A Comprehensive Review of a particular Skin Injury: Pathogenesis, triggers, and current Treatment Options

Taranjeet Kukreja¹, Arushi Saloki¹, Swarnlata Saraf^1*

¹University Institute of Pharmacy, Pandit Ravishankar Shukla University, Raipur – 492010, Chhattisgarh, India.

 

Abstract: By definition, an open injury is any severe break in the continuity of the skin and deep tissue. Because contusions are healed injuries, the term given above does not apply to them. The classification of injuries is essential for both therapeutic and medico-legal purposes. Burn injuries are comparable to other injuries in that they require the same basic principles for healing and care, but they differ in that they have a greater impact on the patient's overall health and are essential to the patient's eventual survival, the development of deformity, and rehabilitation. Treatment of burn injuries has always been the responsibility of burn specialists. Both local and systemic therapy have long been advised for treating burn injuries and minimizing burn scars. This review summarizes the treatment of burn injuries brought on by a variety of physical and chemical agents requires unique regimens that are completely different from those used to treat any other traumatic injuries. Other acute injuries that undergo entire blood loss result in shock, but major burns that experience significant plasma loss due to increased capillary permeability result in distress. Burn injuries are initially sterile compared to the majority of other injuries, however, due to the immunocompromised state of burn patients and injury infection frequently ends in death in serious burns. We have discussed the pathophysiology, primary care therapies, nanomaterials used in injury healing therapy and various nanoparticles in injury healing process for burn injuries in this review.

Keywords: Skin injury, injury, injury care, acute injury, management, treatment.

Introduction

Injuries

The most typical sort of injury is a burn, which is an injury to the flesh brought on by heat, chemicals, friction, or electricity. Burn injuries come in a variety of forms, but third- and fourth-degree burns are the most challenging to heal. In these situations, the burn damages the circulatory system, deeper tissues, and the skin. Burn injuries, therefore, need to be managed in a way that may keep them free from infections and promote quicker recovery the figure as shown in figure 1[1].

 Burn Injuries

Burns are one of the most prevalent injuries in the home. The term "burn" refers to more than just the sensation of burning caused by this damage. Burns induce significant skin damage, resulting in the death of the damaged skin cells [2]. In other terms, burns are injuries caused by heat, cold, electricity, chemicals, friction, or radiation to the skin and other tissues. Most burns occur as a result of heat from hot liquids, solids, or fires [3].

Also, according to WHO burn is defined as “an injury to the skin or other organic tissue primarily caused by heat or due to radiation, radioactivity, electricity, friction or contact with chemicals.” ([4] After traffic accidents, falls, and interpersonal violence, burns are the fourth most common type of trauma worldwide. Approximately 90% of burns occur in low to medium-income nations, which usually lack the infrastructure needed to lower the incidence and severity of burns [5]

It is reported that burn injuries affect around seven million individuals in India each year, resulting in 1.4 lakh fatalities and 2.4 lakh persons becoming disabled. Burn fatality rates had plummeted in high-income countries [6]. Cooking is the most prevalent activity that causes burn injuries in the home. Burns in children are more likely at home (84 percent) and when they are unattended (80 percent). Adults are as vulnerable to burns at home, outdoors, or at work. Adult females are more likely to be burned at home, but adult males are more likely to be burned outside or at work. The bathroom is the most common location for burns to sustain among older persons, followed by the kitchen. [7]

According to a recent survey in India, over 1 million individuals were moderately or seriously burned last year. Every year, over 1.7 million Bangladeshi youngsters are mildly or severely burned. Children with burns suffer a transitory impairment in Bangladesh, Colombia, Egypt, and Pakistan, i.e., 17%, and a lifelong handicap in 18% of cases. In rural Nepal, burns are the 2nd most prevalent injury, accounting for 5% of disabilities. In the United States of America, around 4,10,000 burn injuries occurred in 2008, with approximately 40000 requiring hospitalizations. [4].

Burn is a well-known phenomenon in our nation, with the majority of cases occurring in the lower socioeconomic strata. It was a type of dichotomy in that this group of people lacked the financial means to cover the charges associated with contemporary burns treatment procedures. Furthermore, the discouraging factors of mortality and Return on Investment rarely made the treatment a profitable proposition from a healthcare business standpoint. The government needed to develop and implement treatment methods that were both economical and effective. This, however, would never be achievable due to the private sector's lack of effort in dealing with this type of trauma.

Currently, only treasury hospitals can treat burns. There is a scarcity of both doctors and trained technical staff for this type of treatment, which explains why there aren’t enough research and thus insufficient Burn Treatment Centers. Because burns primarily affect a socioeconomic group that cannot afford the costly treatment, effective cost management in the treatment of burns in our nation becomes critical.

High treatment costs have not only contributed to the trauma's mortality rate, but have also resulted in some malpractice, in which a patient's funds are siphoned off during the preliminary duration of treatment and then referred to a subsidized government facility, where the patient's condition deteriorates and, in some cases, results in death, due to a lack of proper treatment and adequate care[1].

 Classification of burn injuries

The characteristics of a burn depend upon its depth. So as per the penetration of burns pathologically it may be divided into four major degree burns. The Classification (grouping) of burn injuries is based on the causative factor. There are six groups of burn injuries.

They are-

·     Scalds

·     Contact

·     Burns

·     Fire

·     Chemicals

·     Electrical

·     Radiation

Burns are brought on by a variety of external sources classified as thermal, chemical, electrical, and radiation. The most frequent causes of burns cited in the included fire or flame (44%), chemicals (3%), electricity (4%), hot objects (9%), and scalds (33%). Burn injuries occur in 69% of cases at home or work (9 percent), and the majority are unintentional. Only 2% are caused by another person, and 1-2 percent are caused by a suicide attempt.[8]. Inhalation damage to the airway and lungs can result from these causes in roughly 6% of cases. [9].

Poor people are more likely to suffer from burn damage. In colder climates, fire-related burns are more prevalent [10]. Cooking over open flames, as well as chronic illnesses in adults and developmental problems in children, are all risk factors in underdeveloped nations [11].

Thermal

The most common causes of burns. Scald injuries are most prevalent in children under the age of five [12], and two-thirds of all burns in the United States and Australia are caused by scalds. Burns in youngsters are caused by contact with hot items in the range of 20-30%. Scalds are usually first- or second-degree burns, but third-degree burns can occur after continuous contact [13]. In many nations, fireworks are a common source of burns during the holiday season [14]. Fire and hot liquids are the main causes of fatality in house fires. In the United States, smoking accounts for 25% of fatalities, whereas heating devices account for 22% [15]. The majority of burn casualties are caused by firefighting operations [16]. Scalding is caused by exposure to hot beverages, hot liquids, gases, high-temperature tap water in baths or showers, hot cooking oil, or steam [14].

Chemical

Chemical burns account for 2 to 11% of all burns, and they are responsible for up to 30% of burn-related fatalities. Over 25,000 chemicals can produce chemical burns [12].

The majority of them are either a strong basic compound (55%) or a strong acidic chemical (26%) [13]. Ingestion is the leading cause of mortality from chemical burns. Sulfuric acid, sodium hypochlorite, and halogenated hydrocarbons are some of the most common agents. Burns induced by hydrofluoric acid can be very deep, yet they are usually asymptomatic unless they are exposed. Formic acid can cause a considerable percentage of red blood cells to break down [14].

Muscle contractions

The majority of the damage in high-voltage injuries occurs inside, and the skin is not just responsible for judging numerous of burns [3]. Low or high voltage contact might cause heart arrhythmias or cardiac arrest.

Radiation

These are extremely intense and harmful radiations that are emitted by specific chemicals and can cause burn injuries on our skin. Radiation burns may be caused by

·     Prolonged exposure to ultraviolet light such as from the sun,

·     tanning booths or arc welding

·     From ionizing radiation such as from radiation therapy,

·     X-rays or radioactive fallout.

Electrical

Electrical burns are categorized as:

·     High voltage (≥1000 volts)

·     Low voltage (˂ 1000 volts)

·     Flash burns (secondary to an electric arc).

The most prevalent cause of electrical burns is electrical cables (60%) followed by electrical outlets (14%)[17]Lightening is another element that can cause electrical burns. Outdoor activities such as mountain climbing, field games, and working outside are all risk factors for getting struck. Lightning is responsible for 10% of all deaths. While electrical injuries are most frequently associated with burns, they can also result in fractures or dislocations as a result of blunt force trauma.

Non-accidental

 3–10% of individuals who are hospitalized due to scalds or fire burns are assault victims as shown in fig2.

Child abuse

·     Personal

·     Disputes

·     Spousal

·     Abuse

Elder abuse

Business disputes

A dousing injury or scald indicates child abuse. When an extremity or the lower body (buttock or perineum) is submerged in hot water, this occurs. Spill and immersion scalds are two different types of liquid scalds. Fire burn injuries can be classified into flash and flame burns.

 Other high-risk signs of potential abuse include circumferential burns, a burn of uniform depth, absence of splash marks, and are associated with other signs of abuse. (Gibran NS-2011). Causes of burns is shown in fig 3.

Degrees of burn injuries.

Based on the layers of skin present there are the following degrees of burn injuries, showing their intensities in different layers of the skin is described in table 1. And types of burns shown in fig 4. [18]

Pathogenesis of Burn Injuries

The Pathogenesis of burn injuries is characterized by an inflammatory activity leading to rapid dropsy formation, due to increased microvascular permeability, vasodilatation, and increased extravascular osmosis. The effects are caused by a direct temperature influence on the microvasculature as well as inflammatory transmitters. And the representation of burn injuries is explained in fig 5.

The histamine release leads to vasodilatation and increased venous permeability. Damage to cell membranes is induced by oxygen free radicals generated by polymorph nuclear leucocytes, which also leads to the activation of enzymes that catalyze the hydrolysis of the prostaglandin precursor, arachidonic acid, resulting in the rapid synthesis of prostaglandin. Prostaglandin inhibits nor-epinephrine release and is important in modulating the nervous system which is activated in response to thermal injury.

In the case of heat damage affected by changes in the morphology of the blood lymph barrier, the outcome is an elevation in the membranes of vacuoles and numerous open endothelium intercellular connections. Also, the burn injury provides a wide portal of entry to surface infection with the vulnerability of septic shock. Pathogenesis of Burn Injuries is shown in fig 6 [19].

Systemic Changes

This change involves the changes related to the internal body showing changes inside the body.

This includes in fig 7.:

Burns that are severe cause a reaction that affects practically every organ system. Inflammation, hyper-metabolism, muscle atrophy, and insulin resistance are all characteristics of the pathophysiological response to severe burns, with metabolic abnormalities known to last for years.

Burn resuscitation is classified into two stages. The restorative phase also referred to as the hyper-dynamic" or "ebb phase," takes place initially and lasts for 1 to 3 days. Increased vascular susceptibility, fluid changes leading to intravascular volume deprivation, and edema production define this time. During this phase, the major objective is to restore and preserve tissue perfusion to prevent ischemia from hypovolemic and cellular stress. During this stage, resuscitation is crucial. Multiple formulae are employed, but the Parkland formula is the most frequent, as stated in the "Management" section. Oncotic and hydrostatic fluxes can often become disproportionate. Microvascular permeability is risen vascular heat damage and the release of inflammatory mediators. Because of the enhanced vascular permeability, intravascular fluid and plasma proteins are shifted into the interstitial region, lowering capillary oncotic pressure. The new interstitial particles produce an osmotic gradient, which pushes more fluid into the interstitium and causes edema. Photo-damage is lost into the edema and from the damaged skin surface, resulting in hypo-proteinemia. After a 40 percent TBSA burn, the vascular compartment can lose up to half of the total plasma water in 2 to 3 hours. Massive edema causes intravascular hypovolemia and subsequent haemoconcentration within the first 12 to 24 hours after injury. Around 24 to 72 hours after injury, a "hyper-dynamic and hyper-metabolic flow phase" begins. A decline in vascular permeability, an increase in heart rate, and a decrease in peripheral vascular resistance all contribute to an increase in cardiac output during this period. Microvascular integrity begins to repair 24 to 48 hours after burn damage, and peripheral blood flow is enhanced by a reduction in systemic vascular resistance, with preferential redistribution to the burn site region. 3 to 4 days after a burn injury, cardiac output is more than 1.5 times that of a non-burn, fit patient. In addition, their metabolic rate is roughly 3 times that of their baseline metabolic rate. Showing systemic changes due to burning injury is explained in fig 8.

3.2: Molecular Pathway

Healing and infection prevention both require a localized inflammatory response. SIRS is characterized by high levels of IL-6, IL-2, and IL-8 and lower levels of IL for people with burns (TBSA), even in the absence of infection.

During a systemic response to burns, pro-inflammatory cytokines, such as IL α, are produced by numerous cells in the injury vicinity. In addition to generalized induction of fever and acute-phase proteins, these cytokines also induce the production of TNF-α, is produced by numerous cells in the injury vicinity. In addition to generalized induction of fever and acute Heat causes coagulation necrosis of skin and Decreased cardiac output Altered pulmonary resistance causes Systemic inflammatory response Multi-organ dysfunction syndrome.

Prostaglandin E2(PGE2), IL-6, and platelet-activating factor by endothelial cells and macrophages [20] IL-6 contributes to the activation of T cells, [21], [22]. Although it is unclear whether high levels of IL-6 drive a systemic response or are simply a reflection of burn. Activated T cells polarized toward a TH1 response also produce the pro-inflammatory interferon-gamma (IFN-γ), which is important for the activation of macrophages [23] Immunosuppression is a common component of serious burn injuries, and it makes patients more susceptible to infections. The vigor of the lymphocyte population and, as a result, the extended survival of allografts are signs of immunosuppression. [24], [25] . During serious burns, neutrophil dysfunction has indeed been described [26] including reduction of both chemotaxis and degradation of phagocytosed pathogens including decreased chemotaxis and pathogen breakdown in phagocytosed pathogens [27]

Severity

After a burn injury, macrophages enhance the synthesis of PGE2 while decreasing the production of the pro-inflammatory cytokine IL-12 [28]. This shift away from a pro-inflammatory response leads to diminished functioning and MHC class II expression on antigen-presenting cells, as well as a breakdown in adaptive immune response coordination.  [29]. Suppression of lymphocyte reactivity resulting from increased expression of PGE2 by macrophages [30]  leads to altered numbers of CD4+ T helps cells relative CD8+ suppressor T cells, [31], [32] and, after intial pro-inflammatory phase, the T-cell response becomes polarized to an anti-inflammatory TH2 phenotype [23] with consequent production of anti-inflammatory cytokines, such as IL-4 and IL-10, and decreased production of IL-2 and IL-1β. This in turn leads to decreased lymphocyte proliferation with a decrease in T-cell-dependent immune functions [33], [34]. A variety of systemic hormone responses from the endocrine system, as well as modifications in other signaling cascades, such as increases in growth hormone, catecholamine, and cortisol, may contribute to the shift toward an immunosuppressive response [20]. Glucocorticoids suppress the production of pro-inflammatory cytokines but not anti-inflammatory cytokines [35].

 Complications of burn injuries

Deep and widespread burns can lead to many complications:

Infection

Burns may expose the skin to bacterial infections and induces the risk of sepsis. It increases rapidly over the injuryed site, this might result in shock and organ failure. (Basic of burns-2003). Burn injury infection causes a delay in healing, which leads to scarring and bacteremia, sepsis, or multiple organ dysfunction syndromes, in which organs from various systems are unable to regulate temperature on their own, necessitating rapid medical attention [36]

The most common pathogens of burn injuries are bacteria and fungi. These microbes form biofilms over the injuries within 48-72 hours of injury [37]. The first colonies of bacteria to attack the infected burns consist of Gram-positive bacteria, immediately followed up by gram-negative. After the bulk of bacteria has been eradicated by topical antibiotics, fungal infection is more likely to develop. [36]. Two bacterial species, methicillin-resistant staphylococcus aureus (MRSA) and pseudomonas aeruginous, both contain virulence factors and antimicrobial resistance genes [38]

·     Gram-positive organisms accounted for 66.4% of causative pathogens for bloodstream infections (BSIs).

·     Gram-negative organisms and Candida infections were less commonly seen in pediatric burn patients.

·     Gram-positive (66.4%)

·     Gram-negative (22.1%)

·     Fungi (11.5%)

The etiologic agents of BSIs in children may differ from those in adults of patients with burn injuries, 7% develop hospital-acquired infections.

It causes:

Low body volume

Burns usually damage blood vessels resulting in fluid loss. These symptoms can lead to low blood volume (hypovolemia), significant blood and fluid loss, and the heart not being able to pump enough blood to the body. [1]

Breathing problems

Inhaling hot air or smoke damages the airways and makes breathing difficult. Smoke inhalation results in respiratory failure and lung damage [1].

Scarring

Burns may cause scars. Overgrowth of scar tissue (keloids) results in the ridged area [1].

Bone and joint problems

Deep burns limit the movement of bones and joints. Shortening and tightening of skin and contractures on tendons are produced due to scar tissues resulting in permanent pull out of joints from respected position [1].

 Dangerously low body temperature

It increases the chances of hypothermia, a condition in which the body loses heat faster than it can produce heat (Basics of burn-2003). Severe burn victims are more likely to develop blood clots in their extremities. This develops as a result of the prolonged bed rest necessary for burn rehabilitation. Bed rest can obstruct normal blood flow, resulting in blood clots forming in veins.

The length of time a patient is bedridden is closely connected to the risk of acquiring blood clots. [37].

First Aid

Immediate first aid for burns:

To avoid a more serious burn, first put out the fire.

·     Heat burns (thermal burns)

     Smother any raging flames with a blanket or water. Stop, down, and roll on the ground to smother the flames if your clothes catch fire.

·     Cold temperature burns

Warm the affected regions using first-aid procedures. Small portions of your body that are extremely cold or frozen (ears, face, nose, fingers, toes) can be thawed by blowing warm air on them, tucking them under your clothing, or soaking them in warm water.

·     Liquid scald burns (thermal burns)

For 10 to 20 minutes, run cool tap water over the burn. Ice should not be used.

·     Electrical burns

Check for breathing and a heartbeat after the individual has been disconnected from the electrical source.

·     Chemical burns

Chili peppers, for example, have a chemical that is abrasive to the skin and can induce a burning feeling. When a chemical burn develops, determine which chemical was responsible for the burn. For further information on how to treat a burn, contact your local Poison Control Center or the National Poison Control Hotline.

·     Tar or hot plastic burns

Run cold water over the hot tar or hot plastic immediately to cool it.

§  Next, look for other injuries.

§  The burn may not be the only injury.

§  Remove any jewelry or clothing at the site of the burn.

§   If clothing is stuck to the burn, do not remove it.

§   Carefully cut around the stuck fabric to remove the loose fabric.

§   Remove all jewelry, because it may be hard to remove it later if swelling occurs.

Common first aid remedies for burn injuries are explained in fig 9.

 

Injury healing and phases

Compared to non-burn trauma injury healing, burns are characterized by fundamental damage to tissues that complicates the normal injury healing response. While the tissues damaged from non-burn trauma are largely vital and fed by underlying blood supplies, in severely burned tissues, the cells and vasculature are often destroyed. As a result, burn injuries have a zone of coagulation, which is an area of coagulative necrosis in which tissues are not adequately oxygenated to support life or speedy healing responses. [39] Many of the documented disparities between burn injury healing and non-burn trauma are due to this deficit. An area of less severely burnt tissue known as the zone of stasis, defined by diminished tissue perfusion, surrounds the zone of thrombosis, which is characterized by dead cells incapable of regeneration. The final destiny of tissues in the stasis zone is determined by the injury environment, which can result in either survival or necrosis. The zone of stasis is linked to vessel leakage and vascular injury because the tissue is injured yet remains perfused [40]. Burn injuries are distinguished from other traumatic injuries by their enhanced and widespread capillary permeability.

Hemostasis, inflammation, proliferation, and maturation/remodeling are the four processes that make up successful injury healing. After hemostasis is accomplished, vascular permeability rises, allowing an inflow of leukocytes to react to diverse chemotactic cues. The majority of these early arrivals are neutrophils, which phagocytose bacteria and produce demulsification enzymes that break down necrotic tissue [41]. Burn injuries are particularly difficult to treat because most of the destroyed tissue is unsustainable and has little blood supply. Not only does this inhibit neutrophil access, which requires blood vessels to reach proximal tissues, but it also results in low oxygen tension in necrotic tissues should neutrophils successfully navigate to sites of bacterial injury contamination. The Injury Healing Process is explained in fig 10.

Fibroblasts migrate into the injury and lay down new ECM during the proliferative phase, which follows the inflammatory phase. For many weeks, collagen levels climb consistently before slowing to approach equilibrium. Type I collagen prevails at first, but type III collagen eventually takes its place. Burned tissue is necrotic and encircled by injured tissue that may be unable or ineffective in responding to angiogenesis cues, slowing normal injury healing.

Collagen is restructured into lattice structures that are defined by the molecular features and mechanical qualities of the injury during the maturation phase of injury healing, which can take months or years. In addition to alterations in the ratio of type I-to-type III collagen, the new collagen forms additional cross-links, increasing the tensile strength of the healing injury. The new tissue's maximal strength plateaus at 70%–80% of that of undamaged tissue [42] shown in fig 11. flow chart injury healing process.

 Treatment

The main objective of the health care team is to prevent infection. The current gold standard of treatment and the main surgical approach for decreasing infection risk, length of hospital stay, and improving graft reception is early excision and grafting (Church D-2006). A 2015 Early excision decreased fatality rates in all burnt patients who did not suffer an inhalation injury, according to a meta-analysis of all known randomized controlled studies. [38]

However, donor sites are uncomfortable and burden the patient with their injury-healing requirements. Allografts, xenografts, skin replacements, or a dermal analogue should be taken into consideration if donor sites are insufficient due to a large burn area [36]

To properly care for a injury, devitalized tissue, debris, and any topical antimicrobials that have already been applied should be carefully removed. To provide optimal injury care, a broad-spectrum topical surgical antibacterial scrub, such as chlorhexidine gluconate, should be used in conjunction with sufficient analgesia and prophylactic anxiolytics. Opioids are used for analgesia, but their usage is debatable because they cause tolerance and addiction as well as the possibility of opioid-induced hyperalgesia, a condition where the pain is made worse by the drug [43]

Multimodal pain treatment should so be explored. Opioid-sparing agents include acetaminophen, ketamine, and alpha-adrenergic agonists such as clonidine and dexmedetomidine [43]. Nonsteroidal anti-inflammatory drugs should be avoided since they hinder the healing of injuries and raise the possibility of bleeding and severe renal damage. Topical antimicrobials for the prevention and treatment of burn injury infection include mafenide acetate, silver sulfadiazine, silver nitrate solution, and silver-impregnated dressings. The penetration of antibacterial activity and adverse event profiles of these diverse treatments vary. Results might also be impacted by the antibiotic delivery technique. In a clinical experiment, the effectiveness of a powdered spray version of silver sulfadiazine over a cream formulation was found to be greater [36]. Drug pressure may be linked to silver formulations, leading to infections with fungi or bacteria that are resistant to treatment. In comparison to patients receiving injury dressing or skin substitutes, patients treated with silver sulfadiazine had a statistically significant increase in burn injury infections and a longer length of stay. It's important to emphasize that the included trials have substantial or unclarified bias risks [44] Fusidic acid and gentamycin sulphate can be used topically to treat a localized MRSA burn injury infection. There is also topical vancomycin, which has been shown to be less likely to cause side effects while being more effective than the systemic version [45]. In patients with burns, antibiotic prophylaxis during injury manipulation has also been examined. This use of systemic antibiotics during acute burn surgery has only been somewhat validated by research. In the period before surgery, antibiotics seem to be useless; [44]. Although it has no effect on mortality, surgical prophylaxis in patients with burns of more than 40% TBSA appears to lower the risk of burn injury infections [45]. Systemic antibiotic prophylaxis has little impact on the occurrence of sepsis or burn injury infection in nonsurgical individuals [46]

Since local airway antibiotic prophylaxis has little effect on sepsis or fatality rates, treating airway colonization is not advised [47]. Additionally, the risk of MRSA infection is greatly increased by selective cleaning of the digestive system with non-absorbable antibiotics combined with cefotaxime [10]

Antimicrobial therapy should be focused on the pathogen discovered by culture after an infection has been identified. Empiric treatment should start when there is invasive infection or indications of sepsis. According to reports, 4% of severely sick adult patients with burn injuries had bacteremia.

There are various drugs that are used in the treatment of different degrees of burn injuries, enlisted in table 2.

 Advances

Over the past ten years, significant progress has been achieved in the treatment of burn injuries. Improvements in critical care, metabolic support, infection control, and injury treatment have significantly decreased mortality and morbidity. As with any injury, burn injury healing is influenced by a variety of systemic variables, such as metabolic reaction to damage, nutritional state, the presence of systemic infection, and additional systemic insults including pain and stress. Fortunately, these characteristics have been the focus of improvements in burn injury treatment. One of the advancements in burn treatment is aggressive surgical therapy of deep burns. Another is by definition, an open injury is any severe break in the continuity of the skin and deep tissue. Because contusions are healed injuries, the term given above does not apply to them. The classification of injuries is essential for both therapeutic and medico-legal purposes. Burn injuries are comparable to other injuries in that they require the same basic principles for healing and care, but they differ in that they have a greater impact on the patient's overall health and are essential to the patient's eventual survival, the development of deformity, and rehabilitation. Treatment of burn injuries has always been the responsibility of burn specialists. Both local and systemic therapy have long been advised for treating burn injuries and minimizing burn scars. This review summarizes the treatment of burn injuries brought on by a variety of physical and chemical agents requires unique regimens that are completely different from those used to treat any other traumatic injuries. Other acute injuries that undergo entire blood loss result in shock, but major burns that experience significant plasma loss due to increased capillary permeability result in distress. Burn injuries are initially sterile compared to the majority of other injuries, however, due to the immunocompromised state of burn patients, injury infection and septicaemias frequently end in death in serious burns. We have discussed the pathophysiology and primary care therapies for burn injuries in this review the improvement of the injury healing environment with the use of silver release dressings, better pain control in partial-thickness burns, improved healing of partial-thickness burns with temporary skin replacements, improved functional and aesthetic results of large burns with the use of adjuvant therapies, and optimal management of severe burns in burn centers

A burn is described as skin injury brought on by intense heat or caustic substances. Heat and chemical exposure are the two main causes of burn damage. Full-thickness burns often progress, resulting in quick matrix degradation and cell death, with the injury surface suffering the most serious damage. Depending on the method of therapy, more heat and inflammation cause tissue harm underneath the nonviable surface, which may eventually mend or worsen to severe necrosis.

It is difficult to manage a burn injury because the environment around the injury, the host's reaction to the damage, and the burn injury process all influence how the injury biology changes over time. It's crucial to be flexible while adjusting care to the developing injury.

 

Burns requiring extra care

There is a higher risk of complications and potential functional and aesthetic problems with burns to the face, eyes, ears, hands, feet, and perineum. A burn services team should treat these burns.

Face

Face burns provide a considerable risk of functional and aesthetic damage. Applying an antibiotic ointment like bacitracin 2 to 3 times per day to avoid desiccation and manage lingering Gram-positive organisms is the next step after gently and often cleaning superficial burns to remove any devitalized tissue. The face is treated openly. Temporary skin replacements are advantageous because they relieve pain and protect the injury. More active measures, such as the regular removal of loose necrotic tissue and the use of silver products, are needed to help avoid infection in deeper face burns. Typically, surgical treatment is required.

Ears

Similar to facial burn injuries, superficial ear burns are treated, but the injuryed helix should not be subjected to external pressure. Any compression will exacerbate existing damage to the cartilage in this region since it is already insufficiently vascularized. When controlling pressure when sleeping, pillows or pressure may be removed. Deeper burns, requires more potent topical treatment, often with a silver or mafenide cream. A serious consequence that causes cartilage loss and irreversible deformity is chondritis, or cartilage infection. Systemically used antibiotics are needed.

Hands and feet

Functional incapacity may result from hand or foot burns. A gauze or skin replacement that has been treated with petrolatum is used to treat superficial burns. In particular, for foot injuries, skin substitutes aid in injury protection and pain management. Silver-based treatments are needed for treatment of deeper burns. Each finger should be separately wrapped when the hands or feet are hurt in order to reduce functional handicap, such as web space contractures, and to allow for ongoing mobility and vigorous physical treatment.

Perineum

Due to the increased danger of infection, perineal burns need to be thoroughly cleaned and then treated again with topical medications after urinating or defecating.

Major Burns

Major Burns must be treated by a burn specialist because they can cause considerable morbidity or fatality. They are defined as follows:

·     partial-thickness burns greater than 10% of TBSA

·     burns that involve the face, hands, feet, genitalia, perineum, or major joints

·     full-thickness burns in any age group, over 1% of body surface

·     electrical burns, including lightning injury

·     chemical burns

·     inhalation injury

·     a child with any of the above burn injuries

·     burn injury in patients with preexisting medical disorders that could complicate management

·     Any burned child, if the hospital initially receiving the patient does not have qualified personnel or equipment for children.

Patients with major burns are usually admitted to the hospital and should be treated in a burn center.

 Advances in treatment of burn injury

 Silver-release products

Since ancient times, silver has been used to both prevent and treat a number of illnesses, most notably infections. With concentrations in liquids surpassing 10 parts per million, silver possesses incredibly strong antibacterial capabilities. By changing the deoxyribonucleic acid (DNA) and cell wall of microbes and limiting their respiratory enzyme system (energy generation), silver ions appear to kill bacteria quickly while having no harmful effects on human cells in vivo. The effective biologic use of this noble metal in burn injury care has been constrained by the existing delivery mechanisms, which are frequently in the form of salts.

For the past 40 years, antibacterial silver has been delivered via silver nitrate and silver sulfadiazine. Silver itself is thought to be innocuous to human cells in vivo, but they inhibit fibroblast and epithelial growth, which inhibits healing. The sole side effect that has been documented is the aesthetic anomaly known as argyria, which results in a blue-grey discoloation and is brought on by the precipitation of silver salts in the skin. There is no tissue toxicity, according to clinical assessments. The main issues with silver compounds—namely, nitrate and sulfadiazine—are caused by the complex, or anion, and not by the silver itself. It has been demonstrated that pure silver, which is found in modern silver dressings, has powerful antibacterial action as well as a lack of toxicity to injury cells. A few studies also suggest that pure silver has pro-healing and anti-inflammatory effects, including the ability to inhibit excessive matrix metalloproteinase (MMP) activity.

The antibacterial concentrations of pure silver ions released by modern silver dressings from a membrane surface over a few days. In order to lessen the bacterial load, sustained release of silver is crucial. The cream base in silver sulfadiazine interacts with serous exudate to generate a pseudo-eschar that needs to be removed before the cream can be reapplied in order for silver nitrate to be effective. Silver dressings currently in use may be retained in place for up to seven days. During this time, the injury does not need to be touched, reducing stress to the developing epithelium and the bacterial load on the injury. Additionally, a tiny moisture layer beneath the silver dressing keeps the healing environment wet. Surface desiccation can also result from the available hyperosmolar creams, which have a brief duration of silver action.

Skin substitutes

Significant improvements in patient care have significantly reduced morbidity and death, particularly in cases of severe burns. The present focus of burn injury care is on enhancing quality of life as well as long-term function and look of the healed or replacement skin cover. The use of skin replacements to enhance injury healing, manage pain, speed up closure, improve functional and aesthetic outcomes, and, in the case of severe burns, increase survival has attracted a lot of attention due to the problem of quality of life.

The latest generation of skin replacements is often biologically active to more effectively treat these concerns. Instead than only providing covering, the bioactivity might modify the burn injury. The more inert traditional burn injury dressings have not been replaced by the new solutions. Instead, they have particular indications and are utilized in combination with certain products. Permanent skin replacements are utilized to add or replace the remaining skin components, while temporary injury coverings are used to reduce discomfort and speed up recovery.

Temporary skin substitutes are used to help heal partial-thickness burns or donor sites and close clean excised injuries until skin is available for grafting. Normally, temporary skin replacements do not include any live cells. Temporary skin replacements frequently have a bilayer structure made up of an exterior epidermal analogue and an inner dermal analogue that is more physiologically active. A temporary skin replacement serves two purposes. Closing the injury and shielding it from outside irritants is the primary goal. By introducing dermal elements that activate and encourage injury healing, the second goal is to provide the ideal environment for injury healing. In a partial-thickness burn or an excised lesion, biologically active dermal components are normally naturally delivered to the inner layer, which is subsequently administered to the residual dermis.

Permanent skin substitutes are used to replace lost skin by providing an epidermis, dermis, or both. Compared to thin skin grafts, they deliver skin of a greater grade. The majority of permanent skin replacements include both functional dermal matrix elements and live skin cells.

 Herbal Products

Due to the different complications which are seen in the synthetic drugs that are available for the cure of burn injuries researchers are now trending towards herbal care. Herbs as compared to synthetic products are safer, more effective, and less costly. Also, India has a large diversity of flora and fauna exhibiting a large range of plants with different therapeutic activities. Plants for the treatment of burn injuries are used for a very long time and have produced effective results. Few of the plants which are used for the treatment of burn injuries along with their active phytoconstituent are summarized in Table 3.

  Various Nanomaterials for Burn injuries

Namomaterials such as Nanoparticales (natural Poymeric NPs, synthetic Polymeric NPs, Polymeric NPs, Non Polymeric NPs) and scaffolds (nanofibers, hydrogel) are used for the treatment of burn injury which is being shown in fig 12.

 Conclusion

The term "burn" refers to tissue damage brought on by heat, chemicals, electricity, sunshine, or radiation. The most frequent causes of burns include scalds from hot liquids and steam, building fires, and flammable liquids and gases. Burns can result in swelling, blistering, scarring, shock, and even death in extreme circumstances. Since they harm the barrier that protects your skin from infection, they can potentially cause infections. The type of burn, its depth, and how much of the body it covers all affect how it is treated. Antibiotic creams can either prevent or treat infections. Treatment may be required for more severe burns to ensure the patient receives adequate fluids and nutrients, clean the injury, and restore missing skin.

Due to the severity of the injury, we have attempted to cover every element of burn injuries and their treatment. The primary areas of interest are the clinical, scientific, and social aspects of burn injury injuries. It also covers injury prevention, the epidemiology of such injuries, and all facets of treatment, including the creation of new techniques and technologies as well as the validation of those that already exist.

Topics covered under this review include the data report on burn-in around the world and specifically in India. The advancements in burn injury care have also been facilitated by advances in technology, infection prevention, and skin replacements. Although there are still noticeable distinctions between the pathophysiology and treatment of burn injuries and non-burn injuries, the basic goals of injury care remain universal infection control and quick injury closure. We have also gone through the herbal remedies which are accessible in the market which produce fewer side effects and are more effective towards burn injuries.

 Acknowledgements

The authors are thankful to the University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, for their continuous and practical support. The authors also want to thank Prof. Swarnlata Saraf, University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for her valuable suggestions and guidance.

 Conflicts of interest

The authors declare no conflict of interest related to the submission of this manuscript and the manuscript is approved for publication by all authors.

 Ethical statement

All human and animal studies have not been conducted. 

 Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection, designing and analysis were performed by Taranjeet Kukreja, whereas Arushi Saloki helped with the formatting. This was done under the guidance of Prof. Swarnlata Saraf. The first draft of the manuscript was written by Taranjeet Kukreja and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Authorship

All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted.

 

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