Researchers at the University of Basel have developed a non-invasive breath analysis technique that can monitor propofol concentrations and detect metabolic stress responses during general anaesthesia in children. The pilot study demonstrates robust correlations between exhaled compounds and serum propofol levels whilst revealing oxidative stress markers linked to surgical interventions.
Pic courtesy: University of Basel, Department of Biomedical Engineering
Revolutionary monitoring approach transforms anaesthetic management
A groundbreaking study published in Anesthesiology has unveiled a transformative approach to monitoring general anaesthesia in paediatric patients through real-time breath analysis. The research, led by Professor Pablo Sinues from the Department of Biomedical Engineering at the University of Basel and the University Children’s Hospital Basel, represents a significant advancement in personalised anaesthetic care.
The pilot study examined 10 children undergoing propofol-based anaesthesia for dental surgery, collecting 47 breath samples and 37 blood samples throughout the procedures. Using secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS), researchers achieved remarkable precision in detecting propofol and its metabolites in exhaled breath.
“Propofol is quite volatile and can be easily measured in a person’s breath,” explains Sinues. The study revealed that breath analysis closely matched blood concentrations, with the strongest correlations showing partial R² values exceeding 0.65 and adjusted P values less than 0.001.
Technical precision meets clinical practicality
The SESI-HRMS technique offers exceptional sensitivity and specificity, capturing a comprehensive metabolic profile that extends far beyond traditional drug monitoring. Dr Jiafa Zeng, the study’s first author, collected breath samples using specially developed plastic bags, enabling laboratory analysis within three minutes of collection.
The research identified propofol itself (partial R² = 0.889) and its known metabolite, 2,6-diisopropyl-1,4-quinone (partial R² = 0.693), alongside several additional compounds exhibiting strong associations with serum propofol concentrations. These included propofol isopropyl ether and two unidentified compounds with molecular formulae C9 H12 O and C12 H16 O, both plausibly related to propofol through structural or metabolic modifications.
To distinguish between metabolic origins and potential formulation impurities, researchers analysed the headspace of propofol formulations. The ratio of 2,6-diisopropyl-1,4-quinone to propofol signals was significantly higher in patients’ breath than in the formulation (17% versus 2%; P = 0.005), confirming that the majority of observed signals resulted from hepatic metabolism rather than contamination.
Metabolic fingerprinting reveals surgical stress responses
Beyond drug monitoring, the study uncovered a remarkable metabolic cascade triggered by surgical intervention. Among 958 features detected in positive ion mode, 349 showed significant differences between pre-and post-induction samples after false discovery rate correction. Notably, 173 features were significantly upregulated whilst 78 were downregulated following propofol induction.
The researchers identified 35 compounds through database queries, revealing two distinct chemical groups: fatty aldehydes (comprising 10 compounds) and benzene derivatives (including 9 compounds). The fatty aldehydes, particularly 4-hydroxynonenal, represent wellcharacterised markers of oxidative stress, indicating the body’s response to surgical trauma.
“With this method, we can not only determine the propofol concentration, but also measure how the body reacts to the anaesthesia and the surgery,” notes Sinues. This dual capability could prove invaluable for detecting rare but serious complications, particularly propofol infusion syndrome, which can affect children.
Clinical implications and future applications
The study’s findings hold particular significance for paediatric anaesthesia, where dosing complexities are heightened due to developmental pharmacokinetic variations. Neonates, for instance, may display propofol clearance rates only 10 to 38% of adult levels, with ongoing maturation affecting pharmacokinetics over time.
Current clinical practice relies on target-controlled infusion models incorporating age, weight, height, and sex to improve dosing precision. However, genetic factors, developmental status, and pathophysiological conditions introduce substantial interpatient variability. The breath analysis technique offers real-time feedback that could complement existing approaches.
As the authors note in their discussion: “Advanced TCI models, such as the Eleveld model, already incorporate age, weight, height, and sex to improve dosing precision. Still, genetic factors, developmental status, and pathophysiological conditions introduce interpatient variability in metabolism and clearance.”
Technological integration and clinical workflow
The research demonstrates seamless integration into standard surgical workflows without disrupting routine procedures or causing discomfort to clinicians or patients. Breath samples were analysed on-site using SESI-HRMS, providing mass spectral readouts typically within 15 minutes of collection.
Future developments could reduce this timeframe dramatically. The authors suggest that direct integration of mass spectrometry into ventilator systems could achieve near real-time monitoring within seconds. Indeed, proof-of-concept studies have already demonstrated continuous breath monitoring via SESI-HRMS at 10-second intervals.
Pharmacometabolomics: personalising therapeutic approaches
The study exemplifies the emerging field of pharmacometabolomics, which leverages metabolic profiles to predict individual drug responses and advance precision medicine. Unlike static pharmacogenomics, this approach offers dynamic insights influenced by diet, microbiome composition, disease states, and environmental factors.
The researchers emphasise that “pharmacometabolomics leverages metabolic profiles to predict individual drug responses, thereby advancing precision medicine… This approach is particularly valuable for managing the interindividual variability observed in vulnerable populations, such as pediatric or critically ill patients.”
Oxidative stress monitoring and safety implications
The detection of fatty aldehydes, particularly markers of lipid peroxidation, provides crucial insights into surgical stress responses. These metabolic shifts reflect the body’s response to increased energy demands, muscle protein breakdown, and reactive oxygen species production during surgery.
The correlation network analysis revealed tight regulation among oxidative stress markers, suggesting that breath analysis could serve as an early warning system for metabolic complications. Given that severe metabolic acidosis represents a hallmark of propofol infusion syndrome, this rich metabolic fingerprint could potentially monitor both drug concentrations and flag individual-level adverse effects.
Future directions and clinical validation
Whilst this pilot study demonstrates remarkable proof-of-concept, larger validation studies are essential to confirm clinical utility. The authors acknowledge several limitations, including the substantial capital investment required for SESI-HRMS instrumentation, though cost analysis suggests per-sample expenses (approximately $20) comparable to other clinical tests.
The research team received funding from the Swiss National Science Foundation and conducted the study as part of the Exhaled Breath Analysis by Secondary Electrospray Ionisation– Mass Spectrometry in Children and Adolescents (EBECA) initiative.
Transforming anaesthetic care through metabolic monitoring
This pioneering research represents a significant step towards individualised anaesthetic management through non-invasive breath analysis. By simultaneously monitoring drug concentrations and metabolic responses, the technique offers unprecedented insights into both anaesthetic exposure and physiological impact.
The authors conclude: “On-site SESIHRMS breath pharmacometabolomics can capture robust correlations between exhaled signals and serum propofol concentrations while revealing significant metabolic shifts likely linked to oxidative stress. Integrating these data with established pharmacokinetic models and electroencephalography-based measures could advance individualised anaesthetic management.”
Reference:
Zeng, J., Stankovic, N., Singh, K. D., et. al. (2025). Breath Analysis of Propofol and Associated Metabolic Signatures: A Pilot Study Using Secondary Electrospray Ionization High-resolution Mass Spectrometry. Anesthesiology.
https://doi.org/10.1097/ALN.0000000000005531
