General anesthesia in children: Improved monitoring via breath analysis

Not too much and not too little: the dosage of drugs must be optimally adjusted for general anesthesia. This is no easy task, especially for pediatric patients. A pilot study now shows that breath analysis can help anesthesia personnel administer the optimal dose of a common anesthetic. And that's not all: breath analysis can also be used to determine how the body reacts to the anesthesia.

The air we breathe out carries a large number of tiny molecules from our body. Metabolic products, but also drugs and their degradation products, can be readily detected in our breath using dedicated analytical equipment developed at the University of Basel. Researchers led by Professor Pablo Sinues from the Department of Biomedical Engineering and the University Children's Hospital Basel (UKBB) are taking advantage of this fact: In the journal Anesthesiology, they report that this method can be used to monitor general anesthesia in children better than was previously possible.

The anesthetic propofol has been in use for over 30 years and is considered a safe drug for inducing and maintaining general anesthesia. However, finding the optimal dose can be tricky, especially for children. Right now, height, weight, gender and age are used as a general guide to calculate how much propofol to give a patient. But during surgery, anesthesiologists can only deduce how much of the drug reaches the brain, where it should take effect, on the basis of indirect clues, like vital signs and movements or information from processed brain activity. On this basis, they decide if it’s necessary to adjust the dose of propofol so that the child neither wakes up nor receives too high a concentration.

Complex blood tests

Measuring propofol concentrations in the blood during surgery would be a good proxy to estimate brain exposure to the anesthetic. However, there is no blood test that can deliver results with sufficient speed.

Sinues and his team in collaboration with the Department of Pediatric Anesthesia at UKBB therefore conducted a pilot study to investigate whether breath analysis could help with dosing and deliver results during anesthesia – quasi in real time. “Propofol is quite volatile and can be easily measured in a person’s breath,” says Sinues.

For their study, the researchers took breath and blood samples every 30 minutes before and during general anesthesia from ten children who had to undergo surgery for various medical reasons. Dr. Jiafa Zeng, first author of the study, collected the anesthetized patients' exhaled breath with the help and guidance of the responsible anesthesiologist, Dr. Nikola Stankovic.

To collect and transport the breath samples, the researchers used specially developed plastic bags in order to analyze them in the laboratory using mass spectrometry. “The device is too big to be placed in the operating room,” explains Zeng. The blood samples were analyzed by researchers at the University Hospital Zurich in the days and weeks following each individual anesthesia.

Breath analysis also shows stress in the body

Comparing the measured values showed that the active substance and its degradation products could be reliably detected in the breath. The results of the breath analysis closely matched the blood concentrations.

However, the breath analysis revealed even more, namely a whole range of substances the body produces in reaction to a certain kind of stress typical for anesthesia and surgical interventions – namely oxidative stress. “With this method, we can not only determine the propofol concentration, but also measure how the body reacts to the anesthesia and the surgery,” explains Pablo Sinues. The very rare cases in which propofol leads to complications, especially in children, could possibly be detected and prevented at an early stage using these measured values.

Breathing air instead of blood tests

With the support of an Eccellenza grant from the Swiss National Science Foundation, Sinues and his team have been researching for several years how breath analysis can be used for the diagnosis and individual dosing of medication. Children and older patients in particular could benefit from this method.

In earlier studies, for example, the researchers found that epilepsy medication and its breakdown products can be measured in the breath. This information can help to determine the optimal dose of the medication. Until now, doctors used regular blood tests to adjust the dosage of epilepsy drugs for each patient individually. In a different study, the research team was also able to use breath analysis to monitor the condition of hospitalized children with diabetes.

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