Pain Management With Topical Ibuprofen in Partial-Thickness Burn Wounds and Effects on Wound Healing: A Prospective Randomized Clinical Study

Burn injuries are graded according to the depth of damage to the epidermis and dermis layers of the skin. Whereas first-degree burns are limited to the epidermis, partial dermis damage occurs in superficial and deep second-degree burns. Second-degree burns are also known as partial-thickness burns. Burns involving all layers of the dermis are defined as third-degree burns, and cases where the burn reaches the adipose tissue, muscles, and bones are called fourth-, fifth-, and sixth-degree burns, respectively.¹

Three phases of wound treatment were described in clay inscriptions from 2200 BC: wound cleansing, preparing mortar for application to the wound (various herbs, flax, oil, etc.) and bandaging. These basic rules continue to be valid even today. In partial-thickness skin burns suitable for outpatient follow-up, following wound cleansing, paraffin-impregnated gauze dressing and fixing bandage application are considered sufficient for wound healing.² Today, polyurethane foams are widely used to reduce the frequency of dressing changes and increase patient comfort.² Most of these products consist of an absorbent layer on the wound contact surface and an outermost occlusive layer. The commercial availability of these products in sizes suitable for each wound and their self-adhesive characteristics provide protection due to aseptic conditions and offer ease of use. There are many alternative products to use, including biologic dressing, silver-impregnated dressing, alginate dressing, or a 3% bismuth tribromophenate and USP petrolatum gauze.² Despite the rapid healing potential of biological wound dressings, the risk of infection and high cost are disadvantages. Silver not only prevents infection, but also provides an inhibitory effect on fibroblasts and keratinocytes. Alginates are preferred only for wounds with high exudates. Although dressings such as 3% bismuth tribromophenate and USP petrolatum gauze are inexpensive, their antimicrobial efficacy is limited and hypersensitivity reactions may develop. Additionally, none of these materials have analgesic effects.²

Inflammatory processes have direct effects on normal and impaired wound healing.³ Clinical experience shows that hypertrophic scar formation is an abnormal form of wound healing, involving exaggerated fibroblast function and excessive extracellular matrix deposition.³ Although some studies investigating the effects of controlling the inflammatory process on wound healing suggest that some anti-inflammatory drugs adversely affect skin healing through the reduction of prostaglandin E2 (PGE2), others report that these drugs do not affect wound healing or even have a positive effect.^4-6
Ibuprofen is a non-selective reversible inhibitor of cyclooxygenase isozymes (COX-1 and COX-2), which are responsible for the conversion of arachidonic acid to prostaglandins, including thromboxane and prostacyclin. Prostaglandins play a key role in fever, inflammation. and pain, and both the analgesic and antipyretic effects of ibuprofen are attributed to the inhibition of PGE2 and PGI2.⁷
Biatain Ibu Non-Adhesive (Coloplast) is designed to provide a moist wound healing environment and manage exudate. It consists of soft, flexible, hydrophilic polyurethane foam containing homogeneously dispersed ibuprofen (ibuprofen concentration: 0.5 mg/cm2). Each dressing (10 cm × 10 cm) contains 50 mg of ibuprofen. The foam is bonded to a semi permeable polyurethane film. In the presence of exudate, ibuprofen is continuously released into the wound bed. Although the release rate of ibuprofen depends on the amount of exudate, it shows a linear slow release over 7 days of dressing use.⁸ The slow release of ibuprofen creates a continuous analgesic and anti-inflammatory effect on the wound. Its efficacy in pain management has been demonstrated in various studies examining venous leg ulcers.^9,10 However, research on this product concerning pain management, wound healing, and dressing frequency in burn wounds is limited.¹¹

The majority of burn injuries are partial-thickness burns affecting a small body surface area, which do not require hospitalization and can be managed with outpatient follow-up.¹² In partial-thickness burns, the more superficial the wound, the greater the pain.² In fact, the pain experienced by these patients during dressing changes may be more severe than the pain caused by the first trauma.¹³ Therefore, pain management is one of the most important factors for improving the quality of life of patients and wound healing in the treatment of burns. However, burns are one of the most difficult pain etiologies to manage.¹³ Ideal wound care not only focuses on wound healing but also the patient’s quality of life.¹³

In this clinical randomized controlled study, the efficacy of ibuprofen-containing foam dressing in partial-thickness burn wounds was examined and compared with conventional methods.

Patient selection and randomization.

This randomized controlled study was conducted with adult patients with superficial partial-thickness burns who presented to the Burn Treatment Center of Ankara City Hospital and were suitable for outpatient follow-up. The inclusion criteria were being aged 18–65 years, having superficial partial-thickness burns caused by flame or hot liquid (water, tea, or coffee) that is smaller than 10 cm × 10 cm in size, directly presenting to our clinic within the first 6 hours after burn trauma, being suitable for outpatient follow-up, and agreeing to participate in the study. Burn depth was determined by experienced burn surgeons through physical examination in the outpatient clinic. Patients younger than 18 years or older than 65 years; those with first-degree or deep partial-thickness or full-thickness burns; those with burns of greater than 10 cm × 10 cm in size or located on the neck, face, hands or feet; those with hospitalization indications or comorbidities; smokers; those with a history of substance abuse; those with systemic or localized signs of infection, pregnancy, malignancy, or psychiatric disease; and those who wanted to continue their follow-up in other burn units were excluded from the study.

For randomization, 25 black and 25 white marbles were placed in a black cloth bag. For each patient who met the study criteria, a marble was taken out of the bag. If the drawn marble was black, the patient was included in the study group; if white, s/he was included in the control group (Figure 1).

Wound management and dressing.

In all the patients, the wounds were cleaned using an isotonic solution under outpatient conditions. In wounds containing bullae, unroofing was performed on the bullae. The debris and areas with epidermal desquamation on the wound were cleaned and removed. The wounds of the patients in the control group were treated with paraffin tulle gras dressing (Paranet) and covered with gauze. The patients were called for control every other day, and their dressings were changed. The wound was considered healed if complete epithelialization was achieved. 

The burn areas of the patients in the study group were covered by applying ibuprofen-containing foam dressing, which was fixed on all 4 sides with a surgical tape (Unipore Elastic Surgical Tape), taking care not to cover the middle part of the upper surface to monitor the saturation of the product (Figure 2). The wounds of the patients were opened on the seventh day, when re-cleansing and ibuprofen-containing foam dressing application were performed again in patients without complete wound healing. Ibuprofen foam dressing is an occlusive dressing, and it is stated by the manufacturer that it does not require dressing change for up to 7 days depending on the amount of exudate in the wound. Superficial second-degree burn wounds are not excessively exuding unless they are infected, and since we included uninfected superficial second-degree burn wounds that applied to our clinic for the first time after trauma, we did not generally need to change the dressing before 7 days. Then, these patients were called for control on the 14th day. The wound was considered healed if complete epithelialization was achieved. However, it was sometimes necessary to change the dressings earlier for patient-related reasons (wetting of the dressing, separation of the dressing, removal of the dressing due to itching by the patient).

The visual analogue scale (VAS) is a scoring system that evaluates patients’ pain on a scale of 0 (no pain) to 10 (unbearable pain).14 In the current study, the patients’ pain levels were evaluated with VAS at each visit. The measurements were made 30 min after the dressing and recorded. For patients who required more than one dressing change, the highest pain score was taken into consideration.
The Vancouver scar scale (VSS) evaluates vascularity, length/thickness, elasticity, and pigmentation variables. The scores obtained for each of these parameters are summed to obtain a total VSS score varying between 0 (best) and 13 (worst) points. The patient’s own scar perception was not included in this scoring.15 Although the VSS is a subjective evaluation, it was used in our study as a commonly adopted instrument. On the 90th day after healing the burn wound, the wound area was evaluated by the observer physician in terms of scarring using VSS.
Oral painkillers were not used unless the patients requested them. Age, gender, burn agent, VAS scores, painkiller requirement, number of dressing changes at the outpatient clinic, and VSS scores were recorded for all the patients.

Ethical assurances.

The study was carried out with the approval of the Ethics Committee of Ankara City Hospital (dated 10.13.2021 and numbered E2-21/885). Written informed consent was obtained from all the patients after giving them written and verbal information about the procedures to be performed in the study, potential risks or drawbacks, and/or expected benefits.

Statistical analysis.

All statistical tests were performed using IBM Statistical Package for the Social Sciences (IBM SPSS Corp.), version 18.0, software. The Shapiro-Wilk test was used to assess the normality of data distribution. For continuous variables, mean ± standard deviation (SD) was demonstrated. Differences in continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed using χ2 tests.  A p-value of <0.05 was considered statistically significant.
 

Of the 502 patients who presented to the Burn Treatment Center of Ankara City Hospital between October 2021 and February 2022, 123 were hospitalized. Of the 379 outpatients, 50 who met the study criteria were included in the sample by randomization. In the entire cohort, 29 (58%) patients were female and 21 (42%) were male. The burn agent was hot liquids in 41 (84%) patients and flame in nine (18%). In the study group, burn areas were on the upper extremity in 18 patients (72%), the lower extremities in 5 patients (20%), and the trunk in 2 patients (8%). In the control group, similarly, burn areas were on the upper extremity in 15 (60%), on the lower extremities in 7 (28%), and on the trunk in 3 (12%) patients. Oral painkillers were required in 25 patients. The patients’ age, wound healing time, VAS scores, VSS scores, and number of dressing changes needed are presented in Table 1.

No significant difference was observed between the study group and the control group in terms of sex, age, and burn agent (Table 2).

The wound healing time of the study group was found to be 8.84 ± 2.97 days, which was statistically significantly shorter compared with the control group (P = 0.010), although it does not seem like a significant difference when SD is considered. The dressing frequency was lower in the study group (P = 0.000). The reason for this difference in SD is the dressing changes in 4 patients in the study group (because of wetting of the dressing in 2, separation of the dressing in 1, and removal of the dressing due to itching by the patient in 1) before the scheduled 7 days. The mean VAS score was 5.04 ± 2.44 for the study group and 8.64 ± 1.29 for the control group. The painkiller requirement was also found to be significantly lower in the study group: of the 25 patients who needed painkillers, 5 were from the study group and the remaining 20 were from the control group. In the VAS evaluation performed 30 min after dressing, pain was significantly reduced in the study group compared with the control group. VAS score 5.04 ± 2.44 for the study group and 8.64 ± 1.29 for the control group (P =0.000). In parallel with this result, the need for oral analgesic use was also found to be lower in the study group (5/25, 20%, P = 0.000). In the VSS evaluation, 2 patients from the study group received 1 and 2 points. In the control group, 2 of the 5 patients scored 3 points, 2 patients scored 1 point, and 1 patient scored 2 points. The remaining patients had a VSS score of 0. The VSS score of the study group was lower than that of the control group (Table 3). 

Burns can be caused by various factors, such as hot liquids, contact with hot objects, chemicals, and electricity; however, all burns are accompanied by pain, regardless of aetiology. Given that pain is affected by a wide range of factors, many approaches, from drug therapy to music therapy, have been used in the management of burn pain.¹⁶ Pain management improves the quality of life of burn patients, as in all other patients with pain. Considering that pain is closely related to patient satisfaction and wound healing, pain management is as important as wound healing in burn treatment.⁴

Depending on the degree of thermal damage, partial-thickness or full-thickness burns occur. If superficial partial-thickness burns are treated appropriately and protected from complications such as infection and dryness, they usually heal spontaneously and do not turn into deep second-degree burns that require surgical intervention, such as excision and grafting, unlike full-thickness burns. However, given that nerve endings are exposed and alive in partial-thickness burns, pain is more severe. Therefore, pain management in these cases gains further importance.³ The analgesics that are usually prescribed are paracetamol and nonsteroidal anti-inflammatory drugs, but narcotic analgesics may also be required.² The use of effective topical analgesics, rather than these drugs with proven systemic side effects, clearly has benefits.¹⁷ In addition, with their slow release mechanism, topical products provide more stable pain control by preventing blood level fluctuations in oral or intravenous use.¹⁷

Ibuprofen significantly reduces inflammation and edema when used parenterally in partial-thickness burns.¹⁸ In topical applications, ibuprofen in various pharmaceutical forms is absorbed through the skin and reaches its maximum plasma levels within 4–11 h.¹⁹     

Although no evidence shows that oral or parenteral nonsteroidal anti-inflammatory drugs impair tissue healing, their effects on wound healing remain controversial.^6-8 In this study, we evaluated the effect of a non-adhesive, ibuprofen-containing foam dressing on partial-thickness burns. The use of ibuprofen-containing foam dressing in the treatment of partial-thickness burns provided a shorter wound healing time compared with paraffin gauze dressing. The primary outcome for the study was to determine whether pain control could be achieved with an ibuprofen-containing foam dressing. In addition, since we felt compelled to prove that infrequent dressing changes would not adversely affect wound healing, we analyzed that data as well and concluded that a decrease in dressing frequency can reduce wound trauma and affect healing in a positive way.

Since we predict the condition that positively affects pain control and wound healing is not only slow release of ibuprofen but also reduced dressing change frequency of the wound, we compare the 2 groups by considering all the possibilities offered by the dressing materials. This includes frequent changes in conventional dressing materials and reducing the frequency of change in modern dressing materials.

Previous studies have also shown that dressing frequency affects wound healing time.² During each dressing change, epithelial bulging that begins to form in the wound bed is damaged, delaying healing.² 

We considered that the decreased frequency of ibuprofen-containing foam dressing change shortened the healing time in the study group. In addition, although no change is required for 7 days since ibuprofen-containing foam dressing is non-adherent, it can be evaluated by removing the wound dressing without damaging the epithelium to assess the wound for healing and whether or not to excise in case of conversion to deep second-degree burn. Although the decrease in dressing frequency is considered a disadvantage in evaluating the deepening of the existing burn, no conversion to second-degree deep burn was observed in any of the patients included in this study and the need for excision was not observed. Even though this decrease in dressing frequency affects wound healing positively, clinicians should be aware of this since it will make it difficult to detect the progress in burn depth.    

Another condition that has a positive effect on wound healing is pain management.⁴ In the current study, the study group had a significantly lower VAS score, lower additional analgesic requirement, and shorter healing time compared with the control group, again demonstrating the positive effect of pain management on wound healing.    

Nonsteroidal anti-inflammatory drugs may be beneficial in preventing hypertrophic scar formation by reducing the expression of the iNOS protein and accelerating the wound healing process.⁸ In contrast, some studies have shown that nonsteroidal anti-inflammatory drugs cause hypertrophic scarring by inhibiting COX and decreasing the PGE2 level. Compression garments, frequently used in hypertrophic scar management, also have an effect by increasing the PGE2 level.⁵ In our study, although no significant difference was found between the study and control groups in the evaluation of VSS, the mean score was lower in the study group. We did not observe any hypertrophic scar formation caused by ibuprofen-containing foam dressing in our study, though further research with a larger case series is needed to determine whether it has a preventive effect on hypertrophic scar formation.    

A shorter wound healing time and lower dressing change frequency increases burn patients’ quality of life, given that they will need to visit the hospital less frequently over a shorter period of time. We also thought that the frequency of dressing changes affects wound healing through the wound trauma variable. In order to reveal the effect of different dressing change frequency on wound healing, the difference is highlighted statistically. In the study protocol, the frequency of dressing material change was decided in accordance with the manufacturer’s recommendation, but this can be considered as one of the factors and benefits affecting the wound healing time between the 2 groups.

Although it was not among the objectives of this study, this finding will also positively contribute to the workforce and workload of healthcare professionals, and further research in this area may provide useful findings. 
 

Ibuprofen-containing foam dressing can be safely used in patients with partial-thickness burns as an alternative to conventional methods. In addition to its positive contributions to wound healing, it increases patient comfort by reducing the frequency of dressing and pain. None of the patients participating in the study developed hypertrophic scars. We consider that the widespread use of ibuprofen-containing foam dressing in the outpatient management of burns will make a positive contribution to the workload of healthcare professionals.
    

In this study, we investigated the effects of ibuprofen-containing foam dressing on pain and wound healing in adult patients with small surface area burns. However, the small number of patients, being limited to the adult population, and working on patients with small burn areas are the most important limitations. Future studies with patients with larger burn areas and pediatric burns are needed. Another limitation is the inability to make an optimal assessment of wound healing time due to the frequency of dressing changes. In line with the manufacturer’s recommendation, the inability to frequently evaluate epithelial bulging due to the dressing change protocol can be mentioned among the limitations. As another limitation, the required labor force, workload of healthcare workers, and cost of procedures were not evaluated. The superiority of this study is its prospective design and being one of the few studies on the subject in the literature.

For his support in the design and execution of our study and his contribution to statistics, We would like to thank Prof Dr Ahmet Çınar Yastı.

¹Ali Emre Akgun, MD, Ankara City Hospital, Department of General Surgery, Üniversiteler Mahallesi 1604. Cadde No: 9 Çankaya, Ankara, Turkey
²Merve Akin, MD, Ankara City Hospital, Department of General Surgery, Üniversiteler Mahallesi 1604. Cadde No: 9 Çankaya, Ankara, Turkey
 

Address all correspondence to: Ali Emre Akgun, MD , Ankara City Hospital, Department of General Surgery, Üniversiteler Mahallesi 1604. Cadde No: 9
Çankaya, Ankara, Turkey; email:aeakgun@hotmail.com

none disclosed

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