Successful Management of Complex Pediatric and Neonatal Wounds With Methylene Blue and Gentian Violet Foam Dressings

Pediatric wound management has traditionally involved administering systemic antibiotics and topical antibiotic agents. Unfortunately, these approaches often prove unsuccessful for biofilm prevention, slough removal, and optimal wound bed preparation. Topical antimicrobial application in pediatric, and especially neonatal, patients is challenging. Factors complicating antimicrobial application include increased systemic absorption, damaging inflammatory cytokines, and oxygen radicals released during bacterial death.

Neonatal preterm skin is uniquely challenging. Preterm skin is extremely fragile compared with full-term and pediatric skin. Preterm skin has fewer layers of stratum corneum, resulting in increased transcutaneous epidermal water loss and topical product absorption. In addition, the skin mantle is less acidic, which increases the likelihood of microbial organism colonization. There are also fewer anchoring fibrils at the dermal/epidermal junction, resulting in elevated risk of epidermal stripping with adhesive devices. The dermis and subcutaneous tissue are less robust, which increases the risk of pressure injuries.

Despite these unique challenges, neonatal wounds follow the same 4 stages of wound healing as other wounds: hemostasis, inflammation, proliferation, and remodeling. Wound healing must be supported through this cascade. When selecting wound care products, it is important to consider the specific characteristics of neonatal skin, particularly the deficiency of systemic oxygen radical scavengers and the need to decrease the inflammatory milieu. The ideal product should address all wound bed preparation principles, including keeping the wound moist, decreasing ongoing inflammation, providing antibacterial coverage, and promoting a healthy tissue edge. A product with a painless, infrequent application and atraumatic removal is preferred to minimize epidermal stripping/skin tears and pain. Although negative pressure wound therapy (NPWT) can benefit certain wounds, NPWT in small neonates can be challenging owing to hemodynamic instability, pain, and skin tolerance concerns. Furthermore, NPWT placement can be difficult owing to the small and curvy wound area. In older children, concern for wound infection, osteomyelitis, or challenging anatomic areas may also preclude NPWT.

This case series describes the author’s experiences with methylene blue and gentian violet (MB/GV)-impregnated foam technology—both polyvinyl alcohol (PVA) and polyurethane (PU) foams—in pediatric patients with wounds. This case series included infants with giant omphalocele epidermal stripping, dehisced abdominal wounds, peristomal dermatitis, and peripheral intravenous extravasations and adolescents with stage 4 pressure injuries.

Methylene blue and gentian violet PVA foam or MB/GV PU foam with moisture-retentive backing dressings were used (Hydrofera Blue Ready, Hydrofera Blue Classic; Hydrofera, LLC). Dressings were cut to shape. Polyvinyl alcohol foam was hydrated as needed. Depending on the wound, a secondary dressing was also used. Dressings were changed every 2 to 3 days. Wounds with thick slough underwent gentle mechanical debridement if indicated. Enzymatic debrider (Collagenase; Smith & Nephew) was added in cases 3, 7, and 8 to lift slough synergistically with the foam dressing. During therapy, 3 patients received systemic antibiotics, which were prescribed to address systemic comorbidities that predated the wounds.

Eight cases (100%) demonstrated successful debridement, antibacterial coverage, exudate absorption, decreased wound edge thickness, and appropriate wound bed preparation for successful healing using MB/GV foam dressings. Six wounds (75%) were observed to heal completely, and 2 wounds were healing well when patients were transferred to a different facility and lost to follow-up.

Negative pressure wound therapy was considered for but not used in 3 wounds (cases 5, 7, and 8). Reasons for not using NPWT were as follows: challenging location in all 3 cases, and in 2, both involving pressure injuries, concerns existed for osteomyelitis, which precluded NPWT use. The MB/GV PVA foam was chosen because of the capillary wicking action of this dressing. A clean wound bed was achieved in all cases.

Additional wound care products were administered in 4 cases. Case 3 received hydrolyzed collagen powder (Hycol; Sanara MedTech Inc) because the wound had a slow healing trajectory. Case 4 received medical grade active Leptospermum honey (MediHoney; Integra Lifesciences), which the author’s clinic typically uses in extravasation wounds. In case 8, hydrolyzed collagen powder followed by dehydrated amniotic membrane was used owing to the significant depth of the wound. Case 5 achieved complete slough removal and beginning of granulation tissue formation with the MB/GV PVA dressing alone. Thereafter, hydrolyzed collagen was added to complete closure. No side effects attributable to MB/GV foam dressings were noted. The Table describes the demographics and outcomes of all 8 cases. All cases are described in greater detail herein.

Neonatal cases

Case 1: giant omphalocele

The patient was a 55-day-old infant, born at 33 weeks gestational age, with an almost fully epithelialized giant omphalocele, congenital cardiac defects, persistent pulmonary hypertension, and respiratory insufficiency. Omphalocele is a congenital abdominal wall defect in which an infant’s intestine or other abdominal organs remain outside the body, secondary to failure to return to the intestinal cavity through the umbilical opening (Figure 1A).

In this patient, skin breakdown, slough, and bacterial colonization with methicillin-susceptible Staphylococcus aureus developed on a portion of the omphalocele. The intestines were covered only by a thin layer of amniotic tissue. A sclerotic agent, silver sulfadiazine cream, was used to dry the amnion and epithelialize the omphalocele. Areas of skin breakdown presented with slough, constant thin exudate, and occasional bleeding (Figure 1B). The etiology was likely positional friction and shear against bed linens. Previous treatments were ineffective, including usage of skin polymer, silver foam, and gauze over the course of more than 10 days. Management was changed to MB/GV PVA foam, slightly moistened with normal saline, and covered with Kerlix gauze (Cardinal Health). The dressing was changed every 2 to 3 days. Decreased moisture was observed after the first change on day 2 (Figure 1C). Slough was minimized after 2 dressing changes. Exudate was manageable, and the wound was kept dry and further maceration was prevented. The wound completely healed within 10 days.

Case 2: giant omphalocele

The patient was 76-days-old, born at 36 weeks gestational age, with multiple comorbidities and giant omphalocele with an outer skin breakdown accompanied by constant oozing and maceration. Thin slough was observed. As in case 1, MB/GV PVA foam was applied (Figure 2A). Slough was removed after 2 dressing changes (4 days), and new granulation growth occurred within 1 week (Figure 2B), with complete epithelialization achieved by day 16.

Case 3: neonatal peripheral intravenous catheter extravasation

A 10-day-old patient was born at 33 weeks gestational age, with intrauterine growth retardation and sustained stage 4 extravasation. The wound required debridement because slough was prevalent (Figure 3A). Collagenase was covered by MB/GV PVA foam, and an outer silicone dressing was applied (Figure 3B). In addition, collagenase was applied daily. Noticeable improvement was seen by day 4 (Figure 3C), augmented by gentle mechanical monofilament debridement. The wound bed was clean by day 6. Methylene blue and gentian violet PVA foam was used to enhance debridement and reduce the antibacterial burden. Once the wound bed was clean, the proliferative stage was enhanced with hydrolyzed collagen powder, which was applied to the wound bed every 3 to 4 days and covered by a small piece of a perforated contact layer (Mepitel; Mölnlycke Health Care). The MB/GV foam was continued for 3 more days, after which management was transitioned to collagen covered by a secondary dressing. The wound healed completely by 3 weeks (Figure 3D).

Case 4: neonatal peripheral intravenous catheter extravasation

This 20-day-old preterm patient was born at 29 weeks gestational age with peripheral intravenous extravasation. The wound was very irregular, with thickened edges and significant slough, and was slow to heal. A piece of foam dressing was cut to shape and applied to the wound. This foam dressing was changed every 2 days. The wound bed was clean after 3 changes. Methylene blue and gentian violet foam was continued for 3 more days, after which management was transitioned to medical-grade honey as per the unit’s secondary dressing protocol. The wound healed within 2 weeks.

Case 5: dehisced colonized surgical
abdominal wound

An 8-day-old infant was admitted for nonbilious vomiting, abdominal distention, lethargy, failure to gain weight, and failure to pass stool for the prior 3 days. Radiographic examination raised suspicion for low intestinal obstruction, specifically Hirschsprung disease. Biopsy was positive for the lack of nerve cells (ganglions) in a large segment of the bowel. Part of the bowel was poorly developed and resected; temporary mucous fistula and an ostomy were created to allow growth before definitive surgery. Three days after surgery, the middle area of the original incision dehisced. This dehiscence was particularly challenging because it was between the stoma and mucous fistula (Figure 4). Initially, the surgical team managed the wound using hydrofiber (Aquacel; ConvaTec). However, the wound remained open with increasing slough and thickening edges. Swabs revealed the wound to be colonized with gram-positive bacteria. At that point, management was changed to MB/GV PU foam, which was cut to shape. An ostomy appliance was also placed over the stoma. Within 1 week, the edges were flatter, slough was removed, and the dehisced area was contracting with growing granulation tissue. Hydrolyzed Collagen (Hycol) was added twice, with the second application 3 days after the first, to complete epithelialization.

Case 6: peristomal irritant dermatitis

A 2-month-old infant developed peristomal dermatitis secondary to increased effluent and skin irritation from the appliance. Colostomy was originally performed as a result of intestinal malrotation and volvulus, requiring significant intestinal resection. Feeding intolerance was noted prior to admission, possibly due to the introduction of a new formula; this increased stoma output. Various treatments had been tried for 1 week, including crusting, skin polymer, zinc cream, and powder. An oversized MB/GV PVA ostomy dressing was placed around the stoma. A colostomy barrier ring and colostomy bag were placed on top of that dressing. The dressing successfully retained moisture, which allowed an increased interval between appliance changes (range, 8 hours–36 hours to 48 hours) and facilitated skin healing.

Pediatric Cases

Case 7: sacral pressure injury

A 14-year-old male with Stevens-Johnson syndrome, systemic bacterial infection, shock, respiratory failure requiring intubation, and kidney failure was admitted. He continued to deteriorate and was placed on extracorporeal membrane oxygenation. The patient’s hemodynamic status was very labile, interfering with effective repositioning. Multiple pressure injuries developed, including a stage 4 sacral injury with possible underlying osteomyelitis. This sacral wound required significant enzymatic and autolytic debridement and had copious exudate and thickened edges. Sharp and mechanical debridement were not considered as viable options because the patient was initially on heparin and disseminated intravascular coagulation with thrombocytopenia had also devel0ped. The use of MB/GV PVA foam provided strong wicking, enhanced exudate absorption, and debridement. After 1 week, the wound bed was cleaner. After 10 days, the edges were flatter and granulation tissue had begun to develop. The foam dressing was continued to maintain a healthy wound bed. The patient was transferred to a rehabilitation facility after 3 weeks.

Case 8: sacral pressure injury

A 15-year-old male was admitted for respiratory failure, coming from a long-term rehabilitation facility. He had a history of cerebral palsy, non-mobility, and neurodevelopmental delay. On admission, a stage 4 sacral pressure injury was found. Wound infection was of concern because of the presence of slough, strong odor, tissue friability, periwound erythema, and rolled edges. Culture from the wound, tracheal secretions, and urine grew Escherichia coli. Systemic antibiotics were administered. Previous wound treatments had been attempted at the long-term rehabilitation facility, including silver-based packing, with no improvement (Figure 5A). Management was changed to collagenase covered with MB/GV PVA foam for 1 week (Figure 5B). The dressing was changed every 2 days as it was difficult to keep the wound clean of fecal matter. Mechanical debridement with monofilament pad was done with every change. After 8 days, the wound bed was clean. Management was changed to hydrolyzed collagen powder covered by MB/GV PU foam and eventually dehydrated amniotic membrane. A repeat wound culture on day 5 was negative. The patient was transferred to a rehabilitation facility and lost to final follow-up, but the wound was healing well prior to transfer (Figure 5C).

The following dressing attributes are essential in pediatric wound care: effective debridement that is as painless as possible, a nontoxic antibacterial action, inflammation reduction, and moisture sensitivity. Secondary dressing considerations include promotion of healthy edges, wound protection, and atraumatic removal. The MB/GV antibacterial foam dressings fulfilled these desired attributes for the patients described in this case series.

Several reasons for these desired dressing attributes have been hypothesized. The microporous structure of MB/GV PVA foams enhances absorption and creates a capillary action that resembles the pulling action of NPWT.^1,2 Although NPWT often is beneficial clinically, there are many scenarios in which it cannot be used. Negative pressure wound therapy can be challenging to apply in exceedingly small spaces (eg, some wound locations in neonates) or in certain anatomic locations in older children. In addition, hemodynamically unstable neonates may not be appropriate candidates for NPWT given the concern of negative pressure being higher than mean blood pressure and a potential cause of blood pressure instability, a concern described in the literature. In both PVA and PU foams, bacteria in the exudate draw into the foam, where the bacteria come into contact with GV and MB organic dyes. Therefore, using the microporous structure of MB/GV PVA foam as a pulling capillary action resembles NPWT microstrain action, without the hemodynamic instability or risk of granulation tissue ingrowth into the foam or epidermal stripping during adhesive dressing removal associated with NPWT.

In 2014, the United States Food and Drug Administration approved these dressings as antibacterial.¹ This antibacterial action is as follows. The MB/GV dyes work via interference with the oxidation-reduction (redox) potentials in the electron chain transport steps of oxidative metabolism. Bacteria rely on energy generated via this process. By short-circuiting the energy-generating process, the MB/GV dyes create the equivalent of a hypoxic environment, making metabolism impossible.¹ Gram-positive bacteria, gram-negative bacteria, and fungi appear to be susceptible to this action. Both MB and GV dyes are bound to the foam. When bacteria enter the foam, GV has a preferential binding affinity to gram-positive bacteria, and MB has a higher binding affinity to gram-negative bacteria. Upon contact with the exudate, the dyes do not become diluted or systemically absorbed while killing bacteria on contact with the foam.^3,4 The PVA foam has been shown to be effective in eliminating biofilm and suppressing new bacterial growth.^3-7

The MB/GV PVA foam dressings used in this case series have other advantages, such as effective absorption of exudate, including inflammatory mediators, proteases, bacterial debris, and the wicking away of extra fluid, which likely contributes to decreasing inflammation.⁸ Another interesting property of MB/GV PVA foam dressings is the support of wound edges.⁵ The PVA dressing activates edge keratinocytes and enhances migration across the wound, although the mechanism of action remains unclear. Polyvinyl alcohol dressing flattens rolled edges or epibole, minimizing the need for aggressive debridement.⁵ As dressings, both foams were soft, comfortable, pliable, and easy to remove. Upon dressing removal, the patients’ pain scores did not change, regardless of patient age.

All the wounds in this case series improved with MB/GV foam use. Autolytic debridement was achieved along with anti-inflammatory and antibacterial effects, as appearance of wounds improved and cultures were negative. Published studies of adults support these outcomes, especially in the setting of chronic wounds.^3,4 Woo and Heil³ demonstrated effective debridement and healing of various pressure ulcers and surgical wounds. Some studies have shown synergistic effects of PVA foam with collagenase on wound debridement.^4,9 In 2 separate studies, Sibbald et al⁵ and Coutts et al⁶ demonstrated effective antibacterial, debriding, anti-inflammatory, and edge action of the dressing in adult wounds. Hill¹⁰ presented results regarding removal of devitalized tissue using MB/GV dressings in a variety of adult wounds, including pressure injury, surgical nonhealing wounds, and dehisced surgical wounds. Furtado¹¹ described the use of PVA foam in a premature neonate in whom an open abdomen secondary to intestinal perforation developed. In this case, surgery could not close the abdomen to contain the bowel, and MB/GV foam was used to protect the bowel while acting as a mild NPWT and exudate absorber. Granulation tissue developed after 7 days.

Alternative dressings are also available. Silver- and iodine-infused foams, hydrofiber, and alginates are common in adult practice. Pediatric practitioners should be cautious about using silver and iodine applications, because potential side effects include thyroid dysregulation, argyria, leukopenia, agranulocytosis, and kernicterus, none of which is desired in neonatal and critically ill pediatric patients.¹² In this author’s personal experience, medical-grade honey gel works well but takes a longer time compared with enzymatic or mechanical debridement to enhance autolytic debridement. The desire for minimal moisture precludes the use of medical-grade honey on the omphalocele wounds and peristomal dermatitis described in this case series. Hydroconductive dressings contribute to excellent moisture wicking but do not provide simultaneous antimicrobial coverage. Alginates are known to donate calcium in exchange for sodium, causing potential concern for hypercalcemia. Concern for hypercalcemia, and therefore use of alginate, would be a particular contraindication in neonates and critically ill pediatric patients with renal abnormalities. Dehydration is another concern in managing large neonatal wounds, as alginates are highly viscous hydrophilic products.¹³ Silver-infused hydrofiber was used initially in 3 of the wounds reported herein, with suboptimal outcomes.

The main limitation of this study is that it was a retrospective, single-center case series with a limited number of patients. Outcomes reported reflect the author’s experiences.

To the author’s knowledge, this is the first case series describing the use of MB/GV foams in neonatal and pediatric patients with various wounds. Pediatric wounds, especially neonatal wounds, have unique needs and challenges. By using MB/GV foams, the present author found the following advantages: enhanced debridement, adequate antimicrobial coverage, appropriate granulation tissue support, and superior edge cell stimulation. Caregivers thought that the dressings were comfortable and easy to apply and remove. No local or systemic side effects were noted. In summary, the MB/GV foam dressings fulfilled many aspects of appropriate wound management and supported successful wound healing. These results support MB/GV dressings as a safe alternative for antibacterial and debridement management in neonatal and pediatric patients.

Author: Vita Boyar, MD

Affiliation: Cohen Children’s Medical Center, Great Neck, NY

Correspondence: Vita Boyar, MD, Cohen Children’s Medical Center, 269-01 76 Ave, New Hyde Park, NY 11020; Vboyar@northwell.edu

Disclosure: The author discloses no financial or other conflicts of interest.