Anaesthetics

Risks for the patient who must undergo anaesthesia have been known for many years. Therefore, researchers have been committed to find new more effective anaesthetic techniques, and new anaesthetic compounds, manageable and less toxic for the patient. On the other hand, less attention has been paid to the health risks arising from occupational exposure to anaesthetics in the operating-theatre personnel.
Nowadays, the most commonly administered inhalation anaesthetics are as follows:

• Nitrous oxide(N₂O)
• Halothane
• Enflurane
• Isoflurane

All these substances belong to the group of inert compounds which are first absorbed through the alveolar-capillary membrane and then distributed to the different biological tissues in accordance with their liposolubility.
Since there is no ideal anaesthetic, anaesthesia is usually performed associating nitrous oxide to an halogenated anaesthetic. The halogenated anaesthetic, initially in the liquid state, is vaporized in a thermocompensated device, where it mingles with a gaseous current which usually comes from a centralized system and is made up of 40% Oxygen and 60% nitrous oxide. The concentration of the halogenated anaesthetic in the mixture may reach 4-5% depending on which substance is used and on the type of surgical operation that is going to be performed. This concentration varies during the different phases of the operation, being more elevated in the induction stage, lasting a few minutes, than in the maintenance stage.

It may be estimated that about 10% of workers in the health sector is exposed to anaesthetic gases employed in the operating-theatre. The number of exposed subjects varies between 50.000 and 60.000 workers, including anaesthetists, surgeons, tools assistants, operating-theatre nurses. Up to the 1980s these workers might have been exposed to high concentrations (up to 7-8 times higher than today's limits of environmental tolerance) of anaesthetics. As far as the metabolic conversion is concerned, an important biotransformation has been experimentally proven for all volatile anaesthetics. This biotransformation is important not only because it ends the anaesthetic's action but also because some of the metabolites that originate during the reaction may be held responsible for some of the anaesthetic's acknowledged toxic effects. Of the absorbed and liver-metabolized halothane portion, 18-20% is found in urine as bromide and 12% as trifluoracetic acid. Enflurane undergoes a smaller biotransformation and is eliminated by the lungs for as much as 83%, the remaining percentage being eliminated with urine only 2,4% of the absorbed portion is found as non-volatile metabolites: methoxidifluoracetic acid, oxalic acid, fluorides and chlorides). Among halogenated anaesthetics isoflurane is the least toxic: it is eliminated almost completely by the lungs and only 0,2% is found as metabolites in urine.
N₂O is a substance little soluble in the blood and only partially metabolized by the body; it is quickly eliminated by the lungs at the end of the exposure and very small quantities are excreted unaltered in urine.

Percentages of metabolization, elimination and retention of the main inhalation anaesthetics .

 
ANAESTHETICS  A B C 
Nitrous oxide  / 90% 3%
Halothane 10-20% 60-80% 20-40%
Enflurane  2-10% 83% 35%
Isoflurane  0,2% >70% 40%

A=% of metabolization
B=% of elimination of unaltered substance by the lungs
C=% retention index (quantity of anaesthetic absorbed through the lungs, expressed as percentage of the inhaled portion)

As far as the effects of such substances on health are concerned, a document has been compiled in 1992 by the Study Group on the Occupational Exposure to Inhalation Anaesthetics of the Lombard Association of Occupational Medicine and Industrial Hygiene. This document reads: "Literature analysis has pointed out that there are many doubts about the existence, with the present exposure, of effects on organs and apparatuses once considered target organs". However, most studies point out some effects on the liver and, in particular, on the activity of the liver microsomal enzymes. Neuro-behavioural studies, carried out by different working groups, seem to indicate that moderate and temporary reductions in psychomotor efficiency occur for moderate exposures. It has yet to be established whether these alterations have any effect on the subjects' quality of life and on their working performance and what the exact role of factors other than volatile anaesthetics in their determinism is.
Alterations on the reproductive function were shown with a certain degree of certainty by some epidemiological studies carried out before the 1980s, but the results were then challenged by other epidemiological studies carried out in the Scandinavian countries and in Great Britain, which showed negative results. As far as the effects on heart, kidney, haemopoietic system, immune system and the cytogenetic effects are concerned, very few and contradictory data exist up to the present day".
In many countries the exposure limits to nitrous oxide and halogenated anaesthetics are set by law. Although in Italy no set limit exists, the Ministry of Health has issued a regulation (n.5 of 14 March 1989) concerning occupational exposure to anaesthetics in the operating-theatre.
The regulation provides for a technical limit, in the existing operating theatres, represented by a concentration of N₂O (guide polluting agent) in the air equal to 100 ppm and provides for a lowering of this limit to 50 ppm in the case of restructuring.
No limits are provided for halogenated anaesthetics.
Futhermore, it is established that new operating theatres must be provided with ventilation systems in order to guarantee that the 50 ppm N₂O limit is not exceeded and that microclimate parameters and air pureness standards are observed.

Environmental monitoring of inhalation anaesthetics is usually carried out in two different steps: sampling and analysis.
Measurements can be carried out either in a stationary position, in order to examine the polluting condition of the examined environment, or on the person, in order to evaluate the exposure levels of the different professional figures (anaesthetists, surgeons, nursing personnel).
In the first instance (stationary position sampling) measurements can be carried out by placing the surveying system 160 cm above the floor level; in the second instance (personal sampling) the surveying systems, supplied with tubes and tube-fittings that make it possible to pick up the polluting agents in the respiratory system, can be placed on the professional's belt. The withdrawal flow is predetermined and monitored by precision fluxmeters.

Biological compartments usually chosen or proposed for biological monitoring of anaesthetics absorbed through the respiratory system are:
- the alveolar compartment (middle expiratory compartment);
- the blood compartment (venous);
- the urinary compartment.
Sought substances are the non metabolized compounds and some of the well-known and analysable biotransformation products.
Biological monitoring carried out on alveolar air (middle expired air) or venous blood samples can be performed in different moments, and in general:
- during the exposure
- immediately after the exposure
- at the end of the working week.
The values thus obtained are concentration instant values that must be referred to environmental instant concentration values (if the sampling took place during exposure) or to environmental average concentration values (if the sampling took place after the exposure) of the last period of exposure or of the last day or the last few days of exposure. On the contrary, urinary concentration values are not instant, but well-pondered.
Biological monitoring is thus carried out by using biological reference values; in the regulation of the Ministry of Health n.5 of 1989 biological parameters are reported that are considered, with one accord, indicative of exposure to inhalation anaesthetics.


Biological exposure limit of inhalation anaesthetics

Anaesthetic	Biological marker
Halothane	Hematic trifluoracetic acid: 2.5 mg/l blood (taken at the end of the week and at of the exposure)
Halothane	Alveolar halothane: 0.5 ppm (measured in operating-theatre at the end of the exposure)
Isoflurane	Isoflurane urinary: 18 nM/l urine (measured in the urines at the end of the exposure)
Nitrous oxide	N2O urinary: 27 mcg/l (measured in the urines taken at the end of the exposure; biological equivalent value to 50 ppm of environmental concentration)
Nitrous oxide	N2O urinary: 55 mcg/l (measured in the urines taken at the end of the exposure; biological equivalent value to 100 ppm of environmental concentration)

For additional information

• Anesthetic Gases (Occupational Safety & Health Administration)

Operating theatres

Operating theatres

Anaesthetics