1) Cyanide is released from methacrylonitrile after absorption.

1) Serious exposures may lead to asphyxia and death, although (as in acrylonitrile poisoning) only part of the symptomatology may be due to metabolically released cyanide.

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.

1) SODIUM NITRITE: Adult: 10 mL (300 mg) of a 3% solution IV at a rate of 2.5 to 5 mL/minute; Child (with normal hemoglobin concentration): 0.2 mL/kg (6 mg/kg) of a 3% solution IV at a rate of 2.5 to 5 mL/minute, not to exceed 10 mL (300 mg).
2) Repeat one-half of initial sodium nitrite dose one-half hour later if there is inadequate clinical response. Calculate pediatric doses precisely to avoid potentially life-threatening methemoglobinemia. Use with caution if carbon monoxide poisoning is also suspected. Monitor blood pressure carefully. Reduce nitrite administration rate if hypotension occurs.
3) SODIUM THIOSULFATE: Administer sodium thiosulfate IV immediately following sodium nitrite. DOSE: ADULT: 50 mL (12.5 g) of a 25% solution; CHILD: 1 mL/kg (250 mg/kg) of a 25% solution, not to exceed 50 mL (12.5 g) total dose. A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear.

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.

1) Rarely, clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy. 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.

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Dermal absorption with delayed onset of toxicity (up to several hours) may occur. Prolonged observation in a controlled setting is necessary.

1) A rapid pulse was noted following a convulsion in a dog chronically exposed to methacrylonitrile (Pozzani et al, 1968). This effect has not been reported in exposed humans.

1) Terminal asphyxia leading to death has been described in exposed experimental animals (Plunkett, 1976) ACGIH, 1986). This effect has not been described in exposed humans.

1) Weakness and headache have been described after exposure (Plunkett, 1976).

1) Convulsions and microscopic lesions in the brain have been described in fatally poisoned experimental animals (ACGIH, 1986; (Pozzani et al, 1968). These effects have not been reported in exposed humans.

1) Loss of consciousness was seen in fatally poisoned experimental animals before death and in some exposed animals that survived (Pozzani et al, 1968). This effect has not been reported in exposed humans.

1) Nausea, vomiting, and diarrhea may occur (Plunkett, 1976; Pozzani et al, 1968).

1) Jaundice has been described in exposed experimental animals (Plunkett, 1976; Schwanecke, 1966).

1) WBC ABNORMAL

1) Direct dermal contact with methacrylonitrile causes a delayed onset of mild dermatitis (Grant, 1986; Windholz et al, 1983; McOmie, 1949).

1) Dermal absorption readily occurs, although systemic toxicity may be delayed for up to several hours after cessation of exposure (Grant, 1986; EPA, 1985; Windholz et al, 1983).

1) Methacrylonitrile was a mild skin irritant in rabbit studies using the Standard Draize test (RTECS , 1991).

1) At the time of this review, no human data were available to assess the teratogenic potential of methacryonitrile.
2) RELATED COMPOUNDS - Acrylonitrile, a similar compound, has been shown to be teratogenic in experimental animals (Willhite et al, 1981).

1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

1) Not Listed

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

1) CARCINOMA

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
2) Monitoring whole blood cyanide and thiocyanate levels might be useful in significant exposures (Plunkett, 1976).
3) Interpretation of whole blood cyanide levels is difficult in methacrylonitrile poisoning. Available data for comparison are from cyanide poisoning itself, where continued metabolic release of cyanide is not a factor.
4) Blood Cyanide Levels and Associated Symptoms (Untreated Patients) (Graham et al, 1977):

  a.  No Symptoms:
         less than 0.2 mg/L (mcg/mL)
          (less than 0.02 mg% (mg/dL))
          (SI = less than 7.7 mcmol/L)
  b.  Flushing and Tachycardia:
         0.5 to 1 mg/L (mcg/mL)
          (0.05 to 0.1 mg% (mg/dL))
          (SI = 19.2 to 38.5 mcmol/L)
  c.  Obtundation:
         1 to 2.5 mg/L (mcg/mL)
          (0.1 to 0.25 mg% (mg/dL))
          (SI = 38.5 to 96.1 mcmol/L)
  d.  Coma and Respiratory Depression:
         greater than 2.5 mg/L (mcg/mL)
          (greater than 0.25 mg% (mg/dL))
          (SI = greater than 96.1 mcmol/L)
  e.  Death:
         greater than 3 mg/L (mcg/mL)
          (greater than 0.3 mg% (mg/dL))
          (SI = greater than 115.4 mcmol/L)

5) Blood Cyanide Levels Associated with Smoking (Clark et al, 1981):

  a.  Smokers:  up to 0.5 mg/L (mcg/mL)
                (up to 0.05 mg% (mg/dL))
                (SI = up to 19.2 mcmol/L)

6) Serum lactate levels may be useful in monitoring the severity of poisoning and the efficacy of treatment (Vogel et al, 1981).

1) 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).
2) A "%O2 SATURATION GAP" may exist with decreased MEASURED and normal CALCULATED arterial %O2 saturation values due to the propensity for some cyanide to form cyanhemoglobin which will not bind or transport oxygen (Hall & Rumack, 1986).
3) A REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen (Graham et al, 1977; Paulet, 1955).

1) If amyl and sodium nitrite are administered as antidotes, monitor methemoglobin levels, especially if more than one dose is needed as could be seen with continued metabolic release of cyanide after methacrylonitrile absorption. Maintain methemoglobin levels below 30% in all cases (Hall & Rumack, 1986).

1) Elevated urinary thiocyanate excretion may be noted in significant exposures (Plunkett, 1976).
2) Cyanide and thiocyanate levels can be measured in timed urine collections which may yield useful information on cyanide clearance.

1) MONITORING

a) Cyanide can also be measured in biological fluids by gas chromatography following conversion to cyanogen chloride by reaction with chloramine-T (HSDB, 1990).
b) An ion-specific electrode method has sometimes been used for measuring cyanide in biological specimens (Bismuth et al, 1984).
c) A fluorometric diffusion method based on detection of fluorescing p-benzoquinone derivatives can be used to determine cyanide in biological fluids (HSDB, 1990).

A) All symptomatic patients should be admitted to the hospital following a methacrylonitrile exposure. Whenever the cyanide antidote kit is used, the patient should be admitted to the intensive care unit.

A) There is no role for home management of methacrylonitrile exposure.

A) Consult a poison center or medical toxicologist for assistance in managing symptomatic patients.

A) Asymptomatic patients with a history of significant methacrylonitrile exposure but who are asymptomatic should be observed closely in the hospital. Vascular access should be established, laboratory evaluations performed, and the cyanide antidote kit or hydroxocobalamin ready at the bedside. If laboratory evaluations are normal and the patient remains asymptomatic for at least 8 hours, they may be discharged from the hospital with appropriate follow-up instructions.

1) In symptomatic patients, skip decontamination steps until other major emergency measures including use of the cyanide antidote kit, airway management, and administration of 100% supplemental oxygen have been instituted.

1) Do NOT induce EMESIS

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) 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).
2) PRECAUTIONS:
3) LAVAGE FLUID:
4) COMPLICATIONS:
5) CONTRAINDICATIONS:

1) Administer 100% oxygen to maintain an elevated pO2. Oxygen may reverse the cyanide-cytochrome oxidase complex and facilitate the conversion of cyanide to thiocyanate following sodium thiosulfate administration (Graham et al, 1977).
2) HYPERBARIC OXYGEN (HBO) THERAPY: is approved for the treatment of cyanide poisoning as a Category 1 condition (approved for third party reimbursement and known effective as treatment) by the Undersea Medical Society (Myers & Schnitzer, 1984). HBO treatment might be considered in patients with methacrylonitrile poisoning not responsive to supportive and antidotal therapy.

1) IV ACCESS: Establish at least one secure large bore intravenous line.
2) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
3) HYDROXOCOBALAMIN - CYANOKIT(R)
4) CYANIDE ANTIDOTE KIT

1) LABORATORY: Obtain blood for arterial blood gases with CALCULATED and MEASURED %O2 saturation, electrolytes, serum lactate, and cyanide and thiocyanate levels.
2) The following set of laboratory values suggest poisoning with an agent that produces an abnormal hemoglobin and inhibits oxidative phosphorylation (ie, cyanide, hydrogen sulfide, carbon monoxide) (Hall & Rumack, 1986). Carbon monoxide and hydrogen sulfide exposure can often be excluded by history. Acute carbon monoxide poisoning may also be excluded by a carboxyhemoglobin level. Cyanide and hydrogen sulfide poisoning are treated in essentially the same manner, (See Hydrogen Sulfide Management) with the exception of lack of efficacy of sodium thiosulfate in hydrogen sulfide poisoning. Administering sodium thiosulfate will do no harm to a hydrogen sulfide poisoned patient.

1) Administer sodium bicarbonate, 1 mEq/kg IV to acidotic patients. Base further sodium bicarbonate administration on serial arterial blood gas determinations.

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur in children receiving excessive nitrite doses.
2) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause 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
5) METHYLENE BLUE
6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

1) ALTERNATE ANTIDOTES

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE

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).
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).

1) In studies with mice, N-acetylcysteine (NAC, Mucomyst(R), Parvolex(R), used in the treatment of acetaminophen poisoning), was an effective methacrylonitrile antidote except at the very highest air concentrations (Peter & Bolt, 1985). The cyanide antidotes 4-dimethylaminophenol and sodium thiosulfate were also efficacious in this experiment, even at the highest air methacrylonitrile concentrations (Peter & Bolt, 1985).
2) The place of N-acetylcysteine in the treatment of human methacrylonitrile poisoning is presently undetermined. If considered, a dosing regimen similar to that used for acetaminophen (paracetamol) poisoning has been generally found to be safe.

1) All patients with methacrylonitrile exposure resulting in symptoms should be admitted to the hospital. Whenever the cyanide antidote kit is used, the patient should be admitted to the intensive care unit.

1) Patients with a history of significant methacrylonitrile exposure but who are asymptomatic should be observed closely in the hospital with an intravenous line in place and the antidotes ready at the bedside. If they remain asymptomatic for a period of 12 to 24 hours, they may be released from the hospital.

1) DELAYED ONSET: Following brief exposure to high vapor concentrations, experimental animals had a DELAYED ONSET of loss of consciousness, suggesting that humans briefly exposed to such concentrations should have a prolonged period of observation and monitoring in a controlled setting (Pozzani et al, 1968).

1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.

1) SYSTEMIC ABSORPTION: No cases of systemic cyanide poisoning in humans following methacrylonitrile ocular exposure have been reported.

1) 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).

1) SYSTEMIC ABSORPTION: Patients with dermal exposure should be evaluated immediately to determine the extent. If a severe exposure is suspected, observation and treatment as described in the ORAL EXPOSURE section should be followed.
2) DELAYED ONSET: Dermal absorption and delayed onset (up to several hours) of signs and symptoms of cyanide poisoning have been reported with other nitrile compounds such as acetonitrile (Amdur, 1959; Dequidt et al, 1974).

a) It has, however, been used in only one reported case, and antidote therapy with sodium nitrite and sodium thiosulfate was also administered (Wesson et al, 1985).
b) Limited animal studies, using historical controls and only a few animals, have so far shown some potential effectiveness when combined with thiosulfate infusion (Gonzales & Sabatini, 1989).
c) Hemodialysis cannot be considered standard therapy for cyanide poisoning at this time.

a) The outcome in this case was no different than that of other patients treated similarly without hemoperfusion.
b) Hemoperfusion cannot be considered standard therapy for cyanide poisoning at this time.

1) GENERAL
2) FATAL WHOLE BLOOD CYANIDE LEVELS AFTER ORAL INGESTION -

a) Adopted Value
b) Notice of Intended Changes

1) Listed as: Methylacrylonitrile
2) REL:
3) IDLH: Not Listed

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Methylacrylonitrile
2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Methylacrylonitrile
3) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Methacrylonitrile
4) 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
5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Methylacrylonitrile
6) MAK (DFG, 2002): Not Listed
7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

1) Not Listed

1) 250 mg/kg (Sax, 1989a)

a) Cytochrome oxidase inhibition causes cellular inability to utilize oxygen in oxidative phosphorylation, resulting in severely decreased ATP production, exhaustion of cellular energy stores, and a shift to anaerobic metabolism with resultant lactic acid production and metabolic acidosis (Vogel et al, 1981; Hall & Rumack, 1986).

a) These effects produce both stagnation and hypoxemic hypoxia in addition to histotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase.