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Topical anesthesia
TOPICAL EFFECT FRANK NEW
C.
ON TISSUE REGENERATION M.D.,
COMBES,
YORK,
ANESTHESIA-
NEW
MORRIS NEW
YORK
RESCHKE,
YORK,
NEW
M.D. YORK
AND ROSE
B.
SAPERSTEIN,
LOS ANGELES,
are generaIIy agreed for that there are certain prerequisites normal repair of injured tissues. These are adequate amounts of ascorbic acid, equibbrium of serum proteins and normal carbohydrate metabolism. According to HoIten and Crile, Jr., there is IittIe evidence that a good physical condition and vitamins other than ascorbic acid are necessary.’ However, in recent years there have been indications that Iocal anesthesia may play a significant part, especia1Iy where pain is a prominent factor. Leriche2 beIieves that anesthesia is important since trauma initiates an excitation of nerve impulses along vasomotor afferent neurons which produce excessive VasodiIatation, with edema, pain, tenderness and muscuIar spasm. If pain is ehminated there is, therefore, destruction of the impuIseswhich emanate in autonomic waves from traumatized areas with a subsequent return of vasomotor tone, thus effecting norma :iutonomic equilibrium. CuIIumbine, Rice and others” have treated minor fractures with I or 2 per cent soIutions of procaine hydrochIoride injected into the fracture site. It was observed that better aIignment of bones was obtainabIe under good IocaI anesthesia, pain was promptIy reheved, the patient was able to waIk immediateIy in many instances and heaIing was rapid. ExceIIent resuIts have been reported4 foIlowing singIe injections of simiIar soIutions
P
* From Service
HYSIOLOGISTS
M.D.
CALIFORNIA
into sprained joints and torn ligaments Most of the patients were abIe to use the injured joint immediately; onIy few required an additiona injection. ApparentIy the procaine hydrochIoride prevents the vasodiIatation and edema responsib1e for pain and disability. Rivaz-Diez and DeIrio5 discuss the use of IocaI anesthetics in the therapy of burns. They use four methods: Iocal anesthesia in small burns, nerve bIock in Iarger burns of the extremities, intravenous injections of procaine in extensive burns and intra-arteria1 injections of a procaine hydrochIoride soIution. They found that with diminution of circuIatory congestion, edema and exudation, not onIy was the pain Iess intense but the rate of epitheIization was acceIerated. It has been repeatedIy demonstrated that chemicaIs are more potent cutaneous sensitizers when appIied in concentrated soIutions. Therefore, an ointment was used which contained Iess than I per cent of the para-aminobenzoates .6 A smaI1 quantity of cod liver oi1 was added for its heaIing and anaIgesic properties. 7 Cod Iiver oiI stimuIates granuIation tissue and its use is aImost invariabIy foIIowed by soft, suppIe cicatrices. AIthough some authors have attributed many of the benefits of the oil to its bacteriostatic action, GoertzerP has shown experimentaIIy that it is not germicidaI. He beIieves the healing effects of cod Iiver oil are due to its abiIity to protect the tissues against dehydration and to
the Department of DermatoIogy, New York University College of Medicine, and the Dermatological of the Third (New York IJniversity) Medical Division, ReIIevue Hospital, service of Dr. Frank C. C,~brs. -#*i
46 *me&an
Journal of Surgery
Combes
et aI.-TopicaI
promote granulation tissue. The antiseptic properties of the ointment were enhanced by the presence of sodium propionate.9 Since burns and hypostatic uIcers offer the most convenient exampIe of painfu1 cutaneous Iesions, and since both in many respects present identica1 chemopathoIogicaI changes they were seIected to determine the effects of a IocaI anesthetic ointment on tissue regeneration. In view of the possibiIity of cutaneous irritation from the aminobenzoates, sixty subjects were tested according to FederaI Trade Commission recommendations (240 patches) for primary irritation and hyperaIIergization. OnIy one patient reacted positiveIy to the ointment. Patch tests were done with the various ingredients and this patient was found to be sensitive to benzy1 benzoate. Procedure. One hundred three patients were treated; sixty-six had burns of varying degree. In no instance did the burn invoIve more than one-eighth of the body surface. Dhbridement was performed after cIeansing the-area with tincture of green soap prior to appIication of the ointment* and a steriIe dressing. The patients were instructed to return to the cIinic in twentyfour hours for observation. The outpatients were redressed twice weekIy and hospitaIized patients were dressed as necessary (one to three times weekIy). AI1 the patients treated for burns were comfortabIe and abIe to work throughout the treatment time. * An ointment of the lipophilic type was used in this investigation and was designated “S. P. goI.” Its composition was as follows: Lanolin......................... 25. Petrolatum.. .. . . . 25. Water.......................... 15. Iso-beeswax.. . . . . . . , . . . . 8. Cod liver oi1.. . . . . . . . . 20. Corn oil.. . . . . . . . . . . . 5. Amy1 para-amino benzoate. . o. 7 Ethyl para-amino benzoate.. . . o. 2 Benzyl benzoate.. . . I. Sodium propionate. . .. . . . 2. This ointment was supplied by Chatham Pharmaceuticals, Inc., Newark, N. J. and corresponds to their product, Ultracain.
Anesthesia
JULY. 1947
Thirty-one patients suffering from uIcers due to various causes were treated with the ointment, which was appIied directIy to the uIcer and any surrounding dermatitis. The dressings were changed once or twice weekIy. If necessary, the individua1 was TABLE
-
I
BURNS
Average No. of Treatment Days
No. of Patients Treated
Type
1st degree. ....... 2nd degree. ...... 3rddegree ........ Mixed. ...........
15 49 7 5
-
4.0 II.4 21.5
Extremes
5-21
days days
7-35
days
2-
7
I
ULCERS
Hypostatic. Traumatic.
...... ....... Pyogenic......... SickIe cell.
.......
25 4 I I
34 I4 42 no effect
7-90 days 7-28 days
hospitaIized. Patients with vascuIar insufto wear an ficiency were encouraged elastic bandage. When the epidermis had compIeteIy regenerated, even in the presence of some erythema, the wound (burn or uIcer) was considered heaIed and no Ionger in need of topica therapy. Results. Every patient reported reIief of pain at the site of the burn or the uIcer immediateIy upon appIication of the ointment. We observed no infection during the course of treatment. The scars were soft and pIiabIe with very IittIe evidence of contracture even in third degree burns. No adverse reactions to the ointment were encountered when its use was restricted to denuded areas. The heaIing time impressed us as being unusuaIIy short. TabIe I. Of the sixty-six patients treated for burns, onIy one deveIoped a surrounding dermatitis. This patient was a chiId who was cared for at home in an uncIean environment. Three patients with uIcers were irritated by the ointment; (one with a
LIJL.LSXIV.NO.I
Combes
et aI.--TopicaI
hypostatic uIcer devetoped a vesicular dermatitis after the ulcer had heaIed; one patient complained of subjective discomfort but there was no evidence of clermstitis; the third patient deveIoped a dermatitis on continued use of the ointment two months after the uIcer had healed). Patch tests with al1 ingredients were negative in t.hese patients.
Anesthesia
American Jor~rnnl
ofSurgery
47
OnI_ four of 103 patients deveIoped a dermatitis, a11 of them having continued use of the ointment after the uIcer or burn had healed. These patients were patch tested to each ingredient of the ointment and reacted negatively to all. No dermntitis developed during treatment while the area was denuded. SUMMARY
COLhlMENTS
It is important to note that the aminobenzoates present in a concentration of 0.9 per cent were able to produce immediate and adequate topica anesthesia. Most previous reports dealing with the use of para-aminobenzoates as topical anesthetic agents were based on the use of soIutions or ointments containing more than 2 per cent of these drugs. In this series of 103 patients, there were no infected wounds (burns or uIcers) during the treatment period, aIthough many of the burns were not seen unti1 severa days after their occurrence. These were treated as fresh burns; cleansed thoroughIy with green soap and followed by a steriIe dressing of ointment. The inhibition of bacteria1 growth by the ointment no doubt was responsible to a large extent for the relatively short heaIing time. First degree burns, where onIy the epidermis was damaged, heaIed in two to seven days, depending upon the extent of the injury. Second degree burns showed signs of epithehzation as earIy as five days after treatment was started. In the deeper burns and ulcers, epitheIization was more rapid peripherally than centraIIy. The longest healing time was thirty-five days, except in one patient whose burn was severe and extensive, including the entire anterior tibia1 region and knee. The area involved to secondary degree was healed within thirty-five days, whereas the more deepIy burned area around the knee was just about to epitheIize at this time. Pinch grafts were then applied, the resuIting scar being soft and suppIe.
Many investigators have shown that anesthesia pIays a significant part in the promotion of healing. 2. Sixty-six patients with burns and thirty-one patients with uIcers were treated with an ointment containing Iess than I per cent of aminobenzoates. 3. Heating was rapid and scars soft and suppIe. 4. No infection was observed during treatment. 3. No irritation occurred regardless of the Iength of time that the ointment was used on the broken skin. 6. Of the 103 patients treated and 240 patch tests, no cases of benzocaine sensitivity were seen. I.
REFERENCES I. CohmEs,
FRANK C. The Skin and its Technological Hazards. ColIoid Chemistry VI. P. 742. New York, I 946. Reinhold. 2. LERICHE, RENE. The Surgery of Pain. BaItimore, 1939. WiIIiams & W&ins Company. 3. CLX.LUMBINE,H. Treatment of fractures with Iocal anesthesia. Lancet, 237: 552, rg3g. OUTLAND, Tohl and HANLON, C. R. The use of Drocaine hvdrochIoride as a therapeutic agent. J: A. M. A.: ii,: 1330, rg4o. RICE, CARL 0. Infiltration anesthesia and its use in fractures. Surg., Gynec. &* O&t., $2: 887, 193 1. BOHM, E. and FLYGER, G. Elects of local injections of novacaine on heaIing of fractures. Bull. U’ar Med., London, 4: 391, 1944. 4. MOYNAHAN, E. J. Treatment of acute sprains by procaine infiltration. Brit. A4. J., I: 671, x939. RZCLAUGALIN,C. W., JR. Procaine infiItration in the treatment of acute sprains. Mil. Suraeon. ,,,07: 457, 1945. MURPHY, F. C. ,and POSTLETHWAIT, R. W. Novacaine iniections for minor iniurirs in the military service. Surg., Gynec. & O&t., 77: 397, 1943. FRANKEL, E. L. Treatment of sprains b? injection of procaine. Lancet, 2: $97, 1939. BAKS.~, I I. J. and MCCORMICK, G. W. Use of IocaI anesthesia in the treatment of contusions and sprains. IJ. S. Nav. M. Bull., 41: 107, 1943. I
---
48
American Journal of Surgery
Combes
et aI.-TopicaI
5. RIVAZ DIEZ, B. and DELRIO, J. M. A. Local anesthesia in the treatment of burns. Bol. y trab, Acad. urgent. de cir., 28: I 182, 1944. 6. ROSTENBERG, ADOLPH, JR. and KASSOF, NAOMI. J. Ind. Derm., 4: 505, 1941. 7. PUESTOW, CHARLES, PONCHER, HENRY G. and HAMMAT, HAROLD. Vitamin oils in the treatment of burns. Surg., Gynec. @ Obst., 66: 622, 1938. 8. GOERTZEN, JOHANNES. Die Wirkung der in der Medizin GebraeuchIichen OeIe und Salbengrund-
Anesthesia
JULY, 1937
lagen, insbesondere des Lebcrtrans auf tlic Entwicklung von Keimen. Zentralbl. f. Bakt., I 34: 169-181, 1935. Abstract in Zentralbl. f. Haul- IL. Gescblecbtskr., 52: 642, 1935/36. 9. KEENEY, E. L. Fungistatic and fungicida1 effect of sodium propionate on common pathogens. Bull. Johns Hopkins Hosp., 73: 379, 1943. KEENEY, E. L. and BROYLES, E. N. Sodium propionate in treatment of superficia1 fungous infections. Bull. Jobns Hopkins Hosp., 73: 479, 1943.
MANY minor operations in the mouth can be performed under local anesthesia, but if the operation is expected to occupy some Iength of time and bIeeding to be free it is wiser to give a genera1 anaesthetic, preferably with the introduction of an intratrachea1 catheter. RoIIeston and AIlan From “ Minor Surgery ” edited by Humphry Moncrieff (Philosophical Library).
C.
ON TISSUE REGENERATION M.D.,
COMBES,
YORK,
ANESTHESIA-
NEW
MORRIS NEW
YORK
RESCHKE,
YORK,
NEW
M.D. YORK
AND ROSE
B.
SAPERSTEIN,
LOS ANGELES,
are generaIIy agreed for that there are certain prerequisites normal repair of injured tissues. These are adequate amounts of ascorbic acid, equibbrium of serum proteins and normal carbohydrate metabolism. According to HoIten and Crile, Jr., there is IittIe evidence that a good physical condition and vitamins other than ascorbic acid are necessary.’ However, in recent years there have been indications that Iocal anesthesia may play a significant part, especia1Iy where pain is a prominent factor. Leriche2 beIieves that anesthesia is important since trauma initiates an excitation of nerve impulses along vasomotor afferent neurons which produce excessive VasodiIatation, with edema, pain, tenderness and muscuIar spasm. If pain is ehminated there is, therefore, destruction of the impuIseswhich emanate in autonomic waves from traumatized areas with a subsequent return of vasomotor tone, thus effecting norma :iutonomic equilibrium. CuIIumbine, Rice and others” have treated minor fractures with I or 2 per cent soIutions of procaine hydrochIoride injected into the fracture site. It was observed that better aIignment of bones was obtainabIe under good IocaI anesthesia, pain was promptIy reheved, the patient was able to waIk immediateIy in many instances and heaIing was rapid. ExceIIent resuIts have been reported4 foIlowing singIe injections of simiIar soIutions
P
* From Service
HYSIOLOGISTS
M.D.
CALIFORNIA
into sprained joints and torn ligaments Most of the patients were abIe to use the injured joint immediately; onIy few required an additiona injection. ApparentIy the procaine hydrochIoride prevents the vasodiIatation and edema responsib1e for pain and disability. Rivaz-Diez and DeIrio5 discuss the use of IocaI anesthetics in the therapy of burns. They use four methods: Iocal anesthesia in small burns, nerve bIock in Iarger burns of the extremities, intravenous injections of procaine in extensive burns and intra-arteria1 injections of a procaine hydrochIoride soIution. They found that with diminution of circuIatory congestion, edema and exudation, not onIy was the pain Iess intense but the rate of epitheIization was acceIerated. It has been repeatedIy demonstrated that chemicaIs are more potent cutaneous sensitizers when appIied in concentrated soIutions. Therefore, an ointment was used which contained Iess than I per cent of the para-aminobenzoates .6 A smaI1 quantity of cod liver oi1 was added for its heaIing and anaIgesic properties. 7 Cod Iiver oiI stimuIates granuIation tissue and its use is aImost invariabIy foIIowed by soft, suppIe cicatrices. AIthough some authors have attributed many of the benefits of the oil to its bacteriostatic action, GoertzerP has shown experimentaIIy that it is not germicidaI. He beIieves the healing effects of cod Iiver oil are due to its abiIity to protect the tissues against dehydration and to
the Department of DermatoIogy, New York University College of Medicine, and the Dermatological of the Third (New York IJniversity) Medical Division, ReIIevue Hospital, service of Dr. Frank C. C,~brs. -#*i
46 *me&an
Journal of Surgery
Combes
et aI.-TopicaI
promote granulation tissue. The antiseptic properties of the ointment were enhanced by the presence of sodium propionate.9 Since burns and hypostatic uIcers offer the most convenient exampIe of painfu1 cutaneous Iesions, and since both in many respects present identica1 chemopathoIogicaI changes they were seIected to determine the effects of a IocaI anesthetic ointment on tissue regeneration. In view of the possibiIity of cutaneous irritation from the aminobenzoates, sixty subjects were tested according to FederaI Trade Commission recommendations (240 patches) for primary irritation and hyperaIIergization. OnIy one patient reacted positiveIy to the ointment. Patch tests were done with the various ingredients and this patient was found to be sensitive to benzy1 benzoate. Procedure. One hundred three patients were treated; sixty-six had burns of varying degree. In no instance did the burn invoIve more than one-eighth of the body surface. Dhbridement was performed after cIeansing the-area with tincture of green soap prior to appIication of the ointment* and a steriIe dressing. The patients were instructed to return to the cIinic in twentyfour hours for observation. The outpatients were redressed twice weekIy and hospitaIized patients were dressed as necessary (one to three times weekIy). AI1 the patients treated for burns were comfortabIe and abIe to work throughout the treatment time. * An ointment of the lipophilic type was used in this investigation and was designated “S. P. goI.” Its composition was as follows: Lanolin......................... 25. Petrolatum.. .. . . . 25. Water.......................... 15. Iso-beeswax.. . . . . . . , . . . . 8. Cod liver oi1.. . . . . . . . . 20. Corn oil.. . . . . . . . . . . . 5. Amy1 para-amino benzoate. . o. 7 Ethyl para-amino benzoate.. . . o. 2 Benzyl benzoate.. . . I. Sodium propionate. . .. . . . 2. This ointment was supplied by Chatham Pharmaceuticals, Inc., Newark, N. J. and corresponds to their product, Ultracain.
Anesthesia
JULY. 1947
Thirty-one patients suffering from uIcers due to various causes were treated with the ointment, which was appIied directIy to the uIcer and any surrounding dermatitis. The dressings were changed once or twice weekIy. If necessary, the individua1 was TABLE
-
I
BURNS
Average No. of Treatment Days
No. of Patients Treated
Type
1st degree. ....... 2nd degree. ...... 3rddegree ........ Mixed. ...........
15 49 7 5
-
4.0 II.4 21.5
Extremes
5-21
days days
7-35
days
2-
7
I
ULCERS
Hypostatic. Traumatic.
...... ....... Pyogenic......... SickIe cell.
.......
25 4 I I
34 I4 42 no effect
7-90 days 7-28 days
hospitaIized. Patients with vascuIar insufto wear an ficiency were encouraged elastic bandage. When the epidermis had compIeteIy regenerated, even in the presence of some erythema, the wound (burn or uIcer) was considered heaIed and no Ionger in need of topica therapy. Results. Every patient reported reIief of pain at the site of the burn or the uIcer immediateIy upon appIication of the ointment. We observed no infection during the course of treatment. The scars were soft and pIiabIe with very IittIe evidence of contracture even in third degree burns. No adverse reactions to the ointment were encountered when its use was restricted to denuded areas. The heaIing time impressed us as being unusuaIIy short. TabIe I. Of the sixty-six patients treated for burns, onIy one deveIoped a surrounding dermatitis. This patient was a chiId who was cared for at home in an uncIean environment. Three patients with uIcers were irritated by the ointment; (one with a
LIJL.LSXIV.NO.I
Combes
et aI.--TopicaI
hypostatic uIcer devetoped a vesicular dermatitis after the ulcer had heaIed; one patient complained of subjective discomfort but there was no evidence of clermstitis; the third patient deveIoped a dermatitis on continued use of the ointment two months after the uIcer had healed). Patch tests with al1 ingredients were negative in t.hese patients.
Anesthesia
American Jor~rnnl
ofSurgery
47
OnI_ four of 103 patients deveIoped a dermatitis, a11 of them having continued use of the ointment after the uIcer or burn had healed. These patients were patch tested to each ingredient of the ointment and reacted negatively to all. No dermntitis developed during treatment while the area was denuded. SUMMARY
COLhlMENTS
It is important to note that the aminobenzoates present in a concentration of 0.9 per cent were able to produce immediate and adequate topica anesthesia. Most previous reports dealing with the use of para-aminobenzoates as topical anesthetic agents were based on the use of soIutions or ointments containing more than 2 per cent of these drugs. In this series of 103 patients, there were no infected wounds (burns or uIcers) during the treatment period, aIthough many of the burns were not seen unti1 severa days after their occurrence. These were treated as fresh burns; cleansed thoroughIy with green soap and followed by a steriIe dressing of ointment. The inhibition of bacteria1 growth by the ointment no doubt was responsible to a large extent for the relatively short heaIing time. First degree burns, where onIy the epidermis was damaged, heaIed in two to seven days, depending upon the extent of the injury. Second degree burns showed signs of epithehzation as earIy as five days after treatment was started. In the deeper burns and ulcers, epitheIization was more rapid peripherally than centraIIy. The longest healing time was thirty-five days, except in one patient whose burn was severe and extensive, including the entire anterior tibia1 region and knee. The area involved to secondary degree was healed within thirty-five days, whereas the more deepIy burned area around the knee was just about to epitheIize at this time. Pinch grafts were then applied, the resuIting scar being soft and suppIe.
Many investigators have shown that anesthesia pIays a significant part in the promotion of healing. 2. Sixty-six patients with burns and thirty-one patients with uIcers were treated with an ointment containing Iess than I per cent of aminobenzoates. 3. Heating was rapid and scars soft and suppIe. 4. No infection was observed during treatment. 3. No irritation occurred regardless of the Iength of time that the ointment was used on the broken skin. 6. Of the 103 patients treated and 240 patch tests, no cases of benzocaine sensitivity were seen. I.
REFERENCES I. CohmEs,
FRANK C. The Skin and its Technological Hazards. ColIoid Chemistry VI. P. 742. New York, I 946. Reinhold. 2. LERICHE, RENE. The Surgery of Pain. BaItimore, 1939. WiIIiams & W&ins Company. 3. CLX.LUMBINE,H. Treatment of fractures with Iocal anesthesia. Lancet, 237: 552, rg3g. OUTLAND, Tohl and HANLON, C. R. The use of Drocaine hvdrochIoride as a therapeutic agent. J: A. M. A.: ii,: 1330, rg4o. RICE, CARL 0. Infiltration anesthesia and its use in fractures. Surg., Gynec. &* O&t., $2: 887, 193 1. BOHM, E. and FLYGER, G. Elects of local injections of novacaine on heaIing of fractures. Bull. U’ar Med., London, 4: 391, 1944. 4. MOYNAHAN, E. J. Treatment of acute sprains by procaine infiltration. Brit. A4. J., I: 671, x939. RZCLAUGALIN,C. W., JR. Procaine infiItration in the treatment of acute sprains. Mil. Suraeon. ,,,07: 457, 1945. MURPHY, F. C. ,and POSTLETHWAIT, R. W. Novacaine iniections for minor iniurirs in the military service. Surg., Gynec. & O&t., 77: 397, 1943. FRANKEL, E. L. Treatment of sprains b? injection of procaine. Lancet, 2: $97, 1939. BAKS.~, I I. J. and MCCORMICK, G. W. Use of IocaI anesthesia in the treatment of contusions and sprains. IJ. S. Nav. M. Bull., 41: 107, 1943. I
---
48
American Journal of Surgery
Combes
et aI.-TopicaI
5. RIVAZ DIEZ, B. and DELRIO, J. M. A. Local anesthesia in the treatment of burns. Bol. y trab, Acad. urgent. de cir., 28: I 182, 1944. 6. ROSTENBERG, ADOLPH, JR. and KASSOF, NAOMI. J. Ind. Derm., 4: 505, 1941. 7. PUESTOW, CHARLES, PONCHER, HENRY G. and HAMMAT, HAROLD. Vitamin oils in the treatment of burns. Surg., Gynec. @ Obst., 66: 622, 1938. 8. GOERTZEN, JOHANNES. Die Wirkung der in der Medizin GebraeuchIichen OeIe und Salbengrund-
Anesthesia
JULY, 1937
lagen, insbesondere des Lebcrtrans auf tlic Entwicklung von Keimen. Zentralbl. f. Bakt., I 34: 169-181, 1935. Abstract in Zentralbl. f. Haul- IL. Gescblecbtskr., 52: 642, 1935/36. 9. KEENEY, E. L. Fungistatic and fungicida1 effect of sodium propionate on common pathogens. Bull. Johns Hopkins Hosp., 73: 379, 1943. KEENEY, E. L. and BROYLES, E. N. Sodium propionate in treatment of superficia1 fungous infections. Bull. Jobns Hopkins Hosp., 73: 479, 1943.
MANY minor operations in the mouth can be performed under local anesthesia, but if the operation is expected to occupy some Iength of time and bIeeding to be free it is wiser to give a genera1 anaesthetic, preferably with the introduction of an intratrachea1 catheter. RoIIeston and AIlan From “ Minor Surgery ” edited by Humphry Moncrieff (Philosophical Library).