The potential adverse effects of volatile anesthetics on operating room (OR) staff has been the subject of numerous investigations since 1967.1 Among the possible long-term consequences of chronic exposure, investigators described hepatotoxicity and nephrotoxicity, carcinogenesis, decreased immunity, impaired fertility, and adverse effects on fetal development.2–5 Although the development of such events may take years of cumulative exposure, headaches, somatic and mental fatigue, and reduced cognitive ability are more likely to develop, and hence deserve increased attention.6–10 To minimize this potential environmental risk, identification of surgical procedures that are associated with increased release of volatile anesthetics is imperative.
In this context, several investigators have documented that mask induction of anesthesia, the use of uncuffed tracheal tubes, or the use of laryngeal mask airways could increase environmental exposure from leaks, especially if the vaporizer was not turned off before disconnecting from the breathing circuit.11,12 However, there is limited information on whether release of volatile anesthetics from the surgical field may pose an additional risk to the surgeon.
This question seems particularly relevant during neurosurgical operations in which the craniotomy exposes the brain to the OR environment. The brain has high blood perfusion, extensive capillary network, and high fat content, all promoting a relatively rapid and marked tissue accumulation of a lipophylic drug such as sevoflurane, which has a brain:blood partition coefficient of 1.7.13 However, sevoflurane has a low blood:gas partition coefficient (0.69), which may result in significant escape from the blood when the circulation is open for exchange with air. Along these lines, we speculated that exposure of a large surface area of the brain and capillaries during craniotomy for tumor resection might give rise to enhanced release of sevoflurane, which in turn may lead to an increased exposure of the surgeon, whose breathing zone is in close proximity to the craniotomy window. To test this hypothesis, we sought answers to the following specific questions: 1) Are the concentrations of sevoflurane close to the craniotomy window and hence the surgeon’s breathing zone different from those at remote sites in the OR (e.g., at the farthest corner and in the anesthesiologist’s breathing zone) and 2) Is there a correlation between the sevoflurane concentration near the surgical site and the size of the craniotomy window?
Patients (n = 51) undergoing craniotomy for the removal of intracerebral tumors were both women and men aged between 6 and 79 (mean 51.5) yr; the two children included in the study were 6 and 12 yr old. All patients signed an informed consent approved by the local Medical Ethics Committee, and the study was performed in accordance with the Helsinki Declaration II and Good Clinical Practice protocols.
For induction of anesthesia, we used propofol (1–2.5 mg/kg), whereas for maintenance of anesthesia we used the combination of fentanyl-rocuronium-sevoflurane. The sevoflurane-air mixture was administered via an anesthesia machine (Zeus, Dräger Medical AG & Co. KG, Lübeck, Germany) using a low-flow technique (2 L/min fresh gas flow). Tracheal tubes were armored RüschFlex tracheal tubes made of polyvinyl chloride with a low-pressure cuff. Similar to the adults, the two children also received IV induction followed by maintenance with sevoflurane administered via size-matched tracheal tubes. All endotracheal balloons were inflated to pressures slightly above 30 mm Hg. During the full course of the operation, we monitored the following variables: arterial blood pressure, heart rate, O2 saturation using pulse oxymetry, end-tidal CO2 concentration, and end-tidal sevoflurane concentration.
Craniotomy and the opening of the dura were always initiated after the tissue saturation of sevoflurane. The surface area of the craniotomy window was measured in square centimeters. Subsequently, we applied the low-flow anesthesia technique at a sevoflurane concentration ranging from 0.7 to 2.3 V% (mean 1.4 V%), as required to maintain adequate anesthesia.
All operations were performed in recently built ORs with modern ventilation and air-conditioning systems. The OR was also equipped with a scavenging system compliant with international standards. Air was continuously circulated in the OR and changed or refilled (e.g., upon pressure decrease evoked by opening of the doors of the OR) at a rate of approximately 50 m3/min.
Sample Collection and Quantification
For the detection of airborne anesthetics, we used a detection setup that consisted of a portable air sampling pump (224-51TX Air Sampling Pump, SKC, Dorset, England), an integrated tube system, and an absorber ampule coupled to the tube system (Fig. 1). In the first series of sampling that included 35 patients, the distal part of the tube containing the absorber was placed in one of the following three locations: 1) the surgeon’s breathing zone; 2) the anesthesiologist’s breathing zone; or 3) the farthest corner of the OR. In the second series of sampling that included 16 patients, the third air sampling site was changed from the corner of the OR to the close proximity of the patient’s mouth (within 5 cm of the tracheal tube).
A suction pump attached to the sample collector ensured that air samples flowed through the absorber where the anesthetic was collected for later quantification. Because our intention was to estimate evaporation from the craniotomy site, the sample collection was restricted to the period from opening to complete closure of the dura mater. After the termination of sample collection, the ampule containing the absorber was hermetically sealed and sent for quantification by chromatography, as described previously.14 The quantifications were performed by an independent chemist, who was blinded to the origin of the sample and other key variables of the study.
Data quality was checked by scatter plots that revealed the existence of one outlier, which was 165-fold higher than the average of the group (in second series, anesthesiologist group); this value was consequently excluded from the analysis. Results are presented as mean ± sd, unless otherwise indicated. Because the samples did not show normal distribution, comparative statistics were performed by nonparametric tests. Datasets were initially evaluated by Kruskal–Wallis analysis of variance, which, if significant, was followed by pairwise comparison of selected subgroups using Mann–Whitney U-test. The relationship between the quantity of sevoflurane in the absorbers and the area of the craniotomy window was assessed by Spearman rank correlation analysis. Theoretically, because the amount of the anesthetic in the absorber could also be influenced by the duration of the operation, the time-independent association between the size of the craniotomy window and the amount of sevoflurane in the absorbers was also assessed by partial correlation analysis that methodically allows correcting for the potential variation of sevoflurane concentration due to variation in time.15 Differences were considered statistically significant if P < 0.05. Statistical analysis was performed using Statistica for Windows (StatSoft, Tulsa, OK) software.
The demographic characteristics (age, body mass index, and gender distribution) and study-specific variables (duration of operation and area of the craniotomy window) are summarized in Table 1.
Sevoflurane Exposure at Different Detection Sites
Figure 2 shows the sevoflurane concentrations detected at the three sampling locations. Absorbers collecting samples in the surgeon’s breathing zone revealed quantities of volatile anesthetic that were comparable with those obtained at the farthest corner of the OR. In contrast, concentrations detected by absorbers placed in the anesthesiologist’s breathing zone were about sixfold higher compared with those found at the other two detection sites (P < 0.001).
Relationship Between the Size of the Craniotomy Window and Sevoflurane Release
There was no significant correlation between the area of exposure (craniotomy size) and the concentration of sevoflurane in the surgeon’s breathing zone or the other two detection sites (Table 2). Similarly, there was no significant correlation between the craniotomy size and sevoflurane concentration at the three detection sites when the analysis was adjusted for the duration of surgery.
Sevoflurane Release as a Function of Tumor Type
To exclude other potential confounders, we also assessed whether sevoflurane concentrations measured in the surgeon’s breathing zone differed depending on the type of the resected tumor, in an attempt to account for differences in tumor vascularity. Comparison of meningiomas (0.28 ± 0.20 ppm, n = 17), gliomatous tumors (gliomas, glioblastomas, astrocytomas, and oligodendrogliomas) (0.19 ± 0.19 ppm, n = 20), metastatic tumors (0.20 ± 0.07 ppm, n = 9), and other lesions including medulloblastomas and cavernomas (0.19 ± 0.09 ppm, n = 5) did not reveal significant differences, suggesting negligible influence of tumor vascularity on sevoflurane release from the craniotomy window.
The only significant correlation identified by the analysis was between the amount of sevoflurane detected in the surgeon’s breathing zone and the amount of sevoflurane detected in the farthest corner of the OR (r = 0.50, P = 0.002).
Sevoflurane Release at the Patient’s Mouth
In the second series of sampling, we collected data from the surgeon’s and the anesthesiologist’s breathing zones and from the close proximity of the patient’s mouth. Average exposure of the detectors at the three sites is indicated in Figure 3. Sevoflurane concentrations at the patient’s mouth were higher than those in the anesthesiologist’s breathing zone. Sevoflurane accumulation in absorbers in the surgeon’s breathing zone was about sixfold to sevenfold lower than sevoflurane concentration at the anesthesiologist’s and patient’s breathing zones (P < 0.01).
The main findings of the study were as follows: 1) during intracerebral surgery, the surgeon’s exposure to sevoflurane does not exceed magnitudes measurable in the farthest corner of the OR; 2) the surgeon’s sevoflurane exposure appears to be independent of the size of the craniotomy window; 3) the anesthesiologist’s exposure was about sixfold higher than the surgeon’s exposure; and 4) the increased exposure of the anesthesiologist can be, at least in part, associated with “escape” of the anesthetic from the circuit, most likely representing a leak of sevoflurane around the tracheal cuff.
This report addresses the possible contribution of direct release of a volatile anesthetic from the incised brain tissue during intracerebral tumor surgery. The rationale for addressing this issue was that the brain is a site of high accumulation of anesthetics,13 and when incised, brain tissue and open capillaries may theoretically become sources of sevoflurane release. The first to receive additional exposure from these sources would be the surgeon, whose breathing zone is in the closest proximity to the craniotomy window. Our measurements, however, did not corroborate this hypothesis and indicated no signs of increased sevoflurane concentrations at this detection site. In fact, sevoflurane in absorbers placed in the surgeon’s breathing zone was not different from that in absorbers placed at the farthest corner of the OR. Furthermore, despite a fairly large variation in the size of the craniotomy window (3–70 cm2), we found no significant correlation with the amount of sevoflurane captured by absorbers in the surgeon’s breathing zone, not even when correcting for the duration of surgery. Finally, we were not able to identify any tumor type that was associated with more significant sevoflurane exposure of the surgeon. Collectively, these observations suggest that intracerebral surgery does not pose additional environmental risks for the operating neurosurgeon.
The other significant finding of our study is the increased exposure of the anesthesiologist that exceeded the surgeon’s exposure by about sixfold. Our finding is consistent with several previous reports that underscored the increased exposure of the anesthesiologist to volatile anesthetic during various types of surgeries.11,12,16–18 It should be emphasized, however, that sevoflurane values measured in this study did not exceed the safe limits (2 ppm) defined by international guidelines11 and were also comparable with values previously reported by independent groups.19,20 Nevertheless, even these values may gain clinical significance if evaluating the personnel’s cumulative exposure over many years. For instance, studies have demonstrated significant alterations in exploratory behavior, lower scores in learning and memory tests, and an overall increase in anxiety in rats chronically exposed to subanesthetic doses of sevoflurane, desflurane, or halothane.21,22
In attempting to identify the source of the anesthesiologist’s increased exposure, we considered the possibility that it may be related to the anesthesiologist’s position during surgery and their proximity to the patient. During intracerebral surgery, the anesthesiologist and the anesthesia machine are at the patient’s right or left side, not at the head as with other surgery types. Furthermore, the isolation of the patient’s head is such that the tracheal tube is always within the reach of the anesthesiologist for necessary adjustments. If there is any significant escape of sevoflurane from the patient’s mouth, it could easily lead to a higher exposure of the anesthesiologist who is sitting close by. To test this hypothesis, we placed absorbers in the proximity of the tracheal tube at the patient’s mouth and compared the absorbed sevoflurane concentration with the concentrations at the surgeon’s and the anesthesiologist’s breathing zones. The highest sevoflurane values were indeed revealed by absorbers placed in the proximity of the patient’s mouth. This finding is also supported by previous observations by several independent groups describing “escape” of volatile anesthetics around the tracheal tube, despite adequate inflation of the tracheal cuff.10,12 Having identified the source, we speculate that the surgeon’s lower exposure can be ascribed to the fact that passive diffusion of the volatile anesthetic is diminished with increasing distance from the source (tracheal tube) and further decreased by the barrier posed by the surgical drapes that separate the surgeon from the patient’s airway and the anesthesiologist.
A word of caution should be made regarding the role of the ventilation system in the context of our observations. The findings that sevoflurane in the absorbers placed in the surgeon’s breathing zone and in the corner of the OR showed about sixfold lower concentrations compared with absorbers placed in the anesthesiologist’s breathing zone seem to eliminate concerns regarding the contribution of poor ventilation (otherwise all three detectors would have showed comparable values). Another issue worth mentioning is that during more demanding operations, when an assistant has to leave the room for additional tools or supplies, opening of the OR door produces an atmospheric pressure decrease. This in turn accelerates airflow and air clearance and facilitates the restoration of the internal atmospheric pressure in the OR. Importantly, clearance of airborne sevoflurane by the ventilation system can explain why we found low concentrations of sevoflurane in the absorbers during these extended operations and why we did not find a significant correlation between released sevoflurane and duration of the surgery.
In summary, our study does not corroborate the notion that significant release of sevoflurane from the brain through the craniotomy window poses an additional source of environmental exposure for the operating neurosurgeon during intracerebral surgery and underscores the need to focus on improving the working conditions for the anesthesiologist, who is the subject of much higher exposure during these types of surgical operations. Herein, we call on further studies to explore the causal factors of sevoflurane “escape” and to define adequate countermeasures.
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