A straightforward method for determination of the sevoflurane metabolite hexafluoroisopropanol in urinary occupational medical samples by headspace-gas chromatography mass spectrometry.

Biological monitoring of the unmodified sevoflurane and its metabolite hexafluoroisopropanol (HFIP) in urine samples was proposed to determine the individual exposure levels of the medical staff. In this study, a method for simultaneous determination of both compounds in urine using static headspace-gas chromatography-mass spectrometry (HS-GC-MS) was developed. The method is linear over a broad concentration range from 1 to 1000 µg/L (r2 > 0.999) and shows high precision. Limits of quantification (LOQ) are 0.6 µg/L for sevoflurane and 3 µg/L for HFIP, representing an excellent sensitivity without the necessity of analyte enrichment. The method was successfully applied in a German pilot-study to monitor both compounds in samples from medical personnel working in operating theatres. Urinary concentrations of HFIP ranged between < LOQ and 145 µg/L, while sevoflurane was below the LOD in all samples.

Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study.

BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·(Equation is included in full-text article.)·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; (Equation is included in full-text article.): respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L (15.53 µg·L; median: 2.11 µg·L, interquartile range [IQR]: 4.58 µg·L) and in all postoperative samples (25.42 µg·L [21.39 µg·L]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (ß = 216.89; P < .001) and to the calculated masses of inhaled SEVO (ß = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting.

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.

Exposure Assessment, Biological Monitoring, and Liver Function Tests of Operating Room Personnel Exposed to Halothane in Hamedan Hospitals, West of Iran.

BACKGROUND: Occupational exposure to halogenated hydrocarbons has been associated with halothane hepatitis, an increase of liver enzymes, and congenital malformations. The objectives of this study were to investigate whether bromide, a urinary metabolite of halothane, could be used as a biological marker of exposure to this anesthetic gas and assessment of associated exposure to halothane with any significant changes in conventional parameters of liver function (serum aminotransferase activities). STUDY DESIGN: A cross-sectional study. METHODS: Seventy-five anesthesiologists, anesthesia nurses, operating room nurses, and surgeons (exposed group) and 75 matched unexposed individuals (reference group) were selected randomly from two public hospitals in Hamadan City, western Iran.  Atmospheric concentrations of halothane in the breathing zone of the exposed subjects and urinary bromide levels were measured by headspace gas chromatography. Similarly, serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by the enzymatic method using an automatic Prestige instrument. RESULTS: Mean atmospheric concentrations of halothane and urinary bromide levels for exposed subjects were 1.49 ±1.36 ppm and 0.83 ±0.29 mM, respectively. A relatively good correlation was found between exposure to halothane and urinary bromide levels (r=0.38). The chi-squared test results showed that the proportions of the subjects with abnormal ALT and AST among the women exposed were significantly higher than those of reference individuals (P<0.05). CONCLUSIONS: Urinary bromide can be used as a potential biomarker of exposure to halothane, although additional studies are necessary to further validate these initial findings.

Occupational exposure to nitrous oxide during procedural pain control in children: a comparison of different inhalation techniques and scavenging systems.

BACKGROUND: Nitrous oxide (N2 O 50% in oxygen) is commonly used for painful procedures in children. Potential negative health effects associated with chronic workplace exposure limit its use. Safe occupational N2 O exposure concentrations are below 25 ppm environmental concentration as a time-weighted average (TWA) and below 200 ppm as a short-time exposure level (STEL) of 15 min. AIM: The aim was to assess occupational exposure of staff during nitrous oxide administration to children using different inhalation delivery devices and scavenging systems. METHODS: Staff nitrous oxide exposure during use of a double face mask (DFM) with or without a demand valve (DV) was compared with a conventional single face mask (FM). We also compared exposure using the hospital central scavenging system with a portable evacuation system. N2 O concentrations, representing exposure values, were monitored within proximity to staff. Urine N2 O concentration was measured in staff administering the N2 O at the end of the procedural session. RESULTS: The mean and median values of TWA and STEL within the working area were lower than recommended values in the DFM (10.8, 11.6 ppm for TWA; 13.9, 11.0 ppm for STEL) and DFM-DV groups (2.3, 2.8 ppm for TWA; 4.4, 3.5 ppm for STEL) using the portable evacuation system. The N2 O urine exposure in DFM-DV group was lower than DFM group: a mean difference of 9.56 ppm (95% CI 2.65-16.46). Staff N2 O urinary concentrations were within safe biological limits in both the DFM and DFM-DV groups. High exposure concentrations to N2 O were recorded in all FM and FM-DV environmental and biological samples. CONCLUSIONS: The DFM system, with or without a DV, connected to a portable evacuation system during N2 O administration to children for painful procedures kept N2 O levels within the local environment below recommended limits.

Biomonitoring occupational sevoflurane exposure at low levels by urinary sevoflurane and hexafluoroisopropanol.

This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to assess and discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello(®), and assaying Sev-U and HFIP concentrations in their urine collected at the end of the operating room session. All analyses were performed by gas chromatography-mass spectrometry. Environmental sevoflurane levels in the operating rooms were also monitored continuously using an infrared photoacoustic analyzer. Our results showed very low individual sevoflurane exposure levels, generally below 0.5 ppm (mean 0.116 ppm; range 0.007-0.940 ppm). Sev-U and HFIP concentrations were in the range of 0.1-17.28 µg/L and 5-550 µg/L, respectively. Both biomarkers showed a statistically significant correlation with the environmental exposure levels (Sev-U, r=0.49; HFIP, r=0.52), albeit showing fairly scattered values. Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers' very different half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit values.

[Air and biomonitoring of occupational exposure to anesthetic gases in the health care workers of a large hospital in Milan]. / Il monitoraggio ambientale e biologico dell'esposizione professionale a gas anestetici presso le sale operatorie di un grande ospedale milanese.

In this study exposure to anesthetic gases in health care workers of a hospital of Milan was investigated. The evaluation focused on the period 2007-2010 and was performed by environmental monitoring (20 operating rooms and 54 samples) and biological monitoring (180 workers and 242 urine samples). Mean airborne exposure was 3:15 and 0.34 ppm for nitrogen protoxide (N2O) and sevorane; in end-of-exposure urine samples the concentration of N2O and hexafluoroisopropanol, metabolite of sevorane, were 4.85 mg/L and 0.21 mg/L, with 80 and 21% of values below the quantification limit. Sevorane monitoring exceeded or equaled the environmental limit value of 0.5 ppm and the biological exposure index in 17 and 11% of measures. There were no observed exceedances of the limit for N2O. The anesthetist and scrub nurse were tasks with greater exposure. There was a significant correlation between airborne halogenated gases and urinary hexafluoroisopropanol. The results of this study indicates that further efforts are needed to improve the hygienic conditions in the investigated hospital.

Neuromotor effects of short-term and long-term exposures to trichloroethylene in workers.

BACKGROUND: Health effects of long-term exposure to organic solvents at low levels are a major concern in industrialized countries. To assess the neuromotor impact of trichloroethylene objectively, static postural sway and hand tremor parameters, along with urinary trichloroethanol (TCOH) and trichloroacetic acid (TCAA) levels, were investigated in 57 workers without obvious neurological disorders and 60 control subjects. METHODS: The workers had been occupationally exposed to trichloroethylene for 0.1-37 years. The cumulative exposure index (CEI) was calculated from their occupational history and total trichloro-compounds (TCOH + TCAA). RESULTS: Median levels in the workers were 1.7 mg/L for TCOH and 2.5 mg/L for TCAA, and the maximum ambient trichloroethylene concentration was estimated to be <22 ppm from the previously reported equation using TCOH + TCAA. Sway parameters with eyes open and tremor intensity in dominant hand were significantly larger in the exposed workers than in the control subjects when adjusting for possible confounders. A significant dose-effect association was seen between two sway parameters and urinary TCOH level in the workers. Tremor intensities in non-dominant hand differed significantly among three groups of the workers divided according to the CEI. CONCLUSIONS: These findings suggest that trichloroethylene exposure, even at low levels of less than the short-term exposure limit by the ACGIH, can affect the neuromotor function of workers. The postural instability appears to result from recent exposure, and the increased tremor may occur due to short-term and long-term exposures. Hereafter, such objective measures, along with subjective symptoms, should be carefully used for the occupational exposure limit setting.

Exposure of personnel to sevoflurane during paediatric anaesthesia: influence of professional role and anaesthetic procedure.

BACKGROUND AND OBJECTIVE: This study was performed to determine the individual exposure of paediatric operating theatre personnel to sevoflurane and to evaluate the impact of inhalation induction and various airway approaches on exposure to airborne sevoflurane. METHODS: Mean individual environmental (workplace air) exposure to sevoflurane and a biomarker of exposure (urinary sevoflurane) were monitored in 36 subjects (10 anaesthetists, 10 surgeons, 12 nurses and 4 auxiliary personnel) working in two paediatric operating rooms. RESULTS: Environmental and urinary values were significantly greater in anaesthetists compared with other groups, with median values of 0.65ppm (interquartile range 1.36; 95th percentile 4.36) for breathing zone sevoflurane and 2.1 microgL(-1) urine (interquartile range 2.6; 95th percentile 7.6) for urinary sevoflurane. Anaesthetists exceeded the 2ppm maximum allowed environmental concentration recommended by the National Institute for Occupational Safety and Health in 4 of 22 cases (18.1%). A positive correlation was found between the number of patients undergoing inhalational induction each day and mean values of breathing zone and urinary sevoflurane. An increase in the number of daily laryngeal mask insertions, or the use of rigid bronchoscopy, are statistically related to higher environmental and urinary values (P < 0.01 and <0.00001 for breathing zone sevoflurane, P < 0.05 and <0.01 for urinary sevoflurane, respectively). CONCLUSIONS: Anaesthesia with sevoflurane can pose a hazard of chronic exposure with anaesthetists having the highest risk. Endotracheal intubation offers considerable protection against exposure. Routine anaesthesia using a standard facemask, a laryngeal mask or rigid bronchoscopy are risk factors for increased anaesthetic exposure.

Use of 19F-nuclear magnetic resonance and gas chromatography-electron capture detection in the quantitative analysis of fluorine-containing metabolites in urine of sevoflurane-anaesthetized patients.

1: The use of fluorine-19 nuclear magnetic resonance (19F-NMR) and gas chromatography-electron capture detection (GC-ECD) in the analysis of fluorine-containing products in the urine of sevoflurane-exposed patients was explored. 2: Ten patients were anaesthetized by sevoflurane for 135-660 min at a flow rate of 6 l min(-1). Urine samples were collected before, directly after and 24 h after discontinuation of anaesthesia. 3: 19F-NMR analysis of the urines showed the presence of several fluorine-containing metabolites. The main oxidative metabolite, hexafluoroisopropanol (HFIP)-glucuronide, showed two strong quartet signals in the 19F-NMR spectrum. HFIP concentrations after beta-glucuronidase treatment were quantified by (19)F-nuclear magnetic resonance. Concentrations directly after and 24 h after discontinuation of anaesthesia were 131 +/- 41 (mean +/- SEM) and 61 +/- 19 mol mg(-1) creatinine, respectively. Urinary HFIP excretions correlated with sevoflurane exposure. 4: Longer scanning times enabled the measurement of signals from two compound A-derived metabolites, i.e. compound A mercapturic acid I (CAMA-I) and compound A mercapturic acid II (CAMA-II), as well as products from beta-lyase activation of the respective cysteine conjugates of compound A. The signals of the mercapturic acids, 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid were visible after combining and concentrating the patient urines. CAMA-I and -II excretions in patients were completed after 24 h. 5: Since 19F-nuclear magnetic resonance is not sensitive enough, urinary mercapturic acids concentrations were quantified by gas chromatography-electron capture detection. CAMA-I and -II urinary concentrations were 2.3 +/- 0.7 and 1.4 +/- 0.4 mol mg(-1) creatinine, respectively. Urinary excretion of CAMA-I showed a correlation with sevoflurane exposure, whereas CAMA-II did not. 6. The results show that 19F-nuclear magnetic resonance is a very selective and convenient technique to detect and quantify HFIP in non-concentrated human urine. 19F-nuclear magnetic resonance can also be used to monitor the oxidative biotransformation of sevoflurane in anaesthetized patients. Compound A-derived mercapturic acids and 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid, however, require more sensitive techniques such as gas chromatography-electron capture detection and/or gas chromatography-mass spectrometry for quantification.

Biological indices of kidney involvement in personnel exposed to sevoflurane in surgical areas.

BACKGROUND: Fluoride, a main metabolite, and one degradation product of sevoflurane (SEV), called Compound A, are known to cause kidney effects in experimental animals. Other than in volunteers and patients, no research is available on exposed workers. The possible effects on the kidney in workers exposed in surgical areas were studied. METHODS: Subjects exposed to SEV and nitrous oxide (N(2)O) in surgical areas (N = 61) using open (N = 25) or semi-closed (N = 36) circuits were submitted to biological monitoring. The same biological indices were determined in 43 controls also. Sevoflurane (SEVU), nitrous oxide (N(2)OU), total urinary proteins (TUP), N-acetyl-beta-D-glucosaminidase (NAGU), and glutamine synthetase (GSU) were measured in urine. RESULTS: The mean values of environmental exposure were 31.3 ppm (range 0.9-111.6 ppm) for N(2)O and 0.28 ppm (range 0-1.88 ppm) for SEV. Exposed subjects had significantly higher excretion of TUP; a higher, not significant, excretion of GSU was also observed in subjects using open circuits. A significant correlation was found in all exposed subjects between NAGU and SEVU (r = 0.303, P < 0.05), GSU and N(2)OU (r = 0.382, P < 0.01) and, especially, GSU and SEVU (r = 0.650, P < 0.001). These correlations appeared to be influenced by the use of open circuits; infact, NAGU was well correlated to N(2)OU (r = 0.770, P < 0.001) and SEVU (r = 0.863, P < 0.001); GSU to N(2)OU (r = 0.468, P < 0.05) and SEVU (r = 0.735, P < 0.001). CONCLUSIONS: Results show that no relevant effect on the kidney is present for the levels of exposure studied. Nevertheless, correlation between dose and response urinary indices supports that SEV, other than N(2)O, may influence kidney function, especially when open circuits are used.

Serum fluoride concentrations, biochemical and histopathological changes associated with prolonged sevoflurane anaesthesia in horses.

The volatile anaesthetic sevoflurane is degraded to fluoride (F-) and a vinyl ether (Compound A), which have the potential to harm kidney and liver. Whether renal and hepatic injuries can occur in horses is unknown. Cardiopulmonary, biochemical and histopathological changes were studied in six healthy thoroughbred horses undergoing 18 h of low-flow sevoflurane anaesthesia. Serum F- concentrations were measured and clinical laboratory tests performed to assess hepatic and renal function before and during anaesthesia. Necropsy specimens of kidney and liver were harvested for microscopic examination and compared to pre-experimental needle biopsies. Cardiopulmonary parameters were maintained at clinically acceptable levels throughout anaesthesia. Immediately after initiation of sevoflurane inhalation, serum F- levels began to rise, reaching an ongoing 38-45 micromol 1(-1) plateau at 8 h of anaesthesia. Serum biochemical analysis revealed only mild increases in glucose and creatinine kinase and a decrease in total calcium. Beyond 10 h of anaesthesia mild, time-related changes in urine included increased volume, glucosuria and enzymuria. Histological examination revealed mild microscopic changes in the kidney involving mainly the distal tubule, but no remarkable alterations in liver tissue. These results indicate that horses can be maintained in a systemically healthy state during unusually prolonged sevoflurane anaesthesia with minimal risk of hepatocellular damage from this anaesthetic. Furthermore, changes in renal function and morphology observed after sevoflurane inhalation are judged minimal and appear to be clinically irrelevant; they may be the result of anaesthetic duration, physiological stressors, sevoflurane (or its degradation products) or other unkown factors associated with these animals and study conditions.

[Biological monitoring of occupational exposure to sevoflurane]. / Monitoraggio biologico dell'esposizione professionale a sevoflurane.

Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.

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).

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.

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.

Neurobehavioral functions in operating theatre personnel: a multicenter study.

The study was conducted to evaluate neuropsychological symptoms, subjective stress and response speed functions in subjects occupationally exposed to low levels of anesthetic gases. A group of 112 operating theatre personnel exposed to anesthetic gases (nitrous oxide and isoflurane), and 135 non exposed hospital workers from 10 hospitals in Northern Italy were examined before and after the shift on the first and the last day of the working week. Three different tasks were administered: a complex reaction time test (the Stroop Color Word); a questionnaire for neuropsychological symptoms (EURO-QUEST); the block design subtest (WAIS). Biological and atmospheric indicators of exposure were measured. In the exposed group, the geometric mean of urinary nitrous oxide at the end of the shift was 7.1 micrograms/l (95th percentile 12.4, range 1.5-43) on the first and 7.8 micrograms/l (95th percentile 21.5, range 1.0-73.3) on the last day of the working week. On the same days, end of shift urinary isoflurane was 0.7 microgram/l (95th percentile 2.6, range 0-4.7) on the first day and 0.8 microgram/l (95th percentile 2.0, range 0-5.6) on the last. The exposed and control subjects were comparable for both basic intellectual abilities and subjective stress levels. No statistical differences were observed between exposed and control subjects for neuropsychological tests and symptoms. No dose-effect relationships were observed between the exposure indicators and the test results. In conclusion, no early behavioral effect on the central nervous system was detectable at the exposure levels measured. The biological exposure limits of 13 micrograms/l for nitrous oxide and 1.8 micrograms/l for isoflurane corresponding respectively to the atmospheric concentrations of 25 ppm and 0.5 ppm seem to be adequately protective for the integrity of workers' neurobehavioral functions, as measured with the tests used.