General anaesthesia with volatile anaesthetic agents is the most common technique for children, especially small children. The major advantage of this method lies in its great flexibility, allowing the necessary level of anaesthesia to be applied depending on the time required for the surgical procedure. Mask induction remains a widely used technique, particularly for small children in whom intravenous (i.v.) cannulation may be difficult. Furthermore, mask induction has a low incidence of complications such as coughing, laryngospasm and bronchospasm in newborns, infants and in children with respiratory diseases .
Sevoflurane is presently the volatile anaesthetic of choice for induction and maintenance of general anaesthesia in children. It has a pleasant odour and does not irritate the airways. The solubility in blood is poor with a blood/gas partition coefficient at 37°C of 0.63-0.69. These properties make it a useful drug for anaesthesia in children because of the rapid and smooth induction and fast recovery .
Chronic occupational exposure to anaesthetic agents is a well known and still unresolved problem that may affect the health of operating theatre personnel. However, in recent years considerable progress has been made in keeping the exposure of staff below a safe level. The degree of pollution in operating theatres depends firstly on the efficiency of the active scavenging system, and secondly on additional factors such as floor area, number of air exchanges per hour, anaesthetic techniques, and the inspiratory and expiratory concentrations of the inhalation anaesthetics [3,4]. The periodic measurement of volatile anaesthetics in the breathing zone and the urinary concentrations in operating theatre staff are useful tools for monitoring the chronic exposure to these chemicals. Certain disorders, mainly reproductive and lymphopoietic, have been reported after long-term exposure to mixtures of nitrous oxide and halogenated anaesthetics [5,6]. Although no epidemiological evidence is available regarding the adverse effects of sevoflurane, exposure to this agent should nevertheless be minimized as a precaution.
The first aim of this study was to determine the degree of individual exposure to sevoflurane in persons of different professional groups in an operating theatre exclusively dedicated to paediatric surgery. The entire staff (anaesthetists, surgeons, nurses and auxiliary personnel) were subjected to environmental and biological monitoring and mean breathing zone sevoflurane and urinary sevoflurane concentrations were measured. A second aim of the study was to evaluate the impact of mask induction and of various different methods of airway management such as tracheal intubation with cuffed or uncuffed tubes, laryngeal mask as well as endoscopy with a rigid bronchoscope on the exposure of the operating theatre staff to sevoflurane.
The study was conducted during a period of 2 weeks on 36 subjects (13 males, 23 females, aged 26-63 yr) working as anaesthetists (n = 10), surgeons (n = 10), nurses (n = 12) or auxiliary personnel (n = 4) in a neonatal and paediatric operating room located in our paediatric department. The paediatric operating unit consists of two operating rooms where both conventional operations as well as laparo-thoracoscopic surgical procedures are performed. Endoscopic procedures with a rigid bronchoscope are also carried out by the anaesthetists. The anaesthetists have to combine their activity in the operating theatre with on-call duty in the paediatric intensive care unit. Surgery is performed during the morning half-shift (daily exposure time, 3-6 h). The total number of surgical sessions monitored during the survey was 20.
All anaesthesia inductions carried out during the study were performed in the operating rooms before surgery. Both operating rooms had a floor area, ceiling height and room volume of 41 m2, 2.7 m and 111 m3, respectively. The gas scavenging system provided 15 air exchanges per hour in both rooms: all ventilation consisted of fresh air.
The Institutional Ethics Committee approved the study and written, informed parental consent was obtained from 33 children (19 males, 14 females; median age 5.1 (range 1.2-6.7) yr, median weight 20.0 (range 10.5-26.7) kg, underwent general anaesthesia for elective paediatric surgical and tracheobronchoscopic procedures. Exclusion criteria of patients were ASA IV and high probability of a difficult airway.
All patients were premedicated with diazepam (0.2 mg kg−1) and atropine (0.015 mg kg−1) orally 1 h preoperatively. In children older than 6 yr, general anaesthesia was induced i.v. with propofol (3 mg kg−1). In patients under 6 yr, anaesthesia was induced by mask with sevoflurane concentrations increasing from 1% to 8%. General anaesthesia was maintained with sevoflurane (expired concentration is 1.5-3%). Nitrous oxide was not used. Anaesthesia was supplemented with fentanyl (2-4 μg kg−1 h−1) or with caudal anaesthesia with ropivacaine 2 mg kg−1. Cisatracurium (0.2 mg kg−1) was given for muscle relaxation according to surgical needs.
A closely fitting facemask connected to a Jackson-Rees' T-piece anaesthesia system was used during induction . Airway management was by laryngeal mask in surgical procedures expected to last less than 1 h and with maintenance of spontaneous breathing, or by endotracheal tube in operations expected to last more than 1 h or requiring controlled ventilation of the lungs. A cuffed tracheal tube was used in patients above 7 yr, and an uncuffed tube was used in younger patients. Laryngeal mask airways of size 1.5, 2 or 2.5 were used for children under 10 kg, from 10 to 20 kg and 21 to 30 kg body weight, respectively. The laryngeal mask airway was inserted and secured according to the manufacturer's recommendations. The size of the uncuffed tracheal tube was calculated as four plus one-quarter the age of the patients in years. A semi-open circuit in connection with a Servo® ventilator 900C (Siemens Elema, Solna, Sweden) was used during maintenance of anaesthesia. During endoscopy with rigid instruments, the Jackson-Rees' T-piece system was connected to the bronchoscope and spontaneous breathing was maintained. End-tidal CO2 and inspiratory and expiratory sevoflurane concentrations were monitored continuously (5250 RGM Ohmeda; Louisville, CO, USA). The ventilation breathing circuit was connected to a scavenging system connected to the hospital vacuum system (aspiration rate is 45 L min−1) during both induction and maintenance of anaesthesia.
Mean individual environmental (workplace air) exposure to sevoflurane and urinary sevoflurane concentrations were monitored repeatedly in the 36 subjects during a 2-week study period. Briefly, each subject was equipped with a diffusive passive sampler (Radiello cod. 130; Aquaria, Milan, Italy) which conforms to the CEN/TC 264 WG 11 standard. The samplers were attached to the coat, near the breathing zone, of each subject at the beginning of the morning operating shift, after bladder voiding. After exposure (median 3.5 h, range 2-6 h), the individual samplers were collected and the absorbing cartridges stored at 4°C before analysis. At the same time, post-shift spot urine samples were collected. Immediately (within 5 min of voiding to avoid analysate loss), a fixed volume of 10 mL of each fresh urine sample was transferred to a 20-mL pre-sealed vial with a disposable syringe [8,9].
To quantify the excreted unmodified sevoflurane, a headspace technique coupled with a GC-MS method was used . After equilibrating each vial at 41°C for 120 min, 1 mL of headspace was injected at 200°C into the chromatographic system, equipped with a capillary PoraplotQ column (27 m × 0.25 mm ID, 8 μm thickness) (Varian, Walnut Creek, CA, USA) at helium flow is 1 mL min−1. Each Radiello cartridge was desorbed into a 20 mL headspace vial using 10 mL of water: methanol (60: 40, v:v); after equilibrium at 45°C for 60 min, the same GC-MS method was used. The amounts of sevoflurane (retention time is 13.2 min) were calculated using a selected-ionmonitoring (SIM) method, by detecting the 131/51 (quantifier/qualifier ions, Q1/Q2) m/z window. The method was sensitive and its overall inter-day precision was within 10% relative standard deviation.
Exposure to sevoflurane was monitored in all operating theatre personnel with different professional roles (anaesthetists, surgeons, nurses and auxiliary personnel). The National Institute for Occupational Safety and Health (NIOSH) threshold was taken as the reference value for the breathing zone, which recommends that no worker be exposed to a maximum allowed concentration (MAC) greater than 2 parts per million (ppm) for any halogenated anaesthetic agent (without concomitant nitrous oxide exposure) .
Statistical analysis was carried out using the Intercooled Stata® software (version 7.0) (Stata Corporation, College Station, TX, USA). Kruskal-Wallis and Wilcoxon signed rank sum tests were used to compare non-parametric variables. A linear regression model was used to relate variables. P < 0.05 was regarded as significant.
Of the 33 children during the study period, 25 were submitted to inhalation induction and maintenance with sevoflurane, while in 8 cases an i.v. induction with propofol and inhalation maintenance with sevoflurane were carried out. An uncuffed tube was used in 18 cases, a cuffed tube in 5 cases, a laryngeal mask in 5 cases and a rigid bronchoscopy in 5 cases. No important adverse events were reported. None of the patients had perioperative anaesthetic problems that could have a diverse effect on the samplings, such as complications during induction of patients, difficult intubation, accidental extubation of the child and incorrect positioning of the laryngeal mask.
The individual exposure of the paediatric operating theatre personnel to sevoflurane was measured daily during the 2-week survey. The median and interquartile range (IQR) values for breathing zone and urinary sevoflurane (used as an internal dose biomarker of exposure) were 0.13 ppm (IQR 0.43 ppm) and 0.6 μg L−1 (IQR 1.3 μg L−1), respectively. The occupational role was seen to be a key determinant of sevoflurane exposure and intake (Table 1). Environmental and urinary sevoflurane values were significantly greater in anaesthetists than in other personnel (surgeons, nurses and auxiliary personnel), with median values of breathing zone sevoflurane of 0.65 ppm (IQR 1.36 ppm; 95th percentile 4.36 ppm) and urinary sevoflurane of 2.1 μg L−1 (IQR 2.6 μg L−1; 95th percentile 7.6 μg L−1). Notably, anaesthetists exceeded the 2 ppm environmental MAC value recommended by NIOSH in 4 of 22 cases (18.1%).
Nurses had lower values than anaesthetists, with median breathing zone sevoflurane exposure values of 0.17 ppm (IQR 0.25 ppm). Median urinary sevoflurane was 0.7 μg L−1 (IQR 0.9 μg L−1) in this group. Only one of a total of 30 samples taken from nurses (3.3%) exceeded the 2 ppm environmental level. The surgeons had significantly lower values of breathing zone sevoflurane (median 0.07 ppm; IQR 0.04 ppm) and urinary sevoflurane (median 0.4 μg L−1; IQR 0.3 μg L−1) and the 2 ppm environmental MAC was never exceeded. Auxiliary personnel were exposed to negligible amounts of sevoflurane (median environmental concentration 0.04 ppm; median urinary concentration 0.2 μg L−1).
Log-transformed urinary concentrations appear to be closely related to the breathing zone concentrations for anaesthetists (n = 21; r2 = 0.583, P < 0.0005) and nurses (n = 29; r2 = 0.712, P < 0.0005) (Fig. 1), but a weaker relationship was seen in surgeons (n = 13; r2 = 0.003, P = 0.846) and auxiliary personnel (n = 11; r2 = 0.136, P = 0.264).
By splitting the nurses' group into three subgroups according to their tasks (nurses assisting anaesthetists, scrub nurses and circulating nurses) some interesting, though not statistically significant, differences are highlighted (Table 2). The nurses assisting the anaesthetists had the highest exposure levels (both environmental and urinary), followed by the scrub nurses and circulating nurses. The only environmental exposure value above 2 ppm was found in a nurse assisting the anaesthetists.
As far as the influence of anaesthetic procedures is concerned, the operating theatre staff on the whole showed a positive correlation between the number of patients undergoing inhalational induction each day and the mean values of breathing zone and urinary sevoflurane (Fig. 2). The influence of airway management (tracheal intubation with cuffed tube, tracheal intubation with uncuffed tube, laryngeal mask insertion and use of rigid bronchoscope) on individual exposure to sevoflurane showed that the number of daily laryngeal mask insertions was statistically related to increasing environmental and urinary values throughout the whole sample (Table 3). An increased number of daily tracheal intubations with cuffed (from 0 to 2) or uncuffed (from 0 to 3) tube did not lead to any apparent increase in environmental or urinary values of sevoflurane exposure. On the other hand, a single rigid bronchoscopy in a surgical session appears to be sufficient to increase exposure to sevoflurane only in the directly involved personnel (anaesthetists and nurses assisting anaesthetists), while other roles are not affected (Table 4).
Chronic occupational exposure to significant concentrations of inhaled anaesthetics may result in various adverse common health effects such as headaches and neurobehavioral changes [11,12]. Moreover, epidemiological evidence suggests that trace concentrations of anaesthetics are associated with spontaneous abortion and infertility  or may cause genetic damage in operating room personnel [13,14]. Athough the long-term consequences are not known with certainty, the NIOSH recommends that exposure to waste anaesthetic gas be minimized to the greatest extent possible. Current recommendations suggest MAC values of 2 ppm for halogenated agents (1 h sampling) and 25 ppm for nitrous oxide alone, and 0.5 ppm for halogenated agents in combination with 25 ppm for nitrous oxide .
Although, in adult patients, most modern anaesthetic procedures are performed with i.v. or regional techniques and increasing levels of safety are offered by the equipment used for inhalation anaesthesia, such as ventilators used in closed or semi-closed circuits and efficient scavenging system, in similar circumstances during paediatric anaesthesia the operating room atmosphere can be contaminated by the anaesthetic. In our study, the workplace air concentrations of sevoflurane were clearly lower than the NIOSH-defined limits. Numerous studies agree that low anaesthetic concentrations in the operating room air depend on an efficient scavenger system and an adequate air exchange rate [3,4]. Several studies have shown that gas concentrations in properly scavenged operating rooms generally comply with the NIOSH-recommended exposure limits [15,16]. Anaesthetic vapour concentrations in the operating room appear to be higher when air turnover is lower and the fraction of fresh air is smaller. Relatively high concentrations have been observed, e.g. in poorly ventilated post-anaesthesia units, as well as in non-operating theatre areas [17,18]. However, such data may be considered of limited value bearing in mind the close relationship between the mean environmental exposure value and the professional role of the operators. Anaesthetists have by far the greatest risk of sevoflurane exposure. Our results agree with those of other reports in the literature, especially studies concerning operating rooms dedicated to neonatal and paediatric surgery [19,20]. In the present study, the breathing zone concentrations measured of nurses and surgeons were always far below those of the anaesthetists. However, it is noticeable that among the nurses, the highest values were found for those assisting the anaesthetists. Breathing zone values were lower for the surgeons; none reached the threshold of 2 ppm, thus confirming the safety for chronic exposure to inhaled anaesthetics in this professional group .
Biological monitoring was performed by measuring post-shift urinary sevoflurane concentrations. This marker has been shown to be particularly effective since it reflects the mean concentration in the breathing zone during the exposure time [9,21]. An alternative biomonitoring method that measures urinary hexafluoroisopropanol resulting from cytochrome P4502E1-mediated metabolism of sevoflurane has some disadvantages, including longer sample preparation time, lower sensitivity and a possible influence of enzyme induction or genetic polymorphisms [22,23]. The biomonitoring data recorded in the present study correlate well with the breathing zone data in the two most exposed professional categories (anaesthetists and nurses), confirming that urinary sevoflurane is a specific and reliable exposure biomarker. Urinary concentrations of sevoflurane exceeded the biological equivalent limit of 3.6 μg sevoflurane per litre of urine  in 7 instances (6 anaesthetists and 1 nurse). This is consistent with previously published data . Interestingly, this study shows that in the presence of very low workplace air mean concentrations (as found in surgeons and auxiliary personnel), urinary sevoflurane can be more affected by individual factors, such as lung capacity and urine excretion. Moreover, the correlation with airborne concentrations may be poor due to the small number of individuals in low-exposed groups.
The results of the present study reveal that environmental and urinary values increase with the number of the daily mask inductions with sevoflurane. This can be explained by the greater dispersion of anaesthetic gas during inhalation induction [19,24]. The high exposure concentrations of anaesthetic gases during mask induction are in fact caused by the particularly high fresh gas flows often applied without scavenging devices and by the induction being carried out with a loosely fitting mask . The gas flow should always be turned off when the breathing system is not being applied to the patient. Mask induction generally involves the anaesthetists and nurses assisting the anaesthetists, but when the induction is performed in the same operating room where the surgical intervention will take place, the high gas dispersion has been demonstrated to cause an increase of values in all those present, despite efficient air exchange systems .
The method of airway management adopted during anaesthesia has a major influence on the contamination of the operating room by waste gases. In the present study, no correlation was found between high environmental and urinary values and the number of patients with endotracheal intubation with either cuffed or uncuffed tubes. On the other hand, the use of the laryngeal mask is associated with an increase in both breathing zone and urinary sevoflurane. Tracheal intubation with cuffed tube has long been considered an approach able to reduce pollution by volatile anaesthetic agents . Although the use of an uncuffed endotracheal tube can result in considerable volatile anaesthetic contamination of the operating room via a gas leak around the endotracheal tube , the use of tube of a suitable size for the tracheal lumen has been shown to reduce such leaks [26,28]. Our choice of a suitable uncuffed endotracheal tube was in fact able to limit the problem of leaking, resulting in low sevoflurane pollution. As an alternative solution, a recent study has also suggested a particularly effective method which makes use of an anaesthetic scavenging hood placed on children undergoing general endotracheal anaesthesia via an uncuffed endotracheal tube .
There are conflicting data regarding exposure to significant concentrations of inhaled anaesthetics during the use of the laryngeal mask; studies similar to the present investigation report a high incidence of environmental pollution , while others show a low incidence during the use of the laryngeal mask [30,31]. A recent study compared exposure to sevoflurane during ventilation using the facemask, laryngeal mask and cuffed oropharyngeal airway, and concludes that, unlike the face mask, the use of the latter two methods of airway management in patients undergoing short surgical interventions is not necessarily associated with increased waste gas exposure .
We found a positive correlation between high environmental and urinary values and the use of a rigid bronchoscope by the anaesthetists. This fact is widely accepted by many studies already, which observe that exposure is higher than the limits given in all known health regulation guidelines during inhalation anaesthesia with sevoflurane for paediatric bronchoscopy [33,34]. A possible explanation could be that the rigid bronchoscope is an open system with a high contamination probability. Other likely causes include: (a) the use of a rigid bronchoscope of a smaller size than the tracheal tube in order to reach the distal segments of the bronchial tree; (b) the use of high inhaled concentrations of the anaesthetic to prevent complications such as coughing and bronchospasm; (c) the fact that the operator remains very close to the source of fresh gases for a particularly long time. In conclusion, inhalation anaesthesia with sevoflurane can represent a true hazard for chronic occupational exposure to significant concentrations of inhaled anaesthetics, and anaesthetists are those with the greatest risk. To effectively reduce occupational exposure, well-adjusted and maintained scavenging systems and low-leakage working practices are of primary importance. Endotracheal intubation with cuffed or uncuffed tubes offers a high level of safety regarding inhaled anaesthetic pollution. Nevertheless, especially during paediatric anaesthesia, all of the following factors represent increased risk of anaesthetic exposure for all operators present: the daily number of inhaled anaesthesia inductions, the use of laryngeal mask and the use of airway endoscopic procedures with a rigid instrument.
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