Inhaled anesthetics are widely used because the dose can be readily controlled. However, waste anesthetic gas (WAG) can leak into an operating room (OR). Medical personnel in ORs suffer long-term exposure to WAG [
The study was approved (approval no. 2017-MZK-001) by the Medical Ethics Committee of Zhujiang Hospital, part of the Southern Medical University, and was registered in the Chinese Clinical Trial Registry (registration no.
The Zhujiang Hospital ORs used for the study were equipped with air conditioning systems and scavenging devices. Sevoflurane has been the only available inhaled anesthetic for several decades and is used frequently to induce and maintain anesthesia. Air samples were collected from different sites within the ORs between 8:00 and 8:30 a.m. on weekdays. Anesthetists and anesthetic nurses each wore a sampler close to (~10 cm from) the respiratory area during personal exposure (P1). Each sampler was turned on as soon as sevoflurane started to be administered. Each sampler had a flow rate of 100 mL/min, and the sampling tube was replaced every 2 h. Sampling continued for 8 h. Samplers were also placed on the nurses’ tables in the ORs (P2). Each sampling tube was sealed immediately after the sample collection period had ended and then sent to the laboratory, where the sevoflurane concentration was determined using an HP6890N gas chromatograph (Agilent Technologies, Santa Clara, CA, USA).
Demographic data for each participant (including age, sex, body mass index, length of service, occupation, smoking habits, and drinking habits) and clinical characteristics (including medical history and current medication) were recorded. Blood samples were collected from all of the participants and were preserved.
Peripheral venous blood (2 mL) was obtained from each participant into a sterile tube containing heparin (an anticoagulant). The blood was centrifuged at 3500 revolutions/min for 10 min; then, the supernatant was transferred to a fresh tube and stored at −20°C until analysis. Each sampling tube was given a unique label, stored in a portable refrigerator, and transferred to the laboratory for processing within 3 h of collection. The investigators did not know which participant was allocated to which group. The superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-px) activity, and malondialdehyde (MDA) concentration in each plasma sample were determined to allow oxidative stress to be assessed. The SOD activity, GSH-px activity, and MDA concentration were prepared using a superoxide dismutase assay kit (Beyotime Biotechnology, Shanghai, China), a lipid oxidation assay kit (Beyotime Biotechnology), and a glutathione peroxidase assay kit (Nanjing Jiancheng Bioengineering Institute, Nanjing, China), respectively, and the prepared samples were analyzed using a DR5000 ultraviolet/visible spectrophotometer.
Peripheral venous blood (2 mL) was obtained from each participant into a sterile tube containing heparin and then diluted to 4 mL. The sample was then slowly added to a lymphocyte separation solution in a 20 mL centrifuge tube. The mixture was then centrifuged at 1500 revolutions/min for 20 min. The liquid separated into three layers. The upper layer was light yellow plasma, the middle layer was milky white and contained the white blood cells, and the bottom layer contained the blood cells. The white blood cell layer was collected using a pipette and placed in a sterile 1.5 mL centrifuge tube. The liquid was then centrifuged at 10000 revolutions/min for 5 min, and the white precipitate was transferred to another tube and stored at −80°C for Western blot analysis. Additional DNA damage was avoided by performing every step under indirect light.
Peripheral venous blood (2 mL) was obtained from each participant into a tube containing EDTA (an anticoagulant) to allow a complete blood count to be performed, and 4 mL of venous blood was obtained into a dry tube without additives for use in biochemical tests to assess blood lipid concentrations, liver function, and renal function. Each tube was labeled and then analyzed. Complete blood counts were performed using an SE5000 automatic blood cell analyzer. Blood biochemical analyses were performed on the day the blood samples were collected using a Mindray BS2001 automatic biochemical analyzer. A 12-lead electrocardiogram (ECG) of each subject in a resting state was acquired in the morning using an ECG-9620P2 ECG machine (Shanghai). The same technician acquired the ECGs of all the participants. The ECG results were analyzed by another technician who did not know to which group each participant had been allocated.
The sample size was calculated using Formula 1, which was published previously [
Formula 1 is used to determine the sample size (
Data analysis was performed using the SPSS 20.0 software (IBM, Armonk, NY, USA). If a dataset had a normal distribution, the data were represented as
A total of 172 air samples from 22 ORs were collected. The sevoflurane concentration in each sample was determined. A total of 88 of the samples were collected in areas in which anesthesiologists or anesthesia nurses worked (P1), and 84 samples were collected from areas in which OR nurses worked (P2). The sevoflurane concentrations were 0.07–3.84 ppm (mean
Sevoflurane concentrations in the different working areas. Notes. P1: anesthesiologist and anesthesia nurse working areas; P2: operating room nurse working areas.
A total of 180 members of staff were screened for eligibility, and 153 met the inclusion criteria. A total of 150 members of staff were included in the study (one was excluded because of pregnancy, one because of a chronic infectious disease, and one because the serum creatinine concentration was above the upper limit of the normal range). Of the 150 participants, 68 were OR personnel (anesthesiologists, anesthesia nurses, itinerant nurses, and instrument nurses) and were assigned to the exposure group. The control group contained 82 non-OR staff from the departments of digestive medicine, hematology, rehabilitation, rheumatic immunology, ultrasound, respiratory medicine, pediatrics, and geriatrics. There were no significant differences between the demographic characteristics of the two groups. The demographic characteristics of the groups are shown in Table
Demographic characteristics of the exposure and control groups
Group | Exposure group ( | Control group ( | |
---|---|---|---|
Sex | |||
Man | 19 | 26 | 0.72 |
Woman | 49 | 56 | |
Age | 0.06 | ||
LOS | 0.39 | ||
Smoking | |||
Yes | 4 | 6 | 0.72 |
No | 64 | 76 | |
Drinking | |||
Yes | 6 | 9 | 0.78 |
No | 62 | 73 | |
BMI | 0.88 |
Notes. (1) Smoking was defined as smoking at least one cigarette per day for more than a year or having quit smoking for <1 y. (2) Drinking was defined as consuming alcohol at least once per week for more than half a year. (3) LOS: length of service. (4) BMI: body mass index.
Normal distribution tests were performed on the SOD activity, GSH-px activity, and MDA concentration data. The SOD activity data did not follow a normal distribution, so the median and quartiles were used in comparative analyses. The median (lower quartile, upper quartile) SOD activities were 51.42 (49.80, 52.27) U/mL for the exposure group and 52.11 (51.19, 52.80) U/mL for the control group. A nonparametric rank-sum test indicated that the SOD activities for the exposure and control groups were significantly different (
Superoxide dismutase (SOD) activities, glutathione peroxidase (GSH-px) activities, and malondialdehyde (MDA) concentrations for the exposure and control groups. Note. (1) Compared with the control group; (2)
Western blot analysis was performed to detect the
The hemoglobin concentrations in the exposure and control group samples were
Complete blood count results for the exposure and control groups (
Indexes | Exposure group ( | Control group ( | |
---|---|---|---|
HGB (g/L) | 0.02 | ||
WBC (109/L) | 0.21 | ||
PLT (109/L) | 0.76 | ||
RBC (1012/L) | 0.16 | ||
NEUT (109/L) | 0.99 | ||
LYM (109/L) | 0.04 | ||
EON (109/L) | 0.10 (0.06, 0.19) | 0.11 (0.07, 0.25) | 0.54 |
BASON (109/L) | 0.50 |
Notes. HGB: hemoglobin; RBC: red blood cell count; WBC: white blood cell count; PLT: blood platelet count; LYM: lymphocyte count; NEUT: neutrophil count; EON: eosinophil count; BASON: basophil cell count.
The total protein concentrations were much lower in the serum samples from the exposure group than in the serum samples from the control group (
Blood biochemical test results for the exposure and control groups (
Indexes | Exposure group ( | Control group ( | |
---|---|---|---|
CHO (mmol/L) | 0.77 | ||
TG (mmol/L) | 0.83 (0.58, 1.23) | 0.89 (0.65, 1.47) | 0.39 |
TP (g/L) | 0.03 | ||
T-BIL ( | 0.03 | ||
D-BIL ( | 0.73 | ||
ALT (u/L) | 15.00 (12.00, 19.00) | 14.50 (10.75, 27.25) | 0.76 |
AST (u/L) | 0.16 | ||
CRE ( | 0.02 | ||
BUN (mmol/L) | 0.32 | ||
UA ( | 0.25 |
Notes. CHO: total cholesterol; TG: triglycerides; TP: total protein; T-BIL: total bilirubin; D-BIL: direct bilirubin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen; CRE: creatinine; UA: uric acid.
The ECGs indicated that one person in the exposure group had coronary sinus rhythm, four had sinus arrhythmia, three had sinus arrhythmia, three had sinus bradycardia accompanied by arrhythmia, one had sinus arrhythmia and occasional atrial premature contraction, two had sinus arrhythmia with ST segment changes, four had sinus rhythm with ST segment changes, one had sinus rhythm with occasional ventricular premature contraction, two had sinus rhythm with left ventricular high voltage, two had sinus rhythm with clockwise transposition, two had sinus rhythm with incomplete right bundle branch block, and 46 had normal ECG. The ECGs indicated that three people in the control group had sinus arrhythmia, two had sinus bradycardia accompanied by arrhythmia, one had sinus arrhythmia with occasional premature atrial contraction, one had sinus tachycardia with T-wave changes, two had sinus arrhythmia with ST segment changes, four had sinus rhythm with ST segment changes, one had sinus rhythm with occasional premature ventricular contraction, one had sinus rhythm with preexcitation syndrome, two had sinus rhythm with a prolonged P–R interval, one had sinus rhythm with incomplete right bundle branch block, one had sinus rhythm with complete right bundle branch block, and 63 had normal ECG. The normal ECGs only included sinus rhythm and sinus rhythm with limb lead low voltage. Abnormal ECGs were found for 22 of the 68 people in the exposure group and 19 of the 82 people in the control group. The numbers of abnormal ECGs for the exposure and control groups were not significantly different (Table
Electrocardiogram results for the exposure and control groups.
ECG results | Exposure group ( | Control group ( | ||
---|---|---|---|---|
Normal | 22 | 19 | 1.578 | 0.27 |
Abnormal | 46 | 63 |
Electrocardiogram characteristics for the exposure and control groups (
Indexes | Exposure group ( | Control group ( | |
---|---|---|---|
HR (bpm) | 0.00 | ||
PR (ms) | 0.38 | ||
QRS (ms) | 0.13 | ||
QT (ms) | 387.00 (372.00, 394.50) | 372.00 (360.00, 388.00) | 0.01 |
QTc(ms) | 0.00 | ||
RV5(mV) | 0.75 | ||
SV1(mV) | 0.69 | ||
RV5+SV1(mV) | 0.74 |
Even though the ORs had laminar flow and scavenging systems, the antioxidant defense systems and vital organ functions of staff exposed to WAG in the long term could have been affected. However, no difference in DNA damage markers was found between the exposure and control groups. The time-weighted average sevoflurane concentrations in the ORs were lower than the Chinese limit of 2 ppm, but 28% of the air samples from the anesthesiologist work areas and 8% of the air samples from the OR nurse work areas had sevoflurane
Volatile inhaled anesthetics are widely used in ORs. However, anesthetic gas may escape into the OR while the anesthetic is being administered [
A series of stress responses can occur once DNA damage has occurred in a cell. These stress responses induce a signal cascade and even stop the cell cycle until the damage has been repaired. One of the main components of the signal cascade is H2AX, which can be phosphorylated when DNA double-strand breaks (DSBs) occur and then initiate the damage repair mechanism. H2AX plays an extremely important role in the DSB identification and repair process [
The blood lipid concentrations and liver and renal functions of the people exposed to WAG for a long time were compared. The total protein concentration in the peripheral blood and the total bilirubin and creatinine concentrations were significantly lower in the exposed group than the control group. The other biochemical indicators (total cholesterol, triglycerides, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and uric acid concentrations) in the exposed group and control group samples were not significantly different. In medical workers, exposure to low concentrations of anesthetic exhaust gas has been found to increase alanine aminotransferase, glutamyltransferase, and total bilirubin concentrations and lymphocyte and neutrophil counts [
The sevoflurane concentrations were, overall, lower than the Chinese workplace limit, but some OR staff (particularly anesthesiologists and anesthesia nurses, who work near their patients) could be exposed to sevoflurane concentrations higher than the Chinese workplace limit. Better laminar flow and ventilation systems therefore need to be installed in ORs, anesthesia delivery equipment needs to be inspected regularly for leaks, medical supervision needs to be maintained, and hazard awareness training is required. Actions to control WAG emissions (particularly installing and maintaining scavenging systems, using double masks, adequately managing airflow, and using closed or semiclosed low-flow anesthesia procedures) are required to decrease the exposure of OR staff to WAG as much as possible [
No significant difference was found between the rates of abnormal ECGs for the exposure and control groups. The HR was significantly lower for the exposed group than the control group, and the QT interval and QTc interval were significantly longer for the exposed group than the control group, although both were within the normal ranges. The PR intervals and RV5, SV1, and RV5+SV1 amplitudes for the exposure and control groups were not significantly different. Many factors (e.g., antiarrhythmic drugs, antibiotics, electrolyte disturbances, antipsychotic drugs, and sympathetic nerve excitement) affect the HR, QT interval, and QTc interval. Further studies are required to determine whether long-term exposure to sevoflurane at low concentrations changes the ECG parameters of anesthesiology staff.
The study had some limitations. First, the study was performed at a single site. Second, some biometric indicators (e.g., the concentrations of sevoflurane and its metabolite hexafluoroisopropanol in urine and blood) were not used to measure exposure to WAG. Third, only
All data used to support the findings of this study are available from the corresponding author upon request.
The authors declare no competing financial interests.
Hai-Xin Hua and Hai-Bo Deng contributed equally to this work.
The work was supported by a Guangdong Science and Technology Project (grant no. 2014A020213018) awarded to Ye-Hua Cai.