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CYANOPHENOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cyanophenol (p-cyanophenol) is an aromatic nitrile and a phenol. Its toxicity is expected to more closely resemble that of phenol than of cyanide.

Specific Substances

    A) No Synonyms were found in group or single elements

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Little information is available on the toxicity of cyanophenol.
    1) It may potentially exhibit toxicologic properties of both phenol and aromatic nitriles.
    a) From theoretical considerations, it would be expected that the para-nitrile group could activate the phenol, and the para-phenol group to deactivate the nitrile. In other words, cyanophenol should behave more like a phenol and less like a nitrile toxicologically.
    b) Given the lack of experimental data, however, it should be assumed that both properties are potential sources of toxicity.
    B) The following review is based on the properties of phenols and nitriles. Any effects attributed specifically to cyanophenol are identified.
    C) Phenols can be strongly irritating or corrosive to the eyes, skin, and respiratory system. They may cause severe burns. They can induce nausea, vomiting, diarrhea, methemoglobinemia, hypotension, cardiac dysrhythmias, pulmonary edema, tachypnea, lethargy, seizures, and coma. Liver and renal injury may also occur.
    D) The major concern about nitriles is their ability to liberate CYANIDE. Cyanide can theoretically be released either metabolically or as a combustion product in a fire. The metabolic release of cyanide may be delayed by several hours after exposure.
    1) As a rule, nitriles are less toxic than cyanide itself on a molar basis. Benzonitrile, which is closely chemically related to cyanophenol, did not liberate detectable cyanide when given orally to rats (HSDB, 1995).
    a) By extension, it is unlikely that cyanophenol would generate cyanide metabolically. However, HYDROGEN CYANIDE gas could be released as a combustion product and may contribute significantly to the combustion toxicity of cyanophenol.
    2) Cyanide is a metabolic poison which can tightly bind to cytochrome oxidase, thus preventing the cellular utilization of oxygen.
    3) Signs and symptoms of cyanide poisoning include nausea, vomiting, tonic-clonic seizures, palpitations, dilated pupils, hypoventilation, shock, coma, cyanosis, metabolic acidosis, initial tachycardia and hypertension, and hypotension in cases of serious poisoning.
    4) Agressive treatment for cyanide poisoning (ie, use of the Lilly Cyanide Antidote Kit or other antidotes) should NOT be undertaken unless there is evidence that cyanide poisoning has actually occurred, because of potential iatrogenic toxicity.
    E) Cyanophenol would be expected to liberate cyanide, carbon monoxide, and possibly other toxic gases under conditions of thermal decomposition.
    0.2.3) VITAL SIGNS
    A) Phenols can cause hypotension and tachycardia with severe toxicity. Tachypnea and hypothermia can also occur.
    0.2.4) HEENT
    A) Ingestion of phenols may result in oral burns. The affected area generally turns white and is without pain, but may become necrotic several days later. Eye exposure may result in severe burns or photophobia.
    B) HEENT effects due to cyanide poisoning include mydriasis and burning sensation in the mouth or throat.
    0.2.5) CARDIOVASCULAR
    A) Hypotension and tachycardia are commonly reported with exposure to phenols. Dysrhythmias have developed in patients following oral ingestion and dermal contact with phenol.
    B) Cardiovascular effects from cyanide poisoning include tachycardia and hypertension in the initial phases, followed by bradycardia and hypotension in late stages. EKG changes and dysrhythmias have been noted in severe cyanide poisoning.
    0.2.6) RESPIRATORY
    A) Tachypnea, pulmonary edema, bronchospasm, stridor, and respiratory arrest have been reported from exposure to phenol.
    B) Hyperpnea, apnea, and noncardiogenic pulmonary edema have occurred in cyanide poisoning.
    0.2.7) NEUROLOGIC
    A) Phenols can cause initial CNS excitation, including seizures, often followed by CNS depression ranging from lethargy to coma and death.
    B) Cyanide poisoning involves headache, CNS stimulation, seizures, paralysis, and coma.
    0.2.8) GASTROINTESTINAL
    A) Concentration solutions of phenols can be extremely corrosive and may cause oral and esophageal burns following ingestion. Nausea, vomiting, and diarrhea are generally associated with the burns.
    B) Nausea, vomiting and abdominal pain may occur in cyanide poisoning, especially after exposure by the oral route.
    0.2.9) HEPATIC
    A) Hepatic injury can follow exposure to phenols in 3 to 5 days.
    0.2.10) GENITOURINARY
    A) Renal toxicity associated with oliguria or anuria may occur following exposure to phenols.
    0.2.11) ACID-BASE
    A) Metabolic acidosis can ensue from oral ingestion of phenols and in cyanide poisoning.
    0.2.13) HEMATOLOGIC
    A) Methemoglobinemia may occur following exposure to some phenols. Injection of strong phenol has caused deep venous thrombosis.
    0.2.14) DERMATOLOGIC
    A) Dermal contact with phenolic compounds may result in irritation, dermatitis, abnormal pigmentation, and burns. Dermatitis and depigmentation appear to be the most common adverse effects. Diaphoresis may develop with systemic toxicity.
    0.2.19) IMMUNOLOGIC
    A) Phenols may be potentially immunotoxic, as shown in animal studies.
    0.2.20) REPRODUCTIVE
    A) Cyanophenol was not teratogenic in rats.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) Toxic shock syndrome has developed after dermal exposure to phenol.

Laboratory Monitoring

    A) Obtain CBC, electrolytes, and urinalysis.
    B) Determine hemoglobin, methemoglobin, arterial blood gases, venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, and whole blood cyanide levels.
    C) Monitor chest x-ray, arterial blood gases, and pulmonary function tests in cases with significant inhalation exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) AVOID DILUTION which may enhance the absorption of phenols.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) Oral administration of castor oil to delay absorption of phenols from the stomach is NOT RECOMMENDED because no clinical documentation for efficacy has been reported.
    E) Treatment is primarily supportive and includes monitoring for the development of methemoglobinemia, seizures, and dysrhythmias. Kidney and liver function should be monitored, and monitoring of acid-base balance is suggested.
    F) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 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).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    G) Obtain an ECG, and institute continuous cardiac monitoring.
    H) VENTRICULAR DYSRHYTHMIAS/SUMMARY: Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    I) If significant cyanide release is suspected or confirmed, refer to CYANIDE document. Do not use aggressive treatment for cyanide poisoning (ie, nitrites and thiosulfate) because of the risk of iatrogenic toxicity, especially because of the possibility that cyanophenol itself may induce methemoglobinemia.
    J) METHEMOGLOBINEMIA
    1) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause release of cyanide from the cyanmethemoglobin complex. Such authors have suggested that emergency exchange transfusion is the treatment of choice. Hyperbaric oxygen therapy could be used to support the patient while preparations for exchange transfusion are being made.
    2) However, methylene or toluidine blue have been used successfully in this setting without worsening the course of the cyanide poisoning. 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.
    3) METHEMOGLOBINEMIA: 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.
    4) 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.
    5) 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.
    K) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. 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.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) INHALATION: Administer oxygen. If respiratory symptoms develop obtain chest x-ray, monitor pulse oximetry and/or blood gases. Treat bronchospasm with inhaled beta2-adrenergic agonists. If acute lung injury develops, consider PEEP. Evaluate for esophageal, dermal and eye burns as indicated.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    B) EYE ASSESSMENT: The extent of eye injury (degree of corneal opacification and perilimbal whitening) may not be apparent for 48 to 72 hours after the burn.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Undiluted polyethylene glycol 300 to 400 or isopropyl alcohol are useful for removal of phenol prior to washing, and may also be helpful for cyanophenol. Wash exposed areas twice with large quantities of water. A physician may need to examine the exposed area if irritation or pain persist after the area is washed.
    2) Treatment of chemical burns may involve debridement and topical or systemic antibiotics.

Range Of Toxicity

    A) The minimum lethal human dose to this agent has not been delineated.
    B) The maximum tolerated human exposure to this agent has not been delineated.
    C) From limited animal data, cyanophenol would appear to be much less acutely toxic than either cyanide or phenol.

Clinical Effects

Vital Signs

    3.3.1) SUMMARY
    A) Phenols can cause hypotension and tachycardia with severe toxicity. Tachypnea and hypothermia can also occur.
    3.3.3) TEMPERATURE
    A) HYPOTHERMIA may occur as a systemic toxicity of phenol (Goldfrank et al, 1994).
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION may develop with severe phenol poisoning.
    3.3.5) PULSE
    A) TACHYCARDIA may develop with severe poisoning from phenols (Haddad et al, 1979).

Heent

    3.4.1) SUMMARY
    A) Ingestion of phenols may result in oral burns. The affected area generally turns white and is without pain, but may become necrotic several days later. Eye exposure may result in severe burns or photophobia.
    B) HEENT effects due to cyanide poisoning include mydriasis and burning sensation in the mouth or throat.
    3.4.3) EYES
    A) PHOTOPHOBIA is common with exposure to phenolic fluids or vapors.
    B) CORNEAL BURNS - Concentrated solutions of strong phenols may be extremely corrosive upon direct contact with the eyes. Injury may include epithelial ulceration and stromal opacity. Partial or total loss of vision may occur.
    C) MYDRIASIS - Dilated pupils are common in severe cyanide poisoning (Vogel et al, 1981).
    3.4.6) THROAT
    A) BURNING SENSATION - A burning sensation in the mouth and throat may occur with hydrogen cyanide exposure (Vogel et al, 1981).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension and tachycardia are commonly reported with exposure to phenols. Dysrhythmias have developed in patients following oral ingestion and dermal contact with phenol.
    B) Cardiovascular effects from cyanide poisoning include tachycardia and hypertension in the initial phases, followed by bradycardia and hypotension in late stages. EKG changes and dysrhythmias have been noted in severe cyanide poisoning.
    3.5.2) CLINICAL EFFECTS
    A) CONDUCTION DISORDER OF THE HEART
    1) Cardiac dysrhythmias have been seen in persons with dermal and oral exposure to phenol (Truppman & Ellenby, 1979; Haddad et al, 1979). Dysrhythmias included premature ventricular contraction, bigeminy, paroxysmal atrial tachycardia, and ventricular tachycardia (Truppman & Ellenby, 1979).
    2) Tachycardia and hypertension may be seen in the initial phases of cyanide poisoning, followed by bradycardia and hypotension in later stages (Vogel et al, 1981; Hall & Rumack, 1986). EKG changes including erratic atrial and ventricular rhythms with varying degrees of atrioventricular block followed by asystole have also been noted in severe cyanide poisoning (Hall & Rumack, 1986).
    B) ATRIAL FIBRILLATION
    1) Atrial fibrillation occurred commonly in persons having dermal contact with phenol (Gross, 1983) Stuzin et al, 1883).

Respiratory

    3.6.1) SUMMARY
    A) Tachypnea, pulmonary edema, bronchospasm, stridor, and respiratory arrest have been reported from exposure to phenol.
    B) Hyperpnea, apnea, and noncardiogenic pulmonary edema have occurred in cyanide poisoning.
    3.6.2) CLINICAL EFFECTS
    A) HYPERVENTILATION
    1) Tachypnea occurs commonly with exposure to phenols. It is also part of the initial presentation of cyanide poisoning (Hall & Rumack, 1986).
    B) APNEA
    1) Later phases of cyanide poisoning may involve hypoventilation progressing to apnea; apnea is a major cause of death (Vogel et al, 1981).
    2) Respiratory arrest occurred 30 minutes postingestion of 26.7 grams of phenol (Haddad et al, 1979).
    C) ACUTE LUNG INJURY
    1) Pulmonary edema has been reported after exposure to phenol. It has also been seen in cases of cyanide poisoning (Graham et al, 1977).
    D) BRONCHOSPASM
    1) Inspiratory and expiratory wheezing and ronchi which were relieved by albuterol developed in a male following intercostal nerve block with phenol (Atkinson & Shupak, 1989).
    E) EPIGLOTTITIS
    1) Acute epiglottitis resulting in life-threatening airway obstruction developed in a woman after direct contact of phenol with the throat (Ho & Hollinrake, 1989).
    F) STRIDOR
    1) Upper airway injury may result in stridor, as reported in 5% (4/72) of patients after oral ingestion of 26% phenol in a 5-year retrospective study (Spiller et al, 1993).
    G) CYANOSIS
    1) Cyanosis is a late finding in cyanide poisoning and does not occur until the stage of apnea and circulatory collapse (Hall & Rumack, 1986).

Neurologic

    3.7.1) SUMMARY
    A) Phenols can cause initial CNS excitation, including seizures, often followed by CNS depression ranging from lethargy to coma and death.
    B) Cyanide poisoning involves headache, CNS stimulation, seizures, paralysis, and coma.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Headache can be an early sign of cyanide poisoning (Vogel et al, 1981).
    B) CENTRAL STIMULANT ADVERSE REACTION
    1) CNS stimulation with varied presentations from anxiety to agitation and combative behavior may be seen in the early stages of cyanide poisoning (Vogel et al, 1981).
    C) SEIZURE
    1) Seizures were reported following ingestion of 1 ounce of 89% phenol and dermal exposure to pure 2,4-dichlorophenol (Haddad et al, 1979; Kintz et al, 1992). Seizures are also common in cyanide poisoning (Hall & Rumack, 1986).
    D) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Fleeting excitation may occur after exposure to phenols, but can be quickly followed by lethargy and coma (Spiller et al, 1993). Coma is also common in severe cyanide poisoning (Hall & Rumack, 1986).
    E) FACIAL PALSY
    1) Exposure to vapors of chlorocresol produced left-sided facial palsies in a woman (Dossing et al, 1986).
    F) PARALYSIS
    1) Opisthotonos, trismus, and paralysis have occurred rarely in cyanide poisoning (De Busk & Seidl, 1969).

Gastrointestinal

    3.8.1) SUMMARY
    A) Concentration solutions of phenols can be extremely corrosive and may cause oral and esophageal burns following ingestion. Nausea, vomiting, and diarrhea are generally associated with the burns.
    B) Nausea, vomiting and abdominal pain may occur in cyanide poisoning, especially after exposure by the oral route.
    3.8.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) Strong phenols can denature the protein of the mucous membranes of the upper alimentary tract and produce corrosive effects (Spiller et al, 1993).
    a) FINDINGS - The area generally turns white and is without pain, but is usually surrounded by a zone of erythema prior to its becoming necrotic several days later.
    b) SIGNS/SYMPTOMS - Nausea, vomiting, and diarrhea accompanied by hyperactivity are the usual first signs.

Hepatic

    3.9.1) SUMMARY
    A) Hepatic injury can follow exposure to phenols in 3 to 5 days.
    3.9.2) CLINICAL EFFECTS
    A) HEPATIC NECROSIS
    1) JAUNDICE due to hepatic necrosis may be noted 3 to 5 days after ingestion of phenolics.

Genitourinary

    3.10.1) SUMMARY
    A) Renal toxicity associated with oliguria or anuria may occur following exposure to phenols.
    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) Oliguria or anuria have been reported following exposure to phenols. Urine color may be dark green or black. Dark urine (bilirubin-negative) has been a prominent feature of occupational exposure to vaporized phenol (Goldfrank et al, 1994).

Acid-Base

    3.11.1) SUMMARY
    A) Metabolic acidosis can ensue from oral ingestion of phenols and in cyanide poisoning.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) CASE REPORT - Mixed acid-base disturbance characterized by respiratory alkalosis and metabolic acidosis developed in a 52-year-old woman after ingestion of 1 ounce of 89% phenol (Haddad et al, 1979).
    2) Elevated anion gap metabolic acidosis and elevated serum lactate levels are frequently found in cyanide poisoning (Hall & Rumack),

Hematologic

    3.13.1) SUMMARY
    A) Methemoglobinemia may occur following exposure to some phenols. Injection of strong phenol has caused deep venous thrombosis.
    3.13.2) CLINICAL EFFECTS
    A) METHEMOGLOBINEMIA
    1) Some phenols can cause methemoglobinemia. Whether or not this is true of cyanophenol is not known.
    2) Note that use of amyl and/or sodium nitrite in treatment of cyanide poisoning induces methemoglobinemia. Therefore, these cyanide antidotes should be used with caution in cases of cyanophenol exposure, and only when actual exposure to cyanide is known or strongly suspected, or laboratory values indicate cyanide exposure.
    B) DEEP THROMBOPHLEBITIS
    1) Injection of dilute phenol solutions for medical procedures produced deep venous thrombosis (Macek, 1983).

Dermatologic

    3.14.1) SUMMARY
    A) Dermal contact with phenolic compounds may result in irritation, dermatitis, abnormal pigmentation, and burns. Dermatitis and depigmentation appear to be the most common adverse effects. Diaphoresis may develop with systemic toxicity.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) Skin irritation and sensitization may occur from direct contact with phenolics.
    2) Allergic contact dermatitis has rarely occurred following topical application of phenolics (Langeland & Braathen, 1987).
    3) One case of contact allergy to phenol has been reported as a result of a phenol-formaldehyde resin in a knee guard. Patch tests were negative to formaldehyde, but positive for phenol (Vincenzi et al, 1992).
    B) DISCOLORATION OF SKIN
    1) Abnormal pigmentation commonly occurs following dermal contact with phenolic compounds (Saunders et al, 1988).
    2) Types of abnormal pigmentation have included leukoderma similar to vitiligo and a rusty-red pigmentary dermatosis (Tosti et al, 1991; Abbate et al, 1989).
    C) CHEMICAL BURN
    1) Concentrated phenolics can be extremely corrosive and may cause severe burns. Contact with the skin for prolonged periods may result in denaturation and gangrene followed by necrosis (Fisher, 1980).
    2) Phenols may have some local anesthetic properties that allow extensive damage to occur before any pain is recognized. Dull gray skin discoloration may occur and may progress to black gangrene (Saydjari et al, 1986).
    3) Desquamation and partial thickness burns developed in two children who were splashed with cresol solutions (Pegg & Campbell, 1985).
    D) EXCESSIVE SWEATING
    1) Intense diaphoresis may occur soon after exposure.

Immunologic

    3.19.1) SUMMARY
    A) Phenols may be potentially immunotoxic, as shown in animal studies.
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) WBC ABNORMAL
    a) Phenol suppressed stimulation of cultured mouse splenic lymphocytes after oral exposure (Hsieh et al, 1992).

Reproductive

    3.20.1) SUMMARY
    A) Cyanophenol was not teratogenic in rats.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) Cyanophenol was not teratogenic in rats given a single gavage dose of 1000 mg/kg on day 11 of gestation (Copeland et al, 1990).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS611-20-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Summary Of Exposure

    A) Little information is available on the toxicity of cyanophenol.
    1) It may potentially exhibit toxicologic properties of both phenol and aromatic nitriles.
    a) From theoretical considerations, it would be expected that the para-nitrile group could activate the phenol, and the para-phenol group to deactivate the nitrile. In other words, cyanophenol should behave more like a phenol and less like a nitrile toxicologically.
    b) Given the lack of experimental data, however, it should be assumed that both properties are potential sources of toxicity.
    B) The following review is based on the properties of phenols and nitriles. Any effects attributed specifically to cyanophenol are identified.
    C) Phenols can be strongly irritating or corrosive to the eyes, skin, and respiratory system. They may cause severe burns. They can induce nausea, vomiting, diarrhea, methemoglobinemia, hypotension, cardiac dysrhythmias, pulmonary edema, tachypnea, lethargy, seizures, and coma. Liver and renal injury may also occur.
    D) The major concern about nitriles is their ability to liberate CYANIDE. Cyanide can theoretically be released either metabolically or as a combustion product in a fire. The metabolic release of cyanide may be delayed by several hours after exposure.
    1) As a rule, nitriles are less toxic than cyanide itself on a molar basis. Benzonitrile, which is closely chemically related to cyanophenol, did not liberate detectable cyanide when given orally to rats (HSDB, 1995).
    a) By extension, it is unlikely that cyanophenol would generate cyanide metabolically. However, HYDROGEN CYANIDE gas could be released as a combustion product and may contribute significantly to the combustion toxicity of cyanophenol.
    2) Cyanide is a metabolic poison which can tightly bind to cytochrome oxidase, thus preventing the cellular utilization of oxygen.
    3) Signs and symptoms of cyanide poisoning include nausea, vomiting, tonic-clonic seizures, palpitations, dilated pupils, hypoventilation, shock, coma, cyanosis, metabolic acidosis, initial tachycardia and hypertension, and hypotension in cases of serious poisoning.
    4) Agressive treatment for cyanide poisoning (ie, use of the Lilly Cyanide Antidote Kit or other antidotes) should NOT be undertaken unless there is evidence that cyanide poisoning has actually occurred, because of potential iatrogenic toxicity.
    E) Cyanophenol would be expected to liberate cyanide, carbon monoxide, and possibly other toxic gases under conditions of thermal decomposition.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain CBC, electrolytes, and urinalysis.
    B) Determine hemoglobin, methemoglobin, arterial blood gases, venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, and whole blood cyanide levels.
    C) Monitor chest x-ray, arterial blood gases, and pulmonary function tests in cases with significant inhalation exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Serum or plasma levels of cyanophenol are not useful for clinical management.
    2) Determine electrolytes, serum lactate, and whole blood cyanide levels.
    3) Obtain baseline liver and renal function tests.
    B) HEMATOLOGIC
    1) Determine hemoglobin and methemoglobin.
    C) ACID/BASE
    1) Monitor acid-base balance closely. Measure arterial blood gases, venous pO2 or measured venous %O2 saturation
    D) OTHER
    1) DETERMINATION OF CYANIDE POISONING - Arterial blood gases and serum electrolytes are useful in the assessment of potential elevated anion gap metabolic acidosis in patients poisoned with cyanide (Hall & Rumack, 1986; Vogel et al, 1981).
    a) A REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2
    1) SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen (Graham et al, 1977; Paulet, 1955). Arteriolization of venous blood gases (elevated venous pO2 or measured venous %O2 saturation) may serve as an early clue in the diagnosis of cyanide poisoning (Hall & Rumack, 1986; Johnson & Mellors, 1988).
    b) Serum lactate levels may be useful in monitoring the severity of poisoning and the efficacy of treatment (Vogel et al, 1981).
    4.1.3) URINE
    A) URINARY LEVELS
    1) Cyanide and thiocyanate levels can also be measured in timed urine collections which may yield useful information on cyanide generation and/or clearance. However, such testing is seldom done clinically; it is more a research tool.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor cardiac function closely.
    b) Monitor pulmonary function in cases of inhalation exposure.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Monitor chest X-ray in cases of significant inhalation exposure or respiratory distress.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with significant exposure should be observed in a controlled medical setting overnight because of possible delayed metabolic generation of cyanide.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Patients with significant exposure should be observed in a controlled medical setting overnight because of possible delayed metabolic generation of cyanide.

Monitoring

    A) Obtain CBC, electrolytes, and urinalysis.
    B) Determine hemoglobin, methemoglobin, arterial blood gases, venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, and whole blood cyanide levels.
    C) Monitor chest x-ray, arterial blood gases, and pulmonary function tests in cases with significant inhalation exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) These treatment recommendations are based on those for Phenol and related compounds.
    B) Prevention of absorption may be accomplished by gastric lavage and/or activated charcoal/cathartic. Dilution should also be avoided since it may enhance absorption.
    C) Peritoneal or hemodialysis will not enhance the elimination of phenolic compounds.
    D) Exposed eyes or skin should be irrigated with copious amounts of water.
    1) Decontamination of exposed skin with polyethylene 300 or 400 or isopropyl alcohol may be considered.
    E) Inhalation exposures should be treated with adequate ventilation and oxygenation. Patients should be monitored for respiratory distress.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Prevention of absorption may be accomplished by gastric lavage and/or activated charcoal/cathartic. Cyanophenol may exhibit irritant and caustic properties similar to phenol. The potential benefits of gastric lavage must be carefully weighed against the risk of further injury to burned mucosa. Dilution and the use of castor oil should also be avoided.
    B) ACTIVATED CHARCOAL
    1) If endoscopy is to be performed, activated charcoal may interfere with visualization of involved areas. However, phenol is adsorbed to activated charcoal in vitro (Decker et al, 1968), and it is likely that cyanophenol may also be adsorbed.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) PRECAUTIONS: Cyanophenol may exhibit irritant and caustic properties similar to phenol. The potential benefits of gastric lavage must be carefully weighed against the risk of further injury to burned mucosa.
    2) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    3) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    4) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    5) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    6) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    D) CONTRAINDICATION
    1) DILUTION may enhance absorption of phenol (Conning & Hayes, 1970).
    2) Giving CASTOR OIL to slow phenol absorption from the stomach is NOT RECOMMENDED. Phenols are soluble in oil, and the benefit of treating with castor oil has not been documented by clinical studies.
    6.5.3) TREATMENT
    A) 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).
    7) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).
    B) VENTRICULAR ARRHYTHMIA
    1) VENTRICULAR DYSRHYTHMIAS SUMMARY
    a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
    2) LIDOCAINE
    a) LIDOCAINE/INDICATIONS
    1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).
    b) LIDOCAINE/DOSE
    1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
    a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
    2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).
    c) LIDOCAINE/MAJOR ADVERSE REACTIONS
    1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).
    d) LIDOCAINE/MONITORING PARAMETERS
    1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
    3) AMIODARONE
    a) AMIODARONE/INDICATIONS
    1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
    b) AMIODARONE/ADULT DOSE
    1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).
    c) AMIODARONE/PEDIATRIC DOSE
    1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
    d) ADVERSE EFFECTS
    1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).
    4) PROCAINAMIDE
    a) PROCAINAMIDE/INDICATIONS
    1) An alternative drug in the treatment of PVCs or recurrent ventricular tachycardia when lidocaine is contraindicated or not effective. It should be avoided when the ingestion involves agents with quinidine-like effects (e.g. tricyclic antidepressants, phenothiazines, chloroquine, antidysrhythmics) and when the ECG reveals QRS widening or QT prolongation suspected to be secondary to overdose(Neumar et al, 2010; Vanden Hoek,TL,et al).
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) TOXIC EFFECT OF CYANIDE
    1) CYANIDE POISONING: If significant cyanide poisoning is suspected or confirmed, refer to the CYANIDE document for more information. DO NOT use aggressive treatment for cyanide poisoning (ie, nitrites and thiosulfate) unless there is reason to believe cyanide is present because of the risk of iatrogenic toxicity, and because there is a possibility that cyanophenol itself may induce methemoglobinemia.
    E) METHEMOGLOBINEMIA
    1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur only 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 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.
    F) ENDOSCOPIC PROCEDURE
    1) There is little information regarding the use of endoscopy, corticosteroids or surgery in the setting of concentrated cyanophenol ingestion. The following information is derived from experience with other corrosives.
    2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
    3) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
    4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
    a) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)
    5) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):
    a) Advancing across the cricopharynx under direct vision
    b) Gently advancing with minimal air insufflation
    c) Never retroverting or retroflexing the endoscope
    d) Using a pediatric flexible endoscope
    e) Using extreme caution in advancing beyond burn lesion areas
    f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).
    6) GRADING
    a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
    b) Grade 0 - Normal examination
    c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
    d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
    e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
    f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
    g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.
    7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
    8) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
    9) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).
    G) CORTICOSTEROID
    1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
    2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
    3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
    4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
    5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
    6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
    7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
    8) STUDIES
    a) ANIMAL
    1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
    2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
    3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).
    b) HUMAN
    1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
    2) META ANALYSIS
    a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
    b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
    c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).
    3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
    4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
    5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).
    a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
    b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
    c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
    d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
    e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).
    6) ADVERSE EFFECTS
    a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).
    H) SURGICAL PROCEDURE
    1) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
    2) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
    3) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).
    a) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).
    4) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
    5) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
    6) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).
    a) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

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) CAUSTIC INHALATION: Administer humidified oxygen, and remove from exposure. Monitor patient for respiratory distress; if a cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, and pneumonitis.
    E) Patients with upper airway burns may develop significant edema abruptly; early intubation is advised.
    F) Determine pulse oximetry and/or blood gases, obtain chest x-ray, perform endotracheal intubation and provide mechanical ventilation as clinically indicated.
    G) Administer inhaled beta2-adrenergic agonists in patients with bronchospasm (National Heart,Lung,and Blood Institute, 2007). If acute lung injury develops, consider PEEP (Haas, 2011; Leaver & Evans, 2007; Stolbach & Hoffman, 2011).
    H) Evaluate for esophageal, dermal and eye burns as indicated.
    6.7.2) TREATMENT
    A) OXYGEN
    1) If symptoms are not relieved by exposure to fresh air, oxygen should be administered until blood gases can be measured. Assisted ventilation may be required if symptoms are severe or prolonged.
    B) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) CAUSTIC INHALATION: Administer humidified oxygen, and remove from exposure. Monitor patient for respiratory distress; if a cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, and pneumonitis.
    3) Patients with upper airway burns may develop significant edema abruptly; early intubation is advised.
    4) Determine pulse oximetry and/or blood gases, obtain chest x-ray, perform endotracheal intubation and provide mechanical ventilation as clinically indicated.
    5) Administer inhaled beta2-adrenergic agonists in patients with bronchospasm (National Heart,Lung,and Blood Institute, 2007). If acute lung injury develops, consider PEEP (Haas, 2011; Leaver & Evans, 2007; Stolbach & Hoffman, 2011).
    6) Evaluate for esophageal, dermal and eye burns as indicated.
    C) 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).
    D) BRONCHOSPASM
    1) The patient should be removed from possible future chronic exposures to prevent worsening of the condition.
    2) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    3) Chronic treatment with inhaled sympathomimetic agents and/or steroids may be required.
    E) 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).
    7) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).
    F) TOXIC EFFECT OF CYANIDE
    1) CYANIDE POISONING: If significant cyanide poisoning is suspected or confirmed, refer to the CYANIDE document for more information. DO NOT use aggressive treatment for cyanide poisoning (ie, nitrites and thiosulfate) unless there is reason to believe cyanide is present because of the risk of iatrogenic toxicity, and because there is a possibility that cyanophenol itself may induce methemoglobinemia.
    G) METHEMOGLOBINEMIA
    1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur only 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 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.
    H) 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).
    6.8.2) TREATMENT
    A) SUPPORT
    1) DAMAGE ASSESSMENT
    a) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000).
    b) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000; Singh et al, 2013):
    1) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
    2) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
    3) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
    4) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.
    c) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):
    1) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
    2) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
    3) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
    4) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
    5) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
    6) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.
    2) MINOR DAMAGE
    a) SUMMARY
    1) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.
    b) ARTIFICIAL TEARS
    1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    c) TOPICAL CYCLOPLEGIC
    1) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000a; Grant & Schuman, 1993). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    d) TOPICAL ANTIBIOTICS
    1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000a; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008).
    e) PAIN CONTROL
    1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).
    3) EXTENSIVE DAMAGE
    a) SUMMARY
    1) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.
    b) ARTIFICIAL TEARS
    1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    c) PAIN CONTROL
    1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).
    d) CARBONIC ANHYDRASE INHIBITOR
    1) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    e) TOPICAL STEROIDS
    1) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993a).
    2) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
    3) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000b).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000b).
    f) ASCORBATE
    1) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
    2) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
    3) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993a). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000b).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000b).
    g) CITRATE
    1) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
    2) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
    3) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993a). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000b).
    a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000b).
    h) COLLAGENASE INHIBITORS
    1) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
    2) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
    3) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).
    i) ANTIBIOTICS
    1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000a; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).
    j) TOPICAL CYCLOPLEGIC
    1) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).
    k) SOFT CONTACT LENSES
    1) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.
    4) LATE TREATMENT
    a) SURGICAL THERAPY CAUSTIC EYE INJURY
    1) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
    2) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
    3) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
    4) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
    5) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
    6) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) SUMMARY
    1) Polyethylene glycol 300 or 400, isopropyl alcohol, or copious amounts of water are useful for decontamination of phenol, and may be helpful for cyanophenol. Decontamination personnel should take precautions.
    B) DECONTAMINANTS
    1) A solvent cleaner with both hydrophilic and hydrophobic portions may be useful to remove cyanophenol from the skin surface if readily available prior to irrigation.
    2) Undiluted polyethylene glycol 300 or 400 may be a useful solvent (Brown et al, 1975) and is available in bulk (non-sterile) from Sigma Chemical Co; however it was not shown to be more effective than copious (deluge) quantities of water for removal of phenol from swine, which are thought to be a good model for human skin (Pullin et al, 1978).
    3) Based on the animal model, isopropyl alcohol appears to be the decontaminant of choice in the treatment of limited phenol burns (less than 5% total body surface). Isopropyl alcohol is readily available, more efficacious than water, and allows less systemic absorption than water (Hunter et al, 1992).
    4) 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).
    C) PERSONNEL PROTECTION
    1) Decontamination personnel should wear rubber gloves. A soapy bath should be taken after treatment.
    6.9.2) TREATMENT
    A) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) Peritoneal and hemodialysis are of no value in removal of phenol and related compounds, but hemodialysis may be used to support uncontrolled acid-base or fluid electrolyte problems.

Range Of Toxicity

Summary

    A) The minimum lethal human dose to this agent has not been delineated.
    B) The maximum tolerated human exposure to this agent has not been delineated.
    C) From limited animal data, cyanophenol would appear to be much less acutely toxic than either cyanide or phenol.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) ANIMAL DATA
    1) Cyanophenol would appear to be much less toxic than either cyanide or phenol: pregnant rats survived a single oral gavage dose of 1000 mg/kg (Copeland et al, 1990).
    2) Cyanophenol appears to have similar acute potency as the closely related compound, BENZONITRILE. The latter has an oral LD50 in rats of 971 mg/kg (HSDB, 1995).

Workplace Standards

    A) ACGIH TLV Values for CAS611-20-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS611-20-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS611-20-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS611-20-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) AMA Department of DrugsAMA Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.
    14) Abbate C, Polito I, & Puglisi A: Dermatosis from resorcinal in tyre makers. Br J Industr Med 1989; 46:212-214.
    15) Aceto T Jr, Terplan K, & Fiore RR: Chemical burns of the esophagus in children and glucocorticoid therapy. J Med 1970; 1:101-109.
    16) Adam JS & Brick HG: Pediatric caustic ingestion. Ann Otol Laryngol 1982; 91:656-658.
    17) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    18) Anderson KD, Touse TM, & Randolph JG: A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990; 323:637-640.
    19) Artigas A, Bernard GR, Carlet J, et al: The American-European consensus conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling.. Am J Respir Crit Care Med 1998; 157:1332-1347.
    20) Atkinson GL & Shupak RC: Acute bronchospasm complicating intercostal nerve block with phenol. Anesth Analg 1989; 68:400-401.
    21) Azuara-Blanco A, Pillai CT, & Dua HS: Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol 1999; 83:399-402.
    22) Berlin CM Jr: Treatment of cyanide poisoning in children. Pediatrics 1970; 46:793-796.
    23) Boukthir S, Fetni I, Mrad SM, et al: [High doses of steroids in the management of caustic esophageal burns in children]. Arch Pediatr 2004; 11(1):13-17.
    24) Brodovsky SC, McCarty AC, & Snibson G: Management of alkali burns an 11-year retrospective review. Ophthalmology 2000; 107:1829-1835.
    25) Brodovsky SC, McCarty CA, & Snibson G: Management of alkali burns an 11-year retrospective review. Ophthalmology 2000b; 107:1829-1835.
    26) Brodovsky SC, McCarty CA, & Snibson G: Management of alkali burns an 11-year review. Ophthalmology 2000a; 107:1829-1835.
    27) Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.
    28) Brower RG, Matthay AM, & Morris A: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med 2000; 342:1301-1308.
    29) Brown VKH, Box VL, & Simpson BJ: Decontamination procedures for skin exposed to phenolic substances. Arch Environ Health 1975; 30:1-6.
    30) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    31) Caravati EM, Knight HH, & Linscott MS: Esophageal laceration and charcoal mediastinum complicating gastric lavage. J Emerg Med 2001; 20:273-276.
    32) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    33) Carvajal HF & Stewart CE: Emergency management of burn patients: the first few hours. Emerg Med Reports 1987; 8:129-136.
    34) Cataletto M: Respiratory Distress Syndrome, Acute(ARDS). In: Domino FJ, ed. The 5-Minute Clinical Consult 2012, 20th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2012.
    35) Cattan P, Munoz-Bongrand N, & Berney T: Extensive abdominal surgery after caustic ingestion. Ann Surg 2000; 231:519-523.
    36) Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.
    37) Chiene KY, Wang PY, & Lu KS: Esophagoplasty of corrosive stricture of the esophagus. Ann Surg 1974; 179:510-515.
    38) Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.
    39) Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.
    40) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    41) Cleveland WW, Chandler JR, & Lawson RB: Treatment of caustic burns of the esophagus. JAMA 1963; 186:182-183.
    42) Coln D & Chang JHT: Experience with esophageal stenting for caustic burns in children. J Pediatr Surg 1986; 21:588-592.
    43) Conning DM & Hayes MJ: The dermal toxicity of phenol: an investigation of the most effective first-aid measures. Br J Industr Med 1970; 27:155.
    44) Crain EF, Gershel JC, & Mezey AP: Caustic ingestions. Symptoms as predictors of esophageal injury. Am J Dis Child 1984a; 138(9):863-865.
    45) Crain EF, Gershel JC, & Mezey AP: Caustic ingestions; symptoms as predictors of esophageal injury. Am J Dis Child 1984; 138:863-865.
    46) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    47) De Busk RF & Seidl LG: Attempted suicide by cyanide: a report of two cases. Calif Med 1969; 110:394-396.
    48) Decker WJ, Combs HF, & Corby DG: Adsorption of drugs and poisons by activated charcoal. Toxicol Appl Pharmacol 1968; 13:454-460.
    49) Dmytryshyn JR, Gribble MJ, & Kassen BO: Chemical face peel complicated by toxic shock syndrome. Arch Otolaryngol 1983; 109:170-171.
    50) Dogan Y, Erkan T, Cokugras FC, et al: Caustic gastroesophageal lesions in childhood: an analysis of 473 cases. Clin Pediatr (Phila) 2006; 45(5):435-438.
    51) Dossing M, Wulff CH, & Olsen PZ: Repeated facial palsies after chlorocresol inhalation. J Neurol Neurosurg Psychiatr 1986; 49:1452-1454.
    52) Dunipace AJ, Beaven R, Noblitt T, et al: Mutagenic potential of toluidine blue evaluated in the Ames test. Mutat Res 1992; 279(4):255-259.
    53) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    54) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    55) Estrera A, Taylor W, & Mills LJ: Corrosive burns of the esophagus and stomach: a recommendation of an aggressive surgical approach. Ann Thorac Surg 1986; 41:276-283.
    56) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    57) Ferguson MK, Migliore M, & Staszak VM: Early evaluation and therapy for caustic esophageal injury. Am J Surg 1989; 157:116-120.
    58) Fish R & Davidson RS: Management of ocular thermal and chemical injuries, including amniotic membrane therapy. Curr Opin Ophthalmol 2010; 21(4):317-321.
    59) Fisher AA: Irritant and toxic reactions to phenol in topical medications. Cutis 1980; 26:363-392.
    60) Gandhi RP, Cooper A, & Barlow BA: Successful management of esophageal stricture without resection or replacement. J Pediatr 1989; 24:745-750.
    61) Gaudreault P, Parent M, & McGuigan MA: Predictability of esophageal injury from signs and symptoms: a study of caustic ingestion in 378 children. Pediatrics 1983; 71:761-770.
    62) Gaudreault P, Parent M, McGuigan MA, et al: Predictability of esophageal injury from signs and symptoms: a study of caustic ingestion in 378 children. Pediatrics 1983a; 71(5):767-770.
    63) Goldfrank LR, Flomenbaum NE, & Lewin NA: Goldfrank's Toxicologic Emergencies, 5th. Appleton-Century-Crofts, Norwalk, CT, USA, 1994.
    64) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    65) Gorman RL, Khin-Maung-Gyi MT, & Klein-Schwartz W: Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestions. Am J Emerg Med 1992; 10:89-94.
    66) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    67) Graham DL, Laman D, & Theodore J: Acute cyanide poisoning complicated by lactic acidosis and pulmonary edema. Arch Intern Med 1977; 137:1051-1055.
    68) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993.
    69) Grant WM & Schuman JS: Toxicology of the Eye, 4th ed, Charles C Thomas, Springfield, IL, 1993a.
    70) Gross BG: Cardiac arrhythmias during phenol face peeling. Plas Reconstr Surg 1983; 73:590-594.
    71) Gundogdu HZ, Tanyel FC, & Buyukpamukcu N: Conservative treatment of caustic esophageal strictures in children. J Pediatr Surg 1992; 27:767-770.
    72) Gupta SK, Croffie JM, & Fitzgerald JF: Is esophagogastroduodenoscopy necessary in all caustic ingestions?. J Ped Gastroenterol Nutr 2001; 32:50-53.
    73) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    74) Haddad LM, Dimond KA, & Schweistris JE: Phenol poisoning. JACEP 1979; 8:267.
    75) Hall AH & Rumack BH: Clinical toxicology of cyanide. Ann Emerg Med 1986; 15:1067-1074.
    76) Haller JA & Bachman K: The comparative effect of current therapy on experimental caustic burns of the esophagus. Pediatrics 1964; 236-245.
    77) Haller JA, Andrews HG, & White JJ: Pathophysiology and management of acute corrosive burns of the esophagus. J Pediatr Surg 1971; 6:578-584.
    78) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    79) Hawkins DB, Demeter MJ, & Barnett TE: Caustic ingestion: controversies in management. A review of 214 cases. Laryngoscope 1980; 90:98-109.
    80) Haynes BW Jr: Emergency department management of minor burns. Top Emerg Med 1981; 3:35-40.
    81) Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.
    82) Herman MI, Chyka PA, & Butlse AY: Methylene blue by intraosseous infusion for methemoglobinemia. Ann Emerg Med 1999; 33:111-113.
    83) Hix WR & Wilson WR: Toluidine blue staining of the esophagus: a useful adjunct in the panendoscopic evaluation of patients with squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1987; 113(8):864-865.
    84) Hjelt K, Lund JT, Scherling B, et al: Methaemoglobinaemia among neonates in a neonatal intensive care unit. Acta Paediatr 1995; 84(4):365-370.
    85) Ho SL & Hollinrake K: Acute epiglottitis and Chloraseptic. Br Med J 1989; 298:1584.
    86) Hogan RB & Polter DE: Nonsurgical management of lye-induced antral strictures with hydrostatic balloon dilation. Gastrointest Endosc 1986; 32:228-230.
    87) Howell JM, Dalsey WC, & Hartsell FW: Steroids for the treatment of corrosive esophageal injury: a statistical analysis of past studies. Am J Emerg Med 1992; 10:421-425.
    88) Howell JM: Alkaline ingestions. Ann Emerg Med 1987; 15:820-825.
    89) Howland MA: Antidotes in Depth. In: Goldfrank LR, Flomenbaum N, Hoffman RS, et al, eds. Goldfrank's Toxicologic Emergencies. 8th ed., 8th ed. McGraw-Hill, New York, NY, 2006, pp 826-828.
    90) Hsieh GC, Sharma RP, & Parker RDR: Immunological and neurobiochemical alterations induced by repeated oral exposure of phenol in mice. Eur J Pharmacother 1992; 228:107-114.
    91) Hunter DM, Timerding BL, & Leonard RB: Effects of isopropyl alcohol, ethanol, and polyethylene glycol/industrial methylated spirits in the treatment of acute phenol burns. Ann Emerg Med 1992; 21:1303-1307.
    92) Huy PTB & Celerier M: Management of severe caustic stenosis of the hypopharynx and esophagus by ileocolic transposition via suprahyoid or transepiglottic approach. Ann Surg 1988; 207:439-445.
    93) Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.
    94) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    95) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    96) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    97) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    98) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    99) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    100) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    101) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    102) Johnson RP & Mellors JW: Arteriolization of venous blood gases: a clue to the diagnosis of cyanide poisoning. J Emerg Med 1988; 6:401-404.
    103) Kamijo Y, Kondo I, Kokuto M, et al: Miniprobe ultrasonography for determining prognosis in corrosive esophagitis. Am J Gastroenterol 2004; 99(5):851-854.
    104) Kiese M , Lorcher W , Weger N , et al: Comparative studies on the effects of toluidine blue and methylene blue on the reduction of ferrihaemoglobin in man and dog. Eur J Clin Pharmacol 1972; 4(2):115-118.
    105) Kintz P, Tracqui A, & Mangin P: Accidental death caused by the absorption of 2,4-dichlorophenol through the skin. Arch Toxicol 1992; 66:298-299.
    106) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    107) Knox WG, Scott JR, & Zintel HA: Bouginage and steroids used singly or in combination in experimental corrosive esophagitis. Ann Surg 1967; 166:930-941.
    108) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    109) Lamireau T, Rebouissoux L, & Denis D: Accidental caustic ingestion in children: is endoscopy always mandatory?. J Ped Gastroenterol Nutr 2001; 33:81-84.
    110) Langeland T & Braathen LR: Allergic contact dermatitis from resorcinol. Contact Dermatitis 1987; 17:126.
    111) Leaver SK & Evans TW: Acute respiratory distress syndrome. BMJ 2007; 335(7616):389-394.
    112) Lindenmann J, Matzi V, Kaufmann P, et al: Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report. Inhal Toxicol 2006; 18(13):1047-1049.
    113) Link MS, Berkow LC, Kudenchuk PJ, et al: Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S444-S464.
    114) Little AG, Naunheim KS, & Ferguson MK: Surgical management of esophageal strictures. Ann Thorac Surg 1988; 45:144-147.
    115) LoVecchio F, Hamilton R, & Sturman K: A meta-analysis of the use of steroids in the prevention of stricture formation from second degree caustic burns of the esophagus (abstract). J Toxicol-Clin Toxicol 1996; 35:579-580.
    116) Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.
    117) Macek C: Venous thrombosis results from some phenol injections. JAMA 1983; 249:1807.
    118) Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.
    119) Marquez A & Todd M: Acute hemolytic anemia and agranulocytosis following intravenous administration of toluidine blue. Am Pract 1959; 10:1548-1550.
    120) Marshall F II: Caustic burns of the esophagus: ten year results of aggressive care. South Med J 1979; 72:1236-1237.
    121) Meller D, Pires RT, & Mack RJS: Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000; 107:980-990.
    122) Meredith JW, Kon ND, & Thompson JN: Management of injuries from liquid lye ingestion. J Trauma 1988; 28:1173-1180.
    123) Millar AJW, Numanoglu A, & Mann M: Detection of caustid oesophageal injury tiwh technetium 99m-labelled sucralfate. J Ped SUrg 2001; 36:262-265.
    124) Moazam F, Talbert JL, & Miller D: Caustic ingestion and its sequelae in children. South Med J 1987; 80:187-188.
    125) Morgan S & Murray A: Limbal autotransplantation in the acute and chronic phases of severe chemical injuries. Eye 1996; 10:349-354.
    126) Moylan JA: Burn care after thermal injury. Top Emerg Med 1980; 2:39-52.
    127) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    128) NHLBI ARDS Network: Mechanical ventilation protocol summary. Massachusetts General Hospital. Boston, MA. 2008. Available from URL: http://www.ardsnet.org/system/files/6mlcardsmall_2008update_final_JULY2008.pdf. As accessed 2013-08-07.
    129) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    130) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    131) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    132) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    133) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    140) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    141) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    142) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    143) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    144) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    145) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    146) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    147) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    148) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    149) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    150) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    151) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    152) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    153) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    154) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    155) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    156) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    157) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    158) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    159) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    160) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    161) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    162) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    163) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    164) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    165) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    166) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    167) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    168) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    169) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    170) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    171) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    172) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    173) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    174) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    175) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    176) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    177) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    178) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    179) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    180) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    181) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    182) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    183) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    184) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    185) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    186) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    187) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    188) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    189) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    190) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    191) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    192) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    193) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    194) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    195) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    196) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    197) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    198) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    199) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    200) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    201) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    202) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    203) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    204) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    205) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    206) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    207) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    208) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    209) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    210) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    211) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    212) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    213) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    214) Nemec K: Antidotes in acute poisoning. Eur J Hosp Pharm Sci Pract 2011; 17(4):53-55.
    215) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S729-S767.
    216) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    217) Nuutinen M, Uhari M, & Karvali T: Consequences of caustic ingestions in children. Acta Paediatr 1994; 83:1200-1205.
    218) Oakes DD, Sherck JP, & Mark JBD: Lye ingestion. J Thorac Cardiovasc Surg 1982; 83:194-204.
    219) Paulet G: Valeur et mecanisme d'action de l'oxygenotherapie dans le traitement de l'intoxication cyanhydrique. Arch Internat de Physiologie et de Biochimie 1955; 63:340-360.
    220) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    221) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    222) Pegg SP & Campbell DC: Children's burns due to cresol. Burns 1985; 11:294-296.
    223) Pelclova D & Navratil T: Do corticosteroids prevent oesophageal stricture after corrosive ingestion?. Toxicol Rev 2005; 24(2):125-129.
    224) Perry HD, Hodes LW, & Seedor JA: Effect of doxycycline hyclate on corneal epithelial wound healing in the rabbit alkali-burn model. Preliminary observations. Cornea 1993; 12:379-82.
    225) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    226) Previtera C, Giusti F, & Gugliemi M: Predictive value of visible lesions (cheeks, lips, oropharynx) in suspected caustic ingestion: may endoscopy reasonably be omitted in completely negative pediatric patients?. Pediatr Emerg Care 1990; 6:176-178.
    227) Product Information: CEREBYX(R) intravenous injection, fosphenytoin sodium intravenous injection. Pfizer Labs (per FDA), New York, NY, 2014.
    228) Product Information: Cordarone(R) oral tablets, amiodarone HCl oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadelphia, PA, 2015.
    229) Product Information: Dilantin(R) intravenous injection, intramuscular injection, phenytoin sodium intravenous injection, intramuscular injection. Parke-Davis (per FDA), New York, NY, 2013.
    230) Product Information: Lidocaine HCl intravenous injection solution, lidocaine HCl intravenous injection solution. Hospira (per manufacturer), Lake Forest, IL, 2006.
    231) Product Information: PROVAYBLUE(TM) intravenous injection, methylene blue intravenous injection. American Regent (per FDA), Shirley, NY, 2016.
    232) Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.
    233) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    234) Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.
    235) Product Information: methylene blue 1% IV injection, methylene blue 1% IV injection. American Regent, Inc (per manufacturer), Shirley, NY, 2011.
    236) Product Information: methylene blue 1% intravenous injection, methylene blue 1% intravenous injection. Akorn, Inc. (per manufacturer), Lake Forest, IL, 2011.
    237) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    238) Pullin TG, Pinkerton MN, & Johnston RV: Decontamination of the skin of swine following phenol exposure: a comparison of the relative efficacy of water versus polyethylene glycol/Industrial Methylated Spirits. Toxicol Appl Pharmacol 1978; 43:199-206.
    239) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    240) Reyes HM, Lin CY, & Schluhk FF: Experimental treatment of corrosive esophageal burns. J Pediatr Surg 1974; 9:317-327.
    241) Roberts JR: Minor burns (Pt II). Emerg Med Ambulatory Care News 1988; 10:4-5.
    242) Ronk JF, Ruiz-Esmenjaud S, & Osorio M: Limbal conjunctival autograft in subacute alkaline corneal burn. Cornea 1994; 13:465-468.
    243) Rosenberg N, Kunderman PJ, & Vroman L: Prevention of experimental esophageal stricture by cortisone II. Arch Surg 1953; 66:593-598.
    244) Saedi S, Nyhus LM, & Gabrys BF: Pharmacological prevention of esophageal stricture: an experimental study in the cat. Am Surg 1973a; 39:465-469.
    245) Saedi S, Nyhust LM, & Gabrys BF: Pharmacological prevention of esophageal stricture: an experimental study in the cat. Am Surg 1973; 39:465-469.
    246) Saunders A, Geddes L, & Elliott P: Are phenolic disinfectants toxic to staff members?. Aust Nurses J 1988; 17:25-26.
    247) Saydjari R, Abston S, & Desai MH: Chemical burns. J Burn Care Rehabil 1986; 7:404-408.
    248) Schild JA: Caustic ingestion in adult patients. Laryngoscope 1985; 95:1199-1201.
    249) Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.
    250) Seedor JA, Perry HD, & McNamara TF: Systemic tetracycline treatment of alkali-induced corneal ulceration in rabbits. Arch Ophthalmol 1987; 105:268-271.
    251) Shepherd G & Keyes DC: Methylene blue. In: Dart,RC, ed. Medical Toxicology, 3rd ed. 3rd ed, Philadelphia, PA, 2004, pp -.
    252) Singh P, Tyagi M, Kumar Y, et al: Ocular chemical injuries and their management. Oman J Ophthalmol 2013; 6(2):83-86.
    253) Spector J & Fernandez WG: Chemical, thermal, and biological ocular exposures. Emerg Med Clin North Am 2008; 26(1):125-136.
    254) Spiller HA, Quadranikushner DA, & Cleveland P: A 5-year evaluation of acute exposures to phenol disinfectant (26-percent). J Toxicol-Clin Toxicol 1993; 31:307-313.
    255) Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; Epub:Epub.
    256) Sridhar MS, Bansal AK, & Sangwan VS: Amniotic membrans transplantation in acute chemical and thermal injury. Am J Ophthalmol 2000; 130:134-137.
    257) Stanford SC , Stanford BJ , & Gillman PK : Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol 2010; 24(10):1433-1438.
    258) Stolbach A & Hoffman RS: Respiratory Principles. In: Nelson LS, Hoffman RS, Lewin NA, et al, eds. Goldfrank's Toxicologic Emergencies, 9th ed. McGraw Hill Medical, New York, NY, 2011.
    259) Su CY & Lin CP: Combined use of an amniotic membrane and tissue adhesive in treating corneal perforation: a case report. Ophtalmic Sufr Lasers 2000; 31:151-154.
    260) Sugawa C & Lucas CE: Caustic injury of the upper gastrointestinal tract in adults: a clinical and endoscopic study. Surgery 1989; 106:802-807.
    261) Symbas PN, Vlasis SE, & Hatcher CR Jr: Esophagitis secondary to ingestion of caustic material. Ann Thorac Surg 1983; 36:73-77.
    262) Teunis BS, Leftwich EI, & Pierce LE: Acute methemoglobinemia and hemolytic anemia due to toluidine blue. Arch Surg 1970; 101:527-531.
    263) Tosti A, Gaddoni G, & Piraccini BM: Occupational leukoderma due to phenolic compounds in the ceramics industry?. Contact Dermatitis 1991; 25:67-68.
    264) Treem WR, Long WR, & Friedman D: Successful management of an acquired gastric outlet obstruction with endoscopy guided balloon dilatation. J Pediatr Gastroenterol Nutr 1987; 6:992-996.
    265) Truppman ES & Ellenby JD: Major electrocardiographic changes during chemical face peeling. Plast Reconstr Surg 1979; 63:44-48.
    266) Tuft SJ & Shortt AJ: Surgical rehabilitation following severe ocular burns. Eye (Lond) 2009; 23(10):1966-1971.
    267) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    268) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    269) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    270) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    271) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    272) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    273) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    274) U.S. Food and Drug Administration: FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration. Silver Spring, MD. 2011. Available from URL: http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm. As accessed 2011-07-26.
    275) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    276) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    277) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    278) Vale JA, Kulig K, American Academy of Clinical Toxicology, et al: Position paper: Gastric lavage. J Toxicol Clin Toxicol 2004; 42:933-943.
    279) Vale JA: Position Statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711-719.
    280) Vanden Hoek TL, Morrison LJ, Shuster M, et al: Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S829-S861.
    281) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.
    282) Vergauwen p, Moulin D, & Buts JP: Caustic burns of the upper digestive and respiratory tracts. Eur J Pediatr 1991; 150:700-703.
    283) Vogel SN, Sultan TR, & Ten Eyck RP: Cyanide poisoning. Clin Toxicol 1981; 18:367-383.
    284) Wallace KL: Toxin-Induced Seizures. In: Brent J, Wallace KL, Burkhart KK, et al, eds. Critical Care Toxicology, Elsevier Mosby, Philadelphia, PA, 2005.
    285) Wijburg FA, Beukers MM, & Heymans HS: Nasogastric intubation as sole treatment of caustic esophageal lesions. Ann Otol Rhinol Laryngol 1985; 94:337-341.
    286) Wijburg FA, Heymans HS, & Urbanus NA: Caustic esophageal lesions in childhood: prevention of stricture formation. J Pediatr Surg 1989; 24(2):171-173.
    287) Willson DF, Truwit JD, Conaway MR, et al: The adult calfactant in acute respiratory distress syndrome (CARDS) trial. Chest 2015; 148(2):356-364.
    288) Wilson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. JAMA 2005; 293:470-476.
    289) Winek CL, Collom WD, & Martineau P: Toluidine blue intoxication. Clin Toxicol 1969; 2:1-3.
    290) Wu MH & Lai WW: Surgical management of extensive corrosive injuries of the alimentary tract. Surg Gynecol Obstetr 1993; 177:12-16.
    291) Yarington CT & Heatly CA: Steroids, antibiotics, and early esophagoscopy in caustic esophageal trauma. N Y State J Med 1963; 63:2960-2963.
    292) Zargar SA, Kochhar R, & Mehta S: The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. Gastrointest Endosc 1991; 37:165-169.
    293) Zargar SA, Kochhar R, & Nagi B: Ingestion of corrosive acids: spectrum of injury to upper gastrointestinal tract and natural history. Gastroenterology 1989; 97:702-707.
    294) de Caen AR, Berg MD, Chameides L, et al: Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S526-S542.
    295) do Nascimento TS, Pereira RO, de Mello HL, et al: Methemoglobinemia: from diagnosis to treatment. Rev Bras Anestesiol 2008; 58(6):651-664.
    296) van Heijst ANP, Douze JMC, & van Kasteren RG: Therapeutic problems in cyanide poisoning. Clin Toxicol 1987; 25:383-398.