Trichloroethylene and Parkinson’s disease
The Association of Anaesthetists
is aware of a cluster of cases of
Parkinson’s disease in retired
anaesthetists in one region of
the UK. It was suggested to us
that a common factor might
be occupational exposure to
trichloroethylene. We were asked
if we knew of any other cases or
clusters, but we do not keep any
records of members’ medical
conditions. As an organisation with
a significant interest in wellbeing,
this clearly is not because we are
not interested! We don’t have
access to medical records, nor
would we wish to start collecting
personal, confidential information
on our members (active, retired,
or former members), unless it
was part of a properly conducted
research project with due attention
to confidentiality and governance.
Figure 1. James Parkinson’s premises at No.1 Hoxton Square, London
Parkinson’s disease and parkinsonism
James Parkinson is credited with the first description of the condition
when he wrote about the Shaking Palsy in 1817, although the condition
had probably been described already [Figure 1]. Most will know about
the common signs of bradykinesia, rigidity, tremor and postural instability.
The term ‘idiopathic Parkinson’s disease’ is reserved for a specific,
pathologically-defined condition with typical Lewy body and α-synuclein
protein accumulation, and ‘parkinsonism’ is used for other causes of a similar
constellation of signs deriving from the basal ganglia, most commonly
caused by toxic/ metabolic causes or vascular disease of the brain.
Parkinson’s disease presents a progressive, asymmetrical condition which,
by definition, responds well to levodopa therapy. The signs of parkinsonism
tend to be symmetrical, and levodopa response is absent or minimal.
Trichloroethylene exposure and parkinsonism
There are a number of reports of occupational exposure to trichloroethylene
and the development of parkinsonism. In 1999 a case report described
parkinsonism in a 47-year woman exposed to trichloroethylene for seven
years [1]. Gash et al. found three cases of parkinsonism in co-workers at a
factory where they were exposed to trichloroethylene [2]. Fourteen others
who worked nearby in the same factory had some features of parkinsonism.
Goldman et al. studied twins with Parkinson’s disease and found that
exposure to trichloroethylene was associated with an increased risk of
the disease (odds ratio 6.1; 95%CI: 1.2-33.0; p = 0.034) [3]. In the first two
papers, further animal work linked trichloroethylene exposure to toxicity in
dopaminergic neurons.
Trichloroethylene exposure may cause a metabolic parkinsonism, it may be
an environmental factor in the development of idiopathic Parkinson’s disease
in those with a genetic susceptibility, or both mechanisms may be relevant.
What next?
We would be interested, in the first instance, to hear of any other
anecdotal reports of parkinsonism or Parkinson’s disease in
anaesthetists, and whether they used, or were likely to have used,
trichloroethylene during their careers. We hope to determine
if there are any other clusters or cases, in other words to see if
Parkinson’s disease seems more common in anaesthetists. If there
does seem to be an association, we will proceed to a more formal
survey. Let us know at [email protected]. While we
aim to preserve confidentiality, please note this call is not part of a
formal research proposal at this stage, so only send us information if
you are happy for it to be shared with us and with other Association
Board members and staff, and for anonymised details to be
published as part of a report.
When one considers that the first medical use of trichloroethylene
was to treat trigeminal neuralgia, how paradoxical would it be if
we now found a link between this agent and a neurodegenerative
condition in those exposed occupationally?
Mike Nathanson
President
Association of Anaesthetists
David Wilkinson
Retired Anaesthetist
Former Honorary Secretary and Honorary Treasurer
Association of Anaesthetists
Gillian Sare
Consultant Neurologist
Nottingham University Hospitals
Twitter: @mikenathanson61
References
- Guehl D, Bezard E, Dovero S, Boraud T, Bioulac B, Gross C. Trichloroethylene
and parkinsonism: a human and experimental observation. European Journal of
Neurology 1999; 6: 609-11.
- Gash DM, Rutland K, Hudson NL, et al. Trichloroethylene: Parkinsonism and
complex 1 mitochondrial neurotoxicity. Annals of Neurology 2008; 63: 184-92.
- Goldman SM, Quinlan PJ, Ross GW, et al. Solvent exposure and Parkinson disease
risk in twins. Annals of Neurology 2012; 71: 776-84.
A short history of trichloroethylene (Trilene) anaesthesia
Trichlorethylene was first synthesised by Fischer in 1864 [1]. Initially
it was used as a solvent for organic compounds, and then as a
degreasing agent. Toxic effects were soon noted, and Plessner
reported four cases of trigeminal analgesia in 1915 [2]. This led
to its use in the treatment of trigeminal neuralgia with varied
levels of success [3]. In 1933 Jackson and Herzberg successfully
anaesthetised a series of dogs [4], and within a couple of years had
demonstrated effective anaesthesia in several hundred patients [5].
This work was reviewed by Waters who used the agent on a series
of animals and found significant cardiac effects [6]. Interest in this
drug then waned in the USA.
In 1939 the UK government asked a Joint Committee of the Medical
Research Committee and the Royal Society of Medicine to find a
non-explosive, cheap anaesthetic that could be used during the
war and which was safer than chloroform. At some point in 1940, a
North London chemist called Chalmers contacted Charles Hadfield
at St Bartholomew’s Hospital, and told him of his personal use of
trichloroethylene to produce anaesthesia. Christopher Langton
Hewer, Hadfield’s colleague, obtained a Winchester bottle of the
drug and tried it, initially on his registrar, Rex Marrett, while they
were working together at Hill End Hospital, St Albans. Hewer
thought it was interesting and within a few months had collected
127 cases and reported the findings in the British Medical Journal
[7]. It was soon apparent that the drug decomposed in the presence
of heat to produce dangerous toxins; this meant that it should never
be used in closed circuit systems with soda lime. The drug was
manufactured by ICI and sold as ‘Trilene’ with a colouring agent,
Waxolene Blue, to distinguish it from chloroform.
As a sole anaesthetic, trichloroethylene had the drawbacks of
slow onset and offset, together with a tendency to cause a severe
tachypnoea. It was, however, a very potent analgesic, cheap and
non-explosive. For decades, trainees at St Bartholomew’s Hospital
were taught to use the drug, initially from a Boyles bottle and then
using a Tritec vapouriser. The effectiveness of trichloroethylene
as an analgesic at concentrations between 0.3% and 0.5% in air
were soon noted. At these concentrations it did not produce
unconsciousness, and soon many specialised vapourisers were
being manufactured for use in obstetric practice and short painful
surgical procedures.
The Siebe-Gorman-Hyatt, the Trilite, the Cyprane, the Airlene, the
Freedman, the Marrett, the Tecota and the Emotril were all popular
in the UK, but only the Emotril and Tecota Mark 6 were permitted
to be used by trained but unsupervised midwives. These latter two
vapourisers soon replaced all of the rest. In America, Ron Stephens
created the Duke Inhaler for tricholoroethylene, and there was also
a Trimar inhaler, but neither were hugely popular.
With the introduction of halothane in the late 1950s, combinations
of trichloroethylene and halothane were soon being advocated by
Barts-trained staff. The drugs were not mixed but the vapourisers,
either Boyles bottles or Tec vapourisers, were used in series on
the back bar. The halothane created an anaesthetic state and the
tricholoroethylene, added at around 0.3-0.5%, provided analgesia
which extended into the immediate recovery period. These
techniques stopped when the Selectatec back bar started to be
introduced in the 1980s. This system only permitted the use of
one vapouriser at a time, and the days of trichloroethylene were
numbered. With the introduction of Entonox for use in obstetrics
and the increasing utilisation of epidural analgesia, trichloroethylene
became obsolete in this branch of medicine as well.
David Wilkinson
Retired Anaesthetist
Former Honorary Secretary and Honorary Treasurer Association of
Anaesthetists
References
- Fischer E. Über die Einwirkung von Wasserstoff auf Einfach-Chlorkohlenstoff.
Jenaische Zeitschrift für Medizin und Naturwissenschaft 1864: 1; 123-4.
- Plessner W. Über Trigeminuserkrankung infolge von Trichloraethylenvergiftung.
Neurologisches Zentralblatt 1915: 34; 916-8.
- 3. Oljenick I. Trichlorethylene treatment of trigeminal neuralgia. Journal of the American
Medical Association 1928: 91; 1085-7.
- Jackson DE. Herzberg M. A study of analgesia and anesthesia, with special reference
to such substances as trichloroethylene and vinesthene (divinyl ether), together with
apparatus for their administration. Current Researches in Anesthesia and Analgesia
1934: 13; 198-204.
- Striker C, Goldblatt S, Warm IS, Jackson DE. Clinical experiences with the use of
trichloroethylene in the production of over 300 analgesias and anesthesias. Current
Researches in Anesthesia and Analgesia 1935: 14; 68-71.
- Waters RM, Orth OS, Gillespie NA. Trichlorethylene anesthesia and cardiac rhythm.
Anesthesiology 1943: 4; 1-5.
- Hewer CL, Hadfield CF. Trichlorethylene as an inhalational anaesthetic. British Medical
Journal 1941: 1; 924-7.