03 August 2022: Clinical Research
Evaluation of Bromelain-Based Enzymatic Debridement Combined with Laser Doppler Imaging and Healing of Burn WoundsTomasz Korzeniowski12ABCDEFG*, Jerzy Strużyna13ABCDEF, Kamil Torres2ABCDFG
Med Sci Monit 2022; 28:e936713
BACKGROUND: Accurate estimation of burn depth is crucial for correct treatment decision making. Bromelain-based enzymatic debridement (ED) may improve clinical assessment of burn depth. Laser Doppler imaging (LDI) provides a valuable indicator of burn depth by analyzing microcirculation within tissue beds. This study aimed to evaluate bromelain-based enzymatic debridement combined with laser Doppler imaging and healing of 42 wounds in 19 patients with mixed second- and third-degree thermal burns.
MATERIAL AND METHODS: We included 42 wounds in 19 patients with mixed deep dermal and full-thickness thermal burns. All patients were treated with eschar-specific removal agent for ED. The perfusion of each wound after ED was assessed using LDI. Healing time was estimated by 2 experienced burn surgeons and marked by the observation of epithelization. The usefulness of the LDI performed after ED in predicting healing time was estimated. The findings were analyzed to determine a cut-off value for LDI that indicates if a burn will heal spontaneously.
RESULTS: We observed that burn wounds with higher mean perfusion healed faster. The analysis showed a strong relationship between perfusion after ED and healing time (Spearman rank correlation coefficient=-0.803). A mean perfusion greater than 296.89 indicated that the wound could heal spontaneously and does not require skin grafting.
CONCLUSIONS: LDI examination of an already debrided wound allows for a reliable assessment of perfusion at an early stage of treatment. The use of a safe and effective debridement method in conjunction with a non-invasive diagnostic tool could improve burn management.
Keywords: Burns, Debridement, Laser-Doppler Flowmetry, Perfusion, Wound Healing
Burns depth estimation is a challenging task that requires objective techniques to accomplish. Distinguishing between burn wounds that will heal spontaneously and those that will need surgery is critical to patient outcomes, providing better quality of care and keeping medical costs down. This requires a method that is effective in terms of accuracy and timely decision making [1,2].
Clinical assessment is the most common technique used to determine the burn depth. However, it is accurate in only 60 to 75% of cases, even when carried out by an experienced burn surgeon . Biopsy with histological examination is considered the criterion standard and is regarded as an excellent method for experimental research. However, biopsy is an invasive method, leaves additional scars, and needs an experienced pathologist to interpret specimens. Its application therefore has limited practical application in the clinical setting .
The management plan and prognosis for superficial and deep burns are entirely different; therefore, an accurate burn depth diagnosis is crucial. Superficial burns usually heal in 3 weeks without pathological scars. On the contrary, deep burns are associated with burn scar pigmentation disorders, hypertrophic scarring, and even contracture formation . An appropriate treatment strategy is selected based on the assessment of burn depth [6,7]. Clinically, burns can be divided into superficial, which are treated conservatively, and deep burn wounds requiring surgical therapy [8,9]. An overly aggressive strategy of treatment for superficial burns will cause unnecessary damage to healthy tissues. In contrast, conservative treatment of deep burns may lead to prolonged healing and significantly worse outcomes . In addition, the choice of an adequate method of treatment is made more demanding by the fact that most of the burned surface is not uniform in depth. Tangential excision is insufficiently selective because both necrotic and healthy tissue are excised. The principal drawback of fascia excision is that the debridement inevitably involves removing some portion of healthy and viable subcutaneous tissue. Another disadvantage is that this method may create a considerable contour deformity .
Enzymatic debridement (ED) proved to be an effective method for selective eschar removal [12,13]. Nexobrid®, a form of bromelain-based debridement agent that is derived from pineapple stems, has gained popularity in recent years. Its benefits are mainly due to eschar removal without removing any viable tissue. ED is particularly useful in deep partial and full-thickness wounds and has been evaluated in several studies .
Clinical examination of debrided wound appears to be a promising technique. ED may improve clinical assessment of burn depth, increasing its specificity and sensitivity .
Various technologies have been developed to obtain a more precise estimation of burn depth: high-frequency ultrasound, magnetic resonance imaging, vital dyes, indocyanine green videoangiography, thermography, near-infrared spectroscopy and laser Doppler imaging (LDI). The latter seems to be the most advantageous technique for the evaluation of burn wound and thus for the determination of wound healing potential. LDI is a non-invasive, non-contact method of measuring blood flow in tissue. It works by analyzing microcirculation within tissue beds [16–19].
Therefore, this study aimed to evaluate bromelain-based enzymatic debridement combined with laser Doppler imaging and healing of 42 wounds in 19 patients with mixed second- and third-degree thermal burns.
Material and Methods
The study protocol received approval from the Ethics Committee of the Medical University of Lublin (reference: KE-0254/249/2020). Informed consent was obtained from the patients, allowing the authors to include the pictures and treatment details in this study.
We included 42 burn wounds in 19 patients presenting in the East Centre of Burns Treatment and Reconstructive Surgery, District Hospital in Łęczna (Poland) in 2020. We enrolled patients with mixed deep dermal and full-thickness thermal burns who underwent ED and diagnosis with LDI. The procedure was done between days 1–3 of the burn injury. Of the 42 wounds included in the study, all were classified in visual assessment as mixed second- and third-degree burns.
ED was performed using Nexobrid (MediWound GmbH, Germany), which consists of proteolytic enzymes enriched in bromelain derived from stems of pineapple plants and is indicated for the removal of dead tissue in thermal burns . ED is highly recommended in mixed mid-to-deep dermal or indeterminate burns to preserve as much viable dermis as possible for improved functional and esthetic outcome. Patients were treated following the protocol used in the Burn Center according to the manufacturer’s instructions and European consensus guidelines [21–23]. The entire procedure of ED was performed either under general anesthesia in the operation room/intensive care unit for severe burns when additional procedures were required or bedside in the burn ward by applying analgo-sedation protocol in spontaneously breathing patients. First, the wound was prepared by removing blisters and necrotic epidermis. Then, the mixture of Nexobrid was prepared and applied to the wound along with an occlusive foil dressing for 4 hours (Figure 1).
The perfusion of each wound was assessed after enzymatic treatment. Each time, before the examination, the wound bed was thoroughly prepared by removing dissolved eschar, exudates, and the remnant of the preparation via scraping with a sterile tongue depressor and gauze.
After the ED procedure and LDI examination, followed by soaking the wound for at least 2 hours, dressings were changed with polyhexanide gel and paraffin gauze every other day. If there was no significant progress in epithelization between 14–21 days after ED, autologous skin grafting was applied. In the postoperative period, care of the skin-grafted wounds in these patients was performed similarly to the patients treated conservatively, and the first dressing change was postponed to 3 days after skin grafting. Healing time was estimated by 2 physicians and marked by the observation of epithelization. Clinical assessment was performed by burn surgeons with several years of experience. Wound healing time was assessed as the time between injury and complete epithelialization, calculated in post-burn days.
LDI scans were done using PeriScan PIM 3 (Perimed AB, Stockholm, Sweden). The PeriScan PIM 3 System is a blood perfusion imager based on laser Doppler technology which uses a low-power, 670-nm, solid-state laser beam. The system can visualize spatial blood perfusion over time in selected measurement areas.
The experienced burn surgeons defined regions of interest (ROI) according to their clinical diagnosis at the time of the LDI scan. Determination of ROIs was based on clinical evaluation of intermediate depth. The mean surface area of the ROI ranged from 12 to 44 cm2 (mean 20 cm2), with the head of the LDI unit placed perpendicularly to the wound. The immobility of the examined area was ensured as far as possible. The average distance from the scanner to the top of the wound was 14 cm (Figure 2).
Blood perfusion was presented with a color-coded palette ranging from dark blue to red, numerically corresponding to perfusion units (PU). Moreover, camera and greyscale photos were obtained (Figure 3). Mean PU for each ROI was calculated using the software of the LDI System. Mean PU reflects the average concentration and velocity of blood cells, which is proportional to tissue perfusion.
The potential of the LDI performed after ED was estimated. The findings were analyzed to determine a cut-off value for LDI that indicates if a burn will heal spontaneously and agreement accuracy between the LDI outcome/healing potential category and actual healing results.
Data were summarized as means±SD. Differences were considered significant when the P value was less than 0.05. The relationship between perfusion and healing time was calculated using the Spearman correlation coefficient. The usefulness of LDI in assessing the potential for burn wound healing was evaluated using receiver operating characteristic (ROC) curve analysis.
A total of 42 burn wounds among 19 patients were selected as ROIs (1 to 4 ROIs/patient). The mean age of the patients was 35 years. Within the study group, the most common cause of injury was flame (72%). Scald burns accounted for 11% of total cases. The burn size ranged from 3% to 48% total body surface area (Table 1).
Eleven wounds (26.2%) healed spontaneously, while 31 wounds (73.8%) needed to be covered with skin grafts. The healing time ranged from 8 to 49 days (median, 21.5 days). We observed that burn wounds with higher mean PU healed faster. The healing time became shorter as the mean PU increased (Figure 4). The statistical analysis showed a strong relationship, with Spearman rank correlation coefficient = −0.803 (P<0.0001).
The receiver operating characteristic curve (ROC) showed that the mean PU determined by LDI after ED could be an excellent objective tool in predicting the potential for burn wound healing. The area under the ROC curve was 0.997 (95% CI=0.988–1.000). A mean PU greater than 296.89 could indicate that the wound would heal spontaneously and would not require skin grafting (Figure 5). The agreement accuracy between the LDI outcome/healing potential category and actual healing results was 97.62% (Table 2).
This is the first study investigating the use of a combination of ED and LDI in the assessment of burn depth, and it has some limitations. The combined technique may generate higher costs and be time-consuming. However, this novel approach can evaluate burn wound depth more precisely, predict outcome, and help make a decision for surgery in the early stages of care for patients with indeterminate burns. Some factors may affect the measurement, such as the presence or absence of burn shock, debridement, and examination of various parts of the body with different thickness or wound temperature. Notwithstanding these drawbacks, the ED/LDI combined technique proved more effective when compared to a single LDI method . The optimal scan time is important, as the burn evolves over 48–72 hours. For that reason, it is recommended to perform the LDI at least 48 hours after injury [34–36]. Examination of an already debrided wound allows for a reliable assessment of perfusion at a very early stage of treatment.
Laser Doppler imaging examination of an already enzymatically debrided wound allows for a reliable assessment of perfusion at a very early stage of treatment. The use of a safe and effective debridement method in conjunction with a non-invasive diagnostic tool may ultimately meet a high number of requirements for burn assessment in routine clinical use.
FiguresFigure 1. Enzymatic debridement procedure (A – preparation of the Nexobrid, B – Nexobrid application, C – occlusive dressing, D – effect of enzymatic debridement). Figure 2. Laser Doppler examination (Periscan PIM 3, Perimed AB, Stockholm, Sweden). Figure 3. Laser Doppler image of the enzymatically debrided forearm burn wound and corresponding clinical photograph. Figure 4. Relationship between mean PU (perfusion units) and healing time. Figure 5. ROC (receiver operating characteristic) curve for mean PU (perfusion units) after enzymatic debridement in predicting the spontaneously healing.
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