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FIRE HAZARDS (TOXIC PRODUCTS OF COMBUSTION)

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) DEFINITION: A toxic product of combustion is any substance which exerts deleterious effects upon the individual and is evolved during the pyrolysis or combustion of seemingly innocuous or inert materials.
    B) BASIC PRODUCTS OF COMBUSTION
    1) Toxic products of combustion are an insidious hazard and clinically elusive. Fire hazards are made up of various components such as smoke, heat and flame, all of which play a role.
    2) FLAME: Visible, luminous gas.
    3) HEAT
    a) 200 degrees C may be lethal in 5 minutes.
    b) 350 to 500 degrees C may produce tracheitis. Burns of the nasal passages and oropharyngeal mucosa are often seen but thermal burns below the vocal cords are seen in under 5% of patients with surface burns (Phillips et al, 1963; Pruitt et al, 1975).
    c) Steam inhalation is more likely to produce lower airway passage burns (Moritz et al, 1945; Stone et al, 1973; Fineberg et al, 1954).
    d) Heat sufficient to harm the lungs is often sufficient to cause fatal obstructive glottal edema (Watanabe & Makino, 1985).
    4) SMOKE
    a) Particulate Fraction
    1) THE CLINICAL RELEVANCE is that smoke may obscure vision or be irritating.
    2) CARBON PARTICLES
    a) Though biological effects are imprecisely defined, at concentrations of 1000 mg/m(2) immediate respiratory distress may be seen due to simple mechanical irritation. Carbon particles may enhance toxic gas uptake by adsorption (Dyer & Esch, 1976; Pasternak et al, 1982).
    b) Inhalation of carbon dust may increase airway resistance (Widdicombe et al, 1962).
    3) COATINGS
    a) ACROLEIN: Highly irritating, life-threatening concentrations may be produced.
    b) ACIDS
    c) ALDEHYDES
    4) PARTICLE SIZE: Those particles larger than 5 microns are usually deposited in the upper airway, those in the 1 to 5 micron range in the tracheobronchial tree and those under 1 micron in the alveolar spaces (Prien & Traber, 1988a).
    b) GASES
    1) CARBON MONOXIDE: Most common and serious hazard. In concentrations of 0.5 to 1% it may be lethal in 5 minutes.
    a) Carbon monoxide did not appear to be the primary etiologic agent of smoke inhalation injury in a sheep model (Shimazu et al, 1990).
    2) CARBON DIOXIDE: No acute hazard (elevates respiratory rate). A 2% increase will elevate respiratory rate 50%, 3% increases it by 100%.
    3) In a study by Treitman et al (1980) gases were sampled in 200 structural fires. They concluded that in comparison with known concentrations, NO2, HCl, HCN and benzene represented no acute hazard.
    4) FACTORS EFFECTING TOXIC GAS PRODUCTION
    a) Oxygen supply
    b) Temperature
    c) Rate of heating
    d) Material
    5) TARGET ORGANS
    a) Skin
    b) Mucus membranes
    c) Small airways (bronchospasm)
    d) Upper airway (laryngeal and supraglottic edema)

Specific Substances

    1) Varies
    2) COMBUSTION PRODUCTS
    3) PRODUCTS OF COMBUSTION
    4) TOXIC COMBUSTION PRODUCTS
    5) TOXIC PRODUCTS OF COMBUSTION

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) SOURCES: Includes a variety of compounds that can be generated in a fire, including: Soot, smoke, acetic acid, acrolein, aldehydes, ammonia, carbon dioxide, carbon monoxide, formaldehyde, formic acid, hydrogen chloride, hydrogen cyanide, hydrogen fluoride, methane, nitrogen oxides, phosgene.
    B) TOXICOLOGY: Products of combustion include eye and respiratory irritants, simple asphyxiants (displace oxygen), and cellular asphyxiants (interfere with oxygen delivery to or use by cells).
    C) PRESENTATION: The spectrum of presentation may range from a nonproductive cough with eye irritation, behavioral dysfunction, confusion, anxiety, compromised judgment, physical impairment of mobility, lacrimation, respiratory distress and hypoxia, narcosis to coma, burns, and trauma. Symptoms seen are often combined effects of irritants and asphyxiants.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Headache, dizziness, nausea, vomiting, confusion or anxiety, eye irritation, cough, dyspnea, chest pain with vital signs may be normal in a mildly toxic patient, but tachycardia, hypotension and tachypnea most will likely be present in a moderately toxic patient.
    2) SEVERE TOXICITY: VITAL SIGNS: tachycardia, tachypnea, hypotension, hypothermia or hyperthermia. CNS: Altered level of consciousness, hallucinations, seizures, CV: myocardia ischemia/infarction, dysrhythmias , significant cardiovascular compromise, hypovolemia. RESPIRATORY: singed nasal hairs, soot-stained upper airway, stridor, hoarseness, cough, carbonaceous sputum, tachypnea, dyspnea, cyanosis, wheezing, rales, rib fractures, pneumothorax, upper airway burns, neck pain, and sore throat. MUSCULOSKELETAL: Skull fractures, long bone fractures or cervical fractures may be present. DERMATOLOGIC: Examine for depth, extent, and location of burns. HEENT: Eye irritation is predominant, corneal or thermal burns may be present.
    0.2.4) HEENT
    A) Chemical burns may be seen, particularly with HCl. Thermal burns are also possible(Woodson, 2009).
    0.2.6) RESPIRATORY
    A) Thermal and chemical injury may result in edema or stricture sufficient for airway obstruction of the upper airway. The lower airway is protected from thermal burns, but may experience chemical injury due to inhaled inhalants.
    0.2.7) NEUROLOGIC
    A) Neurologic symptoms may occur due to chemical insult or the effects of hypoxemia(Woodson, 2009).
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, or abdominal pain may occur.
    0.2.13) HEMATOLOGIC
    A) Specific chemicals may cause a multitude of hematologic problems in fires. Specific toxic effects are difficult to predict.
    0.2.14) DERMATOLOGIC
    A) Both thermal and chemical skin burns may be present.
    0.2.22) OTHER
    A) WITH POISONING/EXPOSURE
    1) CYANIDE POISONING
    a) Cyanide poisoning can be the primary cause of death from smoke inhalation, even in patients with minor symptoms. Cyanide poisoning has been attributed to approximately 33% to 90% of deaths from smoke inhalation and appears to occur as commonly as carbon monoxide poisoning. Cyanide gas can be created during the combustion of various materials, including mattresses made with polyurethane. Physical signs (not always present) in cyanide poisoning include normal to pink skin color, bright red retinal veins and arteries, and bitter almond breath. The risk of cyanide poisoning from smoke inhalation is increased when the victim was exposed to fire smoke in a closed space, has soot in the mouth and or nose, and has altered mental status. Symptoms of cyanide poisoning can occur in early and advanced stages, as described below (Eckstein & Maniscalco, 2006):
    1) EARLY CYANIDE POISONING
    a) Patients with early cyanide poisoning experience giddiness, headache, vertigo, confusion, a drunken behavior, and shortness of breath (Eckstein & Maniscalco, 2006).
    2) ADVANCED CYANIDE POISONING
    a) Patients with late cyanide poisoning experience nausea/vomiting, hypotension, generalized seizures, coma, cardiac arrhythmias, asystole, apnea, and noncardiac pulmonary edema(Eckstein & Maniscalco, 2006).

Laboratory Monitoring

    A) Obtain arterial blood gases, carboxyhemoglobin, methemoglobin and a chest radiographic immediately upon arrival.
    B) Monitor vital signs, ABGs, CBC, electrolytes, serum lactate, methemoglobin levels, pulmonary function tests, mental status and perform a Mini-Mental State Exam.
    C) Preform a slit lamp exam of the eyes and indirect laryngoscopy and as necessary.
    D) Consider a head CT and obtain an ethanol level and toxicological screen in comatose patients.
    E) Cyanide levels can be measured to confirm exposure is suspected cases, but are usually not available in a timely manner to be clinically useful and treatment with antidote should not be delayed until exposure confirmation.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) The primary route of exposure is by inhalation, therefore gastrointestinal decontamination is not recommended.
    0.4.3) INHALATION EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Administer 100% humidified high-flow oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta adrenergic agonists if bronchospasm develops. Exposed skin and eyes should be flushed with copious amounts of water. Patients exposed to closed-space smoke with laboratory or clinical evidence consistent with cyanide poisoning should be treated for cyanide exposure without waiting for laboratory confirmation. Establish intravenous access immediately.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) In addition to oxygen supplementation, patients who are comatose or patients with smoke inhalation injuries may need mechanical respiratory support. Standard treatment protocols for hypotension and cardiac dysrhythmias should be followed. Fluid resuscitation of associated burn injuries should be vigorous as fluid requirements of patients with burns and associated inhalation injury are increased. Use bronchodilators (ie, albuterol, ipratropium) for bronchospasm. For close-spaced smoke exposure, cyanide poisoning should be assumed; consider cyanide antidote or hyperbaric oxygen therapy. Standard ACLS or PALS therapy should be provided to manage symptoms.
    C) EVALUATION
    1) Patient should first have a general evaluation with special attention to the amount, location of soot, unusual odors, obvious trauma, burns, life-threatening airway obstruction, or hemodynamic compromise. This should be followed by a target organ system evaluation involving the eyes, heart, respiratory system, skin, temperature regulation and CNS status. EXPOSURE SETTING: An evaluation of the exposure setting may help the physician determine the amount and type of toxic substances to which the victim has been exposed. Factors of potential importance include open vs closed space, estimated length of exposure, presence or absence of steam, explosion, nature of burning material and packaging, status of other victims and the amount, color, and odor of smoke. Considered most important is the presence of a closed-space accident with the presence of heavy smoke and a victim who is found unconscious. Delayed poisoning with cyanide gas can also occur. PAST MEDICAL HISTORY: Past medical history of significance would include cardiac or cerebral vascular disease, chronic obstructive pulmonary disease, occupational exposures, chronic illnesses, depression or suicidal ideation, and alcohol or drug abuse, any physical or mental impairment.
    D) DECONTAMINATION
    1) PREHOSPITAL: Remove victim from environment, secure airway, ventilate, establish IV access, monitor cardiac rhythm, splint fractures, and dress lacerations.
    2) HOSPITAL: Evaluate and assess airway patency, ventilate, establish IV access, monitor cardiac rhythm, treat pulmonary edema, commence burn care, splint fractures, and dress lacerations. Consider physiologic antagonist, notify regional poison center, identify all trauma, stabilize, identify candidates as to admission. Asymptomatic patients with a high probability of significant exposure should be admitted/observed for 24 hours.
    E) AIRWAY MANAGEMENT
    1) Manage airway aggressively. Direct evaluation of the upper airway may be necessary to assess upper airway patency and to evaluate the degree of inhalation injury. Intubate any patient with evidence of upper airway injury, significant stridor, respiratory distress, or in patients undergoing aggressive fluid management secondary to dermal burns. Be prepared to perform a cricothyrotomy or tracheostomy as intubation may be difficult secondary to edema.
    F) BRONCHOSPASM
    1) Use oxygen and albuterol 0.15 mg/kg (maximum 10 mg) in saline with humidified oxygen via nebulizer every 20 to 30 minutes until peak expiratory flow rate is above 90% of predicted.
    G) ACUTE LUNG INJURY
    1) Treatment of progressive respiratory failure should include: maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed. Corticosteroids may be useful in victims of smoke inhalation to limit inflammation.
    H) TOXIC EFFECT OF CYANIDE
    1) Combustion of many plastics produces cyanide gas. Poisoning must be treated presumptively before confirmation is available in patients with signs and symptoms of cyanide poisoning. Suspect in presence of coma, severe metabolic acidosis, severe cardiac dysrhythmias without significant hypoxia. Initial treat with 100% oxygen therapy, followed by administration of hydroxocobalamin (preferred) or cyanide antidote kit. If cyanide toxicity develops concurrent with carbon monoxide poisoning (eg, closed space fire), hydroxocobalamin is the preferred antidote. If that is not available, sodium thiosulfate may be used alone. Use of sodium nitrite will cause methemoglobinemia, further reducing oxygen carrying capacity. HYDROXOCOBALAMIN: ADULT: Administer 5 g IV over 15 minutes. A second dose may be given (infused over 15 to 120 minutes) in patients with severe toxicity. PEDIATRIC: A dose of 70 mg/kg has been used. Hydroxocobalamin forms cyanocobalamin which is a nontoxic, water soluble metabolite that is eliminated in the urine. It is generally safer and easier to use than other antidotes (i.e., nitrite and thiosulfate kits). Sodium thiosulfate may also be administered with hydroxocobalamin, but it is not part of the kit. ADVERSE EFFECTS: Flushing is common. Hydroxocobalamin is bright red and causes discoloration of the skin, urine, and serum. It can also interfere with many colorimetric based tests. Cyanide Antidote Kit (Nitrites and Thiosulfate): This kit consists of sodium nitrite and sodium thiosulfate. Use sodium nitrite with caution if carbon monoxide poisoning is also suspected. SODIUM NITRITE: ADULT: Administer 300 mg (10 mL of 3% solution) IV at a rate of 2.5 to 5 mL/minute; PEDIATRIC (with normal hemoglobin concentration): 0.2 mL/kg of a 3% solution (6 mg/kg) IV at a rate of 2.5 to 5 mL/minute. The dose may be lowered if the patient is severely anemic, but administration should not be delayed for laboratory results. Blood methemoglobin levels should be monitored for 30 to 60 minutes following the infusion to prevent severe toxicity. If methemoglobin concentration is greater than 30% it should likely be reversed with methylene blue. Nitrites may also cause vasodilatory effects which may contribute to hypotension. A second dose, on-half of the first dose, may be administered 30 minutes later if there is inadequate clinical response. Use with caution if carbon monoxide poisoning is also suspected. SODIUM THIOSULFATE: Follow sodium nitrite with IV sodium thiosulfate. ADULT: Administer 12.5 g (50 mL of a 25% solution) IV; PEDIATRIC: 1 mL/kg of a 25% solution (250 mg/kg), not to exceed 50 mL (12.5 g) total dose. A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear. This agent enhances conversion of cyanide to thiocyanate which is eliminated in the urine. Patients with renal failure may need dialysis to eliminate thiocyanate. ALTERNATE ANTIDOTES: Kelocyanor(R) (dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are among the cyanide antidotes in clinical use outside the US
    I) ANTIDOTE
    1) HYDROGEN CYANIDE: A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to symptomatic patients. If cyanide toxicity develops concurrent with carbon monoxide poisoning (eg, closed space fire), hydroxocobalamin is the preferred antidote. If that is not available, sodium thiosulfate may be used alone. Use of sodium nitrite will cause methemoglobinemia, further reducing oxygen carrying capacity.
    2) CARBON MONOXIDE: Administer 100% oxygen to the patient via nonrebreather and continued until the patient is asymptomatic and carboxyhemoglobin levels are below 5% for patients with carbon monoxide exposure. Pregnant women need to be treated for a longer time since CO elimination may be slower in the fetus. Some evidence supports the use of hyperbaric oxygen to prevent delayed cognitive and neurologic sequelae; however, there is controversy around the use of hyperbaric therapy. In general, the risks of hyperbaric oxygen treatment (which include seizures and barotrauma) are low. In complex cases, a poison center or hyperbaric center should be contacted.
    J) METHEMOGLOBINEMIA
    1) Initiate oxygen therapy. Treat with methylene blue if patient is symptomatic (usually at methemoglobin concentrations greater than 20% to 30% or at lower concentrations in patients with anemia, underlying pulmonary or cardiovascular disease). METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
    K) HYPERBARIC OXYGEN THERAPY
    1) Consider the use of hyperbaric oxygen, especially in those cases where carbon monoxide and hydrogen cyanide are thought to be present. Recommended for patients who are unconscious, or symptomatic, have a markedly elevated carboxyhemoglobin or who are pregnant and have an elevated carboxyhemoglobin level of greater than 15%.
    L) HYPOTENSION
    1) Treat hypotension with aggressive fluid resuscitation.
    M) BURN INJURY
    1) Treat burns prophylactically for infection. Once irrigation is completed, standard burn therapy should be instituted including tetanus prophylaxis, dressings, and careful follow-up to observe for complications and infection.
    N) ENHANCED ELIMINATION
    1) Oxygen increases the elimination of CO. Cyanide antidotes increase the elimination of cyanide.
    O) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients with brief exposures to small fires may be observed at home.
    2) OBSERVATION CRITERIA: Suspected cyanide exposures and/or history of high or prolonged exposures must be evaluated in a healthcare facility. Mildly to moderately symptomatic patients should be sent to a healthcare facility for evaluation and should be observed for 6 hours after exposure.
    3) ADMISSION CRITERIA: Asymptomatic patients with high-risk exposure (ie, fascial/nasal burns, confined space exposure, elevated carboxyhemoglobin or age over 40) should be observed for 24 hours.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for cyanide or carbon monoxide treatment.
    5) PATIENT TRANSFER CRITERIA: Patients with the following symptoms should be referred to a facility with a hyperbaric oxygen chamber, regardless of time of exposure: coma at any point during exposure, syncope, seizures, focal neurologic signs, severe metabolic acidosis (pH less than 7.25), or cardiovascular manifestations (ie, hypotension, shock, angina, ECG evidence of ischemia).
    P) PITFALLS
    1) When managing a patient for smoke inhalation, consider other sources of trauma outside of thermal injury. Inhalation injuries are a dynamic process and patients with minor symptoms may be at a high risk of rapid deterioration several hours after exposure. Treatment should not be delayed for laboratory results, if a cyanide exposure is strongly suspected. If cyanide toxicity develops concurrent with carbon monoxide poisoning (eg, closed space fire), hydroxocobalamin is the preferred antidote. If that is not available, sodium thiosulfate may be used alone. Use of sodium nitrite will cause methemoglobinemia, further reducing oxygen carrying capacity.
    Q) DIFFERENTIAL DIAGNOSIS
    1) Includes other causes of pulmonary compromise, such as trauma from falls or explosions. Ethanol or drug intoxication or traumatic brain injury should also be considered in comatose patients.

Clinical Effects

Summary Of Exposure

    A) SOURCES: Includes a variety of compounds that can be generated in a fire, including: Soot, smoke, acetic acid, acrolein, aldehydes, ammonia, carbon dioxide, carbon monoxide, formaldehyde, formic acid, hydrogen chloride, hydrogen cyanide, hydrogen fluoride, methane, nitrogen oxides, phosgene.
    B) TOXICOLOGY: Products of combustion include eye and respiratory irritants, simple asphyxiants (displace oxygen), and cellular asphyxiants (interfere with oxygen delivery to or use by cells).
    C) PRESENTATION: The spectrum of presentation may range from a nonproductive cough with eye irritation, behavioral dysfunction, confusion, anxiety, compromised judgment, physical impairment of mobility, lacrimation, respiratory distress and hypoxia, narcosis to coma, burns, and trauma. Symptoms seen are often combined effects of irritants and asphyxiants.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Headache, dizziness, nausea, vomiting, confusion or anxiety, eye irritation, cough, dyspnea, chest pain with vital signs may be normal in a mildly toxic patient, but tachycardia, hypotension and tachypnea most will likely be present in a moderately toxic patient.
    2) SEVERE TOXICITY: VITAL SIGNS: tachycardia, tachypnea, hypotension, hypothermia or hyperthermia. CNS: Altered level of consciousness, hallucinations, seizures, CV: myocardia ischemia/infarction, dysrhythmias , significant cardiovascular compromise, hypovolemia. RESPIRATORY: singed nasal hairs, soot-stained upper airway, stridor, hoarseness, cough, carbonaceous sputum, tachypnea, dyspnea, cyanosis, wheezing, rales, rib fractures, pneumothorax, upper airway burns, neck pain, and sore throat. MUSCULOSKELETAL: Skull fractures, long bone fractures or cervical fractures may be present. DERMATOLOGIC: Examine for depth, extent, and location of burns. HEENT: Eye irritation is predominant, corneal or thermal burns may be present.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Either hypo- or hyperthermia may be present. Vital signs may be normal in a mildly toxic patient, but tachycardia, hypotension, and tachypnea will most likely be present in a moderately toxic patient (Benner et al, 2009).

Heent

    3.4.1) SUMMARY
    A) Chemical burns may be seen, particularly with HCl. Thermal burns are also possible(Woodson, 2009).
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) Chemical burns may be seen, particularly with HCl. Thermal burns are also possible(Woodson, 2009).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH POISONING/EXPOSURE
    a) Cardiovascular damage may occur due to hypoxemia or chemical insult(Eckstein & Maniscalco, 2006).

Respiratory

    3.6.1) SUMMARY
    A) Thermal and chemical injury may result in edema or stricture sufficient for airway obstruction of the upper airway. The lower airway is protected from thermal burns, but may experience chemical injury due to inhaled inhalants.
    3.6.2) CLINICAL EFFECTS
    A) INJURY OF UPPER RESPIRATORY TRACT
    1) WITH POISONING/EXPOSURE
    a) Thermal and chemical injury results in edema of structures sufficient for airway obstruction(Woodson, 2009).
    B) INJURY OF RESPIRATORY SYSTEM
    1) WITH POISONING/EXPOSURE
    a) The lower airway is protected from thermal burns due to heat exchange efficiency of upper airway, with the exception of steam exposure (4000 times the heat capacity of air).
    b) Chemical injury due to inhaled irritants may produce tracheitis, bronchitis, ciliary paralysis, and bronchorrhea. Narrowing of the air passages occurs secondary to bronchospasm, edema, and debris(Woodson, 2009).
    C) PNEUMONITIS
    1) WITH POISONING/EXPOSURE
    a) LUNG PARENCHYMA: Chemically induced pneumonitis with increased capillary permeability may be seen. There may be decreased lung surfactant leading to an ARDS-type pulmonary edema. Bacterial pneumonia may supervene.
    D) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Asthma and asthma-like symptoms may be seen from pyrolysis products (ie, polyvinyl chloride) (Moisan, 1991).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) OXIDATION
    a) LUNG LIPID PEROXIDATION: Sheep were prepared with a 15% total body surface third-degree burn, including lungs, and were administered smoke inhalation. The combination of burn and smoke inhalation caused an increased lung lipid peroxidation, which indicates further lung oxidant activity (Lalonde et al, 1992).

Neurologic

    3.7.1) SUMMARY
    A) Neurologic symptoms may occur due to chemical insult or the effects of hypoxemia(Woodson, 2009).
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) Neurologic symptoms may occur due to chemical insult or the effects of hypoxemia or hemodynamic insult(Eckstein & Maniscalco, 2006).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, or abdominal pain may occur.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, or abdominal pain may be seen after exposure(Eckstein & Maniscalco, 2006).

Hematologic

    3.13.1) SUMMARY
    A) Specific chemicals may cause a multitude of hematologic problems in fires. Specific toxic effects are difficult to predict.
    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH POISONING/EXPOSURE
    a) SPECIFIC AGENT
    1) Specific chemicals may cause a multitude of problems in fire exposures (ie, benzene). Specific toxic effects are difficult to predict, unless the chemicals involved in the exposures are identified.
    B) BLOOD COAGULATION PATHWAY FINDING
    1) WITH POISONING/EXPOSURE
    a) Smoke inhalation may cause complement activation and start of the coagulation cascade (Fein, 1989).
    C) METHEMOGLOBINEMIA
    1) WITH POISONING/EXPOSURE
    a) Methemoglobinemia has been seen as a result of smoke inhalation (Hoffman & Sauter, 1989; Katsumata et al, 1980).

Dermatologic

    3.14.1) SUMMARY
    A) Both thermal and chemical skin burns may be present.
    3.14.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) WITH POISONING/EXPOSURE
    a) Both thermal and chemical skin burns may be present. Again, the exact amount of dermal irritation will depend upon not only the chemicals involved in the fire, but the amount and type of protection afforded the victims(Woodson, 2009).
    B) EDEMA
    1) WITH POISONING/EXPOSURE
    a) Burn edema appears to be accentuated by a moderate smoke inhalation injury in sheep. Protein-rich burn tissue lymph flow increased greater than tenfold in burn-inhalation injury (Lalonde et al, 1992).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) PATHOLOGICAL FRACTURE
    1) WITH POISONING/EXPOSURE
    a) Trauma at the fire ground may result in various types of fractures.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain arterial blood gases, carboxyhemoglobin, methemoglobin and a chest radiographic immediately upon arrival.
    B) Monitor vital signs, ABGs, CBC, electrolytes, serum lactate, methemoglobin levels, pulmonary function tests, mental status and perform a Mini-Mental State Exam.
    C) Preform a slit lamp exam of the eyes and indirect laryngoscopy and as necessary.
    D) Consider a head CT and obtain an ethanol level and toxicological screen in comatose patients.
    E) Cyanide levels can be measured to confirm exposure is suspected cases, but are usually not available in a timely manner to be clinically useful and treatment with antidote should not be delayed until exposure confirmation.
    4.1.2) SERUM/BLOOD
    A) Monitor lab tests (CBC, electrolytes, glucose, BUN, and creatinine) as clinically indicated.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) The following tests may be of value when evaluating fire exposure victims.
    b) ABG's - Acidosis, hypoxemia - obtain measured oxygen saturation.
    c) CXR - Insensitive indicator of parenchymal damage, patchy infiltrates seen after 24 hours. Pulmonary edema, fractured ribs, pneumothroax, pulmonary contusions should also be noted (Lee & O'Connell, 1988).
    1) Bronchial wall thickening may indicate parenchymal injury. Subglottic edema suggests upper airway injury (Lee & O'Connell, 1988).
    d) CO CONCENTRATION - Significant diminution may occur if patient intubated and received high-flow oxygen. May suggest exposure time and setting.
    e) CN CONCENTRATION - In presence of persistent metabolic acidosis, or with combustion of known material. It has been recommended in cases where carboxyhemoglobin is elevated. Cyanide levels are difficult to correlate with the need for specific therapy.
    1) Shiono et al (1991) found a positive correlation between blood cyanide and carboxyhemoglobin content. The site of sampling at autopsy was important. A higher concentration was detected in left ventricular blood than in the right.
    f) EKG - Arrhythmia and MI recognition.
    g) ETOH Level.
    h) Electrolytes, glucose, BUN, and creatinine.
    i) CAT SCAN - If indicated for head trauma, persistent CNS dysfunction.
    j) Fluorescein and slit lamp exam of the eyes.
    k) Indirect laryngoscopy for evaluation of upper airway burns and as index of exposure (soot staining).
    l) Pulmonary function tests, particularly measuring for airway obstruction.
    m) Xenon 133 lung scan may identify parenchymal and lower airway injury (accuracy of 87% to 92%) (Sataloff & Sataloff, 1984; Lull et al, 1980).
    n) Bronchoscopy for elevation of lower airway damage.
    o) 99mTc DTPA clearance measures alveolar epithelial permeability, providing an indication of alveolar-capillary permeability (Witten et al, 1988).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Asymptomatic patients with high-risk exposure (ie, fascial/nasal burns, confined space exposure, elevated carboxyhemoglobin or age over 40) should be observed for 24 hours.
    6.3.3.2) HOME CRITERIA/INHALATION
    A) Asymptomatic patients with brief exposures to small fires may be observed at home.
    6.3.3.3) CONSULT CRITERIA/INHALATION
    A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for cyanide or carbon monoxide treatment.
    6.3.3.4) PATIENT TRANSFER/INHALATION
    A) Patients with the following symptoms should be referred to a facility with an HBO chamber, regardless of time of exposure: coma at any point during exposure, syncope, seizures, focal neurologic signs, severe metabolic acidosis (pH less than 7.25), or cardiovascular manifestations (ie, hypotension, shock, angina, ECG evidence of ischemia).
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Suspected cyanide exposures and/or history of high or prolonged exposures must be evaluated in a healthcare facility. Mildly to moderately symptomatic patients should be sent to a healthcare facility for evaluation and should be observed for 6 hours after exposure.

Monitoring

    A) Obtain arterial blood gases, carboxyhemoglobin, methemoglobin and a chest radiographic immediately upon arrival.
    B) Monitor vital signs, ABGs, CBC, electrolytes, serum lactate, methemoglobin levels, pulmonary function tests, mental status and perform a Mini-Mental State Exam.
    C) Preform a slit lamp exam of the eyes and indirect laryngoscopy and as necessary.
    D) Consider a head CT and obtain an ethanol level and toxicological screen in comatose patients.
    E) Cyanide levels can be measured to confirm exposure is suspected cases, but are usually not available in a timely manner to be clinically useful and treatment with antidote should not be delayed until exposure confirmation.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) The primary route of exposure is by inhalation, therefore gastrointestinal decontamination is NOT recommended.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) The primary route of exposure is by inhalation, therefore gastrointestinal decontamination is not recommended.
    6.5.3) TREATMENT
    A) SUPPORT
    1) The primary route of exposure is by inhalation.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) MONITORING OF PATIENT
    1) Obtain arterial blood gases, carboxyhemoglobin, methemoglobin and a chest radiographic immediately upon arrival.
    2) Monitor vital signs, ABGs, CBC, electrolytes, serum lactate, methemoglobin levels, pulmonary function tests, and mental status.
    3) Direct evaluation of the upper airway may be necessary to assess upper airway patency and to evaluate the degree of inhalation injury.
    4) Perform a slit lamp exam of the eyes.
    5) Consider a head CT and obtain an ethanol level and toxicological screen in a comatose patient.
    6) Cyanide levels can be measured to confirm exposure in a suspected case, but are usually not available in a timely manner to be clinically useful and treatment with an antidote should not be delayed until exposure confirmation.
    B) OXYGEN
    1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    C) AIRWAY MANAGEMENT
    1) Manage airway aggressively. Direct evaluation of the upper airway may be necessary to assess upper airway patency and to evaluate the degree of inhalation injury. Intubate any patient with evidence of upper airway injury, significant stridor, respiratory distress, or in patients undergoing aggressive fluid management secondary to dermal burns. Be prepared to perform a cricothyrotomy or tracheostomy as intubation may be difficult secondary to edema.
    D) BRONCHOSPASM
    1) BRONCHOSPASM SUMMARY
    a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.
    2) ALBUTEROL/ADULT DOSE
    a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    3) ALBUTEROL/PEDIATRIC DOSE
    a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).
    4) ALBUTEROL/CAUTIONS
    a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.
    5) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).
    E) ACUTE LUNG INJURY
    1) Progressive lung injury may develop. Corticosteroids may be useful in victims of smoke inhalation to limit inflammation.
    2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    3) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    4) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    7) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    8) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    F) CYANIDE ANTIDOTE
    1) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to symptomatic patients (ie, impaired consciousness, convulsions, acidosis, or unstable vital signs). OBTAIN AND PREPARE for administration a CYANOKIT OR CYANIDE ANTIDOTE KIT.
    a) In patients with carbon monoxide poisoning in addition suspected cyanide poisoning, only the sodium thiosulfate portion of the US cyanide antidote kit should be used. Use of the sodium nitrite portion of the kit will induce methemoglobinemia that will further impair tissue oxygen delivery.
    2) HYDROXOCOBALAMIN
    a) ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
    b) PEDIATRIC DOSE: A dose of 70 mg/kg has been used in pediatric patients, based on limited post-marketing experience outside the US (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
    c) INDICATIONS: Known or suspected cyanide poisoning.
    d) ADVERSE EFFECTS: Transient hypertension, allergic reactions (including anaphylaxis), nausea, headache, rash. Hydroxocobalamin's deep red color causes red-colored urine in all patients, and erythema of the skin in most (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
    e) LABORATORY INTERFERENCE: Because of its' color, hydroxocobalamin interferes with colorimetric determination of various laboratory parameters. It may artificially increase serum creatinine, bilirubin, triglycerides, cholesterol, total protein, glucose, albumin , alkaline phosphatase and hemoglobin. It may artificially decrease serum ALT and amylase. It may artificially increase urinary pH, glucose, protein, erythrocytes, leukocytes, ketones, bilirubin, urobilinogen, and nitrate (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
    f) HEMODIALYSIS INTERFERENCE: Dialysis machines have a spectrophotometric safety measure that can shut down after detecting blood leaking across the dialysis membrane. Hydroxocobalamin has a deep red color and can permeate the dialysis membrane, coloring the dialysate and causing the hemodialysis machine to shut down erroneously. In one case report, a patient with cyanide poisoning underwent dialysis after receiving 5 g of IV hydroxocobalamin because of refractory acidemia, reduced kidney function and hyperkalemia. A blood leak alarm caused the dialysis machine to shut down erroneously, delaying therapy, and resulting in the death of the patient (Stellpflug et al, 2013).
    g) The initial dose is 5 g given by rapid IV infusion; the usual dose required is 5 to 10 g. Each reconstituted vial of 2.5 g should be given rapidly over 7.5 minutes (15 minutes for the total 5 g). Additional doses, if required, should be administered more slowly, over 30 minutes to 2 hours (Prod Info Cyanokit(R) IV injection, 2011).
    h) Hydroxocobalamin reverses cyanide toxicity by combining with cyanide to form cyanocobalamin (vitamin B12) (Prod Info Cyanokit(R) IV injection, 2011; Hall & Rumack, 1987).
    i) NOTE: Commercially available hydroxocobalamin preparations (1 mg/mL for intramuscular injection) are available in the US and are used for the treatment of cobalamin deficiency (Prod Info hydroxocobalamin intramuscular solution, 2000). It would require FOUR to FIVE LITERS of this preparation for an adequate antidote dose, and therefore this PREPARATION SHOULD NOT BE USED. They are not intended for use in the treatment of cyanide poisoning.
    3) CYANIDE ANTIDOTE KIT
    a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT, consisting of sodium nitrite and sodium thiosulfate.
    1) Antidotes should be used only in significantly symptomatic patients (ie, impaired consciousness, convulsions, acidosis, or unstable vital signs).
    2) Even when patients are rendered comatose by the inhalation of hydrogen cyanide gas, antidotes may not be necessary if the exposure is rapidly terminated, the patient has regained consciousness on arrival at the medical facility, and there is no acidosis or abnormality of the vital signs (Peden et al, 1986).
    4) SODIUM NITRITE
    a) INDICATION
    1) Sodium nitrite should be given initially and administered as soon as vascular access is established.
    2) Further administration of sodium nitrite is dictated only by the clinical situation, provided no significant complications (hypotension, excessive methemoglobinemia) are present. Use with caution if carbon monoxide poisoning is also suspected.
    3) The goal of nitrite therapy is to achieve a methemoglobin level of 20% to 30%. This level is not based on clinical data, but represents the tolerated concentration without significant adverse symptoms from methemoglobin in an otherwise healthy individual. Clinical response has been reported to occur with methemoglobin levels in the range of 3.6% to 9.2% (DiNapoli et al, 1989; Johnson et al, 1989; Johnson & Mellors, 1988).
    b) ADULT DOSE
    1) 10 mL of a 3% solution (300 mg) administered intravenously at a rate of 2.5 to 5 mL/minute (Prod Info NITHIODOTE intravenous injection solution, 2011). Frequent blood pressure monitoring must accompany sodium nitrite injection and the rate slowed if hypotension occurs.
    2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011).
    c) PEDIATRIC DOSE
    1) The recommended pediatric sodium nitrite dose is 0.2 mL/kg of a 3% solution (6 mg/kg) administered intravenously at a rate of 2.5 to 5 mL/minute, not to exceed 10 mL (300 mg) (Prod Info NITHIODOTE intravenous injection solution, 2011).
    2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011; Berlin, 1970a).
    3) PRESENCE OF ANEMIA: If there is a reason to suspect the presence of anemia, the following initial sodium nitrite doses should be given, depending on the child's hemoglobin (sodium nitrite should not exceed the doses listed below; fatal methemoglobinemia may result) (Berlin, 1970a):
    a) Hemoglobin: 8 g/dL - Initial 3% sodium nitrite dose: 0.22 mL/kg (6.6 mg/kg)
    b) Hemoglobin: 10 g/dL - Initial 3% sodium nitrite dose: 0.27 mL/kg (8.7 mg/kg)
    c) Hemoglobin: 12 g/dL (average child) - Initial 3% sodium nitrite dose: 0.33 mL/kg (10 mg/kg)
    d) Hemoglobin: 14 g/dL - Initial 3% sodium nitrite dose: 0.39 mL/kg (11.6 mg/kg)
    d) It is highly recommended that total hemoglobin and methemoglobin concentrations be rapidly measured (30 minutes after dose), when possible, before repeating a dose of sodium nitrite to be sure that dangerous methemoglobinemia will not occur, especially in the pediatric patient.
    e) Monitor blood pressure frequently and treat hypotension by slowing infusion rate and giving crystalloids and vasopressors. Consider possible excessive methemoglobin formation if patient deteriorates during therapy.
    f) Excessive methemoglobinemia and hypotension are potential complications of nitrite therapy.
    g) In individuals with G6PD deficiency, therapy with methemoglobin-inducing agents is contraindicated because of the likelihood of serious hemolysis.
    5) SODIUM THIOSULFATE
    a) Sodium thiosulfate is the second component of the cyanide antidote kit. It is supplied as 50 mL of a 25% solution and it is administered intravenously. There are no adverse reactions to thiosulfate itself. The pediatric dose is adjusted for weight and not hemoglobin concentration.
    b) Sodium thiosulfate supplies sulfur for the rhodanese reaction, and is recommended after sodium nitrite, hydroxocobalamin, or 4-DMAP (4-dimethylaminophenol) administration (Marrs, 1988; Hall & Rumack, 1987).
    c) DOSE
    1) Follow sodium nitrite with IV sodium thiosulfate. ADULT: Administer 50 mL (12.5 g) of a 25% solution IV; PEDIATRIC: 1 mL/kg of a 25% solution (250 mg/kg), not to exceed 50 mL (12.5 g) total dose (Prod Info NITHIODOTE intravenous injection solution, 2011).
    2) A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear (Prod Info NITHIODOTE intravenous injection solution, 2011).
    3) Sodium thiosulfate is usually used in combination with sodium nitrite but may be used alone (Prod Info sodium thiosulfate IV injection, 2003).
    4) Sodium thiosulfate can be administered without sodium nitrite in patients at risk to develop further methemoglobinemia (ie excessive methemoglobinemia or hypotension after initial sodium nitrite administration or in the presence of methemoglobinemia or carboxyhemoglobin in patients with smoke inhalation due to fire). Sodium thiosulfate can also be used in combination with hydroxocobalamin to treat cyanide poisoning (Howland, 2011)
    5) CONTINUOUS INFUSION: It has been suggested that a continuous infusion of sodium thiosulfate be given after the initial bolus to maintain high thiosulfate levels. Low sodium intravenous fluids are required to avoid sodium overload. If large amounts of sodium thiosulfate are required, hemodialysis may be necessary to maintain a physiologic serum sodium level (Turchen et al, 1991).
    6) ADVERSE EVENTS: Sodium thiosulfate does not usually produce significant toxicity. Possible adverse events include hypotension, headache, nausea, vomiting, disorientation, and prolonged bleeding time (Prod Info NITHIODOTE intravenous injection solution, 2011).
    6) DICOBALT EDETATE
    a) Kelocyanor(R) (dicobalt-EDTA) is a highly effective cyanide chelating agent currently used clinically in Europe, Israel, and Australia (Davison, 1969; Hillman et al, 1974). It is not available in the US.
    b) PRECAUTIONS
    1) Significant toxicity from the antidote (severe hypertension or hypotension, cardiac ischemia or arrhythmias) may be seen in patients incorrectly diagnosed as being poisoned with cyanide and administered this antidote (Pronczuk de Garbino & Bismuth, 1981; Tyrer, 1981). Therefore, KELOCYANOR(R) SHOULD NOT BE USED in CASES of MILD CYANIDE POISONING or DIAGNOSTIC UNCERTAINTY (Peden et al, 1986; Tyrer, 1981).
    2) Severe anaphylactoid reactions with periorbital and massive facial edema and airway compromise may also occur (Dodds & McKnight, 1985; Wright & Vesey, 1986).
    3) ADVERSE EFFECTS can include nausea, vomiting, tachycardia, hypotension, hypertension, anaphylactic reactions, facial and neck edema, chest pain, diaphoresis, nervousness, tremulousness, gastrointestinal hemorrhages, convulsions, cardiac irregularities, and rashes (Prod Info, 1986; Prod Info, 1987) (Davison, 1969; Tyrer, 1981; Hillman et al, 1974).
    c) DOSE
    1) ADULTS: One to two 20 mL ampules (300 to 600 mg) injected IV over about 1 to 5 minutes (Beasley & Glass, 1998; Prod Info KELOCYANOR IV solution for injection, 1997; Davison, 1969).
    a) A third 20 mL ampule (300 mg) can be injected IV over about 1 to 5 minutes, 5 minutes after the first 1 to 2 ampules if there is not sufficient clinical improvement (Beasley & Glass, 1998; Prod Info KELOCYANOR IV solution for injection, 1997; Davison, 1969).
    b) Manufacturers recommend following the Kelocyanor(R) injection with IV injection of 50 mL of 50% dextrose in water (Prod Info KELOCYANOR IV solution for injection, 1997).
    c) Kelocyanor(R) can be used with other standard cyanide antidotes (Prod Info, 1978).
    2) CHILDREN: Pediatric doses have not been established by manufacturers. A suggested dose used in Israel for children is 0.5 mL/kg (not to exceed 20 mL) (Personal Communication, Uri Taitelman, MD, 1963).
    d) Kelocyanor(R) is supplied in 20 mL ampules containing 300 mg of dicobalt-EDTA and 4 g of dextrose in water for injection (Prod Info, 1978; Prod Info, 1986; Prod Info, 1987).
    G) HYPERBARIC OXYGEN THERAPY
    1) Carbon Monoxide Poisoning: The need for hyperbaric oxygen (HBO) is more accurately reflected by neurologic and cardiovascular clinical findings than by COHb levels. Recommended for patients who are unconscious, or symptomatic, have a markedly elevated carboxyhemoglobin or who are pregnant and have an elevated carboxyhemoglobin level of grater than 15%.
    a) Patients with the following symptoms should be referred to a facility with an HBO chamber, regardless of time of exposure: coma at any point during exposure, syncope, seizures, focal neurologic signs, severe metabolic acidosis (pH less than 7.25), or cardiovascular manifestations (hypotension, shock, angina, ECG evidence of ischemia) (Myers, 1984; Myers et al, 1981).
    b) The efficacy of hyperbaric oxygen therapy in preventing delayed sequelae after carbon monoxide poisoning is unclear(Weaver et al, 2002; Scheinkestel et al, 1999). Patients with neurologic impairment (abnormal psychometric test results, disorientation, confusion, irritability, aggressive behavior) should be considered for treatment regardless of the COHb level (Werner et al, 1985; Myers, 1984).
    c) Meyer et al (1991) suggest treatment start within 4 hours and consist of 3 ATA for 30 minutes, and then 2.5 ATA for 60 minutes. Additional 1.5 to 2 ATA treatments at 2 to 6 hours may be given if symptoms persist (Meyer et al, 1991).
    d) Three atmospheres of hyperbaric oxygen reduces the CO half-life to 23 minutes.
    H) EXTRACORPOREAL MEMBRANE OXYGENATION
    1) Cases have been reported of children who had respiratory failure secondary to smoke inhalation injury, being discharged to home, breathing room air after requiring extracorporeal membrane oxygenation (ECMO) therapy (Lessin et al, 1996).
    2) Veno-venous ECMO has been successfully used to treat children (O'Toole et al, 1998) and adults (Patton et al, 1998) with inhalation injury refractory to maximum ventilatory support.
    I) HYPOTENSIVE EPISODE
    1) Treat hypotension with aggressive fluid resuscitation. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    J) METHEMOGLOBINEMIA
    1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur in children receiving excessive nitrite doses.
    2) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause the release of cyanide from the cyanmethemoglobin complex. Such authors have suggested that emergency exchange transfusion is the treatment of choice (Berlin, 1970). Hyperbaric oxygen therapy could be used to support the patient while preparations for exchange transfusion are being made.
    3) However, methylene or toluidine blue have been used successfully in this setting without worsening the course of the cyanide poisoning (van Heijst et al, 1987). There is some controversy over whether or not the induction of methemoglobinemia is the sodium nitrite mechanism of action in cyanide poisoning. As long as intensive care monitoring and further antidote doses (if required) are available, methylene blue can most likely be safely administered in this setting.
    4) SUMMARY
    a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
    5) METHYLENE BLUE
    a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
    b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
    c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
    d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).
    6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)
    a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
    b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
    c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.
    K) EXPERIMENTAL THERAPY
    1) NEBULIZED UNFRACTIONATED HEPARIN AND N-ACETYLCYSTEINE
    a) A single-center retrospective study looked at 30 ventilated patients with bronchoscopy confirmed smoke inhalation injury; 14 in the historical control group and 16 in the treatment group. The control group was treated with ventilator support plus albuterol sulfate, and the treatment group received nebulized heparin sulfate, N-acetylcysteine and albuterol sulfate. Data and parameters were collected over the first 7 days of therapy.
    1) Overall, treatment with the combination of heparin and N-acetylcysteine significantly improved pulmonary function (p less than 0.05) by decreasing lung injury scores and respiratory resistance. There was statistically significant survival benefit for the treatment group; mortality was decreased by 38% with a number needed to treat of 2.7 to prevent one death. The survival benefit was most pronounced for patients with APACHE III scores greater than 35.
    a) The authors speculate these results are due to heparin's inhibition of airway fibrin clot formation, mucolysis by N-acetylcysteine, and bronchodilation by albuterol sulfate. A larger, prospective study will need to be completed to confirm these preliminary findings (Miller et al, 2009).
    L) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) BURN INJURY
    1) Treat burns prophylactically for infection.
    2) Once irrigation is completed, standard burn therapy should be instituted including tetanus prophylaxis, dressings, and careful follow-up to observe for complications and infection.
    3) GRAFTS: Skin grafts are often required for severe burns (Husain et al, 1989; Mozingo et al, 1988; Dominic et al, 1987; Sawada & Doi, 1984).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

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