The Paradox of Pressure: A Case of Ceftriaxone-Induced Hypertensive Anaphylaxis Where Collapse Meets Surge – A Case Report

The Paradox of Pressure: A Case of Ceftriaxone-Induced Hypertensive Anaphylaxis Where Collapse Meets Surge – A Case Report | 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 The Paradox of Pressure: A Case of Ceftriaxone-Induced Hypertensive Anaphylaxis Where Collapse Meets Surge – A Case Report Bekele Asegahegn This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6959425/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 Anaphylaxis is a potentially life-threatening hypersensitivity reaction, most commonly associated with beta-lactam antibiotics. Although hypotension is a hallmark clinical feature, paradoxical presentations such as hypertensive responses have been documented. We report a case of a 40-year-old male who developed severe respiratory distress and hypertensive anaphylaxis following intravenous administration of ceftriaxone. The case emphasizes the need for clinical vigilance and timely intervention even in atypical anaphylactic presentations. Critical Care & Emergency Medicine Anaphylaxis ceftriaxone Hypertensive anaphylaxis Introduction Ceftriaxone, a third-generation cephalosporin, is widely utilized for the treatment of severe bacterial infections, including meningitis, pneumonia, and sepsis. Its adverse effect profile includes hypersensitivity reactions, occurring in 1–3% of patients, with anaphylaxis being exceedingly rare (0.001–0.1%) [ 1 ]. Anaphylaxis typically presents with hypotension, respiratory distress, mucocutaneous signs, or gastrointestinal symptoms. However, emerging evidence suggests a subset of patients may paradoxically develop hypertension during anaphylactic episodes, possibly due to endogenous catecholamine release or vasoconstrictor mechanisms [ 2 ]. Case Presentation A 40-year-old male, with a 3-year history of bronchial asthma but not on maintenance controller therapy, presented to the emergency department of Leku General Hospital with a 2-day history of worsening shortness of breath, chest tightness, wheezing, productive cough, and low-grade fever. He had no history of orthopnea, paroxysmal nocturnal dyspnea, palpitations, trauma, or known drug allergies. There was no significant surgical or family history. On presentation: General appearance: Alert, conscious, in severe respiratory distress (nasal flaring, use of accessory muscles, speaking in short phrases) Vital signs: BP 120/70 mmHg, HR 110 bpm, RR 36/min, Temp 37.8°C, SpO₂ 80% on room air Systemic exam: Chest: Increased work of breathing, Diffuse bilateral wheezing CVS: Normal S1 and S2, no murmur or gallop, JVP not elevated Abdomen: Soft, moves with respiration CNS: Conscious, oriented, normal sensorimotor exam He was diagnosed with a severe acute exacerbation of bronchial asthma likely triggered by community-acquired pneumonia (CAP). Immediate management included: 5 L/min oxygen via nasal prongs (SpO₂ improved to 98%) Salbutamol inhalation: 6 puffs every 20 minutes for 1 hour, then every hour for 4 hours IV hydrocortisone: 200 mg bolus, followed by 100 mg every 6 hours Antibiotics: Ceftriaxone (initially unavailable) After two hours of treatment, he showed marked clinical improvement: Vital signs: BP 120/70 mmHg, HR 84 bpm, RR 22/min, SpO₂ 89% on room air Decreased oxygen demand (from 5 L/min to 1 L/min) Reduced wheezing and respiratory distress Upon availability, 1 g IV ceftriaxone was administered. Within minutes, the patient developed sudden-onset respiratory distress, upper extremity pruritus, agitation, and audible inspiratory stridor. New vital signs: BP increased to 160/100 mmHg, then 180/100 mmHg 190/120 mmHg HR 120–140 bpm, RR 42–50/min SpO₂ dropped to 32% on 5 L/min oxygen, improved to 97% only with 15 L/min via non-rebreather mask Chest auscultation revealed inspiratory and expiratory wheezing with audible stridor A diagnosis of ceftriaxone-induced hypertensive anaphylaxis with impending airway obstruction was made. Management included: Immediate discontinuation of ceftriaxone 15 L/min oxygen via non-rebreather mask Re-administration of IV hydrocortisone Intramuscular and nebulized epinephrine Following epinephrine administration, the patient’s airway symptoms, blood pressure, and respiratory parameters gradually improved. He was admitted to the medical ward, switched to an alternative antibiotic, and continued asthma controller therapy. He was discharged in stable condition after three days. Discussion Anaphylaxis is a severe, systemic hypersensitivity reaction often mediated by IgE. While hypotension is a diagnostic hallmark, a paradoxical hypertensive response, though rare, has been observed in 10–15% of cases [ 3 , 4 ]. World Allergy Organization (WAO) 2020 criteria define anaphylaxis as: Acute onset of mucocutaneous symptoms with respiratory compromise or hypotension OR acute hypotension, bronchospasm, or laryngeal involvement after exposure to a known allergen, even without skin symptoms [ 5 ] In this case, hypertension rather than hypotension was the predominant cardiovascular feature. This paradoxical hypertension could be explained by: Compensatory release of catecholamines (epinephrine, norepinephrine) Activation of the renin-angiotensin system and endothelin-1 Mast cell–derived serotonin acting via vascular receptors Such atypical presentations underscore the importance of considering anaphylaxis even when hypotension is absent. Immediate use of epinephrine remains the cornerstone of therapy, regardless of blood pressure profile. Epinephrine acts by reversing airway obstruction, inhibiting mediator release, and improving vascular tone. Conclusion Ceftriaxone-induced anaphylaxis, though rare, can present atypically with hypertension rather than hypotension. Clinicians should maintain a high index of suspicion for anaphylaxis in any patient presenting with acute respiratory distress or airway compromise following drug exposure, regardless of the hemodynamic profile. Prompt recognition and early administration of epinephrine are critical for optimal outcomes. In conclusion Not all anaphylaxis collapses, some rise. Declarations Written informed consent was obtained from the patient for the publication of this case report. References Pichichero ME (2006) Cephalosporins can be prescribed safely for penicillin-allergic patients. J Fam Pract Muraro A et al (2014) Anaphylaxis: Guidelines from the European Academy of Allergy and Clinical Immunology. Allergy Simons FE et al (2012) World Allergy Organization Anaphylaxis Guidelines: 2012 Update. World Allergy Organ J James JM et al (2010) Hypertensive Anaphylaxis: Clinical Observations. Clin Exp Allergy World Allergy Organization Anaphylaxis Guidelines – 2020 Revision 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. 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-6959425","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":475362977,"identity":"020642c6-167e-4ed4-9535-83cdcd1dafa3","order_by":0,"name":"Bekele Asegahegn","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Bekele","middleName":"","lastName":"Asegahegn","suffix":""}],"badges":[],"createdAt":"2025-06-23 19:08:48","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6959425/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6959425/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85344054,"identity":"cc9a3635-6451-44a0-b57a-1c2963444774","added_by":"auto","created_at":"2025-06-25 01:30:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":245379,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6959425/v1/90ec7f21-5721-4dd2-a33a-306bd8b32019.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eThe Paradox of Pressure: A Case of Ceftriaxone-Induced Hypertensive Anaphylaxis Where Collapse Meets Surge – A Case Report\u003cbr\u003e\n\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCeftriaxone, a third-generation cephalosporin, is widely utilized for the treatment of severe bacterial infections, including meningitis, pneumonia, and sepsis. Its adverse effect profile includes hypersensitivity reactions, occurring in 1\u0026ndash;3% of patients, with anaphylaxis being exceedingly rare (0.001\u0026ndash;0.1%) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Anaphylaxis typically presents with hypotension, respiratory distress, mucocutaneous signs, or gastrointestinal symptoms. However, emerging evidence suggests a subset of patients may paradoxically develop hypertension during anaphylactic episodes, possibly due to endogenous catecholamine release or vasoconstrictor mechanisms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 40-year-old male, with a 3-year history of bronchial asthma but not on maintenance controller therapy, presented to the emergency department of Leku General Hospital with a 2-day history of worsening shortness of breath, chest tightness, wheezing, productive cough, and low-grade fever. He had no history of orthopnea, paroxysmal nocturnal dyspnea, palpitations, trauma, or known drug allergies. There was no significant surgical or family history.\u003c/p\u003e \u003cp\u003eOn presentation:\u003c/p\u003e \u003cp\u003eGeneral appearance: Alert, conscious, in severe respiratory distress (nasal flaring, use of accessory muscles, speaking in short phrases)\u003c/p\u003e \u003cp\u003eVital signs: BP 120/70 mmHg, HR 110 bpm, RR 36/min, Temp 37.8\u0026deg;C, SpO₂ 80% on room air\u003c/p\u003e \u003cp\u003eSystemic exam:\u003c/p\u003e \u003cp\u003eChest: Increased work of breathing, Diffuse bilateral wheezing\u003c/p\u003e \u003cp\u003eCVS: Normal S1 and S2, no murmur or gallop, JVP not elevated\u003c/p\u003e \u003cp\u003eAbdomen: Soft, moves with respiration\u003c/p\u003e \u003cp\u003eCNS: Conscious, oriented, normal sensorimotor exam\u003c/p\u003e \u003cp\u003eHe was diagnosed with a severe acute exacerbation of bronchial asthma likely triggered by community-acquired pneumonia (CAP). Immediate management included:\u003c/p\u003e \u003cp\u003e\u0026thinsp;5 L/min oxygen via nasal prongs (SpO₂ improved to 98%)\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSalbutamol inhalation: 6 puffs every 20 minutes for 1 hour, then every hour for 4 hours\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIV hydrocortisone: 200 mg bolus, followed by 100 mg every 6 hours\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAntibiotics: Ceftriaxone (initially unavailable)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAfter two hours of treatment, he showed marked clinical improvement:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eVital signs: BP 120/70 mmHg, HR 84 bpm, RR 22/min, SpO₂ 89% on room air\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDecreased oxygen demand (from 5 L/min to 1 L/min)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eReduced wheezing and respiratory distress\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eUpon availability, 1 g IV ceftriaxone was administered. Within minutes, the patient developed sudden-onset respiratory distress, upper extremity pruritus, agitation, and audible inspiratory stridor.\u003c/p\u003e \u003cp\u003eNew vital signs:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eBP increased to 160/100 mmHg, then 180/100 mmHg 190/120 mmHg\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHR 120\u0026ndash;140 bpm, RR 42\u0026ndash;50/min\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSpO₂ dropped to 32% on 5 L/min oxygen, improved to 97% only with 15 L/min via non-rebreather mask\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eChest auscultation revealed inspiratory and expiratory wheezing with audible stridor\u003c/p\u003e \u003cp\u003eA diagnosis of ceftriaxone-induced hypertensive anaphylaxis with impending airway obstruction was made.\u003c/p\u003e \u003cp\u003eManagement included:\u003c/p\u003e \u003cp\u003eImmediate discontinuation of ceftriaxone\u003c/p\u003e \u003cp\u003e\u0026thinsp;15 L/min oxygen via non-rebreather mask\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eRe-administration of IV hydrocortisone\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIntramuscular and nebulized epinephrine\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFollowing epinephrine administration, the patient\u0026rsquo;s airway symptoms, blood pressure, and respiratory parameters gradually improved. He was admitted to the medical ward, switched to an alternative antibiotic, and continued asthma controller therapy. He was discharged in stable condition after three days.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnaphylaxis is a severe, systemic hypersensitivity reaction often mediated by IgE. While hypotension is a diagnostic hallmark, a paradoxical hypertensive response, though rare, has been observed in 10\u0026ndash;15% of cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWorld Allergy Organization (WAO) 2020 criteria define anaphylaxis as:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAcute onset of mucocutaneous symptoms with respiratory compromise or hypotension\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eOR acute hypotension, bronchospasm, or laryngeal involvement after exposure to a known allergen, even without skin symptoms [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eIn this case, hypertension rather than hypotension was the predominant cardiovascular feature. This paradoxical hypertension could be explained by:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eCompensatory release of catecholamines (epinephrine, norepinephrine)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eActivation of the renin-angiotensin system and endothelin-1\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMast cell\u0026ndash;derived serotonin acting via vascular receptors\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eSuch atypical presentations underscore the importance of considering anaphylaxis even when hypotension is absent. Immediate use of epinephrine remains the cornerstone of therapy, regardless of blood pressure profile. Epinephrine acts by reversing airway obstruction, inhibiting mediator release, and improving vascular tone.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCeftriaxone-induced anaphylaxis, though rare, can present atypically with hypertension rather than hypotension. Clinicians should maintain a high index of suspicion for anaphylaxis in any patient presenting with acute respiratory distress or airway compromise following drug exposure, regardless of the hemodynamic profile. Prompt recognition and early administration of epinephrine are critical for optimal outcomes. In conclusion \u003cb\u003eNot all anaphylaxis collapses, some rise.\u003c/b\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePichichero ME (2006) Cephalosporins can be prescribed safely for penicillin-allergic patients. J Fam Pract\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuraro A et al (2014) Anaphylaxis: Guidelines from the European Academy of Allergy and Clinical Immunology. Allergy\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimons FE et al (2012) World Allergy Organization Anaphylaxis Guidelines: 2012 Update. World Allergy Organ J\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJames JM et al (2010) Hypertensive Anaphylaxis: Clinical Observations. Clin Exp Allergy\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Allergy Organization Anaphylaxis Guidelines \u0026ndash; 2020 Revision\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":"Leku General Hospital","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":"Anaphylaxis,ceftriaxone, Hypertensive anaphylaxis ","lastPublishedDoi":"10.21203/rs.3.rs-6959425/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6959425/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnaphylaxis is a potentially life-threatening hypersensitivity reaction, most commonly associated with beta-lactam antibiotics. Although hypotension is a hallmark clinical feature, paradoxical presentations such as hypertensive responses have been documented. We report a case of a 40-year-old male who developed severe respiratory distress and hypertensive anaphylaxis following intravenous administration of ceftriaxone. The case emphasizes the need for clinical vigilance and timely intervention even in atypical anaphylactic presentations.\u003c/p\u003e","manuscriptTitle":"The Paradox of Pressure: A Case of Ceftriaxone-Induced Hypertensive Anaphylaxis Where Collapse Meets Surge – A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 01:14:46","doi":"10.21203/rs.3.rs-6959425/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":"c2544d4e-33c5-4f09-92e9-b2e3aea720b4","owner":[],"postedDate":"June 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":50545283,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2025-06-25T01:14:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-25 01:14:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6959425","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6959425","identity":"rs-6959425","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}