{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:53:13Z","timestamp":1790477593716,"version":"4.1.0"},"reference-count":180,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Kounis syndrome is an allergic acute coronary syndrome precipitated by coronary vasospasm, plaque destabilization, stent thrombosis, or bypass occlusion. Cardiac surgery represents a uniquely high-risk setting due to cardiopulmonary bypass\u2013associated inflammation and exposure to multiple pharmaceutical agents. Importantly, Kounis syndrome remains underrecognized in this context, as classical signs of anaphylaxis may be masked under general anesthesia and cardiopulmonary bypass, while ischemic manifestations may be misattributed to other perioperative conditions. Methods: A narrative review of PubMed-indexed literature was conducted to synthesize current evidence on the pathophysiology, perioperative triggers, clinical presentation, diagnostic strategies, and management of Kounis syndrome in cardiac surgery, with emphasis on intraoperative recognition and surgical decision-making. Published cases were retrieved involving perioperative cardiac surgery patients with a definite diagnosis of Kounis syndrome. Additionally, cases presenting with severe perioperative anaphylaxis and life-threatening cardiovascular involvement (grade III with cardiovascular collapse and grade IV with cardiac arrest) were included as possible Kounis syndrome, reflecting real-world diagnostic uncertainty in the intraoperative setting. Results: The literature review identified five cases of definite Kounis syndrome and ten cases of possible Kounis syndrome, including three cases with cardiovascular collapse and seven cases with cardiac arrest. Recurrent episodes were reported in several patients, particularly due to re-exposure to the triggering agent. In the context of cardiac surgery, Kounis syndrome is most frequently triggered by chlorhexidine, protamine, antibiotic prophylaxis, and anesthetic agents. The clinical presentation is often subtle during cardiopulmonary bypass. Vasoplegia, pulmonary hypertension, ventricular dysfunction, new regional wall-motion abnormalities, and hyperdynamic ventricles on transesophageal echocardiography commonly precede overt electrocardiographic changes. Diagnosis is primarily clinical and relies on intraoperative ultrasound, hemodynamic monitoring, serum tryptase, serum troponin, and, when indicated, coronary angiography. A dual-pathway approach addressing both anaphylaxis and myocardial ischemia is essential; however, one component may predominate, particularly in perioperative patients with limited clinical information, potentially leading to misdiagnosis. A multidisciplinary approach is therefore required for rapid diagnosis and individualized management. In refractory cases, cardiopulmonary bypass or ventricular assist devices may provide lifesaving support. Conclusions: Kounis syndrome remains underrecognized in cardiac surgery but carries significant morbidity. Increased clinical awareness, multidisciplinary collaboration, structured diagnostic approaches, and preventive strategies are essential to improve outcomes and reduce the risk of recurrence during future procedures.<\/jats:p>","DOI":"10.3390\/medsci14020207","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:04:59Z","timestamp":1776963899000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kounis Syndrome in Cardiac Surgery: Pathophysiology, Antimicrobial Triggers, and Perioperative Recognition and Management"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-0059","authenticated-orcid":false,"given":"Vasileios","family":"Leivaditis","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery, Westpfalz Klinikum, 67655 Kaiserslautern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5449-0911","authenticated-orcid":false,"given":"Christodoulos","family":"Chatzigrigoriadis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, General University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-4047","authenticated-orcid":false,"given":"Efstratios","family":"Koletsis","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, General University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1610-0156","authenticated-orcid":false,"given":"Virginia","family":"Mplani","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, General University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis","family":"Dousdampanis","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Saint Andrews State General Hospital, 26221 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-2628","authenticated-orcid":false,"given":"Francesk","family":"Mulita","sequence":"additional","affiliation":[{"name":"Department of General Surgery, General Hospital of Eastern Achaia\u2013Unit of Aigio, 25100 Aigio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-6710","authenticated-orcid":false,"given":"Nicholas G.","family":"Kounis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, General University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-3681","authenticated-orcid":false,"given":"Stelios F.","family":"Assimakopoulos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, General University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1742-1241.1991.tb10251.x","article-title":"Histamine-induced coronary artery spasm: The concept of allergic angina","volume":"45","author":"Kounis","year":"1991","journal-title":"Br. 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