Anaphylaxis to Mannitol: A Rare but Serious Threat in Neurocritical Care

Mannitol, an osmotically active and commonly employed agent in neurocritical care which is well tolerated. However, isolated case reports of IgE-mediated anaphylaxis impose a potential immunological risk, pertaining to CCD-sensitized or atopically predisposed subjects. This review summarizes recent studies of hypersensitivity to mannitol included with emphasis on immunopathogenesis, case reports, diagnostic possibilities, and clinical issues. A comprehensive literature search was conducted in PubMed, Web of Science, and EMBASE from inception through December 2025. Search terms included “mannitol,” “anaphylaxis,” “hypersensitivity,” “cross-reactive carbohydrate determinants,” and “neurocritical care,” using Boolean operators and Medical Subject Headings where applicable. The review followed PRISMA guidelines for study identification, screening, eligibility, and inclusion. Reference lists of relevant articles were manually screened to identify additional publications. Only English-language human studies were included. While uncommon, anaphylaxis from mannitol has been documented, especially in cross-reactive carbohydrate determinant (CCD)-sensitized patients. IgE-CCD interaction facilitated by the molecular structure of mannitol can result in mast cell degranulation and systemic hypersensitivity. Several reports of intraoperative deaths highlight the need for increased awareness. Alternatives such as hypertonic saline should be considered in high-risk cases. Allergic history screening in mannitol-dependent individuals should be performed by medical practitioners. Tests for CCD sensitization are not used appropriately but can reduce risk. Hypertonic saline provides a safer option in appropriately chosen cases.