administering chloroform, and various forms of apparatus have been
devised which claim to reduce to a minimum the dangers of anæsthesia.
Assuming a most skilled and competent administrator, an ideal method of
administration, and a suitable patient, an unsatisfactory result can
only be attributed to the chloroform employed. Purity of chloroform
is a most important factor in contributing to safe anæsthesia. The
physician claims that absolute purity shall characterise all medicinal
agents, and the justice of the claim is acknowledged by the trend of
recent legislation. Purity is a prime essential of any anæsthetic.
The presence of impurities largely increases the risk inseparable
from the use of chloroform. The train of symptoms observed during the
normal process of anæsthesia may be masked and altered, and dangerous
results may supervene under the most competent, careful and observant
administrator.
[Illustration: AN OPERATION IN THE TWENTIETH CENTURY]
[Sidenote: Expert testimony]
That some of the chloroform offered to the profession may reasonably
be regarded with suspicion is evidenced by the words of a prominent
obstetrician, based on the experience of 40 years in the use of
chloroform; this authority expresses himself as follows: “I may say I
fear the chloroform in common use is often far from being as pure as it
should be, and is sometimes very defective in this respect.”
[Sidenote: Effects of impurities]
Impurities may result from the process of manufacture, or from
decomposition. Conspicuous amongst these undesirable elements are
chlorine, hydrochloric acid and carbonyl chloride (phosgene), which
irritate the lining membrane of the respiratory tract and interfere
with the normal process of respiration. Such irritation may result in
arrest of cardiac action or may produce a severe form of bronchitis.
It is obviously of great importance that chloroform should be free
from irritating properties, that the respiratory passages should
not be obstructed, and that during anæsthesia the breathing and the
circulation should approximate the normal. Superadded to these results,
produced by local irritation, is the effect of other impurities which
exert their action after absorption. These latter markedly increase the
cardiac depression which has been shown to follow the administration
of pure chloroform. Such an action is difficult of detection, and is,
probably, in large degree responsible for a considerable number of the
accidents reported.
[Sidenote: Contradictory results]
[Sidenote: Recent research]
[Sidenote: Ethyl chloride]
Of recent years increased knowledge has elaborated exact tests, which
ensure the absence of these impurities. Nevertheless, anæsthetists of
wide experience have obtained results which could not be reconciled
with the use of pure chloroform. It has been observed that
different chloroforms, all of which answer the official tests for
purity, give effects which are difficult to harmonise, and the
interpretation of which only appears satisfactory on the assumption
that the chloroforms differ in composition. Whilst one chloroform acts
most satisfactorily, another produces, during the early stages of
administration, a marked excitement and an irregularity of breathing,
which prolongs the period of induction. Further investigation has
therefore been deemed necessary, and a comprehensive and careful
research has elucidated the cause of these hitherto unexplained
phenomena (Wade and Finnemore, “Journal of the Chemical Society,”
1904, 85, 938). In the chloroforms which produced anæsthesia in a
satisfactory manner, has been demonstrated the presence of ethyl
chloride in minute and varying quantities. When the undesirable
effects were noted, no ethyl chloride was detected in the anæsthetic.
A physiological test conclusively proved that ethyl chloride was the
factor which determined these differences.
[Sidenote: Value of the investigation]
A chloroform which had previously given undesirable effects, and
in which the presence of ethyl chloride could not be demonstrated,
was modified so as to contain a small proportion of the latter. The
chloroform then proved a most satisfactory anæsthetic, and there
was entire absence of the excitement and respiratory irregularity
previously observed. The results of this research are of the utmost
value. In the initial stages of the induction of chloroform anæsthesia,
the presence of a small quantity of ethyl chloride has a beneficial
effect, leading to the absence of mental excitement, and steadies
the breathing. The respiration is stimulated and becomes regular and
deep. In these circumstances, satisfactory anæsthesia is induced with
rapidity and ease.
A CHRONOLOGICAL TABLE OF CHIEF EVENTS AND DISCOVERIES IN THE HISTORY
OF ANÆSTHESIA
NITROUS OXIDE
Joseph Priestley 1776
Humphry Davy 1800
Horace Wells (Colton, Riggs, Evans, Best) 1844
ALCOHOL
Collier 1835–42
ETHER
Michael Faraday 1818
W. E. Clarke 1839
Crawford W. Long 1842
E. E. Marcy 1844
W. T. G. Morton 1846
Charles T. Jackson 1846
First surgical operation in America October 16, 1846
First surgical operation in Great Britain December 21, 1846
(Warren, Hayward, Bigelow, Boote, Robinson, Liston, Buchanan,
Louget, Snow, Simpson, Bernard, Clover)
CHLOROFORM
Guthrie 1831
Waldie 1847
James Young Simpson 1847
First surgical operation under chloroform,
in Edinburgh November 15, 1847
(Soubeiran, Liebig, Dumas, Flourens, M. Duncan, G. Keith,
Snow, Nunneley, James Arnott)
COCAINE
Gädeke 1855
Hughes Bennett 1874
Von Anrep 1880
Koller 1884
[Illustration: ‘Wellcome’ Brand Chloroform, 1/4 lb. in
drop bottle--exact size]
‘WELLCOME’ BRAND CHLOROFORM
[Sidenote: Ethyl chloride]
[Sidenote: Conforms to B.P.]
‘Wellcome’ Brand Chloroform represents the results of the most recent
researches. It embodies the essentials of purity and uniformity,
the necessary basis of a satisfactory chloroform. Some chloroforms
which satisfy official standards have yet been shown to vary in
composition and in effect, the result depending on the occurrence in
the preparation of a small and varying quantity of ethyl chloride.
‘Wellcome’ Brand Chloroform is of constant composition and gives
uniform effects. It conforms in every respect to the requirements
of the B.P., and contains a small and definite proportion of ethyl
chloride, which has been found to assist the satisfactory induction of
anæsthesia.
[Illustration: ‘Wellcome’ Brand Chloroform, 30 c.c., in
hermetically-sealed tube. Length of tube, 5-1/4 in.]
[Sidenote: Proved value]
[Sidenote: Confidence in administration]
‘Wellcome’ Brand Chloroform is the result of prolonged laboratory
experiment and careful clinical observation. Its reception by the
profession verifies the theory upon which its production is based. It
has been largely used in hospital and in private practice, and with
gratifying results. Reports from most experienced anæsthetists agree
in regarding ‘Wellcome’ Brand Chloroform as a distinct advance. Its
constancy in composition gives confidence in administration, and its
freedom from irritating and depressant principles removes the source
of many of the accidents which have hitherto been regarded as grave
objections to the employment of chloroform as an anæsthetic.
‘Wellcome’ Brand Chloroform is issued in 2 oz., 1/4 lb., 1/2 lb.
and 1 lb. amber-coloured bottles; also in 30 c.c. and 60 c.c.
hermetically-sealed tubes, as illustrated on the previous page.
‘WELLCOME’ BRAND ETHER
‘Wellcome’ Brand Ether is prepared specially for anæsthesia and is
thoroughly pure and reliable. When the administration of ether is
desired, this product will be found eminently suitable.
[Sidenote: Ideal packing]
The method of packing in hermetically-sealed tubes is especially
desirable with such a volatile substance as ether, and the shape of
the glass tube admits of the contents being readily transferred to the
graduated bottles usually employed.
[Sidenote: Conforms to B.P.]
‘Wellcome’ Brand Ether conforms to the requirements of the British
Pharmacopœia for _Æther Purificatus_, and has a specific gravity
of 0·720.
‘Wellcome’ Brand Ether is issued in hermetically-sealed tubes
containing 30 c.c. and 60 c.c., similar to the Chloroform packing
illustrated on the previous page.
The anæsthetics issued under the ‘Wellcome’ Brand denote the highest
degree of perfection and purity.
‘WELLCOME’ BRAND PRODUCTS
It is well known that considerable variation exists in the quality and
activity of the medicinal chemicals of commerce.
[Sidenote: The need for reliable Medicinal Chemicals]
Purity and reliability are matters of the utmost importance to
prescriber, dispenser and patient alike, and every opportunity should
therefore be taken to ensure the supply of only those chemicals and
galenicals which are known to be thoroughly pure and trustworthy.
In order that goods answering to this description in the highest sense
may be at the disposal of the profession, Burroughs Wellcome & Co.
manufacture and issue a series of fine chemicals, alkaloids, etc., to
which they have recently added a series of standardised liquid and
granular extracts and concentrated tinctures, under the distinctive
title of the ‘Wellcome’ Brand.
[Sidenote: Standardised galenicals]
[Sidenote: Physiological standards]
The advantages of galenicals containing a definite proportion of active
principle over those that vary in strength with every sample of drug
employed are now fully recognised, and several such have been admitted
into the Pharmacopœia. With regard to galenicals, Burroughs Wellcome
& Co. have extended the standardisation by total alkaloid assay, and
have never adopted the basis of total extractive, regarding it as
misleading and useless. Total alkaloid estimations have been adopted
in so far as they secured definite standards of truly representative
activity, but the firm has not been content to rely on this means
alone. As the result of extensive research, they are able to offer
many other standardised preparations in addition to the official ones.
Those galenicals which are known to be extremely variable in their
character and action, and by their nature do not admit of exact control
by chemical means, have been the subject of physiological research. Not
being satisfied with the methods hitherto available, special processes
of standardisation have been developed which give more complete
control over the finished products. This subject is still one of
continuous research.
The standards adopted have been chosen after the examination of
very many different samples of drugs, and represent the average of
the amounts of active principle found in preparations made from
good specimens. Thus the dose remains the same as that of the older
preparation, but the prescriber is certain of always obtaining the
proper effect instead of one varying from time to time with the
particular batch of extract of tincture used, and the advantage of this
certainty, both to the reputation of the prescriber and the health of
the patient, can hardly be over-estimated.
[Sidenote: Prolonged scientific research]
[Sidenote: ‘Ergotoxine’]
To attain the highest standard in these as in other preparations
for medicinal use, extensive scientific research and many technical
experiments have been made. Long-continued researches in the Wellcome
Chemical and Physiological Research Laboratories led to the issue of
‘Hemisine,’ a physiologically standardised product which presents the
active principle of the medulla of the supra-renal gland in a dry,
soluble state. It is perfectly stable in all climates, and permits of
the instant preparation of fresh reliable solutions possessing the
characteristic hæmostatic and other properties of the supra-renal
gland. Similarly, as the result of researches carried out at the
Wellcome Physiological Research Laboratories, crystalline salts of a
specific alkaloid, which produces the characteristic effects of ergot
on the blood-pressure and the uterus, have been obtained in a state
of chemical purity. To this alkaloid the scientific name “Ergotoxine”
has been given. In ‘Ernutin,’ Burroughs Wellcome & Co. are enabled
to present a preparation of uniform potency, containing the specific
active therapeutic principles of ergot, chief of which is the alkaloid
ergotoxine, in a state of purity which up to the present has never
been approached. It is physiologically standardised by observation of
its effects on the vaso-motor functions of the sympathetic nervous
system.
[Sidenote: Aconitine]
ACONITINE as met with in commerce has been found to vary greatly in
purity, and therefore in physiological effect. It is of the utmost
importance that a definite strength should uniformly attach to so
powerful a drug, and this is secured in the ‘Wellcome’ Brand product,
which is free from pseudaconitine and japaconitine, and from the
non-toxic aconine and benzaconine.
[Sidenote: Atropine Cocaine]
The alkaloid ATROPINE is, under this brand, issued free from hyoscine
and hyoscyamine. COCAINE and its hydrochloride are prepared in a state
of purity answering fully the most rigid tests.
[Sidenote: Aloin, Crystal]
ALOIN (CRYSTAL). This greatly improved product is barbaloin in
well-defined crystals, and is free from resin.
[Sidenote: Bismuth Salicylate]
The bismuth salts have received much attention, a notable improvement
being made in the quality of BISMUTH SALICYLATE. It is well known that
there has been a lack of uniformity in the composition of this article,
and that not infrequently preparations have been sold under this name
which have consisted merely of a mixture of salicylic acid with the
oxide or some salt of bismuth. ‘WELLCOME’ BRAND BISMUTH SALICYLATE
is made from physiologically pure salicylic acid, and is uniform in
composition.
[Sidenote: Stable and soluble]
The scale salt known as BISMUTH AND AMMONIUM CITRATE is a very
unsatisfactory preparation. BISMUTH CITRATE (SOLUBLE), ‘WELLCOME’
BRAND, has the same therapeutic properties, but is much more stable in
character. Being very freely soluble in water and yielding a bright
solution, it is well adapted for the extemporaneous preparation of a
solution corresponding to Solution of Bismuth and Ammonium Citrate,
B.P., or for preparations in which the U.S.P. salt is used. Like the
latter, which it is designed to supersede, it is not compatible with
acid liquids.
BISMUTH AND LITHIUM CITRATE (SOLUBLE), ‘WELLCOME’ BRAND. This new
combination, in the form of handsome colourless scales, is readily
soluble in water. It is thus particularly convenient when the effects
of both lithium and bismuth are desired, as in gouty dyspepsia.
[Sidenote: Sedative and hæmatinic]
BISMUTH AND IRON CITRATE (SOLUBLE), ‘WELLCOME’ BRAND, permits the
sedative properties of the bismuth to be exerted on the digestive
organs, while the iron, which is presented in a soluble, non-irritating
and non-astringent condition, is readily absorbed to attack the anæmia
which is the exciting cause in some cases of dyspepsia. The salt is in
the form of yellowish-green scales, readily soluble in water.
[Sidenote: Definite composition]
IRON ARSENATE (SOLUBLE), ‘WELLCOME’ BRAND, differs from the insoluble
amorphous powders, of indefinite composition, so often prepared under
this name, in being a scale preparation readily soluble in water,
and containing an amount of arsenic equivalent to 34–35 per cent. of
anhydrous ferric arsenate.
[Sidenote: Soluble Manganese Salts]
A series of _soluble_ MANGANESE SALTS and combinations of the same
with Arsenic, Quinine or Strychnine are unique forms in which this
chemical may be prescribed with the best effect.
[Sidenote: Pilocarpine]
The ‘WELLCOME’ BRAND salts of PILOCARPINE, as a result of prolonged and
costly investigations, are free from the less active isopilocarpine
and the inactive pilocarpidine with which they are usually found to be
associated. The melting point indicates the high purity of these salts.
[Sidenote: Quinine Sulphate]
A special feature is made of QUININE SULPHATE in the convenient form
of _compact crystals_ occupying one-third the space of the bulky
chemical ordinarily offered.