WORKUP	Section 5 of 10
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Lab Studies:

• Electrolyte testing can identify an anion gap acidosis.

• Elevated lactate levels may be a source of metabolic acidosis secondary to CN, methemoglobinemia, CO, or hypoxia. Lactate levels higher than 10 mmol/L are a sensitive indicator of CN levels higher than 1 mg/mg; therefore, they should be treated.

• BUN and creatinine levels should be obtained for baseline renal function in patients in shock or rhabdomyolysis. Patients with large cutaneous burns, crush injuries, or prolonged immobilization should have their serum creatine kinase (CK) checked and, if appropriate, urine myoglobin.

• Thermal degradation products of various compounds, including phosphorous-based fire retardants, are capable of impairing cholinesterase activity. A prospective study measured serum erythrocyte cholinesterase activity at the scene of residential fires for 49 victims. A significant lower level of cholinesterase activity was noted in these patients as compared to controls. Obviously, further investigation into the clinical significance of this lower enzymatic activity is needed before it can be used clinically.

• The pulse oximeter can be misleading in the setting of CO exposure or methemoglobinemia because it uses only 2 wavelengths of light (the red and the infrared spectrum), which detect oxygenated and deoxygenated hemoglobin (Hb) only and not any other form of Hb. Cooximeters transmit 4 wavelengths of light through a blood sample and are capable of detecting methemoglobin and Hb-CO (in addition to Hb and oxyhemoglobin [HbO₂]).

• Be aware that, on routine blood gas analysis, the percent saturation of Hb is calculated from the alveolar-arterial difference in partial pressure of oxygen (PaO₂), which can give a falsely elevated saturation. The difference between saturations obtained by cooximetry and calculated figures is known as the saturation gap and is an indicator that a dyshemoglobinemia is present.

• Finally, light reflection in methemoglobinemia is similar to that in reduced Hb, and a depressed saturation may be shown on pulse oximetry, but the decrease does not accurately reflect the level of methemoglobinemia. In fact, as levels reach 30% or higher, the pulse oximeter does not go below 85%.

• A recent study has shown that acute exposure to smoke results in a transient increase of Clara cell protein (CC16). This small protein molecule is made and secreted by the Clara cells, which reside in the terminal and respiratory bronchioles. Further studies are needed, but this may be an early and sensitive indicator of acute airway injury caused by SI.

• Lead-containing paint is common in structures built before 1977, and this element can become aerosolized and absorbed directly into the bloodstream from the lungs. While it is true that severe SI has been shown to increase serum lead levels more than 2-fold, no evidence suggests that these elevations are clinically relevant.

Imaging Studies:

• Chest radiography

• Obtain chest x-ray films (CXRs) in patients with a history of significant exposure or pulmonary symptoms.

• Most x-ray film findings are normal after SI; initial CXR is only 8% sensitive for SI.

• Findings may include atelectasis, pulmonary edema, and acute respiratory distress syndrome (ARDS).

• Insensitivity of the CXR and lack of reliability of clinical signs of inhalation injury may necessitate use of other diagnostic techniques.

• Xenon ventilation-perfusion scan

• As even bronchoscopic examination may fail to detect injury caused by inhalation of fine particulate aerosol material that may reach terminal bronchioles, consider xenon ventilation-perfusion scans in any patient suspected of having an inhalation injury even if bronchoscopic examination has been negative. This is because bronchoscopy does not evaluate the lower airways and, although 90% of particles measuring 5-10 microns in diameter impact in the upper airways, those measuring 0.5-3 microns reach the terminal bronchioles. In fact, particles this size may escape some filtration devices worn by firefighters.

• Unequal lung field radiation density and/or retention of the radiolabeled gas in the lung field for longer than 90 seconds constitutes a positive scan.

• Although the accuracy is reported as 87%, xenon ventilation-perfusion scan lacks specificity in patients with preexisting pulmonary disease.

• This test may be more appropriate for use in a burn unit or intensive care unit rather than the ED.

• Single-photon emission computed tomography

• In patients with severe CO toxicity, the most common neuropathologic finding on single-photon emission computed tomography (SPECT) in acute and delayed CO encephalopathy is ischemia and necrosis of the basal ganglion.

• This finding is highly specific for CO insult unlike focal cortical hypoperfusion, which is nonspecific.

• Besides this increase in specificity, SPECT is also more sensitive than CT in detecting CO brain injury.

Other Tests:

• Perform electrocardiogram (ECG) in any patient presenting with SI. Potential for decreased oxygen delivery from asphyxiation, dyshemoglobinemia, and cessation of electron transport system can result in myocardial ischemia.

• Pulmonary function test results are abnormal soon after inhalation injuries.

• In atelectasis, consolidation, and ARDS, vital capacity, pulmonary compliance, and functional residual capacity are reduced.

• In patients with bronchospasm, forced expiratory volume in 1 second (FEV₁), peak flow, and midexpiratory flow rates are reduced.

• Diagnostic accuracy is 91%.

Procedures:

• Bronchoscopy can be diagnostic as well as therapeutic, particularly when lobar atelectasis is present.

• This procedure examines the airways from the oropharynx to the lobar bronchi.

• Although it may be performed in the ED, the burn unit may be a more appropriate setting, especially in patients who are intubated.

• Erythema, charring, deposition of soot, edema, and/or mucosal ulceration may be present.

• Impending airway obstruction may be inferred and intubation may be facilitated by this technique.

• Diagnostic accuracy is reported to be 86%.

• A recent study found a 96% correlation between bronchoscopic findings and the triad of closed-space smoke exposure, HbCO levels of 10% or greater, and carbonaceous sputum.

• Another study reports that serial bronchoscopy was twice as sensitive for diagnosing inhalation injury as clinical findings alone.

	TREATMENT	Section 6 of 10
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Prehospital Care:

• Deliver high-flow oxygen by mask.

• If respiratory failure is present, the patient should have assisted ventilation and/or endotracheal intubation.

• Perform cricothyrotomy if airway obstruction is present or impending and an airway cannot be secured orally.

• Secure IV access, but do not delay transport of patient to the hospital in any way.

• In a consecutive case series of 18 patients, cardiac arrest complicating CO toxicity was uniformly fatal, despite administration of hyperbaric oxygen (HBO) therapy after the initial resuscitation. The prognosis of this condition should be considered when making triage decisions for these patients.

Emergency Department Care:

• Presently, no specific treatment exists to ameliorate the tissue damage and reduce the vulnerability to infection induced by SI. Once the CO toxicity, CN toxicity, and methemoglobinemia have been corrected, subsequent treatment is predominantly supportive.

• High-flow humidified oxygen is critical to reverse or prevent hypoxia and assist displacement of CO from Hb.

• The most urgent concern in patients relates to the patency of the upper airway and adequacy of ventilation.
  • About 50% of patients with an inhalation injury require endotracheal intubation. The proportion of patients requiring this procedure is higher for those who also have a burn injury: 62% with a burn versus 12% without a thermal injury.

  • It is of vital importance that the magnitude of the swelling in the areas of the face and mandible be closely scrutinized when making decisions about the need for an artificial airway. Threshold for intubation should be lower than in other patients due to rapid development of airway edema. Delays create the possibility that critical airway compromise may be unrecognized or develop quickly, making endotracheal intubation technically impossible.

• If systemic paralysis is necessary, succinylcholine can be used safely in the immediate postburn phase and up to several days out. Inflate tube cuff to minimal levels, even allowing a small leak, in order to prevent iatrogenic tracheal damage in patients with an already compromised tracheal mucosa.

• Studies have shown that positive pressure ventilation with positive end-expiratory pressure (PEEP) initiated immediately after the inhalation injury significantly increases short-term survival and is associated with decreased tracheobronchial cast formation. The mechanism by which PEEP works may be from "splinting" the alveoli and preventing bronchial cast formation and protein-rich fluid from entrapping the airway.

• Other recent studies have shown that high-frequency ventilation also decreases mortality and the incidence of pneumonia and barotrauma. This modality generates pulsatile flow at up to 600 cycles per minute, which entrains the humidified gas by effect on molecular diffusion. Clearance of airway secretions may improve, and continued patency of the lower airways may be allowed. While not as commonly used in the ED, many burn centers consider this standard therapy.

• Administer IV fluids to assure euvolia and adequate perfusion. Use formulas (eg, Parkland) to calculate fluid resuscitation if severe burns are present.

• Assume elevated levels of HbCO in all fire victims.
  • The half-life of CO is 320 minutes on room air, 90 minutes on 100% oxygen, and 23 minutes in a hyperbaric chamber at 3 atmospheres absolute (ATA). Elimination of CO depends primarily on the law of mass action, so alveolar PO₂, rather than alveolar ventilation, is the critical factor in its removal.

  • A recent study has shown that the half-life in the clinical setting, as opposed to an experimental laboratory setting, is approximately 75 minutes breathing 100% oxygen via a nonrebreather face mask or endotracheal tube. This same study also points out that the half-life, while very much dependent upon the PaO₂, is not dependent upon gender, age, history of loss of consciousness, concurrent tobacco smoking, degree of initial metabolic acidosis or initial CO level.

  • CO is not only responsible for most prehospital deaths in SI, it is the leading cause of injury/death due to poisons in general worldwide.

• The main reason for use of HBO therapy is to prevent delayed neurological sequelae.
  • Literature suggests that hypoxic encephalopathy secondary to CO poisoning results from a reperfusion injury in which the products of lipid peroxidation and free radical formation contribute to morbidity and mortality. In addition, improvement in mitochondrial oxidative metabolism, impairment of adherence of neutrophils to cerebral vasculature (decreases inflammation), and preservation of adenosine triphosphate activity was shown with HBO therapy. This partially explains why HbCO levels are poor indicators of the severity of intoxication and why patients with significant toxicity may have low levels. In fact, at the time of the initial HBO treatment, patients enrolled in most studies have normal or near-normal COHb levels.

  • In a recent landmark study, Weaver has recently shown in a prospective, double blind manner that in patients with symptomatic acute CO poisoning, 3 HBO treatments, in comparison to normobaric oxygen therapy, decrease the incidence of cognitive sequelae by 46% at 6 weeks. Furthermore, a benefit continued to be seen at 12-month follow-up. Essentially, for every 6 patients treated with HBO, one case of delayed neurologic sequelae could be avoided. The study had to be stopped before its completion because of the evidence.

  • Neurologic abnormalities and a history of loss of consciousness are the primary clinical features used to define severe CO toxicity. HBO use is indicated in any of these patients as well as those with a base excess lower than -2 mmol/L, a CO level greater than 25% (or >15% in pregnancy), signs of cerebellar dysfunction, cardiovascular dysfunction, pulmonary edema, and in the extremes of age.

• Management of CN toxicity involves creation of an alternate binding site for CN to compete with cytochrome oxidase and also to provide substrate necessary to convert CN to a nontoxic metabolite.
  • The CN antidote kit contains amyl and sodium nitrite to create a methemoglobin level of 3% and 20-30%, respectively, which, in turn, has a higher affinity for CN than for cytochrome a₃. Also included is sodium thiosulfate, which provides substrate for the enzyme rhodanese, which combines thiosulfate and CN to form a nontoxic compound, thiocyanate, which is excreted renally.

  • Induction of methemoglobinemia is theoretically dangerous in the setting of HbCO, and the clinician should consider withholding the nitrite portion of the kit. In one prospective study in which the CN antidote kit was administered to patients requiring intubation, all but one patient, who died of anoxic encephalopathy on the sixth day, had good recovery. This paper, although a small series, may indicate the ability to give the CN antidote kit in its entirely without obvious adverse sequelae. Authors also noted that methemoglobin levels peaked at 50 minutes, by which time the CO level should already be falling in patients treated with HBO. Sodium thiosulfate remains the definitive treatment. A definite statement on the use of nitrites in SI currently cannot be made.

• Methemoglobinemia in SI is relatively rare and rarely requires treatment with methylene blue. This antidote is reduced by the nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase enzyme and in return reduces methemoglobin to normal hemoglobin. Indications for treatment are a change in mental status, acidosis, ECG changes, and ischemic chest pain. Levels lower than 30% may not require treatment, depending on the patient's cardiorespiratory reserve.

• A small subset of patients manifests bronchospasm and may benefit from the use of bronchodilators, although this is not well documented. This is especially true of patients with underlying COPD or asthma.

• Although the pathophysiology of SI involves irritants setting off the inflammatory response, no benefit has been shown with corticosteroid therapy. In fact, many studies report an increased rate of pulmonary infection.

• Inhalation injuries clearly predispose the airways to infection after several days because of cellular injury, reduction of mucociliary clearance, and poor macrophage function. Despite this, prophylaxis with parenteral antibiotics has not shown any benefit. Acute bacterial colonization and invasion peaks at 2-3 days after SI injury. Consider cultures and possible treatment at this time.

• Recent studies on experimental induction of SI confirm the presence of an acute surfactant deficiency. Instillation of artificial surfactant shortly after injury was beneficial. Larger studies are needed before instituting such therapy.

• Since oxidants are released during the inflammatory cascade and are potentiated via the release of free iron stores, studies have shown that aerosolized deferoxamine, an effective iron chelator, may prevent the injury process. More studies are needed before this modality is used. Also, oxidant injury eventually leads to cast formation of cellular debris in the airways, thus contributing to pulmonary failure. A recent pediatric study has shown that aerosolized heparin/N-acetylcysteine decreases the incidence of atelectasis, reintubation rates, and overall mortality.

	MISCELLANEOUS	Section 9 of 10
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Medical/Legal Pitfalls:

• As SI can lead to serious morbidity and mortality, make every effort to diagnose and treat this condition. Avoid the following potential errors in treating SI:

• Beware that patients may appear asymptomatic on arrival but may develop significant signs and symptoms as long as 36 hours after exposure, especially in fires that produce small particles with low water solubility.

• Avoid relying on the HbCO level obtained in the ED. This level does not correlate with tissue hypoxia or long-term neurological sequelae. Ideally, an HbCO level at the scene would be most valuable.

• Be aware of pertinent historical risk factors in treating patients with potential SI injury. These include closed-space fires, carbonaceous sputum, elevated CO levels, and central facial burns.

• While the mortality rate of isolated SI injury is lower than 10%, the coexistence of a burn injury may almost quadruple this mortality rate.

• A significant amount of patients may present with a paucity of upper airway signs or symptoms but still may have serious subglottic injury. The threshold for performing diagnostic bronchoscopy should be low.