Leukopenia in Acute Thermal Injury: Evidence Against Topical Silver Sulfadiazine as the Causative Agent

Thomson, Philip D.; Moore, N P; Rice, Ted L.; Prasad, J.K.

doi:10.1097/00004630-198909000-00008

Cited by 27 publications

(17 citation statements)

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“…In support of this assertion, silver sulfadiazine was applied to mice with full-thickness skin excision covering 10% of the body surface, resulting in a reduction in total peripheral blood leukocyte counts (Gamelli et al, 1993). The findings of 2 controlled human studies have not supported that silver sulfadiazine induces leukopenia (Kiker et al, 1977;Thomson et al, 1989), and neutropenia sometimes occurs as an adverse effect of sulfadiazine in the absence of silver (Chen et al, 1991;Finland et al, 1984;Marshall et al, 1950;McMillin, 1951;Trepanier, 2004). However, in absence of sulfadiazine, leukopenia was reported in a burn patient treated with a silver-containing silicone foam dressing for 7 days (McCague and Joe, 2015).…”

Section: Hematological Toxicitymentioning

confidence: 99%

Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review

Hadrup

Sharma

Loeschner

2018

Regulatory Toxicology and Pharmacology

255

178

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Silver is used in different applications that result in contact with skin and mucosal surfaces (e.g., jewelry, wound dressings, or eye drops). Intact skin poses an effective barrier against the absorption of silver. Mucosal surfaces are observed to be less effective barriers and compromised skin is often a poor barrier. Silver can deposit as particles in the human body causing a blue-gray discoloration known as argyria. Urine and feces are reported pathways of excretion. Acute human mortality has been observed following an abortion procedure involving the intrauterine administration of 7 g silver nitrate (64 mg silver/kg body weight). Localized argyria has been reported with exposure to silver ions, metallic surfaces, and nanocrystalline silver. Generalized argyria was observed with ionic and nanocrystalline silver in humans at cumulative doses in the range of 70-1500 mg silver/kg body weight. Silver is observed to have a low potential for skin irritation. Eye irritation and some cases of allergic contact dermatitis have been reported. Silver may cause genotoxicity, but additional data are required to assess its carcinogenic potential. Other reported toxicities include hepatic, renal, neurological, and hematological effects.

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Section: Hematological Toxicitymentioning

confidence: 99%

Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review

Hadrup

Sharma

Loeschner

2018

Regulatory Toxicology and Pharmacology

255

178

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“…Since its introduction in 1968 and clinical marketing in the USA in 1973 [116], SSD has been frequently documented as a cause of leukopenia and lowered granulocyte counts, but these changes have normalised when therapy has been discontinued. Thus, Thomson et al [117] recorded reduced white blood cell counts (WBC) of ≤5000/mm 3 in burn-wound patients treated with either SSD or silver nitrate within 3 days of injury (40 of 84 after SSD and 13 of 30 following silver nitrate therapy). Choban and Marshall confirmed this risk in patients with 15% total body surface burn wounds, but demonstrated that WBC normalised when SSD or silver nitrate therapy was withdrawn with no further complications [118].…”

Section: Manifestations Of Silver Toxicitymentioning

confidence: 99%

A Pharmacological and Toxicological Profile of Silver as an Antimicrobial Agent in Medical Devices

Lansdown

2010

Advances in Pharmacological Sciences

233

219

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Silver is used widely in wound dressings and medical devices as a broad-spectrum antibiotic. Metallic silver and most inorganic silver compounds ionise in moisture, body fluids, and secretions to release biologically active Ag+. The ion is absorbed into the systemic circulation from the diet and drinking water, by inhalation and through intraparenteral administration. Percutaneous absorption of Ag+ through intact or damaged skin is low. Ag+ binds strongly to metallothionein, albumins, and macroglobulins and is metabolised to all tissues other than the brain and the central nervous system. Silver sulphide or silver selenide precipitates, bound lysosomally in soft tissues, are inert and not associated with an irreversible toxic change. Argyria and argyrosis are the principle effects associated with heavy deposition of insoluble silver precipitates in the dermis and cornea/conjunctiva. Whilst these changes may be profoundly disfiguring and persistent, they are not associated with pathological damage in any tissue. The present paper discusses the mechanisms of absorption and metabolism of silver in the human body, presumed mechanisms of argyria and argyrosis, and the elimination of silver-protein complexes in the bile and urine. Minimum blood silver levels consistent with early signs of argyria or argyrosis are not known. Silver allergy does occur but the extent of the problem is not known. Reference values for silver exposure are discussed.

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“…70,73 Its bone marrow toxicity has been controversial because most of these studies are in burn patients who exhibit a reactive leukopenia, with or without application of silver sulfadiazine. 68,69,71,75,76 The extent of leukopenia appears to be related to the total body surface area undergoing application (> 30% total body surface area results in a higher risk of leukopenia) and the use of other medicines that may contribute to bone marrow suppression, such as cimetidine. Silver sulfadiazine has excellent antimicrobial activity against gram-positive and gram-negative bacteria, as well as yeast.…”

Section: Topical Antibioticsmentioning

confidence: 99%

Update on the Use of Antibiotics in Cutaneous Surgery

Messingham¹,

Arpey²

2005

Dermatologic Surgery

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BACKGROUND. Antibiotics are often prescribed in perioperative settings, including dermatologic surgery. Given the continued evolution in the breadth and complexity of cutaneous procedures performed and inevitable localized or distant infections that occasionally occur, it seems prudent to periodically evaluate findings and recommendations from the literature regarding the use of antibiotics in cutaneous surgery.

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Leukopenia in Acute Thermal Injury: Evidence Against Topical Silver Sulfadiazine as the Causative Agent

Cited by 27 publications

References 0 publications

Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review

Toxicity of silver ions, metallic silver, and silver nanoparticle materials after in vivo dermal and mucosal surface exposure: A review

A Pharmacological and Toxicological Profile of Silver as an Antimicrobial Agent in Medical Devices

Update on the Use of Antibiotics in Cutaneous Surgery

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