EFFECT OF TETRAETHYLAMMONIUM
CHLORIDE
(ETAMON
CHLORIDE)
ON
MUSCLE
SPASM
IN POLIOMYELITIS
By DWAIN N. WALCHER,M.D., JOHNR. SCOTT,M.D., ANDFRANCESC. EKSTAM,R.P.T.
Indianapolis
T HE constant search for improvement and simplification of the present accepted form of treatment of muscle spasm in the acute poliomyelitis patient prompted the authors to repeat the work of L@nnon and Braudo' when tetraethylammonium chloride
(etamon
chloride*)wasmadeavailable
in June1949.Thetetraethylammonium
ionhas
been shown by Acheson and Moe2 to act as a blocking agent in the autonomic ganglia.
Though
the total number of patients
(259)
admitted to this hospital in 1949 with
the diagnosis of acute poliomyelitis far exceeded that of any previous year, many patients were found to be unsuited to this particular study, as they had either respiratory, bulbar
or encephalitic
symptoms. None of these patients was placed on tetraethylammonium
chloride as an adverse course of events in these more complicated cases could not easily be attributed to the disease and absolutely dissociated from the therapy. Patients whose spasm was early, transient and unassociated with the ultimate development of true muscle weakness were not included in the study. No further selection of cases was made.
At times not all patients available were used since detailed observations could not be
recorded on more than five patients at a time.
Preliminary work was done with tetraethylammonium chloride, administering it intra muscularly and intravenously in varying amounts. The patients complained of moderate
local pain when the medication was given intramuscularly. Adequate relaxation for physical therapy was obtained with 7 mg./kg. intravenously and, therefore, a greater dosage was not attempted. The intravenous route with a standard dosage of 7 mg./kg. was thus chosen for the study. The transient side effects previously desctibed were noted
in these patients whenever the medication was given. All experienced diplopia, loss of
accommodation, tingling parasthesias, metallic taste in the mouth, and ptosis. An occa sional patient experienced nausea. These symptoms usually were present within five minutes following injection and remained for 45 to 60 minutes. Since all were bed patients, no one complained of weakness or tiredness following injections. Tetraethylam monium chloride was given in the morning and again in the afternoon. A senior extern was in constant observation for several hours after administration of the medication, noting subjective comments and recording blood pressure determinations. Prior to the administration of tetraethylammonium chloride the mean blood pressure recording was 116/76 mm.Hg; within five minutes the mean recording was 108/74 mm.Hg. Thereafter there was a gradual return to normal over the next two hours.
The control group received warm, moist packs which were applied by the nursing staff
From the Department of Pediatrics and the Division of Physical Therapy, Department of Orthopedics, Indiana University Medical Center, Indianapolis.
Aided by grants from the James Whitcomb Riley Memorial Association. (Received for publication Aug. 17, 1950.)
TETRAETHYLAMMONIUM
CHLORIDE
IN POLIOMYELITIS
525
in the currently
accepted manner.
Each patient
received four packs daily except on
Sunday. None of the patients was packed during the night.
Twice daily both groups received physical therapy consisting of muscle stretching to
the point of tolerance. With few exceptions the same therapist was involved throughout
the entire study, so that the degree of stretching was more nearly constant. Measurements
were obtained by only one of the authors (F.E. ) to avoid variation in determining the
range of motion. Changes in the range of motion of the joints studied were measured in
angular degrees with a goniometer. Patients were not included in the study until they had
become afebrile, at which time the first goniometer measurement was taken. Subsequent measurements were made at 1 to 6 day intervals: Observations were terminated at times
TABLE 1 Hie FLEXION—PACKGROUP
Total angular Average daily
Patient degrees of Total days studied improvement in (l@ improvement angular degrees
1 15 15 1.00 0.0196
2 0 11 0.00 1.2996
3 25 15 1.67 0.2809
4 15 18 0.83 0.0961
5 10 18 0.56 0.3364
6 10 11 0.91 0.0329
7 10 11 0.91 0.0529
8 35 12 2.92 3.1684
9 10 11 0.91 0.0529
10 15 15 1.00 0.0196
11 20 12 1.67 0.2809
12 20 15 1.33 0.0361
N1=12 X=1.14 @d,2=5.6963
somewhat prematurely for lack of bed space and the necessity for transferring the patients to a convalescent center.
Convulsions occurred in one patient who had been given tetraethylammonium chloride. He received intramuscular medication for two days in the preliminary study, following
which he received intravenous
tetraethylammonium
chloride twice daily, being given
7 mg./kg. During the evening of the fifth day he had two mild generalized convulsions lasting 2 to 3 minutes and 30 seconds, respectively. He was removed from the tetra
ethylammonium chloride series and, though his improvement was impressive, the infor mation was not included in the statistical analysis because of the short duration of the
observations. He received packs throughout the remainder of his hospitalization. An
electroencephalogram recorded five days after the convulsions consisted of an irregular 7 to 9/second activity with many bursts of hypersynchronous 3 to 5/second waves. These
findings suggest that the slow activity was due to a diffuse cerebral disorder. The patient
complained of headache, vomited frequently, and was lethargic for nine days. Thereafter
his convalescence was uneventful. An EEG seven months later was normal.
did not have equivalent involvement. A total of 232 muscle functions were thus evaluated. Observations were recorded for hip flexion, knee flexion, hip adduction, hip abduction,
dorsiflexion,
knee extension, elbow extension in the neutral position, elbow extension
with pronation, shoulder abduction, elbow extension with supination, shoulder flexion
with the elbow flexed, shoulder flexion with the elbow extended, and wrist extension.
It was not possible to devise an accurate means of recording variations in the spasm of the neck and back muscles.
An example of the manner in which the data were recorded is given in table 1. In
this group where hip flexion was studied using hot packs there were 12 (N, 12) pa
tients. The average daily improvement in angular degrees was 1. 14 (X, = 1. 14) . The
sum of the square of the deviation of the average daily improvement for each patient from
‘l'ABLE 2
t AND 1' VALUES FOR FuNcTioNs STUDIED
t @i N, X2 N2 P
Hipflexion
Knee flexion
0.1209
0 .82361.14 1.4912 111.19 1.0517
> .90 17 > .40Hipadduction Hip abduction Dorsiflexion . 0.5889 0.0239 0 .38031.11 0.82 0 .3410 12 131.40 0.83 0 .2619 > .50 16 > .90 15 > .70Knee
extension 0 .02231 .04101 .0318 >
.90Elbowextension (neutral) Elbow extension with pronation
Shoulder abduction 1.1515 0 .4938 I .92242.12 1.67 0.922 2 80.89 1 .05 2.523 > .30 3 > .60 4 > .05, <.10Elbow
extension with supination ....
Shoulder flexion (elbow flexed) Shoulder flexion (elbow extended) - - . . Wrist extension I .6456 0. 7804 0 .2915 0 .24432.02 1.32
1 . 63 0 . 822
9 6 90.67 2 .62 2 .05 0 .983 > .10 3 > .40 3 > .70 5 > .80
the mean of the daily improvement for the group was 5.6963 The data obtained were subjected to the Fisher t test using
I'
@d12+@d2'
o-=i1/p, N1+N,—2
1Lx1_@2 I _____
@
N1+N2
(@d12 = 5.6963). the following formulae:
— the sum of the square of the deviation of the average daily improvement for
each patient from the mean of the daily improvement of the group.
N, = the number of patients in the pack series.
N2 _ the number of patients in the tetraethylammonium chloride series.
@1= the average daily improvement in the pack series.
x2
the averagedailyimprovementin the tetraethylammonium
chlorideseries.
TETRAETHYLAMMONIUM CHLORIDE IN POLIOMYELITIS 527
functions fell below 2. That for elbow extension (neutral) was 1.1515, for shoulder abduction, 1.9224, and for elbow extension with supination, 1.6456. When compared
with the P value the only one of possible significance was that of shoulder abduction with a value of >.05 and <.10. This gave preference to the etamon chloride group over the pack group. From the other figures one could not say that the etamon chloride group was either better or worse than the pack group, since the t values ranged from .0223 to .8236, and the P values ranged from > . 10 to > .90.
DISCUSSION
From a statistical analysis of the data one can not draw categorical conclusions from the
study, as the total number of patients involved was not sufficiently great. However, one
can say that there was no significant difference between the results of the two groups. If spasm in the neck and back could have been recorded, a more complete evaluation of
the two methods of treatment would have been forthcoming. The impression was that this spasm did not respond well to either form of therapy, and that its resolution, there
fore, becomes of significance in such a study.
Lannon and Braudo reported dramatic results with the use of tetraethylammonium chloride, particularly when it was given in amounts greater than the recommended
7 mg./kg. intravenously. In this series that single dosage was not exceeded. Additional data not reported in detail here were obtained to show that increasing the total daily
dosage by more frequent administration of the medication did not produce significant
variation in the reduction of spasm. Perhaps the discrepancy in the resolution of spasm observed by the present investigators and that observed by Lannon and Braudo can
partially be explained by the fact that all patients included in this series were sufficiently
involved to be ultimately paralytic.
Certainly the ward personnel preferred the tetraethylammonium chloride routine to
the pack routine, for it was time-saving for the nurses. Many patients preferred
the
intravenous medication to packing, and when they were placed on pack routine prepara tory to transfer to the convalescent home, they voluntarily requested return to the
intravenous treatment.
SU M MARY
A series of 232 muscle functions were carefully evaluated on 17 patients, comparing
the results obtained in the reduction of spasm using the intravenous administration of tetraethylammonium chloride (etamon chloride) with frequent stretching as opposed to the conventional hot packs with frequent stretching.
The results were not statistically significant in showing the virtues of one form of therapy as opposed to the other. The subjective impression of the personnel involved and
the preference of the patients for the medication make it seem reasonable to enlarge the
series studied to determine its true place in the current poliomyelitis therapy.
ACKNOWLEDGM ENT
The authors wish to acknowledge the assistance of Verne G. Robinson and Joan Reid of the Division of Public Health Statistics of the Indiana State Board of Health in the
statistical analysis of the data.
ADDENDUM
be remembered
that this study is based on intravenous administration
of tetraethylam
monium chloride. The intramuscular route was abandoned in the preliminary work, as it was somewhat painful, and greater relaxation was obtained with the intravenous adminis tration. In no instance was there noted a permanent increase in involvement. There was the casual patient who showed increased spasm on single observations, but the over-all picture was always one of improvement.
REFERENCES
1. Lannon, J,, and Braudo, J., Muscle spasm in poliomyelitis, its treatment and suggested etiology, South African M. J. 23:30, 1949.
2. Acheson, G., and Moe, G., Action of tetraethylammonium ion on mammalian circulation, J.
Pharmacol. & Exper. Therap. 87:220, 1946.
SPANISH ABSTRACT
Efectos del Tetraethylammonium
Chloride
(Etamon
Chloride)
en el
Espasmo
Muscular
de la Polkmielitis
Cloruro de tetraethylammonium, que actua como un agente inhibitorio de los centros (ganglia) autonomicos, se le administró a niños con poliomielitis paralItica al principio de Ia convalescencia.
La propiedad de este medicamento en aliviar el espasmo muscular y por consiguiente de modificar
los cambios en la extension de los n'tovimientos medidos en grados angulares mediante el uso de un
goniometro ; fuécomparada con los resultados t)btenidos en pacientes tratados con compresas calientes de uso convencional.
Los resultados obtenidos en este estudio no fueron suficientes en demostrar las virtudes de un metodo sobre el otro. La impresión subjectiva del personal implicado en este estudio y la preferencia
de los pacientes por esta medicaciónsugiere aumentar Ia serie de casos estudiados, para asI poder
determinar su valor correspondiente en Ia presente terapia de la poliomielitis.
