Pharmacology and Therapeutics
DEXTRANOMER IN DERMATOLOGIC CONDITIONS
LAWRENCE CHARLES PARISH, M.D. AND K^SEPH A. WITKdVVSKI, M.D.
from the Department nt Dermatology, University of Pennsylvania School of Medicine. Philadelphia, Pennsylvania
ABSTRACT: Dvxtranomvr, a high molecular weight dextran derivative, was evaluated in 4 3 patients, and found to be the treatment of choice for decubitus ulcers. It is useful in most leg ulcers and cutaneous wounds, and can aid m the nursing care of terminal patients with gangrene or ulcerating carcinoma. Dextranomer hastens the postoperative course in dermabrasion patienis. Although patients with bacterial infection show no change with dextranomer, it is useful in hastening the rvsniution of herpes simplex and herpes zoster lesions.
We have evaluated dextranomer, a powder with intensely hydrophilic propertJes, Jn a vaPresented at ihe Canadian Dermatological Association, Toronto, Canada, lune 26. 1979, Supported in part by Pharmacia Laboratories, Piscataway, N|, dnd the Herman and Rulh Goodman Foundalion. Inc., New York, NY. Address tor reprinls: Lawrence Charles Parish, M.D., 1601 Walnut Street, Philadelphia, Pa 14104.
riety ot dermatologic conditions since mid1977. The unique capabilitJes of this high molecular weight dextran had been known tor several years, since Rothman, working in Malmo, Sweden, utilized this information for treating a laboratory-induced burn. He noted that the lesions healed more rapidly and that the pain was less intense. Since that time, dextranomer has been used in Sweden for the treatment of burns and infected wounds. Two years ago, dextranomer became available in America, initially on an Jnvestigational basis. Because there was no experience in its use Jn dermatologic practice, we embarked on a pilot study to determine which cutaneous entities might be treated effectively.'-^ Materials and Methods Forty-three patients, observed in botb our private and hospital practices, were entered into the study. Necessary permission was obtained. The ulcer or area to be treated was initially washed with water or saline and then damp dried. A layer of dextranomer powder at least
0011-W59/7y/0700/0480/$00.75 © Inlfrnational Society ot TropK.il DermatoloRy, Inc
480
No. 6
DEXTRANOMER IN DERMATOLOGIC CONDITIONS
Parish and Witkowski
481
Table 1.
Condition 1. decubitus ulcers 2. arterrosclerotic ulcers 3. sickle cell ulcer 4, traumatic ulcers 5. intecrted surgical wound 6. dermabrasion
7. 8. 9. 10.
gangrene inoperable carcinoma bacterial inlections viral infections
Number of Patients 14 (42 ulcers) 9 1 4 1 5 1 I 2
5
3 mm thjck was poured Into the lesjon. When the treatment site presented on an anatomic site difficult to fill, the lesion was first rimmed with petroleum jelly to keep the powder from spjiljng out. The wound was then covered with a dry dressing held in place wjth tape. Dressings and powder were changed when the dextranomer became wet or discolored. Before reapplyingthe powder, the wound was gently cleansed to remove any powder remaining from the previous application and then retreated. Powder remaining in crevices could be gently dislodged with a spoon or tongue blade. Initially the treatments were re[leated every eight hours. Within a few days one application daily was found sufficient. Results
Table 1 illustrates the types of conditions encountered in the study. 1. Decubitus ulcers: 14 patients with 42 ulcers were treated. Dextranomer was helpful in removing debris and decreasing exudation from moist ulcers, thereby allowing granulation tissue to proliferate and epithelium to grow over the void. Ulcers often changed very little in size for many weeks, but once filled with granulation tissue, healing occurred
Recommendations treatment of choice useful when blood supply adequate very helpful useful helpful adjunct treatment of choice tor post-operative period helpful adjund helpful ad|unct too awkward more investigation needed
rapidly. Dry ulcers did not respond to treatment. In some instances, however, initial treatment with enzymatic debriding agents or S'fluorfjurt il removed some necrotic debris and seemed to encourage a subsequent response to dextranomer. Lesions with large amounts of necrotic debris or those covered with an eschar should be surgically debrided before using the powder. Dextranomer was invaluable in preparing large iesions for grafting or flap procedure. 2. Arteriosclerotic ulcers: 9 patients were studied. Moist ulcers, probabiy those with adequate collateral circulation, healed rapidly. Two patients were able to undergo successful grafting after dextranomer treatment. As might be expected, the powder was ineffective on ulcers without sufficient blood supply. 3. Sickle cell ulcers: This patient had been reported previously.^ Following dextranomer applications, pain was considerably reduced and partial re-epithilealization accomplished. Noncompliance and poor circulation prevented complete resolution. The patient was treated again some months later. This time the ulcer was successfully prepared for a graft. 4. Traumatic ulcers: Four patients with traumatic ulcers on various locations on the
482
INTERNATIONAL JOURNAL OE DERMATOLOGY
body surface healed on the average within thirty days. 5. Infected surgical wound: A sixty-seven year old man developed oozing and crusting at the site of removal of a basal cell cancer. Application of dextranomercleared the debris and permitted healing within five days. 6. Dermabrasion: Dextranomer was applied either immediately or on the first postoperative day following dermabrasion of five patients. Healing occurred in four to five days. A faster response was noted in patients where dextranomer was applied immediately after dermabrasion. This was a decided improvement over previous regimens consisting of postdermabrasion compresses and dressings where healing occurred in eight to twelve days. 7. Gangrene: A terminally ill patient with a maggot infested, reeking gangrenous leg was treated with dextranomer. Applications of the powder reduced the odor and made nursing care easier. 8. Inoperable carcinoma: Dextranomer was used as an adjuctjve treatment on a patient with inoperable carcinoma of the bladder with ulceration of the perineum. Cleasing of tbe wound was more easily accomplished and the odor was decreased. 9. Bacterial infection: Two patients with impetiginized dermatitis of the arms and legs found the use of dextranomer too awkard. The results were unremarkable. 10. Viral infections: Two patients with berpes zoster and three patients with herpes simplex were treated with dextranomer after erosions and oozing surfaces appeared. All lesions dried quickly and crusting was reduced. The patients believed this procedure was belpful, but this is difficult to evaluate. Discussion A fundamental principle in the management of wounds involves keeping the surface free of exudate, bacteria and necrotic debris. A unique feature of dextranomer is the way it
luly-AuRusl 1979
Vol. 18
accomplishes this feat. It virtually effects a chromatographic separation of substances within the wound. Dextranomer consists of beds which have a diameter of 1 to 3 mm and which are sterilized by gamma radiation. They are insoluble and highly hydrophilic due to their hydroxyl group content. Substances of low molecular weight (MW < 5000) are absorbed by the dextranomer beads. These include water, prostaglandins and other inflammatory mediators. Higher weight molecular substances (MW > 5000) are sucked up between the beads whlcli can generate a suction force of up to 200 mm Hg. This would explain why bacteria, plasminogens and fibrin split products are absorbed by the beads. As a result of the continuous cleansing, natural wound healing is permitted. Granulation tissue is allowed to proliferate and the formation of eschars is retarded. Normal reepithelialization can occur or graft and flap procedures can be accomplished much quicker. Dextranomer acts as a physical agent and is pharmacologically inert. There is no observaable chemical action, either upon normal or diseased tissue. No allergic or irritant contact dermatitis bas been found. Complete removal of dextranomer from a wound is necessary for good therapeutic effect. Incomplete removal may retard the action of fresh beads, but it will not cause any outward problems, even when beads are hidden in a cul-de-sacs of deep ulcers for several days. Histologic examination of tissues following deep implantation of dextranomer in animals revealed reactions comparable to those around non-absorbable sutures."* Only wounds with exudating surfaces will respond to the application of dextranomer. Thedry wound, the debris-filled wound or the eschar-covered ulcer will not be helped by dextranomer, as there is nothing for the beads to absorb or adsorb. For the dry ulcer, enzymatic debridement, destruction with topical
No. 6
DEXTRANOMER IN DERMATOLOGIC CONDITK^NS
and Witkowsh
483
Figs. 1A-C. A 24-year-old woman had atopic dermatitis for many years. Four months before treatment, she began to layer stockings on her legs and never removed them. A tourniquet effect created the ulcerations. Top left, admission. Top center, 27 days ot' dextranomer treatment. Top right, 43 days of dextranomer treatment. Eigs. 2A-C. This 71-year-old man had stasis dermatitis for nearly two decades. Numerous modalities had effected little change and surgical procedures had tailed. Middle left, before treatment. Middle center and rif^ht, one month of dextranomer improved the ulcer base so that grafting was subsequently su( cessful. Eigs. 3A-C. This 23-yeaf-old woman underwent dermabrasion and dextranomor was applied immediately. It was reapplied three times a day for six days. 8o(fom left, first postoperative day. Bottom c enter, 4th postoperative day. Bottom right. 12th postoperative day. Healing was much more rapid.
5-fl()urourcil, or tbe application of benzoyl peroxide may provide a partial solution; however, there is no substitute for surgical debridement of eschars or large wounds crammed with debris. Patients have almost no subjective complaints about the use ol dextranomer. An occasional patient might complain of a iTilld burning when the beads are applied to open areas, but no other symptoms have been observed. Nurses often become advocates of tbe use of dextranomer. Treatment shouid take very little time and can often be performed by the unskilled personnel.
Conclusions 1. Dextranomer is a most useful treatment for decubitus ulcers. Our results have been remarkably good, even though this disease is highly variable. Although the bodies of debilitated patients often cannot be healed, dextranomer will keep their ulcers clean. 2. Leg ulcers are highly variable. When the patient has healing capabilities, tbe results are impressive, but when the vascular supply to the ulcer is poor or absent, no topical modality will effect a cure. 3. Traumatic ulcers and surgical wounds have all healed more rapidly w ith dextranomer.
484
INTERNATIONAL IOURNAL OF DERMATOLOGY
4. Applications ot' dextranomer shorten the postoperative course following dermabrasion. 5. The tiursing care of terminally ill patients who have odoriferous cutaneous ulcers is aided by dextranomer applicalion. 6. Although bacterial infections do not seem to be altered by the use of dextranomer, the course of herpes simplex and /cjster infections appears to be shorter. Newer delivery systems for dextranomer are needed to prof>erlv evaluate treatment lor these diseases.
Drug Name dextranomer: DebrJsan
luly-Aiigust
Vol. 18
References 1. iJiobssun, S , Rollimdn, U., Arturson, G., l, K., H.5eger, K., and Juhlin. I.: A new principle ror fhe tlt'.insing of intecled wounds, Stdnd. |. Plast. Reronstr. Surg. 10:65, 1476. 2. Paavolainen, P., and Sundell, B.: The effect ot dexIranomer (debris^n) on hand burns. Ann. Chirurg. Gynaecol. 65:313, 1976. 3. Parish, L. C: Sickle tell leg Liker. Arch. Dermafol. 106:754, 1972. 4. latobsson, S., )onsson, L., Rank, T., eta!.: Sludieson healing of debrisan trealed wounds. Sc and. |. Recons!r. Surg. 10:47, 1976. 5. Parish, L. C, and Collins, E.: Decubiius ukers: a comparative study. Cutis 23:106. 1979. 6. Pace, W. E.: Cutaneous Lilcers heal completely with applications of DPB l>eads. Dermatol. News n (81:1, 1978.
Diagnosis of Granulomatous Disorders The Kveim-Siltzbach test remains an enigma. The cumulative experience of over two decades has resulted in a wide acceptance of the test as a useful aid to diagnosis while attempts to identify the active principal involved have been unsuccessful. Chemical analysis suggests that the active principle is particulate and lodges in the membrane components of sarcoid tissue cells. Experimental work in mice has shown that a possible transmissible agent in sarcoidosis is inactivated if homogenates used in transmission studies are prepared from slow-frozen human sarcoid tissue stored at minus 20*'C or are irradiated by ''"C—conditions under which valid Kveim-Siltzbach test suspensions retain activity.—Notes and news. Lancet 2:55, 1978.
DEXTRANOMER IN DERMATOLOGIC CONDITIONS
LAWRENCE CHARLES PARISH, M.D. AND K^SEPH A. WITKdVVSKI, M.D.
from the Department nt Dermatology, University of Pennsylvania School of Medicine. Philadelphia, Pennsylvania
ABSTRACT: Dvxtranomvr, a high molecular weight dextran derivative, was evaluated in 4 3 patients, and found to be the treatment of choice for decubitus ulcers. It is useful in most leg ulcers and cutaneous wounds, and can aid m the nursing care of terminal patients with gangrene or ulcerating carcinoma. Dextranomer hastens the postoperative course in dermabrasion patienis. Although patients with bacterial infection show no change with dextranomer, it is useful in hastening the rvsniution of herpes simplex and herpes zoster lesions.
We have evaluated dextranomer, a powder with intensely hydrophilic propertJes, Jn a vaPresented at ihe Canadian Dermatological Association, Toronto, Canada, lune 26. 1979, Supported in part by Pharmacia Laboratories, Piscataway, N|, dnd the Herman and Rulh Goodman Foundalion. Inc., New York, NY. Address tor reprinls: Lawrence Charles Parish, M.D., 1601 Walnut Street, Philadelphia, Pa 14104.
riety ot dermatologic conditions since mid1977. The unique capabilitJes of this high molecular weight dextran had been known tor several years, since Rothman, working in Malmo, Sweden, utilized this information for treating a laboratory-induced burn. He noted that the lesions healed more rapidly and that the pain was less intense. Since that time, dextranomer has been used in Sweden for the treatment of burns and infected wounds. Two years ago, dextranomer became available in America, initially on an Jnvestigational basis. Because there was no experience in its use Jn dermatologic practice, we embarked on a pilot study to determine which cutaneous entities might be treated effectively.'-^ Materials and Methods Forty-three patients, observed in botb our private and hospital practices, were entered into the study. Necessary permission was obtained. The ulcer or area to be treated was initially washed with water or saline and then damp dried. A layer of dextranomer powder at least
0011-W59/7y/0700/0480/$00.75 © Inlfrnational Society ot TropK.il DermatoloRy, Inc
480
No. 6
DEXTRANOMER IN DERMATOLOGIC CONDITIONS
Parish and Witkowski
481
Table 1.
Condition 1. decubitus ulcers 2. arterrosclerotic ulcers 3. sickle cell ulcer 4, traumatic ulcers 5. intecrted surgical wound 6. dermabrasion
7. 8. 9. 10.
gangrene inoperable carcinoma bacterial inlections viral infections
Number of Patients 14 (42 ulcers) 9 1 4 1 5 1 I 2
5
3 mm thjck was poured Into the lesjon. When the treatment site presented on an anatomic site difficult to fill, the lesion was first rimmed with petroleum jelly to keep the powder from spjiljng out. The wound was then covered with a dry dressing held in place wjth tape. Dressings and powder were changed when the dextranomer became wet or discolored. Before reapplyingthe powder, the wound was gently cleansed to remove any powder remaining from the previous application and then retreated. Powder remaining in crevices could be gently dislodged with a spoon or tongue blade. Initially the treatments were re[leated every eight hours. Within a few days one application daily was found sufficient. Results
Table 1 illustrates the types of conditions encountered in the study. 1. Decubitus ulcers: 14 patients with 42 ulcers were treated. Dextranomer was helpful in removing debris and decreasing exudation from moist ulcers, thereby allowing granulation tissue to proliferate and epithelium to grow over the void. Ulcers often changed very little in size for many weeks, but once filled with granulation tissue, healing occurred
Recommendations treatment of choice useful when blood supply adequate very helpful useful helpful adjunct treatment of choice tor post-operative period helpful adjund helpful ad|unct too awkward more investigation needed
rapidly. Dry ulcers did not respond to treatment. In some instances, however, initial treatment with enzymatic debriding agents or S'fluorfjurt il removed some necrotic debris and seemed to encourage a subsequent response to dextranomer. Lesions with large amounts of necrotic debris or those covered with an eschar should be surgically debrided before using the powder. Dextranomer was invaluable in preparing large iesions for grafting or flap procedure. 2. Arteriosclerotic ulcers: 9 patients were studied. Moist ulcers, probabiy those with adequate collateral circulation, healed rapidly. Two patients were able to undergo successful grafting after dextranomer treatment. As might be expected, the powder was ineffective on ulcers without sufficient blood supply. 3. Sickle cell ulcers: This patient had been reported previously.^ Following dextranomer applications, pain was considerably reduced and partial re-epithilealization accomplished. Noncompliance and poor circulation prevented complete resolution. The patient was treated again some months later. This time the ulcer was successfully prepared for a graft. 4. Traumatic ulcers: Four patients with traumatic ulcers on various locations on the
482
INTERNATIONAL JOURNAL OE DERMATOLOGY
body surface healed on the average within thirty days. 5. Infected surgical wound: A sixty-seven year old man developed oozing and crusting at the site of removal of a basal cell cancer. Application of dextranomercleared the debris and permitted healing within five days. 6. Dermabrasion: Dextranomer was applied either immediately or on the first postoperative day following dermabrasion of five patients. Healing occurred in four to five days. A faster response was noted in patients where dextranomer was applied immediately after dermabrasion. This was a decided improvement over previous regimens consisting of postdermabrasion compresses and dressings where healing occurred in eight to twelve days. 7. Gangrene: A terminally ill patient with a maggot infested, reeking gangrenous leg was treated with dextranomer. Applications of the powder reduced the odor and made nursing care easier. 8. Inoperable carcinoma: Dextranomer was used as an adjuctjve treatment on a patient with inoperable carcinoma of the bladder with ulceration of the perineum. Cleasing of tbe wound was more easily accomplished and the odor was decreased. 9. Bacterial infection: Two patients with impetiginized dermatitis of the arms and legs found the use of dextranomer too awkard. The results were unremarkable. 10. Viral infections: Two patients with berpes zoster and three patients with herpes simplex were treated with dextranomer after erosions and oozing surfaces appeared. All lesions dried quickly and crusting was reduced. The patients believed this procedure was belpful, but this is difficult to evaluate. Discussion A fundamental principle in the management of wounds involves keeping the surface free of exudate, bacteria and necrotic debris. A unique feature of dextranomer is the way it
luly-AuRusl 1979
Vol. 18
accomplishes this feat. It virtually effects a chromatographic separation of substances within the wound. Dextranomer consists of beds which have a diameter of 1 to 3 mm and which are sterilized by gamma radiation. They are insoluble and highly hydrophilic due to their hydroxyl group content. Substances of low molecular weight (MW < 5000) are absorbed by the dextranomer beads. These include water, prostaglandins and other inflammatory mediators. Higher weight molecular substances (MW > 5000) are sucked up between the beads whlcli can generate a suction force of up to 200 mm Hg. This would explain why bacteria, plasminogens and fibrin split products are absorbed by the beads. As a result of the continuous cleansing, natural wound healing is permitted. Granulation tissue is allowed to proliferate and the formation of eschars is retarded. Normal reepithelialization can occur or graft and flap procedures can be accomplished much quicker. Dextranomer acts as a physical agent and is pharmacologically inert. There is no observaable chemical action, either upon normal or diseased tissue. No allergic or irritant contact dermatitis bas been found. Complete removal of dextranomer from a wound is necessary for good therapeutic effect. Incomplete removal may retard the action of fresh beads, but it will not cause any outward problems, even when beads are hidden in a cul-de-sacs of deep ulcers for several days. Histologic examination of tissues following deep implantation of dextranomer in animals revealed reactions comparable to those around non-absorbable sutures."* Only wounds with exudating surfaces will respond to the application of dextranomer. Thedry wound, the debris-filled wound or the eschar-covered ulcer will not be helped by dextranomer, as there is nothing for the beads to absorb or adsorb. For the dry ulcer, enzymatic debridement, destruction with topical
No. 6
DEXTRANOMER IN DERMATOLOGIC CONDITK^NS
and Witkowsh
483
Figs. 1A-C. A 24-year-old woman had atopic dermatitis for many years. Four months before treatment, she began to layer stockings on her legs and never removed them. A tourniquet effect created the ulcerations. Top left, admission. Top center, 27 days ot' dextranomer treatment. Top right, 43 days of dextranomer treatment. Eigs. 2A-C. This 71-year-old man had stasis dermatitis for nearly two decades. Numerous modalities had effected little change and surgical procedures had tailed. Middle left, before treatment. Middle center and rif^ht, one month of dextranomer improved the ulcer base so that grafting was subsequently su( cessful. Eigs. 3A-C. This 23-yeaf-old woman underwent dermabrasion and dextranomor was applied immediately. It was reapplied three times a day for six days. 8o(fom left, first postoperative day. Bottom c enter, 4th postoperative day. Bottom right. 12th postoperative day. Healing was much more rapid.
5-fl()urourcil, or tbe application of benzoyl peroxide may provide a partial solution; however, there is no substitute for surgical debridement of eschars or large wounds crammed with debris. Patients have almost no subjective complaints about the use ol dextranomer. An occasional patient might complain of a iTilld burning when the beads are applied to open areas, but no other symptoms have been observed. Nurses often become advocates of tbe use of dextranomer. Treatment shouid take very little time and can often be performed by the unskilled personnel.
Conclusions 1. Dextranomer is a most useful treatment for decubitus ulcers. Our results have been remarkably good, even though this disease is highly variable. Although the bodies of debilitated patients often cannot be healed, dextranomer will keep their ulcers clean. 2. Leg ulcers are highly variable. When the patient has healing capabilities, tbe results are impressive, but when the vascular supply to the ulcer is poor or absent, no topical modality will effect a cure. 3. Traumatic ulcers and surgical wounds have all healed more rapidly w ith dextranomer.
484
INTERNATIONAL IOURNAL OF DERMATOLOGY
4. Applications ot' dextranomer shorten the postoperative course following dermabrasion. 5. The tiursing care of terminally ill patients who have odoriferous cutaneous ulcers is aided by dextranomer applicalion. 6. Although bacterial infections do not seem to be altered by the use of dextranomer, the course of herpes simplex and /cjster infections appears to be shorter. Newer delivery systems for dextranomer are needed to prof>erlv evaluate treatment lor these diseases.
Drug Name dextranomer: DebrJsan
luly-Aiigust
Vol. 18
References 1. iJiobssun, S , Rollimdn, U., Arturson, G., l, K., H.5eger, K., and Juhlin. I.: A new principle ror fhe tlt'.insing of intecled wounds, Stdnd. |. Plast. Reronstr. Surg. 10:65, 1476. 2. Paavolainen, P., and Sundell, B.: The effect ot dexIranomer (debris^n) on hand burns. Ann. Chirurg. Gynaecol. 65:313, 1976. 3. Parish, L. C: Sickle tell leg Liker. Arch. Dermafol. 106:754, 1972. 4. latobsson, S., )onsson, L., Rank, T., eta!.: Sludieson healing of debrisan trealed wounds. Sc and. |. Recons!r. Surg. 10:47, 1976. 5. Parish, L. C, and Collins, E.: Decubiius ukers: a comparative study. Cutis 23:106. 1979. 6. Pace, W. E.: Cutaneous Lilcers heal completely with applications of DPB l>eads. Dermatol. News n (81:1, 1978.
Diagnosis of Granulomatous Disorders The Kveim-Siltzbach test remains an enigma. The cumulative experience of over two decades has resulted in a wide acceptance of the test as a useful aid to diagnosis while attempts to identify the active principal involved have been unsuccessful. Chemical analysis suggests that the active principle is particulate and lodges in the membrane components of sarcoid tissue cells. Experimental work in mice has shown that a possible transmissible agent in sarcoidosis is inactivated if homogenates used in transmission studies are prepared from slow-frozen human sarcoid tissue stored at minus 20*'C or are irradiated by ''"C—conditions under which valid Kveim-Siltzbach test suspensions retain activity.—Notes and news. Lancet 2:55, 1978.
