Abstract

Background: Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disorder triggered by volatile anesthetics and depolarizing neuromuscular blockers. It is characterized by uncontrolled calcium release in skeletal muscle cells, leading to a hypermetabolic crisis. Despite advances in anesthetic safety, diagnosing MH remains challenging due to its clinical variability and genetic complexity.

Objective: This narrative review examines the diagnostic challenges of MH, its diverse clinical presentations, and the implications of genetic mutations. The aim is to enhance perioperative recognition and optimize management strategies

Methods: A comprehensive search of PubMed, Scopus, and Web of Science identified studies published between 2005 and January 2025. The review includes case reports, clinical guidelines, expert recommendations, and observational studies addressing MH diagnosis, clinical variability, genetic predisposition, and perioperative management.

Results: MH presents with a spectrum of clinical manifestations, from acute crises to delayed-onset forms. The in vitro contracture test (IVCT) remains the diagnostic gold standard, while genetic testing for RYR1 and CACNA1S mutations aids in risk assessment. Emerging evidence suggests broader genetic heterogeneity, complicating diagnosis. Early recognition and timely dantrolene administration are critical for reducing morbidity and mortality. Promising advances in metabolomic profiling and artificial intelligence may enable non-invasive risk assessment.

Conclusion: Despite improved diagnostic methods, MH remains a significant perioperative challenge. Enhancing early recognition and broadening genetic testing may reduce adverse outcomes. Future research should focus on non-invasive biomarkers and global standardization of diagnostic protocols.