Real-time breath drug metabolic monitoring under stellate ganglion block with lidocaine: a proof-of-concept study

Stellate ganglion block (SGB) using lidocaine has been widely employed in clinical practice to manage sympathetic-mediated pain and other autonomic‐related conditions. However, the systemic metabolic response to this procedure is incompletely understood. In this pilot study, we enrolled 28 participants—17 healthy volunteers and 11 patients with sympathetically maintained pain—to investigate real-time metabolic changes induced by lidocaine‐based SGB. Each participant received a 5 mL injection of 1% lidocaine under ultrasound guidance at the stellate ganglion, and exhaled breath samples were collected immediately before- and 5–30 min post‐procedure. High‐resolution mass spectrometry coupled with secondary electrospray ionization (SESI‐HRMS) was used to detect changes in breath‐borne metabolites. A total of 309 features were significantly altered (q-value < 0.01 and |mean(log 2 FC)| >1.5) following lidocaine injection, with 233 upregulated and 76 downregulated. Among the most pronounced changes were lidocaine-derived metabolites, including 2,6-Dimethylaniline (2,6‐DMA) and 2‐amino‐3‐methylbenzoate, confirming that SESI‐HRMS can rapidly track drug metabolism via breath. Hierarchical clustering further revealed a subgroup of healthy volunteers exhibiting especially robust metabolic shifts, suggesting inter‐individual variability. Besides drug‐related signals, several endogenous pathways appeared modulated, as indicated by altered levels of acylcarnitines, amino‐acid derivatives, monoterpenes, and short‐chain aldehydes, commonly implicated in fatty‐acid β‐oxidation, branched‐chain amino‐acid catabolism, and sympathetic regulation. These findings highlight real-time breath analysis as a feasible approach to capture both drug‐specific (e.g., lidocaine metabolites) and host metabolic responses to SGB. By demonstrating clear inter‐individual differences, this study supports the potential for breath‐based pharmacometabolomics in monitoring and possibly optimizing lidocaine‐SGB interventions in clinical settings.