Does The Scientific Evidence Support The Idea of Promoting Sucralfate As The First Aid Topical Management for Burn Wound? A Literature Review

ABSTRACT


INTRODUCTION
A burn injury occurs when the skin contacts a heat source such as heat, chemicals, radiation, or electricity.The severity of a burn injury varies, and the extent of the body surface area affected significantly impacts both wound morbidity and patient mortality. 1Burn associations classify burn injuries based on various factors, including severity, affected area, and depth.The American Burn Association (ABA) classifies burns by depth and severity: 2 • Superficial partial-thickness burns, or first-and seconddegree burns, affect the epidermis and possibly part of the dermis, causing redness, blisters, or white, edematous skin.
• Full-thickness burns, or third-degree burns, penetrate the entire epidermis and dermis, resulting in whitish or charred skin and eschar formation.
• Fourth-degree burns extend into the subdermal fat and may involve deeper tissues such as muscle or bone.Early and effective burn wound management is crucial in mitigating both short-and long-term consequences.Prompt treatment significantly reduces the risk of infection, a common complication following burn injuries. 3Early management also prevents further tissue damage and complications such as contractures, which severely impair mobility and quality of life.Prioritizing immediate and appropriate care greatly improves outcomes, facilitating smoother recovery and better overall prognosis. 1,4arious medications and topical treatments manage burn injuries.Sucralfate, composed of sucrose sulfate and aluminum hydroxide (see Figure 1), is a potent mucoprotective agent initially used for peptic ulcers. 5One study noted that sucralfate adheres to wounds and forms a protective layer, reducing pain, stimulating healing, and preventing secondary infections. 6Sucralfate also has antiinflammatory effects and accelerates tissue regeneration.Based on those theoretical foundation, clinicians have regularly applied sucralfate as the first aid topical therapy for burn wound.We conducted this review to find out whether the scientific evidence support such idea, or it may need further research to validate potential benefits of sucralfate in burn wound management. 5,7igure 1.Sucralfate molecular structure PHARMACOLOGICAL PROPERTIES OF SUCRALFATE Sucralfate, a medication primarily used to treat and prevent ulcers, particularly in the duodenum, forms a protective barrier over ulcers. 8Comprising a basic aluminum compound with sucrose octasulfate, sucralfate shields ulcers from stomach acid and promotes healing.Beyond ulcer management, sucralfate treats various conditions such as epithelial wounds, mucositis caused by chemotherapy, radiation proctitis, ulcers related to Behcet's disease, and burn injuries. 9The gel-like substance created by sucralfate stimulates prostaglandin secretion, enhancing ulcer healing.Additionally, sucralfate binds to proteins in the ulcer bed, forming a complex that strengthens the local defense mechanisms of gastrointestinal mucosa. 10,11esearchers have extensively studied the pharmacokinetics of sucralfate.Haller and colleagues found that sucralfate has low bioavailability because most of it is not absorbed in the digestive tract and is excreted through feces.Consequently, sucralfate concentrations in the blood remain low, resulting in minimal systemic effects.Despite low absorption, sucralfate can penetrate injured stomach and intestinal tissues, where it acts locally to stimulate healing. 11nderstanding the safety profile and potential side effects of a drug is crucial.Sucralfate is generally safe, with the most common side effects being mild gastrointestinal disorders such as constipation or diarrhea, which typically resolve on their own.Allergic reactions to sucralfate are rare.However, medical supervision is essential, especially for patients with a history of allergies or other conditions that may affect drug tolerance. 11,12FICACY OF SUCRALFATE IN BURN WOUND HEALING* Sucralfate, commonly used for gastrointestinal issues, shows promising potential in topical wound healing.Applied externally, sucralfate forms a protective layer over wounds, shielding them from irritants and creating an optimal healing environment.Its adhesion to mucosal surfaces extends to the skin, acting as a barrier to prevent infection and reduce inflammation.Sucralfate also stimulates the secretion of growth factors, enhancing tissue regeneration. 13,14arious clinical studies have evaluated effectiveness of sucralfate in patients with burn injuries.Smith and colleagues found that sucralfate significantly improved wound healing in low-and moderate-grade burns.5][16] These studies highlight the potential of sucralfate in improving burn wound care, although further research is necessary to validate these findings more broadly. 15,16oshariya and colleagues studied 50 patients, comparing topical sucralfate with silver sulfadiazine.They found sucralfate effective in healing burn wounds, reducing pain without causing adverse reactions.Sucralfate accelerated cell proliferation in superficial skin layers, thickening the epidermis and dermis. 7Lumintang and colleagues also found sucralfate cost-effective and free of systemic side effects in second-degree burns, particularly beneficial in developing countries. 17ase reports and series, such as those by Brown and colleagues and also by White and colleagues provide additional evidence of efficacy of sucralfate in burn wound healing, though these findings should be interpreted cautiously. 18,19Comparative studies, like that of Johnson and colleagues, show the advantage of sucralfate over standard therapies such as silver sulfadiazine in accelerating wound healing and reducing pain. 20haker and colleagues conducted a one-year randomized controlled trial comparing sucralfate and silver sulfadiazine in second-degree burns.They found sucralfate more effective in promoting early granulation, with equivalent antibacterial activity. 21Clinical evidence supports the benefits of sucralfate for various wound types, including burns, cutaneous erosions, mucositis, and non-healing ulcers.Sucralfate increases basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) concentrations in wound tissue, inhibits pro-inflammatory cytokines, and promotes angiogenesis and granulation tissue development. 17,18,22urther research is needed to determine the optimal dosage, duration, and patient selection for sucralfate use.Existing evidence indicates the great potential of sucralfate in burn wound healing.While more studies are required to establish clearer guidelines, current findings suggest sucralfate as a valuable addition to burn wound management, aiming to improve care and outcomes for burn patients.

MECHANISMS UNDERLYING THE EFFECTS OF SUCRALFATE
Pharmacologically, sucralfate enhances mucosal vascular integrity and blood flow, increases bicarbonate and mucus secretion, and binds to fibroblast growth factor (FGF) and epidermal growth factor (EGF), improving growth factor function and promoting angiogenesis, granulation tissue formation, and epithelialization.This summarily boosts epithelial wound regeneration. 7,13he crucial mechanism in epithelial wound healing is interaction of sucralfate with fibroblast growth factor (FGF), a class of heparin-binding proteins including basic fibroblast growth factor (bFGF) and acid fibroblast growth factor (aFGF), which later stimulate mitotic, chemotactic, and angiogenic activity in epithelial cells as well as supporting endothelial cells, chondrocytes, and fibroblast activities.
Sucralfate binds to bFGF, protecting it from acid degradation and inactivation, while its soluble potassium salt and insoluble aluminum salt of sucrose octasulfate bind with high affinity to stabilize aFGF against denaturation, preserving its mitotic and angiogenic abilities.By promoting affinity of fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFr), sucralfate induces angiogenesis and cell proliferation at the wound border.Sucralfate also binds to epidermal growth factor (EGF), increasing its availability and promoting wound healing through increased cell proliferation. 7,13,18rostaglandin E2 (PGE2) plays a crucial role in angiogenesis and anti-inflammatory functions.Tumor necrosis factor alpha (TNF-α) promotes a cyclooxygenase-2 (COX-2) -mediated mechanism, enhancing wound healing and angiogenesis through bFGF.Studies showed sucralfate administration increased PGE2 levels in patients with ulcers.It also raises levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1α, an anti-platelet-aggregation agent and vasodilator), thromboxane B2, and phospholipase A2.Prostaglandin E2 (PGE2) also stimulates vascular endothelial growth factor (VEGF) release through EP4 receptor activation, promoting angiogenesis. 7,13ucralfate also offers antimicrobial benefits, acting more bacteriostatic than bactericidal, especially against gramnegative bacteria.It lowers the minimum inhibitory concentration of antibiotics like metronidazole, tetracycline, erythromycin, and amoxicillin, enhancing their antimicrobial activity in gastric ulcers. 7,13orresponding Author: Angela Maria Linata CONSIDERATIONS FOR CLINICAL PRACTICE Sucralfate, widely patented as a topical agent, enhances wound healing.Studies and reports showed how it treats anorectal diseases like hemorrhoids, dermal wounds, aphthous ulcers, and various tissue conditions.3][24] Sucralfate also treats dental conditions, painful anal conditions when combined with nitroglycerin, and burn-related skin irritations.When combined with other drugs, sucralfate improves skin appearance and treats scars and rosacea.It also increases the bioavailability of growth factors and delivers TGF-for mucositis treatment.A new method for transdermal sucralfate delivery has been patented for various disease applications. 14n clinical practice of burn cases, selecting appropriate patients for sucralfate therapy ensures its effectiveness.
Optimal formulation techniques and integration with standard burn wound care protocols also play key roles in successfully using sucralfate for burn wound therapy.Sucralfate, without current guideline interference, may complement topical silver sulfadiazine to enhance wound healing.The American Burn Association (ABA) recommends applying a topical dressing for debris blisters over 2 cm, fullthickness burns, and partial-thickness burns.Cream can be applied directly to the burn or impregnated into gauze.The topical dressing includes primary and secondary dressings.The primary dressing usually involves topical antimicrobial medication, such as silver sulfadiazine (SSD) 1% and bacitracin.Other topical dressings may be used alone or in combination, depending on the wound depth.Sucralfate can be added as a secondary dressing, providing mechanical protection directly or indirectly through impregnated gauze, ensuring it does not interfere with perfusion. 2he European Burn Association (EBA) recommends assessing possible wound infections alongside burn injuries and using prophylactic antibiotics.Antimicrobial dressings are used appropriately to reduce the risk of burn wound infection.The principal aim of burn wound dressing is to maintain a moist wound environment, manage exudate, minimize biofilm formation or infection, and ensure comfort.
The EBA acknowledges that no ideal dressing exists and suggests that dressing selection should be based on individual clinical conditions. 25

LIMITATIONS AND FUTURE DIRECTIONS
Sucralfate therapy has emerged as a significant pharmacological option for treating burns and various digestive issues.This agent offers the potential to accelerate healing and alleviate symptoms associated with these conditions.However, uncertainties and limitations still obscure our understanding of the true effects and broad clinical applications of sucralfate.

Figure 2 .
Figure 2. The molecular mechanism of action of sucralfate in epidermal and dermal wound healing.
CONCLUSIONSucralfate, traditionally used for gastrointestinal ulcers, shows promising potential as a first aid topical therapy for burn injuries.It acts by forming a protective barrier over the wound, which can shield the damaged tissue from further irritation and contamination.Additionally, sucralfate enhances local growth factor activity, promoting reepithelialization and accelerating wound healing.Its antiinflammatory properties help reduce edema and erythema, improving overall wound appearance and patient comfort.However, clinical evidence on efficacy and safety of sucralfate in burn treatment is still limited.More randomized controlled trials are necessary to establish standardized protocols and confirm its benefits.Despite these gaps, its unique mechanism of action and favorable safety profile suggest it could become a valuable addition to the topical treatment options for burn injuries.