Anaesthesia ~ 0 1 2 3110 4 October 1968

___- __ -- _- _.

Chloroform anaesthesia
A clinical comparison of chloroform and halothane administered from
precision vaporisers

S. A. Oduntan

Chloroform and halothane are potent anaesthetic agents which are also
chemically related. Halothane was introduced into clinical anaesthesia in
1956 at a time when anaesthesia had been fully developed. Chloroform
was first used in 1847 by James Young Simpson when anaesthesia was in
its infancy. It is reported in the literature that John Snow gave 4,000
chloroform anaesthetics without a single death, but for many years the
use of chloroform was fraught with dangers especially in the hands of the
unskilled administrator. The difficulties that were encountered were two-
fold: sudden cardiac arrest (probably resulting from direct chemical or
reflex nervous stimuli leading to ventricular fibrillation or syncope132 and
delayed chloroform poisoning due to hepatic damage.
Recent studies have, however, indicated that chloroform may be a safer
agent than was previously supposed. Pohle 3 showed that chloroform
anaesthesia did not produce hepatic damage any more frequently than the
other commonly used anaesthetic agents provided that it was administered
by highly trained physicians who gave special attention to the maintenance
of adequate gaseous exchange with a high concentration of inspired
oxygen.
Sims and his colleagues4, who, like Pohle3, wrote from the University of
Wisconsin confirm his work. They report that hypoxia or hypercarbia
considerably increase the frequency and severity of hepatic injury, as
judged by a battery of liver function tests, irrespective of the anaesthetic
agent which is used. With optimal tensions of oxygen and carbon-dioxide
in the blood they found that chloroform and ether gave roughly the same
amount of hepatic impairment.
Waters5 in his important monograph which was published in 1951
gave a call for a change of heart towards the safety of chloroform anaes-
thesia. More recently Jones6 in 1963 and Whitaker & Jones7 in 1964
found that chloroform anaesthesia when administered with care from a
precision vaporiser is just as safe as halothane.
With all this evidence in mind, it was decided to investigate the respir-
atory and circulatory effects of chloroform and to compare them with those
S. A . Oriunfan, A I B , FFARCSI, Seiirot Lectrrrer, Departmenf of Anaesfhesia, Universify
College Hospital, Ibndoii, Niprici.

552
 13652044, 1968, 4, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1968.tb00118.x by Iraq Hinari NPL, Wiley Online Library on [25/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthesia 1,0123 110 4 October 1968

of halothane anaesthesia and to study the effects of the two agents on the
liver as judged by a number of tests of hepatic function.

METHOD

In this study, 50 cases of chloroform anacsthesia were compared with 50

similar cases of halothane anaesthesia under the same clinical conditions.
Patients with history of jaundice, liver disease and severe malnutrition
were eliminated from the series. A single anaesthetist administered all the
anaesthetics. The patients were allocated to either group by random
sampling. The anaesthetic vapours were delivered from precision
vaporisers - the Fluotec for the halothane and Chlorotec for the chloro-
form. A non-rebreathing circuit with a Ruben valve and high flow of
nitrous oxide and oxygen (up to 8-10 litres for adults) were used. The
concentration of oxygen in the inspired mixture was never less than 33; %,.
Prernedication consisted of atropine 0.6mg only. Induction of anaes-
thesia was achieved with the inhalational agent alone or with a sleeping
dose of thiopentone which did not exceed 25Omg for an adult. When using
the inhalational agent for induction of anaesthesia, the vaporiser was set
initially at 1 % and this was increased by 0.5 % every 4 breaths or so until
a concentration of 3 % was reached for chloroform and 4 % for halothane.
When it was deemed essential for the particular surgical operation, endo-
tracheal intubation was performed using suxamethonium. As soon as an
appropriate anaesthetic depth for the surgical procedure was achieved, the
concentration of the inhalational agent was gradually reduced to main-
tenance level; this was between 1.0 and 1.5% for halothane and 0.75 and
1.O % for chloroform. All patients breathed spontaneously except during
intubation.
The effects of each anaesthetic agent on systolic blood pressure, pulse,
respiratory rate, minute volume and on the electrocardiograph were re-
corded as soon as a stable anaesthetic state had been reached, but before
surgery was started; this was usually between 5 and 10 minutes after the
induction of anaesthesia. The duration and quality of anaesthesia, the
recovery (waking-up) time and the post-operative condition of the patient
and the incidence of nausea and vomiting were also noted. Blood was
taken for liver function studies before the induction of anaesthesia, after
24 hours and on the 7th post-operative day.

RESULTS

The two agents were used for a variety of operations for which general
anaesthesia is usually considered acceptable. The groups were comparable
in respect of type of procedure (table 1) and age, sex, weight and duration
of anaesthesia (tables 2 and 3). The induction techniques employed are
shown in table 4.
553
 13652044, 1968, 4, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1968.tb00118.x by Iraq Hinari NPL, Wiley Online Library on [25/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthesia pol23 no 4 October 1968

TABLE 1
Operations p brrned
CHLOROFORM HALOTHANE
~~

G.vnuer.ologica1
Dilatation and curettage of cervix 5 3
Colporrhaphy 2. 1
Repair of vesicwvaginal fistula 3 1
Ophthalmic
Evisceration of eye 4 5
Ear, nose and rhrooc
Caldwell-Luc 5 7
Antrostomy 4 2
Mastoidectomy 3 5
General siirgery
Herniorrhaphy I2 15
Orthopaedic
Osteotomy-femur 7 4
Open-reduction 3 2
Verir*srrrgerv
lntra-cranial 2 4
TOTAL 50 50

TABLE 2

Sex distribution M:F

Age (years) mean f S D
Ser, age and body weight

Body weight (Ibs) meanfSD

I CHLOROFORM
I 27:23
31.8 f l I .97
128 f30.44
1
I HAWTHANE

24~26
30.9f 11.2
132*32.06

TABLE 3
Durution of anaesthesia
) NUMBER OF ANAESTHETICS

5 3
11-20 9
20 - 60 28
60- 120 6
120- 4
TlITAt 1 50 I 50

TABLE 4
Induction techniques
I CHLOROFORM I HALOIWANE I TOTAL

1
1 1
With thiopentone 40 35
Without thiopentone 10 15
I
ig
Total number of
patients 50 50 100

TABLE 5
Effertc on cardic-pulmonary Jiinction and the gastro-intestinal tract
1 CHLOROFORM 1 HALOTHANE

Minute volume
mean fSD
*Number showing tachypnoea
7.25*0.96
10
1 4.60&0.36
22
Number showing bradycardia 7 : 9
*Number showing tachycardia 13 17
1
~

Number showing arrythmia 0

*Rise in BP 19' 8
*Fall in BP I 10 25
Retching 5 1

554
 13652044, 1968, 4, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1968.tb00118.x by Iraq Hinari NPL, Wiley Online Library on [25/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthesia vol23 no 4 October I968

Table 5 shows the effects of the two agents on the cardio-pulmonary

and gastro-intestinal systems. It was our impression that chloroform
stimulated respiration and halothane depressed it. Certainly, in so far as a
comparison is possible, minute volumes (taken when a stable anaesthetic
state had been established but before surgery was started usually 5 to 10
minutes after induction), were, on average, lower in the halothane series
than in the chloroform series.
Nearly 50 % in the halothane group developed tachypnoea as against
20 % in the chloroform group; tachypnoea was taken as being a respiratory
rate of 30 per minute or faster.
Bradycardia was defined as a decrease in pulse rate in excess of 10% of
the pre-anaesthetic level, the incidence was nearly the same in the two
groups. In most instances the bradycardia occurred when the operation
was of long duration and the atropine premedication had worn off. The
bradycardia was easily reversed by intravenous atropine. Tachycardia
was defined as a rise in pulse rate in excess of 10% of the pre-anaesthetic
level; the incidence was found to be more common in the halothane group
than in the chloroform group.
The incidence of arrythmia was very low in the chloroform group and
completely absent in the halothane group. 40 % in the chloroform group
showed a rise in systolic blood pressure as against 16 % in the halothane
group. There was a fall in systolic BP in 50 of the patients in the halothane

TABLE 6
Recovery time
NUMBER OF PATIENTS
WAKING TIME IN MINUTES

0- 10 minutes
10-20 ,,
Over 20 ,, 0

TABLE 7
Liver function resis

I___-
I CHLOROFORM I HALOTHANE

1
LIVER FUNCTION
TEST

Bilirubin (mg):
range
mean zk SD
PRE-OP

0.3-1.3
0.692*0.27
2 4 ~ 0 ~ ~7THDAY
POST-OP

0.3-1.8
0.716f0.39
s
POST*P

I0.1-1.0
0.512f0.21
i
0.3-1.4
PRE-OP

0.680f0.25
~ ~ H O U R S 7THDAY
POST-OP

0.3-1.8
0.722*0.44
~- POST-P

0.1-1.2
0.502jz0.18
Alkaline
phosphatase
(KA units):
range 5 - 18 5-20 5 - 14 5 - 18 5-20 5-16
meanzkSD 10.24k4.59 10.32jz5.36 9.16f3.28 10.22f3.28 10.36f5.41 9.08f3.32
SOOT
range 6-38 6-40 7 - 34 6 - 36 6-42 6 - 34
meanzkSD 15.32k9.67 15.4f8.75 17.44f6.89 15.34&9.71 15.43f8.65 17.20f7.20
SOPT
range 7 - 28 2-20 2-23 7-26 2-22 2-20
meankSD 14.56*5.54 9.72*4.15 12.56f5.66 14.52zk5.40 10.69f4.54 12.82f5.57
Thymol turbidity
range 1-3 1-2 1-3 1-3 1-2 1-3
mean*SD 1.48f0.64 1.44&0.50 1.32jz0.61 1.46f0.60 1.4310.55 1.38jz0.54
Thymol flocculation -ve -ve -ve -ve -ve -ve
 13652044, 1968, 4, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1968.tb00118.x by Iraq Hinari NPL, Wiley Online Library on [25/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Atmesthesin 110123 no 4 October 1968

group, falls occurred in only 20 ”/, of the chloroform group. The effects of
the two agents i n causing nausea and \orniting were also studied. 20% of
the chloroform group had nausea and vomiting as against 2x in the
halothane group.
The recovery time was defined as the time elapsing between the end of
the anaesthetic and the time when the patient responded to simple orders
and questions. Table 6 indicates that the recovery time is more prolonged
after chloroform anaesthesia than after halothane anaesthesia.
Table 7 shows the effccts of the tivo agents on liver function tests. N o
deleterious effects on the li\er could be chown in either group by the
battery of tests employed.

DISCUSSION

Chloroform and halothane are non-flammable anaesthetic agents with

high boiling points. Chloroform is cheap whereas halothane is expensive.
If it can be shown that chloroform is comparable with halothane with
respect to the quality of anaesthesia and safety to the patient, it might
again take its place as a popular anaesthetic agent. In the underdeveloped
countrics, where money is still a great problem, chloroform anaesthesia
may play a very important role if it can be administered with the care and
attention that the use of such a potent anaesthetic agent demands. Chloro-
form,’air enriched with oxygen would be a simple and cheap anaesthetic
which any small peripheral hospital could afford. A precision vaporiser
such as the Chlorotec would be essential.
Respiratory volumes (minute volumes) appeared to be increased under
chloroform anaesthesia. This stimulation of respiration is a desirable
effect as it will help to keep arterial P c o ~ ,p H and Po2 within normal
limits. The bradycardia that was noticed in the two groups suggests that
premedication with atropine is desirable. Tachycardia was more common
in the halothane group; this is probably due to its lack of analgesic
property. No analgesic drug was given with the premedication in this
series.
Cardiac syncope is perhaps the most feared complication of chloroform
anaesthesia. No such incident occurred in this series. Only two cases of
arrhythmias were noticed in the chloroform series ;these were extrasystoles.
As regards arrythmia formation during anaesthesia abnormal levels of
Pco2, Po2 and pH are probably just as important as the agent itself. No
exogenous adrenaline was permitted in either series.
Recovery after chloroform anaesthesia is not as rapid as after halothane,
but it is important to note that the protective reflexes were regained just as
quickly after chloroform as after halothane.
The effects of the two agents on liver function appear not to differ at all.
The results show that with the technique employed neither agent caused
556
 13652044, 1968, 4, Downloaded from https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1968.tb00118.x by Iraq Hinari NPL, Wiley Online Library on [25/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
huesthesin 110123 no 4 October I968

hepatic damage as judged by the particular liver function tests which were
used. Great attention was paid to ensuring adequate oxygenation, efficient
removal of carbon-dioxide and the maintenance of adequate blood
pressure during the administration of these anaesthetics. Earlier workers
3 9 4 , 8 have shown that hypoxia, hypercapnia or both considerably increase
the frequency and severity of hepatic damage irrespective of the anaes-
thetic agent used.

SUMMARY

50 cases of chloroform anaesthesia were compared with 50 similar cases

of halothane anaesthesia under the same clinical conditions. The effects of
the two agents on the respiratory and cardiovascular system and on liver
function were studied. Chloroform anaesthesia was found to be comparable
with halothane anaesthesia when it is administered with the care and
attention which the use of any potent anaesthetic agent demands.
It is suggested that chloroform anaesthesia should be re-investigated
further with a view to popularising its use in the under-developed countries
where expense is still a great problem.
Ackno w~lecigeinetits
My thanks are due to Professor V. A. Ngu and his surgical colleagues at the University
College Hospital, Ibadan, who allowed this work to be carried out o n their patients, to
Mr I. Oforofua of the Department of Chemical Pathology, UCH, lbadan for performing
all the liver function tests and to D r L. M. Beckham, Head of the Department of
Anaesthesia for reading the script. I am most grateful to Cyprane Ltd for the loan of a
Chlorotec vaporizer without which this work would have been impossible.

Rejerences
1 EMBLEY, E. H. (1902). The causation of death during the administration of chloroform.
Br. med. J., I , 951
2 LEVY, A. G . (1922). ChloruJbrtn Airnesfhesin. London: John Bale, Sons and Danielsson
3 POHLE, F. J. (1948). Anesthesia and liver function, Wis. med. J., 47,476
4 SIMS, J. L . , MORRIS, L. E., ORTH, o. s. and WATERS, R. M. (1951). The influence of oxygen
and carbon-dioxide levels during anesthesia upon postsurgical hepatic damage.
J. Lab. din. Med., 38, 388
5 WATERS, R . M. Ed. (1951). Cldoroform: A study crffer 100 years. Wisconsin: University
of Wisconsin Press
6 JONES, c. s. (1963). A clinical comparison of halothane and chloroform anaesthesia.
Ccirr. Res. Anesth. Analg., 42, 348
7 WWITAKER, A. M. and JONES, c. s. (1965). Report of 1,500 chloroform anesthetics
administered with a precision vaporizer. Curr. Res. Anesth. Analg., 44, 60
8 GOLDSCHMIDT, s., RAVDIN, I. s. and LUCK& 8 . (1937). Anesthesia and liver damage;
The protective action of oxygen against the necrotising effect of certain anesthetics
on the liver. J. Phnrniac. exp. Tl7er., 59, I

557