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Cationic detergents as antiseptics
CATIONIC DETERGENTS AS ANTISEPTICS EMIL
D.
W. HAUSER,M.D.
AND
Attending Orthopedic Surgeon, Passavent lLlemoria1 Hospital CHICAGO,
LIEUT. MEDICAL
(J.G.)
WILLIAM
CORPS,
UNITED
W.
CUTTER
STATES
NAVY
ILLINOJS
T
HE advantages of cIeanIiness in the care of wounds were observed in the earIiest stages of surgery. The introduction of antiseptic procedures by Lister marked a new era in surgery. Ever since Lister’s time the search for an ideal antiseptic has been going on. We have gone through various phases of new antiseptics, but each time they have faIlen short of the hoped-for requirements. At the present time re-emphasis has been placed, and properIy, upon the action of the Iiving tissue as the best antiseptic action against invasive bacteria.’ The emphasis now is on cIeansing the wound with non-irritating substances like soap and water,2 the forming of the dtbridement to remove the devitahzed tissue, insuring adequate drainage by opening the fascia1 spaces, and compIete immobiIization of the tissue” with compression to prevent edema. The introduction of the suIfonamides and penici!Iin have again aroused the hopes for a miracuIous substance to cure a11 infections. Some disadvantages of the suIfonamides are now we11 estabIished. PeniciIIin has not yet been used in sufficient quantities to estabIish its fuI1 vaIue; cer-
tainIy it promises a great dea1. We wish to draw more attention to a new group of antiseptics, one of which we have found to be an exceIIent preoperative preparation as we11 as an antiseptic and cIeansing materia1 in the dressing of wounds, both in cIearing up infection and in the prevention of infection. This disinfectant was first described by Domagk in Ig35.4 A series of chemica1 derivatives had been previousIy deveIoped as detergents. The group is designated by foIIowing formuIa in Figure I: 352
+
CH, I
R-N-_-H, I CH, FK.
cr-
I.
are ammonium They chIoride derivatives with an R radicaI consisting of an aIky1 radica1 of about 12 carbon atoms. A series of these products was deveIopedj in the Iaboratory and tested for their bactericida1 effectiveness.6 The preparation that was finaIIy deveIoped as the most effective disinfectant was a water soIution of a high moIecuIar aIky1 dimethy benzyl ammonium chIoride. This substance goes under the trade name of Zephiran. Domagk first pointed out some of the physica properties. It is a coIorIess, odorIess Auid which foams upon shaking. It is sIightIy aIkaIine to Iitmus. It does not precipitatewith aIkaIis, remains clear when tap water is added, and there is no precipitate or Ioss of disinfectant power with the addition of acids. The substance is compatibIe with iodine, cocaine, ephedrine, epinephrine, procaine hydrochloride, sulfonamides and with most substances with which it is IikeIy to come into contact. It is incompatibIe with soap; to get its greatest disinfectant vaIue it must, therefore, not be combined with soap. Since Zephiran has the quaIities of soap and water, and is an exceIIent detergent, there is no need to use soap and water.
Hauser,
NEwSERIESVOL.LXIV,NO.~
Cutter-Antiseptics
Zephiran has a surface tension one-half that of distihed water.’ This is of importance since the low surface tension indi-
American Journnl of Surgery
353
simiIar chemical structure, of quaternary ammonium salts, has important interface modification properties. Long before their
84
to 66 2g 60 '-j54 u a) 48 3 :; 42
-
% c-36 2
Zephiran
-0--*Soap
30
U Water 10 min., and alcohol Control5 (no scrubbin<)
-_-_-
2 k 24 a" 18 12 6,
01 0
5% 12
Minutes
3
4
5
6
7
of scrubbIn@
8
9
10
_
FIG. 2.
In this cates the penetrating power. connection, White, Collins and Newman* made fuII thickness biopsies in which the skin was prepared with the sohrtion. In fifty-one cases in which biopsy cultures were taken from such treated skin, growth occurred in two instances; biopsy cuItures of untreated skin showed growth in every case. The substance, as pointed out by Dunn,g is very stabIe; neither freezing temperatures nor proIonged exposure to heat (122'~. to 5o”c.) caused any reduction of its germicida1 action. Storage at room temperatures for more than eight months caused no aIteration in its germicida1 properties. Zephiran is an emuIsifier and a detergent and Iike the other substances which have a
bactericida1 action was known they were used as emuIsifiers, detergents and wetting In preparation of the skin for agents. surgery, these substances, as WaIterlO has demonstrated, possess a detergent, karatoIytic, emuIsifying and emolient action. The cleansing action is evident when it is used to wash dirt and grime from the hands; it is more effective than soap and water for the same Iength of time. Tests to compare detergency vaIues have been made, using Zephiran and simiIar products against soap soIutions. Soiled woo1 cIoths were washed, one with soap and water, and the other with Zephiran soIution. The reflection of light from the cIoth was then measured. The amount of reffectance was then expressed in percentages. The
35-l
American Journal of Surgery
Hauser,
Cutter--Antiseptics
comparative study showed that .o3 per cent Zephiran with the chemical formula-alkyl dimethy benzy1 ammonium
JUNE. 1w.s
static action. Pure cultures of highIy pathogenic bacteria were utiIized to test the disinfectant action by Domagk4 and Total number of cultureg taken = 50 -
Zephiran, Imin. v Water 10min. and alcohol Controls
*-*-Soap -----
0 1 2 3 4 5 6 7 8 9 10 11 12 I3 14 15 16 17 18 19 20
Experiment
number
FIG.
16 per cent refIectance, chloride-gave whiIe .I per cent of soap gave 8 per cent. In other words, Zephiran was seven times more efficient than the soap soIution. In preoperative preparation there is a keroIytic action, as demonstrated by the detritus that occurs in washing the skin with Zephiran. The emoIient action of the skin was evident when a surgica1 gIove was worn on one hand dry, and on the other hand wet, with I :s,ooo Zephiran solution. The hand wet by the Zephiran soIution was soft and smooth and remained so for several hours after the skin was dry. In addition to the important cIeansing abiIity of this substance, Zephiran, Iike the other quaternary ammonium saIts, possesses high bactericida1 and bacterio-
3.
his associates. They used bacteria in various media and to show that the disinfectant did not act on the cuIture media they used the suspension method as we11 as the bacteria1 carrier method. They recognized the importance of the difference in viruIence of various bacteria. They found that in dealing with highIy viruIent BaciIIus coIi I :200 dilution of and staphyIococcus, Zephiran was required to get a germicida1 effect in two and one haIf minutes, but with the ordinary run of bacteria they were abIe to get the same effect with a diIution of I :z,goo. To obtain the same effect with creoso1 soIution diIutions of I :IOO were required. Against gram-positive staphyIococcus, streptococcus and pneumococcus, the two and one-haIf minute effect was
Hauser,
NEW SERES VOL. LXIV. No. 3
Cutter-Antiseptics
obtained with Zephiran diIuted I :jo,ooo. After the two and one-haIf minute test they obtained no further growth in the materia1 upon Ietting it stand, so that apparentIy it was not a bacteriostatic action. Furthermore, twenty-four hours Iater they added fresh cuItures of the bacteria in great numbers, and found that further growth of the bacteria was prevented. Further work in determining the bactericida1 effect has been carried out by other investigators. Dunn9 reports a bactericida1 effect in high diIutions of organic ammonium chIorides. He expressed the average vaIues for the highest diIution of organic ammonium chIorides destroying the organism in ten minutes, in the foIIowing chart: HIGHEST
DILUTION
DESTROYING FIVE
OF
THE
ORGANIC
AMMONIUM
ORGANISM
MINUTES
IN
(AVERAGE
Organisms
TEN
CHLORIDES
BUT
2o”c.
StaphyIococcus aureus.. Escherichia coli.. . . EbertheIla typhosa. Streptococcus Cryptococcus
_.
.
I-
.~._
I-35,000 I-40,000 I-70,000
I-20,000 I-20,000 I-20,000
hemoIyticus. viridans.. hominis.
IN
37Oc.
,
-
StreptOCOCcuS
NOT
VALUES)
I-qo,ooo
‘-95,000 I-65,000 I-70,000
I-35,000
I-24,000
I
I
He ran a simiIar series of tests checking the phenol coe&cient of the organic ammonium chIorides in I :I ,000 diIutions. He reported the foIIowing pheno1 coeflicients : PHENOL ORGANIC
COEFFICIENTS AMMONIUM
OF
CHLORIDES
(F.D.A.)
(I--1000
diIu_
Organisms
--
tions)
~-
2o”c.
I EbertheIIa typhosa. Staphylococcus aureus. Escherichia coIi. .. . Streptococcus pyogenes. . Streptococcus hemolyticus. Streptococcus viridans.
37Oc.
-./ -~250 279 160
429 408 358 272 579 434
. 435 384
. I
I
-
1
American
Journal
of Surgery
355
The pheno1 coefi?cients of EbertheIla typhosa have aIso been reported by Maier and MiIIer,” who found them to be 150 at 20’~. Heineman7 reports the pheno1 coeffIcient of the same bacteria as 275 at 37’c., Lawrence12 as 230 at 20’~. For StaphyIococcus aureus the pheno1 coefficient has been reported by Heineman as 275, by Maier and MiIIer at 200 and by Lawrence at 365, at 20’~. Dunn9 aIso showed comparative figures with the ordinary antiseptic preparations used at the present time, showing that the ammonium chIoride preparations were much more effective. Another comparative study was made by Thompson, Isaacs and Khorazo,13 who showed that the Zephiran chIoride acted with much greater rapidity. It has aIso been demonstrated that there is some retardation of the effect in the presence of organic matter, but this is comparatively much Iess than other germicida1 products. Its effect has been found to be decreased Iess by egg white media than any other disinfectant in use.14 A comparative study of the bactericida1 effect of severa types of the detergents was made by Baker, Harrison and MiIIer,‘” and they found that the cationic detergents exhibit a marked bactericidal effect on gram-positive organisms and a somewhat Iess action on gram-negative organisms, whereas the anionic detergents were germicida1 onIy against gram-positive organisms and were considerabiy Iess effective than the cationic compounds. In a group of experiments which we ran, the concern was with the preoperative preparation of the hands. Two to four cuItures of the hands were taken each day as foIIows: two (or one) of our staff scrubbed in soap and water for ten minutes, foIIowing which they soaked the hands in aIcoho1 (75 per cent), and then steriIe water, in the usual manner. The other two (or one) of our staff washed their hands in Zephiran chIoride for one minute without the use of brush, cloth or gauze. The hands were dried in the accustomed way and pIaced upon bIood agar pIates. Twenty
356
American
Journal
of Surgery
Hauser,
Cutter-Antiseptics
cultures of each method were taken. There were five persons incIuded in the experiment with constant aIternating of cIeansing between the Zephiran chIoride and the soap, water and aIcoho1. Two controIs of each performer were taken. AI1 of the experiments were carried out on our surgica1 floor in order to imitate actua1 conditions in preoperative preparation of the hands: caps, masks and scrub suits were donned; steriIe brushes, steriIe containers for the Zephiran, aIcoho1 and steriIe water were empIoyed, as we11 as steriIe towels for the drying of the hands. The charts and graphs show our resu1t.s. (Figs. 2 and 3.) AI1 controls, of course, showed positive cuhures; the usua1 manner of scrubbing with soap and water with aIcoho1 and steriIe water soaks showed 75 per cent positive cuItures, and the cuItures of the Zephiran chIoride preparation showed 5 per cent positive cuItures (one in twenty cuItures). The speed of action of this coconut oi1. derivative is effectiveIy shown in Figure 2, whiIe Figure 3 shows the number of coIonies in each cuIture. The vaIue of any bactericide is definiteIy Iimited by any toxic effect or irritation that it may cause to tissue. The toxic and irritative effects have been studied repeatedIy. The fact that the skin is not irritated in concentrations that wiI1 act as antiseptics has been demonstrated in our experiments with the washing of the hands and in skin preoperative preparation. Experimenta studies were carried out by injecting I :2000 soIution of the Zephiran (benzyI-triaIkonium chIoride) into the ear and into the peritonea1 cavity of rabbits, and no irritation was found, nor were any toxic effects observed. 4 ProIonged ora administration of potabIe soIutions of ammonium chIoride preparation were we11 toIerated and daily intraperitonea1 injections of diIute soIutions in the guinea pig gave no deIeterious effects. InstaIIations of drops in the human eye of diIutions suitabIe for effective use as a bactericide produced minima1 subjective symptoms.g
JUNE,
1944
The skin in various regions of the body, as we11 as the mucous membranes in the orifices, showed no signs of irritation after being washed with I :I,OOO dilutions of ammonium chIoride preparation. lo We have found that repeated use by severa members of the hospita1 staff have at no time given any irritating effect; others have found simiIar resuIts, notabIy Dunn.g We found two instances on record of surgeons who couId not use soap and water scrubs without getting dermatitis, who found they were abIe to get surgica1 preparation of their hands with the quaternary ammonium chIoride soIution without any signs of irritation. The germicida1 effect for the quaternary ammonium chIoride is within the range of I to 3,000, which is non-irritating for mucous membranes and apparentIy, as far as we could estabIish, non-irritating for vita1 tissue. We have been abIe to wash wounds with a I : 3,000 soIution without irritating effect and with evidence of an antiseptic effect. The infection cIeared up and heaIing took pIace. It is dificuIt to make comparative studies. In our opinion, Zephiran I :3,000 is an exceIIent substance for cleansing infected wounds, and compares favorabIy with the use of soap and water. In a series of seventy-six cases reported by White, CoIIins and Newman,* ammonium chIoride detergent was used as a germicide for preoperative preparation, and infection occurred in one case, or 1.3 per cent, whereas a comparative study of twenty-five cases in which 3.5 per cent of tincture of iodine was used as a disinfectant showed there were seven infected cases. We have used aIky1 dimethy benzy1 ammonium chloride in soIution of I :I,OOO as a routine preparation of the skin in orthopedic procedures, in&ding surgery for interna derangements of the knee, haIIux valgus and reconstruction operations, without infections. The skin was washed with the aqueous soIution for at least two minutes and a tincture containing a stain was used to cIeIineate the operative fieId. We have used I :3,000
NEWSERIES VOL.LXIV, No. 3
Hauser,
Cutter-Antiseptics
aqueous soIution to cIeanse chronic uIcers, osteomyeIitic wounds and infected compound fractures with exceIIent resuIts. We have found it a convenient and safe antiseptic in cIeansing wounds in minor surgery, convenient since it saves time. SUMMARY
We wished to establish the value, if any, of the cationic detergents as antiseptics. We found that the primary vaIue of aIky1 dimethy benzy1 ammonium chIoride, one of the cationic detergents, was its cIeansing effect. Experiments seemed to confirm the findings of others, that it has a high bactericidal and bacteriostatic effect. Our. cIinica1 experiments showed that it can be safeIy used as a preoperative cIeansing materia1 for the surgeon’s hands, as we11 as the operative fieId. We found it satisfactory for cIeansing wounds in minor surgery. We have used it in cleansing infected wounds without signs of irritation to tissue. After using it over a year, we beIieve that aIky1 dimethy .benzyI ammonium chIoride, one of the cationic detergents, is a rapid, safe and effective surgica1 antiseptic. PREOPERATIVE PREPARATION OF THE HANDS ZEPHIRAN-I MlN”TE Meagre growth: 1-5 coIonies Moderate growth: bzo coIonies Heavv., _. growth: Above 20 colonies. AI1 48 hours II. w. c. Negative I. J. S. Negative 2. W. c. Negative 12. D. K. Negative 3. D. K. Negative 13. D. K. Negative 4. J. S. Negative 14. B. S. Meagre hemolytic Staphylococcus AIbus 5. w. c. Negative 15. W. C. Negative 6. D. K. Negative 16. H. S. Negative Negative 7. H. S. Negative 17. D. K. 18. B. S. Negative 8. W. C. Negative Negative rg. H. S. Negative g. J. S. IO. D. K. Negative 20. W. C. Negative -. 20 Experiments: I (5%) Positive Culture rg (95 %) Negative Cultures PREOPERATIVE PREPARATION OF THE HANDS SOAP AND WATER-IO MINUTES-AND ALCOHOL Meagre growth: r-5 coIonies Moderate growth: 6-20 coIonies Heavy growth: Above 20 coIonies. AI1 48 hours I. D. K. Meagre Hemolytic and non-hemoIytic StaphyIococcus aIbus Moderate HemoIytic Staphylococcus 2. H. S. aIbus
American Journal of Surgery
3. J. S.
Moderate
4. D. K.
5. H. S.
Negative Moderate
6. W. C.
Meagre
7. J. S.
Moderate
8. D. K. g. H. S.
Negative Moderate
IO. W. C. II. B.S.
Negative Moderate
12. H. S.
Heavy
13. W. C.
Meagre
14. H. S.
Meagre
15. D. K. 16. B. S. 17. W. C.
Negative Negative Moderate
18. H. S.
Moderate
rg. B. S.
Meagre
20. D. K.
Moderate
20 Experiments
r5 5
357
Hemolytic Staphylococcus aureus and albus Hemolytic StaphyIococcus albus Hemolytic StaphyIococcus albus HemoIytic Staphylococcus aureus and aIbus HemoIytic and non-hemolytic StaphyIococcus aIbus Hemolytic Staphylococcus aIbus Hemolytic StaphyIococcus albus and aureus HemoIytic Staphylococcus aIbus HemoIytic StaphyIococcus albus
HemoIytic Staphylococcus aureus and aIbus Hemolytic Staphylococcus aIbus Hemolytic Staphylococcus albus HemoIytic Staphylococcus aureus and albus (75 70) Positive Cultures (25 %) Negative CuItures
REFERENCES
TRUETA, J. The PrincipIes and Practice of War Surgery. St. Louis, 1943. C. V. Mosby. 2. KOCH, S. L. Prevention and treatment of infections of the hand. J. A. A4. A., 116: 1365-1367, rg4r. 3. ORR, H. W. The physiologic factors invoIved in protecting the patient against infection in the heaIing of fractures and compound wounds. Tr. ti Studies, Cal. Pbys. of Pbiladelpbia, IO: I.
187-193, 1943.
4. DOMAGK. G.. Eine neue klasse von desinfektionsmittem. deutscbe med. Wcbnscbr., 61: 829-832, ‘935. 5. SCHULEMANNVON TAUB. Cited in Domagk.4 I; 6. KUHN, R. and BIELIG, H. J. Uber invertseifen die einwirkung von invertseifen auf eiweissstoffe. Deutscbe cben. Gesellscb., 73: 1080-rogr, 1940. properties of aIkyI7. HEINEMAN, P. G. Antiseptic dimethyI-benzyl-ammonium chloride. J. A. Pbar. A., 26: 1937. 711-717, 1937. 8. WHITE, C. S., COLLINS, J. L. and NEWMAN, H. E. The cIinica1 use of aIkyI-dimethyI-benzyIammonium chloride (zephiran); a preIiminary report. Am. J. Surg., 39: 6o74og. 1938. Tecb9. DUNN, C. G. There are good germicides. nology Rev., 40: 271-272, 284, 286-290, Ig371938. 10. WALTER, C. W. The use of a mixture of coconut oil derivatives as a bactericide in the operating room. Surg., Gynec. u Obst., 67: 683-688, 1938.
358
American
Journal
Hauser,
of Surgery
Cutter-Antiseptics
1I. ~IAIER, E. and MULLER, E. Die wirksamkeit der gebrauchhchen desinfektionsmitte1. Forts&r. d. Tberap., 12: 204-21 I, 1936. v2. LAWRENCE, C. A. Comments on Council’s report on Zephiran of August IS, 1941. Submitted with CounciI’s Ietter of January 8, 1942. (Laboratory report, unpublished). 13. THOMPSON, R., ISAACS, M. L. and KHORAZO, D. A Iaboratory study of some antiseptics with
BECAUSE the larynx
is composed
some cIosely related to the supporting it by considerabIe injury
Myerson
“TubercuIosis (Charles
reference to ocuIar application. Am. J. Opbtbolmol., 20: ro87-1098, 1937. 14. BAKER, Z., HARRISON, R. W. and MILLER, B. F. Bactericidal action of synthetic detergents. J. Exper. Med., 74: 611-620, 1941. 15. BAKER, Z., HARRISON, R. W. and MILLER, B. F. Inhibition of phospholipids of the action of synthetic detergents on bacteria. J. Exper. Med., 74: 621, 1941.
of cartilages structures,
loose areolar tissue, the reaction
by the tubercle
From
bacillus of the
C. Thomas).
is quite different Ear,
JUNE,,944
Nose,
covered
with soft tissues,
and others separated of the laryngeal
from
tissues to
than that of the lung.
and Throat,”
by Mervin
C.
D.
W. HAUSER,M.D.
AND
Attending Orthopedic Surgeon, Passavent lLlemoria1 Hospital CHICAGO,
LIEUT. MEDICAL
(J.G.)
WILLIAM
CORPS,
UNITED
W.
CUTTER
STATES
NAVY
ILLINOJS
T
HE advantages of cIeanIiness in the care of wounds were observed in the earIiest stages of surgery. The introduction of antiseptic procedures by Lister marked a new era in surgery. Ever since Lister’s time the search for an ideal antiseptic has been going on. We have gone through various phases of new antiseptics, but each time they have faIlen short of the hoped-for requirements. At the present time re-emphasis has been placed, and properIy, upon the action of the Iiving tissue as the best antiseptic action against invasive bacteria.’ The emphasis now is on cIeansing the wound with non-irritating substances like soap and water,2 the forming of the dtbridement to remove the devitahzed tissue, insuring adequate drainage by opening the fascia1 spaces, and compIete immobiIization of the tissue” with compression to prevent edema. The introduction of the suIfonamides and penici!Iin have again aroused the hopes for a miracuIous substance to cure a11 infections. Some disadvantages of the suIfonamides are now we11 estabIished. PeniciIIin has not yet been used in sufficient quantities to estabIish its fuI1 vaIue; cer-
tainIy it promises a great dea1. We wish to draw more attention to a new group of antiseptics, one of which we have found to be an exceIIent preoperative preparation as we11 as an antiseptic and cIeansing materia1 in the dressing of wounds, both in cIearing up infection and in the prevention of infection. This disinfectant was first described by Domagk in Ig35.4 A series of chemica1 derivatives had been previousIy deveIoped as detergents. The group is designated by foIIowing formuIa in Figure I: 352
+
CH, I
R-N-_-H, I CH, FK.
cr-
I.
are ammonium They chIoride derivatives with an R radicaI consisting of an aIky1 radica1 of about 12 carbon atoms. A series of these products was deveIopedj in the Iaboratory and tested for their bactericida1 effectiveness.6 The preparation that was finaIIy deveIoped as the most effective disinfectant was a water soIution of a high moIecuIar aIky1 dimethy benzyl ammonium chIoride. This substance goes under the trade name of Zephiran. Domagk first pointed out some of the physica properties. It is a coIorIess, odorIess Auid which foams upon shaking. It is sIightIy aIkaIine to Iitmus. It does not precipitatewith aIkaIis, remains clear when tap water is added, and there is no precipitate or Ioss of disinfectant power with the addition of acids. The substance is compatibIe with iodine, cocaine, ephedrine, epinephrine, procaine hydrochloride, sulfonamides and with most substances with which it is IikeIy to come into contact. It is incompatibIe with soap; to get its greatest disinfectant vaIue it must, therefore, not be combined with soap. Since Zephiran has the quaIities of soap and water, and is an exceIIent detergent, there is no need to use soap and water.
Hauser,
NEwSERIESVOL.LXIV,NO.~
Cutter-Antiseptics
Zephiran has a surface tension one-half that of distihed water.’ This is of importance since the low surface tension indi-
American Journnl of Surgery
353
simiIar chemical structure, of quaternary ammonium salts, has important interface modification properties. Long before their
84
to 66 2g 60 '-j54 u a) 48 3 :; 42
-
% c-36 2
Zephiran
-0--*Soap
30
U Water 10 min., and alcohol Control5 (no scrubbin<)
-_-_-
2 k 24 a" 18 12 6,
01 0
5% 12
Minutes
3
4
5
6
7
of scrubbIn@
8
9
10
_
FIG. 2.
In this cates the penetrating power. connection, White, Collins and Newman* made fuII thickness biopsies in which the skin was prepared with the sohrtion. In fifty-one cases in which biopsy cultures were taken from such treated skin, growth occurred in two instances; biopsy cuItures of untreated skin showed growth in every case. The substance, as pointed out by Dunn,g is very stabIe; neither freezing temperatures nor proIonged exposure to heat (122'~. to 5o”c.) caused any reduction of its germicida1 action. Storage at room temperatures for more than eight months caused no aIteration in its germicida1 properties. Zephiran is an emuIsifier and a detergent and Iike the other substances which have a
bactericida1 action was known they were used as emuIsifiers, detergents and wetting In preparation of the skin for agents. surgery, these substances, as WaIterlO has demonstrated, possess a detergent, karatoIytic, emuIsifying and emolient action. The cleansing action is evident when it is used to wash dirt and grime from the hands; it is more effective than soap and water for the same Iength of time. Tests to compare detergency vaIues have been made, using Zephiran and simiIar products against soap soIutions. Soiled woo1 cIoths were washed, one with soap and water, and the other with Zephiran soIution. The reflection of light from the cIoth was then measured. The amount of reffectance was then expressed in percentages. The
35-l
American Journal of Surgery
Hauser,
Cutter--Antiseptics
comparative study showed that .o3 per cent Zephiran with the chemical formula-alkyl dimethy benzy1 ammonium
JUNE. 1w.s
static action. Pure cultures of highIy pathogenic bacteria were utiIized to test the disinfectant action by Domagk4 and Total number of cultureg taken = 50 -
Zephiran, Imin. v Water 10min. and alcohol Controls
*-*-Soap -----
0 1 2 3 4 5 6 7 8 9 10 11 12 I3 14 15 16 17 18 19 20
Experiment
number
FIG.
16 per cent refIectance, chloride-gave whiIe .I per cent of soap gave 8 per cent. In other words, Zephiran was seven times more efficient than the soap soIution. In preoperative preparation there is a keroIytic action, as demonstrated by the detritus that occurs in washing the skin with Zephiran. The emoIient action of the skin was evident when a surgica1 gIove was worn on one hand dry, and on the other hand wet, with I :s,ooo Zephiran solution. The hand wet by the Zephiran soIution was soft and smooth and remained so for several hours after the skin was dry. In addition to the important cIeansing abiIity of this substance, Zephiran, Iike the other quaternary ammonium saIts, possesses high bactericida1 and bacterio-
3.
his associates. They used bacteria in various media and to show that the disinfectant did not act on the cuIture media they used the suspension method as we11 as the bacteria1 carrier method. They recognized the importance of the difference in viruIence of various bacteria. They found that in dealing with highIy viruIent BaciIIus coIi I :200 dilution of and staphyIococcus, Zephiran was required to get a germicida1 effect in two and one haIf minutes, but with the ordinary run of bacteria they were abIe to get the same effect with a diIution of I :z,goo. To obtain the same effect with creoso1 soIution diIutions of I :IOO were required. Against gram-positive staphyIococcus, streptococcus and pneumococcus, the two and one-haIf minute effect was
Hauser,
NEW SERES VOL. LXIV. No. 3
Cutter-Antiseptics
obtained with Zephiran diIuted I :jo,ooo. After the two and one-haIf minute test they obtained no further growth in the materia1 upon Ietting it stand, so that apparentIy it was not a bacteriostatic action. Furthermore, twenty-four hours Iater they added fresh cuItures of the bacteria in great numbers, and found that further growth of the bacteria was prevented. Further work in determining the bactericida1 effect has been carried out by other investigators. Dunn9 reports a bactericida1 effect in high diIutions of organic ammonium chIorides. He expressed the average vaIues for the highest diIution of organic ammonium chIorides destroying the organism in ten minutes, in the foIIowing chart: HIGHEST
DILUTION
DESTROYING FIVE
OF
THE
ORGANIC
AMMONIUM
ORGANISM
MINUTES
IN
(AVERAGE
Organisms
TEN
CHLORIDES
BUT
2o”c.
StaphyIococcus aureus.. Escherichia coli.. . . EbertheIla typhosa. Streptococcus Cryptococcus
_.
.
I-
.~._
I-35,000 I-40,000 I-70,000
I-20,000 I-20,000 I-20,000
hemoIyticus. viridans.. hominis.
IN
37Oc.
,
-
StreptOCOCcuS
NOT
VALUES)
I-qo,ooo
‘-95,000 I-65,000 I-70,000
I-35,000
I-24,000
I
I
He ran a simiIar series of tests checking the phenol coe&cient of the organic ammonium chIorides in I :I ,000 diIutions. He reported the foIIowing pheno1 coeflicients : PHENOL ORGANIC
COEFFICIENTS AMMONIUM
OF
CHLORIDES
(F.D.A.)
(I--1000
diIu_
Organisms
--
tions)
~-
2o”c.
I EbertheIIa typhosa. Staphylococcus aureus. Escherichia coIi. .. . Streptococcus pyogenes. . Streptococcus hemolyticus. Streptococcus viridans.
37Oc.
-./ -~250 279 160
429 408 358 272 579 434
. 435 384
. I
I
-
1
American
Journal
of Surgery
355
The pheno1 coefi?cients of EbertheIla typhosa have aIso been reported by Maier and MiIIer,” who found them to be 150 at 20’~. Heineman7 reports the pheno1 coeffIcient of the same bacteria as 275 at 37’c., Lawrence12 as 230 at 20’~. For StaphyIococcus aureus the pheno1 coefficient has been reported by Heineman as 275, by Maier and MiIIer at 200 and by Lawrence at 365, at 20’~. Dunn9 aIso showed comparative figures with the ordinary antiseptic preparations used at the present time, showing that the ammonium chIoride preparations were much more effective. Another comparative study was made by Thompson, Isaacs and Khorazo,13 who showed that the Zephiran chIoride acted with much greater rapidity. It has aIso been demonstrated that there is some retardation of the effect in the presence of organic matter, but this is comparatively much Iess than other germicida1 products. Its effect has been found to be decreased Iess by egg white media than any other disinfectant in use.14 A comparative study of the bactericida1 effect of severa types of the detergents was made by Baker, Harrison and MiIIer,‘” and they found that the cationic detergents exhibit a marked bactericidal effect on gram-positive organisms and a somewhat Iess action on gram-negative organisms, whereas the anionic detergents were germicida1 onIy against gram-positive organisms and were considerabiy Iess effective than the cationic compounds. In a group of experiments which we ran, the concern was with the preoperative preparation of the hands. Two to four cuItures of the hands were taken each day as foIIows: two (or one) of our staff scrubbed in soap and water for ten minutes, foIIowing which they soaked the hands in aIcoho1 (75 per cent), and then steriIe water, in the usual manner. The other two (or one) of our staff washed their hands in Zephiran chIoride for one minute without the use of brush, cloth or gauze. The hands were dried in the accustomed way and pIaced upon bIood agar pIates. Twenty
356
American
Journal
of Surgery
Hauser,
Cutter-Antiseptics
cultures of each method were taken. There were five persons incIuded in the experiment with constant aIternating of cIeansing between the Zephiran chIoride and the soap, water and aIcoho1. Two controIs of each performer were taken. AI1 of the experiments were carried out on our surgica1 floor in order to imitate actua1 conditions in preoperative preparation of the hands: caps, masks and scrub suits were donned; steriIe brushes, steriIe containers for the Zephiran, aIcoho1 and steriIe water were empIoyed, as we11 as steriIe towels for the drying of the hands. The charts and graphs show our resu1t.s. (Figs. 2 and 3.) AI1 controls, of course, showed positive cuhures; the usua1 manner of scrubbing with soap and water with aIcoho1 and steriIe water soaks showed 75 per cent positive cuItures, and the cuItures of the Zephiran chIoride preparation showed 5 per cent positive cuItures (one in twenty cuItures). The speed of action of this coconut oi1. derivative is effectiveIy shown in Figure 2, whiIe Figure 3 shows the number of coIonies in each cuIture. The vaIue of any bactericide is definiteIy Iimited by any toxic effect or irritation that it may cause to tissue. The toxic and irritative effects have been studied repeatedIy. The fact that the skin is not irritated in concentrations that wiI1 act as antiseptics has been demonstrated in our experiments with the washing of the hands and in skin preoperative preparation. Experimenta studies were carried out by injecting I :2000 soIution of the Zephiran (benzyI-triaIkonium chIoride) into the ear and into the peritonea1 cavity of rabbits, and no irritation was found, nor were any toxic effects observed. 4 ProIonged ora administration of potabIe soIutions of ammonium chIoride preparation were we11 toIerated and daily intraperitonea1 injections of diIute soIutions in the guinea pig gave no deIeterious effects. InstaIIations of drops in the human eye of diIutions suitabIe for effective use as a bactericide produced minima1 subjective symptoms.g
JUNE,
1944
The skin in various regions of the body, as we11 as the mucous membranes in the orifices, showed no signs of irritation after being washed with I :I,OOO dilutions of ammonium chIoride preparation. lo We have found that repeated use by severa members of the hospita1 staff have at no time given any irritating effect; others have found simiIar resuIts, notabIy Dunn.g We found two instances on record of surgeons who couId not use soap and water scrubs without getting dermatitis, who found they were abIe to get surgica1 preparation of their hands with the quaternary ammonium chIoride soIution without any signs of irritation. The germicida1 effect for the quaternary ammonium chIoride is within the range of I to 3,000, which is non-irritating for mucous membranes and apparentIy, as far as we could estabIish, non-irritating for vita1 tissue. We have been abIe to wash wounds with a I : 3,000 soIution without irritating effect and with evidence of an antiseptic effect. The infection cIeared up and heaIing took pIace. It is dificuIt to make comparative studies. In our opinion, Zephiran I :3,000 is an exceIIent substance for cleansing infected wounds, and compares favorabIy with the use of soap and water. In a series of seventy-six cases reported by White, CoIIins and Newman,* ammonium chIoride detergent was used as a germicide for preoperative preparation, and infection occurred in one case, or 1.3 per cent, whereas a comparative study of twenty-five cases in which 3.5 per cent of tincture of iodine was used as a disinfectant showed there were seven infected cases. We have used aIky1 dimethy benzy1 ammonium chloride in soIution of I :I,OOO as a routine preparation of the skin in orthopedic procedures, in&ding surgery for interna derangements of the knee, haIIux valgus and reconstruction operations, without infections. The skin was washed with the aqueous soIution for at least two minutes and a tincture containing a stain was used to cIeIineate the operative fieId. We have used I :3,000
NEWSERIES VOL.LXIV, No. 3
Hauser,
Cutter-Antiseptics
aqueous soIution to cIeanse chronic uIcers, osteomyeIitic wounds and infected compound fractures with exceIIent resuIts. We have found it a convenient and safe antiseptic in cIeansing wounds in minor surgery, convenient since it saves time. SUMMARY
We wished to establish the value, if any, of the cationic detergents as antiseptics. We found that the primary vaIue of aIky1 dimethy benzy1 ammonium chIoride, one of the cationic detergents, was its cIeansing effect. Experiments seemed to confirm the findings of others, that it has a high bactericidal and bacteriostatic effect. Our. cIinica1 experiments showed that it can be safeIy used as a preoperative cIeansing materia1 for the surgeon’s hands, as we11 as the operative fieId. We found it satisfactory for cIeansing wounds in minor surgery. We have used it in cleansing infected wounds without signs of irritation to tissue. After using it over a year, we beIieve that aIky1 dimethy .benzyI ammonium chIoride, one of the cationic detergents, is a rapid, safe and effective surgica1 antiseptic. PREOPERATIVE PREPARATION OF THE HANDS ZEPHIRAN-I MlN”TE Meagre growth: 1-5 coIonies Moderate growth: bzo coIonies Heavv., _. growth: Above 20 colonies. AI1 48 hours II. w. c. Negative I. J. S. Negative 2. W. c. Negative 12. D. K. Negative 3. D. K. Negative 13. D. K. Negative 4. J. S. Negative 14. B. S. Meagre hemolytic Staphylococcus AIbus 5. w. c. Negative 15. W. C. Negative 6. D. K. Negative 16. H. S. Negative Negative 7. H. S. Negative 17. D. K. 18. B. S. Negative 8. W. C. Negative Negative rg. H. S. Negative g. J. S. IO. D. K. Negative 20. W. C. Negative -. 20 Experiments: I (5%) Positive Culture rg (95 %) Negative Cultures PREOPERATIVE PREPARATION OF THE HANDS SOAP AND WATER-IO MINUTES-AND ALCOHOL Meagre growth: r-5 coIonies Moderate growth: 6-20 coIonies Heavy growth: Above 20 coIonies. AI1 48 hours I. D. K. Meagre Hemolytic and non-hemoIytic StaphyIococcus aIbus Moderate HemoIytic Staphylococcus 2. H. S. aIbus
American Journal of Surgery
3. J. S.
Moderate
4. D. K.
5. H. S.
Negative Moderate
6. W. C.
Meagre
7. J. S.
Moderate
8. D. K. g. H. S.
Negative Moderate
IO. W. C. II. B.S.
Negative Moderate
12. H. S.
Heavy
13. W. C.
Meagre
14. H. S.
Meagre
15. D. K. 16. B. S. 17. W. C.
Negative Negative Moderate
18. H. S.
Moderate
rg. B. S.
Meagre
20. D. K.
Moderate
20 Experiments
r5 5
357
Hemolytic Staphylococcus aureus and albus Hemolytic StaphyIococcus albus Hemolytic StaphyIococcus albus HemoIytic Staphylococcus aureus and aIbus HemoIytic and non-hemolytic StaphyIococcus aIbus Hemolytic Staphylococcus aIbus Hemolytic StaphyIococcus albus and aureus HemoIytic Staphylococcus aIbus HemoIytic StaphyIococcus albus
HemoIytic Staphylococcus aureus and aIbus Hemolytic Staphylococcus aIbus Hemolytic Staphylococcus albus HemoIytic Staphylococcus aureus and albus (75 70) Positive Cultures (25 %) Negative CuItures
REFERENCES
TRUETA, J. The PrincipIes and Practice of War Surgery. St. Louis, 1943. C. V. Mosby. 2. KOCH, S. L. Prevention and treatment of infections of the hand. J. A. A4. A., 116: 1365-1367, rg4r. 3. ORR, H. W. The physiologic factors invoIved in protecting the patient against infection in the heaIing of fractures and compound wounds. Tr. ti Studies, Cal. Pbys. of Pbiladelpbia, IO: I.
187-193, 1943.
4. DOMAGK. G.. Eine neue klasse von desinfektionsmittem. deutscbe med. Wcbnscbr., 61: 829-832, ‘935. 5. SCHULEMANNVON TAUB. Cited in Domagk.4 I; 6. KUHN, R. and BIELIG, H. J. Uber invertseifen die einwirkung von invertseifen auf eiweissstoffe. Deutscbe cben. Gesellscb., 73: 1080-rogr, 1940. properties of aIkyI7. HEINEMAN, P. G. Antiseptic dimethyI-benzyl-ammonium chloride. J. A. Pbar. A., 26: 1937. 711-717, 1937. 8. WHITE, C. S., COLLINS, J. L. and NEWMAN, H. E. The cIinica1 use of aIkyI-dimethyI-benzyIammonium chloride (zephiran); a preIiminary report. Am. J. Surg., 39: 6o74og. 1938. Tecb9. DUNN, C. G. There are good germicides. nology Rev., 40: 271-272, 284, 286-290, Ig371938. 10. WALTER, C. W. The use of a mixture of coconut oil derivatives as a bactericide in the operating room. Surg., Gynec. u Obst., 67: 683-688, 1938.
358
American
Journal
Hauser,
of Surgery
Cutter-Antiseptics
1I. ~IAIER, E. and MULLER, E. Die wirksamkeit der gebrauchhchen desinfektionsmitte1. Forts&r. d. Tberap., 12: 204-21 I, 1936. v2. LAWRENCE, C. A. Comments on Council’s report on Zephiran of August IS, 1941. Submitted with CounciI’s Ietter of January 8, 1942. (Laboratory report, unpublished). 13. THOMPSON, R., ISAACS, M. L. and KHORAZO, D. A Iaboratory study of some antiseptics with
BECAUSE the larynx
is composed
some cIosely related to the supporting it by considerabIe injury
Myerson
“TubercuIosis (Charles
reference to ocuIar application. Am. J. Opbtbolmol., 20: ro87-1098, 1937. 14. BAKER, Z., HARRISON, R. W. and MILLER, B. F. Bactericidal action of synthetic detergents. J. Exper. Med., 74: 611-620, 1941. 15. BAKER, Z., HARRISON, R. W. and MILLER, B. F. Inhibition of phospholipids of the action of synthetic detergents on bacteria. J. Exper. Med., 74: 621, 1941.
of cartilages structures,
loose areolar tissue, the reaction
by the tubercle
From
bacillus of the
C. Thomas).
is quite different Ear,
JUNE,,944
Nose,
covered
with soft tissues,
and others separated of the laryngeal
from
tissues to
than that of the lung.
and Throat,”
by Mervin
C.