{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:27:23Z","timestamp":1780486043931,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: General and local anaesthetics are widely used during surgery. These drugs have peculiar safety profiles, being commonly associated with mild and reversible local adverse drug reactions (ADRs), but also with more severe and systemic ADRs, including respiratory and cardiovascular depression and anaphylaxis. Methods and Objectives: We carried out a descriptive analysis of Individual Case Safety Reports (ICSRs) sent to the Campania Regional Centre of Pharmacovigilance (Southern Italy) from 2001 to 2021 that reported general or local anaesthetics as suspected drugs, with the aim of describing their overall characteristics, focussing on the ADRs\u2019 seriousness and distribution by System Organ Class (SOC) and Preferred Term (PT). Results: A total of 110 ICSRs documenting general or local anaesthetics were sent to the Italian pharmacovigilance database during 20 years of spontaneous reporting activities in the Campania region. ADRs mainly occurred in patients with a median age of 48 years and in a slightly higher percentage of men. ADRs were more commonly classified as not serious and had a favourable outcome. In terms of ADRs\u2019 distribution by SOC and PT, both general and local anaesthetics were associated with general and cutaneous disorders, with common ADRs that included lack of efficacy, rash, and erythema. In addition, general anaesthetics were associated with the occurrence of respiratory ADRs, while local anaesthetics were associated with the occurrence of nervous ADRs. Conclusion: Even though a limited number of ICSRs documenting anaesthetics-induced ADRs were retrieved from the Italian spontaneous reporting database in the Campania region, we believe that the continuous monitoring of these drugs is highly recommended, especially among the frail population.<\/jats:p>","DOI":"10.3390\/ph14121261","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Safety Profile of General and Local Anaesthetic Agents: Data Collected during 20 Years of Spontaneous Reporting Activities in the Campania Region (Southern Italy)"],"prefix":"10.3390","volume":"14","author":[{"given":"Francesca","family":"Gargano","sequence":"first","affiliation":[{"name":"UOC Anestesia e Rianimazione, Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-922X","authenticated-orcid":false,"given":"Cristina","family":"Scavone","sequence":"additional","affiliation":[{"name":"Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"di Mauro","sequence":"additional","affiliation":[{"name":"Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Della","family":"Corte","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Zoccoli","sequence":"additional","affiliation":[{"name":"Clinical Innovation Office, Universit\u00e0 Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Rossi","sequence":"additional","affiliation":[{"name":"Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Clinical Innovation Office, Universit\u00e0 Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Francesco","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical Surgical and Dental Sciences, Plastic Surgery Unit, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Capuano","sequence":"additional","affiliation":[{"name":"Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4236\/pp.2019.1010033","article-title":"Designing General Anesthetics That Have a Better Safety Profile","volume":"10","author":"Raffa","year":"2019","journal-title":"Pharmacol. Pharm."},{"key":"ref_2","unstructured":"Skibiski, J., and Abdijadid, S. (2021, November 01). Barbiturates, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539731\/."},{"key":"ref_3","first-page":"329","article-title":"The history of barbiturates a century after their clinical introduction","volume":"1","author":"Alamo","year":"2005","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/00000542-198503000-00017","article-title":"Midazolam: Pharmacology and uses","volume":"62","author":"Reves","year":"1985","journal-title":"Anesthesiology"},{"key":"ref_5","first-page":"S9","article-title":"Co-induction: A practical application of anesthetic drug interaction","volume":"6","author":"Vinik","year":"1993","journal-title":"Curr. Opin. Anesthesiol."},{"key":"ref_6","first-page":"172","article-title":"General anesthesia","volume":"38","author":"Rosenberg","year":"1991","journal-title":"Anesth. Prog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2741\/4241","article-title":"Mechanisms of action of general anesthetics","volume":"19","author":"Diao","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1051\/ject\/200537227","article-title":"General anesthesia in cardiac surgery: A review of drugs and practices","volume":"37","author":"Alwardt","year":"2005","journal-title":"J. Extra. Corpor. Technol."},{"key":"ref_9","unstructured":"Garmon, E.H., and Huecker, M.R. (2021, November 01). Topical, Local, and Regional Anesthesia and Anesthetics, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK430894\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.abd.2019.09.025","article-title":"Safety of local anesthetics","volume":"95","author":"Cherobin","year":"2020","journal-title":"An. Bras. Dermatol."},{"key":"ref_11","unstructured":"Smith, G., D\u2019Cruz, J.R., Rondeau, B., and Goldman, J. (2021, November 01). General Anesthesia for Surgeons, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK493199\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2146\/ajhp050460","article-title":"Inhaled anesthetic agents","volume":"63","author":"Stachnik","year":"2006","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_13","unstructured":"Lingamchetty, T.N., Hosseini, S.A., and Saadabadi, A. (2021, November 01). Midazolam, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK537321\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1007\/BF03012303","article-title":"Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia","volume":"45","author":"Whalley","year":"1998","journal-title":"Can J. Anaesth."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2165\/00003495-200161070-00003","article-title":"Newer Neuromuscular Blocking Agents","volume":"61","author":"Sparr","year":"2001","journal-title":"Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/DSS.0000000000000887","article-title":"A review of local anesthetics: Minimizing risk and side effects in cutaneous surgery","volume":"43","author":"Park","year":"2017","journal-title":"Derm. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1097\/AAP.0000000000000320","article-title":"A review of local anesthetic systemic toxicity cases since publication of the American Society of Regional Anesthesia Recommendations","volume":"40","author":"Vasques","year":"2015","journal-title":"Reg. Anesth. Pain. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"i46","DOI":"10.1093\/bja\/aev213","article-title":"The Ageing Brain: Age-dependent changes in the electroencephalogram during propofol and sevoflurane general anaesthesia","volume":"115","author":"Purdon","year":"2015","journal-title":"Br. J. Anaesth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.jamcollsurg.2006.08.026","article-title":"Surgical risk factors, morbidity, and mortality in elderly patients","volume":"203","author":"Turrentine","year":"2006","journal-title":"J. Am. Coll. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S0952-8180(03)00030-8","article-title":"A study of anesthetic drug utilization in different age groups","volume":"15","author":"Martin","year":"2003","journal-title":"J. Clin. Anesth."},{"key":"ref_21","first-page":"175","article-title":"Anesthesia for the elderly","volume":"11","author":"Kanonidou","year":"2007","journal-title":"Hippokratia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2165\/00128071-200102060-00001","article-title":"Do women have more adverse drug reactions?","volume":"2","author":"Rademaker","year":"2001","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00228-008-0494-6","article-title":"Women encounter ADRs more often than do men","volume":"64","author":"Zopf","year":"2008","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/14740338.2019.1598969","article-title":"Surveillance of adverse events following immunization related to human papillomavirus vaccines: 12 years of vaccinovigilance in Southern Italy","volume":"18","author":"Scavone","year":"2019","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.3389\/fphar.2018.01003","article-title":"Did the New Italian Law on Mandatory Vaccines Affect Adverse Event Following Immunization\u2019s Reporting? A Pharmacovigilance Study in Southern Italy","volume":"9","author":"Scavone","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3389\/fphar.2020.00830","article-title":"Immune Checkpoint Inhibitors and Immune-RelatedAdverseDrugReactions: Data from ItalianPharmacovigilance Database","volume":"11","author":"Ruggiero","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tips.2009.12.001","article-title":"Gender differences in drug toxicity","volume":"31","author":"Nicolson","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2344\/0003-3006-61.1.26","article-title":"Adverse drug reactions in dental practice","volume":"61","author":"Becker","year":"2014","journal-title":"Anesth. Prog."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.iac.2014.03.004","article-title":"Local and general anesthetics immediate hypersensitivity reactions","volume":"34","author":"Volcheck","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.mcna.2010.04.002","article-title":"Perioperative anaphylaxis","volume":"94","author":"Mertes","year":"2010","journal-title":"Med. Clin. N. Am."},{"key":"ref_31","first-page":"1664","article-title":"The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan","volume":"41","author":"Mitsuhata","year":"1992","journal-title":"Masui"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/pds.1196","article-title":"Adverse effects of neuromuscular blocking agents based on yellow card reporting in the U.K.: Are there differences between males and females?","volume":"15","author":"Light","year":"2006","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bja\/aet117","article-title":"Survival from perioperative anaphylaxis in Western Australia 2000\u20132009","volume":"111","author":"Gibbs","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/21556660.2019.1566137","article-title":"Healthcare professionals\u2019 pharmacovigilance knowledge and adverse drug reaction reporting behavior and factors determining the reporting rates","volume":"8","author":"Ekmekci","year":"2019","journal-title":"J. Drug Assess."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40264-020-01021-3","article-title":"PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database","volume":"44","author":"Zinzi","year":"2021","journal-title":"Drug Saf."},{"key":"ref_36","unstructured":"European Medicines Agency (2021, September 12). Guideline on Good Pharmacovigilance Practices (GVP). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/draft-guideline-good-pharmacovigilance-practices-module-vi-management-reporting-adverse-reactions_en.pdf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.4103\/0976-500X.120942","article-title":"Pharmacovigilance in Italy: An overview","volume":"4","author":"Russo","year":"2013","journal-title":"J. Pharm. Pharmacother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2165\/00023210-199810020-00004","article-title":"Adverse Effects of General Anaesthetics: Incidence and Therapeutic Implications","volume":"10","author":"Naguib","year":"1998","journal-title":"CNS Drugs"},{"key":"ref_39","first-page":"469","article-title":"Is anesthesia dangerous?","volume":"108","author":"Gottschalk","year":"2011","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1046\/j.1365-2044.2002.02565.x","article-title":"Awareness during general anaesthesia: A review of 81 cases from the Anaesthetic Incident Monitoring Study","volume":"57","author":"Bergman","year":"2002","journal-title":"Anaesthesia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2165\/00002018-200932040-00008","article-title":"Adverse drug reactions to local anaesthetics: A review of the French pharmacovigilance database","volume":"32","author":"Fuzier","year":"2009","journal-title":"Drug Saf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12630-012-9853-y","article-title":"Review article: Improving drug safety for patients undergoing anesthesia and surgery","volume":"60","author":"Orser","year":"2013","journal-title":"Can. J. Anesth."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/bjd.19677","article-title":"The value of case reports and spontaneous reporting systems for pharmacovigilance and clinical practice","volume":"184","author":"Raschi","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_44","unstructured":"(2021, September 16). ICH E2D Post-Approval Safety Data Management|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use_en-12.pdf."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/12\/1261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:27Z","timestamp":1760168367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/12\/1261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,3]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ph14121261"],"URL":"https:\/\/doi.org\/10.3390\/ph14121261","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,3]]}}}