) and the drugs they knew to be compatible (PKCD). Contributing factors may include the mixing of drugs based on empirical knowledge and the predominant use of different medications in various emergency departments. In fact, some physicians, when asked which drugs they would like to know can be mixed, listed the same drugs they had already reported administering.\u003c/p\u003e \u003cp\u003eOne physician reported administering a ceftriaxone-vitamin C mixture. This mixture was found to be y-site incompatible in three sources (with 4 references in each database). For admix or in-syringe administration, the result was 'No Data'. In Stabilis (Ss), there was no result at all. Furthermore, this physician specified the mixture as ceftriaxone\u0026thinsp;+\u0026thinsp;hyoscine butylbromide\u0026thinsp;+\u0026thinsp;metoclopramide\u0026thinsp;+\u0026thinsp;vitamin B complex\u0026thinsp;+\u0026thinsp;vitamin C\u0026thinsp;+\u0026thinsp;dexketoprofen. Since the B vitamin complex is yellow in color, it is difficult to visually assess the physical compatibility of this mixture. While the results for the acetaminophen-dexketoprofen and pantoprazole-metoclopramide mixtures showed differences, a potentially more significant problem was observed with the ceftriaxone-metronidazole mixture. Specifically, while it appeared compatible in DM and LD, it was found to be uncertain in CP and Ss. This serves as a good example of how relying on a single database can lead to negative outcomes. These databases are tertiary references, and it is crucial to evaluate and verify information from multiple tertiary sources.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePheniramine is not listed in any of the four sources. Therefore, it is not possible to assess the compatibility of pheniramine using these databases. This study should draw attention to this issue. It is observed that physicians, in the additional questions and contributions section of the survey, requested \"robust,\" \"simple,\" and \"practical\" resources. While the results are variable even for a drug that is available in the sources, the complete absence of some drugs is far from meeting this demand from physicians. Physicians working in the demanding conditions of an emergency department need to work with fewer resources and fewer confusing factors. The pheniramine-dexamethasone pair, which is frequently used in our emergency departments but for which compatibility data is insufficient, was the most common PMD in this study. In a previous study we conducted, this mixture was found to be physiochemically compatible.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Furthermore, additional studies on pheniramine compatibility are still needed. A physician in this study stated that they have \"witnessed pheniramine sometimes causing some drugs to deteriorate\". Chlorpheniramine is available in DM, LD, and CP; however, from a chemical standpoint, its use as a substitute for pheniramine would not be appropriate. For the same reason, substituting ketoprofen for dexketoprofen was also not deemed appropriate. Indeed, when ketoprofen is selected instead of dexketoprofen in sources that do contain dexketoprofen, different results are observed. Ketoprofen is available in both DM and CP. Piracetam is another drug that continues to be frequently used in emergency departments, yet an entry for it is found only in LD. In contrast, there is no entry for another commonly used drug, thiocolchicoside, in LD. Although tenoxicam is not used as frequently, its absence from the free database Ss may be another potential drawback for physicians. This is also the case for the vitamin B complex, which is not found in Ss. Furthermore, even if the active ingredients of the preparations used for vitamin B complex are the same, the variation in excipients (auxiliary substances)(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) indicates that checking a single database is not a definitive solution. Brousseau et al. indeed reported observing precipitation in a mixture when they used a new preparation with the same active ingredient from a different manufacturer.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Updates addressing this excipient issue could be implemented in the databases. Differences in excipients (e.g., lidocaine content) may alter compatibility, requiring caution.\u003c/p\u003e \u003cp\u003eThe source used for IV compatibility in DM, CP, and LD is stated to be the Trissel\u0026rsquo;s 2 Clinical Pharmaceutics Database. Users might assume that because the source name is the same, the databases are identical in all aspects; however, this study has shown that this is not the case. Trissel\u0026rsquo;s has been regarded as a fundamental resource for drug information for many years,(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) which suggests that ensuring consistency and standardization among the databases that use it would be beneficial for users. A study from 2009, for example, demonstrated that resources based on Trissel\u0026rsquo;s performed better than other incompatibility checkers.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) The positive aspects of Ss include its free nature and the fact that its authors draw on a wide variety of languages.\u003c/p\u003e \u003cp\u003e The data obtained from these databases and the literature review, taking personal experiences into account, could be useful in preparing templates or guidelines; however, this is a short-term solution. All drugs mentioned by the physicians should be investigated, but particular attention should be paid to the drugs that physicians listed as \"mixed\" (PMD) but did not list as \"known to be compatible\" (PKCD). This suggests that physicians may be using these mixtures without being certain of their compatibility. This is further supported by physicians' requests in the additional questions and contributions section to \"learn whether the drugs they mentioned can be mixed\". This study can serve as a pilot study for larger and more advanced research that could be conducted with different surveys.\u003c/p\u003e \u003cp\u003eThe fact that some mixtures are listed as 'No Data' (ND) in the sources may be because certain drugs have never been tested due to their chemical structure. For example, pantoprazole is an acid-labile drug and can be affected by the pH of hyoscine butylbromide,(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) while diclofenac sodium is alkaline.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) Mixtures that are ND in databases but have such theoretical chemical risks should be avoided if possible. While it was anticipated that the pantoprazole-hyoscine butylbromide mixture might be chemically incompatible, our laboratory study did not observe significant pH changes; however, incompatibility signals were seen in the optical density values.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Considering that physicians reported using this mixture and that pantoprazole is one of the most common causes of incompatibility,(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) this is highly significant. Three mixtures containing pantoprazole were reported in this study, and the results for all three were either ND or uncertain.\u003c/p\u003e \u003cp\u003eStudies on intravenous incompatibility have been found to be insufficient. Garcia et al. noted that this limitation is particularly pronounced in the \"national scenario\".(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) This statement is consistent with the findings of our study. Furthermore, while metamizole is frequently used in Brazil, compatibility studies on it are inadequate.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) In our country, metamizole use is also common, and physicians reported mixing it with some drugs. However, no data is available in the databases. During the analysis phase of this study, the names of the active ingredient salts from the commercial preparations specified by the physicians were used. For example, instead of methylprednisolone acetate, methylprednisolone sodium succinate salt was selected in the database.\u003c/p\u003e \u003cp\u003eIt is evident that healthcare professionals need more training on this topic. Almost all of the physicians in our study (n\u0026thinsp;=\u0026thinsp;30) answered \"yes\" to the question of whether they needed more information. Notably, one of the two physicians who selected \"I am not sure\" was a specialist using Medscape for IV compatibility, while the other was a general practitioner who left most of the questions blank. Of the physicians who answered \"no,\" one only mentioned the diclofenac-thiocolchicoside mixture. It can be inferred that this physician was not very interested in the topic or did not feel the need for more information. The other physician who answered \"no,\" however, stated that although drugs should not be mixed, they do so due to high workload and a lack of personnel, which highlights the need for further discussion on this issue. Indeed, our study included physicians who reported being \"hesitant about mixing drugs\" and requested suggestions for simple, practical templates, apps, or websites.\u003c/p\u003e \u003cp\u003eAlthough the sample size was limited, the participants were from many different cities. The consistency of their answers suggests that this list effectively captures the national practice. Regarding the analysis, we did not perform complex statistical tests. Since our goal was to simply map the current situation and the lack of database data, we chose to present the results with descriptive statistics only. Finally, while the survey structure might appear detailed, it was deliberately designed to be sufficient for the planned scope of this study, offering valuable insights into the gap between theoretical knowledge and clinical habits.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003eThe author declares no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eFinancial Support:\u003c/h2\u003e \u003cp\u003eNo financial or institutional support was received for this study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contributions:\u003c/h2\u003e \u003cp\u003eConcept and design: A\u0026Ouml;; Data collection: A\u0026Ouml;; Analysis and interpretation: A\u0026Ouml;; Manuscript drafting and revision: A\u0026Ouml;; Final approval of the manuscript: A\u0026Ouml;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSriram S, Aishwarya S, Moithu A, Sebastian A, Kumar A (2020) Intravenous Drug Incompatibilities in the Intensive Care Unit of a Tertiary Care Hospital in India: Are they Preventable? 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Instituto Israelita de Ensino e Pesquisa Albert Einstein 14:185\u0026ndash;189. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1590/S1679-45082016AO3723\u003c/span\u003e\u003cspan address=\"10.1590/S1679-45082016AO3723\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Drug Information Databases, Emergency Medicine, Intravenous Drug Incompatibility, Medication Safety","lastPublishedDoi":"10.21203/rs.3.rs-9354196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9354196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eIntravenous (IV) drug incompatibility represents a significant patient safety concern in emergency departments, where multiple medications are frequently administered under time pressure. This study aimed to evaluate physicians\u0026rsquo; real-world IV drug mixing practices and to assess the consistency of major IV compatibility databases with these practices.\u003c/p\u003e\u003ch2\u003eMaterial and Methods\u003c/h2\u003e \u003cp\u003eThis nationwide, cross-sectional study was conducted using an anonymous online survey distributed to emergency department physicians across T\u0026uuml;rkiye. The survey collected data on drugs commonly mixed in clinical practice, drugs perceived as compatible, and information sources used for compatibility checks. All reported drug combinations were evaluated using four major IV compatibility databases. Analyses were limited to descriptive statistics and are presented as frequencies and percentages.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 34 physicians participated in the study. Clinical experience was the most frequently used source for assessing IV drug compatibility (n\u0026thinsp;=\u0026thinsp;30, 88.2%). Significant discrepancies were observed between clinical practice and database information. Several commonly mixed drugs had no compatibility data available in any of the databases. Among evaluated combinations, some were classified inconsistently across sources, being reported as compatible, incompatible, or uncertain depending on the database. Overall, substantial gaps and inconsistencies in IV compatibility information were identified.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEmergency physicians predominantly rely on informal knowledge when mixing IV drugs, while available compatibility databases demonstrate notable data gaps and inter-database inconsistencies. These findings highlight the need for improved clinician education, expansion of compatibility database content\u0026mdash;particularly for commonly used agents\u0026mdash;and the development of practical decision-support tools to enhance medication safety in emergency settings.\u003c/p\u003e","manuscriptTitle":"Drug Incompatibility in Emergency Departments: A Comparative Evaluation of Clinical Practices and Pharmaceutical Interaction Sources","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 16:33:18","doi":"10.21203/rs.3.rs-9354196/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"90cc9cca-272c-45b6-bd26-692e3bf88462","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65918198,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2026-04-09T16:33:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 16:33:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9354196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9354196","identity":"rs-9354196","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}