Numerous factors may alter wound healing, a normally ordered process mediated by overlapping and interconnected biochemical interactions and cells. When healing stalls, one of the wound bed preparation players is off-balance. Whether the problem is compromised tissue needing debridement, infection (from colonization to actual infection), moisture balance, or an unhealthy wound edge, the cause(s) have to be addressed. Bacterial colonization and infection always come to mind (especially in immunocompromised populations; see cases to follow), but other factors to consider include ischemia, lack of extracellular matrix, poor nutrition (eg, compromised protein and essential nutrient uptake that commonly affect premature neonates and chronically challenged, oncologically affected immunocompromised children), medication that interferes with healing, biologic inflammatory milieu imbalance, edema, and moisture imbalance.
Many of these factors have been discussed in previous columns. This month I discuss methylene blue (MB) and gentian violet (GV) and their topical antimicrobial and drying utility both as separate entities and in combination with an absorbent foam to help heal wounds that had been refractory to other interventions.
GV. GV is a triarylmethane dye with antibacterial/antifungal/helminthic (immunotherapeutic) properties that hinder mitochondrial activity, decrease energy supply (altered oxidation-reduction [redox] potential, inhibition of reduced nicotinamide adenine dinucleotide phosphate oxidase, and free radical formation), and cause microbial death.1 GV is thought to inhibit bacterial protein synthesis, uncouple oxidative phosphorylation, and inhibit formation of bacterial cell walls; it also has antitumor and antiangiogenic properties (reducing overly proliferative granulation tissue). GV is highly effective against gram-positive microbes, especially Staphylococcus aureus1 and has been shown to be effective in treating dermatitis, particularly radiation and atopic dermatitis.2 Cells with atopic dermatitis express high levels of the protein angiopoietin-2, which accounts for their vascular permeability and erythema and frequent gram-positive colonization. GV can impact bacterial colonization and proinflammatory mediators. Case reports mention the theoretical oncogenic potential of GV (if consumed systemically) because it can interact with the DNA of cells, but to date no cases of cancer have been definitively linked to GV. I initially started using a 1% solution of GV after coming across a publication describing its antimicrobial/drying effects on periostomy skin injury from exudate in children.
MB. MB is an organic antimicrobial cationic dye with a strong affinity for dead cells. MB is especially potent for gram-negative bacteria and fungi and attaches to protein-rich exudate and infectious debris. MB affects redox potential in many electron transport components of oxidative metabolism, “short circuiting” the bacterial electron transport pathway. MB reduces antimicrobial burden, decreases hypergranulation, and has a drying effect without harming healthy cells. Similar to GV, MB is easy to apply, water-soluble, and dries quickly; its effect is potentiated with light application.
GV and MB solutions can be used in conjunction with enzymatic debriders, hydrogels, and advanced dressings. Original research studies have shown MB has the ability to inactivate antioxidant enzymes such as superoxide dismutase, catalase, and peroxidase, leading to decreased extracellular matrix degradation. MB decreases nitric oxide-mediated vasodilation, thereby decreasing tissue ischemia, edema, and weepy/macerated wounds.
MB contraindications. Use of MB is contraindicted in persons with a history of hypersensitivity, renal insufficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and/or hemolytic anemia with Heinz bodies. It is not recommended for use in pregnant women or neonates due to increased hyperbilirubinemia in G6PD-deficient neonates and those with hemolytic anemia. In general, MB is used in various systemic conditions in large doses and its safety record is excellent.
Combination of MB/GV. Using a polyvinyl foam imbued with GV/MB provides all of the aforementioned effects in addition to exudate wicking, debridement, enhanced reepithelialization, prevention of rolled edges or epibole, pain relief (it is considered a nonadherent dressing when appropriately moist), and antimicrobial action without systemic absorbtion.3