Anaphylactic Shock Following Intravenous Ranitidine: A Near-Fatal Case from Rural Nepal and Lessons for Low-Resource Settings

Anaphylactic Shock Following Intravenous Ranitidine: A Near-Fatal Case from Rural Nepal and Lessons for Low-Resource Settings | 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 Anaphylactic Shock Following Intravenous Ranitidine: A Near-Fatal Case from Rural Nepal and Lessons for Low-Resource Settings Rojee Shrestha, Ashal Timalsina, Arjun Gaire, Roshan Acharya, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7949094/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Dec, 2025 Read the published version in International Journal of Emergency Medicine → Version 1 posted 14 You are reading this latest preprint version Abstract Background Ranitidine, a histamine-2 (H2) receptor antagonist, is widely used for acid-peptic disorders. Although generally safe, it is a rare but recognized cause of drug-induced anaphylaxis, with an estimated incidence of 0.2–0.7% for H2 receptor blockers and proton pump inhibitors. We report a near-fatal case of ranitidine-induced anaphylactic shock successfully managed in a rural hospital. Case presentation A 35-year-old female developed sudden shortness of breath, hypotension, and drowsiness within minutes of receiving a 50 mg intravenous dose of ranitidine for epigastric discomfort at a local clinic. She had no prior exposure to ranitidine or known allergies. On arrival, her blood pressure was 60 mmHg systolic, pulse 130/min, and SpO₂ 60%. She had diffuse urticaria and wheezing. A diagnosis of anaphylactic shock was made. Immediate management included high-flow oxygen, intramuscular epinephrine (0.5 mg, 1:1000), followed by intravenous hydrocortisone. Significant improvement occurred within 10 minutes and she was discharged after 24 hours of observation. Conclusion This case underscores the need for awareness that even common drugs like ranitidine can trigger anaphylaxis. In low-resource settings, early recognition, prompt epinephrine use and the availability of life-saving medications are crucial to prevent fatal outcomes. Ranitidine Anaphylaxis Epinephrine Shock Background Ranitidine, a histamine-2 (H2) receptor antagonist, is a widely used drug for its anti-secretory properties of gastric acid, given usually for acid peptic disorders. ( 1 ) While generally considered safe, it is a rarely reported but well-documented cause of anaphylaxis. The incidence of anaphylactic reaction to H2 receptor blockers (Cimetidine and Ranitidine) and PPI (Pantoprazole, Omeprazole and lansoprazole) was together found to be 0.2 to 0.7%. ( 2 ) We report a case of near-fatal anaphylactic shock following IV ranitidine, successfully resuscitated in a rural hospital, to reinforce awareness of this adverse event and discuss the practical management challenges in such settings. Case Presentation A 35-year-old female presented to our rural district hospital with an acute onset of difficulty breathing, lethargy and an inability to stand. According to the accompanying personnel, the symptoms began approximately 5 to 10 minutes after she received a single 50 mg intravenous dose of ranitidine at a local clinic for a complaint of burning epigastric pain. The administration was performed by a paramedic without direct physician supervision. The patient also had an involuntary passage of stool and urine and was noted to be drowsy. Past Medical History: The patient had no history of chronic illnesses, no prior surgeries, and no known drug or food allergies. This was her first documented exposure to an H2 receptor antagonist (Ranitidine). Examination Findings at ER Vital Signs: Blood pressure 60/- mmHg, pulse 130 beats per minute, regular, respiratory rate 32 breaths per minute, SpO2 60% on room air. General: Drowsy, but oriented to time, place, and person (GCS 15/15). Pallor present, cool and clammy skin with visible widespread urticaria. Systemic Examination: Respiratory: Tachypneic with use of accessory muscles. Bilateral air entry was decreased with diffuse wheeze on auscultation. Cardiovascular: Tachycardic heart sounds with no murmurs. Neurological: No focal deficits. Investigation: ECG: Sinus tachycardia with regular rhythm, no ischemic changes. GRBS: 98 mg/dl Routine Labs (sent after stabilization): Complete Blood Count, Renal Function Tests, and Liver Function Tests were all within normal limits. Management and Clinical Course A diagnosis of anaphylactic shock was made immediately based on the temporal relationship to the drug, the multi-system involvement (respiratory, cardiovascular, neurological) and the profound shock state. The management followed a sequential protocol: Immediate Interventions: The patient was placed in a supine position with legs elevated. Airway & Breathing: High-flow oxygen at 15 L/min was administered via a face mask with a reservoir. Circulation: · Two large-bore (16G) IV cannulas were secured. · A rapid intravenous crystalloid fluid bolus (Normal Saline) was initiated. · Inj. Epinephrine 0.5 mg (0.5 mL of 1:1000 solution) was administered intramuscularly into the anterolateral thigh. 4. Adjunct Medications: · Inj. Hydrocortisone 200 mg IV Response to Treatment: Within 5–10 minutes of epinephrine administration, a dramatic improvement was noted. The patient became more alert, her blood pressure improved to 130/80 mmHg, heart rate decreased to 90 bpm, and SpO2 rose to 98% on oxygen. The wheezing resolved. Oxygen was successfully weaned off after 30 minutes as she maintained SpO2 > 95% on room air. She was monitored in the hospital for 24 hours and was discharged the next day in a stable condition with complete resolution of symptoms. She was explicitly counseled to avoid all H2 receptor antagonists in the future and was provided with a written allergy alert. Discussion Anaphylaxis is a severe, systemic hypersensitivity reaction that is rapid in onset and characterized by life-threatening airway, breathing, and/or circulatory problems, and that is usually associated with skin and mucosal changes.( 3 ) A study showed that most cases (57%) of anaphylaxis are due to unspecified triggers, 27% cases are associated with food and 12% of cases are medication associated.( 4 ) The drug categories most frequently linked to anaphylaxis include antibiotics, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. In contrast, the classes most commonly associated with fatal anaphylactic reactions are antibiotics, radiocontrast agents, and medications used during surgical procedures.( 5 ) The overall mortality rate from anaphylaxis across all causes ranged from 0.002 to 2.51 deaths per million person-years. Fatal anaphylaxis triggered by food (0.002–0.29 per million person-years) was comparatively uncommon, whereas drug-induced anaphylaxis showed a higher mortality range (0.004–0.56), exceeding that associated with Hymenoptera venom (0.02–0.61). This highlights that medications are a leading contributor to fatal anaphylactic events.( 6 ) The most commonly reported adverse effects of Ranitidine include headache, fatigue, dizziness, and mild gastrointestinal symptoms such as diarrhoea, constipation, and nausea.( 7 ) Hypersensitivity reactions to ranitidine are uncommon; however, their clinical presentation can vary widely. Most cases involve mild to moderate skin and mucosal manifestations, while severe reactions such as bronchospasm and anaphylaxis occur only rarely.( 8 ) H2-antihistamines are sometimes used as adjunctive therapy in the management of anaphylaxis, both with and without circulatory shock.( 9 ) Interestingly, although H2-antihistamines help manage allergic reactions, they themselves have been implicated in rare cases of anaphylaxis, with drugs like ranitidine reported to trigger severe hypersensitivity reactions in certain individuals. Clinical manifestations of anaphylaxis result from IgE mediated direct release of histamine and other inflammatory mediators from mast cells.( 10 ) U Rethnam reported a case of ranitidine anaphylaxis in a case of acute pancreatitis.( 11 ) Anaphylaxis occurring upon first exposure to ranitidine has been reported in the literature. In a study by Antonicelli et al., an 18-year-old male developed intraoperative anaphylaxis with elevated serum levels of ranitidine-specific IgE.( 12 ). Similarly, in our case, the patient had no known previous exposure to ranitidine, further supporting the likelihood of an anaphylactic reaction occurring upon first contact with the drug. Prompt administration of epinephrine is the cornerstone of anaphylaxis management, as early treatment significantly improves patient outcomes and helps prevent progression to severe or fatal reactions. Conversely, delayed use or failure to administer epinephrine has been strongly associated with increased mortality.( 13 ) Multiple studies have demonstrated that epinephrine is often underutilized in the management of anaphylaxis. This underuse is primarily attributed to a lack of timely recognition of anaphylaxis, limited knowledge regarding the appropriate indications for epinephrine administration and insufficient confidence in its use.( 14 , 15 ) These challenges are likely to be even more pronounced in low-resource settings, where limited training opportunities may further hinder prompt and effective treatment. In our case, epinephrine was administered promptly, followed by corticosteroids, as evidence suggests that corticosteroid therapy may help prevent or shorten the duration of protracted or biphasic anaphylactic reactions.( 16 ) Conclusion This case highlights an important lesson for healthcare providers in low-resource settings about the need for a high index of suspicion for anaphylaxis, even when administering commonly used medications. It underscores the importance of ensuring that life-saving drugs such as epinephrine are readily available at all times and that medical personnel are adequately trained to promptly recognize and manage anaphylactic reactions. Abbreviations H2 Histamine 2 mg milligrams mmHg millimeters of mercury PPI Proton Pump Inhibitor Iv Intravenous ER Emergency Room GCS Glasgow coma scale GRBS General Random Blood Sugar dl deciliter L Liter ml milliliters Inj Injection IV intravenous Declarations Acknowledgements We thank all the clinicians involved in the management of this patient. Authors’ contributions RS: Writing original draft, literature review and manuscript preparation AT: Literature review and manuscript preparation. AG: Review and editing. RA: Conceptualization and Supervision. AS: Clinical management, investigation, manuscript preparation. AyS: Literature review and consent. All authors read and approved the final manuscript. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Data availability No datasets were generated or analyzed during the current study Ethics approval and consent to participate As per the policy of our center, case reports not involving biomedical research are exempt from Institutional Review Committee (IRC) approval. Informed written consent has been obtained from the patient to participate. Consent for publication Informed written consent for publication of the patient’s case was obtained. Competing interests The authors declare no competing interests. References Ranitidine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2025 Oct 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548867/ Demirkan K, Bozkurt B, Karakaya G, Kalyoncu AF. Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature. J Investig Allergol Clin Immunol. 2006;16(3):203–9. Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017;140(2):335–48. Motosue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL. Increasing Emergency Department Visits for Anaphylaxis, 2005–2014. J Allergy Clin Immunol Pract. 2017;5(1):171–e1753. Yu RJ, Krantz MS, Phillips EJ, Stone CA. Emerging Causes of Drug–Induced Anaphylaxis: A Review of Anaphylaxis–Associated Reports in the FDA Adverse Event Reporting System (FAERS). J Allergy Clin Immunol Pract. 2021;9(2):819–e8292. Perez-Codesido S, Rosado-Ingelmo A, Privitera-Torres M, Pérez Fernández E, Nieto-Nieto A, Gonzalez-Moreno A, et al. Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies. J Investig Allergol Clin Immunol. 2022 July;22(4):245–60. Vial T, Goubier C, Bergeret A, Cabrera F, Evreux JC, Descotes J. Side effects of ranitidine. Drug Saf. 1991;6(2):94–117. Bocșan IC, Sabin O, Matei D, Muntean A, Buzoianu AD. How often we diagnose allergy to ranitidine? Eur Rev Med Pharmacol Sci. 2020;24(20):10812–8. Nurmatov UB, Rhatigan E, Simons FER, Sheikh A. H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2014;112(2):126–31. Stevens WW, Kraft M, Eisenbarth SC. Recent Insights into the Mechanisms of Anaphylaxis. Curr Opin Immunol. 2023;81:102288. Rethnam U, Yesupalan RS. Anaphylactic reaction associated with Ranitidine in a patient with acute pancreatitis: a case report. J Med Case Rep. 2007;1:75. Antonicelli L, Stagnozzi G, Massaccesi C, Manfredi M, Valentini M, Campi P. Intraoperative anaphylaxis: a case report of allergy to ranitidine. Eur Ann Allergy Clin Immunol. 2012;44(6):253–5. Navalpakam A, Thanaputkaiporn N, Poowuttikul P. Management of Anaphylaxis. Immunol Allergy Clin North Am. 2022;42(1):65–76. Prince BT, Mikhail I, Stukus DR. Underuse of epinephrine for the treatment of anaphylaxis: missed opportunities. J Asthma Allergy 2018 June 20;11:143–51. Bernstein DI, Blaiss M, Dellon ES, Rance K. Benefits of Epinephrine for Anaphylaxis Outweigh Potential Harm—A Safety Review. J Allergy Clin Immunol Pract [Internet]. 2025 Apr 18 [cited 2025 Oct 26]; Available from: https://www.sciencedirect.com/science/article/pii/S2213219825003757 Dodd A, Hughes A, Sargant N, Whyte AF, Soar J, Turner PJ. Evidence update for the treatment of anaphylaxis. Resuscitation. 2021 June;163:86–96. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Dec, 2025 Read the published version in International Journal of Emergency Medicine → Version 1 posted Editorial decision: Revision requested 14 Nov, 2025 Reviews received at journal 14 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviewers agreed at journal 10 Nov, 2025 Reviewers agreed at journal 10 Nov, 2025 Reviews received at journal 09 Nov, 2025 Reviewers agreed at journal 08 Nov, 2025 Reviewers agreed at journal 06 Nov, 2025 Reviewers agreed at journal 05 Nov, 2025 Reviewers invited by journal 03 Nov, 2025 Editor assigned by journal 29 Oct, 2025 Submission checks completed at journal 29 Oct, 2025 First submitted to journal 26 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Settings\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eRanitidine, a histamine-2 (H2) receptor antagonist, is a widely used drug for its anti-secretory properties of gastric acid, given usually for acid peptic disorders. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) While generally considered safe, it is a rarely reported but well-documented cause of anaphylaxis. The incidence of anaphylactic reaction to H2 receptor blockers (Cimetidine and Ranitidine) and PPI (Pantoprazole, Omeprazole and lansoprazole) was together found to be 0.2 to 0.7%. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) We report a case of near-fatal anaphylactic shock following IV ranitidine, successfully resuscitated in a rural hospital, to reinforce awareness of this adverse event and discuss the practical management challenges in such settings.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 35-year-old female presented to our rural district hospital with an acute onset of difficulty breathing, lethargy and an inability to stand. According to the accompanying personnel, the symptoms began approximately 5 to 10 minutes after she received a single 50 mg intravenous dose of ranitidine at a local clinic for a complaint of burning epigastric pain. The administration was performed by a paramedic without direct physician supervision. The patient also had an involuntary passage of stool and urine and was noted to be drowsy.\u003c/p\u003e\u003cp\u003ePast Medical History: The patient had no history of chronic illnesses, no prior surgeries, and no known drug or food allergies. This was her first documented exposure to an H2 receptor antagonist (Ranitidine).\u003c/p\u003e\u003cp\u003eExamination Findings at ER\u003c/p\u003e\u003cp\u003eVital Signs: Blood pressure 60/- mmHg, pulse 130 beats per minute, regular, respiratory rate 32 breaths per minute, SpO2 60% on room air.\u003c/p\u003e\u003cp\u003eGeneral: Drowsy, but oriented to time, place, and person (GCS 15/15). Pallor present, cool and clammy skin with visible widespread urticaria.\u003c/p\u003e\u003cp\u003eSystemic Examination:\u003c/p\u003e\u003cp\u003eRespiratory: Tachypneic with use of accessory muscles. Bilateral air entry was decreased with diffuse wheeze on auscultation.\u003c/p\u003e\u003cp\u003eCardiovascular: Tachycardic heart sounds with no murmurs.\u003c/p\u003e\u003cp\u003eNeurological: No focal deficits.\u003c/p\u003e\u003cp\u003eInvestigation:\u003c/p\u003e\u003cp\u003eECG: Sinus tachycardia with regular rhythm, no ischemic changes.\u003c/p\u003e\u003cp\u003eGRBS: 98 mg/dl\u003c/p\u003e\u003cp\u003eRoutine Labs (sent after stabilization): Complete Blood Count, Renal Function Tests, and Liver Function Tests were all within normal limits.\u003c/p\u003e\u003cp\u003eManagement and Clinical Course\u003c/p\u003e\u003cp\u003eA diagnosis of anaphylactic shock was made immediately based on the temporal relationship to the drug, the multi-system involvement (respiratory, cardiovascular, neurological) and the profound shock state.\u003c/p\u003e\u003cp\u003eThe management followed a sequential protocol:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eImmediate Interventions: The patient was placed in a supine position with legs elevated.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAirway \u0026amp; Breathing: High-flow oxygen at 15 L/min was administered via a face mask with a reservoir.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eCirculation:\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003e\u0026middot; Two large-bore (16G) IV cannulas were secured.\u003c/p\u003e\u003cp\u003e\u0026middot; A rapid intravenous crystalloid fluid bolus (Normal Saline) was initiated.\u003c/p\u003e\u003cp\u003e\u0026middot; Inj. Epinephrine 0.5 mg (0.5 mL of 1:1000 solution) was administered intramuscularly into the anterolateral thigh.\u003c/p\u003e\u003cp\u003e4. Adjunct Medications:\u003c/p\u003e\u003cp\u003e\u0026middot; Inj. Hydrocortisone 200 mg IV\u003c/p\u003e\u003cp\u003eResponse to Treatment: Within 5\u0026ndash;10 minutes of epinephrine administration, a dramatic improvement was noted. The patient became more alert, her blood pressure improved to 130/80 mmHg, heart rate decreased to 90 bpm, and SpO2 rose to 98% on oxygen. The wheezing resolved. Oxygen was successfully weaned off after 30 minutes as she maintained SpO2\u0026thinsp;\u0026gt;\u0026thinsp;95% on room air. She was monitored in the hospital for 24 hours and was discharged the next day in a stable condition with complete resolution of symptoms. She was explicitly counseled to avoid all H2 receptor antagonists in the future and was provided with a written allergy alert.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnaphylaxis is a severe, systemic hypersensitivity reaction that is rapid in onset and characterized by life-threatening airway, breathing, and/or circulatory problems, and that is usually associated with skin and mucosal changes.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eA study showed that most cases (57%) of anaphylaxis are due to unspecified triggers, 27% cases are associated with food and 12% of cases are medication associated.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The drug categories most frequently linked to anaphylaxis include antibiotics, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. In contrast, the classes most commonly associated with fatal anaphylactic reactions are antibiotics, radiocontrast agents, and medications used during surgical procedures.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe overall mortality rate from anaphylaxis across all causes ranged from 0.002 to 2.51 deaths per million person-years. Fatal anaphylaxis triggered by food (0.002\u0026ndash;0.29 per million person-years) was comparatively uncommon, whereas drug-induced anaphylaxis showed a higher mortality range (0.004\u0026ndash;0.56), exceeding that associated with Hymenoptera venom (0.02\u0026ndash;0.61). This highlights that medications are a leading contributor to fatal anaphylactic events.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe most commonly reported adverse effects of Ranitidine include headache, fatigue, dizziness, and mild gastrointestinal symptoms such as diarrhoea, constipation, and nausea.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Hypersensitivity reactions to ranitidine are uncommon; however, their clinical presentation can vary widely. Most cases involve mild to moderate skin and mucosal manifestations, while severe reactions such as bronchospasm and anaphylaxis occur only rarely.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eH2-antihistamines are sometimes used as adjunctive therapy in the management of anaphylaxis, both with and without circulatory shock.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Interestingly, although H2-antihistamines help manage allergic reactions, they themselves have been implicated in rare cases of anaphylaxis, with drugs like ranitidine reported to trigger severe hypersensitivity reactions in certain individuals. Clinical manifestations of anaphylaxis result from IgE mediated direct release of histamine and other inflammatory mediators from mast cells.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eU Rethnam reported a case of ranitidine anaphylaxis in a case of acute pancreatitis.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Anaphylaxis occurring upon first exposure to ranitidine has been reported in the literature. In a study by Antonicelli et al., an 18-year-old male developed intraoperative anaphylaxis with elevated serum levels of ranitidine-specific IgE.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Similarly, in our case, the patient had no known previous exposure to ranitidine, further supporting the likelihood of an anaphylactic reaction occurring upon first contact with the drug.\u003c/p\u003e\u003cp\u003ePrompt administration of epinephrine is the cornerstone of anaphylaxis management, as early treatment significantly improves patient outcomes and helps prevent progression to severe or fatal reactions. Conversely, delayed use or failure to administer epinephrine has been strongly associated with increased mortality.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Multiple studies have demonstrated that epinephrine is often underutilized in the management of anaphylaxis. This underuse is primarily attributed to a lack of timely recognition of anaphylaxis, limited knowledge regarding the appropriate indications for epinephrine administration and insufficient confidence in its use.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) These challenges are likely to be even more pronounced in low-resource settings, where limited training opportunities may further hinder prompt and effective treatment. In our case, epinephrine was administered promptly, followed by corticosteroids, as evidence suggests that corticosteroid therapy may help prevent or shorten the duration of protracted or biphasic anaphylactic reactions.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights an important lesson for healthcare providers in low-resource settings about the need for a high index of suspicion for anaphylaxis, even when administering commonly used medications. It underscores the importance of ensuring that life-saving drugs such as epinephrine are readily available at all times and that medical personnel are adequately trained to promptly recognize and manage anaphylactic reactions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eH2\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHistamine 2\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003emg\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emilligrams\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003emmHg\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emillimeters of mercury\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePPI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProton Pump Inhibitor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIv\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eER\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEmergency Room\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGCS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGlasgow coma scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGRBS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGeneral Random Blood Sugar\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003edl\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003edeciliter\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLiter\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eml\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emilliliters\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eInj\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInjection\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the clinicians involved in the management of this patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRS: Writing original draft, literature review and manuscript preparation AT: Literature review and manuscript preparation. AG: Review and editing. RA: Conceptualization and Supervision. AS: Clinical management, investigation, manuscript preparation. AyS: Literature review and consent.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analyzed during the current study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs per the policy of our center, case reports not involving biomedical research are exempt from Institutional Review Committee (IRC) approval. Informed written consent has been obtained from the patient to participate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed written consent for publication of the patient\u0026rsquo;s case was obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRanitidine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2025 Oct 24]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/books/NBK548867/\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/books/NBK548867/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDemirkan K, Bozkurt B, Karakaya G, Kalyoncu AF. Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature. J Investig Allergol Clin Immunol. 2006;16(3):203\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017;140(2):335\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMotosue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL. Increasing Emergency Department Visits for Anaphylaxis, 2005\u0026ndash;2014. J Allergy Clin Immunol Pract. 2017;5(1):171\u0026ndash;e1753.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu RJ, Krantz MS, Phillips EJ, Stone CA. Emerging Causes of Drug\u0026ndash;Induced Anaphylaxis: A Review of Anaphylaxis\u0026ndash;Associated Reports in the FDA Adverse Event Reporting System (FAERS). J Allergy Clin Immunol Pract. 2021;9(2):819\u0026ndash;e8292.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerez-Codesido S, Rosado-Ingelmo A, Privitera-Torres M, P\u0026eacute;rez Fern\u0026aacute;ndez E, Nieto-Nieto A, Gonzalez-Moreno A, et al. Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies. J Investig Allergol Clin Immunol. 2022 July;22(4):245\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVial T, Goubier C, Bergeret A, Cabrera F, Evreux JC, Descotes J. Side effects of ranitidine. Drug Saf. 1991;6(2):94\u0026ndash;117.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBocșan IC, Sabin O, Matei D, Muntean A, Buzoianu AD. How often we diagnose allergy to ranitidine? Eur Rev Med Pharmacol Sci. 2020;24(20):10812\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNurmatov UB, Rhatigan E, Simons FER, Sheikh A. H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2014;112(2):126\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStevens WW, Kraft M, Eisenbarth SC. Recent Insights into the Mechanisms of Anaphylaxis. Curr Opin Immunol. 2023;81:102288.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRethnam U, Yesupalan RS. Anaphylactic reaction associated with Ranitidine in a patient with acute pancreatitis: a case report. J Med Case Rep. 2007;1:75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAntonicelli L, Stagnozzi G, Massaccesi C, Manfredi M, Valentini M, Campi P. Intraoperative anaphylaxis: a case report of allergy to ranitidine. Eur Ann Allergy Clin Immunol. 2012;44(6):253\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNavalpakam A, Thanaputkaiporn N, Poowuttikul P. Management of Anaphylaxis. Immunol Allergy Clin North Am. 2022;42(1):65\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrince BT, Mikhail I, Stukus DR. Underuse of epinephrine for the treatment of anaphylaxis: missed opportunities. J Asthma Allergy 2018 June 20;11:143\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBernstein DI, Blaiss M, Dellon ES, Rance K. Benefits of Epinephrine for Anaphylaxis Outweigh Potential Harm\u0026mdash;A Safety Review. J Allergy Clin Immunol Pract [Internet]. 2025 Apr 18 [cited 2025 Oct 26]; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sciencedirect.com/science/article/pii/S2213219825003757\u003c/span\u003e\u003cspan address=\"https://www.sciencedirect.com/science/article/pii/S2213219825003757\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDodd A, Hughes A, Sargant N, Whyte AF, Soar J, Turner PJ. Evidence update for the treatment of anaphylaxis. Resuscitation. 2021 June;163:86\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"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":"Ranitidine, Anaphylaxis, Epinephrine, Shock","lastPublishedDoi":"10.21203/rs.3.rs-7949094/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7949094/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRanitidine, a histamine-2 (H2) receptor antagonist, is widely used for acid-peptic disorders. Although generally safe, it is a rare but recognized cause of drug-induced anaphylaxis, with an estimated incidence of 0.2–0.7% for H2 receptor blockers and proton pump inhibitors. We report a near-fatal case of ranitidine-induced anaphylactic shock successfully managed in a rural hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 35-year-old female developed sudden shortness of breath, hypotension, and drowsiness within minutes of receiving a 50 mg intravenous dose of ranitidine for epigastric discomfort at a local clinic. She had no prior exposure to ranitidine or known allergies. On arrival, her blood pressure was 60 mmHg systolic, pulse 130/min, and SpO₂ 60%. She had diffuse urticaria and wheezing. A diagnosis of anaphylactic shock was made. Immediate management included high-flow oxygen, intramuscular epinephrine (0.5 mg, 1:1000), followed by intravenous hydrocortisone. Significant improvement occurred within 10 minutes and she was discharged after 24 hours of observation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case underscores the need for awareness that even common drugs like ranitidine can trigger anaphylaxis. In low-resource settings, early recognition, prompt epinephrine use and the availability of life-saving medications are crucial to prevent fatal outcomes.\u003c/p\u003e","manuscriptTitle":"Anaphylactic Shock Following Intravenous Ranitidine: A Near-Fatal Case from Rural Nepal and Lessons for Low-Resource Settings","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 11:42:00","doi":"10.21203/rs.3.rs-7949094/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-14T19:25:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-14T18:52:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-13T01:44:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T05:44:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253797061122354431504575315179503728404","date":"2025-11-11T01:19:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150808486492196899714077877292125425552","date":"2025-11-10T21:31:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-09T15:47:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"130415204846556968379465899321341263724","date":"2025-11-08T14:43:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"138175974631641041488703563778544527657","date":"2025-11-06T05:25:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"266170703441491026959726536199932409597","date":"2025-11-06T03:08:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-03T20:10:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-29T13:09:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-29T13:06:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Emergency Medicine","date":"2025-10-26T04:59:25+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":"ac8c12c8-5b51-4ba3-b269-be7bdf629855","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T16:04:40+00:00","versionOfRecord":{"articleIdentity":"rs-7949094","link":"https://doi.org/10.1186/s12245-025-01101-0","journal":{"identity":"international-journal-of-emergency-medicine","isVorOnly":false,"title":"International Journal of Emergency Medicine"},"publishedOn":"2025-12-16 15:57:40","publishedOnDateReadable":"December 16th, 2025"},"versionCreatedAt":"2025-11-13 11:42:00","video":"","vorDoi":"10.1186/s12245-025-01101-0","vorDoiUrl":"https://doi.org/10.1186/s12245-025-01101-0","workflowStages":[]},"version":"v1","identity":"rs-7949094","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7949094","identity":"rs-7949094","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}