Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function

Abstract

Sevoflurane (SEV), a commonly used anesthetic agent for invasive surgery, is directly eliminated via exhaled breath and indirectly by metabolic conversion to inorganic fluoride and hexafluoroisopropanol (HFIP), which is also eliminated in the breath. We studied the post-operative elimination of SEV and HFIP of six patients that had undergone a variety of surgeries lasting between 2.5 to 8.5 h using exhaled breath analysis. A classical three compartments pharmacokinetic model developed for the study of environmental contaminants was fitted to the breath data. We found that SEV kinetic behavior following surgery (for up to six days) is consistent across all subjects whereas the production and elimination of HFIP varies to some extent. We developed subject specific parameters for HFIP metabolism and interpreted the differences in the context of timing and dose of anesthesia, type of surgery, and specific host factors. We propose methods for assessing individual patient liver function using SEV as a probe molecule for assessing efficiency of liver metabolism to HFIP. This work is valuable not only for the clinical study of metabolism recovery, but potentially also for the study of the interaction of other manufactured and environmental compounds with human systems biology in controlled exposure and observational studies.

Targeted breath analysis: exogenous volatile organic compounds (EVOC) as metabolic pathway-specific probes

“…Together, these studies indicate that exogenous VOCs, introduced as an experimental tool or through daily exposure, can be exploited to identify population subgroups and to assess specific disease-associated processes. In line with this concept, monitoring breath excretion of volatile anaesthetics, and corresponding metabolic products, has been suggested as a strategy to assess organ function [76,77].…”

Exhaled Breath Condensate as an Alternative Sample for Drug Monitoring

“…Drug levels in exhaled breath/exhaled breath condensate A number of drugs have been analyzed in EB/EBC in various studies [8][9][10][11][12][13][14][15][16][17][18][19]. However, there are two problems when comparing these reported levels of drugs in EBC: there are very wide variations in the reported levels (e.g., 4.8-29,800 pg/min for methadone [12]) and the different units (i.e., pg/filter, pg/min, mg/l and parts per million by volume) used to express the EBC levels of the analyte which cannot easily be converted for comparison with each other.…”

Breath biomarkers in toxicology

“…Breath analysis tools are still in use for assessing the progression of anesthesia and evaluation of organ function. (Miekisch et al 2008;Ghimenti et al 2013;Lirk et al 2004). Breath ADME approaches have been extended to exploring toxicity of exogenous VOCs by determining the rate constants of uptake and elimination for suites of compounds implicated in human carcinogenicity including chloroform, benzene, methyl tertiary butyl ether, toluene, naphthalene, vinyl chloride, carbon tetrachloride, trichloroethylene, dichlorobenzene (Pellizzari et al 1992;Pleil and Lindstrom 1997;Pleil et al 2007).…”