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\begin{document}

\title{Bioinformatics-guided Disproportionality Analysis of Sevoflurane-Induced
Nephrogenic Diabetes Insipidus using the FDA Adverse Event Reporting
System (FAERS) Database.}



\author[1]{Akhil T Jacob}%
\author[1]{Ankitha  Hari Kumar }%
\author[1]{Gayethri H}%
\author[2]{Lipin Lukose}%
\author[3]{Subeesh Viswam}%
\affil[1]{Oxbridge College of Pharmacy}%
\affil[2]{Manipal Academy of Higher Education}%
\affil[3]{Affiliation not available}%


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  \date{May 14, 2024}


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\begin{abstract}
C. Abstract AIM: Sevoflurane is an ether-based inhalational anesthetic
that induces and maintains general anesthesia. Our study aimed to detect
sevoflurane-induced nephrogenic diabetes insipidus using Data Mining
Algorithms (DMAs) and molecular docking. The FAERS database was analyzed
using OpenVigil 2.1 for disproportionality analysis. Methods: We
analyzed FAERS data from 2004 to 2022 to determine the incidence of
nephrogenic diabetes insipidus associated with sevoflurane. Reporting
Odds Ratios (RORs) and Proportional Odds 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
reporting odds ratios (ROR) of 76.012 (95\% CI: 44.67-129.35) and
proportional odds ratios (PRR) of 75.72 (Chi-sq: 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 AVRP2 (6U1N) with docking scores of -4.9 and -5.3,
respectively. Conclusion: 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.%
\end{abstract}%



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