Table 3.

Limitations of common topical agents used in wound healing.

Name	Side effects and limitation	References
Silver nitrate	(1) Skin discoloration and irritation	[169]
	(2) Toxicity to epithelium	[170]
	(3) The bacterial reduction of nitrate to nitrite may lead to methemoglobinemia with the use of this topical agent	[171]
Silver	Absorption, systemic distribution, and excretion in urine	[169]
Polyhexamethylene biguanide	Ineffective when there is a measurable degree of wound fluid suppuration because of its short residence times on the wound site	[172]
Proflavine	Induces mutations in bacterial and cell cultures	[173]
Povidone iodine	(1) Short residence times on the wound site	[172]
	(2) Can cause severe metabolic acidosis	[174]
	(3) Cytotoxicity against leukocytes, fibroblasts, and keratinocytes	[175]
	(4) Polymorphonuclear leukocytes are inhibited by this topical agent	[176]
	(5) Povidone iodine has also reportedly been inactivated by wound exudates	[177]
	(6) May “harden” wound eschar rather than softening it, thus increasing the difficulty and discomfort of wound debridement	[178]
	(7) Should not be used during pregnancy, on a newborn, on small children, or on patients with suspected or known thyroid disease	[179]
Hydrogen peroxide	(1) Formation of air emboli in wounds	[180]
	(2) The mechanical cleansing effect of hydrogen peroxide, often attributed to its “fizzing” (which is caused by its decomposition into oxygen and water when it comes in contact with blood and tissue fluids), is questionable	[181]
	(3) Is toxic to fibroblasts	[182]
	(4) Impairs the microcirculation of wounds	[183]
	(5) Limited bactericidal effectiveness	[182]
Diluted iodine solutions (iodine solution USP [United States Pharmacopeia]  [2% iodine, 2.5% sodium iodide] and Iodine tincture USP [2% iodine, 2.5% sodium iodide, 50% alcohol])	May irritate tissue, stain the skin, and cause sensitization	[184]
Povidone iodine	Contact dermatitis has been reported with prolonged uninjured skin exposure to ointment	[185]
Chlorhexidine	(1) Associated with few adverse effects on healing	[175]
	(2) MRSA resistance has been found	[186]
Chlorhexidine gluconate solution	Prolonged, repeated use may lead to contact dermatitis	[187]
Acetic acid 0.5%.	(1) Acetic acid has demonstrated toxicity to fibroblasts in culture	[188]
	(2) Reduced epithelial cell proliferation in culture	[189]
	(3) Delayed healing of cultured epithelial autografts has been reported at 0.25% strength	[190]
	(4) Acetic acid has been shown to reduce PMN function	[176]
Sodium hypochlorite (Dakin's solution)	(1) Has caused toxicity to fibroblasts in culture	[170]
	(2) Toxicity to keratinocytes in culture	[170]
	(3) Polymorphonuclear leukocyte viability is inhibited	[176]
	(4) Acidosis may result from continuous use over large-area wounds. This solution may also cause pain	[178]
Topical pharmaceutical semisolid formulations (ointments and creams)
Silver sulfadiazine cream	(1) Not effective for highly exuding wounds; rapidly absorbs fluid, loses its rheological characteristics, and becomes mobile as it remains on wounds for longer periods of time	[172]
	(2) 3–5% incidence of reversible leucopenia	[191]
	(3) There is evidence that silver sulfadiazine is toxic to human keratinocytes and fibroblasts in vitro	[170]
	(4) Should be avoided during pregnancy, on premature infants or on infants younger than 2 months of age	[192]
Silver nitrate ointment	Same problems as silver sulfadiazine cream	[172]
Neosporin	Hypersensitivity is more common because of the presence of neomycin in the ointment	[178]
Nitrofurazone 0.2% compound	(1) Bacteria may develop mild resistance with prolonged use	[178]
	(2) Detrimental effects on the growth and migration of keratinocytes in culture	[170]
	(3) The development of the usual symptoms of contact dermatitis (rash, local edema, and pruritus)	[178]
Gentamicin 0.1% cream	(1) Can inhibit PMN activity	[176]
	(2) Skin hypersensitivity has been reported	[178]
	(3) Ototoxicity and nephrotoxicity can occur, particularly when used in large volumes or for an extended period of time	[193]
Mafenide acetate 0.5% cream (Sulfamylon)	(1) Inhibits human keratinocytes and fibroblasts in vitro	[170]
	(2) Mafenide suppresses PMN and lymphocyte activity	[31, 51]
	(3) The chance of a sulfa allergy is higher with mafenide acetate, and rashes may be seen in approximately 50% of patients receiving mafenide treatment	[177]
	(4) Toxicity may increase in correlation with the duration of treatment and size of the treated area	[194]
	(5) Painful upon application	[195]
Neomycin ointment	(1) Hypersensitivity reactions, particularly skin rashes, also occur more frequently with neomycin (occurring in 5%–8% of patients)	[196]
	(2) Ototoxicity and nephrotoxicity have been reported for large wounds	[193]