Background:
Propofol is a widely used anesthetic for total IV anesthesia. Although it is generally safe, rare but serious complications can occur in vulnerable groups, such as critically ill patients and children. Clinicians often rely on surrogate measures (e.g., predicted effect-site concentrations or Bispectral Index), yet more direct indicators of anesthetic exposure and metabolic stress would be valuable. The authors hypothesized that pharmacometabolomics via breath analysis could yield real-time insights into propofol concentrations as well as accompanying metabolic responses to surgery.
Methods:
In this pilot study, 10 pediatric patients (median age, 5.9 yr; interquartile range, 4.3 to 6.6) undergoing propofol anesthesia contributed 47 breath samples (10 preinduction, 37 postinduction) and 37 blood samples. All samples were analyzed by high-resolution mass spectrometry. Linear mixed-effects models examined associations between exhaled compounds and serum propofol concentrations while accounting for repeated measures in individual patients. Volcano plots were used to identify differential changes in metabolites after propofol induction.
Results:
Propofol, its metabolites, and endogenous metabolites were readily detected in exhaled breath, demonstrating strong correlations with serum propofol concentrations (partial R² ≥ 0.65; adjusted P < 0.001). Differential analysis showed significant upregulation of endogenous fatty aldehydes (log2 [postinduction/preinduction] ≥ 1; adjusted P ≤ 0.05), suggestive of lipid peroxidation and oxidative stress. Exogenous compounds, including benzene and phenols, were also observed, reflecting propofol metabolism in vivo.
Conclusions:
This pilot study highlights a robust breath–serum relationship for propofol and reveals surgery-associated shifts in metabolic pathways, including evidence of oxidative stress. These findings underscore the feasibility of exhaled-breath pharmacometabolomics for individualized anesthetic care. Further validation in larger cohorts is warranted to confirm clinical utility and to determine whether real-time breath analysis could ultimately serve as a useful adjunct for guiding anesthetic management and monitoring perioperative metabolic responses.
Editor’s Perspective
What We Already Know about This Topic
During total IV anesthesia with propofol, direct blood concentration measurement is not routinely achievable, and thus, clinicians rely on surrogate measures such as predicted effect-site concentrations or Bispectral Index
Breath analysis by secondary electrospray ionization–high-resolution mass spectrometry is emerging as a noninvasive metabolomics technique that may be applicable to clinical contexts
What This Article Tells Us That Is New
This pilot study in children having propofol-based anesthesia found that on-site secondary electrospray ionization–high-resolution mass spectrometry breath pharmacometabolomics can capture robust correlations between exhaled signals and serum propofol concentrations while revealing significant metabolic shifts likely linked to oxidative stress