Alone asking this question suggests a bias, and I
must therefore recommend the reader to exert caution to a possibly imbalanced
search.
Only one Swedish study [1] is so far available, suggesting
a connection – and while being available only as an abstract, it shall
be considered to a greater detail here:
The authors requested in the occupational
magazine of Swedish anaesthesia nurses plus a magazine issued by an organization
for neurological handicaped. 90 anaesthesia nurses responded, among whom
10 with definite MS had had at least one year of exposure to anaesthetic
gases before diagnosis of MS in 1980-99. This is compared with an expected
level (adjusted for age and sex) of 2.8 (1.3-5.2) from MS registers in
Denmark and Sweden among the little more than 2000 (2046-83) jobs as anaesthesia
nurses.
The study has methodological weaknesses,
as pointed out by its authors: The incidence might be higher with a more
systematical analysis. On the other hand, the positions of anaesthesia
nurse shows a certain fluctuancy. However, this study is the first indication
of a possible connection.
But then, if there is a link between
inhalation of vaporous and gaseous anaesthetics, any other country than
Sweden would be better to show the connection – save that the authors are
Swedish – since this is the country in which the sharpest initiatives have
been taken to reduce the occupational exposure. Other countries may have
the same borderline levels but only in Scandinavia are they also controlled
and respected, leading to the invention of Swedish scavenging measures
still hardly understood outside the Nordic countries [2-6]. Still, even
in other countries, one must remember that both the exposing agents and
the magnitude of exposure has changed in the course of time. There is hardly
any reason to consider drugs for i.v. injection, to which the anaesthetist
or anaesthesia nurse never had any direct contact. If there is a connection,
it must be caused by nitrous oxide or various volatile agents, possibly
both.
In a large epidemiological study,
involving 49,585 exposed operating room personal and 23,911 unexposed controls,
interrogared by the American Society of Anaesthetists [7], a significant
in crease of leukaemia and lymphomas (along with liver diseases, among
others) was found in the exposed group. Among anaesthetists themselves,
increased exposure to general anaesthetics resulted in a 2-3 fold increase
in various cerebral symptoms [8]. It deserves mention, though not quotation,
that quite a number of studies exist, with controversial conclusions, concerning
cognitive parameters among anaesthetists in dependence of exposure.
Apart from such, unfortunately non-existing epidemiological
studies, only two study sources would seem appropriate for appoaching the
problem: 1) Effect of anaesthetics on patients with an already established
MS and 2) experimental study concerning cellular effects of anaesthetic
gaseous or volatile agents.
Effect of anaesthetics on patients with MS
For patients with MS, anaesthesia presents only a brief
exposure and the cause of anaesthesia (accident or larger operation) may
deteriorate defense mechanisms, prompting a relapse.
Most reviews have dealt with the forensic
aspects of performing a regional anaesthesia in MS patients. Obviously,
the presence of peripheral neural defects and the expectancy of more to
come has led to fear among anaesthesists that the foreseen development
might be contributed to regional anaesthesia. Typical for contemporary
medicine, the fear of forensic prosecution often overweighs the desire
to perform the best possible measurement but the mutual conclusion, that
regional anaesthesia can be performed as well in MS patients as in other
subjects, has been confirmed in several reviews.
On the contrary, the actual effect
of a general anaesthesia cannot be estimated according to the study of
patients. Although massive, the exposition is of a brief duration and MS
yields no sensitive parameter which could indicate a temporary deterioration,
as if it was possible to segregate anaesthesia from what has made it necessary.
Only experimental studies may therefore offer some insight into this problem.
Cellular effects of anaesthetic gaseous or volatile agents
The literature is dominated by the interest for the effect
of halothane upon the liver, but the free-radical intermediates may both
be active in other tissues or generated there. In a review of the matter,
Morio et al. [9] emphasized that anaerobic metabolism of halothane
is increased by hypoxia and its intermediate production produces a free
radical. Even in the absence of hypoxia, halothane biotransformation by
cytochrome P-450 produces reactive intermediates along both oxidative (acyl
chloride) and reductive (free radical) pathways [10]. These free radical
intermediates may initiate lipid peroxidation [11.
In guinea pigs, Tsuchiya et al.
[12] found that halothane causes an increase of superoxide production,
which is correlated with (and possibly caused by) an activation of phospholipid-dependent
protein kinase C. In these animals, American authors [10] found that inhibition
of oxidative metabolism with deuterated halothane reduces resultant injury
in our guinea pig model of acute halothane hepatoxicity. Similarly, Durak
et al. [13] found in guinea pigs that halothane causes impairment
in the hepatic antioxidant defense system and accelerates peroxidation
reactions. Although vitamin E prevents peroxidative damage, it does not
ameliorate ultrastructural changes caused by halothane treatment. Also
in rats [12], dogs [14] and rabbits [15], halothane-induced lipid peroxidation
was demonstrated.
Following inhalation of halothane
8-12 ppm for 8 hours a day, 5 days a week (a dose relating to the anaesthetists
working condition without scavenging measures), central nervous damages
were demonstrated in two experimental studies on rats [16,17].
Additional exposures
To a certain degree, operating room staff are exposed
to increased levels of ionizing radiation. The scarce protection of the
trunk rather increases exposure to the rest of the body, in particular
head and arms. In two case-control studies, Axelson et al. [18]
reported an odds ratio of 4.4 for radiological work. In one of the studies,
5 cases but none of the controls had been treated with ionizing radiation.
Another exposure is the anaesthetist’s
close contact to the patients salivation, until recently only rarely protected
by gloves. This undoubtedly predisposes anaesthetists to microbes, but
if these are of importance in the pathogenesis of MS is again another
matter.
Nitrous oxide and Vit B12
The intensive care unit has, unfortunately, developed
a human toxicological test station for adverse effects of anaesthetics.
These drugs have been designed for a brief use in the operating but are
then transferred to the ICU in order to create tolerance to intolerable
ventilatory measures. Once this use has been discovered to be associated
with adverse effects, the drug tested (or shall we say, just used) is apt
to loose favour as an anaesthetic as well. The list of anaesthesics, falling
into disrepute in the ICU, is rather long, but the first drug losing favour
among ventilated patients was nitrous oxide [19].
Prolonged exposure to nitrous oxide
(but unknown in which minimal concentration) will disturb the metabolism
of vitamin B12 [VitB12]. Neurological
defects have been shown following prolonged exposure [20,21], but with
a preexistant deficiency of VitB12, it is possible that neurological defects
may result following a single anaesthesia [22]. The role of this vitamin
in the generation of MS will be emphasized shortly here.
In Summary,
the subject has not received the attention it deserves.
This seems indeed to be a neglected area of medical studies, in spite of
the 3-fold increase in prevalence of MS in the cited study. From the experimental
studies, all of halothane effects in the liver, there seems to be some
indication that free oxygen radicals may act
causative, but without direct study of the matter, even this conclusion
seems to be weak.
Acknowledgement:
Thanks to Dr. Olav Axelson, Linköping (Sweden) for
important suggestings and supportive literature.
References
Inserted February 16, 2002