{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:41:50Z","timestamp":1787730110195,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intramuscular adrenaline (epinephrine) is the first\u2010line treatment for anaphylaxis. This recommendation is based purely on consensus, not randomised controlled trials. In humans, hypotension and shock strongly correlate with plasma histamine concentrations. The efficacy of intramuscular adrenaline in reversing histamine\u2010induced hypotension remains unproven. This trial evaluated whether intramuscular adrenaline reverses histamine\u2010induced shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted an exploratory open\u2010label trial and a confirmatory randomised, double\u2010blind, placebo\u2010controlled, crossover trial. Healthy volunteers received a 15\u2010min continuous intravenous histamine infusion to induce hypotension. At 5\u2009min, participants received either intramuscular adrenaline (300\u2013500\u2009\u03bcg) or placebo. A second adrenaline dose was administered if the mean arterial pressure (MAP) remained below 60\u2009mmHg at 10\u2009min. The primary endpoint was area under the effect curve for change in MAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During histamine\u2010induced hypotension, intramuscular adrenaline failed to produce a pressor response and was indistinguishable from placebo in the majority of participants. Excluding two subjects who needed a simultaneous dose reduction of histamine, only 5 of 20 participants (25%; 95% CI 8.7%\u201349.1%) demonstrated a transient MAP recovery after a single dose. A second adrenaline dose administered to participants who did not reach a MAP &gt;\u200960\u2009mmHg also failed to reverse hypotension. The primary outcome in the confirmatory cohort, excluding two subjects with histamine dose adjustments, was not different between treatments (adrenaline\u2010placebo: 7\u2009mmHg\u00b7min, 95% CI \u22122 to 25;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.06).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this study of a limited number of healthy human subjects, intramuscular adrenaline injections did not provide a sustained response in severe histamine\u2010mediated hypotension in a majority of recipients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      CTIS (2022\u2013003591\u201016) and ISRCTN (Nr. 11335622;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1186\/ISRCTN11335622\">https:\/\/doi.org\/10.1186\/ISRCTN11335622<\/jats:ext-link>\n                      )\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70277","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:44:12Z","timestamp":1773013452000},"page":"2490-2499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of Intramuscular Adrenaline on Histamine\u2010Induced Hypotension: A Randomised Placebo\u2010Controlled Pilot Trial"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-9091","authenticated-orcid":false,"given":"Matthias","family":"Weiss\u2010Tessbach","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Vienna 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Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u2010Luise","family":"Ritter\u2010Hobl","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-2166","authenticated-orcid":false,"given":"Barbara","family":"Steinlechner","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Sonnberger","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Gelbenegger","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-1635","authenticated-orcid":false,"given":"Jolanta M.","family":"Siller\u2010Matula","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Division of Cardiology Medical University of Vienna  Vienna 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