Bioinformatics‐guided disproportionality analysis of sevoflurane‐induced nephrogenic diabetes insipidus using the FDA Adverse Event Reporting System database

• Published in: British journal of clinical pharmacology 2024-08, Vol.90 (8), p.1804-1810
• Main Authors: Jacob, Akhil T., Kumar, Ankitha Hari, Halivana, Gayethri, Lukose, Lipin, Nair, Gouri, Subeesh, Viswam
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse Drug Reaction Reporting Systems - statistics & numerical data; Aged; Anesthetics, Inhalation - adverse effects; AQP2; AVPR2; Child; Child, Preschool; Computational Biology; Data Mining; Databases, Factual - statistics & numerical data; Diabetes Insipidus, Nephrogenic - chemically induced; Diabetes Insipidus, Nephrogenic - epidemiology; FAERS; Female; Humans; Incidence; Infant; Male; Middle Aged; Molecular Docking Simulation; nephrogenic diabetes insipidus (NDI); sevoflurane; Sevoflurane - adverse effects; United States - epidemiology; United States Food and Drug Administration; Young Adult
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.15869

Aims Sevoflurane is an ether‐based inhalational anaesthetic that induces and maintains general anaesthesia. Our study aimed to detect sevoflurane‐induced nephrogenic diabetes insipidus using data mining algorithms (DMAs) and molecular docking. The FAERS database was analysed using OpenVigil 2.1 for disproportionality analysis. Methods We analysed FAERS data from 2004 to 2022 to determine the incidence of nephrogenic diabetes insipidus associated with sevoflurane. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) with 95% confidence intervals were calculated. We also used molecular docking with AutoDock Vina to examine sevoflurane's binding affinity to relevant receptors. Results A total of 554 nephrogenic diabetes insipidus cases were reported in FAERS, of which 2.5% (14 cases) were associated with sevoflurane. Positive signals were observed for sevoflurane with ROR of 76.012 (95% CI: 44.67–129.35) and PRR of 75.72 (χ2: 934.688). Of the 14 cases, 50% required hospitalization, 14% resulted in death, and the remaining cases were categorized as other outcomes. Molecular docking analysis showed that sevoflurane exhibited high binding affinity towards AQP2 (4NEF) and AVPR2 (6U1N) with docking scores of −4.9 and −5.3, respectively. Conclusions Sevoflurane use is significantly associated with the incidence of nephrogenic diabetes insipidus. Healthcare professionals should be cautious when using this medication and report any adverse events to regulatory agencies. Further research is needed to validate these findings and identify risk factors while performing statistical adjustments to prevent false‐positives. Clinical monitoring is crucial to validate potential adverse effects of sevoflurane.