Health effects associated with exposure to anaesthetic gases in Ontario hospital personnel.

In a retrospective study (by questionnaire) of 8032 personnel exposed to anaesthetic gases in operating and recovery rooms in Ontario hospitals, and 2525 non-exposed hospital staff, the response was 78.8% for the exposed and 87.2% for the unexposed personnel during the period 1981-5. Logistic regression analysis, with age and smoking standardised, showed that women in the exposed group had significantly increased frequencies of spontaneous abortion and their children had significantly more congenital abnormalities (p less than 0.05). No chronic disease was significantly associated with the exposed group. These findings, together with similar ones from other studies, suggest that it is prudent to minimise exposure to waste anaesthetic gases.     

Cytogenetic tests performed on operating room personnel (the use of anaesthetic gases)

Objectives: Personnel exposure to anaesthetic gases in the health sector, whether in the operating room, recovery room, or in the context of outpatient clinics, may entail a health risk. The goal of this research was to study the cytogenetic effects of chronic exposure to small doses of pollutants in operating theatres. Methods: Results of cytogenetic analyses [structural chromosomal aberrations (SCAs), sister chromatid exchange (SCE) and micronucleus (MN) test] of anaesthetists and other personnel handling anaesthetic gases, who only occasionally work in zones of ionizing radiation, were compared with results from radiologists, occupationally exposed to ionizing radiation only, and with the results obtained from a group of Slovene citizens who were never exposed to genotoxic agents. Results: This study involved 153 workers handling anaesthetic gases. The average frequency of SCAs in the group working with anaesthesia was 2.693. The result was statistically significantly higher than in the group of radiologists and Slovene citizens. The frequency of SCE and MN was also statistically significant. A number of authors, who used the same cytogenetic tests, found similar results in the group of anaesthetist. Conclusion: The results of our study indicate that exposure to anaesthetic gases induced changes in human chromosomes.     

Genetic damage in operating room personnel exposed to isoflurane and nitrous oxide

OBJECTIVES: To evaluate genetic damage as the frequency of sister chromatid exchanges and micronuclei in lymphocytes of peripheral blood of operating room personnel exposed to waste anaesthetic gases. METHODS: Occupational exposure was measured with a direct reading instrument. Venous blood samples were drawn from 10 non-smokers working in the operating room and 10 non-smoking controls (matched by age, sex, and smoking habits). Lymphocytes were cultured separately over 72 hours for each assay with standard protocols. At the end of the culture time, the cells were harvested, stained, and coded for blind scoring. The exchanges of DNA material were evaluated by counting the number of sister chromatid exchanges in 30 metaphases per probe or by counting the frequency of micronuclei in 2000 binucleated cells. Also, the mitotic and proliferative indices were measured. RESULTS: The operating room personnel at the hospital were exposed to an 8 hour time weighted average of 12.8 ppm nitrous oxide and 5.3 ppm isoflurane. The mean (SD) frequency of sister chromatid exchanges was significantly higher (10.2 (1.9) v 7.4 (2.4)) in exposed workers than controls (p = 0.036) the proportion of micronuclei (micronuclei/500 binucleated cells) was also higher (8.7 (2.9) v 6.8 (2.5)), but was not significant (p = 0.10). CONCLUSION: Exposure even to trace concentrations of waste anaesthetic gases may cause dose-dependent genetic damage. Concerning the micronuclei test, no clastogenic potential could be detected after average chronic exposure to waste anaesthetic gas. However, an increased frequency of sister chromatid exchanges in human lymphocytes could be detected. Although the measured differences were low, they were comparable with smoking 11-20 cigarettes a day. Due to these findings, the increased proportion of micronuclei and rates of sister chromatid exchanges may be relevant long term and need further investigation.

 

     

Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test

Genetic damage induced by anaesthetic gases in occupationally exposed populations was investigated using the comet assay and micronucleus test. The study included two groups of subjects: 50 operating theatre medical workers (anaesthesiologists, technicians and nurses) and 50 control subjects corresponding in sex, age and smoking habit. The exposed group revealed an increase in genome damage in both tests. In the comet assay, exposure to anaesthetics was a highly significant predictor of the tail length for technicians, while sex proved to be significant predictor of tail moment for women in exposed group. Micronucleus frequency increased significantly, showing threefold increase in exposed groups (RR>3.029). Univariate analysis showed significant influence of duration of exposure, while multivariate analysis showed age to be significant predictor of micronucleus frequency. The obtained results call for further, targeted investigation of exposure risk.     

Persistent cognitive functioning deficits in operating rooms: two cases

BACKGROUND: To date, chronic toxic encephalopathy (CTE) has never been described in operating room personnel. CASE REPORT: We report two cases of anaesthetists who developed this pathology. They have both used anaesthetic gases for many years in paediatric surgery. Air conditioning was deficient during three years in operating rooms and atmospheric anaesthetics concentration was high (N(2)O mean concentration: 311 ppm, peak levels 1,600 ppm; halogenated: 16 ppm, peak levels: 1,600 ppm). CLINICAL SYMPTOMS: Mood troubles and non-specific neuropsychic deficits gradually evolved until they had to stop working. Neuropsychological assessment showed important deficits in attention, executive functioning, short-term memory and visuo-spatial organization. Blood tests, VEPs, MRI, neuroSPECT and cardiovascular exams were normal. Troubles had slowly improved after cessation of exposure and sequels still remain. CONCLUSION: These CTE cases seem to be the consequence of a long-term exposure to important levels of anaesthetic gases, and particularly nitrous oxide. It points out the importance of preventive measures in operating rooms, where occupational hazards are varied.     

Techniques for administering inhalation anesthetic agents, professional exposure, and early neurobehavioral effects

BACKGROUND: Occupational exposure to high concentrations of anaesthetic gases can cause neurobehavioral effects in operating room personnel. The measures taken to reduce waste gas exposures, including the installation of active scavenging devices and airconditioning systems, are not effective, so that the NIOSH recommendations for maximum exposure are currently unattainable in practice. OBJECTIVES: The aim of the present study was to measure operating room pollution and neurobehavioral functions in a group of anaesthesiologists during open-system and low-flow anaesthesia. METHODS: Environmental concentrations of N2O and isoflurance were measured by an infrared gas analyzer (Brüel & Kjaer) in open system and in low flow anaesthesia. Under the same stress condition, but with different exposure levels to anaesthetic gases, psychomotor vigilance and response speed were evaluated four times with the Reaction Time Test at the beginning and at the end of the first weekday shift and at the beginning and at the end of the last weekday shift. Exclusion criteria were considered excessive alcohol and coffee intake and use of CNS medication. RESULTS: Concentrations of N2O and isoflurane in the operating room were 4.83 ppm and 0.4 ppm respectively, which are lower compared with open systems: 301 ppm and 11.1 ppm respectively. The mean of the Reaction Time was significantly higher (p < 0.01) during work with the open system compared to work in low flow at the end of the first weekday shift and at the end of the last weekday shift. CONCLUSIONS: Low-flow anaesthesia appears to be effective in reducing waste gas exposure: lower flows produced lower values and protect the integrity of neurobehavioral functions.     

Neuropsychological symptoms and occupational exposure to anaesthetics.

OBJECTIVE--To analyse the relation between symptoms regularly reported by hospital personnel and exposure to anaesthetics. SETTING--Personnel of 18 hospitals in Paris from 1987 to 1989. DESIGN--An exposed group that included all operating theatre members except for doctors, and which was divided into three subgroups depending on the degree of exposure--exposure was measured by the frequency of the use of the scavenging system--and a control group that included other hospital personnel matched by hospital, sex, occupation, age, and duration of service. SUBJECTS--557 exposed workers and 566 unexposed workers. MAIN OUTCOME MEASURES--The groups were compared according to the crude rates of regular symptoms. Adjusted odds ratios were calculated to estimate the risks associated with exposure to anaesthetic gas. Liver transaminase activities (alanine aminotransferase, aspartate aminotransferase (s-ASAT, and gamma-glutamyl transpeptidase) were measured and compared between groups of exposure. RESULTS--After controlling for working conditions and matching factors, neuropsychological symptoms and tiredness were reported more by workers in less often scavenged theatres than by controls. No difference was found between workers of the well scavenged theatres and controls. Among the exposed workers, the members of paediatric surgical staffs reported a higher rate of neurological complaints (tingling, numbness, cramps) and tiredness than the members of the other surgical staffs. They had a high value of s-ASAT more frequently than the other exposed workers. CONCLUSION--These results strengthen the hypothesis of a causal relation between exposure to anaesthetics and neuropsychological symptoms, and show a dose-response effect. They suggest that the use of ventilating systems in operating rooms is an effective means of prevention.     

Neuropsychological symptoms and occupational exposure to anaesthetics.

OBJECTIVE--To analyse the relation between symptoms regularly reported by hospital personnel and exposure to anaesthetics. SETTING--Personnel of 18 hospitals in Paris from 1987 to 1989. DESIGN--An exposed group that included all operating theatre members except for doctors, and which was divided into three subgroups depending on the degree of exposure--exposure was measured by the frequency of the use of the scavenging system--and a control group that included other hospital personnel matched by hospital, sex, occupation, age, and duration of service. SUBJECTS--557 exposed workers and 566 unexposed workers. MAIN OUTCOME MEASURES--The groups were compared according to the crude rates of regular symptoms. Adjusted odds ratios were calculated to estimate the risks associated with exposure to anaesthetic gas. Liver transaminase activities (alanine aminotransferase, aspartate aminotransferase (s-ASAT, and gamma-glutamyl transpeptidase) were measured and compared between groups of exposure. RESULTS--After controlling for working conditions and matching factors, neuropsychological symptoms and tiredness were reported more by workers in less often scavenged theatres than by controls. No difference was found between workers of the well scavenged theatres and controls. Among the exposed workers, the members of paediatric surgical staffs reported a higher rate of neurological complaints (tingling, numbness, cramps) and tiredness than the members of the other surgical staffs. They had a high value of s-ASAT more frequently than the other exposed workers. CONCLUSION--These results strengthen the hypothesis of a causal relation between exposure to anaesthetics and neuropsychological symptoms, and show a dose-response effect. They suggest that the use of ventilating systems in operating rooms is an effective means of prevention.     

Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a meta-analysis.

OBJECTIVES: To determine the association between maternal occupational exposure to anaesthetic gases and risk of spontaneous abortion. METHODS: A meta-analysis was performed of published epidemiological studies identified from literature reviews, unsystematic perusal of reference lists of relevant publications, and two Medline searches (1984-92, keywords: anaesthetic gases; anaesthetics; anaesthetics, local; operating rooms; operating room nursing; pregnancy; abortion; 1985-92, keywords: anaesthetics; adverse effects; occupational exposure; anaesthesia, inhalation; operating room nursing; pregnancy; abortion). All peer reviewed studies were retained. Student theses were excluded, as were conference abstracts, unpublished material, and two studies in which data on paternal and maternal occupational exposures were pooled. The relative risk of spontaneous abortion was estimated. RESULTS: One study found no increase in risk of abortion when gases were scavenged or when the exposure to unscavenged gases was low. None of the studies included ambient gas sampling. 24 comparisons between exposed and unexposed women, obtained from 19 reports, were included. The overall relative risk was 1.48 (95% confidence interval (95% CI), 1.4 to 1.58). To test whether this result was influenced by the quality of the studies, the validity of the reviewed papers was rated on the basis of three criteria: appropriateness of the unexposed comparison group, control for non-occupational confounding variables, and response rate. The estimate of risk increased to 1.9 (95% CI, 1.72 to 2.09) when analysis was restricted to the six comparisons which were rated the most rigorous. CONCLUSIONS: Epidemiological studies based on data obtained in the prescavenging era indicate an increased risk of spontaneous abortion. The estimated increased risk was not diminished but rather increased by exclusion of the more methodologically flawed studies.     

Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome.

Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilising gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.     

The role of antioxidant supplementation in occupational exposure to waste anaesthetic gases

Objectives: Although the genotoxicity related to waste anaesthetic gases is controversial, a consistent number of observations have provided evidence for an increased level of DNA strand breaks. The goal of the research was to investigate this hypothesis and estimate the genoprotective role of antioxidant supplementation in technical anaesthesiology staff working in operating theatres. Methods: Heparinized venous blood samples were collected from 17 exposed technical anaesthesiology staff (mean age 34.3 ± 3.5 years) and non-exposed control group (mean age 32.2 ± 3.4 years) and examined in the alkaline comet assay for DNA strand breakage. Vitamin E (300 mg/day) plus vitamin C (500 mg/day) were supplemented to the technical anaesthesiology staff for 12 weeks and blood samples were retaken and evaluated by comet assay. Results: The DNA breakage observed in the lymphocytes of the technical anaesthesiology staff was 21.5 ± 5.0, as calculated by total comet score (TCS). This score was significantly higher (P < 0.001) than in the controls (8.6 ± 4.7) before antioxidant treatment. Supplementation of vitamins E plus C significantly (P < 0.01) reduced the mean TCS as 14.2 ± 6.1. Conclusion: The results of our study indicate that occupational exposure to anaesthetic gases induces oxidative DNA damage. Supplementation of the diet for 12 weeks with vitamin C and vitamin E resulted in a significant decrease in the DNA damage.     

Chromosome aberrations and micronucleus frequency in anaesthesiology personnel

Occupational exposure to anaesthetic gases is associated with various adverse health effects. Genetic material is a sensitive target of numerous harmful agents. The aim of this study was to examine whether chromosomal damage could serve to indicate exposure to anaesthetics. Twenty-eight anaesthesiologists, 16 technicians, and 32 control subjects were examined for chromosome aberrations and micronucleus frequency. An increase in chromosome damage was found in both exposed groups. Micronucleus frequency increased significantly, showing higher rates in women. The observed differences between the sexes in respect to the exposure risk call for further, targeted investigation.     

Cancer incidence and mortality in aircraft maintenance workers

BACKGROUND: A cancer incidence and mortality study was conducted in response to health concerns raised by workers from F-111 aircraft deseal/reseal fuel tank maintenance programs, to determine whether personnel exposed to deseal/reseal had an excess of cancers and mortality. METHODS: Number of deaths and cancers for individuals involved in F-111 DSRS activities were matched against two Air Force comparison groups. Analyses were weighted to adjust for differences in age, exposure period and rank. RESULTS: Eight hundred seventy-three exposed, 7,577 comparison group one, and 9,408 comparison group two individuals were matched against death and cancer data, with 431 cancers and 431 deaths. Cancer incidence was higher in the exposed group, with marginally significant increases of 40-50% (cancer incidence rate ratio range 1.45-1.62). Exposed group mortality was significantly lower than both comparison groups, likely due to survivor bias in the exposed group (mortality rate ratio range 0.33-0.44). CONCLUSIONS: On the balance of probabilities, there is an increased risk of cancer associated with participation in F-111 deseal/reseal activities.     

Spirometric abnormalities among welders

A group of manual welders (N = 57) engaged in gas welding joint faces of moulded brasswares, age group 13-60 years (mean: 29.2 +/- 1.37 years), having a mean exposure period of 12.4 +/- 1.12 years (range: 1-35 years) were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The findings were compared with those obtained from a reference group (N = 131) (mean age: 31.2 +/- 1.35 years) engaged in nonwelding jobs such as packing, labelling, and transportation of the finished brassware articles. The welders showed a significantly higher prevalence of respiratory impairment (28.0%) than that observed among the unexposed controls (6.1%) (P less than 0.001), as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the exposed group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders (40.0 vs 18.7%) (P less than 0.10). A similar trend was observed in the control group indicating that smoking had a deteriorating effect on spirometric tests. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment (12.3%) followed by a mixed ventilatory defect (8.7%) among the welders. The effect of age on pulmonary impairment was not discernible either in the exposed or unexposed group. The analysis of data in relation to duration of exposure showed significant correlation between the prevalence of respiratory abnormalities and length of exposure. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years (44.4 vs 13.3%) (P less than 0.01) thereby showing that occupational exposure to welding fumes resulted in increased prevalence of pulmonary impairment in the welders. Smoking also had a contributory role thereby suggesting an interaction between smoking and welding exposure on the prevalence of pulmonary impairment in the welders engaged in brassware industries.     

Oxidative and antioxidative effects of desflurane and sevoflurane on rat tissue in vivo

General anaesthetics are often used in patients who are under oxidative stress due to a critical illness or surgical trauma. Some anaesthetics may worsen oxidative stress and some may act as antioxidants. The aim of this study was to evaluate liver, brain, kidney, and lung tissue oxidative stress in rats exposed to desflurane and sevoflurane and in unexposed rats. The animals were divided in three groups: control (received only air); sevoflurane (8 %), and desflurane (4 %). After four hours of exposure, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Cu, and Zn. Exposure to either of the anaesthetics significantly increased lung MDA levels compared to control (Mann-Whitney U test; P<0.05), probably because it is the tissue directly exposed to anaesthetic gases. Oxidative stress and antioxidant activity in other tissues varied between the desflurane and sevoflurane groups. Our results suggest that anaesthesiologist should not only be aware of the oxidative or antioxidative potential of anaesthetics they use, but should also base their choices on organs which are the most affected by their oxidative action.     

新生儿窒息生后早期血气、电解质与脑电图相关性分析

目的:探讨新生儿窒息生后早期血气、电解质与新生儿脑电图的相关性。方法:对75例新生儿窒息患儿于生后1h内进行动脉血气、电解质测定,12～48h进行脑电图检查。结果:75例窒息儿其中轻度窒息56例,重度窒息19例,并据动脉血气异常与否分为血气正常型及血气异常型。脑电图异常率分别为:轻度窒息组46.4%,重度窒息组52.6%,脑电图重度异常发生率两组分别为:3.6%及26.3%;血气正常型脑电图异常率为:42.1%,血气异常型54.1%,脑电图重度异常发生率分别为:2.6%及16.2%。研究表明出生早期有动脉血气异常的窒息儿,脑电图重度异常率高于血气正常的窒息儿(P<0.05),同时重度窒息组脑电图重度异常率也高于轻度窒息组(P<0.05),差异有统计学意义。电解质及血色素值异常与脑电图异常率的差异无统计学意义,但电解质异常的窒息儿脑电图异常率也达到了55%,其中包括重度异常1例,因而也不能忽视电解质异常所造成的影响,结论:提示出生早期动脉血气异常的窒息儿与重度窒息儿脑血流再灌注损伤更明显,预后不良的可能性会增加,更应注意脑损伤的预防与修复。同时提示早期新生儿血气可作为判断新生儿窒息有无及程度、预后的指标之一。总之积极纠正血气、电解质,使之尽快达到正常范围在窒息复苏中是很重要的。     

Hygiene aspects of occupational exposure to waste anaesthetic gases in Ontario hospitals

Exposure of workers to waste anaesthetic gases in the operating and recovery rooms of hospitals is an ongoing concern because a number of epidemiological and mortality studies have reported significant adverse effects. To evaluate the health risks if any, and to assist in the development of guidelines or regulations for the hospital sector in Ontario, the Health and Safety Support Services Branch of the Ontario Ministry of Labour conducted this extensive study. The results of the hygiene study show that exposure to waste anaesthetic occurs because of leaks in the anesthetic equipment. The three major sources of leaks (i.e. exhalation valves, masks and high-pressure fittings) produced concentrations above the limit of detection of nitrous oxide (1000 ppm of N2O) in a significant number of samples. Of the samples taken at leak sources those taken at the exhalation valve had the highest percentage of samples above 1000 ppm, which suggested that scavenging systems were not receiving proper service and maintenance. Only 23% of the operating rooms surveyed met the Ontario Ministry of Health Criterion of 24 air changes per hour. Dilution ventilation was less effective than scavenging in keeping down concentrations of air contaminants. The sampling data show that the anaesthetists have the highest time-weighted average exposure (median value range 56-79 ppm) of the major group of occupations surveyed and that the general surgeons' TWA is much lower (28 ppm). It was concluded that the dilution ventilation rate of 24 air changes per hour should be maintained in all operating rooms and that there should be no recirculation of exhaust air when operations are in progress. To keep down concentrations of anaesthetic gases scavenging systems should be provided in all operating rooms. In each hospital maintenance should be the responsibility of a qualified staff member who has been adequately trained in the repair and maintenance of anaesthetic delivery systems. Finally, a qualified staff member should be responsible for conducting periodic personal monitoring in operating rooms (ORs) and recovery rooms (RRs) and the sampling strategy should include individuals and the exhaust grilles.     

DNA damage, glutathione, and total antioxidant capacity in anesthesia nurses

The possibilities of a potential mutagenic/carcinogenic action of waste anesthetic gases in occupationally exposed anesthesia personnel have been previously reported in several studies. The aim of this study was to assess the DNA damage, reduced glutathione (GSH), and total antioxidant capacity (TAC) in anesthesia nurses. DNA damage was determined with comet assay, GSH levels were measured spectrophotometrically, and TAC was determined by using Randox kit. Anesthesia nurses (n = 40) showed increased DNA damage in terms of mean percentage of the total DNA in the comet tail compared to controls (n = 40) (p < .001). Mean TAC and GSH levels of the anesthesia nurses were significantly lower than that of the controls (p < .001, p < .05, respectively). The results of this study indicate that occupational exposure to anesthetic gases induce DNA damage, which may lead to changes in TAC and GSH levels.     

特殊作业人员6523名心电图结果分析

目的了解特殊作业人员心电图表现，为职业健康监护提供依据。方法以佛山市职业病防治所门诊体检的特殊作业人员年审职业健康检查的心电图与同期初学者体检的心电图作比较。结果年审的特殊作业人员心电图异常率（14．95％）比初学者（6．11％）高（P〈0.01）。结论特殊作业人员的工作需高度集中精力，部分工种作业人员尚需高空或高温作业等，可能致心电图异常率增高，必须加强对其进行健康监护。     

某家电制造企业职工五官科查体情况分析

目的 了解某家电制造企业职业健康检查五官科查体情况，为预防职业相关疾病提供依据。
方法 以该企业在岗及离岗人员为接触组，对其职业健康体检中五官科结果进行统计分析；并以岗前人员为对照组，就危害因素对2组人群进行分析比较。
结果 该企业职业病危害因素包括噪声、粉尘、高温、紫外线、苯乙烯、锰及其化合物、苯及苯系物等60多种。该企业接触组五官科总异常检出率为25.78%，接触组的五官科异常率高于对照组（P < 0.05），接触组男性的异常检出率高于女性（P < 0.05），不同年龄工人异常检出率差异有统计学意义（P < 0.05），接害工龄越长，异常检出率越高（P < 0.05）。五官各部位异常检出率亦有差异，其中以耳部的异常检出率最高；眼部、耳部、鼻部、咽部的主要检出病症分别为翼状胬肉、耵聍栓塞、鼻炎、咽炎。不同危害因素接触组的五官科异常检出率差异并无统计学意义（P>0.05），但噪声、紫外线+电焊烟尘、噪声+粉尘、苯及苯系物接触者的异常检出率处于较高水平。
结论 性别、年龄、工龄、接触职业病危害因素均可能影响五官科异常检出率，应采取积极的针对性预防措施。