Environmental and biological measurements of isoflurane and sevoflurane in operating room personnel.

PURPOSE: The present study aimed to compare the concentration of isoflurane and sevoflurane in the individual's breathing zone and ambient air of operating rooms (ORs), to investigate the correlation between breathing zone levels and urinary concentrations, and to evaluate the ORs pollution in the different working hours and weeks. METHODS: Environmental and biological concentrations of isoflurane and sevoflurane were evaluated at 9ORs. Air samples were collected by active sampling method and urine samples were collected from each subject at the end of the work shift. All samples were analyzed using gas chromatography. RESULTS: The geometric mean ± GSD concentration of isoflurane and sevoflurane in breathing zone air were 1.41 ± 2.27 and 0.005 ± 1.74 ppm, respectively, while in post-shift urine were 2.42 ± 2.86 and 0.006 ± 3.83 µg/lurine, respectively. A significant positive correlation was found between the urinary and environmental concentration of isoflurane (r 2 = 0.724, P < 0.0001). The geometric mean ± GSD values of isoflurane and sevoflurane in ambient air were 2.30 ± 2.43 and 0.004 ± 1.56 ppm, respectively. The isoflurane concentration was different for three studied weeks and significantly increased over time in the ambient air of ORs. CONCLUSIONS: The occupational exposure of OR personnel to isoflurane and sevoflurane was lower than national recommended exposure limits. The urinary isoflurane could be a good internal dose biomarker for monitoring of occupational isoflurane exposure. Considering the accumulation of anesthetic waste gases in the studied ORs, real-time air monitoring is better to be done at the end of the work shift.

Development and validation of a direct headspace GC-FID method for the determination of sevoflurane, desflurane and other volatile compounds of forensic interest in biological fluids: application on clinical and post-mortem samples.

A simple and reliable headspace GC-flame ionization detection (HS-GC-FID) method has been developed and validated for the simultaneous determination of seven volatile compounds of forensic interest: sevoflurane, desflurane, ethanol, methanol, 1-propanol, acetone and acetaldehyde. All seven compounds including acetonitrile (internal standard) eluted within 10 min and were well resolved with no endogenous interference. Good linearity was observed in the range of 1-12 mg/dL for both anesthetics and 2.5-40 mg/dL for the other five analytes. The method showed good precision, sensitivity and repeatability. Most of the analytes remained stable during the storage of samples at 4°C. Desflurane and acetone degraded (>10%), when the samples remained on the autosampler for more than 2 and 3 h, respectively. The method was finally applied on clinical and post-mortem blood and urine samples. The clinical samples were collected both from patients who underwent surgery, as well as from the occupationally exposed medical and nursing staff of the university hospital, working in the operating rooms. The hospital staff samples were found negative for all compounds, while the patients' samples were found positive for the anesthetic administered to the patient. The post-mortem blood samples were found positive for ethanol and acetaldehyde.

Biomonitoring of exposure to nitrous oxide, sevoflurane, isoflurane and halothane by automated GC/MS headspace urinalysis.

OBJECTIVES: The goal of the present study was to develop an automated method to assess by biological monitoring, the volatile-anaesthetic exposure (nitrous oxide, sevoflurane, isoflurane and halothane) in operating theatre personnel. METHODS: Post-shift urine samples were analysed by gas chromatography-mass spectrometry coupled with static headspace sampling (GC-MS/ HSS); intra-assay %-RSD (n= 10) was less than 5% for nitrous oxide and less than 7% for each halogenated vapour. The biomonitoring method was validated with air monitoring data, obtained by personal samplers and a similar GC-MS method. The sensitivity achieved by single ion monitoring (SIM) was sufficient to reveal low biological and environmental exposure averages down to 1 microg/l(urine) and 0.5 ppm for nitrous oxide and 0.1 microg/l(urine) and 50 ppb for halogenated compounds, respectively. RESULTS: In 1998 we collected and analysed 714 post-shift urine samples for the biological monitoring of volatile anaesthetics in the urine of the operating-theatre personnel of Sant'Orsola-Malpighi Hospital (Bologna, Italy). Our data showed that nitrous oxide (N20), the anaesthetic most largely used in general anaesthesia, is still the decisive factor in operating-theatre pollution. Moreover, on the basis of our results, working in close contact with anaesthetics seems to be the main determinant of risk: surgical nurses and anaesthesiologists are the most-exposed professional categories (mean post-shift urinary N2O approximately 65 microg/l(urine)) while general theatre staff, surgeons, and auxiliary personnel have significantly lower exposure. CONCLUSIONS: The biological monitoring of post-shift unmodified urinary volatile anaesthetics was confirmed to be a useful tool for evaluating individual exposure to these chemicals. The urinary concentrations of N2O and of halogenated vapours might reflect, to a certain extent, the external exposure to these compounds, and respiratory air-monitoring data support the validity of biological monitoring. Furthermore, the good relationship between air and urinary concentration of anaesthetics in people working in closer contact with these chemicals may be a good indirect means of revealing the bad air conditions of operating rooms, and may contribute to the highlighting and correction of service defects in anaesthesiology equipment and of human errors.

Solid-phase microextraction gas chromatographic-mass spectrometric method for the determination of inhalation anesthetics in urine.

Solid-phase microextraction (SPME) has been applied to the headspace sampling of inhalation anesthetics (i.e. nitrous oxide, isoflurane and halothane) in human urine. Analysis was carried out by gas chromatography-mass spectrometry using a capillary column with a divinylbenzene porous polymeric stationary phase. A SPME divinylbenzene-Carboxen-polydimethylsiloxane coated fiber, 2 cm long, was used, and its performances were compared with those of a Carboxen-PDMS in terms of sensitivity, extraction efficiency, extraction time, fiber coating-urine distribution coefficient. For both fibers, linearity was established over four orders of magnitude, limits of detection were below 100 ng/l for nitrous oxide and below 30 ng/l for halogenated. Precision calculated as %RSD was within 3-13% for all intra- and inter-day determinations. The method was applied to the quantitative analysis of anesthetics in the urine of occupationally exposed people (operating room personnel).

The biological monitoring of inhalation anaesthetics.

The biological monitoring of inhalation anaesthetics. Occupational exposure to inhalation anaesthetics is an undesired consequence of the work in the operating theatre. Anaesthesia is currently practised using nitrous oxide associated with one or more potent anaesthetics (halothane, enflurane, isoflurane). In the present study we evaluated the occupational exposure to inhalation anaesthetics during anaesthesia in 190 operating theatres of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane, isoflurane were detected in the urine of 1521 exposed subjects (anaesthetists, surgeons and nurses). Significant correlations were found between the anaesthetic concentrations in urine produced during the shift (Cu) and anaesthetic environmental concentrations (CI). The results show that the urinary anaesthetic concentration can be used as an appropriate biological exposure index. The biological threshold values (urinary concentration values) proposed are the following: nitrous oxide, 15, 28 and 57 micrograms/L for an environmental exposure of 25, 50 and 100 ppm respectively; halothane, 97 micrograms/L (for an environmental exposure of 50 ppm), 6.1 micrograms/L (for an environmental exposure of 2 ppm) and 3.3 micrograms/L (for an environmental exposure of 0.5 ppm); enflurane, 145 micrograms/L (for an environmental exposure of 50 ppm), 22.7 micrograms/L (for an environmental exposure of 10 ppm), 3.7 micrograms/L (for an environmental exposure of 1 ppm); isoflurane, 5.3 micrograms/L (for an environmental exposure of 2 ppm) and 1.8 micrograms/L (for an environmental exposure of 0.5 ppm). These values apply to urine samples collected at the end of 4-hours' exposure to the anaesthetics.

[The biological monitoring of occupational exposure to anesthetic gas and vapors: the determination of nitrogen protoxide, halothane and isoflurane in the urine]. / Monitoraggio biologico dell'esposizione professionale a gas e vapori anestetici: determinazione di protossido d'azoto, alotano e isofluorano nell'urina.

A gas-chromatographic method has been developed for measuring urinary nitrous oxide, halothane and isoflurane concentrations. A volume of head-space gases obtained from biological samples is analyzed by ECD-GC on a steel column (2 mm ID) serially packed with Porapak Q (1.2 m) and MS-5A (0.30 m), operated at 160 degrees C. The detection limit (ranging from 0.03 micrograms/l for halothane to 1 microgram/l for nitrous oxide), between-day precision (CV < 6%) and working linear range (up to 100 micrograms/l for halothane and 2000 micrograms/l for nitrous oxide) were determined. A two-year experience in biological monitoring of occupationally exposed surgical staff with the proposed method is reported and confounding factors are discussed. The method is easy to perform, free from interferences and suitable for use in routine analysis in toxicological laboratories.

[Evaluation of several neuropsychological parameters in subjects occupationally exposed to anesthetics]. / Valutazione di alcuni parametri neuropsicologici in soggetti professionalmente esposti ad anestetici.

51 workers, occupationally exposed to anaesthetic gases and vapours (nitrous oxide, halothane, and isoflurane), were studied monitoring their environmental and biological exposure. Moreover, they were tested for visual reaction times and neurobehavioural batteries. There was no evidence of important neurotoxic effects nor of neurobehavioural problems with low concentrations of anaesthetics.

Biotransformation of isoflurane: urinary and serum fluoride ion and organic fluorine.

The serum and urinary concentrations of fluorinated metabolites of isoflurane after inhalation of three different concentrations of isoflurane were studied in 18 ASA physical status 1 or 2 patients, scheduled for orthopedic or otolaryngeal surgery. Isoflurane was administered for 60 min during fentanyl-nitrous oxide-oxygen, and its end-tidal concentration was maintained at 0.3, 0.6, or 1.15% (groups I, II, and III). The organic fluorine was determined by combustion and fluoride ions were analyzed by ion chromatography. The amounts were expressed in terms of fluoride ion. The concentrations of serum fluoride ion and organic fluorine increased significantly 15 min after the onset of inhalation of isoflurane. The mean peak values of fluoride ions were 3.8 +/- 1.1, 3.9 +/- 1.4, and 4.2 +/- 0.9 mumole/1 (M +/- SD) in patients in groups I, II, and III, respectively. The half-lives of fluoride ion and of organic fluorine as metabolites of isoflurane, calculated from the amounts excreted in urine, were 36 h and 41 h, respectively. The cumulative amounts of fluoride ion and organic fluorine excreted up to the 6th postoperative day were 548 +/- 230 and 785 +/- 452 mumoles in group I, 594 +/- 138 and 1,378 +/- 807 mumoles in group II, and 1,032 +/- 496 and 728 +/- 265 mumoles (M +/- SD) in group III, respectively. The urinary excreted fluoride ion increased in proportion to the dose of isoflurane and approximately 1.3 mmol was excreted per 1 MAC X hour inhalation of isoflurane. The authors concluded that isoflurane might be biotransformed to a greater extent than reported previously, although the serum fluoride ion level was found to be low.

Evaluation of exposure to isoflurane (Forane): environmental and biological measurements in operating room personnel.

The concentration of isoflurane (Forane) in the ambient atmosphere was determined in 11 operating theaters of 5 hospitals in Italy. The concentration of isoflurane in the ambient air exceeds the recommended time-weighted average exposure levels (median value: 113 mumol/m3). Isoflurane was detected in the urine of 45 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the isoflurane concentration in urine produced during the shift (Cu' nmol/l) and isoflurane environmental concentration (Cl' mumol/m3) (Cu = 0.243 X Cl + 3.712) (r = .90). The results show that the urinary isoflurane concentration can be used as an appropriate biological exposure index. The authors suggest a biological exposure index of 18 nmol/l (3.4 micrograms/l). This is the biological value obtained after 4 h of an average environmental exposure to 81 mumol/m3 (2 ppm).