Inhalation injury from heat, smoke, or chemical irritants

INTRODUCTION — Inhalation injury or smoke inhalation injury remains one of the leading causes of death. The pathophysiology, clinical features, diagnosis, initial management, subsequent management, and special considerations of inhalation injury are reviewed here.

The emergency care of thermal burns is discussed separately. (See "Emergency care of moderate and severe thermal burns in adults" and "Moderate and severe thermal burns in children: Emergency management".)

DEFINITION — Inhalation injury is a nonspecific term that refers to damage to the respiratory tract or lung tissue from heat, smoke, or chemical irritants carried into the airway during inspiration [1]. The term is often used synonymously with smoke inhalation injury.

EPIDEMIOLOGY — In 2020, local fire departments in the United States responded to an estimated 1.4 million fires [2,3]. These fires caused 3500 civilian fire deaths and 15,200 reported civilian fire injuries. Property damage was estimated at USD $21.9 billion. Pulmonary complications following burns and inhalation injury are responsible for up to 77 percent of the deaths, among which the majority are due to carbon monoxide poisoning [4,5]. Inhalation injury is common following burn injury and increases in incidence with the size of the burn injury and age of the patient [6,7]. In addition, inhalation injury has been shown to be an independent predictor of mortality in burn patients [8].

PATHOPHYSIOLOGY AND CLASSIFICATION — Inhalation injury can affect the airways as well as result in systemic toxicity [9]. The location and severity of injury depend on several factors, including the ignition source, the size and diameter of the particles in the smoke, the duration of the exposure, and the solubility of the gases [10,11]. Direct toxin damage is caused by the lower-molecular-weight constituents of smoke because of their pH, ability to form free radicals, and ability to reach the distal airways and alveoli [12-16]. Based upon the primary localization of the insult, inhalation injury is classified into injuries of the upper airway, the tracheobronchial system, or the lung parenchyma [9,17].

Upper airway injury — The leading injury in the upper airway (above the vocal cords) is thermal injury due to the efficient heat exchange in the oro- and nasopharynx. The immediate injury results in erythema, ulcerations, and edema [18]. In combined burn and inhalation injury, aggressive fluid administration required to treat burn shock promotes early edema formation [19]. In addition, burns to the face and neck may cause anatomic distortion or external compression of the upper airway, complicating airway management [20]. In addition to the acute inflammation, damage of ciliary function impairs physiological clearance processes of the airway, leading to an increased risk of bacterial infection for several weeks. Furthermore, the increased production of thick secretions can cause distal airway obstruction, atelectasis, and impaired gas exchange [11,20,21].

Tracheobronchial injury — With the exception of inhalation of steam, injury to the tracheobronchial tree (figure 1) is usually caused by chemicals in smoke. However, toxic inhalation of noxious gases (eg, chlorine), liquids (eg, acid), and direct airway fire (eg, intraoperative) can also be associated with a similar process. Clinical symptoms include persistent coughing and wheezing, soot-containing airway secretions (ie, melanoptysis), increased work of breathing resulting in hypoventilation, erythema, hyperemia, and increased pulmonary shunting from lobar collapse or atelectasis [11,20].

The tracheobronchial area is richly innervated by vasomotor and sensory nerve endings [11,22]. Smoke inhalation stimulates these nerves to release neuropeptides. These neuropeptides then induce bronchoconstriction and nitric oxide synthase (NOS) to generate reactive oxygen species (ROS) [11,23-25]. These neuropeptides can function as tachykinins, inducing an inflammatory response with the downstream effects of bronchoconstriction, increased vascular permeability, and vasodilation [25]. These factors potentiate local cellular damage and the loss of hypoxic pulmonary vasoconstriction, which causes bronchial blood flow to increase manyfold. In addition, the increased bronchial blood flow delivers activated polymorphonuclear leukocytes and cytokines to the lung, increasing the host inflammatory response [25]. Furthermore, the loss of an intact bronchial epithelium and the effects of ROS result in a loss of plasma proteins and fluid from the intravascular space into the alveoli and bronchioles [25,26]. The transvascular shift of protein results in exudate and cast formation within the airways, leading to alveolar collapse [25,26]. These processes contribute to ventilation-perfusion mismatch as a primary mechanism of hypoxemia following the inhalation injury [26,27].

Parenchymal injury — Damage to the lung parenchyma is delayed. The time difference from the initial injury to the occurrence of a decrease in arterial oxygen tension to inspiratory oxygen fraction ratio (PaO₂:FiO₂ ratio) is correlated with the severity of the lung injury [11,17]. A faster time is associated with more severe injury. Injury to the lung parenchyma is characterized by atelectasis and alveolar collapse resulting in increased transvascular fluid flux, a decrease in surfactant, and a loss of hypoxic vasoconstriction and therefore impaired oxygenation. Furthermore, a severe imbalance in alveolar hemostasis and decreased fibrinolytic activity, with massive fibrin deposition in the airways, causes a ventilation-perfusion mismatch [11,28]. This mismatch is made worse by the formation of nitric oxide, which causes vasodilation, increasing blood flow to poorly ventilated bronchioles [29].

Airway obstruction and atelectasis increases the risk for pneumonia. The risk for pneumonia is increased because of the impaired function of alveolar macrophages, polymorphonuclear leukocytes, and mucociliary clearance mechanisms [30-32].

Systemic toxicity — Direct systemic effect of inhalation injury is caused by breathing toxic substances formed via combustion or pyrolysis. The two most relevant gases associated with increased morbidity and mortality are carbon monoxide and hydrogen cyanide [11].

●Carbon monoxide poisoning – Carbon monoxide is one of the most frequent immediate causes of death following inhalation injury [11]. Carbon monoxide is a colorless, odorless gas with an affinity for hemoglobin more than 200 times higher than that of oxygen. Carboxyhemoglobin shifts the oxyhemoglobin dissociation curve to the left, impairing release of oxygen at the tissues and utilization of oxygen in mitochondria, leading to tissue hypoxia [33]. The table shows signs and symptoms at various concentrations of carboxyhemoglobin (table 1).

Carbon monoxide poisoning should be suspected in all patients who present following inhalation injury or house fires until it is excluded by a normal blood carboxyhemoglobin level. Pulse oximetry cannot screen for carbon monoxide exposure, as it does not differentiate carboxyhemoglobin from oxyhemoglobin. Carboxyhemoglobin levels are measured with CO-oximetry on arterial or venous blood. Treatment indications are given in the table (table 2). (See "Carbon monoxide poisoning" and "Pulse oximetry", section on 'Co-oximetry'.)

●Hydrogen cyanide – Hydrogen cyanide is the gaseous form of cyanide (CN), which is a colorless gas with the odor of bitter almonds [11]. Cyanide poisoning is difficult to confirm during the initial postburn period because the symptoms are nonspecific and cyanide levels cannot be measured soon enough to be clinically meaningful. Given the high probability of its presence at a fire scene, cyanide toxicity should be considered in every patient with an inhalation injury. Treatment for cyanide poisoning should be considered in any patient being treated for smoke inhalation (table 3). The use of hydroxocobalamin in patients with known or suspected cyanide poisoning from smoke inhalation was reported to decrease hospital cost and contribute to more efficient health care resource utilization [34]. Treatment can be initiated in those at risk who display depressed level of consciousness, cardiac arrest, or cardiac decompensation in the absence of laboratory confirmation. (See "Cyanide poisoning".)

CLINICAL FEATURES

History and physical — Inhalation injury should be suspected based on a history of exposure to heat, smoke, or chemicals, and supporting clinical features. When presented with a patient with a suspected inhalation injury, the clinician should first review the history and reported mechanism of injury. Pertinent information includes exposure to flame, smoke, or chemicals; duration of exposure; exposure in an enclosed space; and a history of loss of consciousness [25,35].

Generalized symptoms such as dizziness, nausea, or vomiting may be reported. Carbon monoxide poisoning should be presumed in any patient who presents following smoke inhalation until it is excluded by a normal carboxyhemoglobin level as measured by CO-oximetry. The physical signs and symptoms of various concentrations of carboxyhemoglobin are given in the table (table 1). (See "Carbon monoxide poisoning" and "Pulse oximetry", section on 'Co-oximetry'.)

Clinical symptoms of upper airway injury, such as difficulty breathing, might not be immediately obvious until edema is severe enough to significantly impair airway diameter [11,17]. Symptoms of lower respiratory tract injury may include shortness of breath and productive cough.

Physical findings include burns to the face, singed nasal vibrissae, soot in the oropharynx, nasal passages, proximal airways, and carbonaceous sputum [9,25,36,37]. Other signs of upper airway injury include hoarseness and stridor, which increase the work of breathing and may lead to respiratory fatigue with sub- and suprasternal retractions. Signs of lower respiratory tract injury may include any or all of the following: tachypnea, decreased breath sounds, wheezing, rales, rhonchi, or use of accessory respiratory muscles.

Laboratory findings — Standard laboratory studies should be obtained, including a complete blood count, electrolytes, blood urea nitrogen, creatinine, lactate level, and toxicology screen. An arterial blood gas (ABG) should be sent for CO-oximetric measurement of the oxyhemoglobin saturation, carboxyhemoglobin concentration (table 1), methemoglobin concentration, and cyanide levels, as indicated. The reason for measuring the oxyhemoglobin saturation via CO-oximetry is that standard pulse oximetry cannot distinguish oxyhemoglobin from carboxyhemoglobin. (See "Carbon monoxide poisoning" and "Pulse oximetry", section on 'Co-oximetry'.)

Chest imaging — Chest radiography is typically obtained in the initial evaluation of the injured patient but has low sensitivity for inhalation injury [13]. Most patients with inhalation injury have a normal chest radiograph at presentation, and for those with abnormal findings, the degree of injury is usually underestimated [11]. The presence of pulmonary opacities on initial chest films has been implicated as a marker of severe injury and a poor prognosis [38].

We do not routinely obtain computed tomography (CT) of the chest solely to evaluate the lungs for inhalation injury, though patients with concomitant injuries may undergo chest CT for other indications. Some have suggested that chest CT may be helpful as an early predictor of smoke inhalation severity [39,40]. In these studies, the airway wall thickness to total bronchial diameter (T/D) ratio is measured. In a study of 40 patients, the number of days of mechanical ventilation correlated with the T/D ratio.

DIAGNOSIS — The diagnosis of inhalation injury may be suspected based upon clinical findings in the setting of smoke exposure, but a definitive diagnosis relies upon direct examination of the airways.

Direct airway examination — Once the airway is secured and the patient is hemodynamically stabilized, a suspected diagnosis of inhalation injury should be confirmed with visual inspection of the airways. Nasopharyngoscopy or direct laryngoscopy can be used for a limited direct examination of the upper airways for obvious signs of smoke inhalation. However, fiberoptic bronchoscopy allows examination of the airways from the oropharynx to the lobar bronchi and is the standard for confirming a diagnosis of inhalation injury [1,9,37]. Clinical signs of inhalation injury include mucosal erythema and edema, blistering, ulceration, or bronchorrhea, fibrin casts, or evidence of charring [25].

Injury severity scoring — Findings on bronchoscopy can help predict the risk and severity of acute lung injury, which aid in subsequent management (eg, fluid therapy, treatment of tracheobronchitis) [25]. Multiple studies have shown that inhalation injury is a graded phenomenon with increasing severity correlating with worse outcomes [25,41,42]. Several scoring systems have been proposed, but the standardization and validity of these are controversial [1,25]. The Abbreviated Injury Score (AIS) grading scale using bronchoscopy correlates well with mortality as well as gas exchange (table 4) [25,43-45]. Increasing severity of injury as reflected in increasing AIS also correlates with a greater need for supportive treatment.

AIS grading of inhalation injury by bronchoscopy is as follows [43]:

●0 (no injury) – Absence of carbonaceous deposits, erythema, edema, bronchorrhea, or obstruction

●1 (mild injury) – Minor or patchy areas of erythema or carbonaceous deposits in the proximal or distal bronchi

●2 (moderate injury) – Moderate degree of erythema, carbonaceous deposits, bronchorrhea, or bronchial obstruction

●3 (severe injury) – Severe inflammation with friability, copious carbonaceous deposits, bronchorrhea, or obstruction

●4 (massive injury) – Evidence of mucosal sloughing, necrosis, endoluminal obliteration

MANAGEMENT OVERVIEW

Initial management — The first priority in the prehospital setting is to rescue the victim from the source of fire and to limit time of exposure. Assessment of the patient's airway, breathing, and circulation should be performed expeditiously. The initial diagnosis and management of accompanying traumatic or burn-related injuries is based upon Advanced Trauma Life Support (ATLS) protocols. Immediately life-threatening injuries take precedence [11,20].

For patients with suspected inhalation injury who are not intubated initially, the adequacy of breathing as assessed by respiratory rate, chest wall motion, and auscultation of air movement should be frequently reevaluated [11,20]. If possible, information about comorbidities should be obtained [11]. (See "Pediatric considerations in prehospital care" and "Initial management of trauma in adults" and "Emergency care of moderate and severe thermal burns in adults", section on 'Initial assessment and treatment'.)

Securing the airway — Proper airway security and management is critical in patients with inhalation injury. Loss of an airway in patients with burns and inhalation injury can be catastrophic. The anesthesiologist, intensivist, surgeon, and/or critical care physician should decide the most appropriate method of airway management either by endotracheal intubation or placement of a tracheostomy. Endotracheal intubation is frequently needed for supportive therapy in the management of inhalation injury. In one reported series, up to 80 percent of patients with inhalation injury required intubation at least for short-term management [46]. Some patients will ultimately require tracheostomy. (See 'Tracheostomy' below.)

Data are conflicted over the appropriateness of early intubation in burn patients. In general, intubation is indicated to improve oxygenation or ventilation or to maintain a compromised airway [47]. A decision for early intubation should be based upon any of the following signs: deep burns to the face or neck, blisters or edema of the oropharynx, stridor, use of accessory muscles, respiratory distress, sub- and suprasternal retractions, or hypoventilation. The American Burn Association's Advanced Life Support protocol suggests that if there is any question about the security of the patient's airway, the patient should be intubated prior to transfer to a trauma or burn center [48,49]. The endotracheal tube can be removed, if indicated, once the patient has been safely transported. Intubated patients with concern for carbon monoxide poisoning should also be placed on humidified 100 percent oxygen until carboxyhemoglobin levels normalize. Humidified oxygen helps to avoid the development of inspissated secretions. Carbon monoxide poisoning should be presumed in any patient who presents following smoke inhalation until it is excluded by a normal carboxyhemoglobin. (See 'Systemic toxicity' above and "Cyanide poisoning" and "Carbon monoxide poisoning".)

The proper-sized tube to allow secretion clearance and the passage of a bronchoscope, tube placement, and stabilization techniques are all important considerations. The most experienced provider available should establish and secure the airway. Maintenance of an endotracheal tube on a burned face is a significant challenge, and accidental extubation is a concern. A large study of the American burn centers reported securing endotracheal tubes using linen nonadhesive tape in 59 percent of cases, manufactured devices in 48 percent, and orthodontic techniques in 24 percent [50]. Septal ties have been used to secure nasal intubations at the Shriners Hospital for Children-Galveston for over 20 years without accidental extubation or septic sinusitis complications [51]. The security of the tube needs to be checked frequently as airway edema increases or decreases. (See "Direct laryngoscopy and endotracheal intubation in adults" and "Rapid sequence intubation in adults for emergency medicine and critical care".)

Patients who do not require intubation should receive humidified 100 percent oxygen by face mask to displace carbon monoxide, if not already initiated [52,53]. For those at risk of developing oxygen-induced hypercapnia (eg, patients with a history of chronic obstructive pulmonary disease or obstructive sleep apnea), a low threshold to treat the patient with noninvasive ventilation or mechanical ventilation is prudent. Tissue hypoxia is multifactorial and can quickly lead to death. Hypoxia is due, in part, to the inspiration of air with an FiO₂ <15 percent during the fire (fire consumes ambient oxygen) and is also related to impaired delivery and utilization of oxygen by the tissues from carbon monoxide and cyanide poisoning [52,54].

The care of patients who require intubation are described below. (See 'Ventilator management' below.)

Disposition — Patients with any of the following clinical findings should be hospitalized, typically in a monitored setting until inhalation injury can be ruled out or clinical findings resolve [55]:

●History of closed space entrapment

●History of syncope

●Carbonaceous sputum

●Arterial PaO₂ <60 mmHg

●Metabolic acidosis

●Carboxyhemoglobin levels greater than 15 percent

●Bronchospasm/wheezing

●Facial burns

The presence of inhalation injury in a burn-injured patient is an indication for referral to a regional burn center (table 5) [56]. The patient may require interim care at the hospital to which they presented until transfer can be arranged. (See "Overview of the management of the severely burned patient", section on 'Emergency burn care'.)

Patients with an appropriate history (eg, escaped a fire) but a low risk for inhalation injury based on clinical findings and without cutaneous burns need to be monitored for a minimum of four to six hours. If the vital signs remain stable, the patient can usually be discharged with instructions to return if any symptoms develop.

GENERAL CARE — After initial stabilization and transfer to the intensive care unit, treatment for inhalation injury is mainly supportive. In the early phase (<36 hours), treatment is focused on treating systemic toxicity (carbon monoxide, hydrogen cyanide) and monitoring for early airway edema and bronchospasm and other complications.

Monitoring the airway — After inhalation injury, upper and lower airway inflammation may result in increased airway edema, mucosal slough, and cast formation, which result in impaired gas exchange. These are managed with aggressive pulmonary toilet and may require therapeutic bronchoscopies. (See 'Pulmonary care' below and 'Example treatment protocol for nonintubated patients' below.)

Intubation for altered mental status, imminent airway obstruction, or respiratory failure may become necessary during the subsequent hospital course since the development of upper airway inflammation and edema may be delayed by 24 hours and lower airway edema delayed by 36 hours [57]. Other reasons for needing intubation include complications that develop during the hospital course, such as sepsis, acute respiratory distress syndrome, pneumonia, pulmonary toilet, and for operative procedures.

For those who are intubated, changing the endotracheal tube and reintubation for unplanned extubation are dangerous in the presence of upper airway edema, and aggressive monitoring to ensure airway security is essential to avoid problems [58].

Monitoring for complications — Patients are monitored and treated, as needed, for the following during hospitalization:

●Pneumonia – Although the risk of nosocomial pneumonia is increased, there is no benefit for prophylactic antimicrobial therapy for inhalational injury. (See "Overview of the management of the severely burned patient", section on 'Antimicrobial therapy'.)

●Acute respiratory distress syndrome – Acute respiratory distress syndrome (ARDS) may also develop several days after the exposure [38]. The presentation, diagnosis, and management of ARDS caused by smoke inhalation are similar to those for ARDS due to other etiologies. (See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults" and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults" and "Acute respiratory distress syndrome: Ventilator management strategies for adults".)

●Fluid overload – What constitutes appropriate fluid resuscitation for patients with inhalation injury remains debated. However, inhalation injury associated with burn injury increases the fluid requirements over and above what is predicted by the depth and size of their burns [11,25,59]. Thus, close monitoring of fluid balance is needed to ensure adequate resuscitation and to avoid complications. (See "Emergency care of moderate and severe thermal burns in adults", section on 'Fluid resuscitation' and "Overview of the management of the severely burned patient", section on 'Initial stabilization' and "Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults", section on 'Etiologies and predisposing factors'.)

●Hypermetabolism/malnutrition – Patients with inhalation injury may also demonstrate marked hypermetabolism. An increased production of carbon dioxide requires a high minute ventilation to maintain a normal pCO₂ and may require ventilatory support to achieve. Enteral nutrition formulas with a low respiratory quotient may help limit carbon dioxide production, improving the patient's ability to keep up with respiratory demands. (See "Hypermetabolic response to moderate-to-severe burn injury and management" and "Clinical assessment and monitoring of nutrition support in adult surgical patients" and "Overview of nutrition support in burn patients".)

PULMONARY CARE — Treatment of inhalation injury is supportive and aimed at relieving bronchospasm, reducing pulmonary secretions, and clearing the airways of fibrin casts and sloughed, necrotic bronchial epithelium, which can cause airway obstruction and atelectasis leading to pneumonia. Prophylactic antibiotics are not indicated. (See 'Pathophysiology and classification' above.)

Supportive treatments — Supportive treatment includes the use of bronchodilators for wheezing and airway clearance measures such as administration of aerosolized mucolytic agents alternating with aerosolized heparin, chest physiotherapy, and postural drainage. Intubation and therapeutic bronchoscopy may be necessary to control secretions, which should diminish within 7 to 10 days in the absence of pulmonary infection.

The routine administration of corticosteroids does not appear to confer any benefit following smoke inhalation [60].

Bronchodilators — Aerosolized bronchodilators should be given when wheezing or bronchospasm occurs. Bronchodilators relax bronchial muscle, stimulate mucociliary clearance, decrease airflow resistance, and improve dynamic compliance [25,61]. Bronchodilators that are useful in the treatment of inhalation injury include albuterol or levalbuterol for wheezing/bronchospasm, and racemic epinephrine for stridor or retractions, typically administered every four hours [61].

Mucolytic agents — Clearing the airways is an essential component of the management of patients with inhalation injury. This can be achieved with a combination of inhaled pharmacologic agents (eg, N-acetylcysteine) and mechanical means, such as therapeutic coughing, chest physiotherapy, airway suctioning, early ambulation, and, if necessary, intubation with suctioning or therapeutic bronchoscopy [62].

N-acetylcysteine (NAC) is a powerful mucolytic agent that can be useful in treatment of inhalation injury. N-acetylcysteine contains a thiol group and is a strong reducing agent that breaks the disulfide bonds that give stability to the mucoprotein network of molecules in mucus [61]. However, NAC is also an airway irritant and may produce bronchoconstriction. A bronchodilator should be added if wheezing or bronchospasm occurs with NAC treatment. Generally, a NAC dose of 3 mL of a 20% solution every four hours is used. Similar outcomes were reported from a trial comparing on-demand administration based upon strict clinical parameters with routine administration (every six hours) [63].

The combination of NAC and aerosolized heparin has been shown to be effective for the treatment of inhalation injury in animal studies [64]. Inhaled anticoagulants decrease the formation of fibrin casts following inhalation injury but do not alter systemic markers of clotting and anticoagulation [65]. A systematic review identified five retrospective studies using inhaled anticoagulants for the treatment of inhalation injury in children and adults [64,66-69]. In some, but not all, studies, inhaled anticoagulants have reduced morbidity or were associated with increased survival. Nebulized heparin/NAC significantly reduced reintubation rates and the incidence of atelectasis and improved mortality in one study [66], and, in another, the two agents resulted in better lung compliance, less pulmonary edema, and less airway obstruction compared with controls [67]. In a separate retrospective study, nebulized heparin in conjunction with a beta-agonist and mucolytic significantly decreased the duration of mechanical ventilation and increased the number of ventilator-free days in patients with inhalation injury [70]. When used, we dose inhaled heparin at 5000 to 10,000 units in 3 mL normal saline, every four hours. Of note, one randomized trial comparing differing doses of inhaled heparin found no significant differences between 5000 and 10,000 units [65].

Example treatment protocol for nonintubated patients — An example protocol approach used by the author to treat inhalation injury in nonintubated patients is given below. Individual aspects of pulmonary care are discussed in more detail below. (See 'Pulmonary care' above.)

●Titrate humidified high-flow oxygen to maintain oxygen saturation >90 percent

●Supervise the patient performing coughing and deep breathing exercises every two hours

●Turn the patient side to side every two hours

●Administer chest physiotherapy every two hours

●Provide nebulizer treatments every two hours alternating aerosolized NAC / bronchodilator (if wheezing) as one treatment and aerosolized heparin/saline as the other

●Perform nasotracheal suctioning as needed

●Encourage early ambulation

●Educate the patient, their family, or other caregivers about the disease process and prognosis

Ventilator management — Patients with inhalation injury and concomitant burn injury frequently require mechanical ventilator support. An estimated 33 percent of burn patients require mechanical ventilation, and the incidence increases significantly in the presence of inhalation injury [71]. However, the optimal ventilator strategy for patients with burns and inhalation injury is not well defined [72]. A survey of mechanical ventilator practices across burn centers in North America has shown no single ventilator mode is used consistently in the management of burn patients, regardless of their insult [72]. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit".)

Tidal volumes — Based upon the Acute Respiratory Distress Syndrome (ARDS) Network Study, low tidal volumes and limiting plateau pressures are the currently accepted lung-protective practices for mechanical ventilation [73]. However, burn patients and patients with inhalation injury were not included in the studies that led to the widespread acceptance of these mechanical ventilation strategies [46,50]. The tidal volume selected for burn patients with inhalation injury varies between 6 to 8 mL/kg of predicted body weight [61]. However, a large retrospective study suggests that the use of higher tidal volumes decreases ARDS, atelectasis, and ventilator days when compared with low tidal volumes in pediatric burn patients with inhalation injury [74]. The exact tidal volumes needed for a patient with burns and inhalation injury still needs to be determined. A good rule of thumb would be to limit tidal volumes and plateau pressures to the lowest level tolerated by the patient's compliance, airway resistance, and work of breathing. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults".)

Modes of ventilation — Pulmonary management of patients with burns and inhalation injury may deviate from typical ventilator management practices in the general intensive care unit (eg, larger-than-typical tidal volumes). Randomized clinical trials identifying the best strategies for burn patients are lacking. From observational studies, no single ventilator mode prevails. In one survey, pressure support ventilation and volume-assist control modes were the most commonly reported initial modes used in burn patients with or without inhalation injury [50]. Open lung techniques of mechanical ventilation, including high-frequency percussive ventilation, high-frequency oscillatory ventilation [75], and airway pressure release ventilation, have also been used in the management of patients with inhalation injury with varying degrees of success [50]. (See "Modes of mechanical ventilation".)

Extubation criteria — Extubation criteria include a wide variety of physiological variables that have been proposed to aid in discontinuing mechanical ventilation in burn patients with inhalation injury. Additional extubation criteria for burn patients with inhalation injury suggest the use of the rapid shallow breathing index, evaluation of the work of breathing, Glasgow coma scale, Richmond Agitation Sedation Scale, and the Confusion Assessment Method for the intensive care unit [50]. Furthermore, a daily sedation vacation and daily weaning trial is suggested to determine success of weaning from mechanical ventilation and a successful extubation. Importantly, patients should show signs of resolving airway edema and inflammation with minimal secretions and/or an ability to cough and clear secretions when they develop. (See "Extubation management in the adult intensive care unit" and "Initial weaning strategy in mechanically ventilated adults" and "Weaning from mechanical ventilation: Readiness testing" and "Weaning from mechanical ventilation: Readiness testing", section on 'Rapid shallow breathing index'.)

Suggested criteria include [4]:

●PaO₂/FiO₂ ratio >250 mmHg

●Maximal inspiratory pressure >60 cm H₂O

●Vital capacity at least 15 to 20 mL/kg

●Spontaneous tidal volume 5 to 7 mL/kg

●Maximal voluntary ventilation two times the minute volume

●Resolution of the need for intubation

●Audible leak around the endotracheal tube

Tracheostomy — Some burn centers elect to place a tracheostomy tube in all patients with burns and inhalation injury. However, although one trial found improved patient comfort and security with early tracheostomy, there were no significant differences in length of stay, incidence of pneumonia, survival, or duration of intubation for early compared with later tracheostomy. We typically proceed with tracheostomy after three failed extubation attempts or after 21 days [76]. In the setting of anterior neck burns, tracheostomy should be delayed until five to seven days after skin grafting [77]. Tracheostomy is reviewed separately. (See "Tracheostomy: Rationale, indications, and contraindications", section on 'Optimal timing in mechanically ventilated patients'.)

SPECIAL POPULATIONS

Children — In pediatric patients, airway compromise is the most common cause of severe morbidity and mortality, likely due to the small size of the airway. It is essential that the clinician frequently evaluate the magnitude of swelling in the face and neck to prevent airway compromise. In addition, pediatric patients with burns and inhalation injury are tachypneic and can exhibit an increased work of breathing. Vigilance and frequent clinical assessments are warranted. (See 'Clinical features' above.)

The threshold for intubation needs to be lower in pediatric patients due to the potential for rapid development of airway edema. Endotracheal tube size needs to be specifically tailored for the pediatric patient with inhalation injury. Due to their anatomy, the chance of accidental extubation is higher in pediatric patients than adults. Endotracheal tube security is essential to maintaining a patent airway. Loss of an airway in this population can result in airway compromise and is potentially fatal. An emergency airway box with appropriate-sized equipment is recommended to be kept at the bedside. (See "Technique of emergency endotracheal intubation in children".)

Older adults — Adults over 65 years of age have a mortality from burns that is six times the national average [78]. Due to lower physiological reserves and comorbidities, treatment of this patient population presents a unique challenge. A number of existing risk factors are present in older adults. These include increased risk of infections, pulmonary diseases, and comorbidities. Older adults have a decrease in pulmonary reserve, lung mechanics, and a decreased lean body mass, as well as coronary artery disease. Additionally, pneumonia and urinary tract infections are the most prevalent complications in older adult burn patients. Treatment options are identical to younger patients, keeping in mind the physiological differences due to aging and comorbidities. No evidence supports changing treatment protocols [78].

Inhalation injury other than smoke — While the optimal management strategy is unknown, patients with inhalation injury due to agents other than smoke are typically managed in the same fashion as for smoke in inhalation, with the exception of monitoring for carbon monoxide poisoning. (See "Carbon monoxide poisoning", section on 'Management'.)

Additional information can be found at the Agency for Toxic Substances and Disease Registry, a health agency of the US Department of Health and Human Services [79].

MORBIDITY AND MORTALITY — Inhalation injury is an independent predictor of mortality in burn patients. Pulmonary-related complications following burns and inhalation injury are responsible for up to 77 percent of the deaths, most of which are related to carbon monoxide poisoning. In a review that identified 769 patients with smoke inhalation-related acute lung injury, the in-hospital mortality rate was 26 percent, and among those with associated severe burns (>20 percent total body surface area [TBSA]), it was 50 percent [80]. In addition to severe associated burns, other clinical factors associated with in-hospital mortality included burn age >60 years and vasopressor use.

The National Burn Repository of the American Burn Association found that patients with inhalation injury had a higher case fatality for a given Baux score (age plus total burn surface area) compared with those with no inhalation injury, but the added risk was not constant [81]. As an example, the presence of inhalation injury increases mortality nearly 24-fold for burn patients under the age of 60 with a total burned surface area <20 percent. From another study, the mortality of burn patients increased by 20 percent in the presence of smoke inhalation [37]. The need for mechanical ventilation and evidence of severe inhalation injury on bronchoscopy predict increased mortality in patients with inhalation injury due to burns [82].

Long-term sequelae — Most patients do not suffer long-term functional impairment following smoke inhalation. In one study of 23 patients with a history of severe smoke inhalation, there were no changes in spirometry, nonspecific airway hyperresponsiveness, or cardiac or pulmonary variables when measured during maximal exertion approximately four years after the exposure [83]. However, one review reported pulmonary function changes up to 8 years post-injury in a group of severely burned children with inhalation injury [61,84]. Another long-term study on lung function reported a restrictive lung impairment and significant reduction in diffusion capacity following burns and smoke inhalation [85]. Rare long-term sequelae include tracheal stenosis, bronchiectasis, interstitial fibrosis, reactive airways dysfunction syndrome, and bronchiolitis obliterans [86,87], although most of these cases appear to have followed severe chemical bronchitis or nosocomial pneumonia at the time of injury. One study showed that inhalation injury did not appear to significantly impact the quality of life of pediatric patients with inhalation injury eight years after follow-up [88]. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Care of the patient with burn injury".)

SUMMARY AND RECOMMENDATIONS

●Inhalation injury – Inhalation injury is a nonspecific term that refers to damage to the respiratory tract or pulmonary parenchyma by heat, smoke, or chemical irritants. (See 'Introduction' above and 'Epidemiology' above and 'Morbidity and mortality' above.)

●Associated conditions – Inhalation injury also causes systemic toxicity owing to toxic gases (eg, carbon monoxide, hydrogen cyanide). About one-third of patients with burn injuries have a concomitant inhalation injury. Pulmonary-related complications following burns and inhalation injury are responsible for up to 77 percent of deaths related to burn injury.

•Carbon monoxide poisoning – Carbon monoxide poisoning should be presumed in any patient who presents following smoke inhalation until it is excluded by a normal carboxyhemoglobin level on CO-oximetry. The initial approach to presumed carbon monoxide poisoning involves administering supplemental oxygen at FiO₂ of 100 percent. (See 'Initial management' above and 'Systemic toxicity' above.)

•Burns and traumatic injury – The evaluation and initial management of accompanying trauma or burn injuries is prioritized using Advanced Trauma Life Support protocols. Transfer to a burn center should be initiated for patients with inhalation injury and burns who meet the American Burn Association referral criteria (table 5). (See 'Management overview' above.)

●Airway management – Proper airway management is critical in patients with inhalation injury. Early intubation is justified for any patient with suspected inhalation injury and signs of respiratory distress (stridor, use of accessory respiratory muscles), hypoxemia, hypoventilation, deep burns to the face or neck, or blistering or edema of the oropharynx. Loss of an airway in patients with burns and inhalation injury can be catastrophic. The most experienced practitioner available should establish and secure the airway. Tube security needs to be checked frequently as swelling increases or decreases. (See 'Securing the airway' above and 'Initial management' above.)

●Diagnosis – For patients with clinical features suspicious for inhalation injury, such as a history of smoke exposure in an enclosed space, and physical findings (eg, facial burns, singed nasal vibrissae, soot in the oropharynx, nasal passages, and proximal airways), we suggest the use of bronchoscopy to confirm the diagnosis of inhalation injury. (See 'Diagnosis' above.)

●Supportive care and monitoring – The inpatient management of patients with inhalation injury treatment is mainly supportive and consists of monitoring the patient for subsequent development of airway compromise. Upper airway problems tend to occur within 24 hours of inhalation injury and are managed by intubation until the upper edema subsides, while lower airway compromise tends to occur later (one to three days after injury). (See 'Supportive treatments' above.)

•Aerosolized bronchodilators are effective in several ways and should be given when wheezing or bronchospasm occurs (table 6). Bronchodilators relax bronchial muscle, stimulate mucociliary clearance, decrease airflow resistance, and improve dynamic compliance.

•Clearing the airways is an essential component in the management of patients with inhalation injury. This can be achieved with a combination of inhaled pharmacologic agents (N-acetylcysteine, heparin) and mechanical means, such as therapeutic coughing, chest physiotherapy, airway suctioning, early ambulation, and, if necessary, intubation with suctioning or therapeutic bronchoscopy.

●Ventilator management – Mechanical ventilation of patients with inhalation injury should begin with low tidal volumes (6 to 8 mL/kg), adjusting them based upon the patient's condition, compliance, airway resistance, and tolerance. There is no consensus on the optimal mode of mechanical ventilation, but if the patient develops acute respiratory distress syndrome, a lung-protective strategy should be used. Assessing readiness for extubation and daily weaning trials should be evaluated every morning, and the patient should be removed from mechanical ventilation as soon as they meet criteria. (See 'Ventilator management' above.)

●Long-term sequelae – Most patients do not suffer long-term respiratory impairment following smoke inhalation; however, although rare, residual long-term sequelae may include tracheal stenosis, bronchiectasis, interstitial fibrosis reactive airway disease, and bronchiolitis obliterans. These are usually associated with severe injury. (See 'Morbidity and mortality' above.)