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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 688-693

Biochemical and immunological changes as prognostic factors after homografts application for the management of major burn patients


Department of Plastic and Reconstructive Surgery, Menoufia University Hospital, Menoufia, Egypt

Date of Submission25-Jan-2019
Date of Decision27-Feb-2019
Date of Acceptance02-Mar-2019
Date of Web Publication27-Jun-2020

Correspondence Address:
Mohamed I Ghazal
Shebin Elkoom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_32_19

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  Abstract 


Objectives
To study the immunological and biochemical changes occurring after the application of homografts in the management of major burns and their implication as prognostic indices.
Background
Early excision of deep burn has been one of the critical advances in burn care. The advantages of early burn excision and closure is well established and it is generally accepted that it is a life-saving procedure.
Patients and methods
This study was done at the Plastic and Reconstructive Surgery Department, Menoufia University Hospitals as well as Al-Babtain Plastic Surgery and Burn Center in Kuwait. It was done from April 2016 to October 2018 on 15 patients with a follow- up period of more than 1 year in some cases. All patients were subjected to early excision of the burn eschar and then immediate coverage with either homografts, cadaveric grafts, or debridement only when grafts were not available. The changes in the laboratory parameters after 72 h postsurgery were compared with those 24 h before surgery to detect the effect of each technique on the clinical outcome.
Results
Three groups were investigated with the most significant fluctuation in the parameters measured in the first group of living donor homografts as compared with the second group cadaveric homograft and sole burn debridement as the third group.
Conclusion
The immunological parameters and inflammatory cytokines were improved by the use of homografts; detecting these changes in burned patients can anticipate whether the course of treatment is favorable or not.

Keywords: biochemical, burn, homografts, immunological, major


How to cite this article:
Megahed MA, El Kashty SM, Nassar AT, Ghazal MI. Biochemical and immunological changes as prognostic factors after homografts application for the management of major burn patients. Menoufia Med J 2020;33:688-93

How to cite this URL:
Megahed MA, El Kashty SM, Nassar AT, Ghazal MI. Biochemical and immunological changes as prognostic factors after homografts application for the management of major burn patients. Menoufia Med J [serial online] 2020 [cited 2020 Oct 22];33:688-93. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/688/287780




  Introduction Top


Early excision of deep burn wounds has been one of the most critical advances in modern burn care. The advantages of early burn wound excision and closure is well established and it is generally accepted that this technique is a life-saving procedure[1]. Split thickness skin autografting is the gold standard surgical treatment for coverage of deep partial and full-thickness burn wounds. Autografting has very important functions including epidermal function and prevention of infection, protein loss, and hypothermia. However, coverage of the wounds of patients with major burns is commonly limited by the lack of available skin graft donor sites[2].

A suitable solution can be human skin allografts, as temporary dressing to prevent fluid and electrolytes imbalance and also microbial contamination[3].

Allografts, also called homografts, are tissues or organs transplanted from a donor of the same species but of a different genetic constitution. In wound care in general, and burn care in particular, the primary types of allografts used are amnion membrane and cadaver skin[4].

The main indication for allografts is partial thickness burns where they are known to promote reepithelialization and pain relief. Human allografts are also widely used for wound bed preparation after excision of deep dermal or full thickness burns[5].

Several markers have been used as tools to predict the outcome in burn patients like procalcitonin, interleukin 2 (IL2), IL6, lymphocytes, tumor necrosis factor (TNF), albumin level, platelet counts, and acute-phase proteins[6].

Burn trauma is in need for prognostic indices. These aim for realistic expectations of the prognosis and for facilitating patient stratifications for different therapeutic strategies. It is still believed that we still lack proper prognostic indicators in burn patients[7].

The aim of this study was to study the changes occurring at the immunological and biochemical parameters after the usage of homografts in the management of major burn patients and their implication as prognostic indices for these patients.


  Patients and Methods Top


Patients

This prospective study was done at the Plastic and Reconstructive Surgery Department, Menoufia University Hospitals as well as Al-Babtain Plastic Surgery and Burn Center in Kuwait. It was done in the period from April 2016 to October 2018 on 15 patients with a follow-up period of more than 1 year in some cases.

Inclusion criteria

Major burn patients (≥10% total body surface area in children or ≥15% total body surface area) with limited donor site availability for autografts.

Exclusion criteria

  1. Superficial burn that is suspected to heal conservatively without need for graft in appropriate time
  2. Critically ill patients that cannot tolerate anesthesia and operation
  3. Patients who refuse operation.


The patients were divided into three groups:

Group A: included six patients in which procedures were performed in The Department of Plastic and Reconstructive Surgery, Menoufia University Hospitals; burn excision was followed by coverage using homografts taken from one of the first-degree relatives in most of the patients or excised skin from other patients who underwent operation with excision of excess skin as abdominoplasty or breast reduction operation. The prepared homografts were then applied to the recipient patient immediately after preparation of the burnt areas.

Group B: included five patientsin which procedures were performed in Al-Babtain Plastic Surgery and Burn Center in Kuwait; burn debridement was followed by coverage using cadaveric skin grafts.

Group C: included four patientsin which burn debridement (escharectomy) was only done.

Methods

Approval of the local ethics committee was obtained for the research.

For each patient in the inclusion criteria

Patient selection, communication, and establishing of the patient's expectations are done. Consent form of the procedure and associated complications are discussed.

The preoperative evaluation will include

All patients were subjected to history taking, general examination, local examination, and investigations. The routine laboratory workup was done 24 h prior to surgery and 72 h after surgery including: biochemical profile (renal function tests, liver function tests, etc.), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL6, and TNFα.

The levels of IL6 and TNF were measured by the use of a capture ELISA (ELISA; R and D Systems, Minneapolis, MN, USA).

All of the patients were admitted to Intensive Care Burn Unit or burn unit according to the percentage of burn wound, presence or absence of inhalation injury or presence or absence of other comorbidities. All of them were received their primary resuscitation treatment and after stabilization they were prepared for debridement.

Operative technique

Under general anesthesia, sterilization of the wound was done, escharectomy was done using the tangential excision technique till the well-bleeding surface was obtained and coverage either with skin homograft or using cadaveric skin but when grafts were not available debridement alone was done.

Homograft harvesting from the donor person

All of the donors were checked for virology investigations including hepatitis B and C viral infection and HIV viral infection for prophylaxis against disease transmission, routine preoperative investigation, and consent for donation of their skin.

Under general anesthesia or spinal anesthesia, sterilization of the donor site was done. Split thickness skin graft harvesting was done using a humpy knife [Figure 1]. In all patients, the thigh is the preferred donor site. The prepared homografts were then applied to the recipient site immediately after preparation of the burnt areas [Figure 2].
Figure 1: Sheet and meshed homograft after harvesting from the donor.

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Figure 2: Steps of burn debridement and application of living donor homografts with postoperative outcome. Application of prepared homografts to the recipient site immediately after preparation of the burnt areas. (a) before depridement (b) preparation of the site before deperdment (c) deperdment of part of burned region (d) complete depridment.

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Cadaveric skin preparation

Cadaveric skin in its containers as it comes from the manufacturer with the label donating the surface area and expiry date. It was prepared in a normal saline-containing tray followed by skin spreading over sheets for easy transfer to the recipient[Figure 3]. The prepared sheets were then applied to the recipient site immediately after preparation of the burn areas [Figure 4].
Figure 3: Cadaveric skin preparation in a normal saline-containing tray. (a) Cadaver skin as it comes in container (b) prepared in normal saline containing tray (c) Spreading the graft (d) Applying the graft over sheet.

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Figure 4: Steps of burn debridement and cadaveric graft application with postoperative outcome. Application of prepared sheets to the recipient site immediately after preparation of the burn areas. (a) spreading the graft before applying to burn area (b) spread over the recipient raw area (c) Bandage the site

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Follow-up

After the first dressing with good graft taken every other day, dressing is done until exposure of the wound was possible, with exposure of the wound and improving of the general condition of the patient, the patients were discharged with outpatient clinic follow-up on regular basis.

If there was any sign of considerable graft rejection, infection or loss, the patient is kept in the hospital and prepared for another session of homograft or autograft if possible.

Statistical analysis

Data were collected throughout history, basic clinical examination, laboratory investigations, and outcome measures were coded, entered, and analyzed using Microsoft Excel software. Data were then imported into the Statistical Package for the Social Sciences (SPSS, version 20.0) software for analysis through the SPSS 17 (SPSS Inc., Chicago, Illinois, USA). Parametric data were analyzed by one-way analysis of variance test and post-hoc Turkey's HSD test and presented as mean ± SD, while, categorical data (nonparametric data) were presented as number and percent after it was analyzed by χ2 test. Significant changes were considered whenever the P value was less than 0.05.


  Results Top


The study was conducted on 15 patients suffering of acute burn injury. Group A included six patients with a mean age of 4.583 years and percentage of burn to total body surface area with a mean age of 16.167%. Group B included five patients with a mean age of 15.50 years and percentage of burn to total body surface area with a mean of 28.60. Group C included four patients with a mean age of 33.00 years and percentage of burn above 10% of total body surface area with a mean of 56.25%. The level of the following parameters [white blood cells (WBCs), ESR, CRP, IL6, and TNFα] were measured 24 h before surgery and 72 after surgery using one-way analysis of variance test and post-hoc Turkey's HSD test to evaluate the changes that occur according to the type of interference. P represents a comparison between WBCs before the surgery and 72 h after the surgery; P1 represents a comparison between first and second groups, P2 represents a comparison between first and third groups, and P3 represents a comparison between second and third groups.

The mean values of the WBCs before and after the surgery in the studied groups were analyzed which denotes a significant difference; P2: 0.014 and P3: 0.044. The mean values of the ESR denotes significant difference in P2: 0.007. The mean values of the CRP denotes significant difference in P: 0.007, P1: 0.0002, P2: less than 0.0001 and P3: 0.0005. The mean values of the IL6 denotes a significant difference in P1: 0.033 and P2: 0.008. The mean values of the TNF denotes a significant difference in P1: 0.011 and P2: 0.0004 as shown in [Table 1].
Table 1: Changes before and after the surgery

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The patients' outcome in the studied groups regarding the need for autografting, time for healing, cosmetic outcome, and survival were analyzed by the aid of χ2 test denoting significant difference as shown in [Table 2].
Table 2: The patients' outcome in the studied groups

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  Discussion Top


Major burn injury induces an inflammatory response that is characterized by the activation of inflammatory pathways and the release of various cytokines. Inflammation is controlled by the balance between proinflammatory and anti-inflammatory mediators in a complex cytokine network. The uncontrolled release of proinflammatory and anti-inflammatory cytokines promotes immunological dysfunction and significant systemic inflammation, which result in tissue damage, multiple organ failure, or death in burn patients[8].

For many years, it was thought that these two responses were sequential. However, at both the transcript[9] and protein[10],[11] levels, data has recently emerged that challenges this longstanding paradigm, with evidence of a simultaneous increase in proinflammatory and anti-inflammatory responses postburn.

Although there have been several studies on the various immunological parameters and cytokines in burn patients, the pathogenic and prognostic role of each cytokine has not been fully elucidated[12]. In this network, one cytokine can influence multiple cell types (pleiotropy), and multiple cytokines can have similar biological effects on the same cell type (redundancy). Hence, the action of one cytokine can be compensated by another cytokine[13].

The purpose of the present study was fluctuations in immunological parameters and cytokines with different usage of homografts from either living [Figure 3] or cadaveric sources [Figure 4] or even with the sole use of burn debridement.

The first simple prognostic score developed by Weidenfeld 1902 is still working and believed in many burn centers in developing countries. Overall, many trials did not adequately state clear patient clinical variation which may affect their result[14].

According to our study, three groups have investigated on the most significant fluctuation in the parameters measured in the first group of living donor homografts as compared with the second group cadaveric homograft and sole burn debridement as in the third group.

However, there is little evidence to suggest that these associations are of any diagnostic or prognostic value. Thus, in recent years, with the aim of improving patient care, the emphasis of much trauma research has switched to biomarker discovery. Utilizing the recent technological advancements in the fields of genomics, proteomics, and metabolomics, several groups have performed detailed systems-based analysis of the immune and inflammatory response to major traumatic and thermal injury in an attempt to identify a single or combination of biomarkers that are of diagnostic and/or prognostic significance[15],[16].

The differences in the time to peak cytokine concentration between individuals or studies could result from increases in the concentration of the cytokines due to multiple factors, rather than by a single factor, some of which can increase concentrations by tens of thousands of times. It is reported that cytokine concentration fluctuates in seriously ill patients and that a variety of factors affect circulating cytokine levels[17].

In our study, we defined that surgical intervention with homografts can significantly alter the levels of immunological parameters as well as cytokines level. There was significant difference between the living donor homografts group and the sole burn debridement group in the measurement of all immunological and cytokine parameters. As the living donor homograft group was associated with better clinical outcome, we can assume the beneficial role of the measured parameter as a tool to predict the prognosis and the clinical outcome of treatment.

We observed that the patients with significant changes in their immunological and inflammatory cytokines following a certain type of surgical intervention have better clinical outcome than those who do not, regarding survival, need for autografting, time needed for healing, and cosmetic outcome.

Further studies of the changes occurring in the immunological parameters of the burn patients along the course of treatment need to be investigated to develop a solid prognostic index for burn management.


  Conclusion Top


In our study, we observed that the patients with significant changes in their immunological and inflammatory cytokines following a certain type of surgical intervention have better clinical outcome than those who do not, regarding survival, need for autografting, time needed for healing, and cosmetic outcome.

We showed that immunological parameters and the expression of inflammatory cytokines were improved by the use of homografts; by determining these changes in burned patients we can anticipate whether the course of treatment is favorable or not for the patient. We suggest that with further studies we can have a tool to predict the clinical outcome based on the fluctuations in immunological parameters and inflammatory cytokines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
Coruh A, Yontar Y. Application of split-thickness dermal grafts in deep partial- and full-thickness burns: a new source of auto-skin grafting. J Burn Care Res 2012; 33 :94–100.  Back to cited text no. 2
    
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Mahdavi-Mazdeh M, NozaryHeshmati B, Tavakoli SAH, Ayaz M, Azmoudeh Ardalan F, Momeni M. Human split-thickness skin allograft: skin substitutein the treatment of burn. Int J Org Transplant Med 2013; 4 :96–101.  Back to cited text no. 3
    
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Hermans MH. Preservation methods of allografts and their lack of influence on clinical results in partial thickness burns. Burns 2011; 37 :873–881.  Back to cited text no. 4
    
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8.
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Ferreira LC, Regner A, Miotto KD, Moura S, Ikuta N, Vargas AE, et al. Increased levels of interleukin-6, -8 and -10 are associated with fatal outcome following severe traumatic brain injury. Brain Inj 2014; 28 :1311–1316.  Back to cited text no. 10
    
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Jastrow KM III, Gonzalez EA, McGuire MF, Suliburk JW, Kozar RA, Iyengar S, et al. Early cytokine production risk stratifies trauma patients for multiple organ failure. J Am Coll Surg 2009; 209 :320–331.  Back to cited text no. 11
    
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Jeschke MG, Gauglitz GG, Kulp GA, Finnerty CC, Williams FN, Kraft R, et al. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS ONE 2011; 6 :e21245.  Back to cited text no. 12
    
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Ozaki K, Leonard WJ. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem 2002; 277 :29355–29358.  Back to cited text no. 13
    
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Hur J, Yang HT, Chun W, Kim JH, Shin SH, Kang HJ, et al. Inflammatory cytokines and their prognostic ability in cases of major burn injury. Ann Lab Med 2015; 35 :105–110.  Back to cited text no. 15
    
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Jeschke MG, Gauglitz GG, Finnerty CC, Kraft R, Mlcak RP, Herndon DN. Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories. Ann Surg 2014; 259 :814–823.  Back to cited text no. 16
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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