Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

03 August 2022: Clinical Research  

Evaluation of Bromelain-Based Enzymatic Debridement Combined with Laser Doppler Imaging and Healing of Burn Wounds

Tomasz Korzeniowski12ABCDEFG*, Jerzy Strużyna13ABCDEF, Kamil Torres2ABCDFG

DOI: 10.12659/MSM.936713

Med Sci Monit 2022; 28:e936713

0 Comments

Abstract

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, Bromelains, Humans, Lasers, Skin

Background

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 [3]. 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 [4].

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 [5]. 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 [10]. 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 [11].

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 [14].

Clinical examination of debrided wound appears to be a promising technique. ED may improve clinical assessment of burn depth, increasing its specificity and sensitivity [15].

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 [20]. 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.

Results

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).

Discussion

LIMITATIONS:

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 [33]. 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.

Conclusions

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.

References

1. Jaspers MEH, van Haasterecht L, van Zuijlen PPM, Mokkink LB, A systematic review on the quality of measurement techniques for the assessment of burn wound depth or healing potential: Burns, 2019; 45(2); 261-81

2. Nitzschke SL, Aden JK, Serio-Melvin ML, Wound healing trajectories in burn patients and their impact on mortality: J Burn Care Res, 2014; 35; 474-79

3. Monstrey S, Hoeksema H, Verbelen J, Assessment of burn depth and burn wound healing potential: Burns, 2008; 34(6); 761-69

4. Watts AM, Tyler MP, Perry ME, Burn depth and its histological measurement: Burns, 2001; 27(2); 154-60

5. Wang Y, Beekman J, Hew J, Burn injury: Challenges and advances in burn wound healing, infection, pain, and scarring: Adv Drug Deliv Rev, 2018; 123; 3-17

6. Toussaint J, Singer AJ, The evaluation and management of thermal injuries: 2014 update: Clin Exp Emerg Med, 2014; 1(1); 8-18

7. Siegwart LC, Böcker AH, Diehm YF, Enzymatic debridement for burn wound care: Interrater reliability and impact of experience in post-intervention therapy decision: J Burn Care Res, 2021; 42(5); 953-61

8. Atiyeh BS, Gunn SW, Hayek SN, State of the art in burn treatment: World J Surg, 2005; 29(2); 131-48

9. Surowiecka-Pastewka A, Witkowski W, Kawecki M, A new triage method for burn disasters: Fast triage in burns (FTB): Med Sci Monit, 2018; 24; 1894-901

10. Finnerty CC, Jeschke MG, Branski LK, Hypertrophic scarring: The greatest unmet challenge after burn injury: Lancet, 2016; 388(10052); 1427-36

11. Hofmaenner DA, Steiger P, Schuepbach RA, Safety of enzymatic debridement in extensive burns larger than 15% total body surface area: Burns, 2021; 47(4); 796-804

12. Rosenberg L, Krieger Y, Bogdanov-Berezovski A, A novel rapid and selective enzymatic debridement agent for burn wound management: A multi-center RCT: Burns, 2014; 40(3); 466-74

13. Bernagozzi F, Orlandi C, Purpura V, The enzymatic debridement for the treatment of burns of indeterminate depth: J Burn Care Res, 2020; 41(5); 1084-91

14. Loo YL, Goh BKL, Jeffery S: J Burn Care Res, 2018; 39(6); 932-38

15. Mataro I, Giudice G, Elia R, The accuracy of burn depth diagnosis: Clinical assessment before and after enzymatic debridement: Burns Open, 2021; 5(4); 36-39

16. Rajan V, Varghese B, van Leeuwen TG, Steenbergen W, Review of methodological developments in laser Doppler flowmetry: Lasers Med Sci, 2009; 24(2); 269-83

17. Shin JY, Yi HS, Diagnostic accuracy of laser Doppler imaging in burn depth assessment: Systematic review and meta-analysis: Burns, 2016; 42(7); 1369-76

18. Hemington-Gorse SJ, A comparison of laser Doppler imaging with other measurement techniques to assess burn depth: J Wound Care, 2005; 14(4); 151-53

19. Hoeksema H, Van de Sijpe K, Tondu T, Accuracy of early burn depth assessment by laser Doppler imaging on different days post-burn: Burns, 2009; 35(1); 36-45

20. Ziegler B, Hundeshagen G, Cordts T, State of the art in enzymatic debridement: Plast Aesthet Res, 2018; 5; 33

21. Hirche C, Citterio A, Hoeksema H: Burns, 2017; 43(8); 1640-53

22. Hirche C, Kreken Almeland S, Dheansa B: Burns, 2020; 46(4); 782-96

23. Korzeniowski T, Strużyna J, Chrapusta AM: Med Sci Monit, 2022; 28; e935632

24. Gacto-Sanchez P, Surgical treatment and management of the severely burned patient: Review and update: Med Intensiva, 2017; 41(6); 356-64

25. Burke-Smith A, Collier J, Jones I, A comparison of non-invasive imaging modalities: Infrared thermography, spectrophotometric intracutaneous analysis, and laser Doppler imaging to assess adult burns: Burns, 2015; 41(8); 1695-707

26. Hoeksema H, Baker RD, Holland AJ, A new, fast LDI for assessment of burns: A multi-center clinical evaluation: Burns, 2014; 40(7); 1274-82

27. Stewart TL, Ball B, Schembri PJWound Healing Research Group, The use of laser Doppler imaging as a predictor of burn depth and hypertrophic scar postburn injury: J Burn Care Res, 2012; 33(6); 764-71

28. Wearn C, Lee KC, Hardwicke J, Prospective comparative evaluation study of Laser Doppler Imaging and thermal imaging in the assessment of burn depth: Burns, 2018; 44(1); 124-33

29. Erba P, Espinoza D, Koch N, FluxEXPLORER: A new high-speed laser Doppler imaging system for the assessment of burn injuries: Skin Res Technol, 2012; 18(4); 456-61

30. Cho JK, Moon DJ, Kim SG, Relationship between healing time and mean perfusion units of laser Doppler imaging (LDI) in pediatric burns: Burns, 2009; 35(6); 818-23

31. Jeng JC, Bridgeman A, Shivnan L, Laser Doppler imaging determines need for excision and grafting in advance of clinical judgment: A prospective blinded trial: Burns, 2003; 29(7); 665-70

32. Jan SN, Khan FA, Bashir MM, Comparison of laser Doppler imaging (LDI) and clinical assessment in differentiating between superficial and deep partial-thickness burn wounds: Burns, 2018; 44(2); 405-13

33. Claes KEY, De Decker I, Monstrey S, Helpful hints in deciding what and when to operate after enzymatic debridement: Burns, 2022 [Online ahead of print]

34. Jaskille AD, Ramella-Roman JC, Shupp JW, Critical review of burn depth assessment techniques: Part II. Review of laser doppler technology: J Burn Care Res, 2010; 31(1); 151-57

35. Pape SA, Skouras C, Byrne P, An audit of the use of laser Doppler imaging (LDI) in the assessment of burns of intermediate depth: Burns, 2001; 27; 233-39

36. Gill P, The critical evaluation of laser Doppler imaging in determining burn depth: Int J Burns Trauma, 2013; 3(2); 72-77

In Press

21 Feb 2024 : Clinical Research  

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer

Med Sci Monit In Press; DOI: 10.12659/MSM.943049  

22 Feb 2024 : Review article  

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943168  

23 Feb 2024 : Clinical Research  

A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943732  

26 Feb 2024 : Clinical Research  

Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in...

Med Sci Monit In Press; DOI: 10.12659/MSM.942509  

Most Viewed Current Articles

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750