Nicolau syndrome in endodontics: A narrative review on calcium hydroxide extrusion and its therapeutic risks

Nicolau syndrome (NS), a rare iatrogenic complication following calcium hydroxide (CH) extrusion during endodontic treatment, leads to severe tissue necrosis, vascular thrombosis, and neurological deficits. A narrative review was conducted through an electronic search of PubMed and Google Scholar up to February 2025. Eligible studies included case reports, case series, or clinical studies documenting NS or complications of CH extrusion during root canal treatment. Reports of complications from other medicaments or nonendodontic procedures were excluded. Fourteen case reports describing 24 patients met the criteria. Most injuries followed treatment of molar teeth (83.3%), with mandibular molars, especially common (79.2%). Inferior alveolar canal involvement was reported in 75.0%. Nonsetting CH pastes predominated (≥95.8%), and injectable delivery was used in 91.7%. Computed tomography/cone-beam computed tomography was obtained in 66.7%, while angiography and magnetic resonance imaging were each reported in 8.3%. Presentation was dominated by neurosensory disturbance (87.5%); cutaneous or mucosal necrosis occurred in 29.2%. Operative management was undertaken in 79.2%, and functional sensory recovery was reported in 58.3% at the last follow-up. The findings are based on a small number of published case reports, with heterogeneity in documentation, treatment protocols, and follow-up duration, which limits the generalizability of conclusions. CH is essential in endodontics, but extrusion may cause severe complications like NS. Prevention relies on pressure control and careful attention to anatomy: verify working length, ensure hemostasis, avoid force, and keep the tip short of the apical third.