Burns and Skin Grafting

1. Introduction

Thermal injury represents a complex and potentially devastating form of trauma with significant systemic implications. The management of burns and the subsequent need for surgical reconstruction through skin grafting constitute a critical domain within surgery, critical care, and clinical pharmacology. This chapter provides a comprehensive examination of the pathophysiology of burn injuries, the principles of wound healing, and the surgical and pharmacological strategies employed to achieve definitive wound closure. The integration of these disciplines is essential for optimizing patient outcomes, minimizing morbidity, and facilitating functional and aesthetic recovery.

The historical evolution of burn care demonstrates a progression from primarily palliative measures to sophisticated, multidisciplinary approaches. Early 20th-century management focused largely on infection control and basic wound care. The development of fluid resuscitation formulas, such as the Parkland formula, marked a pivotal advancement in addressing burn shock. Concurrently, the refinement of skin grafting techniques, from the use of autografts to the development of temporary biological and synthetic skin substitutes, has dramatically improved survival rates and functional outcomes for patients with extensive burns.

For medical and pharmacy students, understanding this topic is fundamental. Pharmacological management is intricately woven into every phase of burn care, from initial resuscitation and analgesia to infection prophylaxis, nutritional support, and the modulation of wound healing. An appreciation of the surgical principles of skin grafting is equally vital, as it informs the rationale for adjuvant drug therapies and the management of graft-related complications.

Learning Objectives

• Classify burn injuries according to depth, extent, and mechanism, and describe the associated pathophysiological changes at both local and systemic levels.
• Explain the staged process of wound healing, highlighting the distinct challenges and therapeutic targets presented by burn wounds.
• Compare and contrast the types of skin grafts and skin substitutes, including their indications, harvesting techniques, physiological basis for survival, and potential complications.
• Analyze the pharmacological management of burn patients, encompassing fluid resuscitation, analgesia, antimicrobial therapy, and agents that modulate metabolism and healing.
• Integrate surgical and pharmacological principles to develop a coherent management plan for a burn patient, from initial presentation through to rehabilitation.

2. Fundamental Principles

Core Concepts and Definitions

A burn is defined as an injury to the skin or other organic tissue primarily caused by thermal, radiation, chemical, or electrical energy. The skin, as the largest organ, serves critical functions as a barrier against pathogens, a regulator of fluid and temperature homeostasis, and a sensory interface. Its compromise leads to a cascade of local and systemic responses. Skin grafting is a surgical procedure involving the transplantation of skin from a donor site to cover a wound where the native skin has been lost or damaged beyond its capacity for spontaneous repair.

Theoretical Foundations

The theoretical foundation of burn management rests on two pillars: the pathophysiological response to injury and the biology of wound repair. The initial injury triggers a localized zone of coagulation, surrounded by zones of stasis and hyperemia. The systemic response, often termed “burn shock,” is characterized by a massive capillary leak, profound hypovolemia, increased metabolic demand, and immunosuppression. Successful treatment must address these immediate threats to support the patient until definitive wound closure can be achieved.

The biology of wound healing proceeds through overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Burn wounds, particularly deep partial-thickness and full-thickness injuries, disrupt this sequence, often resulting in a prolonged inflammatory state and excessive scar formation. Skin grafting aims to expedite the proliferative phase by providing a scaffold of dermis and/or epidermis, thereby restoring barrier function and modulating the healing environment.

Key Terminology

• Autograft: Skin transplanted from one site to another on the same individual.
• Allograft (Homograft): Skin transplanted from a human donor, typically cadaveric, used as a temporary biological dressing.
• Xenograft (Heterograft): Skin transplanted from another species, commonly porcine, used as a temporary dressing.
• Split-thickness skin graft (STSG): A graft containing the epidermis and a variable portion of the dermis.
• Full-thickness skin graft (FTSG): A graft containing the entire epidermis and dermis.
• Meshing: A technique where a sheet graft is passed through a device that creates a pattern of slits, allowing it to be expanded to cover a larger area.
• Take: The successful adherence and revascularization of a skin graft.
• Donor Site: The area from which a skin graft is harvested.
• Recipient Site (Bed): The wound area prepared to receive a skin graft.

3. Detailed Explanation

Pathophysiology of Burn Injury

The local response to a burn is conceptualized through Jackson’s model of three concentric zones. The innermost zone of coagulation experiences irreversible tissue necrosis due to direct energy transfer. Surrounding this is the zone of stasis, characterized by decreased perfusion and tissue viability that is potentially salvageable with optimal resuscitation; ischemia in this zone can progress to necrosis. The outermost zone of hyperemia exhibits increased blood flow and inflammation as part of the normal healing response.

Systemically, burns exceeding approximately 20% of total body surface area (TBSA) in adults trigger a profound response. The release of inflammatory mediators such as histamine, prostaglandins, and cytokines increases capillary permeability, leading to massive fluid shifts from the intravascular to the interstitial space. This results in hypovolemic shock, hemoconcentration, and edema, including in non-burned tissues. A hypermetabolic state ensues, driven by catecholamines, cortisol, and glucagon, leading to increased oxygen consumption, catabolism, and insulin resistance. Immunosuppression, mediated by impaired neutrophil function and altered cell-mediated immunity, significantly elevates the risk of infection.

Burn Classification

Burn injuries are classified by depth, extent, and etiology, which directly guide management and prognosis.

Classification by Depth

Assessment of Extent: Total Body Surface Area (TBSA)

The “Rule of Nines” is a commonly used tool for rapid initial estimation in adults: the head and each arm represent 9% TBSA, the anterior trunk, posterior trunk, and each leg represent 18% TBSA, and the perineum represents 1%. For children, adjusted charts must be used due to differing body proportions. More precise methods include the Lund and Browder chart.

Biology of Skin Graft Survival

The success of a skin graft depends on a meticulously prepared recipient bed and a sequence of biological events termed “graft take.” This process occurs in three phases. The initial phase of plasmatic imbibition (0-48 hours) involves the graft absorbing nutrient-rich plasma from the wound bed via capillary action, which sustains the graft’s cellular metabolism prior to revascularization. The second phase, inosculation (48-72 hours), is characterized by the alignment of the graft’s existing vessel ends with those in the recipient bed, establishing direct capillary connections. The final phase of neovascularization (day 3-5 onward) involves the ingrowth of new capillary buds from the recipient bed into the graft, establishing a permanent, independent blood supply. Simultaneously, lymphatic connections are re-established, and fibrous tissue anchors the graft in place.

Types of Skin Grafts and Substitutes

Autografts

Autografts are the gold standard for permanent wound closure. Split-thickness skin grafts (STSGs) are harvested at a depth of 0.005 to 0.015 inches using a dermatome. They contain the epidermis and a variable portion of the dermis. Their advantages include the ability to cover large areas, higher likelihood of take on suboptimal beds, and the potential for donor site re-harvesting. Disadvantages include fragility, poor color and texture match, and a tendency to contract. Full-thickness skin grafts (FTSGs) include the entire dermis and are harvested by sharp dissection. They provide superior durability, color match, and growth potential with less contraction, but are limited by donor site availability and a more demanding requirement for a well-vascularized recipient bed.

Skin Substitutes

Skin substitutes are employed when autograft is unavailable or to optimize the wound bed. They are broadly categorized as temporary or permanent, and as epidermal, dermal, or composite.

Factors Affecting Graft Take

Multiple factors can compromise the intricate process of graft survival. Recipient site factors are paramount and include the presence of infection, hematoma or seroma formation (which physically separates the graft from the bed), inadequate vascularity (e.g., exposed bone or tendon without periosteum or paratenon), and mechanical shearing forces. Graft-related factors include excessive thickness, improper handling, or desiccation. Systemic patient factors such as malnutrition, hypoproteinemia, anemia, diabetes mellitus, immunosuppression, and smoking also negatively impact graft take by impairing the inflammatory and proliferative phases of healing.

4. Clinical Significance

Relevance to Drug Therapy

The management of a major burn injury represents one of the most pharmacologically intensive scenarios in clinical medicine. Drug therapy is directed at countering the systemic pathophysiological cascade, preventing complications, and creating an optimal environment for wound healing and graft survival. The pharmacokinetics of many drugs are significantly altered in burn patients due to changes in volume of distribution, protein binding, and renal/hepatic clearance, necessitating careful dose monitoring and adjustment.

Practical Applications in Pharmacological Management

Resuscitation and Hemodynamic Support

The cornerstone of initial burn management is fluid resuscitation, typically guided by the Parkland formula: Total crystalloid volume (L) = 4 mL × body weight (kg) × %TBSA burned. Half is given over the first 8 hours post-injury, and the remainder over the next 16 hours. This formula serves as a starting point, with titration to clinical endpoints such as urine output (0.5-1.0 mL/kg/hr in adults). While crystalloids (Lactated Ringer’s) are first-line, colloids may be considered after the first 24 hours when capillary leak has diminished. Vasoactive agents are rarely first-line but may be required for refractory shock.

Analgesia and Sedation

Burn pain is severe, multifaceted, and requires a multimodal approach. Background pain is managed with scheduled opioids (e.g., morphine, fentanyl) via patient-controlled analgesia (PCA). Procedural pain (e.g., dressing changes, debridement) often requires supplemental short-acting opioids, anxiolytics (e.g., midazolam), and sometimes dissociative agents like ketamine, which provides analgesia without respiratory depression. Non-opioid adjuvants, including acetaminophen, NSAIDs (with caution for renal and gastric effects), and gabapentinoids for neuropathic components, are integral.

Infection Prophylaxis and Treatment

Prophylactic systemic antibiotics are not recommended for general use, as they promote resistance. Topical antimicrobial agents are the mainstay for burn wound prophylaxis. Silver sulfadiazine is widely used but can cause leukopenia and is contraindicated in sulfa allergy. Mafenide acetate penetrates eschar effectively, making it useful for cartilaginous areas like ears, but it is a potent carbonic anhydrase inhibitor and can cause metabolic acidosis. Silver-impregnated dressings provide sustained antimicrobial activity with less frequent changes. Systemic antibiotics are reserved for documented infections, guided by wound culture and sensitivity data, with common pathogens including Pseudomonas aeruginosa, Staphylococcus aureus (including MRSA), and Acinetobacter.

Modulation of Metabolism and Healing

The hypermetabolic response is managed with aggressive nutritional support, often via enteral feeding initiated within 24 hours. Pharmacological modulation may involve the use of beta-blockers (e.g., propranolol) to reduce catecholamine-driven tachycardia and catabolism, and anabolic agents like oxandrolone to promote lean mass synthesis. The role of recombinant human growth hormone remains investigational due to safety concerns. For graft sites, maintaining a moist, protected environment with appropriate dressings is critical. Pharmacological agents to directly promote graft take are limited, but ensuring adequate systemic levels of vitamin C (for collagen synthesis) and zinc (for enzymatic cofactors) is considered supportive.

5. Clinical Applications and Examples

Case Scenario 1: Major Thermal Burn

A 35-year-old male presents with flame burns to his anterior trunk, bilateral arms, and anterior thighs sustained 2 hours prior. Estimated TBSA is 45%. He is alert but in severe pain. Initial assessment reveals soot in the airway.

Management Approach: Primary survey (Airway, Breathing, Circulation) is immediate. Due to the mechanism and location, early endotracheal intubation is performed for airway protection. Two large-bore intravenous lines are established. Fluid resuscitation is calculated using the Parkland formula: 4 mL × 80 kg × 45% TBSA = 14,400 mL over 24 hours. Lactated Ringer’s is initiated at 1800 mL/hr for the first 8 hours. Morphine is administered intravenously for analgesia. A urinary catheter is placed, and urine output is monitored hourly. The wounds are covered with clean sheets, and a thorough secondary survey is performed to rule out associated injuries. Topical mafenide acetate is applied to the burns. Nutritional consultation is obtained for early enteral feeding. After hemodynamic stabilization (≈ day 3-5), the patient undergoes staged surgical excision of deep partial-thickness and full-thickness burns. The wounds are covered with widely meshed autograft (4:1 expansion) from the available donor sites (back, scalp, posterior thighs). The interstices of the meshed graft are covered with a cadaveric allograft to protect the wound bed and promote epithelial spread. The patient subsequently requires multiple, staged autografting procedures to achieve complete closure.

Case Scenario 2: Electrical Burn with Tissue Necrosis

A 25-year-old electrician sustains a high-voltage electrical injury to his right hand and forearm. There is a small entry wound on the palm and a larger exit wound on the forearm. The forearm appears swollen and tense, with diminished capillary refill in the hand.

Management Approach: Electrical injuries are deceptive, with extensive deep tissue damage that far exceeds the visible skin injury. The priority is assessing for cardiac arrhythmias (obtain ECG) and compartment syndrome. The patient likely requires an emergency fasciotomy of the forearm to relieve compartment pressure and preserve limb viability. After stabilization, the wound is managed with repeated surgical debridements to remove all non-viable muscle and tissue. Once a clean, granulating bed is achieved (which may take several debridements), coverage is planned. For the palm, a thick STSG or FTSG may provide adequate pliability. For exposed tendons or bones on the forearm without paratenon or periosteum, a flap (e.g., a radial forearm flap) would be required prior to or instead of a skin graft. Pharmacological management includes tetanus prophylaxis, careful fluid management (as myoglobin release can cause renal injury), and antibiotics targeted at deep tissue pathogens.

Application to Specific Drug Classes: Topical Antimicrobials

The choice of topical antimicrobial agent is a direct clinical application of burn pharmacology, influenced by burn characteristics and patient factors.

• Silver Sulfadiazine: Often first-line for superficial partial-thickness burns. Its creamy base soothes the wound. However, in a patient with a large TBSA burn, its use must be monitored for transient leukopenia. It is avoided in patients with known sulfonamide allergy and is less effective on eschar.
• Mafenide Acetate: Selected for deep burns, especially those involving cartilage (ears) or where eschar penetration is needed. In a patient with a 60% TBSA burn, applying mafenide acetate to the entire surface area could induce a significant metabolic acidosis due to systemic absorption of the carbonic anhydrase inhibitor; therefore, its use may be limited to specific high-risk areas.
• Silver Nitrate Solution (0.5%): Used occasionally, but causes electrolyte leaching (sodium, potassium, calcium) from the wound and stains tissues black. Its use requires close monitoring of serum electrolytes.
• Bacitracin/Polymyxin B: Used for facial burns or superficial wounds, and for coverage of healed autografts and donor sites. They have minimal systemic absorption and low toxicity.

6. Summary and Key Points

Summary of Main Concepts

• Burn injuries are classified by depth (superficial, partial-thickness, full-thickness) and extent (%TBSA), which dictate management strategy and prognosis.
• The systemic response to major burns includes hypovolemic shock, a hypermetabolic state, and immunosuppression, requiring comprehensive supportive care.
• Definitive closure of deep burns requires surgical excision and skin grafting. Autografts provide permanent coverage, while allografts and xenografts serve as temporary biological dressings.
• Skin graft survival depends on plasmatic imbibition, inosculation, and neovascularization, processes vulnerable to infection, fluid collection, and shearing forces.
• Pharmacological management is multifaceted, encompassing aggressive fluid resuscitation, multimodal analgesia, topical and systemic antimicrobials, and agents to modulate the hypermetabolic response.

Clinical Pearls

• The “Rule of Nines” is for rapid initial estimation; use a Lund and Browder chart for more accurate assessment, especially in children.
• Fluid resuscitation formulas are guides only; therapy must be titrated to individual clinical endpoints, primarily urine output.
• Prophylactic systemic antibiotics do not prevent burn wound infection and promote resistance; topical antimicrobials are the standard for wound prophylaxis.
• A moist, protected environment is critical for both graft take and donor site healing. Shearing forces are a common cause of graft failure.
• Electrical and chemical burns often have more extensive deep tissue injury than is apparent on the surface, necessitating a high index of suspicion for compartment syndrome and the need for early surgical intervention.
• Pain management must address both background and procedural pain, typically requiring a scheduled opioid regimen supplemented with short-acting agents and adjuvants for procedures.

References

1. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
2. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
3. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
4. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
5. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
6. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.