From Therapy to Toxicity: Anticholinergic Syndrome After Standard-Dose Atropine

From Therapy to Toxicity: Anticholinergic Syndrome After Standard-Dose Atropine | 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 Case Report From Therapy to Toxicity: Anticholinergic Syndrome After Standard-Dose Atropine Nagihan YILMAZ, Ebru AKKOC, Cumali KUS, Aynur SAHIN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9200764/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Atropine, is an antimuscarinic agent used for symptomatic bradycardia and an antidote for muscarinic toxidrome. The standard treatment protocol involves administering doses of 0.5-1 mg every 3–5 minutes until the desired heart rate is achieved, with a maximum dose of 3 mg. The common side effects include dry mouth, blurred vision, photophobia, and tachycardia. While individual tolerance varies, disturbance of speech, ataxia, disorientation, hallucinations, and delirium are generally not observed at doses exceeding 5 mg. We report a case of a patient treated with standard-dose atropine, and who developed tanticholinergic syndrome without overdose. A 57-year-old female presented to the emergency department with chest tightness, nausea, and vomiting. Initial electrocardiography demonstrated junctional bradycardia. She received standard-dose intravenous atropine. Shortly after atropine administration, her rhythm converted to junctional tachycardia. Approximately two hours later, she developed acute confusion, disorientation, mydriasis, dry mucosa, and orobuccal movements. Based on the symptoms, a diagnosis of anticholinergic syndrome likely induced by atropine was considered. Neuroimaging and laboratory investigations excluded metabolic, infectious, and intracranial causes. The patient was managed conservatively with intravenous fluids and close monitoring. Her symptoms resolved completely within 12 hours. Emergency physicians should recognize that anticholinergic syndrome may develop even after standard-dose atropine administration. Early identification and supportive management are essential, and clinicians should remain aware of possible idiosyncratic reactions. Atropine Anticholinergic syndrome Bradycardia Drug toxicity Figures Figure 1 Figure 2 Figure 3 Background Atropine, an antimuscarinic agent used for symptomatic bradycardia and an antidote for muscarinic toxidrome, functions by inhibiting muscarinic acetylcholine receptors[1]. Current guidelines recommend the early administration of atropine for the medical management of hemodynamically significant bradycardia [2]. The standard treatment protocol involves administering doses of 0.5-1 mg every 3–5 minutes until the desired heart rate is achieved, with a maximum dose of 3 mg [1,2]. The common side effects include dry mouth, blurred vision, photophobia, and tachycardia. While individual tolerance varies, disturbance of speech, ataxia, disorientation, hallucinations, and delirium are generally not observed at doses exceeding 5 mg, become severe at doses over 10 mg, and may be fatal at doses above 65 mg [3]. Anticholinergic syndrome typically follows an overdose of anticholinergic agents; however, mild toxicity can occur at therapeutic doses. Numerous agents including atropine, antidepressants, antihistamines, antiparkinsonian agents, antipsychotics, antispasmodics, and mydriatics, can cause this syndrome. Their toxicity results from competitive antagonism of acetylcholine at muscarinic receptors. The classic symptoms of anticholinergic poisoning are encapsulated by the mnemonic: “red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask,” referring to cutaneous flushing, anhidrosis, mydriasis with blurred vision, delirium, hyperthermia, and urinary retention[4]. This case report describes a patient treated with standard-dose atropine who developed anticholinergic syndrome without overdose, illustrating an uncommon but serious adverse reaction that emergency physicians must be prepared to recognize and manage. Case Presentation A 57-year-old female patient with a history of mitral valve surgery 15 years ago, known arrhythmia, and vertigo, presented to our hospital with chest tightness, nausea and vomiting. She was metoprolol, warfarin, trimetazidine dihydrochloride and betahistine dhydrochloride. She reported ongoing nausea, vomiting, and chest tightness. On physical examination, she appeared alert but mildly distressed with no focal neurological deficits or signs of respiratory distress. Her vital signs were as follows: blood pressure, 140/65 mmHg, heart rate, 46 beats per minute (bpm), and oxygen saturation, 98%. Electrocardiography (ECG) was performed which demonstrated a nodal rhythm with a heart rate of 43 bpm (Figure 1). The patient underwent cardiac monitoring, and intravenous crystalloid infusion was initiated. Three dose of atropine were administered intravenously, with a total dose of 1.5 mg. The cardiology department t evaluated the patient by the cardiology department, and atropine administration was also recommended by the cardiology team. Following atropine administration, the cardiac rhythm was converted to junctional tachycardia with a heart rate of 128 bpm (Figure 2). Subsequently, spontaneous reversion to nodal bradycardia and junctional tachycardia was observed in the absence of further pharmacological intervention. The patients Initial laboratory investigations were within normal limits except for mildly elevated troponin levels (51.7 ng/L at presentation; 53 ng/L at 1 hour). Following the acute management of bradycardia, further evaluation was performed to identify the underlying cause. Detailed history-taking revealed that the patient had initially presented to another hospital, where an ECG revealed supraventricular tachycardia and a 12.5 mg intravenous diltiazem had been administered. Following treatment with intravenous crystalloids, atropine, and ondansetron, the patient's symptoms improved. Shortly thereafter, about 2 hours the initial presentation, the patient developed acute confusion, she was disoriented and non-cooperative, and could not recognize her relatives. On physical examination, her Glasgow Coma Scale (GCS) score was 14, her pupils were isochoric and mydriatic, oral mucosa and skin were dry, and orobuccal movements were observed. Intravenous fluid therapy and antiemetic drugs were initiated, and a urinary catheter was inserted. Brain computed tomography and diffusion-weighted MRI revealed no intracranial pathologies. Based on these symptoms, a diagnosis of anticholinergic syndrome likely induced by atropine was considered. Causality assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 6, indicating a probable adverse drug reactions [5] . Physostigmine therapy was considered to confirm and treat anticholinergic syndrome; however, it was withheld due to concerns about precipitating cholinergic syndrome, particularly given the presence of anticholinergic toxicity symptoms despite therapeutic atropine levels, and the absence of an urgent clinical indication. The patient was instead managed conservatively, with close observation and intravenous hydration. After 12 h of observation, the patient’s clinical status returned to baseline. She was alert, fully oriented, and cooperative (GCS score: 15), with normal-sized pupils, moist oral mucosa, and no neurologic or systemic symptoms. Her ECG showed a sinus rhythm with 51 bpm (Figure 3). Given the full resolution of her symptoms and normalization of vital signs and neurological examination, the patient was discharged in good condition with recommendations for outpatient follow-up. Discussion The diagnosis of anticholinergic toxicity can be challenging, because its clinical presentation often mimics delirium from other etiologies. In our case, the laboratory results supported a non-infectious, non-metabolic cause of the symptoms. Neuroimaging revealed no evidence of intracranial hemorrhage or ischemic stroke. The abrupt onset of symptoms and their temporal association with atropine administration strongly support central anticholinergic toxicity as the underlying cause, rather than an alternative systemic or neurological disorder. The literature contains a few case reports have described anticholinergic syndrome secondary to atropine ophthalmic drops. The reported patients ranged in age from 12 to 65 years, and the timing of exposure varied from 1 to 10 days of use. In these cases, toxicity was attributed to systemic absorption of the drug via the conjunctiva or nasolacrimal duct, with subsequent entry into the cerebral circulation through the angular vein and cavernous sinus. However, it remains unclear why a therapeutic dose of atropine can precipitate anticholinergic syndrome in certain individuals [6–8]. A case similar to ours has been reported in which a single 0.6 mg intramuscular dose of atropine, administered as pre-anesthetic medication before bronchoscopy, induced delirium. After resolution of symptoms, atropine ophthalmic drops were administered for fundoscopic evaluation to exclude neurological disease, and recurrence of delirium. The authors suggested that delirium at therapeutic atropine levels represents an idiosyncratic reaction[9]. Similarly, Cao et al. reported an idiosyncratic reaction triggered by a single 0.5 mg dose of atropine[10]. In our case, the development of bradycardia following standard-dose calcium channel blocker administration, together with the emergence of anticholinergic syndrome after treatment with atropine, raised the consideration of interindividual variability in drug response, including potential pharmacogenetic differences. However, when the distribution and elimination pathways of calcium channel blockers and atropine are considered, a pharmacokinetic or pharmacogenetic basis is unlikely. In this context, as also discussed in previously reported cases, the development of anticholinergic syndrome following a therapeutic-dose of atropine cannot be definitively explained and has been interpreted as an idiosyncratic reaction. Conclusion This case underscores the importance of recognizing atropine-induced anticholinergic syndrome even after standard therapeutic dosing. Emergency physicians should maintain a high index of suspicion when atypical neurological symptoms arise shortly after administration of atropine. Clinicians should consider the potential for individual susceptibility, idiosyncratic reactions, and pharmacogenetic variability when administering medications. Abbreviations ECG: Electrocardiography GCS: Glasgow Coma Scale Declarations Ethical statements and consent to participate Ethical approval was not required for this case report in accordance with institutional policies. Written informed consent was obtained from the patient for publication of this case and accompanying images. Informed consent for publication of the research details and clinical images was obtained from the patient. Conflict of interest The authors have no conflicts of interest to declare. Funding The authors received no financial support for this study. Author contributions Conceptualization: NY, EA; Methodology: CK, AS; Investigation: all authors; Writing–original draft: EA, NY; Writing–review & editing: CK, NY, AS. All authors read and approved the final manuscript. Acknowledgments None References McLendon K, Preuss CV. Atropine. StatPearls, Treasure Island (FL): StatPearls Publishing; 2025. Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2019;140:e382–482. https://doi.org/10.1161/CIR.0000000000000628. Atropine Sulfate - Medical Countermeasures Database - CHEMM n.d. https://chemm.hhs.gov/countermeasure_atropine-sulfate.htm (accessed July 14, 2025). Broderick ED, Metheny H, Crosby B. Anticholinergic Toxicity. StatPearls [Internet], StatPearls Publishing; 2023. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clinical Pharmacology & Therapeutics 1981;30:239–45. https://doi.org/10.1038/clpt.1981.154. Raschka M, Khant M. Ophthalmic Atropine: A Typical Anticholinergic Toxidrome From an Atypical Old Culprit. J Pediatr Pharmacol Ther 2023;28:565–7. https://doi.org/10.5863/1551-6776-28.6.565. Soletchnik M, Rousseau G, Gonzalez L, Laribi S. Central anticholinergic syndrome secondary to atropine eye drops: A case study. Br J Clin Pharmacol 2023;89:541–3. https://doi.org/10.1111/bcp.15408. Maravi P, Mishra DK, Singh A, Niranjan V. Atropine eye-drop-induced acute delirium: a case report. Gen Psychiatr 2020;33:e100125. https://doi.org/10.1136/gpsych-2019-100125. Panchasara A, Mandavia D, Anovadiya AP, Tripathi CB. Central Anti-Cholinergic Syndrome Induced by Single Therapeutic Dose of Atropine. Current Drug Safety 2012;7:35–6. https://doi.org/10.2174/157488612800492799. Cao X, Cui Y, White PF, Tang J, Ma H. Central anticholinergic syndrome vs. idiosyncratic reaction triggered by a small IV dose of atropine. Acta Anaesthesiologica Scandinavica 2016;60:270–3. https://doi.org/10.1111/aas.12638. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 24 Apr, 2026 Reviewers agreed at journal 24 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 30 Mar, 2026 Submission checks completed at journal 30 Mar, 2026 First submitted to journal 23 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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-9200764","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":631066816,"identity":"98510a89-b1a4-4e74-8d47-5d6f83f94246","order_by":0,"name":"Nagihan YILMAZ","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYJCCw0DMwwdifQBiNnZitbABCcYZIC3MRGgBqwFpYeaBc/EAc/bjFw8X7jgswyZ2+PFnm1/b5PmYGRg/fMzBrcWyJ6fg8Mwzh3nYpNMMjHP7bhu2MTMwS87chluLwYGchMO8bSAtCQbJuT23GYFa2Jh58Wk5/wamJf3DYcue2/aEtdxIPwDVkmPYzPDjdiIRWt4wALWkg7QUM/Y23E5uY2Zsxu+X8+mPP/O2WdvzS6dv/vDjz23b+e3NBz98xKMFGIkGQKIZwmZsA5MN+NQDAfsDIFEH5fwhoHgUjIJRMApGJAAA5tVP9sHjNNUAAAAASUVORK5CYII=","orcid":"","institution":"Basaksehir Cam and Sakura City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Nagihan","middleName":"","lastName":"YILMAZ","suffix":""},{"id":631066818,"identity":"1e46c71a-e320-450b-9973-597f70bd10fa","order_by":1,"name":"Ebru AKKOC","email":"","orcid":"","institution":"Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ebru","middleName":"","lastName":"AKKOC","suffix":""},{"id":631066822,"identity":"9747203d-2a07-4bc1-b5fc-9ccf8350bba6","order_by":2,"name":"Cumali KUS","email":"","orcid":"","institution":"Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cumali","middleName":"","lastName":"KUS","suffix":""},{"id":631066824,"identity":"ad4932f4-11df-46ec-a657-2874e0300518","order_by":3,"name":"Aynur SAHIN","email":"","orcid":"","institution":"Basaksehir Cam and Sakura City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aynur","middleName":"","lastName":"SAHIN","suffix":""}],"badges":[],"createdAt":"2026-03-23 12:53:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9200764/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9200764/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108407494,"identity":"06ebd116-4f28-4fea-b686-67acbfc13b27","added_by":"auto","created_at":"2026-05-04 09:52:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":899091,"visible":true,"origin":"","legend":"\u003cp\u003eElectrocardiogram obtained at emergency department presentation demonstrating junctional (nodal) bradycardia with a heart rate of approximately 43 beats per minute.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9200764/v1/de935ca6b6c2cdb9ff45a77b.png"},{"id":108407492,"identity":"2abe9caf-630e-4141-8e5f-feee57b7b798","added_by":"auto","created_at":"2026-05-04 09:52:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":951260,"visible":true,"origin":"","legend":"\u003cp\u003eElectrocardiogram recorded after intravenous atropine administration showing conversion to junctional tachycardia with a rate of approximately 128 beats per minute.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9200764/v1/260fc42f1a84dbe660bfc0a8.png"},{"id":108493460,"identity":"b62b42eb-2105-457d-8994-7ca214f8a995","added_by":"auto","created_at":"2026-05-05 10:00:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":897950,"visible":true,"origin":"","legend":"\u003cp\u003eFollow-up electrocardiogram obtained after resolution of anticholinergic symptoms demonstrating sinus rhythm with a heart rate of 51 beats per minute.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9200764/v1/683568b74577dd7f2f4d539a.png"},{"id":109295955,"identity":"1e2106fc-5feb-464e-959d-f353a4288cc5","added_by":"auto","created_at":"2026-05-15 08:41:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2274937,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9200764/v1/1eaf3db6-7cce-4bf9-9f35-37c268716ed0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"From Therapy to Toxicity: Anticholinergic Syndrome After Standard-Dose Atropine","fulltext":[{"header":"Background","content":"\u003cp\u003eAtropine, an antimuscarinic agent used for symptomatic bradycardia and an antidote for muscarinic toxidrome, functions by inhibiting muscarinic acetylcholine receptors[1]. Current guidelines recommend the early administration of atropine for the medical management of hemodynamically significant bradycardia [2]. The standard treatment protocol involves administering doses of 0.5-1 mg every 3\u0026ndash;5 minutes until the desired heart rate is achieved, with a maximum dose of 3 mg [1,2].\u003c/p\u003e \u003cp\u003eThe common side effects include dry mouth, blurred vision, photophobia, and tachycardia. While individual tolerance varies, disturbance of speech, ataxia, disorientation, hallucinations, and delirium are generally not observed at doses exceeding 5 mg, become severe at doses over 10 mg, and may be fatal at doses above 65 mg [3]. Anticholinergic syndrome typically follows an overdose of anticholinergic agents; however, mild toxicity can occur at therapeutic doses. Numerous agents including atropine, antidepressants, antihistamines, antiparkinsonian agents, antipsychotics, antispasmodics, and mydriatics, can cause this syndrome. Their toxicity results from competitive antagonism of acetylcholine at muscarinic receptors. The classic symptoms of anticholinergic poisoning are encapsulated by the mnemonic: \u0026ldquo;red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask,\u0026rdquo; referring to cutaneous flushing, anhidrosis, mydriasis with blurred vision, delirium, hyperthermia, and urinary retention[4].\u003c/p\u003e \u003cp\u003eThis case report describes a patient treated with standard-dose atropine who developed anticholinergic syndrome without overdose, illustrating an uncommon but serious adverse reaction that emergency physicians must be prepared to recognize and manage.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 57-year-old female patient with a history of mitral valve surgery 15 years ago, known arrhythmia, and vertigo, presented to our hospital with chest tightness, nausea and vomiting. She was metoprolol, warfarin, trimetazidine dihydrochloride and betahistine dhydrochloride.\u003c/p\u003e\n\u003cp\u003eShe reported ongoing nausea, vomiting, and chest tightness. On physical examination, she appeared alert but mildly distressed with no focal neurological deficits or signs of respiratory distress. Her vital signs were as follows: blood pressure, 140/65 mmHg, heart rate, 46 beats per minute (bpm), and oxygen saturation, 98%. Electrocardiography (ECG) was performed which demonstrated a nodal rhythm with a heart rate of 43 bpm (Figure 1). The patient underwent cardiac monitoring, and intravenous crystalloid infusion was initiated. Three dose of atropine were administered intravenously, with a total dose of 1.5 mg. The cardiology department t evaluated the patient by the cardiology department, and atropine administration was also recommended by the cardiology team. Following atropine administration, the cardiac rhythm was converted to junctional tachycardia with a heart rate of 128 bpm (Figure 2). Subsequently, spontaneous reversion to nodal bradycardia and junctional tachycardia was observed in the absence of further pharmacological intervention. The patients Initial laboratory investigations were within normal limits except for mildly elevated troponin levels (51.7 ng/L at presentation; 53 ng/L at 1 hour).\u003c/p\u003e\n\u003cp\u003eFollowing the acute management of bradycardia, further evaluation was performed to identify the underlying cause. Detailed history-taking revealed that the patient had initially presented to another hospital, where an ECG revealed supraventricular tachycardia and a 12.5 mg intravenous diltiazem had been administered. \u003c/p\u003e\n\u003cp\u003eFollowing treatment with intravenous crystalloids, atropine, and ondansetron, the patient\u0026apos;s symptoms improved. Shortly thereafter, about 2 hours the initial presentation, the patient developed acute confusion, she was disoriented and non-cooperative, and could not recognize her relatives. On physical examination, her Glasgow Coma Scale (GCS) score was 14, her pupils were isochoric and mydriatic, oral mucosa and skin were dry, and orobuccal movements were observed. Intravenous fluid therapy and antiemetic drugs were initiated, and a urinary catheter was inserted. Brain computed tomography and diffusion-weighted MRI revealed no intracranial pathologies. Based on these symptoms, a diagnosis of anticholinergic syndrome likely induced by atropine was considered. \u003cstrong\u003eCausality assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 6, indicating a probable adverse drug reactions \u003c/strong\u003e\u003cstrong\u003e[5]\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhysostigmine therapy was considered to confirm and treat anticholinergic syndrome; however, it was withheld due to concerns about precipitating cholinergic syndrome, particularly given the presence of anticholinergic toxicity symptoms despite therapeutic atropine levels, and the absence of an urgent clinical indication. The patient was instead managed conservatively, with close observation and intravenous hydration.\u003c/p\u003e\n\u003cp\u003eAfter 12 h of observation, the patient\u0026rsquo;s clinical status returned to baseline. She was alert, fully oriented, and cooperative (GCS score: 15), with normal-sized pupils, moist oral mucosa, and no neurologic or systemic symptoms. Her ECG showed a sinus rhythm with 51 bpm (Figure 3). Given the full resolution of her symptoms and normalization of vital signs and neurological examination, the patient was discharged in good condition with recommendations for outpatient follow-up. \u003c/p\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of anticholinergic toxicity can be challenging, because its clinical presentation often mimics delirium from other etiologies. In our case, the laboratory results supported a non-infectious, non-metabolic cause of the symptoms. Neuroimaging revealed no evidence of intracranial hemorrhage or ischemic stroke. The abrupt onset of symptoms and their temporal association with atropine administration strongly support central anticholinergic toxicity as the underlying cause, rather than an alternative systemic or neurological disorder.\u003c/p\u003e \u003cp\u003eThe literature contains a few case reports have described anticholinergic syndrome secondary to atropine ophthalmic drops. The reported patients ranged in age from 12 to 65 years, and the timing of exposure varied from 1 to 10 days of use. In these cases, toxicity was attributed to systemic absorption of the drug via the conjunctiva or nasolacrimal duct, with subsequent entry into the cerebral circulation through the angular vein and cavernous sinus. However, it remains unclear why a therapeutic dose of atropine can precipitate anticholinergic syndrome in certain individuals [6\u0026ndash;8].\u003c/p\u003e \u003cp\u003eA case similar to ours has been reported in which a single 0.6 mg intramuscular dose of atropine, administered as pre-anesthetic medication before bronchoscopy, induced delirium. After resolution of symptoms, atropine ophthalmic drops were administered for fundoscopic evaluation to exclude neurological disease, and recurrence of delirium. The authors suggested that delirium at therapeutic atropine levels represents an idiosyncratic reaction[9]. Similarly, Cao et al. reported an idiosyncratic reaction triggered by a single 0.5 mg dose of atropine[10].\u003c/p\u003e \u003cp\u003eIn our case, the development of bradycardia following standard-dose calcium channel blocker administration, together with the emergence of anticholinergic syndrome after treatment with atropine, raised the consideration of interindividual variability in drug response, including potential pharmacogenetic differences. However, when the distribution and elimination pathways of calcium channel blockers and atropine are considered, a pharmacokinetic or pharmacogenetic basis is unlikely. In this context, as also discussed in previously reported cases, the development of anticholinergic syndrome following a therapeutic-dose of atropine cannot be definitively explained and has been interpreted as an idiosyncratic reaction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case underscores the importance of recognizing atropine-induced anticholinergic syndrome even after standard therapeutic dosing. Emergency physicians should maintain a high index of suspicion when atypical neurological symptoms arise shortly after administration of atropine. Clinicians should consider the potential for individual susceptibility, idiosyncratic reactions, and pharmacogenetic variability when administering medications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eECG: Electrocardiography\u003c/p\u003e\n\u003cp\u003eGCS: Glasgow Coma Scale\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003e\u003cstrong\u003eEthical statements and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econsent to participate\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eEthical approval was not required for this case report in accordance with institutional policies. Written informed consent was obtained from the patient for publication of this case and accompanying images.\u003c/p\u003e\n\u003cp\u003eInformed consent for publication of the research details and clinical images was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: NY, EA; Methodology: CK, AS; Investigation: all authors; Writing\u0026ndash;original draft: EA, NY; Writing\u0026ndash;review \u0026amp; editing: CK, NY, AS. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMcLendon K, Preuss CV. Atropine. StatPearls, Treasure Island (FL): StatPearls Publishing; 2025.\u003c/li\u003e\n\u003cli\u003eKusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2019;140:e382\u0026ndash;482. https://doi.org/10.1161/CIR.0000000000000628.\u003c/li\u003e\n\u003cli\u003eAtropine Sulfate - Medical Countermeasures Database - CHEMM n.d. https://chemm.hhs.gov/countermeasure_atropine-sulfate.htm (accessed July 14, 2025).\u003c/li\u003e\n\u003cli\u003eBroderick ED, Metheny H, Crosby B. Anticholinergic Toxicity. StatPearls [Internet], StatPearls Publishing; 2023.\u003c/li\u003e\n\u003cli\u003eNaranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clinical Pharmacology \u0026amp; Therapeutics 1981;30:239\u0026ndash;45. https://doi.org/10.1038/clpt.1981.154.\u003c/li\u003e\n\u003cli\u003eRaschka M, Khant M. Ophthalmic Atropine: A Typical Anticholinergic Toxidrome From an Atypical Old Culprit. J Pediatr Pharmacol Ther 2023;28:565\u0026ndash;7. https://doi.org/10.5863/1551-6776-28.6.565.\u003c/li\u003e\n\u003cli\u003eSoletchnik M, Rousseau G, Gonzalez L, Laribi S. Central anticholinergic syndrome secondary to atropine eye drops: A case study. Br J Clin Pharmacol 2023;89:541\u0026ndash;3. https://doi.org/10.1111/bcp.15408.\u003c/li\u003e\n\u003cli\u003eMaravi P, Mishra DK, Singh A, Niranjan V. Atropine eye-drop-induced acute delirium: a case report. Gen Psychiatr 2020;33:e100125. https://doi.org/10.1136/gpsych-2019-100125.\u003c/li\u003e\n\u003cli\u003ePanchasara A, Mandavia D, Anovadiya AP, Tripathi CB. Central Anti-Cholinergic Syndrome Induced by Single Therapeutic Dose of Atropine. Current Drug Safety 2012;7:35\u0026ndash;6. https://doi.org/10.2174/157488612800492799.\u003c/li\u003e\n\u003cli\u003eCao X, Cui Y, White PF, Tang J, Ma H. Central anticholinergic syndrome vs. idiosyncratic reaction triggered by a small IV dose of atropine. Acta Anaesthesiologica Scandinavica 2016;60:270\u0026ndash;3. https://doi.org/10.1111/aas.12638.\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":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Atropine, Anticholinergic syndrome, Bradycardia, Drug toxicity","lastPublishedDoi":"10.21203/rs.3.rs-9200764/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9200764/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAtropine, is an antimuscarinic agent used for symptomatic bradycardia and an antidote for muscarinic toxidrome. The standard treatment protocol involves administering doses of 0.5-1 mg every 3\u0026ndash;5 minutes until the desired heart rate is achieved, with a maximum dose of 3 mg. The common side effects include dry mouth, blurred vision, photophobia, and tachycardia. While individual tolerance varies, disturbance of speech, ataxia, disorientation, hallucinations, and delirium are generally not observed at doses exceeding 5 mg. We report a case of a patient treated with standard-dose atropine, and who developed tanticholinergic syndrome without overdose.\u003c/p\u003e \u003cp\u003eA 57-year-old female presented to the emergency department with chest tightness, nausea, and vomiting. Initial electrocardiography demonstrated junctional bradycardia. She received standard-dose intravenous atropine. Shortly after atropine administration, her rhythm converted to junctional tachycardia. Approximately two hours later, she developed acute confusion, disorientation, mydriasis, dry mucosa, and orobuccal movements. Based on the symptoms, a diagnosis of anticholinergic syndrome likely induced by atropine was considered. Neuroimaging and laboratory investigations excluded metabolic, infectious, and intracranial causes. The patient was managed conservatively with intravenous fluids and close monitoring. Her symptoms resolved completely within 12 hours.\u003c/p\u003e \u003cp\u003eEmergency physicians should recognize that anticholinergic syndrome may develop even after standard-dose atropine administration. Early identification and supportive management are essential, and clinicians should remain aware of possible idiosyncratic reactions.\u003c/p\u003e","manuscriptTitle":"From Therapy to Toxicity: Anticholinergic Syndrome After Standard-Dose Atropine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 09:52:17","doi":"10.21203/rs.3.rs-9200764/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-24T10:03:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87952996051646392155248592188661475458","date":"2026-04-24T07:38:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T14:12:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-30T09:07:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-30T09:07:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Emergency Medicine","date":"2026-03-23T12:43:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8b0d52bb-2cb3-498f-9159-d7d502099c38","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T09:52:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 09:52:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9200764","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9200764","identity":"rs-9200764","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}