Brit. J. Anaesth.

(1969), 41, 18

THE ANTI-HAEMORRHAGIC ACTIVITY OF ETHAMSYLATE (DICYNENE*)

An Experimental Study
BY
A. R. DE C. DEACOCK AND DOREEN M. BIRLEY

SUMMARY
The haemostatic effect of ethamsylate was examined by means of a controlled, "blind"
trial in which forty-three experiments were performed on a series of twenty-two pigs.
The experimental preparation consisted of a standard wound produced by means of an
electric dermatome and designed to cause capillary haemorrhage. Blood loss was

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estimated by weighing swabs. Statistical evaluation of the results indicates that etham-
sylate is effective in reducing bleeding and that the magnitude of the reduction is
directly proportional to the severity of the unmodified bleeding. No effect of the drug
on pulse rate, blood pressure or platelet count was observed.

Surgery is inevitably accompanied by haemor- OH

rhage, so familiar a phenomenon that it is easy to
lose sight of its implications, both medical and
economic. Much of the resources of the operating
theatre and the efforts of those who work therein
are devoted to dealing with haemorrhage and the
consequences of haemorrhage.
Apart from the direct methods of the surgeon,
various other techniques have been employed in
order to diminish blood loss. These include appro-
priate positioning of the patient, arteriotomy,
blockade of the sympathetic nervous system by
various means and reduction of cardiac output by
means of drugs, all measures designed to reduce
blood pressure. These techniques are, in general,
neither simple nor without danger for the patient.
As an alternative, the systemic administration of a
drug specifically to reduce bleeding would have
obvious advantages, were such an agent available.
Two substances for which this action has been
claimed are adrenochrome monosemicarbazone
(Adrenoxyl) (Beal and Gondaert, 1947; Huyge-
baert, 1949) and, more recently, ethamsylate
(Dicynene). The former has been available for
some twenty years, but it has not become estab-
lished as a clinically effective agent. Ethamsylate,
however, has been generally available only since
1963 and, as yet, it is not clear to what extent it
may be of value in the control of haemorrhage.
Ethamsylate is diethylammonium 1,4-dihydroxy
3-benzenesulphonate and the structural formula is
'so.
OH
FIG. 1
Structural formula of ethamsylate.
shown in figure 1. It is a white, crystalline sub-
stance presented for clinical use in tablet form for
oral administration and in ampoules containing a
solution for parenteral use. Both preparations con-
tain 250 mg of the drug. If administered orally,
ethamsylate is usually given on the evening prior
to surgery. After intravenous injection some 30
minutes is required for the development of the full
haemostatic effect of the drug. Any combination
of oral, intramuscular or intravenous administra-
tion may be adopted and some regimes make use
of all three routes (Hachen, 1967, personal com-
munication). Dosage is usually in the range of
5-20 mg/kg and in clinical use the drug appears
to be virtually non-toxic with no known contra-
indications.
Detailed consideration of the mode of action of
ethamsylate is beyond the scope of this paper, but
A. R. DE C. DEACOCK, F.F.A.R.C.S., Department of
Anaesthesia, Royal Free Hospital, London; DOREEN
M. BIRLEY, F.F.A.R.C.S., Department of Anaesthesia,
Barnet General Hospital, Barnet, Hertfordshire.
* Delandale Laboratories, Canterbury, Kent.
 ANTI-HAEMORRHAGIC ACTIVITY OF ETHAMSYLATE (DICYNENE)
it appears to be connected with blood platelet
activity and, in particular, to thromboplastin for-
mation and platelet agglutination (Hachen, 1964;
Raby and Coupier, 1964; Esteve and Laporte,
1965; Wayoff and Jeannin, 1965). Copley (1963)
and Johnson and others (1966) have stated that
capillary permeability is related to platelet activity
and there have been several reports concerning the
effect of ethamsylate on capillary wall resistance
(Raby and Coupier, 1964; Hachen, 1965a; Plisnier
and Annaert, 1965).
Evaluation of ethamsylate as an anti-haemorrha-
gic agent for use during surgery presents some
difficulty. Certain clinical studies have been based
upon estimations of the bleeding-time (Muller
1962; Cernea and Mazza, 1965; Hachen, 1965b;
Alavoine, Lefebvre and Delpy, 1966; Louis and
Paulus, 1966; Ribuot, 1966; Benoit, Michelet and
Gironet, 1967), but this is not necessarily closely
related to surgical haemorrhage. There have been
a number of reports of clinical trials on patients
undergoing surgery (Gray and Noble, 1966;
Hypher and Carpenter, 1968), but in work of this
type it is difficult to arrange adequately controlled
conditions because of the many variable factors
affecting bleeding and, in addition, accurate
measurement of blood loss is not easy. Possibly
because of these difficulties, the published work
does not always agree as to the value of etham-
sylate as a haemostatic and judgements based upon
"clinical impressions"—notoriously unreliable—
are similarly at variance. The work described in
the present report was undertaken in order to
determine the effect of ethamsylate on surgical
haemorrhage under closely controlled conditions.
METHOD
Animal experiment was selected as the basis for
this investigation since the required standardiza-
tion of technique would not have been possible in
the human subject. In order to produce valid
results it was considered necessary to employ a
"blind", placebo-controlled mediod. There was a
requirement, therefore, for an animal preparation
in which to compare the effects of trial drug and
placebo on haemorrhage from a "standard wound".
In accordance with its mode of action, outlined
above, ethamsylate is said to be most effective in
the control of capillary haemorrhage. For this
reason, it was desirable that the standard wound
19
should be such as to produce haemorrhage of this
type in order to reveal any haemostatic activity to
the best advantage. After several preliminary trials
using different animal preparations the following
experimental method was adopted.
Experimental technique.
The preparation consisted of the intact, anaes-
thetized pig and the standard wound was pro-
duced by means of an electric dermatome of the
type used clinically for the preparation of Thiersch
(split skin) grafts. The skin of the pig is similar
to that of man and it was found that application of
the dermatome produced capillary haemorrhage
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similar to that seen in the human subject. The
animals were all young females weighing between
20 and 35 kg when first used as subjects for the
trial and between 28 and 44 kg at the time of
completion of the work. They were housed (in
indoor sties) and fed in accordance with normal
farming practice.
Each animal was the subject of two experi-
ments, receiving on the one occasion ethamsylate
and on the other placebo (normal saline), both by
the intravenous route. In this way each animal
acted as its own control. For each animal ampoules
of placebo and of the trial drug were made avail-
able, the latter containing 1 g of ethamsylate in 8
ml solution. All ampoules were of similar type
and were identified only by a code number, bear-
ing one figure corresponding to that of die pig for
which they were intended and another to indicate
at which of the two experiments on diat animal
they should be given. On any one day only two
pigs were the subjects of experiments and the
preparation of the ampoules was so arranged that
one animal received the trial drug and the other
the placebo. This resulted in an even "spread" of
ethamsylate and placebo throughout the series and
also ensured that half of the animals received the
trial drug at the first experiment and placebo at
the second whilst for the remainder this sequence
was reversed. At the same time the random ele-
ment was retained in the allocation of trial drug
or placebo to each pair of pigs and, of course,
the person conducting the experiment had no
knowledge as to which substance had been ad-
ministered.
Animals were admitted to the experimental unit
for an acclimatization period of two weeks prior
20
to use in the trial. On the eve of each experiment
the site of operation was shaved and washed.
A standardized anaesthetic technique was em-
ployed, induction being by means of nitrous oxide
and halothane, with oxygen, a cuffed endotracheal
tube being inserted as soon as conditions per-
mitted. Thereafter, anaesthesia was maintained
with nitrous oxide 5 l./min, oxygen 2 l./min,
and halothane 2 per cent (delivered from a Fluotec
vaporizer).
After a stabilization period of 10 minutes the
contents of the appropriate coded ampoule were
given by intravenous injection into an ear vein.
Forty minutes later the dermatome was applied
to the lateral aspect of the thigh. The instrument
was set to cut at a depth of 0.05 inch
(1.27 mm) and a strip of partial thickness of
skin as nearly as possible 3 inches (7.6 cm) in
length was removed. The width of the strip was
governed by the size of the cutting blade which
was approximately 3 inches (7.6 cm) also. Ten
minutes later the blood which had collected on the
wound was removed by wiping quickly with a
large surgical swab. Any blood which trickled
beyond the area of the wound prior to wiping was
also absorbed on the swab, although this was
necessary in only a few cases. Care was taken not
to touch or otherwise disturb the wound itself
during the 10-minute waiting period. As soon as
the swab had been used it was resealed into a
nylon-film bag where it had been kept prior to
use and in which it had previously been weighed
to the nearest 0.001 g on an accurate balance. The
piece of skin which had been excised was sealed
into a second weighed nylon-film bag. Finally, the
dimensions of the wound were measured. Follow-
ing reweighing of the two nylon bags a process of
simple subtraction gave the weight of blood lost
and of skin removed, the latter serving as an indi-
cation of the depth of the wound, as mentioned
below.
The pulse rate of the animals was monitored
throughout by means of a pulse-meter and estima-
tions of the blood pressure were made using an
occlusion cuff in conjunction with the pulse-meter.
The temperature within the operating theatre was
thermostatically controlled. Measurements con-
firmed that a stable temperature was maintained
throughout the series of experiments.
There was an interval of three weeks between
BRITISH JOURNAL OF ANAESTHESIA
the two experiments on each animal in order to
allow full recovery from the effects of the first
before undertaking the second. Opposite limbs
were used on the two occasions and care was taken
to position the dermatome in the same way
throughout the series.
Venous blood samples were withdrawn from six
animals on both occasions on which they were
experimental subjects. This was done immediately
prior to the application of the dermatome. Blood-
platelet estimations were performed on these
samples for comparison with results obtained
using blood collected just before injection of the
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trial drug or placebo.
Twenty-two pigs were used in this work, forty-
three experiments being performed (only one ex-
periment was carried out on one animal—see
below).
RESULTS
Table I presents a summary of the results ob-
tained. Both experiments were successfully com-
pleted on each of the twenty-two pigs with the
exception of No. 21 which became sick after the
first trial and was destroyed. In the case of Nos.
1 and 2 it will be seen that the table is not com-
plete. These animals were the subjects of the first
two experiments, on the same day, and the blood
loss was estimated using a balance measuring only
to the nearest 0.5 g. It was considered that this
level of accuracy was not acceptable and no results
were recorded. For subsequent work a balance
accurate to 0.001 g was used, as described above.
For the reasons just given, pigs 1, 2 and 21 were
omitted from all comparative analyses.
It was found that the "standard wound" was
comparable in depth and size throughout the
series. Variations in area (all within the range
+ 11 to —18 per cent of the mean) were com-
pensated for by assessing haemorrhage on the
basis of blood loss per unit area.
The administration of ethamsylate produced no
observable effect on pulse rate or blood pressure,
these being comparable in the placebo and trial
drug experiments on each individual and, in fact,
throughout the series of animals as a whole. Plate-
let estimations on the venous blood samples from
six of the pigs showed no significant variation
between specimens taken before and after
administration of either placebo or the trial drug.
 TABLE I
Experimental results: tabulation of data.
Placebo Trial drug
Subject 1 2 3 4 5 6 1 2 3 4 5 6 A B
1 7.2X8.0 57.60 _ _ _ _ 7.7x8.0 61.60 6.07 0.0980 0.44 0.0071 _ _
2 7.7X7.4 56.98 5.72 0.1003 0.61 0.0107 7.1X8.0 56.80 _ _ _ _ _ _
3 7.9X8.2 64.78 5.03 0.0776 0.21 0.0032 7.7X8.0 61.60 6.10 0.0990 0.22 0.0035 -0.0003 0.9535
4 7.7 X 8.0 61.60 7.07 0.1147 2.80 0.0454 7.7 X 8.0 61.60 5.31 0.0862 0.58 0.0094 0.0360 4.8275
5 7.7X8.0 61.60 6.28 0.1019 0.25 0.0040 7.5X8.5 63.75 6.72 0.1054 0.09 0.0014 0.0026 2.7777
6 7.9X8.0 63.20 6.99 0.1106 0.76 0.0120 7.4X8.2 60.68 6.50 0.1071 0.63 0.0103 0.0016 1.2063
7 7.4X7.6 56.24 6.32 0.1123 7.80 0.1386 7.5X7.7 57.75 6.31 0.1092 1.70 0.0294 0.1092 4.5882
8 7.4X7.8 57.72 6.17 0.1068 1.26 0.0218 7.5x7.7 57.75 6.42 0.1111 0.51 0.0088 0.0129 2.4705
9 7.1X8.0 56.80 6.92 0.1218 0.93 0.0163 7.6X7.7 58.52 6.93 0.1184 1.36 0.0232 -0.0068 0.6838
10 7.4X7.7 56.98 5.97 0.1047 0.92 0.0161 7.6X7.9 60.04 7.07 0.1177 0.15 0.0024 0.0136 6.1333
11 7.5x7.7 57.75 5.60 0.0969 1.54 0.0266 7.5X7.5 56.25 6.08 0.1080 0.95 0.0168 0.0097 1.6210
12 7.0X7.2 50.40 5.57 0.1105 0.30 0.0059 7.6X7.8 59.28 6.10 0.1029 0.63 0.0106 -0.0046 0.4761
13 7.4X7.9 58.46 6.20 0.1060 2.45 0.0419 7.4X7.9 58.46 5.66 0.0968 0.79 0.0135 0.0283 3.1012
14 7.6X7.9 60.04 6.42 0.1069 1.11 0.0184 7.2x8.1 58.32 5.63 0.0965 1.13 0.0193 -0.0008 0.9823
15 7.5X7.8 58.50 6.56 0.1121 9.32 0.1593 7.6X7.7 58.52 7.37 0.1259 7.98 0.1363 0.0229 1.1679
16 7.2X7.8 56.16 6.50 0.1157 1.26 0.0224 7.3x7.1 51.83 6.20 0.1196 0.59 0.0113 0.0110 2.1355
17 7.4x7.7 56.98 7.73 0.1356 17.14 0.3013 7.2X8.3 59.76 7.37 0.1233 6.71 0.1122 0.1890 2.5543
18 7.4X7.8 57.72 7.10 0.1230 3.65 0.0632 7.3x7.8 56.94 7.58 0.1331 2.42 0.0425 0.0207 1.5082
19 7.3X7.7 56.21 7.60 0.1352 0.77 0.0136 6 8 X 7.0 47.60 6.65 0.1397 0.06 0.0012 0.0124 12.8333
20 7.5X7.9 59.25 8.00 0.1350 1.94 0.0327 7.2X7.6 54.72 6.50 0.1187 2.03 0.0370 -0.0043 0.9556
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21 - - - - - - 6.9X7.0 48.30 7.19 0.1488 0.26 0.0053 -

22 7.5X7.5 56.25 7.34 0.1304 0.17 0.0030 7.4X8.0 59.20 6.46 0.1091 0.52 0.0087 -0.0057 0.3269
n 19 20 20 19 21 21 19
Mean 59.27 2.7595 0.0478 58.03 1.4166 0.0243 0.0294
SE 0.9324 0.4536 0.0121
t 2.4266
P <0.05
Column l = Size of wound in cmXcm. Column 4=Depth of wound expressed as g/sq.cm.
Column 2=Area of wound in sq.cm. Column 5 = Blood loss in g.
Column 3=Weight of excised skin in g. Column 6=Blood loss in g/sq.cm.
Column A=Difference between blood loss under placebo and that under ethamsylate in g/sq.cm (i.e. placebo 6—trial drug 6).
Column B=Ratio of blood loss under placebo to that under ethamsylate (i.e. placebo 6/trial drug 6).
22 BRITISH JOURNAL OF ANAESTHESIA

Statistical interpretation. A better method of evaluation is to examine

Examination of the thickness of the excised skin
by comparing the weight per sq.cm in the placebo
and in the trial drug experiments shows that the
difference is not significantly different from zero
(t=0.5306, P=0.6). This suggests that variation
in the depth of the wound may be excluded as a
source of error.
Evaluation of the data obtained may be carried
out in several ways. If the mean blood loss per
sq.cm in the placebo experiments (0.0478 g/sq.cm)
is compared with that in the trial drug experi-
ments (0.0243 g/sq.cm) it is found that the
the effect of the drug on each individual in turn
and then to pool the data (see column A in
table I). When tested against the null hypothesis
that the drug is ineffective this method gives a
value of <=2.4266, P<0.05. This is an acceptable
level of significance.
A desirable property of a haemostatic drug is
that it should control heavy bleeding at least as
well as it controls light bleeding. From the results,
it appears that the largest difference between the
blood loss in the placebo experiment and that in
the trial drug experiment occurred in those ani-

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difference is not significant. This is only to be
expected in view of the large degree of between-
subject variation and it was in anticipation of this
that the investigation was so arranged that each
animal could act as its own control.
mals where the unmodified haemorrhage was
greatest, i.e. ethamsyiate appeared to be most
effective in individuals having a tendency to bleed
heavily. This apparent effect may be examined
with the aid of the graph shown in figure 2 where

160- e
One point off chart
(Subject 17)

140-
e

s
X 120-
E
u
er
0)
100-

! FIG. 2
% Relationship between blood loss under
placebo (ordinate) and difference
Blood-loas tinder |

ao- between blood loss under placebo

and under ethamsyiate (abscissa)
plotted for 19 animals concerned in
the comparative analysis.
s
60-

e
40-
<B

ffi
e
Regression coefficient 0-5840
Correlation coefficient 0-9126

.•1
—20 0 20 40 60 80 tOO

Reduction in blood-loss following ethamsyiate (g/sq.cm x 101)

ANTI-HAEMORRHAGIC ACTIVITY OF ETHAMSYLATE (DICYNENE) 23

the unmodified (placebo) blood loss is plotted
against the difference between that and the blood
loss after ethamsylate for each of the nineteen
individuals concerned in the comparative analy-
ses. The graph indicates a direct relationship be-
tween the severity of the unmodified bleeding and
the reduction in bleeding following the adminis-
tration of ethamsylate. The associated regression
coefficient is 0.5840 and the correlation coefficient
is 0.9126, both very highly significant, P<0.001.
An additional inference from the high value of the
correlation coefficient is that the experimental
method adopted is satisfactory for the task in
hand.
Copley, A. L. (1963). [Role of fibrin and fibrinolysis
in the integrity of the vascular wall.] Hemostase,
3, 13.
Esteve, A., and Laporte, J. (1965). Au sujet de l'inter-
action dextran—141-E. Hemostase, S, 145.
Gray, A. J., and Noble, W. A. (1966). Ethamsylate and
blood loss during dissection tonsillectomy. Brit. J.
Anaesth., 38, 827.
Hachen, H. J. (1964). [Haemostasis during prostatec-
tomy. Clinical trial with a new haemostatic:
cyclonamine.] Thesis 2916 presented at the
Faculty of Medicine, Geneva University.
(1965a). [The effect of Dicynone upon capillary
permeability. Description and investigation of a
new method.] Med. clinica, 6, 412.
(1965b). Contributions to the experimental and
clinical investigation of the haemostatic Dicynone.
De Med. Tuenda, 3, 91.

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Huygebaert, J. (1949). L'adrenoxyl comme hemo-
Confirmation of the belief that the suppression statique en oto-rhino-laryngologie. Assises Med.,
of bleeding is related to the bleeding tendency is 5, 295.
Hypher, T., and Carpenter, R. (1968). Cyclonamine in
obtained by examining the ratio of blood loss (in cataract surgery: a clinical trial. Brit. J. Ophthal,
g/sq.cm) under placebo to that under ethamsylate. 52, 375.
The values of this ratio in the nineteen animals Johnson, S. A., Van Horn, D. L., Pederson, N. J.,
and Marr, J. (1966). The function of platelets: a
concerned in the comparative analyses are shown review. Transfusion (Philad.), 6, 3.
in table I (column B). For these nineteen values Louis, J., and Paulus, J. M. (1966). [Comparative study
of the ratio, the mean value of their logarithm is of the action of Dicynone and a placebo on bleed-
ing time and capillary resistance. Double-blind
0.2525 and its Standard Error is 0.0915. This technique.] Paper read at International Colloquium
gives a value of ( = 2.7600, P = 0.007. on actions and effects of Dicynone, Barcelona,
October 1966.
Muller, A. (1962). [The use of a new synthetic
CONCLUSIONS haemostatic agent, Dicynone (cyclonamine) in
practical otorhinolaryngology.] Praxis, 21, 552.
Under the conditions described: Plisnier, H., and Annaert, R. (1965). fitude de nouvelle
(1) Ethamsylate is shown to be effective in substance antihemogenique (cyclonamine). Acta
reducing bleeding. oto-rhino-laryng., belg., 19, 950.
(2) The magnitude of the reduction is directly Raby,haemostaticC , and Coupier, J. (1964). [A new synthetic
and antihaemorrhagic] Proc. X Congr.
proportional to the severity of the unmodified int. Soc. Blood Transfusion, Stockholm, 1964,
bleeding. part 5, p. 1241.
Ribuot, E. (1966). [Clinical study of a new antihaemor-
rhagic and haemostatic in odontology.] Rev. franc.
ACKNOWLEDGEMENTS Odontostomat., 13, 213.
We wish to express our thanks to Messrs. Baxter Wayoff, Alexandre, and Jeannin, C. (1965). Le 141
Laboratories Ltd., for the provision of supplies of M.D. (Dicynone) en O.R.L. Nouvel hemostatique
ethamsylate and placebo; to Messrs. Laboratoires Om, et antihemorragique de synthese. Paper read to
Geneva, for very generous financial support; and to the Society of Laryngology of Paris Hospitals,
Mr. D. W. Clarke, for his invaluable and skilled assis- June 21, 1965.
tance in the preparation and care of the animals and
in the administration of anaesthesia. L'EFFET ANTIHEMORRHAGIQUE DE
L'ETHAMSYLATE ("DICYNENE"): UNE
REFERENCES ETUDE PRELIMINAIRE
Alavoine, J., Lefebvre, P., and Delpy, J. (1966). [The SOMMAIRE
indications for Dicynone in otorhinolaryngology.]
Rev. Laryng. (Bordeaux), 87, 610. L'effet hemostatique de l'ethamsylate a 6ti imdte a
Beal, F., and Gondaert, E. (1947). La semicarbazone l'aide d'un essai "aveugle" controle, comprenant 43
de l'adrenochrome. Rev. Stomat. (Paris), 48, 616. experiences sur line serie de 22 cochons. La prepara-
Benoit, P., Michelet, F. X., and Gironet, J. (1967). tion experimentale etait constituee par une blessure
[Effect of an antihaemorrhagic, 141-M.D. or standard, faite avec un dermatome electrique et causant
Dicynone, in odontostomatological practice.] Rev. une hemorrhagie capillaire La perte de sang a ete
Odontostomat., Midi, France, 25, 166. estimee en pesant les compresses. L'evaluation statis-
Cernea, P., and Mazza, R. (1965). [The use of a new tique des resultats indique que l'ithamsylate reduit
antihaemorrhagic agent in stomatology.] Actualites efficacement le saignemenl et que le degre de cette
odontostomat., 72, 447. reduction est directement proportionnclle a la severite
24
du saignement non-modifie. Aucun effet du medica-
ment n'a ete observe sur le pouls, la pression sanguine
ou le nombre de thrombocytes.
DIE ANTIHAMORRHAGISCHE AKTIVITAT
VON ATHAMSYLAT ("DICYNEN"): EINE
EXPERIMENTELLE STUDIE
ZUSAMMENFASSUNG
Der hamostatische Effekt von Athamsylat wurde
mittels eines kontrollierten Blindversuchs untersucht,
in dessen Verlauf 43 Experimente an einer Gruppe
CORRESPONDENCE
THE INFLUENCE OF THE KALLIKREINTRYPSIN INACTIVATOR
"TRASYLOL" ON THE SERUM CHOLINESTERASE
Sir,—Thank you for the opportunity of replying to
Dr. Doenicke's letter.
It is true that in some cases, the serum esterase
activity was higher than the initial values, 60 min after
Trasylol administration. We have pointed out that the
inhibitory activity of Trasylol on the serum cholin-
esterase lasted for 30 min approximately and that
serum esterase activities returned to the initial values
or surpassed them 60 min after Trasylol administra-
tion. The return to even higher values for a relatively
short period of time, after a previous inhibition, is a
well-known pharmacological phenomenon and this fact
confirms in our opinion our findings, and should not
arouse any doubts, as Dr. Doenicke thinks, about the
method used.
The blood samples were centrifuged immediately
after their withdrawal, then they were kept in the re-
frigerator (—2° to —4°C) and the determinations of
serum cholinesterase were done as quickly as possible
(in none of the cases was the time from the withdrawal
of the blood until the determination was done, greater
than 60 min).
None of the patients had an operation or was given
an anaesthetic while the enzyme was determined. Most
of them were in the medical wards, suffering from
different pathological conditions (as can be seen from
tables I and II) and others were in the surgical wards
awaiting surgery, or they had had an operation a few
days previously. Incidentally, case No. 4 was myself,
and I had my serum cholinesterase activity determined
too, before and after Trasylol administration.
No other drugs were administered to those patients
between the time when the control sample was taken
and the last sample of blood was withdrawn (except
Trasylol) and there is no doubt that Trasylol caused
the enzyme inhibition.
We did not claim that the prolonged apnoea observed
in our three cases which received Trasylol under
general anaesthesia with muscle relaxants (Brit. J.
Anaesth. (1966), 38, 838) was due to the inhibition of
BRITISH JOURNAL OF ANAESTHESIA
von 22 Schweinen durchgefiihrt wurden. Die experi-
mentelle Vorbereitung der Versuchstiere bestand im
Setzen einer Standard-Wunde mit einem elektrischen
Dermatom und wurde so durchgefiihrt, dafl es zu
einer kapillaren Blutung kam. Der Blutverlust wurde
durch Wiegen der Blutabstriche geschatzt. Die
statistische Auswertung der Resultate ergibt, dafi
Athamsylat eine Reduzierung der Blutung bewirkt und
dafi das Ausmafi der Reduzierung direkt proportional
dem Schweregrad der unmodifizierten Blutung ist.
Eine Wirkung des Arzneimittels auf Pulsfrequenz,
Blutdruck oder Zahl der Thrombozyten wurde nicht
beobachtet.
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cholinesterase by Trasylol, as two of those cases had
been given rubocurarine as a relaxant. Certainly some
other cause is to be blamed at least for the cases in
which the patients received tubocurarine. Nevertheless,
Trasylol temporarily inhibits the serum cholinesterase,
and we postulated that this too could be a cause of
prolonged apnoea, for a relatively short period of time,
at least in some patients who have suxamethonium as
a relaxant, and in whom their serum cholinesterase
will be inhibited in a higher degree by Trasylol.
G. CHASAPAKIS
Athens
CARDIOVASCULAR EFFECTS OF INTRAVENOUS
ANAESTHETICS IN THE DOG
Sir,—Drs. Conway, Ellis and King are to be congratu-
lated on the excellence of their article published in the
October issue of the Journal. We feel, however, that
important results have bsen omitted. To quote:
"Drugs were given through the catheter into the
inferior vena cava at a constant speed of injection".
It is not clear whether "constant speed" refers to total
dose of drug or whether twice the time was taken to
inject the double dose. The time to make the injection
is also omitted; this is vital if their results are to be
compared with similar work on either animals or man.
A. D. CLARKE
P. W. JACKSON
Manchester
REFERENCE
Conway, C. M., Ellis, D. B., and King, N. W. (1968).
A comparison of the acute haemodynamic effects
of thiopentone, methohexitone and propanidid in
the dog. Brit. J. Anaesth., 40, 736.
Sir,—The standard speed referred to in our paper was
such that the mass of drugs at each dose level was
given over 20 seconds.
C. M. CONWAY
D. B. ELLIS
N. W. KING London