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Chemotherapy in frostbite
CHEMOTHERAPY CASE WILLIAM Instructor
in Surgery, Hahnemann
IN FROSTBITE* REPORT Y.
LEE,
M.D.
Hospital MedicaI SchooI; Junior Surgeon on Staff of Hahnemann PHILADELPHIA,
PENNSYLVANIA
T
lantoin cIeans the wound of those substances which tend to interfere with the bacteriostatic action of the sulfonamide, thus a suitable suIfonamide-allantoin combination not only frees the wound of the infectious process, but at the same time stimulates the growth of healthy granulation tissues. Allantoin, as a stimulator of cel1 growth, was reported on by MacaIister* who used extracts of comfrey root (which on chemical analysis were found to contain large percentages of allantoin) and pure allantoin solution, to treat indolent ulcers, which had failed to respond to a11 other types of therapy. His results convinced him of the efficacy of allantoin as a healing agent in these conditions. The successful results obtained by Baerg in his maggot therapy, which were manifested by debridement of necrotic tissue and the rapidity of healing by the increase of healthy granulation tissues, was shown by Robinson’o to be due to allantoin which was found in the excretions of maggots. On the strength of the reports of Veal it was decided to try the and KIepseF” allantoin-sulfanilamide ointment* in a case of severe frostbite of the right hand.
HE use of allantoin-sulfanilamide ointment using a specially developed, non-greasy, water-miscible base in surgery was first reported by Veal and Klepser. l-4 They found that repeated topical applications of powdered sulfonamides tended to retard healing. The granulation tissues became sluggish, pale and dried out in appearance. By microscopic section of the granulating bed they demonstrated pale staining nuclei in most cells and a marked Iack of blood vessel formation. The probIem of controlIing infection and at the same time encouraging more lively granulating tissues was solved by substituting for the powdered sulfonamides a non-greasy, water-miscibIe base containing IO per cent sulfanilamide, which proved adequate to control infection, and 2 per cent allantoin to stimuIate healthy granulation tissues. They concluded : “Microscopic evidence of greatIy increased vascularity and healing seems to justify the addition of this drug (allantoin) to sulfonamide therapy in certain instances.” Lockwood” had shown that necrotic tissue and pus contain sulfonamide inhibitors which interfere with the bacteriostatic action of sulfonamides. The inhibitor substances were inactivated according to Wallersteiner,6 b y combinations of suIfanilamide-urea, and suIfanilamide-aIlantoin. In a report, Holder and MacKay’ presented the resuhs of wound therapy with ureasulfonamide mixtures, and stressed the removal by the urea of gross sulfonamide inhibitors, or the source of such inhibitors in the form of necrotic tissue and pus. ChemicaI debridement by means of al* Hahnemann
Hospital
CASE
REPORT
J. T., a white, fifty year old male, was admitted to the hospita1 on December 23, 1942, with severe frostbite of the right hand. He remained in the hospital until February 2, During his hospitalization, the right 1943. middle finger was amputated because of dry gangrene. * Allantomide ointment was supplied National Drug Company, Philadelphia, Pa.
Hospital, “3
Philadelphia,
Pa.
by
The
1’4
American
Journal
oI Sur~wy
Lee-Frostbite
Due to very severe pains in the right hand, and areas of gangrene over the dorsal portion, the patient returned to the hospital on Fehru-
APHII,
104i
For the relief of the severe pain, morphine J.4 gr. was ordered at night and continued until March 15th. Venous occlusion (intermittent),
__.
..-
/
-.--“,“--.
FIG. I. FIG. 2. FIG. I. Appearance of hand at start of allantoin-sulfanil~\mide ointment treatment (Mayz6, 1943). FIG. 2. The gangrenous fingers sloughed off May 27th. Appearance of hand on June 24, 1943.
Frc. 3. FIG. 4. with successful FIG. 3. Appearance of hand on August 28, 1943, FIG. 4. Appearance of hand at time of discharge from hospital.
ary, 16, 1943. An x-ray examination on admission revealed the following: (I) Phalanges of little finger missing; (2) distal phalanx of (3) decalcification of second finger missing; carpal bones and proximal ends of metacarpal bones, and (4) considerable pus in the paImar area. Wasserman and Kahn tests were negative. Blood irradiation treatments were given on February 17th and 18th with no apparent benefit to the patient. The patient was transferred to the department of surgery on February 25th. His temA continuous septic perature was 102’F. temperature persisted unti1 April 3rd when it became normal and remained so until released.
skin graft.
one minute on and two minutes off, was untd and continued started immediately, June 25th. Blood cultures taken on ApriI 2nd were negative. Because of the low red blood cell count, a transfusion of $00 cc. of titrated blood was given on May 6th, and aIIantoin-sulfanilamide ointment therapy started. Figure I shows the condition of the hand at the time of starting allantoin-sulfanilamide ointment treatment. Although the fingers were gangrenous, and the palmar surface was covered with slough tissue, these were not disturbed. The ointment in a liberal amount was applied over the whole hand and wrist, and then
NEW SE~IESVOI..LXVIII,NO.
dressed with Vaseline gauze and dry dressings. These dressings were changed after four days, the hand was gently bathed with hydrogen peroxide, and fresh ointment applied. Dressings were changed at four to five-day intervals, the hand being bathed at each dressing period with hydrogen peroxide to remove adherent ointment and loose slough tissues. On Ala> 27th, all of the fingers sloughed off, and there was evidence of epithelization on the dorsal aspect of the hand. The thumb was folded under the site of the index finger and was attached. On June Ioth, the palmar surface was completely sloughed and was trimmed to some degree with forceps and scissors. By June 2qth, the palmar area was clean of all slough tissue, and epithelization was evident. (Fig. 2.) It was decided on August Sth, that the hand was in good condition for skin graft. The skin graft operation was performed on August IGth, at which time the thumb was separated from the palm. AIlantoin-sulfanilamide ointment with a light pressure dressing was applied. A change of dressing on August 28th revealed an excellent take of the graft. (Fig. 3.) The patient was discharged from the hospital on September 2Ist. (Fig. 4.) During the whole course of the allantoinsulfanilamide ointment treatment, laboratory tests for urine and blood sulfanilamide levels were made frequently. At no time during the treatment were suIfanilamide crystals found in the urine. Determination showed 2.4 mg. per cent sulfanilamide in the blood May gth, and 2.3 mg. per cent on June 2nd. After venous occIusion treatment was discontinued (June 25th); blood determinations for sulfanilamide showed only traces of the drug. SUMMARY
A case of believed that
AND
Amrrican JOII~II:LI ol Surgery
Lee-Frostbite
I
CONCLUSION
frostbite is presented. the institution of the
toin-sulfanilamide ointment treatment in the case reported was a big factor in saving the patient’s hand. The ointment, b) chemica1 dbbridement due to aIIantoin, compIeteIy cleansed the hand of sloughed and devitaIized tissue and stimulated new granuIation tissues and epithelium. Infection was definiteIy brought under control. The resuIts obtained in this case indicate that allantoin-sulfanilamide ointment in a SpeciaIIyprepared, non-greasy, water-miscible base is worthy of a trial in the treatment of severe frostbite. REFERENCES I. VEAL, J. Ross and KLEPSER, ROY G. The treatment
2.
3.
4. 5.
6. 7. 8.
9.
10.
It is allan-
115
of pyogenically infected wounds by the topical application sulfanilamide of powdered and sulfanilamide-allantoin ointment. Med. Ann. Dist. of Columbia, 2: 61, 1941. VEAL, J. Ross and KLEPSER, ROY G. Local sulfanilamide therapy in surgical infections. Surpeqr, 10: 947, 1941. VEAL, J. Ross, KLEPSER, ROY G. and DE VITO, M. P. The preparation of superficial wounds for skin grafting bv the Iocal use of sulfanilamide and &lfan&m~de-allantoin ointment. Am. J. Surg., 54: 716, 1941. VEAL. J. ROSS and KLEPSER. ROY G. Sulfonamide theiapy in surgery. Soutb. k. J., 36: 292, 1943. LOCKWOOD, J. S. and LYNCH, H. M. InfIuence of proteolytic products on effectiveness of suIfanilamide. J. A. M. A., I 14: 935, 1940. WALLERSTEIU, W. K. S. Counteracting sulfonamide inhibitors. Nature, 151: 586, 1943. HOLDER, Il. G. and ~~AcKA~, E. RI. Militur,L.%U,$‘eon,90: 509, 1942. MACALISTER, C. J. A new ceil proliferant: its clinical application in the treatment of ulcers. Brit. M. J., I: IO, 1912. BAER, W. S. The treatment of chronic osteomyelitis with maggot. (The larva of the blow fly.) J. Bone PTJoint Surg., 13: 458, 1931. ROBINSON, &'M. Stimulation of healing in nonhealing wounds by allantoin occurring in maggot secretions and of wide biological distribution. J. Hone F-PJoint Surg., 17: 267, ,935.
in Surgery, Hahnemann
IN FROSTBITE* REPORT Y.
LEE,
M.D.
Hospital MedicaI SchooI; Junior Surgeon on Staff of Hahnemann PHILADELPHIA,
PENNSYLVANIA
T
lantoin cIeans the wound of those substances which tend to interfere with the bacteriostatic action of the sulfonamide, thus a suitable suIfonamide-allantoin combination not only frees the wound of the infectious process, but at the same time stimulates the growth of healthy granulation tissues. Allantoin, as a stimulator of cel1 growth, was reported on by MacaIister* who used extracts of comfrey root (which on chemical analysis were found to contain large percentages of allantoin) and pure allantoin solution, to treat indolent ulcers, which had failed to respond to a11 other types of therapy. His results convinced him of the efficacy of allantoin as a healing agent in these conditions. The successful results obtained by Baerg in his maggot therapy, which were manifested by debridement of necrotic tissue and the rapidity of healing by the increase of healthy granulation tissues, was shown by Robinson’o to be due to allantoin which was found in the excretions of maggots. On the strength of the reports of Veal it was decided to try the and KIepseF” allantoin-sulfanilamide ointment* in a case of severe frostbite of the right hand.
HE use of allantoin-sulfanilamide ointment using a specially developed, non-greasy, water-miscible base in surgery was first reported by Veal and Klepser. l-4 They found that repeated topical applications of powdered sulfonamides tended to retard healing. The granulation tissues became sluggish, pale and dried out in appearance. By microscopic section of the granulating bed they demonstrated pale staining nuclei in most cells and a marked Iack of blood vessel formation. The probIem of controlIing infection and at the same time encouraging more lively granulating tissues was solved by substituting for the powdered sulfonamides a non-greasy, water-miscibIe base containing IO per cent sulfanilamide, which proved adequate to control infection, and 2 per cent allantoin to stimuIate healthy granulation tissues. They concluded : “Microscopic evidence of greatIy increased vascularity and healing seems to justify the addition of this drug (allantoin) to sulfonamide therapy in certain instances.” Lockwood” had shown that necrotic tissue and pus contain sulfonamide inhibitors which interfere with the bacteriostatic action of sulfonamides. The inhibitor substances were inactivated according to Wallersteiner,6 b y combinations of suIfanilamide-urea, and suIfanilamide-aIlantoin. In a report, Holder and MacKay’ presented the resuhs of wound therapy with ureasulfonamide mixtures, and stressed the removal by the urea of gross sulfonamide inhibitors, or the source of such inhibitors in the form of necrotic tissue and pus. ChemicaI debridement by means of al* Hahnemann
Hospital
CASE
REPORT
J. T., a white, fifty year old male, was admitted to the hospita1 on December 23, 1942, with severe frostbite of the right hand. He remained in the hospital until February 2, During his hospitalization, the right 1943. middle finger was amputated because of dry gangrene. * Allantomide ointment was supplied National Drug Company, Philadelphia, Pa.
Hospital, “3
Philadelphia,
Pa.
by
The
1’4
American
Journal
oI Sur~wy
Lee-Frostbite
Due to very severe pains in the right hand, and areas of gangrene over the dorsal portion, the patient returned to the hospital on Fehru-
APHII,
104i
For the relief of the severe pain, morphine J.4 gr. was ordered at night and continued until March 15th. Venous occlusion (intermittent),
__.
..-
/
-.--“,“--.
FIG. I. FIG. 2. FIG. I. Appearance of hand at start of allantoin-sulfanil~\mide ointment treatment (Mayz6, 1943). FIG. 2. The gangrenous fingers sloughed off May 27th. Appearance of hand on June 24, 1943.
Frc. 3. FIG. 4. with successful FIG. 3. Appearance of hand on August 28, 1943, FIG. 4. Appearance of hand at time of discharge from hospital.
ary, 16, 1943. An x-ray examination on admission revealed the following: (I) Phalanges of little finger missing; (2) distal phalanx of (3) decalcification of second finger missing; carpal bones and proximal ends of metacarpal bones, and (4) considerable pus in the paImar area. Wasserman and Kahn tests were negative. Blood irradiation treatments were given on February 17th and 18th with no apparent benefit to the patient. The patient was transferred to the department of surgery on February 25th. His temA continuous septic perature was 102’F. temperature persisted unti1 April 3rd when it became normal and remained so until released.
skin graft.
one minute on and two minutes off, was untd and continued started immediately, June 25th. Blood cultures taken on ApriI 2nd were negative. Because of the low red blood cell count, a transfusion of $00 cc. of titrated blood was given on May 6th, and aIIantoin-sulfanilamide ointment therapy started. Figure I shows the condition of the hand at the time of starting allantoin-sulfanilamide ointment treatment. Although the fingers were gangrenous, and the palmar surface was covered with slough tissue, these were not disturbed. The ointment in a liberal amount was applied over the whole hand and wrist, and then
NEW SE~IESVOI..LXVIII,NO.
dressed with Vaseline gauze and dry dressings. These dressings were changed after four days, the hand was gently bathed with hydrogen peroxide, and fresh ointment applied. Dressings were changed at four to five-day intervals, the hand being bathed at each dressing period with hydrogen peroxide to remove adherent ointment and loose slough tissues. On Ala> 27th, all of the fingers sloughed off, and there was evidence of epithelization on the dorsal aspect of the hand. The thumb was folded under the site of the index finger and was attached. On June Ioth, the palmar surface was completely sloughed and was trimmed to some degree with forceps and scissors. By June 2qth, the palmar area was clean of all slough tissue, and epithelization was evident. (Fig. 2.) It was decided on August Sth, that the hand was in good condition for skin graft. The skin graft operation was performed on August IGth, at which time the thumb was separated from the palm. AIlantoin-sulfanilamide ointment with a light pressure dressing was applied. A change of dressing on August 28th revealed an excellent take of the graft. (Fig. 3.) The patient was discharged from the hospital on September 2Ist. (Fig. 4.) During the whole course of the allantoinsulfanilamide ointment treatment, laboratory tests for urine and blood sulfanilamide levels were made frequently. At no time during the treatment were suIfanilamide crystals found in the urine. Determination showed 2.4 mg. per cent sulfanilamide in the blood May gth, and 2.3 mg. per cent on June 2nd. After venous occIusion treatment was discontinued (June 25th); blood determinations for sulfanilamide showed only traces of the drug. SUMMARY
A case of believed that
AND
Amrrican JOII~II:LI ol Surgery
Lee-Frostbite
I
CONCLUSION
frostbite is presented. the institution of the
toin-sulfanilamide ointment treatment in the case reported was a big factor in saving the patient’s hand. The ointment, b) chemica1 dbbridement due to aIIantoin, compIeteIy cleansed the hand of sloughed and devitaIized tissue and stimulated new granuIation tissues and epithelium. Infection was definiteIy brought under control. The resuIts obtained in this case indicate that allantoin-sulfanilamide ointment in a SpeciaIIyprepared, non-greasy, water-miscible base is worthy of a trial in the treatment of severe frostbite. REFERENCES I. VEAL, J. Ross and KLEPSER, ROY G. The treatment
2.
3.
4. 5.
6. 7. 8.
9.
10.
It is allan-
115
of pyogenically infected wounds by the topical application sulfanilamide of powdered and sulfanilamide-allantoin ointment. Med. Ann. Dist. of Columbia, 2: 61, 1941. VEAL, J. Ross and KLEPSER, ROY G. Local sulfanilamide therapy in surgical infections. Surpeqr, 10: 947, 1941. VEAL, J. Ross, KLEPSER, ROY G. and DE VITO, M. P. The preparation of superficial wounds for skin grafting bv the Iocal use of sulfanilamide and &lfan&m~de-allantoin ointment. Am. J. Surg., 54: 716, 1941. VEAL. J. ROSS and KLEPSER. ROY G. Sulfonamide theiapy in surgery. Soutb. k. J., 36: 292, 1943. LOCKWOOD, J. S. and LYNCH, H. M. InfIuence of proteolytic products on effectiveness of suIfanilamide. J. A. M. A., I 14: 935, 1940. WALLERSTEIU, W. K. S. Counteracting sulfonamide inhibitors. Nature, 151: 586, 1943. HOLDER, Il. G. and ~~AcKA~, E. RI. Militur,L.%U,$‘eon,90: 509, 1942. MACALISTER, C. J. A new ceil proliferant: its clinical application in the treatment of ulcers. Brit. M. J., I: IO, 1912. BAER, W. S. The treatment of chronic osteomyelitis with maggot. (The larva of the blow fly.) J. Bone PTJoint Surg., 13: 458, 1931. ROBINSON, &'M. Stimulation of healing in nonhealing wounds by allantoin occurring in maggot secretions and of wide biological distribution. J. Hone F-PJoint Surg., 17: 267, ,935.