Effects of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns
Abstract
To investigate the effect of vitamin C combined with recombinant basic fibroblast growth factor (rbFGF) on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. A retrospective analysis of 98 patients with high-voltage electrical burns admitted to our hospital from January 2021 to April 2022. A total of 98 patients were divided into research group and control group, including 49 cases treated with vitamin C combined with rbFGF and 49 cases treated with only rbFGF. The disappearance time of clinical symptoms, wound healing rate, area of granulation tissue growth, level of inflammatory factors, oxygen environment were compared between two groups after one and three courses of treatment. After treatment, the disappearance time of erythema, pain, swelling, blisters, exudate symptoms, wound healing time, scab formation time, and hospitalisation time in the research group were significantly better than those in control group (P < .05). There was no significant difference in the wound healing rate and area of granulation tissue growth between the two groups after one course of treatment (P > .05), while it is significantly better than those in control group after three courses of treatment (P < .05). The inflammatory factors, succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) scores in research group were significantly better than that in control group after three courses of treatment (P < .05). Vitamin C combined with rbFGF may be worthy to reduce inflammatory factors, regulate oxygen environment, which can be popularised and applied in clinical practice.
1 INTRODUCTION
Electrical burn is a common injury in daily life. It mainly refers to the direct current passing through the human body when it is subjected to electric shock, and the electrical energy is converted into heat energy in the body, which heats the human tissues and damages the tissues and organs of the body.1 In particular, high-voltage (>1000 V) burns will not only cause coagulation necrosis of skin tissue, and even lead to skin carbonisation, but also cause serious damage to the internal tissues and organs of the body.2 And this kind of damage is manifested as “small entrance, large exit, shallow outside, deep inside”(Figure 1), there will be residual current inlet and outlet on the body, and under normal circumstances, the damage of the outlet is far more serious than the inlet.2 The degree of damage varies with the nature of the current in contact with body, the resistance of the skin tissue, the magnitude of the voltage, the humidity of the human skin, the duration of the current acting on human body, the contact area, etc., which can threaten the life of the patient in serious cases.3 Previous studies have pointed out that the amputation rate of extremity high-voltage electrical burns is 10%–60%, and it can lead to complications such as non-healing of the wound, secondary scar residue, and wound infection, which has attracted high attention of clinicians.4
Vitamin C has strong reducibility and is easily oxidised to dehydrovitamin C, which can effectively resist oxidation and free radicals, but its reaction is reversible.5 In addition, vitamin C stimulates the immune system, preventing and treating infections.5 Recombinant basic fibroblast growth factor (rbFGF) is a trace amount of active protein in body, which has the effect of repairing and regenerating the mesodermal and ectodermal cells, can be used to treat fresh burns and chronic wounds.6 At present, domestic research on high-voltage electrical burns is limited to basic experiments, and there are few clinical studies on the efficacy of vitamin C combined with rbFGF in patients with high-voltage electrical burns. Based on this, this study aimed to explore the effects of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns, to provide a theoretical basis for clinicians.
2 MATERIALS AND METHODS
2.1 General patient information
This study is a retrospective study. Patients with high-voltage electrical burns who were treated in our hospital from January 2021 to April 2022 were selected as the research objects. This research protocol complies with the relevant requirements of the Declaration of Helsinki of the World Medical Association, and has been approved by the ethics committee of our hospital.
2.2 Inclusion and exclusion criteria
Inclusion criteria: (1) All patients with second and third-degree burns7; (2) Patients with high-voltage electrical burns as the cause of burns; (3) No cardiovascular and cerebrovascular diseases, diabetes mellitus before injury and other system diseases; (4) No vitamin C and other antioxidant drugs were taken within 3 months before the injury.
Exclusion criteria: (1) simple flame burns, trauma and patients with only electrical shock but no skin damage caused by arcs or sparks igniting items; (2) patients with severe combined injuries and received amputation; (3) patients with allergic constitution to the drugs in this study; (4) patients suffering from chronic diseases such as severe renal insufficiency, coagulation dysfunction, infectious diseases, renal insufficiency, blood system diseases, severe malnutrition, autoimmune diseases, chronic obstructive pulmonary disease and diabetes. According to the inclusion and exclusion criteria, a total of 98 patients were finally included, with 49 cases in research group and 49 cases in the control group.
2.3 Treatment method
After admission, patients of both groups underwent routine treatment such as debridement: removing foreign bodies, dirt, necrotic and devitalised tissue in the wound, using sterile gauze to dry the wound exudate.
The patients in control group were given rbFGF treatment (manufacturer: Beijing Shuanglu Pharmaceutical Co., Ltd.; National medicine permission number: S20140009), 200 mL of normal saline was mixed with rbFGF to make a liquid medicine of 104 IU/mL, and sterile gauze was soaked in the medicine. After soaking, apply it to the wound surface, use the semi-exposure method to bandage, and change the dressing once every other day. Consecutive use was taken for more than 3 weeks, 3 weeks as a course of treatment, three consecutive courses of treatment.
On basis of the above treatment, the research group was given vitamin C injection (manufacturer: Shandong Hualu Pharmaceutical Co., Ltd.; National medicine permission number: H37020858) 150 mg/(kg·d) intravenous drip, one time a day, consecutive use for more than 3 weeks, and 3 weeks as a course of treatment. All patients received at least one course treatment.
2.4 Observation indicators
- The disappearance time of clinical symptoms (including erythema, pain, swelling, blisters, exudation, etc.) of the patients in two groups were recorded, meanwhile, the wound healing time, scab formation time and hospitalisation time were recorded. Blister disappearance time was defined as the time from admission to complete disappearance of blisters on the wound surface. Scab formation time was defined as the time from admission to wound scab formation. Wound healing time was defined as the time from admission to wound completely healing.
- The wound healing rate and area of granulation tissue growth in two groups were recorded after one and three courses of treatment. The calculation of the area of granulation tissue growth was as following. 0 point, the granulation tissue grew obviously and the coverage area was less than 1/4. 1 point, the granulation tissue grew and the coverage area was between 1/4 to 1/2. 2 point, the granulation tissue grew well and covered more than 1/2 of the wound. 3 point, the granulation tissue showed red and grew well, covering all wounds.
- Levels of inflammatory factors: Before treatment and after three courses of treatment, 5 mL of fasting venous blood was collected from patients, centrifuged and sent for examination. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), C-reactive protein (CRP), and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay, and the kits were purchased from Shanghai Yaji Biotechnology Co., Ltd.
- Oxygen environment: Before the intervention and after three courses of treatment, the granulation tissue in the wound centre of the patient was used to melt it, and the temperature was controlled at 2–8°C. Succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay after centrifugation, and the kits were purchased from Shanghai Yaji Biotechnology Co., Ltd.
2.5 Statistical methods
The SPSS software program (version 21.0; IBM Corporation, Chicago, Illinois) was used. Normally distributed measurement data were expressed as mean ± standard deviation (SD), measurement data were compared between two groups using t test. The enumeration data were expressed as percentage (%), and the χ2 test was used for comparison between groups (all enumeration data were analysed by the chi-square test). P < .05 was considered statistically significant.
3 RESULTS
3.1 Comparison of the general conditions of patients in two groups
A total of 98 patients were included in two groups, with 49 cases in each. Research group: aged from 21 to 56 years, with an average age of (43.3 ± 11.8) years; 29 males and 20 females; the time from burn to hospital was 3–23 hours, with an average of (16.3 ± 3.3) hours; Control group: aged from 21 to 57 years, with an average age of (43.3 ± 11.7) years; 28 males and 21 females; the time from burn to hospital was 3–22 hours, with an average of (16.2 ± 3.3) hours. There were no significant differences in gender, age, burn time, burn area, burn location and burn degree between the two groups (P > .05) (Table 1).
| Index | Research group (n = 49) | Control group (n = 49) | t/χ2 | P |
|---|---|---|---|---|
| Age (year) | 43.3 ± 11.8 | 43.3 ± 11.7 | −0.021 | .983 |
| Gender: M/F (n) | 29/20 | 28/21 | 0.042 | .838 |
| Burn time (h) | 16.29 ± 3.29 | 16.22 ± 3.32 | 0.105 | .917 |
| Burn area (%) | 4.42 ± 0.73 | 4.39 ± 0.81 | 0.193 | .847 |
| Burn site (n) | 0.204 | .903 | ||
| Limbs | 17 | 15 | ||
| Trunk | 24 | 25 | ||
| Face and neck | 8 | 9 | ||
| Degree of burn (n) | 0.041 | .839 | ||
| Shallow II degree | 26 | 25 | ||
| Deep II degree | 23 | 24 |
3.2 Comparison of clinical symptoms recovery between patients in two groups
After treatment, the disappearance time of erythema, pain, swelling, blisters and exudate symptoms, as well as wound healing time, crusting time, and hospitalisation time in research group were better than those in control group, the differences were statistically significant (P < .05) (Table 2).
| Index | Research group (n = 49) | Control group (n = 49) | t | P |
|---|---|---|---|---|
| Erythema disappearance time (d) | 5.34 ± 0.82 | 6.67 ± 0.89 | −7.809 | <.001 |
| Pain relief time (d) | 3.18 ± 0.72 | 4.07 ± 0.76 | −5.951 | <.001 |
| Swelling relief time (d) | 5.37 ± 1.28 | 6.02 ± 1.31 | −2.484 | .015 |
| Blister disappearance time (d) | 4.47 ± 0.56 | 5.26 ± 0.63 | −6.561 | <.001 |
| Exudate disappearance time (d) | 5.87 ± 0.47 | 5.01 ± 0.44 | 9.329 | <.001 |
| Wound healing time (d) | 24.38 ± 2.01 | 27.91 ± 2.09 | −8.522 | <.001 |
| Scab formation time (d) | 18.29 ± 2.35 | 20.87 ± 2.29 | −5.504 | <.001 |
| Hospitalisation time (d) | 23.29 ± 2.98 | 26.18 ± 3.01 | −4.776 | <.001 |
3.3 Comparison of wound healing rate and area of granulation tissue growth between two groups
After one course of treatment, there was no significant difference in the wound healing rate and the area of granulation tissue growth between the two groups (P > .05). However, after three courses of treatment, the wound healing rate and the area of granulation tissue growth in research group were better than those in the control group, and the difference was statistically significant (P < .05) (Table 3) (Figure 2).
| Index | Time | Research group (n = 49) | Control group (n = 49) | t | P |
|---|---|---|---|---|---|
| Wound healing rate (%) | After one course of treatment | 51.28 ± 10.29 | 48.71 ± 10.32 | 1.234 | .221 |
| After three course of treatment | 83.32 ± 10.21 | 78.21 ± 10.28 | 2.469 | .015 | |
| Area of granulation tissue growth (cm2) | After one course of treatment | 1.63 ± 0.43 | 1.61 ± 0.41 | 0.236 | .814 |
| After three course of treatment | 2.45 ± 0.47 | 2.21 ± 0.43 | 2.637 | .009 |
3.4 Comparison of the levels of inflammatory factors between the two groups
Before treatment, there was no significant difference in the levels of IL-6, IL-1β, CRP and TNF-α between the two groups (P > .05); After three courses of treatment, the levels of IL-6, IL-1β, CRP and TNF-α in research group were lower than those in the control group, and the difference was statistically significant (P < .05) (Table 4).
| Index | Time | Research group (n = 49) | Control group (n = 49) | t | P |
|---|---|---|---|---|---|
| IL-6 (ng/L) | Before treatment | 218.91 ± 23.19 | 216.21 ± 22.09 | 0.589 | .557 |
| After three courses of treatment | 65.19 ± 6.98 | 69.91 ± 7.27 | −3.278 | .001 | |
| IL-1β (pg/L) | Before treatment | 248.91 ± 23.29 | 247.93 ± 22.28 | 0.213 | .832 |
| After three courses of treatment | 118.81 ± 21.38 | 128.97 ± 24.29 | −2.198 | .029 | |
| CRP (mg/L) | Before treatment | 34.98 ± 5.29 | 34.91 ± 5.32 | 0.065 | .948 |
| After three courses of treatment | 9.08 ± 2.09 | 9.98 ± 2.19 | −2.081 | .039 | |
| TNF-α (pg/L) | Before treatment | 192.91 ± 12.39 | 192.67 ± 11.92 | 0.098 | .922 |
| After three courses of treatment | 137.28 ± 15.09 | 143.84 ± 14.89 | −2.166 | .033 |
- Abbreviations: CRP, C-reactive protein; IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumour necrosis factor-α.
3.5 Comparison of oxygen environment levels between the two groups
Before treatment, there was no significant difference in the levels of SDH and LDH between the two groups (P > .05); After three courses of treatment, the SDH level in the research group was higher than that in the control group, while the LDH level was lower, and the difference was statistically significant (P < .05) (Table 5).
| Index | Time | Research group (n = 49) | Control group (n = 49) | t | P |
|---|---|---|---|---|---|
| SDH (U/L) | Before treatment | 1.91 ± 0.28 | 1.92 ± 0.31 | −0.181 | .857 |
| After three courses of treatment | 2.31 ± 0.24 | 2.13 ± 0.32 | 3.149 | .002 | |
| LDH | Before treatment | 190.28 ± 19.82 | 189.33 ± 19.98 | 0.236 | .814 |
| (U/L) | After three courses of treatment | 136.28 ± 19.92 | 145.29 ± 19.83 | −2.244 | .027 |
- Abbreviations: LDH, lactate dehydrogenase; SDH, succinate dehydrogenase.
4 DISCUSSION
High-voltage electrical burn is a special burn with high morbidity and mortality.8, 9 Electrical burns refer to the damage caused by the conversion of electrical energy into heat energy by electric current flowing through the tissues of the body. Owing to the characteristics of the “exit” and “entrance,” electrical burns not only damage the skin tissue, but also cause damage to the blood vessels, nerves and muscles in the body, even bone necrosis increases the difficulty of treatment.10 In the past, hyperbaric oxygen, laser irradiation, immersion bath therapy, closed negative pressure drainage and other methods were often used in clinical treatment of burns,11 but there are few studies on high-voltage electrical burns. Vitamin C is a polyhydroxy compound with the chemical formula C6H8O6. The structure is similar to glucose, and the two adjacent enol hydroxyl groups on the second and third positions in the molecule are easily dissociated to release H+, so it has the property of acid, also known as ascorbic acid.10 The literature shows that vitamin C is a strong reducing agent with anti-inflammatory, anti-oxidative stress and protection of vascular endothelial cell function.12 It can be used for severe burns, trauma, ischemia–reperfusion injury, sepsis, and many other diseases.12 In addition, rbFGF is a trace amount of active protein in the body. Previous animal experiments have shown that it is of great significance for the regeneration and repair of myoblasts, vascular endothelial cells, nerve cells and tendon tissue and other tissue cells.13
The study by Wojcik14 et al. pointed out that the use of biomaterials containing a mixture of vitamin C to treat chronic wounds and burn patients can benefit patients. Nakajima15 and other studies pointed out that the use of large doses of vitamin C can effectively treat burn patients, and can reduce mortality. Ahn16 believed that rbFGF can effectively shorten the treatment time of patients with deep second-degree burns and has good safety. The research of Zhan17 pointed out that rbFGF can effectively treat burn patients with good safety, which provides a scientific basis for the treatment of clinical burns. The results of our study showed that after treatment, the disappearance time of erythema, pain, swelling, blisters, and exudate symptoms, wound healing time, crusting time, and hospitalisation time in the research group were better than those in the control group, suggesting that vitamin C combined with rbFGF can effectively shorten the time to disappearance of clinical symptoms in patients with high-voltage electrical burns, shortens the time of scabbing and hospitalisation. Studies by Bonucci18 and others pointed out that vitamin C treatment in burn patients can not only improve the wound healing rate and the area of granulation tissue growth, but also regulate the overexpression of related genes. The research of Xiang Guangjun19 pointed out that rbFGF can promote wound healing in patients with second-degree burns. The results of this study showed that after three courses of treatment, the wound healing rate and the area of granulation tissue growth in research group were better than those in control group, suggesting that vitamin C combined with rbFGF can effectively promote the growth of granulation tissue in patients with high-voltage electrical burns and promote wound healing.
Previous related studies have pointed out that burns are highly irritating and traumatic, which can cause ischemia and hypoxia in tissue cells, resulting in excessive activation of inflammatory cells in the body, immune dysfunction, and the production of a large number of anti-inflammatory and pro-inflammatory cytokines. trigger a systemic inflammatory response.20 IL-6 and IL-1β are important factors that mediate acute phase responses such as immunity and inflammation, which can induce stem cells to produce CRP, and are one of the important mediators involved in the pathophysiological process of burns.20 CRP is an acute response protein that participates in the body's immune response, and begins to increase after the inflammatory response occurs, which can reflect the severity of the disease.20 TNF-α is an important pro-inflammatory mediator, which can promote the cytokine cascade reaction, activate related neutrophils, make the body produce a large amount of reactive oxygen species, damage important organs and cause organ failure.20 It can reflect the inflammatory response in the body and is an important indicator of inflammatory infection and poor prognosis.20 The study by George21 pointed out that the levels of inflammatory factors are highly expressed in burn patients, and reducing the levels of inflammatory factors can promote the recovery of burn patients. Studies by L Langlois22 and others pointed out that vitamin C can effectively treat critical illnesses such as burns and sepsis, and the curative effect is obvious. Research by Yu23 et al. pointed out that rbFGF applied to diabetic deep second-degree burn patients has a significant effect, which can reduce the wound exudation rate and shorten the healing time. The results of this study showed that after three courses of treatment, the levels of IL-6, IL-1β, CRP and TNF-α in research group were lower than those in the control group, suggesting that vitamin C combined with rbFGF can effectively reduce the levels of inflammatory factors in patients with high-voltage electrical burns, thereby promoting wound healing.
The growth of granulation tissue at the wound surface indicates that the wound is repairing itself, and the granulation tissue can fill the defect tissue, help the wound to shrink, and improve the anti-infection ability of the wound.24 However, the growth of granulation tissue is closely related to the oxygen environment of the wound tissue.24 SDH is a rate-limiting enzyme with oxidative metabolism, if its activity decreases, it indicates tissue hypoxia; LDH is a core enzyme of glycolysis, which can objectively reflect the level of non-oxidative metabolism in tissues, and its activity is positively correlated with the degree of tissue damage.25 Research by Zhan Weijie26 and others pointed out that effective intervention measures can regulate the oxygen pressure of wounds in middle-aged and elderly patients with chronic lower extremity ulcers and promote wound recovery. Research by Cheng Xin27 and others pointed out that the application of effective interventions in patients with deep second-degree burns can improve the hypoxic state of wound tissue, promote wound healing, shorten hospital stay and help reduce post-healing scar formation. High security. However, there is no clinical research on the oxygen environment of high-voltage electrical burn patients with vitamin C combined with rbFGF. Our results showed that after three courses of treatment, the level of SDH in research was higher than that in the control group, and the level of LDH was lower than that in the control group, suggesting that vitamin C combined with rbFGF can effectively regulate the oxygen environment in patients with high-voltage electrical burns. The reason for this may be that vitamin C can enhance cell differentiation from somatic cells to induced pluripotent stem cells. Based on its redox potential and strong antioxidant capacity, vitamin C is known as the most important antioxidant against the effects of free radicals. Oxygen free radicals, anti-inflammatory, promoting the body's ability to metabolise, enhancing the body's immune function and other functions.12
However, this study also has limitations. Firstly, this study failed to explore the specific mechanism of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. This remained to be investigated in an animal study. Secondly, our sample size is small, and the sample size should be expanded in the later stage. The results of this study were further confirmed.
5 CONCLUSION
Vitamin C combined with rbFGF may be worthy to improve the clinical symptoms of high-voltage electrical burn patients, accelerate wound healing, promote the growth of granulation tissue, reduce the level of inflammatory factors, regulate the oxygen environment, and improve scar hyperplasia, which is worthy of clinical application.
AUTHOR CONTRIBUTIONS
Han Zhang and Guihua Zhang contributed to the conception and design of the study; Beibei Qin, Yankai Zhao, and Rongpin Zhang performed the experiments, collected and analysed data; Han Zhang and Guihua Zhang wrote the manuscript; All authors reviewed and approved the final version of the manuscript.
ACKNOWLEDGEMENTS
None.
FUNDING INFORMATION
No funding was received for this study.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
ETHICS STATEMENT
Ethics approval and consent to participate: The study protocol was approved by the Ethics Committee of Xinji City Second Hospital. Informed consent was obtained from all the study subjects before enrolment.
Open Research
DATA AVAILABILITY STATEMENT
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
