Risk assessment of occupational exposure to anesthesia Isoflurane in the hospital and veterinary settings.

Despite the modern ventilation and waste anesthetic gas (WAG) scavenging systems, occupational exposure to common volatile anesthesia, isoflurane, can occur in the hospital and veterinary settings, but limited information exists on potential exposure and health risk of isoflurane. We assessed exposure dose rates and risks among clinicians and veterinary professionals from occupational exposure to isoflurane. Through a critical review of open literature (1965 to 2020), we summarized potential adverse effects and exposure scenarios of isoflurane among the professional groups, including anesthetists, nurses, operating room personnel, researchers, and/or veterinarians. Deterministic United States National Research Council/Environmental Protection Agency's risk assessment framework (hazard identification, dose-response relationship, exposure assessment and risk characterization) was used to compute inhalation Reference Doses (RfDs), Average Daily Doses (ADDs), and Hazard Quotient (HQ) values-an established measure of non-carcinogenic (systemic) risks-from exposure to isoflurane to workers in hospital and veterinary settings. We identified the central nervous system as the main target for isoflurane, and that isoflurane has dose-dependent effects on cardiac hemodynamics, can impair pulmonary functions and potentially cross the utero-placental barrier leading to congenital malformation in fetus. Based on the modelled RfDs (range 0.8003-7.55 mg/kg-day) and ADDs (range 0.071-1.9617 mg/kg-day), we estimated 56 different HQ values, of which 5 HQs were higher than 1 (range 1.099-2.4512) under high exposure scenarios. Our results suggest a significant non-carcinogenic risk from isoflurane exposures among workers in the occupational settings. The findings underscore the need to significantly minimize isoflurane release to protect workers' health in the hospital and veterinary environments.

Probabilistic health risk assessment of occupational exposure to isoflurane and sevoflurane in the operating room.

Risk assessment is an important tool in predicting the possible risk to health. It heightens awareness by estimating the probability of adverse health effects in humans who are exposed to chemicals in the course of their work. Therefore, the present work aims to determine the occupational exposure of operating room staff to the volatile anesthetic gases, isoflurane and sevoflurane, and estimates non-cancer risk using the United States Environmental Protection Agency method. Air samples from the breathing zone of staff members were collected using the Occupational Safety and Health Administration Method 103 and analyzed using gas chromatography-mass spectroscopy. The results indicate that the measured concentrations of isoflurane and sevoflurane are below the National Institute of Occupational Safety and Health standard (2 ppm) for technicians and nurses, but not for anesthesiologists and surgeons. Moreover, the estimated non-cancer risk due to isoflurane is above the acceptable value for anesthesiologists (but acceptable for other occupational categories). A sensitivity analysis indicates that exposure time has the most effect on calculated risk (53.4%). Occupational exposure to anesthetic gases may endanger the health of operating room personnel. Therefore, control measures, such as daily testing of anesthetic devices, ensuring the effectiveness of ventilation systems, advanced scavenging methods, and regular training of staff are highly recommended.

Determination of sevoflurane and isopropyl alcohol in exhaled breath by thermal desorption gas chromatography-mass spectrometry for exposure assessment of hospital staff.

Volatile anaesthetics and disinfection chemicals pose ubiquitous inhalation and dermal exposure risks in hospital and clinic environments. This work demonstrates specific non-invasive breath biomonitoring methodology for assessing staff exposures to sevoflurane (SEV) anaesthetic, documenting its metabolite hexafluoroisopropanol (HFIP) and measuring exposures to isopropanol (IPA) dermal disinfection fluid. Methods are based on breath sample collection in Nalophan bags, followed by an aliquot transfer to adsorption tube, and subsequent analysis by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Ambient levels of IPA were also monitored. These methods could be generalized to other common volatile chemicals found in medical environments. Calibration curves were linear (r(2)=0.999) in the investigated ranges: 0.01-1000 ppbv for SEV, 0.02-1700 ppbv for IPA, and 0.001-0.1 ppbv for HFIP. The instrumental detection limit was 10 pptv for IPA and 5 pptv for SEV, both estimated by extracted ion-TIC chromatograms, whereas the HFIP minimum detectable concentration was 0.5 pptv as estimated in SIM acquisition mode. The methods were applied to hospital staff working in operating rooms and clinics for blood draws. SEV and HFIP were present in all subjects at concentrations in the range of 0.7-18, and 0.002-0.024 ppbv for SEV and HFIP respectively. Correlation between IPA ambient air and breath concentration confirmed the inhalation pathway of exposure (r=0.95, p<0.001) and breath-borne IPA was measured as high as 1500 ppbv. The methodology is easy to implement and valuable for screening exposures to common hospital chemicals. Although the overall exposures documented were generally below levels of health concern in this limited study, outliers were observed that indicate potential for acute exposures.

Reliability of the volatile agent consumption display in the Draeger Primus™ anesthesia machine.

Knowledge of the consumed amount of volatile anesthetic (VA) expressed in liquid agent is necessary to enable agent sparing dosing measures and for billing purposes. The widespread Draeger Primus™ anesthesia machine displays in its logbook the amount of consumed VA at the end of each anesthesia, but the reliability of this parameter is yet unknown. The objective was to evaluate the precision and reliability of the inbuilt VA consumption display in Draeger Primus™ anesthesia machines as compared with the gold standard of weighing the vaporizer before and after anesthesia. In this prospective laboratory investigation we compared the VA consumption displayed by the Draeger Primus™ anesthesia machine with measured vaporizer weight differences before and after 10 sevoflurane and 10 desflurane anesthesias. We assessed the average difference and spread of values between the predicted (displayed) and measured (control) values for VA consumption. The displayed sevoflurane consumption overestimated the measured values by 4.3 ± 5.4 ml (7.6%). The displayed desflurane consumption underestimated the measured values by -3.5 ± 6.3 ml (6.2%). Nine from 10 sevoflurane pairs of values and all desflurane pairs of values were within ±1.96 SD. The displayed VA consumption calculations for sevoflurane and desflurane in the Draeger Primus™ are sufficiently reliable to estimate the pharmacoeconomic impact of VA delivery during inhalational anesthesia.

[Assessment of occupational exposure of medical personnel to inhalatory anesthetics in Poland]. / Ocena narazenia zawodowego personelu medycznego na anestetyki wziewne w Polsce.

BACKGROUND: Despite common use of inhalatory anesthetics, such as nitrous oxide (N2O), halothane, sevoflurane, and the like, occupational exposure to these substances in operating theatres was not monitored in Poland until 2006. The situation changed when maximum admissible concentration (MAC) values for anesthetics used in Poland were established in 2005 for N2O, and in 2007 for sevoflurane, desflurane and isoflurane. The aim of this work was to assess occupational exposure in operating rooms on the basis of reliable and uniform analytical procedures. MATERIAL AND METHODS: The method for the determination of all anesthetics used in Poland, i.e. nitrous oxide, sevoflurane, isoflurane, desflurane, and halothane, was developed and validated. The measurements were performed in 2006-2010 in 31 hospitals countrywide. The study covered 117 operating rooms; air samples were collected from the breathing zone of 146 anesthesiologists, and 154 nurses, mostly anaesthetic. The measurements were carried out during various surgical operations, mostly on adult patients but also in hospitals for children. RESULTS: Time weighted average concentrations of the anesthetics varied considerably, and the greatest differences were noted for N2O (0.1-1438.5 mg/m3); 40% of the results exceeded the MAC value. Only 3% of halothane, and 2% of sevoflurane concentrations exceeded the respective MAC values. CONCLUSIONS: Working in operating theatres is dangerous to the health of the operating staff. The coefficient of combined exposure to anesthesiologists under study exceeded the admissible value in 130 cases, which makes over 40% of the whole study population. Most of the excessive exposure values were noted for nitrous oxide.

Application of mathematical models in combination with Monte Carlo simulation for prediction of isoflurane concentration in an operation room theater.

Applicability of two mathematical models in inhalation exposure prediction (well mixed room and near field-far field model) were validated against standard sampling method in one operation room for isoflurane. Ninety six air samples were collected from near and far field of the room and quantified by gas chromatography-flame ionization detector. Isoflurane concentration was also predicted by the models. Monte Carlo simulation was used to incorporate the role of parameters variability. The models relatively gave more conservative results than the measurements. There was no significant difference between the models and direct measurements results. There was no difference between the concentration prediction of well mixed room model and near field far field model. It suggests that the dispersion regime in room was close to well mixed situation. Direct sampling showed that the exposure in the same room for same type of operation could be up to 17 times variable which can be incorporated by Monte Carlo simulation. Mathematical models are valuable option for prediction of exposure in operation rooms. Our results also suggest that incorporating the role of parameters variability by conducting Monte Carlo simulation can enhance the strength of prediction in occupational hygiene decision making.

Life cycle greenhouse gas emissions of anesthetic drugs.

BACKGROUND: Anesthesiologists must consider the entire life cycle of drugs in order to include environmental impacts into clinical decisions. In the present study we used life cycle assessment to examine the climate change impacts of 5 anesthetic drugs: sevoflurane, desflurane, isoflurane, nitrous oxide, and propofol. METHODS: A full cradle-to-grave approach was used, encompassing resource extraction, drug manufacturing, transport to health care facilities, drug delivery to the patient, and disposal or emission to the environment. At each stage of the life cycle, energy, material inputs, and emissions were considered, as well as use-specific impacts of each drug. The 4 inhalation anesthetics are greenhouse gases (GHGs), and so life cycle GHG emissions include waste anesthetic gases vented to the atmosphere and emissions (largely carbon dioxide) that arise from other life cycle stages. RESULTS: Desflurane accounts for the largest life cycle GHG impact among the anesthetic drugs considered here: 15 times that of isoflurane and 20 times that of sevoflurane on a per MAC-hour basis when administered in an O(2)/air admixture. GHG emissions increase significantly for all drugs when administered in an N(2)O/O(2) admixture. For all of the inhalation anesthetics, GHG impacts are dominated by uncontrolled emissions of waste anesthetic gases. GHG impacts of propofol are comparatively quite small, nearly 4 orders of magnitude lower than those of desflurane or nitrous oxide. Unlike the inhaled drugs, the GHG impacts of propofol primarily stem from the electricity required for the syringe pump and not from drug production or direct release to the environment. DISCUSSION: Our results reiterate previous published data on the GHG effects of these inhaled drugs, while providing a life cycle context. There are several practical environmental impact mitigation strategies. Desflurane and nitrous oxide should be restricted to cases where they may reduce morbidity and mortality over alternative drugs. Clinicians should avoid unnecessarily high fresh gas flow rates for all inhaled drugs. There are waste anesthetic gas capturing systems, and even in advance of reprocessed gas applications, strong consideration should be given to their use. From our results it appears likely that techniques other than inhalation anesthetics, such as total i.v. anesthesia, neuraxial, or peripheral nerve blocks, would be least harmful to the environment.

Field application of SPME as a novel tool for occupational exposure assessment with inhalational anesthetics.

Occupational exposure to inhalational anesthetics occurs routinely in operating rooms. It could induce serious health hazards and diseases. This exposure assessment is a crucial step in determining risks. In this study, a pen-shaped holder for solid-phase microextraction (SPME) sampler was successfully applied as a time-weighted average sampling tool for workshift exposure assessment of operation room staff to halothane. It proved to be very convenient for use in occupational environments such as operation rooms. Samples were analyzed by a gas chromatography-mass spectrometry. The validity of the SPME method was checked in real-world conditions with Occupational Safety and Health Administration (OSHA) 103 standard method for the determination of inhalational anesthetics. A good agreement between OSHA 103 and SPME methods was obtained and results demonstrated no statistically significant differences in anesthetic concentrations determined by the two analytical methods (p ≥ 0.05). It is concluded that SPME in retracted mode could successfully be applied in occupational exposure assessment purposes.

[Occupational exposure to sevoflurane in pediatric operating rooms: the multi-point sampling method for risk assessment]. / Esposizione professionale al sevoflurano nelle sale operatorie di pertinenza pediatrica: il contributo del monitoraggio ambientale con tecnica multi-punto nella valutazione del rischio.

Several studies have shown that occupational exposure to anesthetic gases might be higher during pediatric surgery, probably due to the increased use of inhalational induction techniques. Our study aims to assess the level of exposure to sevoflurane in two rooms of pediatric surgery, using multi-point sampling method for environmental monitoring. The gas concentrations as well as its dispersion were measured in strategic points in the rooms for a total of 44 surgical interventions. Although the average of these concentrations has been rather low (1.32, SD +/- 1:55 ppm), the results obtained have documented a significant distribution kinetics difference inside the rooms as function of multiple factors among which there were the anesthetic technique used and the team involved. Therefore the method described allows to correctly analyze the spread of anesthetic gases and suggests a different risk stratification which may be dependent on the professional work.

Cuffed endotracheal tubes in children reduce sevoflurane and medical gas consumption and related costs.

BACKGROUND: This study aims to evaluate sevoflurane and anaesthetic gas consumption using uncuffed vs. cuffed endotracheal tubes (ETT) in paediatric surgical patients. METHODS: Uncuffed or cuffed ETT were used in paediatric patients (newborn to 5 years) undergoing elective surgery in a randomized order. Duration of assessment, lowest possible fresh gas flow (minimal allowed FGF: 0.5 l/min) and sevoflurane concentrations used were recorded. Consumption and costs for sevoflurane and medical gases were calculated. RESULTS: Seventy children (35 uncuffed ETT/35 cuffed ETT), aged 1.73 (0.01-4.80) years, were enrolled. No significant differences in patient characteristics, study period and sevoflurane concentrations used were found between the two groups. Lowest possible FGF was significantly lower in the cuffed ETT group [1.0 (0.5-1.0) l/min] than in the uncuffed ETT group [2.0 (0.5-4.3) l/min], P<0.001. Sevoflurane consumption per patient was 16.1 (6.4-82.8) ml in the uncuffed ETT group and 6.2 (1.1-14.9) ml in the cuffed ETT group, P=0.003. Medical gas consumption was 129 (53-552) l in the uncuffed ETT group vs. 46 (9-149) l in the cuffed ETT group, P<0.001. The total costs for sevoflurane and medical gases were 13.4 (6.0-67.3)euro/patient in the uncuffed ETT group and 5.2 (1.0-12.5)euro/patient in the cuffed ETT group, P<0.001. CONCLUSIONS: The use of cuffed ETT in children significantly reduced the costs of sevoflurane and medical gas consumption during anaesthesia. Increased costs for cuffed compared with uncuffed ETT were completely compensated by a reduction in sevoflurane and medical gas consumption.

A closed-circuit neonatal xenon delivery system: a technical and practical neuroprotection feasibility study in newborn pigs.

BACKGROUND: Asphyxia accounts for 23% of the 4 million annual global neonatal deaths. In developed countries, the incidence of death or severe disability after hypoxic-ischemic (HI) encephalopathy is 1-2/1000 infants born at term. Hypothermia (HT) benefits newborns post-HI and is rapidly entering clinical use. Xenon (Xe), a scarce and expensive anesthetic, combined with HT markedly increases neuroprotection in small animal HI models. The low-Xe uptake of the patient favors the use of closed-circuit breathing system for efficiency and economy. We developed a system for delivering Xe to mechanically ventilated neonates, then investigated its technical and practical feasibility in a previously described neonatal pig model approximating the clinical scenario of global HI injury, prolonged Xe delivery with and without HT as a potential therapy, subsequent neonatal intensive care unit management, and tracheal extubation. METHODS: Sixteen newborn pigs underwent a global 45 min HI insult (4%-6% inspired oxygen reducing the electroencephalogram amplitude to <7 microV), then received 16 h 50% inspired Xe during normothermia (39.0 degrees C) or HT (33.5 degrees C). A conventional neonatal ventilator provided breaths of oxygen to a lower chamber compressing a hanging bag within. This bag communicated with the upper closed part of the breathing system containing soda lime, unidirectional valves, Xe/oxygen analyzers, and a tracheal tube connection. At each end-inspiration, this bag emptied fully and a bolus of oxygen, the driving gas, crossed from the lower to upper chamber via an additional valve. This mechanically substituted the gas uptake from the circle during the previous breath cycle (oxygen + small volume of Xe) with an equivalent volume of oxygen creating a slow-rising inspired oxygen concentration. This was offset by manual injection of Xe boluses, infrequently at steady state, due to the low-Xe uptake of the patient. RESULTS: Total mean Xe usage was 0.18 (0.16-0.21) L/h with no differences between Xe-HT and Xe-NT groups, which had weights of 1767 (1657-1877) g and 1818 (1662-1974) g, respectively (95% CI). HT reduced heart rate in the cooled animals; 180 (165-195) vs 148 (142-155) bpm (P < 0.0001) with no differences in arterial blood pressure, oxygen saturation, arterial carbon dioxide tension, or weaning times between these groups. CONCLUSION: We describe a closed-circuit Xe delivery system with automatic mechanical oxygen replenishment, which could be developed as a single use device. Gas exchange was maintained while Xe consumption was minimal (<$2/h at $10/L*). We have shown it is both feasible and cost-efficient to use this Xe delivery method in newborn pigs for up to 16 h with or without concurrent cooling after a severe HI insult.

Paired assessment of volatile anesthetic concentrations with synaptic actions recorded in vitro.

The volatile anesthetic isoflurane poses a number of experimental challenges in the laboratory. Due to its rapid evaporation, the open conditions of most in vitro electrophysiological recording systems make the determination of actual isoflurane concentrations a challenge. Since the absolute anesthetic concentration in solution is directly related to efficacy, concentration measurements are important to allow comparisons between laboratory and clinical studies. In this study we quantify the sources of isoflurane loss during experimentation and describe a method for the measurement of isoflurane concentrations using gas chromatography and mass spectrometry simultaneous to in vitro electrophysiological measurements. Serial samples of perfused bath solution allowed correlation of isoflurane concentrations with ongoing biological effects. Saturated physiological solutions contained 13.4 +/- 0.2 mM isoflurane and were diluted to desired "nominal" concentrations for experiments. The perfusion system established stable isoflurane concentrations within the bath by 2 minutes. However, bath isoflurane concentrations varied substantially and unpredictably between experiments. The magnitudes of such discrepancies in isoflurane concentrations spanned clinically important levels. Our studies suggest that, despite countermeasures, solution handling significantly impacted the isoflurane content in the tissue bath. The magnitude of these discrepancies appears to necessitate systematic direct measurement of bath isoflurane concentrations during most in vitro conditions.

[Identification and evaluation of liver damage in subjects exposed to occupational risk from general anesthetics]. / Identificazione e valutazione del danno epatico in soggetti esposti a rischio occupazionale da anestetici generali.

BACKGROUND: The program Hepascore was produced by an interdisciplinary group working in the Laboratory of Clinical Informatics of the San Giovanni Battista Hospital in Turin with the aim of supporting physicians in the early diagnosis of hepatic damage and in its qualitative and quantitative characterization. The methodology used by this program can be useful especially for investigations concerning Industrial Medicine, which intend to control the occupational risk due to environmental exposure, not only to perform an early diagnosis (secondary prevention), but also to control the temporal evolution of the disease, by comparing significant data in a reproducible way. OBJECTIVE: This study was conducted with the aim of monitoring, by using the screening protocol of Hepascore, a group of workers exposed to an occupational risk by general anaesthetics, assessing the reliability of the proposed model and comparing it to the conventional approach in a cost/effectiveness analysis. METHODS: We evaluated 280 subjects (nurses and physicians) professionally exposed to anaesthetic gas; the environmental presence of anaesthetic agents was tested in all operating room of the hospital by the measurement of halogenated anaesthetics and nitrogen protoxide in the air. All the 280 subjects were submitted to a complete clinical evaluation and laboratory analyses, as recommended by monitoring protocols; in parallel, but independently from the clinical evaluation, also the sequential way used in the program Hepascore (a first screening phase evaluating only a few laboratory parameters, followed by a confirmation phase based on a larger number of blood tests with more restricted limits) was performed. The protocol applied in this study foresaw that subjects in which clinical evaluation and/or Hepascore brought to suspect a 'likely' liver alteration, had to be investigated thoroughly and to be reevaluated after 6 months by clinical examination and by Hepascore. RESULTS: The environmental determinations did never demonstrate the presence of anaesthetics over the threshold value (50 ppm for the N2O and 2 ppm for halogenated anaesthetics). The conventional clinical evaluation recognized as pathological 22 subjects with one or more liver parameters altered, which were explained as mild cytolytic or cholestatic alterations. The screening protocol carried out by Hepascore in the preliminary phase evidenced as pathological 38 subjects on 280 and 22 of them (corresponding to the 22 subjects identified by the clinical evaluation) were confirmed in the following phase (disease likely). CONCLUSIONS: This fact confirms that the sequential approach used by Hepascore provides the same outcomes obtained by performing all tests in the entire population under study, allowing a saving of 57% of the total cost spent for the traditional evaluation. The sequential approach proposed by Hepascore could be employed in all the clinical settings in which an evaluation of liver functional state is required, both in presence of environmental risk factors and in the case of a programme for the optimization of the population's food habits.

[Efficacy of bispectral index monitoring in improving anesthetic management, economics, and use of the operating theater].

This study was designed to assess the efficacy of bispectral index (BIS) monitoring in reducing the amount of volatile anesthetics used and improving recovery profiles. Sixty patients (ASA physical status 1 or 2) undergoing various surgical procedures under sevoflurane/nitrous oxide anesthesia were studied. The patients were randomly assigned to two groups of which anesthesia was carried out with (BIS group) or without (control group) monitoring BIS, and in the latter, anesthesiologist was blinded to the BIS values. In the BIS group, sevoflurane concentration was adjusted to achieve target BIS values between 40-60 during surgery and 60-75 during the final 15 min of the surgery. Drug usage, incidence of intraoperative complications, and recovery parameters were recorded. Demographics were similar between the groups. The BIS values in the BIS group were significantly higher compared with those of control group in which BIS values were blinded during anesthesia. The sevoflurane consumption in the BIS group (17 +/- 3 ml.h-1) was lower than control group (22 +/- 3 ml.h-1). Compared with control group, the patients in BIS group were extubated earlier and became eligible for discharge earlier from recovery room than control group. There was no significant difference in the incidence of intraoperative complications between the groups. Titrating sevoflurane concentration with BIS monitoring during anesthesia decreased anesthetic consumption and improved recovery compared with standard clinical practice.

Air contamination of a closed anesthesia circuit.

Closed-circuit anesthesia (CCA) has certain advantages such as decreased cost, decreased anesthetic gas pollution, improved inhalational gas humidity and temperature in comparison to conventional inhalational anesthesia using a high fresh gas flow, i.e. more than 2 L x min(-1), with a semi-closed breathing circuit. The main disadvantage of CCA is the possibility of hypoxic anesthetic gas delivery. This potentially lethal situation is caused by an insufficient oxygen flow rate for the body metabolism or by the accumulation of inactive gas, usually nitrogen, within the breathing circuit in spite of a sufficient oxygen concentration in the fresh gas supply to the breathing circuit. In the latter case, the accumulation of inactive gas may also lead an increased risk of awareness because of its dilution effect on the concentrations of inhalational anesthetics. We herein present a case of air contamination of the breathing circuit through a sampling line of an anesthetic gas monitor. The air caused a decrease in the oxygen concentration during closed circuit anesthesia.