NICOLAU SYNDROME IN ENDODONTICS: PATHOGENETIC MECHANISMS, RISK FACTORS AND PREVENTIVE-THERAPEUTIC APPROACHES

Abstract

In endodontics, Nicolau syndrome has been described as a rare complication associated with the extrusion of calcium hydroxide agents into the periapical tissues due to their forceful insertion and subsequent entry into the bloodstream. Since the number of documented clinical cases of Nicolau syndrome in endodontics remains limited, its pathogenetic mechanisms, diagnostic criteria, and optimal management strategies have not yet been clearly defined. Objective. To conduct a comprehensive analysis and systematization of the available literature regarding the etiopathogenetic mechanisms, clinical manifestations, diagnostic criteria, therapeutic approaches, and preventive strategies for Nicolau syndrome in the context of endodontic treatment. Methods. Study was conducted as an expanded integrative literature review involving systematic search, critical appraisal, comparison, synthesis, and interpretation of data from a wide range of scientific sources on Nicolau syndrome in endodontics. The search process included: 1) initial broad search in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and specialized dental journal databases; 2) targeted search for highly specific sources, including clinical case reports, thematic reviews, consensus recommendations from professional associations, and analytical reports; 3) retrospective manual search of the reference lists of the retrieved articles and cross-citation tracking. Results. Most reported clinical cases of Nicolau syndrome occurred during the treatment of mandibular molars, typically during attempts to control bleeding from root canals by forceful insertion of calcium hydroxide under pressure. The condition generally followed three successive phases: an initial phase (sudden pain, erythema), an acute phase (induration, livedoid dermatitis), and a final phase (ulceration, scarring). The proposed pathogenesis includes a combination of inflammatory vasculitis, embolic or thrombotic vascular occlusion, and vasospasm, potentially exacerbated by the cytotoxic and corrosive effects of calcium hydroxide on the vascular endothelium. In some cases, injury to adjacent neural structures (especially if the material enters the inferior alveolar nerve canal) has been reported, resulting in variable degrees of neurological deficits. Conclusions. The management of Nicolau syndrome depends on the phase of lesion development and the severity of symptoms; however, early recognition and immediate intervention are critical. Reported therapeutic measures include analgesia, antibiotics, systemic corticosteroids, anticoagulants, hyperbaric oxygen therapy, local anti-inflammatory treatment, and, if indicated, surgical intervention. Nonetheless, literature data emphasize that the most effective and rational approach is prevention, which involves minimizing the depth and pressure and control over the quantity of calcium hydroxide inserted into root canals, avoiding syringe delivery close to the apical foramen, preventing hyper-instrumentation, and preserving apical constriction during endodontic treatment.