Clinical manifestations

Presentation and course

Burns injury leads to swelling, blister formation, scarring of varying severity, and in extensive burn injury, even shock and death. Burn to the skin disrupts its normal function and may produce infection, pain, dehydration, and hypothermia, so it is crucial from a management point of view to evaluate the burn’s extent, depth, and circumferential components. Management decisions depend on this information.

The skin consists of epidermis, dermis, and subcutaneous fat. First-degree burns are superficial and affect only the epidermis or outer layer of skin. First-degree burns are characterized by pain, redness, and mild swelling with no blister formation. Skin may be tender to the touch. Second-degree burns are deeper and in addition to the signs of inflammation, there is also blister formation. Third-degree burns affect all layers of the skin and damage the epidermis, dermis, and subcutaneous tissue. The cutaneous nerves and blood vessels are also destroyed. In third-degree burns, the skin is often white and dry. Fourth-degree burns also destroy the underlying bones, muscles, tendons, and ligaments.

The classification system categorizes burns into either superficial, partial-thickness, or full-thickness groups. This classification is important to determine the need for surgery. Patients with full-thickness burns require surgery if the burn area is larger than 2 cm. Older patients with thin epidermis and dermis often require surgery. The extent of the burn means the total body surface area affected by the burn injury. The most popular method to estimate total burn area in older children and adults is the “rule of nines.” According to this rule, a value of 9% body surface area is assigned to the head and neck region, 9% to each arm (including the hand), 18% to each leg (including the foot), and 18% to each side of the trunk (back, chest and abdomen). The Lund and Browder method is employed for children younger than 10 years of age. According to this method, the size of a child’s palm is roughly 1% of the total body surface area (16; 17; 08).

A variety of CNS and peripheral nervous system manifestations has been described. Burn encephalopathy or burn-induced delirium, often hypoxic and metabolic, has extensively been described in the acute phase of burn injury. A retrospective clinicopathologic study of 139 patients who died following severe burns reported that 53% of the patients had CNS complications. Cerebral infarcts and hemorrhages, metabolic encephalopathies, central pontine myelinolysis, and cerebral trauma were major central nervous system complications in these patients. Eighteen percent of the patients had pathologic evidence of cerebral infarcts. In almost half of the patients, the infarcts were caused by septic arterial occlusions or other complications of the burn, like disseminated intravascular coagulation and septic shock. In only one third of the cases, infarcts were due to atherosclerosis, atrial fibrillation, or other causes prevalent in the general population. Intracranial hemorrhages were only one fifth as frequent as infarcts and were due to disseminated intravascular coagulation and thrombocytopenia caused by bacteremia.

Sixteen percent of the patients had a CNS infection. Candida species, Staphylococcus aureus, and Pseudomonas aeruginosa caused almost 80% of CNS infections. S. aureus and candida caused cerebral microabscesses and septic infarcts. Pseudomonas aeruginosa caused meningitis and infarcts due to meningitis. The major risk factors for CNS infection were an extensive burn, Staphylococcus aureus endocarditis, and a burn wound infection due to candida or Pseudomonas aeruginosa. Patients with burns of less than 30% of the surface area of their body, those without a systemic infection, and those in the first week after their burn were at low risk (46).

Burn injury-induced CNS complications have also been described in children. Among 287 children with burns, 13 (5%) showed evidence of encephalopathy. The major clinical manifestations were an altered sensorium and seizures. In the majority, symptoms began later than 48 hours after the burn and were accompanied by multiple metabolic abnormalities. Eleven children improved to normal. CNS dysfunction was possibly a result of complex metabolic, hematological, and hemodynamic abnormalities rather than a single metabolic abnormality (32). Hypoxia was the principal determinant in children with burn encephalopathy. Other factors that were responsible for CNS alterations were hypovolemia, sepsis, hyponatremia, and cortical vein thrombosis (03). Systemic inflammatory response syndrome following burn injury may affect dysfunction of microcirculation of body resulting in CNS dysfunction (26). A retrospective study observed that patients with multiple sclerosis and concurrent burn injuries need longer hospital stays and burn triage and treatment (28).

The risk of ischemic stroke is significantly higher in hospitalized patients with burn injury in comparison to the general population. In one case-control study, 1763 burn injury patients were matched with 176,300 unexposed patients. The adjusted hazard ratio of ischemic stroke was significantly increased in burn injury patients versus controls (19).

A case series noted a correlation between severe burns and the occurrence of ischemic optic neuropathy. Medina and coworkers described three patients with severe burns who developed visual loss because of bilateral ischemic optic neuropathy during their hospital stay (31). These patients needed more than 25 L of crystalloid fluid within 24 hours, had multiple bouts of sepsis, and required extended pressor support. The authors postulated that ischemic optic neuropathy possibly developed because of shock, sepsis, and the need for large-volume fluid resuscitation. Hughes and colleagues reported another patient with posterior ischemic optic neuropathy following burns (18). They suggested that a high index of suspicion should be kept if a burn patient develops vision loss.

Neuromuscular manifestations are important complications in acute stages as well as later in life as major disabling sequelae. In acute stages, neurologic findings are often missed. Mononeuropathies, mononeuritis multiplex, and polyneuropathies have all been described in burn-injured patients (39). Patients with severe burn injuries are likely to develop rhabdomyolysis and subsequent acute kidney injury (24).

A retrospective study was performed to evaluate neuropathies in patients with burns. Nineteen of a total of 800 patients had signs and symptoms of neuropathy, confirmed on neurophysiological testing. Most patients with neuropathies were severely burned, with 11 patients (69%) having a total burn surface area of greater than 20%. Twenty-eight percent were full-thickness burns. Mononeuritis multiplex was the most common finding in these patients, occurring in 11 (69%). Three patients (19%) had an isolated mononeuropathy, one (6%) had a radiculopathy, and one had a generalized axonal polyneuropathy. The length of hospitalization and severity of the burns were the only factors correlated with the number of affected nerves (27).

In a cohort of 572 patients with major burn injuries, 64 (11%) of patients had clinical evidence of mononeuropathy, peripheral neuropathy, or both. Electrical cause, history of alcohol abuse, and number of days in intensive care were significantly associated with mononeuropathy. The number of days in intensive care and patient age were significantly associated with peripheral neuropathy (25). A system review noted that of the 1533 burn patients, 98 cases (6.39%) later presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies (42).

Tight dressings can cause compression to superficial nerves, and improper and prolonged positioning can cause excessive stretch of nerves. Thus, proper positioning of patients and careful monitoring of wound care can mitigate neuromuscular complications. Poor positioning at the neck and shoulder leads to excessive stretch of the brachial plexus and places the plexus at risk for injury. Also, several bed and intraoperative positions commonly used in the treatment of burn injuries put the patient at risk of developing mononeuropathies or plexopathies. In the upper extremity, the ulnar, median, and radial nerves are common sites for the development of mononeuropathies.

Mononeuritis multiplex is an asymmetric neuropathy that involves two or more isolated peripheral nerves. Involvement of multiple nerves after thermal burns has also been noted among patients with greater than 40% total body surface area. The number of nerves involved per patient ranged from 3 to 7. Upper-extremity nerves were more commonly involved than lower-extremity nerves. Mononeuritis multiplex in burn patients is thought to result from a combination of circulating neurotoxins, metabolic factors, and mechanical compression (11).

Polyneuropathy in burn patients has also been frequently observed. Polyneuropathy is caused by a combination of direct thermal injury on the nerves, circulating neurotoxins, and changes in the distribution of fluid and electrolytes. Critical illness polyneuropathy in burn patients has also been observed. Critical illness polyneuropathy often has a strong link to sepsis, multiple organ failure, and slow ventilatory weaning (09). A review on critical care polyneuropathy in burn-injured patients that included a total of 2755 subjects revealed 128 (4.4%) critical care polyneuropathy patients. The factors associated with critical care polyneuropathy in burns were prolonged ventilation, large burns, and sepsis (30).

In the presence of preexisting diabetic neuropathy, the management of lower-extremity burn injuries becomes difficult. Diabetes-associated factors significantly hamper the healing of such wounds. Many of these patients require amputations after their burn injury (40). It has been noted that among patients with isolated lower limb burns, preexisting diabetes mellitus adversely affects the outcome. Patients with lower limb burns and pre-existing diabetes mellitus had longer hospitalization and increased amputations (36).

Pruritus is a common disabling symptom in the late phases of burns. The exact mechanism of pruritus is not well known. In a prospective cohort study, among 510 burn patients, the reported prevalence rates of mild to severe itching were as high as 87%, 70%, and 67% at 3, 12, and 24 months post-burn event. Significant predictors of itching were deep dermal injury and early posttraumatic stress symptoms. Along with these, total burned surface area and female gender were predictors at 3 months post-burn (43). Axonal sprouting in the dermis is considered a proposed mechanism of pruritus in burn patients.

Burn scars can cause intense pain, even without evidence of underlying nerve damage. The extent of damage by burn injury is the important predicting factor for pain in scars. Scar pain has characteristics of neuropathic pain and is considered caused by an imbalance in C-fibers subtypes. The scar possibly alters the nerve fiber distribution in the damaged tissues, resulting in pain (04). In a retrospective study, 1880 adult burn patients were analyzed (23). In this study, 113 (6%) of the burn patients developed chronic neuropathic pain over 5 years. Old age, alcohol, substance abuse, smoking, large and severe burns, mechanical ventilation, corrective surgeries, and long hospital stays predicted chronic neuropathic pain following burn injury.

Prognosis and complications

In a retrospective review of 1665 patients with acute burn injuries, authors developed probability estimates for the prediction of mortality based on a minimal set of well-defined variables. Three risk factors for death were identified: (1) age greater than 60 years, (2) more than 40% of the body-surface area burned, and (3) inhalation injury. The mortality formula predicts a 90% mortality if all three risk factors are present (38). Approximately 75% of deaths following burn are related to wound infection. Burn patients are also at risk for developing sepsis secondary to pneumonia, catheter-related infections, and suppurative thrombophlebitis (10).

All survivors of burn injuries who had encephalopathic features showed complete neurologic recovery despite severe and prolonged symptoms (03). However, several burn patients suffer long-term cognitive dysfunctions, like memory defect. Cognitive dysfunctions affect quality of life. Several reasons have been ascribed for the cognitive dysfunction in the post-burn period; cerebral inflammation, resulting in the destruction of the blood-brain barrier, is considered a dominant reason (48). Neuropathy after burn injury can affect strength and function. Studies highlight CNS reorganization involving inflammation, afferent dysfunction, and pain as key factors. Emphasizing CNS-focused research and noninvasive brain stimulation methods could significantly enhance treatment and quality of life for burn survivors (37).

Psychiatric disorders are common among burn patients. A study observed that more than 50% of the survivors had some kind of psychiatric disorder 10 years after the burn (34). Posttraumatic stress disorder and depression are common psychiatric disorders in these patients. Body image dissatisfaction is also common in patients with burn injuries. Pain is another serious problem for burn survivors, particularly during the early phases of burn care (12).

Biological basis

Etiology and pathogenesis

The most common types of thermal injuries are caused by flames, hot liquid spills, hot solid materials, and steam. Other types of burn injuries are caused by chemicals, electricity, and radiation. These types of injuries may also damage tissues in a similar manner.

The local and systemic responses to thermal injury are extremely complex. These inflammatory responses result in both local tissue damage and systemic effects. In the acute phase, key features are capillary leak, inhalation injury, and the development of multiple organ failure.

Local responses. There are three concentric zones of tissue injury in fresh burn wounds: (1) maximally damaged tissue in the zone of coagulation; (2) decreased tissue perfusion in the zone of stasis; and (3) edematous tissue in the zone of hyperemia. Tissue in the zones of stasis and hyperemia is at risk for necrosis; it is potentially salvageable unless there is severe sepsis or prolonged hypoperfusion (20). Lack of proper treatment may lead to a partial-thickness burn converting to full-thickness burn. Systemic factors like shock, hypoxia resultant from pulmonary insufficiency, and massive wound sepsis promote burn wound progression.

Systemic responses. The inflammatory reaction starts almost immediately after the burn injury. Extensive burns (30% of total body surface area) are often associated with stress and inflammatory and hypermetabolic changes that lead to hyperdynamic circulation, increased body temperature, glycolysis, proteolysis, lipolysis, and futile substrate cycling. These burn-induced metabolic and inflammatory changes may persist for 3 years after the injury. The relevance of post-burn hypermetabolism and inflammation is that they induce insulin resistance, increased fracture risk, increased liver-size, growth and development retardation, increased cardiac work, cardiac dysfunction, impaired strength and muscle function, hormonal abnormalities, increased risk for infections, and sepsis. All may contribute to causes of morbidity and mortality in burn patients. Cytokines are the primary mediators of this inflammatory reaction to injury. Studies have found a marked increase in serum cytokines in response to burn injury. These cytokines demonstrated an up to 2000-fold increase immediately post-burn and remained significantly high for an extended period of time. Persistently increased glucose and insulin levels are of serious clinical concern as hyperglycemia is often associated with impaired wound healing, increased skin graft loss, increased muscle protein loss, and increased infections. Determination of serum osteocalcin and parathyroid hormone levels also demonstrated significant decreases for 9 and up to 36 months, respectively; these changes were associated with profound decreases in bone mineral content and bone mineral density. Jeschke and colleagues found that urinary norepinephrine, epinephrine, and cortisol increased markedly immediately after burn trauma (21). These changes in catecholamine, glucocorticoid, and glucagon secretion are responsible for a hypermetabolic state. Large burns may adversely affect immune status of the patients.

Cardiovascular changes in patients with burns are characterized by marked tachycardia, increased myocardial oxygen consumption, and increased cardiac output. Cardiac changes are mediated by increased catecholamines. Increased capillary permeability leads to loss of intravascular proteins and fluids into the interstitial space. Myocardial contractility is decreased. Peripheral and splanchnic vasoconstriction occurs. Fluid loss from the wound along with cardiac changes produces systemic hypotension and end-organ hypoperfusion. A large amount of circulating catecholamines is considered detrimental to the myocardium (45). Respiratory changes in burns are often caused by inhalation injury. Several changes 24 to 72 hours after burn injury include pulmonary arterial hypertension, bronchial obstruction, increased airway resistance, reduced pulmonary compliance, atelectasis, and increased pulmonary shunt fraction. Inflammatory mediators may also be responsible for bronchoconstriction. In severe burns, adult respiratory distress syndrome may evolve.

Epidemiology

According to World Health Organization estimates, 180,000 deaths occur annually due to burn injury (47). The majority of burn-related deaths occur in low- and middle-income countries, and almost half occur in Southeast Asia. In 2008, over 410,000 burn injuries occurred in the United States, with approximately 40,000 requiring hospitalization. The higher risk for females in low- and middle-income countries is associated with open-fire cooking or inherently unsafe cookstoves, which can burn loose clothing. Children are particularly vulnerable to burns. Burns are the 11th leading cause of death of children aged 1 to 9 years. The majority (80% to 90%) of burns occur at home. Other factors make people vulnerable for burns include hazardous occupations, poverty, overcrowding, lack of proper safety measures, medical conditions (eg, epilepsy, peripheral neuropathy, and physical and cognitive disabilities), alcohol abuse and smoking, use of kerosene as a fuel source for nonelectric domestic appliances, and inadequate safety measures for liquefied petroleum gas and electricity (47). In Europe, the annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants. Mortality was usually between 1.4% and 18%. Deaths were more frequent in older age, in patients with a larger burned surface area, and in patients with chronic diseases. Multiorgan failure and sepsis were the most frequent causes of death (07).

Patients with epilepsy have higher incidence and severity of burn injury. In a retrospective study, the authors compared patients with and without seizure disorder in a burn unit. Prevalence of seizure disorder was 10.7% among burn patients. Flame injury was most common in patients with seizure disorder, whereas scalds predominated among patients without seizure disorder. Mortality did not differ between the groups, but mean length of hospital stay was longer for patients with seizure disorder (06).

Prevention

Burn injuries are largely preventable. In Southeast Asia, it is mandatory to promote safer cookstoves and less hazardous fuels and to educate regarding loose clothing. It is important to improve the design of cookstoves, particularly with regard to stability and prevention of access by children. In developed countries, promotion of fire safety education and the use of smoke detectors, fire sprinklers, and fire-escape systems in homes are needed. A fire extinguisher near the kitchen is essential, and it should be inspected periodically. Immediate rescue and first-aid measures are mandatory; these measures will help in limiting the extent of injury and preventing some complications of burn injury (47).

The majority of neurologic complications in burn-injured patients are hypoxic or metabolic in origin. Timely attention to the airway, oxygenation, ventilation, and circulation are crucial for preventing hypoxic damage. Smoke inhalation and carbon monoxide poisoning may lead to systemic and metabolic toxicities and subsequent encephalopathies; 100% oxygen administration is required to prevent brain damage. Urgent fluid resuscitation prevents the incidence of renal failure and many neurologic complications. Infection control, especially against multiresistant bacteria, should also be ensured to prevent sepsis-associated encephalopathy. Early excision and grafting of the wound and prompt treatment of sepsis will help in preventing neuromuscular complications of burn injuries.

Differential diagnosis

Confusing conditions

If a burned patient is found unconscious, the reason for this must be ascertained. Asphyxia or head injury are important possibilities that must be excluded. Burning furniture releases toxic fumes, and the patient may suffer from carbon monoxide or cyanide poisoning. Other causes of metabolic encephalopathy should also be considered in this scenario. Villaverde Doménech and coworkers described a case in which skin lesions of pellagra were confused with the lesions of the burn injury (44).

Diagnostic workup

Electrolyte assessment is often essential in patients with large burns requiring aggressive fluid resuscitation. Complete blood count, urinalysis, and blood, urine, sputum, and wound culture tests are required if a patient develops a fever. An arterial blood gas analysis should regularly be done. Prealbumin levels should be used for monitoring the nutritional status of the patient with large burns. Prealbumin levels have been shown to correlate with patient outcomes and are an accurate predictor of patient recovery. Carboxyhemoglobin level needs to be performed in patients with inhalation injury. Lactate levels are a useful predictor of sepsis and mortality in burn patients. Chest radiography can be helpful in patients who are intubated and in patients who have an inhalation injury or who are at risk of developing pneumonia. An electrocardiogram should be used to asses for cardiac abnormalities.

In comatose burn-injured patients, neuroimaging of the brain should always be performed to assess the possibility of closed-head injuries. Electrophysiological assessment may be crucial in patients with nerve injuries requiring nerve reconstruction.

Management

Airway, breathing, and circulation. It is crucial to maintain a patent airway. The airway should be cleared of any foreign material. If the patient is comatose, open the airway with a chin lift and jaw thrust. Patients with severe burns require endotracheal intubation. Urgently, 100% oxygen should be administered. Intravenous access should be established as quickly as possible (16; 17; 08).

Neurologic status. All patients should be quickly evaluated for responsiveness with the help of Glasgow coma scale. There may be several reasons for unresponsiveness or delirium. These include hypoxia, hypovolemia, carbon monoxide poisoning, intoxication (alcohol or drugs), or shock.

Exposure with environment control. Hypothermia can be detrimental. It is important to ensure that the patient is kept warm and covered. All clothing and jewelry should be removed.

Fluids resuscitation. Fluid resuscitation is needed for a patient who has sustained a burn over more than 10% of body area for children, more than 15% for adults; Rule of Nines is a good, quick way of estimating the burn area in adults. Fluid management of major burns improves the survival rates in these patients. The “Parkland” formula is used to calculate the amount of fluid required to resuscitate the patient. During the initial 24 hours, Ringer’s lactate solution 4 ml/kg/% burn for adults and 3 ml/kg/% burn for children should be administered. In next 24 hours, colloid infusion of 5% albumin 0.3 to 1 ml/kg/% burn/16 per hour is provided. Urine output is measured to evaluate the adequacy of fluid resuscitation (16; 17; 08).

Pain control. Pain should be managed with intravenous morphine. Oral analgesics may be used in patients with minor burns.

Wound management. Proper wound management requires cleansing of wound surface, debridement, and dressing. Prophylactic antibiotics are not routinely given to burn patients.

Pruritus. Oral antihistamines are the most frequently prescribed drug for pruritus in burn patients. Pharmacological evidence suggests the involvement of neuropathic mechanisms in burn-related pruritus; gabapentin has been found effective (01).

Beta-blocker. While recovering from massive burns, patients may develop profound sarcopenia, secondary to epinephrine-dependent burn-induced hypermetabolism. Use of the nonselective beta-blocker propranolol may help in suppressing epinephrine-mediated burn-induced hypermetabolism; however, the exact role of beta-blockers in such patients is not established (05).

Special considerations

Pregnancy

The exact incidence of burn during pregnancy is not known, but it can be devastating to both mother and fetus. Several factors, such as the depth and size of the burn, the woman's underlying health and age, associated inhalation injury, and the estimated gestational age of the fetus are likely to affect maternal and fetal outcomes (22). Maternal and perinatal mortality increases significantly when greater than 50% of the total body surface area is burned. However, pregnancy does not seem to alter maternal outcome, and maternal survival is often accompanied by fetal survival (35). A retrospective review presented data from eight patients burned during pregnancy. The total body surface area burned ranged from 1% to 85% in these patients, and all survived the injury. All patients gave birth to healthy children except the most severely burned patient, whose child suffers from cerebral palsy. Authors recommended that all pregnant ladies with burns should be subjected to a prompt fluid resuscitation, early supplemental oxygen administration, early delivery if the pregnancy is in the third trimester, and high suspicion and aggressive treatment for venous thrombosis and sepsis (14).

Anesthesia

Adequate fluid resuscitation and airway management during surgery are of prime importance in burn-injured patients. Pain management through all phases of care is a prime concern of anesthesia care. Total intravenous anesthesia is frequently used for surgeries requiring general anesthesia in severe burn patients. Ketamine is the intravenous anesthetic agent of choice for excision and grafting of the burn wound. Ketamine is preferred in burn patients because it reduces opioid usage and decreases the hemodynamic and respiratory side effects. Ketamine results in increased CNS sympathetic activity and enhanced release of catecholamines. Thus, it has a positive effect on blood pressure and heart rate (02; 29).