Abstract
Background
Several medications and topical agents have been used for burn injuries. Among them, 1% silver sulfadiazine is the most commonly used topical agent for partial thickness burns. Recent studies have reported that the healing of burns is delayed by silver sulfadiazine. Search for the ideal topical agent for burn injuries is an ongoing research. The current study is undertaken with sucralfate as topical agent for dressing of burn injuries.
Aim
To compare the efficacy of topical sucralfate with silver sulfadiazine in the healing of second degree superficial burns.
Study design
A one-year randomized controlled trial
Setting
Department of General Surgery, JN Medical College and KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, India
Methodology
A total of 60 patients with < 50% second degree superficial burns were enrolled for the study. Patients were equally divided into two groups. Patients in group A were treated with topical sucralfate dressing and those in group B were treated with dressing. Demographics, history, physical, and systemic examinations of the patients were recorded. Routine blood investigations and culture and sensitivity were also performed. SPSS 20.0 was used for the analysis.
Results
In group A, the granulation appeared in less than 7 days in 15 (50%) patients, where as in group B, granulation appeared between 15 and 20 days in 17 (56.67%) patients (p = 0.149). The mean day of granulation was 8.11±3.92 days in group A compared to 8.93±3.29 days in group B (p = 0.396). The wound culture on day 1, 7 and 14 (p>0.050) did not differ significantly in both the groups.
Conclusion
Overall, topical sucralfate dressing is efficacious in terms of development of early granulation in the healing of second-degree superficial burns compared to silver sulfadiazine dressing while antimicrobial effect is comparable to that of silver sulfadiazine dressing. It hastened burn wound healing process in second-degree superficial burns and should be used as an alternative agent or in combination with other topical agents. However, multicentric trials with bigger sample size are needed to strengthen the concept.
Keywords: Topical sucralfate, Silver sulfadiazine, Second-degree superficial burns, Granulation, Wound culture
Introduction
Burns are one of the most severe injuries with high mortality and morbidity1. It is a distressful experience not only for the burn victims, but also for their families. Burn injuries are a great burden to the society, as they consume enormous healthcare resources2. Every year, more than 10,00,000 people in the developing countries suffer from moderate to severe burn injuries3. Over the years, improvement in the treatment has resulted in decreasing mortality from burns; however the management of burn injuries still remains a surgical challenge4.
Silver nitrate, sulfamylon, and a combination of a sulfonamide and silver sulfadiazine (SSD) are the topical antimicrobial agents in the burn wound dressings5,6. Among them, sulfamylon has broad-spectrum activity; but its systemic absorption leads to toxic complications. 1% SSD is the most common topical agent for partial thickness burns; it is preferred to other medications such as mafenide acetate and silver nitrate. It is a very effective agent, but causes systemic side effects such as neutropenia, crystalluria, erythema multiforme, and methemoglobinemia5-8. Moreover, more recent studies have reported that healing of partial thickness burns is delayed by SSD9,10. Hence search for a better topical agent for burn dressing continues to be a subject of intense research.
Sucralfate, a basic complex salt of sucrose sulfate and aluminum hydroxide, is used as an effective mucoprotective agent in the treatment of peptic ulcers. Topical sucralfate has been used in the treatment of resistant perineal and peristomal excoriation, stomatitis, decubitus ulcers, as well as radiation proctitis and has been found to improve wound healing and decrease pain. Various sporadic studies have demonstrated the safety and efficacy of topical sucralfate in skin protection and wound repair4,11,15.
The clinical observations also have supported the anti-inflammatory and bacteriostatic properties of sucralfate15,16. Hence, this study was undertaken to compare the efficacy of topical sucralfate with that of SSD, in terms of number of days required for healing or for the appearance of healthy granulation tissue and antibacterial effect in second-degree superficial thermal burns.
Patients & Methods
A randomized controlled trial was conducted at the Department of General Surgery, JN Medical College and KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, India from January 2015 to December 2015. A total of 60 patients were divided sequentially into two groups; 30 patients in group A were treated with topical sucralfate dressing and 30 patients in group B with 1% silver sulfadiazine (SSD) dressing.
All patients with <50% superficial second-degree thermal burns and scalds were included in the study. Patients with >50% burns, comorbidities including diabetes mellitus, Human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS), gross anemia (<5 gm % HB), hypoproteinemia (total protein <5 g/dL) and in a state of debility, electric burns, corrosive burns, and inhalational burns were excluded from the study. All selected patients were informed about the nature of study and a written informed consent was obtained. Prior to the commencement, the study was approved from the Ethical Research Committee, Jawaharlal Nehru Medical College, Belagavi, India.
Data collection
Patients were interviewed and demographic data were recorded. All the patients included in the study were evaluated by a thorough history, physical, as well as systemic examination. These findings were recorded on a predesigned and pretested proforma. Complete blood count, biochemical tests, serological tests, plasma proteins, random blood sugar, renal function tests and culture and sensitivity were performed.
Intervention and outcome variables
The burn wounds were photographed. Discharge was sent for culture and sensitivity. Wounds were dressed and the dressing was changed daily. Wounds were observed for a maximum of 21 days (endpoint of the study) for the healing or the appearance of healthy granulation tissue and the rate of healing was compared.
Statistical analysis
The data were pooled and analyzed using SPSS 20.0. The categorical data were expressed as rates, ratios, and percentages. Continuous data were expressed as mean ± standard deviation and compared using Fishers exact test, chi-square test, and independent sample t-test. p≤0.05 was considered as statistically significant.
Results
Demographic, clinical characteristics, and personal history of the study population is shown in Table 1. Majority of patients were men in both the groups (83.33% vs. 16.67%; p = 1.000). The mean age and built were comparable in both the groups (p = 0.903). Other characteristics including tobacco chewing, smoking, and alcohol consumption, burn area, mean pulse rate, systolic & diastolic BP, respiratory rate, temperature, were comparable in both the groups (p>0.050). However, all the group A patients had burn injury on the right upper limb and all the group B patients had burn injury on the left upper limb. (p<0.001). Ten (33.33%) patients in each group had 41%-50% burns (p = 1.000; Table 2).
Table 1: Demographic data and clinical characteristics of the study population.
| Findings | Group A, n=30 | GroupB, n=30 | p-value |
| Age Mean Age | 29.33±16.94 | 29.87±16.83 | 0.903 |
| Gender | |||
| Male | 25 | 25 | 1 |
| Female | 5 | 5 | |
| Clinical characteristics | |||
| Pulse rate (minute) | 108.53±12.63 | 108.53±12.63 | 1 |
| SBP (mmHg) | 120.00±15.54 | 120±15.54 | 1 |
| DBP (mmHg) | 76.83±10.75 | 76.83±10.75 | 1 |
| Respiratory rate (/minute) | 26.60±2.29 | 26.60±2.29 | 1 |
| Temperature (0C) | 98.60±2.29 | 98.60±2.29 | 1 |
| Appearance | |||
| Moderately built | 30 % | 30 % | 0.806 |
| Moderately built, kyphosis | 3.33 % | 3.33 % | |
| Moderately built, well nourished | 10 % | 6.67 % | |
| Thin built | 30 % | 3.33 % | |
| Well built | 16.67 % | 9.30 % | |
| Well nourished | 10 % | 16.67 % | |
| Site of Injury | |||
| Left upper limb | 0 | 30 (100 %) | <0.001 |
| Right upper limb | 30 (100 %) | 0 | |
| Personal history | |||
| Tobacco consumption | 27 (90 %) | 28 (93.33 %) | 0.5 |
| Smoking | 23 (76.67 %) | 23 (76.67 %) | 1 |
| Alcohol consumption | 29 (96.67 %) | 29 (96.67 %) | 0.754 |
Table 2: Burns surface area.
| Burns area (%) | Group A, n (%) | Group B, n (%) | p-value |
| 11-20 | 7 (23.33) | 7 (23.33) | |
| 21-30 | 9 (30) | 9 (30) | 1.000 |
| 31-40 | 4 (13.33) | 4 (13.33) | |
| 41-50 | 10 (33.33) | 10 (33.33) |
A total of 15 (50%) patients in group A had granulation within 7 days, while in group B, 17 (56.67%) patients had granulation between 15 and 20 days (p = 0.149). The mean day of granulation was 8.11±3.92 days in group A and 8.93±3.29 days in group B (p = 0.396, Table 3). No significant difference in wound culture was observed on day 1, 7 and 14 (p>0.050) in both the groups (Table 4).
Table 3: Day of granulation.
| Day of granulation | Group A, n (%) | Group B, n (%) | p-value |
| <7 | 15 (50) | 7 (23.33) | 0.149 |
| 8 to 14 | 3 (10) | 3 (10) | |
| 15 to 20 | 11 (36.67) | 17 (56.67) | |
| No granulation | 1 (3.33) | 3 (10) |
Table 4: Wound culture.
| Intervals | Findings | Group A, n (%) | Group B, n (%) | p-value |
| Day 1 | Positive | 12 (40) | 9 (30) | 0.416 |
| Negative | 18 (60) | 21 (70) | ||
| Day 7 | Positive | 16 (53.33) | 14 (46.67) | 0.606 |
| Negative | 14 (46.67) | 16 (53.33) | ||
| Day 14 | Positive | 24 (80) | 21 (70) | 0.371 |
| Negative | 6 (20) | 9 (30) |
Discussion
Burns are one of the commonest injuries all over the world. Various types of medications and surface applications have been used in the treatment of burn injuries. The basic purpose of their use is to expedite the epithelial healing and to prevent the formation of a scar.
Sucralfate is known to have multiple beneficial effects on wound repair. Wound repair depends on neoangiogenesis, activation of local immune response, and the presence of growth factors including epidermal growth factor (eGF), transforming growth factor β (TGF-β), and basic fibroblast growth factor (bFGF). Sucralfate acts by increasing both bFGF and eGF concentration in the wound tissue. It also inhibits the release of interleukin-2, interferon gamma, and cytokines from the burnt damaged skin cells and thus prevents inflammation and produces soothing effect4. Moreover, it does not have any adverse effects6. Initially, Hollander et al17 was the first who discovered that oral sucralfate is able to protect the gastric mucosa from injury by ethanol. Tsakayannis et al18 first investigated the use of topical sucralfate ointment in nonhealing venous stasis ulcers and observed a remarkable granulation tissue, neoangiogenesis, and wound contraction. Subsequently many clinical studies reported the effectiveness of topical sucralfate in healing various ulcers of oral mucosa and intestine19,20. Similarly, a study conducted by Burch et al21 on animals showed that sucralfate cream hastens the cell proliferation in superficial skin layer resulting in thickening of the dermis and epidermis. Except few studies which have revealed aluminum toxicity, sucralfate is found to be an effective and safe compound for topical application and oral administration22. Hence, the current study was undertaken to compare the efficacy of topical sucralfate with that of SSD, in the healing of second-degree superficial burns in terms of number of days required for healing or the appearance of healthy granulation tissue and in terms of antibacterial effect. SSD resulted in granulation tissue after 15-20 days in 17/30 patients, whereas sucralfate resulted in the granulation within 7 days in 15/30 patients. The study conducted by Hassanzadeh et al23 showed that the topical application of SSD did not hasten healing of burn injuries in rats; however, it reduced inflammation after second week. Similarly, many studies reported that sucralfate stimulates angiogenesis, which in turn hastens the development of granulation of tissue24,25.
The current study showed the benefit of topical sucralfate dressing over SSD dressing in terms of early granulation in the healing of second-degree superficial burns but no antimicrobial benefit. Although the evidence is not strong, the clinical observations in several other settings tends to support the beneficial effect of sucralfate15. A study conducted by Banati et al4 investigated the role of topical sucralfate in the treatment of burn injuries and showed that sucralfate was able to increase the rate of epithelialization and earlier appearance of healthy granulation tissue in second and third degree burns, respectively. Hence, the results of the present study are in agreement with the observations reported by Banati et al4 despite some methodological differences. Experimental studies conducted by Szabo et al25 have reported that topical sucralfate stimulates angiogenesis, which augments granulation tissue. Behesti et al6 also compared the effects of sucralfate and SSD in second-degree burn wounds in rats and concluded that topical sucralfate accelerates the burn wound healing process in comparison with the control group and SSD group and can be used as an adjunctive or alternative agent in the future.
Wound culture was observed positive and subsequently increased from day 1 to 14 in both groups. Hence, both the sucralfate and SSD did not show antibacterial effect on burn injuries. In contrast to our findings, other studies have shown an antibacterial activity of topical sucralfate22; however, the exact mechanism of action is not known. Further research is essential in this area. Thorough shower bathing, cleaning, and timely wound debridement are the important measures in controlling the bacterial infections.
However, these findings need further evaluation due to the several limitations of the study such as the small sample size, and limited study duration of 21 days only during which all the wounds did not heal completely. Finally, this study was limited to second-degree burns and may not be generalized in all the burn injuries.
Conclusions
The finding of the current study showed that topical sucralfate dressing is efficacious in terms of development of early granulation in the healing of second-degree superficial burns compared to silver sulfadiazine (SSD) dressing while antimicrobial effect is comparable to that of SSD dressing. Overall, topical sucralfate hastened burn wound healing process in second-degree superficial burns and it should be used as an alternative agent or in combination with other topical agents. However, multicentric trials with bigger sample size are needed to strengthen the concept.
Footnotes
Competing Interests: The authors have declared that no competing interests exist.
Grant support: None
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