The use of inhaled anaesthetics was introduced in the decade of 1840 to 1850. The first compounds to be used were diethyl ether, nitrous oxide and chloroform. Cyclopropane and trichloroethylene were introduced many years later (circa 1930-1940), and the use of fluoroxene, halothane and methoxiflurane began in the decade of the 1950s. By the end of the 1960s enflurane was being used and, finally, isoflurane was introduced in the 1980s. Isoflurane is now considered the most widely used inhalation anaesthetic even though it is more expensive than the others. A summary of the physical and chemical characteristics of methoxiflurane, enflurane, halothane, isoflurane and nitrous oxide, the most commonly used anaesthetics, is shown in table 1 (Wade and Stevens 1981).
Table 1. Properties of inhaled anaesthetics
|
Isoflurane, |
Enflurane, |
Halothane, |
Methoxyflurane, |
Dinitrogen oxide, |
|
|
Molecular weight |
184.0 |
184.5 |
197.4 |
165.0 |
44.0 |
|
Boiling point |
48.5°C |
56.5°C |
50.2°C |
104.7°C |
— |
|
Density |
1.50 |
1.52 (25°C) |
1.86 (22°C) |
1.41 (25°C) |
— |
|
Vapour pressure at 20 °C |
250.0 |
175.0 (20°C) |
243.0 (20°C) |
25.0 (20°C) |
— |
|
Smell |
Pleasant, sharp |
Pleasant, like ether |
Pleasant, sweet |
Pleasant, fruity |
Pleasant, sweet |
|
Separation coefficients: |
|||||
|
Blood/gas |
1.40 |
1.9 |
2.3 |
13.0 |
0.47 |
|
Brain/gas |
3.65 |
2.6 |
4.1 |
22.1 |
0.50 |
|
Fat/gas |
94.50 |
105.0 |
185.0 |
890.0 |
1.22 |
|
Liver/gas |
3.50 |
3.8 |
7.2 |
24.8 |
0.38 |
|
Muscle/gas |
5.60 |
3.0 |
6.0 |
20.0 |
0.54 |
|
Oil/gas |
97.80 |
98.5 |
224.0 |
930.0 |
1.4 |
|
Water/gas |
0.61 |
0.8 |
0.7 |
4.5 |
0.47 |
|
Rubber/gas |
0.62 |
74.0 |
120.0 |
630.0 |
1.2 |
|
Metabolic rate |
0.20 |
2.4 |
15–20 |
50.0 |
— |
All of them, with the exception of nitrous oxide (N2O), are hydrocarbons or chlorofluorinated liquid ethers that are applied by vapourization. Isoflurane is the most volatile of these compounds; it is the one that is metabolized at the lowest rate and the one that is least soluble in blood, in fats and in the liver.
Normally, N2O, a gas, is mixed with a halogenated anaesthetic, although they are sometimes used separately, depending on the type of anaesthesia that is required, the characteristics of the patient and the work habits of the anaesthetist. The normally used concentrations are 50 to 66% N2O and up to 2 or 3% of the halogenated anaesthetic (the rest is usually oxygen).
The anaesthesia of the patient is usually started by the injection of a sedative drug followed by an inhaled anaesthetic. The volumes given to the patient are in the order of 4 or 5 litres/minute. Parts of the oxygen and of the anaesthetic gases in the mixture are retained by the patient while the remainder is exhaled directly into the atmosphere or is recycled into the respirator, depending among other things on the type of mask used, on whether the patient is intubated and on whether or not a recycling system is available. If recycling is available, exhaled air can be recycled after it is cleaned or it can be vented to the atmosphere, expelled from the operating room or aspirated by a vacuum. Recycling (closed circuit) is not a common procedure and many respirators do not have exhaust systems; all the air exhaled by the patient, including the waste anaesthetic gases, therefore, ends up in the air of the operating room.
The number of workers occupationally exposed to waste anaesthetic gases is high, because it is not only the anaesthetists and their assistants who are exposed, but all the other people who spend time in operating rooms (surgeons, nurses and support staff), the dentists who perform odontological surgery, the personnel in delivery rooms and intensive care units where patients may be under inhaled anaesthesia and veterinary surgeons. Similarly, the presence of waste anaesthetic gases is detected in recovery rooms, where they are exhaled by patients who are recovering from surgery. They are also detected in other areas adjacent to operating rooms because, for reasons of asepsis, operating rooms are kept at positive pressure and this favours the contamination of surrounding areas.
Health Effects
Problems due to the toxicity of anaesthetic gases were not seriously studied until the 1960s, even though a few years after the use of inhaled anaesthetics became common, the relationship between the illnesses (asthma, nephritis) that affected some of the first professional anaesthetists and their work as such was already suspected (Ginesta 1989). In this regard the appearance of an epidemiological study of more than 300 anaesthetists in the Soviet Union, the Vaisman (1967) survey, was the starting point for several other epidemiological and toxicological studies. These studies—mostly during the 1970s and the first half of the 1980s—focused on the effects of anaesthetic gases, in most cases nitrous oxide and halothane, on people occupationally exposed to them.
The effects observed in most of these studies were an increase in spontaneous abortions among women exposed during or before pregnancy, and among women partners of exposed men; an increase in congenital malformations in children of exposed mothers; and the occurrence of hepatic, renal and neurological problems and of some types of cancer in both men and women (Bruce et al. 1968, 1974; Bruce and Bach 1976). Even though the toxic effects of nitrous oxide and of halothane (and probably its substitutes as well) on the body are not exactly the same, they are commonly studied together, given that exposure generally occurs simultaneously.
It appears likely that there is a correlation between these exposures and an increased risk, particularly for spontaneous abortions and congenital malformations in children of women exposed during pregnancy (Stoklov et al. 1983; Spence 1987; Johnson, Buchan and Reif 1987). As a result, many of the people exposed have expressed great concern. Rigorous statistical analysis of these data, however, casts doubt on the existence of such a relationship. More recent studies reinforce these doubts while chromosomal studies yield ambiguous results.
The works published by Cohen and colleagues (1971, 1974, 1975, 1980), who carried out extensive studies for the American Society of Anaesthetists (ASA), constitute a fairly extensive series of observations. Follow-up publications criticized some of the technical aspects of the earlier studies, particularly with respect to the sampling methodology and, especially, the proper selection of a control group. Other deficiencies included lack of reliable information on the concentrations to which the subjects had been exposed, the methodology for dealing with false positives and the lack of controls for factors such as tobacco and alcohol use, prior reproductive histories and voluntary infertility. Consequently, some of the studies are now even considered invalid (Edling 1980; Buring et al. 1985; Tannenbaum and Goldberg 1985).
Laboratory studies have shown that exposure of animals to ambient concentrations of anaesthetic gases equivalent to those found in operating rooms does cause deterioration in their development, growth and adaptive behaviour (Ferstandig 1978; ACGIH 1991). These are not conclusive, however, since some of these experimental exposures involved anaesthetic or subanaesthetic levels, concentrations significantly higher than the levels of waste gases usually found in operating room air (Saurel-Cubizolles et al. 1994; Tran et al. 1994).
Nevertheless, even acknowledging that a relationship between the deleterious effects and exposures to waste anaesthetic gases has not been definitively established, the fact is that the presence of these gases and their metabolites is readily detected in the air of operating rooms, in exhaled air and in biological fluids. Accordingly, since there is concern about their potential toxicity, and because it is technically feasible to do so without inordinate effort or expense, it would be prudent to take steps to eliminate or reduce to a minimum the concentrations of waste anaesthetic gases in operating rooms and nearby areas (Rosell, Luna and Guardino 1989; NIOSH 1994).
Maximum Allowable Exposure Levels
The American Conference of Governmental Industrial Hygienists (ACGIH) has adopted a threshold limit value-time weighted average (TLV-TWA) of 50 ppm for nitrous oxide and halothane (ACGIH 1994). The TLV-TWA is the guideline for the production of the compound, and the recommendations for operating rooms are that its concentration be kept lower, at a level below 1 ppm (ACGIH 1991). NIOSH sets a limit of 25 ppm for nitrous oxide and of 1 ppm for halogenated anaesthetics, with the additional recommendation that when they are used together, the concentration of halogenated compounds be reduced to a limit of 0.5 ppm (NIOSH 1977b).
With regard to values in biological fluids, the recommended limit for nitrous oxide in urine after 4 hours of exposure at average ambient concentrations of 25 ppm ranges from 13 to 19 μg/L, and for 4 hours of exposure at average ambient concentrations of 50 ppm, the range is 21 to 39 μg/L (Guardino and Rosell 1995). If exposure is to a mixture of a halogenated anaesthetic and nitrous oxide, the measurement of the values from nitrous oxide is used as the basis for controlling exposure, because as higher concentrations are used, quantification becomes easier.
Analytical Measurement
Most of the procedures described for measuring residual anaesthetics in air are based on the capture of these compounds by adsorption or in an inert bag or container, later to be analysed by gas chromatography or infrared spectroscopy (Guardino and Rosell 1985). Gas chromatography is also employed to measure nitrous oxide in urine (Rosell, Luna and Guardino 1989), while isoflurane is not readily metabolized and is therefore seldom measured.
Common Levels of Residual Concentrations in the Air of Operating Rooms
In the absence of preventive measures, such as the extraction of residual gases and/or introducing an adequate supply of new air into the operating suite, personal concentrations of more than 6,000 ppm of nitrous oxide and 85 ppm of halothane have been measured (NIOSH 1977). Concentrations of up to 3,500 ppm and 20 ppm, respectively, in the ambient air of operating rooms, have been measured. The implementation of corrective measures can reduce these concentrations to values below the environmental limits cited earlier (Rosell, Luna and Guardino 1989).
Factors that Affect the Concentration of Waste Anaesthetic Gases
The factors which most directly affect the presence of waste anaesthetic gases in the environment of the operating room are the following.
Method of anaesthesia. The first question to consider is the method of anaesthesia, for example, whether or not the patient is intubated and the type of face mask being used. In dental, laryngeal or other forms of surgery in which intubation is precluded, the patient’s expired air would be an important source of emissions of waste gases, unless equipment specifically designed to trap these exhalations is properly placed near the patient’s breathing zone. Accordingly, dental and oral surgeons are considered to be particularly at risk (Cohen, Belville and Brown 1975; NIOSH 1977a), as are veterinary surgeons (Cohen, Belville and Brown 1974; Moore, Davis and Kaczmarek 1993).
Proximity to the focus of emission. As is usual in industrial hygiene, when the known point of emission of a contaminant exists, proximity to the source is the first factor to consider when dealing with personal exposure. In this case, the anaesthetists and their assistants are the persons most directly affected by the emission of waste anaesthetic gases, and personal concentrations have been measured in the order of two times the average levels found in the air of operating rooms (Guardino and Rosell 1985).
Type of circuit. It goes without saying that in the few cases in which closed circuits are used, with reinspiration after the cleansing of the air and the resupply of oxygen and the necessary anaesthetics, there will be no emissions except in the case of equipment malfunction or if a leak exists. In other cases, it will depend on the characteristics of the system used, as well as on whether or not it is possible to add an extraction system to the circuit.
The concentration of anaesthetic gases. Another factor to take into account is the concentrations of the anaesthetics used since, obviously, those concentrations and the amounts found in the air of the operating room are directly related (Guardino and Rosell 1985). This factor is especially important when it comes to surgical procedures of long duration.
Type of surgical procedures. The duration of the operations, the time elapsed between procedures done in the same operating room and the specific characteristics of each procedure—which often determine which anaesthetics are used—are other factors to consider. The duration of the operation directly affects the residual concentration of anaesthetics in the air. In operating rooms where procedures are scheduled successively, the time elapsed between them also affects the presence of residual gases. Studies done in large hospitals with uninterrupted use of the operating rooms or with emergency operating rooms that are used beyond standard work schedules, or in operating rooms used for prolonged procedures (transplants, laryngotomies), show that substantial levels of waste gases are detected even before the first procedure of the day. This contributes to increased levels of waste gases in subsequent procedures. On the other hand, there are procedures that require temporary interruptions of inhalation anaesthesia (where extracorporeal circulation is needed, for example), and this also interrupts the emission of waste anaesthetic gases into the environment (Guardino and Rosell 1985).
Characteristics specific to the operating room. Studies done in operating rooms of different sizes, design and ventilation (Rosell, Luna and Guardino 1989) have demonstrated that these characteristics greatly influence the concentration of waste anaesthetic gases in the room. Large and non-partitioned operating rooms tend to have the lowest measured concentrations of waste anaesthetic gases, while in small operating rooms (e.g., paediatric operating rooms) the measured concentrations of waste gases are usually higher. The general ventilation system of the operating room and its proper operation is a fundamental factor for the reduction of the concentration of waste anaesthetics; the design of the ventilation system also affects the circulation of waste gases within the operating room and the concentrations in different locations and at various heights, something that can be easily verified by carefully taking samples.
Characteristics specific to the anaesthesia equipment. The emission of gases into the environment of the operating room depends directly on the characteristics of the anaesthesia equipment used. The design of the system, whether it includes a system for the return of excess gases, whether it can be attached to a vacuum or vented out of the operating room, whether it has leaks, disconnected lines and so on are always to be considered when determining the presence of waste anaesthetic gases in the operating room.
Factors specific to the anaesthetist and his or her team. The anaesthetist and his or her team are the last element to consider, but not necessarily the least important. Knowledge of the anaesthesia equipment, of its potential problems and the level of maintenance it receives—both by the team and by the maintenance staff in the hospital—are factors that affect very directly the emission of waste gases into the air of the operating room (Guardino and Rosell 1995). It has been clearly shown that, even when using adequate technology, the reduction of the ambient concentrations of anaesthetic gases cannot be achieved if a preventive philosophy is absent from the work routines of anaesthetists and their assistants (Guardino and Rosell 1992).
Preventive Measures
The basic preventive actions required to reduce occupational exposure to waste anaesthetic gases effectively can be summarized in the following six points:
- Anaesthetic gases should be thought of as occupational hazards. Even if from a scientific standpoint it has not been conclusively shown that anaesthetic gases have a serious deleterious effect on the health of people who are occupationally exposed, there is a high probability that some of the effects mentioned here are directly related to the exposure to waste anaesthetic gases. For that reason it is a good idea to consider them toxic occupational hazards.
- Scavenger systems should be used for waste gases. Scavenger systems are the most effective technical hardware for the reduction of waste gases in the air of the operating room (NIOSH 1975). These systems must fulfil two basic principles: they must store and/or adequately eliminate the whole volume of air expired by the patient, and they must be designed to guarantee that neither the respiration of the patient nor the proper functioning of the anaesthesia equipment will be affected—with separate safety devices for each function. The techniques most commonly employed are: a direct connection to a vacuum outlet with a flexible regulating chamber that allows for the discontinuous emission of gases of the respiratory cycle; directing the flow of the gases exhaled by the patient to the vacuum without a direct connection; and directing the flow of gases coming from the patient to the return of the ventilation system installed in the operating room and expelling these gases from the operating room and from the building. All these systems are technically easy to implement and very cost-efficient; the use of installed respirators as part of the design is recommended. In cases where systems that eliminate waste gases directly cannot be used because of the special characteristics of a procedure, localized extraction can be employed near the source of emission as long as it does not affect the general ventilation system or the positive pressure in the operating room.
- General ventilation with a minimum of 15 renewals/hour in the operating room should be guaranteed. The general ventilation of the operating room should be perfectly regulated. It should not only maintain positive pressure and respond to the thermohygrometric characteristics of the ambient air, but should also provide a minimum of 15 to 18 renewals per hour. Also, a monitoring procedure should be in place to ensure its proper functioning.
- Preventive maintenance of the anaesthesia circuit should be planned and regular. Preventive maintenance procedures should be set up that include regular inspections of the respirators. Verifying that no gases are being emitted to the ambient air should be part of the protocol followed when the equipment is first turned on, and its proper functioning with regard to the safety of the patient should be checked. The proper functioning of the anaesthesia circuit should be verified by checking for leaks, periodically replacing filters and checking the safety valves.
- Environmental and biological controls should be used. The implementation of environmental and biological controls provides information not only about the correct functioning of the various technical elements (extraction of gases, general ventilation) but also about whether the working procedures are adequate for curtailing the emission of waste gases into the air. Today these controls do not present technical problems and they can be implemented economically, which is why they are recommended.
- Education and training of the exposed personnel is crucial. Achieving an effective reduction of occupational exposure to waste anaesthetic gases requires educating all operating room personnel about the potential risks and training them in the required procedures. This is particularly applicable to anaesthetists and their assistants who are most directly involved and those responsible for the maintenance of the anaesthesia and air-conditioning equipment.
Conclusion
Although not definitively proven, there is enough evidence to suggest that exposures to waste anaesthetic gases may be harmful to HCWs. Stillbirths and congenital malformations in infants born to female workers and to the spouses of male workers represent the major forms of toxicity. Since it is technically feasible at a low cost, it is desirable to reduce the concentration of these gases in the ambient air in operating rooms and adjacent areas to a minimum. This requires not only the use and correct maintenance of anaesthesia equipment and ventilation/air conditioning systems but also the education and training of all personnel involved, especially anaesthetists and their assistants, who generally are exposed to higher concentrations. Given the work conditions peculiar to operating rooms, indoctrination in the correct work habits and procedures is very important in trying to reduce the amounts of anaesthetic waste gases in the air to a minimum.