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SYMPTOMATIC CHEMICAL INHALATION

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) This management is intended for use in the absence of a specific treatment protocol for a product or chemical. It should be used when general guidelines maybe needed for patient care. It may also be helpful when an experimental agent has been inhaled and there are no toxicity data available.

Specific Substances

    A) GENERAL TERMS
    1) INHALATION EXPOSURE
    2) INHALATION INJURY
    3) CHEMICAL INHALATION
    4) SYMPTOMATIC CHEMICAL INHALATION INJURY
    5) INHALATION

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) SUMMARY OF COMMON ACUTE EFFECTS -
    1) The most common adverse respiratory system effects resulting from inhalation exposures include one or more of the following: irritation of the mucous membranes of the eyes, nose, and respiratory tract; bronchospasm; metal fume fever; severe pulmonary irritation; chemical pneumonitis; immediate or delayed pulmonary edema; hypoxia or asphyxiation. Some of these conditions can be fatal or may lead to chronic adverse pulmonary effects.
    B) SUMMARY OF COMMON CHRONIC EFFECTS -
    1) Asthma, non-specific airway hyperresponsiveness, bronchitis, emphysema, altered ventilatory capacities in the absence of other significant findings, fibrosis, granuloma formation, bronchiolitis obliterans, and cancer are the most common chronic clinical effects resulting from selected inhalation exposures.
    0.2.22) OTHER
    A) Inhalation exposures can result in adverse systemic effects. Careful history and physical examination may reveal a constellation of signs and symptoms (toxidromes) that suggest exposure to a specific toxin or class of toxins.
    B) Examples of key systemic effects which may result from inhalation exposures include chemical asphyxiation, methemoglobinemia, other hematologic effects, neurological derangements or damage, systemic ocular effects, renal and hepatic injury.

Laboratory Monitoring

    A) Appropriate laboratory evaluation is determined in part by the clinical condition of the patient. Initial history is often inaccurate and many deliberate poisonings involve more than one compound.
    1) Arterial blood gases are useful to assess the degree of hypoxemia. Periodically obtain serum electrolytes to evaluate for metabolic acidosis. Tests of hepatic and renal function, arterial blood gases, pulse oximetry, and chest radiographs should be performed if clinically indicated. A 12-lead electrocardiogram should be performed.
    2) Tests for methemoglobinemia should be performed if clinically indicated. Methemoglobinemia may not develop until several hours (e.g, 1 to 10) after some exposures. Calculated O2 saturation is often inaccurate in cases of methemoglobinemia and carbon monoxide poisoning. Measured O2 saturation should be performed.
    3) ORGANOPHOSPHATE POISONING - Plasma cholinesterase (PChE) and erythrocyte acethylcholinesterase (AChE) activities are the most widely used tests used to initially diagnose.
    4) Pregnancy testing should be considered in women of childbearing potential.
    B) Toxicology screens and drug levels should be performed as indicated by history and clinical signs and symptoms. A variety of tests are available. General toxicology screens rarely provide information that alters the management of the asymptomatic, stable patient.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Refer to "SYMPTOMATIC CHEMICAL INGESTION" management for further information.
    0.4.3) INHALATION EXPOSURE
    A) This management is intended for use in the absence of a specific treatment protocol for a product or chemical when some guidelines may be needed for patient care. It may also be helpful when an experimental agent has been inhaled and there are no data available on its toxicity.
    B) SUMMARY - Treat the patient, not the poison. Symptomatic and supportive care is the mainstay of therapy. In first examining the patient remember to assess life threatening potential. Cardiopulmonary stabilization is mandatory. Decontaminate as necessary. Control seizures, administer oxygen, methylene blue, PEEP, CPAP, hyperbaric oxygen as indicated.
    0.4.4) EYE EXPOSURE
    A) Refer to "SYMPTOMATIC CHEMICAL DERMAL EXPOSURE" management for further information.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Refer to "SYMPTOMATIC CHEMICAL DERMAL EXPOSURE" management for further information.

Range Of Toxicity

    A) The range of toxicity will vary depending upon the specific toxicant or toxicants to which exposure occurred. Refer to existing managements for the individual chemicals.

Clinical Effects

Summary Of Exposure

    A) SUMMARY OF COMMON ACUTE EFFECTS -
    1) The most common adverse respiratory system effects resulting from inhalation exposures include one or more of the following: irritation of the mucous membranes of the eyes, nose, and respiratory tract; bronchospasm; metal fume fever; severe pulmonary irritation; chemical pneumonitis; immediate or delayed pulmonary edema; hypoxia or asphyxiation. Some of these conditions can be fatal or may lead to chronic adverse pulmonary effects.
    B) SUMMARY OF COMMON CHRONIC EFFECTS -
    1) Asthma, non-specific airway hyperresponsiveness, bronchitis, emphysema, altered ventilatory capacities in the absence of other significant findings, fibrosis, granuloma formation, bronchiolitis obliterans, and cancer are the most common chronic clinical effects resulting from selected inhalation exposures.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) UPPER RESPIRATORY INFLAMMATION DUE TO FUMES AND/OR VAPORS
    1) ACUTE TOXICITY
    a) ACUTE IRRITANTS - Water soluble agents are more commonly associated with acute irritation of the mucous membranes and upper respiratory tract. Causative agents may include ammonia, chlorine, sulfur dioxide, halogens and acrolein. Signs and symptoms may include cough; dyspnea; wheezing; lacrimation; and irritation of the eyes, throat and nose. Delayed pneumonitis and pulmonary edema may result from extreme exposure.
    b) ASPIRATION HAZARDS - Examples of causative agents include mineral seal oil, gasoline, kerosene and lighter fluid. Symptoms may include burning sensation of the mouth and throat, dry cough, gaging, grunting respirations, cyanosis, severe sore throat, and progressive respiratory distress.
    c) CHEMICAL PNEUMONITIS - Aspirated hydrocarbons or other chemicals of low viscosity, acid aerosols or mists are examples of causative agents. Symptoms may include dry cough, respiratory difficulty, cyanosis, progressive respiratory distress. Chemicals with low water solubility are more likely to reach the deeper lung structures and cause parenchymal injury.
    d) PULMONARY EDEMA - Aspirated hydrocarbons and exposure to high concentrations of metal oxide fumes, acid mists or aerosols, arsenic dusts, phosgene, ozone, nitrogen oxide, and irritant gases are examples of causative agents. Chemicals with low water solubility are more likely to cause parenchymal injury. Symptoms may develop 1 to 3 days after exposure. Rales, respiratory difficulty, hypoxia and radiographic abnormalities may be noted. Onset of symptoms may be delayed for 24 to 36 hours in some cases.
    e) SIMPLE ASPHYXIANTS - Examples of causative agents includes nitrogen, hydrogen, methane, helium, ethane, nitrous oxygen, carbon dioxide, argon, propane (Becker, 1990). Symptoms of low to moderate exposure may include tachypnea, tachycardia, incoordination, emotional lability, fatigue. Convulsions, apnea, cardiac standstill, and death may occur.
    f) CHEMICAL ASPHYXIANTS - Examples of causative agents include carbon monoxide, cyanide, hydrogen sulfide, nitriles. Symptoms may include headache, shortness of breath, tachypnea, nausea, impaired judgment, and cyanosis. Hypotension, loss of consciousness, convulsions, coma and respiratory arrest may occur.
    g) ACUTE HYPERSENSITIVITY PNEUMONITIS - Causative agents may include toluene diisocyanate, copper sulfate, bacillus subtilis enzymes in detergents, fungi, Thermophilic actinomycetes spores, and animal antigens. Symptoms may include cough, dyspnea, chills, fatigue, and tachypnea developing 4 to 12 hours after exposure.
    h) NONSPECIFIC AIRWAY HYPERSENSITIVITY - Examples of causative agents include sulfur dioxide, nitrogen dioxide, ozone, toluene diisocyanate, dust. Presents as an immediate, reversible airway narrowing in response to the offending agent. Cough and respiratory difficulty may be noted.
    i) METAL FUME FEVER - Examples of causative agents include cadmium oxide fumes, zinc oxide fumes (fumes from welding on galvanized metal). Symptoms may include chills, fever, malaise, dry cough, and metallic taste, and are generally delayed 8 to 12 hrs after exposure. Physiological adaptation (absent or decreased symptom severity) may occur during consecutive exposure, with rebound of symptoms after exposure has been resumed following a few days of no exposure. Delayed pulmonary edema may occur after extreme exposures.
    j) UPPER AIRWAY EDEMA - Life threatening upper airway edema can occur after exposure to caustic vapors or steam. Signs and symptoms include hoarseness, stridor, dyspnea, laryngospasm, dysphagia and drooling.
    k) NONSPECIFIC EFFECTS - Exposure to some chemicals which have a strong odor may result in nonspecific symptoms such as headache, dizziness, weakness, and nausea.
    1) Exposure to some dusts may produce coughing and minor irritation, without significant adverse effects. These dusts, formerly called nuisance dusts and more recently labeled Particulates Not Otherwise Classified, may occasionally cause potentially fatal alveolar proteinosis if very high dust concentrations are inhaled (ACGIH 1994).
    B) RESPIRATORY FINDING
    1) CHRONIC TOXICITY
    a) RESPONSE TO PARTICULATES NOT OTHERWISE CLASSIFIED - Dusts from kaolin, barium, and other non-fibrous, non-crystalline silicates may be associated with minor pulmonary effects which do not produce significant effects on pulmonary structure or function. Signs and symptoms may include increased sputum, coughing, sneezing, dust deposition noted on chest x-ray, and minimal or no changes in pulmonary function tests.
    b) Fibrosis has also been associated with some silicate and metal dusts which have previously been considered to be incapable of causing adverse effects (Gordon & Amdur, 1991). Contamination of the dusts with other toxic substances (e.g., crystalline silica) may have occurred in some instances.
    2) HYPERSENSITIVITY PNEUMONITIS - The chronic form may involve dyspnea, cough, fatigue, weight loss, bibasilar crackles, and cor pulmonale in extreme cases. Granulomas and fibrosis may develop with repeated inhalation of antigenic material. Causative agents may include toluene diisocyanate, copper sulfate, bacillus subtilis enzymes in detergents, fungi, Thermophilic actinomycetes spores, and animal antigens (Lloyd, 1993).
    3) ASTHMA - Causative agents may include isocyanates, metal salts, wood dust, grain dust, dust from cotton, flax or textiles. Symptoms may include chest tightness, wheezing, dyspnea, and reversible air flow limitation after exposure to the offending substance. Onset of symptoms may be early (within minutes), late (hours later), or with early and late manifestations. Nonspecific airway hyperresponsiveness may be noted with methacholine or cold air challenge (Brooks, 1992; Lloyd, 1993; Sheppard et al, 1990).
    4) BERYLLIOSIS - Acute or repeated exposure to beryllium may result in granulomatous pulmonary disease (berylliosis) several years after the exposure. Signs and symptoms may include dyspnea on exertion, fatigue, weight loss, cough, chest pain, rales, hepatosplenomegaly, and evidence of pulmonary hypertension (Lewis, 1990). Sensitization to beryllium can be demonstrated through lymphocyte proliferation assays (NRC, 1989) Newman, 1994).
    5) SILICOSIS - Pulmonary fibrosis involving the bronchioles and alveoli due to the inhalation of crystalline silica. Symptoms may include shortness of breath, rounded opacities or shadows on chest x-ray (silicotic nodule), restrictive or restrictive and obstructive pulmonary function test results.
    a) Onset of symptoms varies with extent of exposure and silica particle characteristics. Disease may be limited in progression (simple silicosis), progress gradually (complicated silicosis), progress more rapidly (accelerated silicosis), or have extremely rapid and fatal progression as a result of exposure to high concentrations of fine, silica flour (US DHHS, 1981).
    6) ASBESTOS RELATED DISEASES - Include asbestosis (fibrosis of bronchioles and alveoli with or without pleural fibrosis), non carcinogenic pleural disorders, malignant mesothelioma, and lung cancer. Fiber and host characteristics which influence the development of disease are reviewed by Rom et al (1991).
    7) PULMONARY CANCER - Examples of known causative carcinogenic agents according to the National Toxicology Program (US DHHS, 1994) include benzene, bis(chloromethyl) ether and technical grade chloromethyl methyl ether, erionite, vinyl chloride. Examples of agents which IARC (IARC, 1987) has concluded to be carcinogenic to humans include certain arsenic compounds, asbestos, benzene, erionite, certain nickel compounds, and vinyl chloride.
    8) INTERSTITIAL FIBROSIS - Clinical effects include dyspnea, decreased exercise tolerance, and restrictive lung disease. Causative agents include aluminum, coal dust, cobalt, copper, diatomaceous earth, mercury fumes, nickel, oil mists, silica and talc (Newman, 1992).
    9) BRONCHIOLITIS OBLITERANS - Clinical effects include fatigue, dyspnea, tachypnea, cough, hemoptysis, cyanosis, rales and wheezing. Causative agents include ammonia, cadmium oxide, chlorine, hydrogen fluoride, hydrogen sulfide, methyl sulfate, oxides of nitrogen, ozone, phosgene, sulfur dioxide and trichloroethylene (Newman, 1992).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Appropriate laboratory evaluation is determined in part by the clinical condition of the patient. Initial history is often inaccurate and many deliberate poisonings involve more than one compound.
    1) Arterial blood gases are useful to assess the degree of hypoxemia. Periodically obtain serum electrolytes to evaluate for metabolic acidosis. Tests of hepatic and renal function, arterial blood gases, pulse oximetry, and chest radiographs should be performed if clinically indicated. A 12-lead electrocardiogram should be performed.
    2) Tests for methemoglobinemia should be performed if clinically indicated. Methemoglobinemia may not develop until several hours (e.g, 1 to 10) after some exposures. Calculated O2 saturation is often inaccurate in cases of methemoglobinemia and carbon monoxide poisoning. Measured O2 saturation should be performed.
    3) ORGANOPHOSPHATE POISONING - Plasma cholinesterase (PChE) and erythrocyte acethylcholinesterase (AChE) activities are the most widely used tests used to initially diagnose.
    4) Pregnancy testing should be considered in women of childbearing potential.
    B) Toxicology screens and drug levels should be performed as indicated by history and clinical signs and symptoms. A variety of tests are available. General toxicology screens rarely provide information that alters the management of the asymptomatic, stable patient.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) If patient is not cyanotic but has been exposed to a methemoglobin producing substance, a baseline methemoglobin level may be drawn.
    a) NOTE - Methemoglobin levels will be artificially low if levels are not analyzed rapidly (few hours). Bedside determination can be made by placing a drop of blood on filter paper with a control drop of blood nearby. With greater than 15% methemoglobinemia, the affected blood will have a chocolate brown color in comparison with the control blood.
    B) ACID/BASE
    1) Obtain a measured O2 saturation on blood gases; calculated saturation is inaccurate with methemoglobinemia and carbon monoxide poisoning. Whenever there is a marked difference between measured and calculated O2 saturations, methemoglobinemia or carbon monoxide poisoning should be suspected.
    C) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    2) CHOLINESTERASE DETERMINATIONS - Blood and urine can be analyzed in order to confirm organophosphate poisoning. However, CLINICAL INTERVENTION SHOULD NOT BE POSTPONED PENDING THE LABORATORY RESULTS IN CASES IN WHICH CLINICAL INDICATORS STRONGLY SUGGEST SIGNIFICANT ORGANOPHOSPHATE INTOXICATION (Aaron & Howland, 1994).
    a) Plasma cholinesterase (PChE) and erythrocyte acethylcholinesterase (AChE) activities are the most widely used tests used to initially diagnose suspected organophosphate poisoning (Ludwig & Besser, 1990; (Marrs, 1993; Aaron & Howland, 1994). Clinical effects, however, do not always correlate with these cholinesterase measurements. These measurements while useful as markers of exposure and as aids in differential diagnosis, are not of great value in following the patient's clinical course (Marrs, 1993).
    b) Specimens should be obtained prior to administration of pralidoxime whenever possible. The levels are useful for confirmation of diagnosis; they should not be used to determine dosage of atropine (POISINDEX, 1994).
    3) DRUG/CHEMICAL PLASMA LEVELS - Toxicology screens and drug levels should be performed as indicated by history and clinical signs and symptoms.
    a) A variety of tests are available. General toxicology screens rarely provide information that alters the management of the asymptomatic, stable patient (Osterloh, 1990).
    4) Pregnancy testing should be considered in women of childbearing potential.
    4.1.3) URINE
    A) URINALYSIS
    1) Urine may show brown or black discoloration, casts, and protein as a result of hemolysis or methemoglobinemia.
    B) URINARY LEVELS
    1) Para-nitrophenol may be measured in the urine following parathion, chlorthion, and O-ethyl-O-p-nitrophenyl phenylphosphothionate exposure (Aaron & Howland, 1994). Not all institutions are able to perform the urinary analysis. Local health departments or the medical examiner may provide assistance.
    4.1.4) OTHER
    A) OTHER
    1) GASTRIC
    a) Combined exposures may exist, particularly in cases of attempted suicide. Save all emesis recovered and send entire amount to laboratory. However, analysis of gastric contents is currently seldom performed.
    b) Gastric lavage - save the initial aspirate separately from the large amount of lavage solution but send both.
    2) OXYGEN SATURATION
    a) INDICATIONS: To obtain continuous, noninvasive measurement of arterial saturation in patients with respiratory complaints and those requiring assisted or mechanical ventilation (Galdun et al, 1989; Jones et al, 1988; Rose & Wolfson, 1989).
    b) ACCURACY: Accurate for saturations between 65% and 100%; correlates well with ABGs (Jones et al, 1988; Yelderman & New, 1983). Factors affecting accuracy include (Galdun et al, 1989; Rose & Wolfson, 1989; Bowes et al, 1989; Phillips et al, 1989):
    1) Decreased cardiac output with poor peripheral perfusion (most significant)
    2) Patient or transducer movement
    3) Increased bilirubin levels
    4) Hypothermia
    5) Electrical or optical interference
    6) Carboxyhemoglobin or methemoglobin
    7) Anemia <5 g/dL Hb
    8) Dark nail polish
    9) Nonpulsating vascular bed
    10) Presence of intravascular dyes
    c) DISADVANTAGES: Relative insensitivity to changes in oxygenation occurring in upper portion of oxyhemoglobin dissociation curve; less sensitive than ABGs for detecting changes in PO2, especially in higher ranges of PO2 values (Rose & Wolfson, 1989).
    3) MONITORING
    a) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    b) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
    4) ECG
    a) A 12-lead electrocardiogram should be performed to evaluate for arrhythmia, tachycardia, or interval prolongation.
    b) If the acidosis and tissue hypoxia are severe enough, ischemic changes, ventricular arrhythmias, and cardiac arrest may result.
    5) PULMONARY FUNCTION TESTS
    a) Pulmonary function testing, including CO diffusion, may be useful in symptomatic patients. Methacholine challenge may be helpful in assessing persistent symptoms after acute exposure.
    6) OTHER
    a) Endoscopy may be helpful in assessing upper airway burns.
    b) BRONCHALVEOLAR LAVAGE - Primarily a research tool; increased lymphocytes in BAL fluid correlate with granulomatous pathology.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

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) ADMISSION CRITERIA
    1) Patients demonstrating any of the following should be admitted: neurological symptoms or signs; abnormal EKG; metabolic acidosis; COHb level above 30% (0.3); cyanosis; respiratory distress; chest pain; methemoglobin level greater than 30% in asymptomatic patients who have a history of exposure to methemoglobin forming agents; measured O2 saturation is different from calculated O2 saturation; significant symptomatology or worsening of symptoms.

Monitoring

    A) Appropriate laboratory evaluation is determined in part by the clinical condition of the patient. Initial history is often inaccurate and many deliberate poisonings involve more than one compound.
    1) Arterial blood gases are useful to assess the degree of hypoxemia. Periodically obtain serum electrolytes to evaluate for metabolic acidosis. Tests of hepatic and renal function, arterial blood gases, pulse oximetry, and chest radiographs should be performed if clinically indicated. A 12-lead electrocardiogram should be performed.
    2) Tests for methemoglobinemia should be performed if clinically indicated. Methemoglobinemia may not develop until several hours (e.g, 1 to 10) after some exposures. Calculated O2 saturation is often inaccurate in cases of methemoglobinemia and carbon monoxide poisoning. Measured O2 saturation should be performed.
    3) ORGANOPHOSPHATE POISONING - Plasma cholinesterase (PChE) and erythrocyte acethylcholinesterase (AChE) activities are the most widely used tests used to initially diagnose.
    4) Pregnancy testing should be considered in women of childbearing potential.
    B) Toxicology screens and drug levels should be performed as indicated by history and clinical signs and symptoms. A variety of tests are available. General toxicology screens rarely provide information that alters the management of the asymptomatic, stable patient.

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.
    D) 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).
    E) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    F) PESTICIDES
    1) 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. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).
    6.7.2) TREATMENT
    A) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    2) BRONCHODILATORS - Recommended for mild to severe bronchospasm.
    a) ALBUTEROL - 0.25 to 0.5 milliliter in 2 to 4.5 milliliters of normal saline delivered every 4 to 6 hours per nebulizer. Children: 100 to 200 micrograms 3 to 6 times a day. In severe cases may be administered every 15 minutes.
    3) STEROIDS - Methylprednisolone 125 milligrams intravenously (in children 4 milligrams/kilogram) followed by 2 milligrams/kilogram every 4 to 6 hours.
    B) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    2) If hypoxia has been severe or prolonged, carefully evaluate for neurologic sequelae and provide supportive treatment as indicated.
    C) OXYGEN
    1) SIMPLE ASPHYXIATION - Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    a) If hypoxia has been severe or prolonged, carefully evaluate for neurologic sequelae and provide supportive treatment as indicated.
    2) CHEMICAL ASPHYXIATION - ADMINISTER 100% OXYGEN - by tight-fitting face mask to reduce the biological half-life of CO and to treat other chemical asphyxiant poisonings.
    a) CONSIDER HYPERBARIC OXYGEN THERAPY (HBO) - for severely poisoned patients.
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    E) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) 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)
    3) 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).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) 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).
    7) 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) METHEMOGLOBINEMIA
    1) 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.
    2) 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).
    3) 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.
    4) Refer to "METHEMOGLOBINEMIA" management for further information.
    G) METAL FEVER
    1) METAL FUME FEVER - Remove from exposure and administer 100% humidified supplemental oxygen with assisted ventilation as required. Observe for and treat the development of pulmonary edema which may be delayed 24 to 72 hours after exposure. Refer to "METAL FUME FEVER" management for further information.
    H) INSECTICIDE
    1) ORGANOPHOSPHATES OR CARBAMATE PESTICIDES
    a) Extensive guidelines for treating organophosphate or carbamate poisoning can be found in the following managements.
    1) Refer to "ORGANOPHOSPHATES" management for further information.
    2) Refer to "CARBAMATE HERBICIDES AND FUNGICIDES" for further information.
    3) Refer to "CARBAMATE INSECTICIDES" management for further information.
    I) ARSINE
    1) Extensive guidelines for treating arsine poisoning can be found in the following management.
    a) Refer to "ARSINE" management for further information.
    J) SUPPORT
    1) If hypoxia has been severe or prolonged, carefully evaluate for neurologic sequelae and provide supportive treatment as indicated.

Range Of Toxicity

Summary

    A) The range of toxicity will vary depending upon the specific toxicant or toxicants to which exposure occurred. Refer to existing managements for the individual chemicals.

References

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