Allergy to muscle relaxants: diagnosis and significance of drug concentrations

Abstract Objectives Allergic reactions to muscle relaxants are a major cause of perioperative anaphylaxis. This study aimed to evaluate how plasma concentrations of muscle relaxants, genetic predispositions, and immunometabolic changes influence the risk and severity of hypersensitivity reactions to improve diagnostic accuracy and support personalised perioperative management. Methods A total of 120 adult patients undergoing general anaesthesia were examined using intradermal testing, ELISA-based assays for specific IgE, basophil activation tests, cytokine profiling, plasma drug concentration measurements (HPLC–MS), molecular genetic analysis of IL-4 and IL-13 polymorphisms, and proton magnetic resonance spectroscopy for metabolic profiling. A control group (n=60) underwent parallel testing. Statistical evaluation included correlation analysis, logistic regression, and ROC curve assessment. Results Positive allergic reactions were observed in 15.8 % of patients, most commonly to atracurium (9.2 %). Patients with positive reactions showed significantly higher plasma concentrations of atracurium (2.8 ± 0.4 μg/mL vs. 1.7 ± 0.3 μg/mL; p<0.01). IL-4 (CC) and IL-13 (AA) genotypes increased the risk of hypersensitivity (OR 3.2 and 2.8, respectively), while their combination markedly elevated the likelihood of severe reactions (OR 5.6). Elevated IL-4 , IL-6 , and TNF-α levels correlated with clinical severity. Metabolic profiling revealed increased lactate, acetate, and pyruvate in allergic patients, indicating systemic inflammatory and anaerobic metabolic responses. ROC analysis confirmed high predictive accuracy for atracurium concentration (AUC=0.82) and genetic markers (AUC=0.79). Conclusions Allergic reactions to muscle relaxants are strongly influenced by drug concentration, genetic susceptibility, and metabolic responses. Combined pharmacokinetic, immunological, and genetic assessment may significantly enhance preoperative risk stratification and support personalised anaesthetic management to improve patient safety.