ETHYL THIOCYANATE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1.2.1) MOLECULAR FORMULA
1) C3-H5-N-S

Available Forms Sources

1) Ethyl thiocyanate is a volatile liquid which is miscible with alcohol and ether, and is insoluble in water (HSDB , 1993). Ethyl thiocyanate is used as an insecticide (EPA, 1985). Aliphatic thiocyanates have rapid paralytic action in insects, attributable to the action of the thiocyano group (White-Stevens, 1971).
2) Little information was available on the health effects of ethyl thiocyanate. Its toxicity is expected to be similar to that of the more well-known aliphatic thiocyanate compounds, LETHANE and THANITE, and is due to the metabolic release of CYANIDE after absorption (Stern et al, 1952).
3) Cyanide acts by inhibiting cellular respiration. It binds strongly to the iron in respiratory proteins, preventing the utilization of oxygen for normal metabolism and cellular energy production. The spectrum of cyanide toxicity resembles that of anoxia (AH Hall , 1993).
4) This review is based on the effects of aliphatic thiocyanates in general and cyanide. Effects attributed specifically to ethyl thiocyanate are noted.

1) Some aliphatic thiocyanates can liberate HYDROGEN CYANIDE after absorption. As the symptoms of poisoning resemble those of cyanide intoxication, cyanide liberation has been considered to be responsible for many of the toxic manifestations of the aliphatic thiocyanates (Gosselin et al, 1984; Cameron et al, 1939; von Oettingen et al, 1936). A direct depressant effect on the medullary respiratory center may also occur (Cameron et al, 1939; von Oettingen et al, 1936).

1) CYANIDE is an extremely toxic respiratory poison in acute exposures, with a probable lethal human dose being <350 mg (HSDB , 1993). It is present in automotive emissions ((3)), in cigarette smoke (HSDB , 1993), and can be a major combustion product in fires, particularly from burning plastics (Peuser, 1984).

Overview

Life Support

Clinical Effects

0.2.1)

A) Ethyl thiocyanate is an aliphatic thiocyanate (rhodanate) compound used as an insecticide. It is a water-insoluble liquid.

1) Little data were available specifically for ethyl thiocyanate. It may be absorbed and produces systemic toxicity following ingestion. No data were available to determine whether or not ethyl thiocyanate can produce systemic toxicity by other routes of exposure.
2) Its toxicity is expected to be similar to that of the more well-known aliphatic thiocyanate compounds, Lethane and Thanite, and is due to the metabolic release of CYANIDE after absorption.

B) Some aliphatic thiocyanates can liberate hydrogen cyanide after absorption. As the symptoms of poisoning resemble those of cyanide intoxication, cyanide liberation has been considered to be responsible for many of the toxic manifestations of the aliphatic thiocyanates.

1) A direct depressant effect on the medullary respiratory centers may also occur.

C) Some of the toxicity may be due to the kerosene vehicle in which these agents are often supplied.
D) Vomiting, respiratory distress, cyanosis, apnea, coma, and convulsions have been described in patients ingesting these agents. Prolonged CNS depression and irritability were noted in a survivor. Aspiration pneumonitis may occur. Pulmonary edema has been reported. Conjunctival and dermal irritation may be seen. Mucosal irritation of the gastrointestinal and respiratory tracts may occur.
E) Onset of symptoms MAY BE DELAYED in some cases.
F) The aliphatic thiocyanate insecticides are direct irritants of eyes, skin, and mucous membranes in the respiratory and gastrointestinal tracts.
G) Ethyl thiocyanate releases toxic fumes of oxides of nitrogen and sulfur on thermal decomposition. Inhalation exposure to such combustion products would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

0.2.3)

A) Experimental animals administered lethane 384 initially have an increased respiratory rate followed rapidly by respiratory depression. One patient with lethane poisoning developed an elevated temperature associated with aspiration pneumonitis. Hypotension and shock were noted in a case of thanite poisoning.

0.2.4)

A) The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat. Exposed experimental animals have shown excessive salivation. Thanite is irritating to the conjunctiva.

0.2.5)

A) Death in cardiovascular collapse has been reported after ingestion of thanite. Experimental animals administered lethane 384 developed hypotension.

0.2.6)

A) Experimental animals exposed to lethane 384 vapor developed respiratory tract irritation, in some cases severe enough to be fatal. Pulmonary edema has occurred in oral poisoning with lethane 384 and thanite.
B) Pulmonary edema may occur in cyanide poisoning. If oxides of nitrogen or sulfur are released from thermal decomposition of aliphatic thiocyanates, pulmonary edema might also develop in exposed patients.

0.2.7)

A) Patients ingesting lethane 384 or thanite have developed coma or CNS depression. Generalized seizure activity or muscular "twitching" have been noted in humans ingesting lethane 384.

0.2.8)

A) Esophageal erosions or petechial hemorrhages have been noted at autopsy following fatal thanite and lethane 384 ingestions. Evidence of gastrointestinal tract mucosa irritation has been found in experimental animals given oral doses of lethane 384.
B) Ascites has been reported at autopsy in one case of human thanite ingestion.
C) Nausea and vomiting may be seen following ingestion.

0.2.9)

A) Liver injury may occur.

0.2.10)

A) Kidney injury may occur.

0.2.11)

A) While not reported in human exposures, the clinical presentation (coma, convulsions, circulatory compromise, and a possible cyanide poisoning component with inhibition of oxidative phosphorylation) of aliphatic thiocyanate poisoning may result in an elevated anion gap metabolic acidosis.

0.2.14)

A) Severe dermal irritation has been noted in exposed experimental animals and in some human exposures. Patch tests with thanite in human volunteers did not show sensitization to this material. Dermal application of lethane 384 in concentrations similar to those used as insecticides did not produce undue irritation in experimental animals.

0.2.20)

A) At the time of this review, no reproductive studies were found for ethyl thiocyanate in humans or experimental animals.
B) Rats housed in special enclosures painted with diluted or undiluted lethane 384 delivered healthy litters which grew normally.
C) Other compounds that release cyanide after absorption such as laetrile, cassava powder, acetonitrile, acrylonitrile, and propionitrile have caused teratogenic effects in the offspring of exposed experimental animals.
D) Some rats chronically administered aliphatic thiocyanates developed regressive testicular lesions with nearly complete absence of spermatic epithelium in the tubules, collapse of the lumina, and calcium concretions in some lumina.

0.2.21)

A) At the time of this review, no studies were found on possible carcinogenic effects of ethyl thiocyanate in humans.

Laboratory Monitoring

1) Cyanide can be measured chemically by several methods but the results cannot be obtained rapidly enough for assist in emergent diagnosis or treatment decisions; initial therapy should be based on clinical examination.

1) A REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen.

Treatment Overview

0.4.2)

A) In symptomatic patients, skip these steps until other major emergency measures including use of cyanide antidote kit and other life support measures have been instituted.
B) Perform gastric lavage with a large bore tube after endotracheal intubation.

1) 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.

a) 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.

C) 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.
D) An abdominal examination should be done in cases of aliphatic thiocyanate ingestion. Abdominal pain or tenderness, fever, hematemesis, or hematochezia should prompt an evaluation for gastrointestinal irritation, bleeding, ulceration, or perforation. In patients with esophageal symptoms, an esophagogram or esophagoscopy may be useful for evaluation.
E) In cases of possible aspiration of aliphatic thiocyanate insecticides containing large percentages of kerosene, obtain a baseline chest x-ray. If the initial chest x-ray is normal, repeat the examination 6 hours later, or sooner if symptoms or signs of respiratory distress or fever are noted.
F) ADMINISTER 100% OXYGEN: HYPERBARIC OXYGEN may be useful in severe cases not responsive to supportive and antidotal therapy.
G) Establish secure large bore IV access.
H) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
I) HYDROXYCOBALAMIN

1) HYDROXOCOBALAMIN: ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition. CHILDREN: Limited experience; a dose of 70 mg/kg has been used in pediatric patients.

J) CYANIDE ANTIDOTE KIT

1) Prepare the Cyanide Antidote Kit for use in symptomatic patients:

a) See Main Document under TREATMENT section by appropriate route of exposure for alternate antidotes not available in the US.
b) 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).
c) 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.
d) Reduce nitrite administration rate if hypotension occurs. Monitor methemoglobin levels; do NOT allow to exceed 30%.

2) 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.

K) SODIUM BICARBONATE: Administer 1 mEq/kg IV to significantly acidotic patients. Monitor arterial blood gases to guide further bicarbonate therapy.
L) 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.

M) METHEMOGLOBINEMIA

1) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause the release of cyanide from the cyanmethemoglobin complex. Such authors have suggested that emergency exchange transfusion is the treatment of choice. 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.

N) 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.
O) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
P) HEMODIALYSIS AND HEMOPERFUSION do not seem to be indicated or efficacious in most cases of cyanide poisoning.
Q) Patients with a history of significant cyanide exposure but who are asymptomatic should be observed closely in the hospital with an IV in place and the drugs drawn up ready at the bedside. If they remain asymptomatic for a period of 12 hours, they may be released from the hospital.

1) As serious toxicity was sometimes delayed for 6 to 12 hours after administration, initially asymptomatic patients should be observed in a controlled setting for at least 12 hours.
2) As delayed onset of serious toxicity may occur 6 to 12 hours following aliphatic thiocyanate exposure, patients with any symptoms should be admitted. Whenever the cyanide antidote kit is used, patients should be admitted to the intensive care unit.

0.4.3)

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) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
C) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.
D) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
E) All patients with significant inhalation exposure should be carefully observed for signs of SYSTEMIC CYANIDE POISONING. The following recommendations should be followed if significant cyanide poisoning is present.
F) 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.
G) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
H) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
I) SYSTEMIC CYANIDE POISONING

1) All patients with significant inhalation exposure should be carefully observed for signs of systemic cyanide poisoning. The following recommendations should be followed if significant cyanide poisoning is present.

J) ADMINISTER 100% OXYGEN; HYPERBARIC OXYGEN may be useful in severe cases not responsive to supportive and antidotal therapy.
K) Establish secure large bore IV access.
L) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
M) HYDROXOCOBALAMIN: ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition. CHILDREN: Limited experience; a dose of 70 mg/kg has been used in pediatric patients.
N) Prepare the cyanide antidote kit for use in symptomatic patients. See Main Document under TREATMENT section by appropriate route of exposure for alternate antidotes not available in the US.

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.

O) SODIUM BICARBONATE: Administer 1 mEq/kg IV to acidotic patients. Monitor arterial blood gases to guide further bicarbonate therapy.
P) 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).

Q) METHEMOGLOBINEMIA

R) 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.
S) HEMODIALYSIS AND HEMOPERFUSION do not seem to be indicated or efficacious in most cases of cyanide poisoning.

0.4.4)

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) SYSTEMIC CYANIDE POISONING from ocular exposure to aliphatic thiocyanate compounds has not been reported.

0.4.5)

A) OVERVIEW

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) No data were found on whether or not ethyl thiocyanate my be absorbed and cause systemic toxicity following dermal exposure.
3) SYSTEMIC CYANIDE POISONING

a) It is possible that systemic cyanide poisoning may occur following significant dermal exposure. The following recommendations should be followed if significant cyanide poisoning is present.
b) ADMINISTER 100% OXYGEN; HYPERBARIC OXYGEN may be useful in severe cases not responsive to supportive and antidotal therapy.
c) Establish secure large bore IV access.
d) A cyanide antidote, either hydroxocobalamin or the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
e) HYDROXOCOBALAMIN: ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition. CHILDREN: Limited experience; a dose of 70 mg/kg has been used in pediatric patients.
f) Prepare the cyanide antidote kit for use in symptomatic patients. See Main Document under TREATMENT section by appropriate route of exposure for alternate antidotes not available in the US.
g) Prepare the CYANIDE ANTIDOTE KIT for use in SYMPTOMATIC PATIENTS.

4) SODIUM BICARBONATE: Administer 1 mEq/kg IV to significantly acidotic patients. Monitor arterial blood gases to guide further bicarbonate therapy.
5) 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).

a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

6) METHEMOGLOBINEMIA

a) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause the release of cyanide from the cyanmethemoglobin complex. Such authors have suggested that emergency exchange transfusion is the treatment of choice. Hyperbaric oxygen therapy could be used to support the patient while preparations for exchange transfusion are being made.
b) 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.
c) 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.
d) 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.
e) 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.

7) 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.
8) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
9) HEMODIALYSIS AND HEMOPERFUSION do not seem to be indicated or efficacious in most cases of cyanide poisoning.
10) Significant toxicity followed dermal exposure in experimental animals, and symptom onset was delayed for 6 to 12 hours in some cases.

a) Patients with significant dermal exposure, especially to concentrated solutions of aliphatic thiocyanates, are at risk to develop delayed systemic toxicity and should be observed in a controlled setting for at least 12 hours.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

1) A direct depressant effect on the medullary respiratory centers may also occur.

Vital Signs

3.3.1)

3.3.2)

A) Experimental animals administered lethane 384 initially have an increased respiratory rate followed rapidly by respiratory depression (Cameron et al, 1939; von Oettingen et al, 1936).

3.3.3)

A) One patient with lethane poisoning developed an elevated temperature associated with aspiration pneumonitis (Guy, 1951).

3.3.4)

A) Hypotension and shock were noted in a case of thanite poisoning (Hayes, 1982). Hypotension was observed in experimental animals administered lethane 384 (von Oettingen et al, 1936).

Heent

3.4.1)

A) The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat. Exposed experimental animals have shown excessive salivation. Thanite is irritating to the conjunctiva.

3.4.3)

A) CONJUNCTIVITIS - Thanite is irritating to the eyes (Grant, 1993; Hayes, 1982).

3.4.5)

A) MUCOSAL IRRITATION - The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat (Gosselin et al, 1984; Hayes, 1982; Plunkett, 1976).

3.4.6)

A) MUCOSAL IRRITATION - The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat (Gosselin et al, 1984; Hayes, 1982; Plunkett, 1976).
B) HYPERSALIVATION - Exposed experimental animals have shown excessive salivation (Cameron et al, 1939).

Cardiovascular

3.5.1)

A) Death in cardiovascular collapse has been reported after ingestion of thanite. Experimental animals administered lethane 384 developed hypotension.

3.5.2)

A) HYPOTENSIVE EPISODE

1) Death in cardiovascular collapse has been reported after ingestion of thanite (Hayes, 1982). Experimental animals administered lethane 384 developed hypotension, although the heart was noted to continue beating for a short time after respiratory arrest occurred (Cameron et al, 1939).

Respiratory

3.6.1)

3.6.2)

A) IRRITATION SYMPTOM

1) Volunteers exposed to an atmosphere containing 60 mg/m(3) of thanite in kerosene developed irritation of the nose and throat that was usually reversible immediately on termination of exposure (Hayes, 1982).
2) Experimental animals exposed to lethane 384 vapor developed respiratory tract irritation, in some cases severe enough to be fatal (von Oettingen et al, 1936).

B) ACUTE LUNG INJURY

1) Pulmonary edema has occurred in oral poisoning with lethane 384 and thanite (Hayes, 1982; Harrison, 1947).
2) Pulmonary edema may occur in cyanide poisoning (Hall & Rumack, 1986). If oxides of nitrogen or sulfur are released from thermal decomposition of aliphatic thiocyanates (Lewis, 1996), pulmonary edema might also develop in exposed patients (Kizer, 1984).

C) ACUTE RESPIRATORY INSUFFICIENCY

1) Death from aliphatic thiocyanate poisoning is usually due to respiratory arrest from paralysis of the medullary centers (Sittig, 1991).

Neurologic

3.7.1)

A) Patients ingesting lethane 384 or thanite have developed coma or CNS depression. Generalized seizure activity or muscular "twitching" have been noted in humans ingesting lethane 384.

3.7.2)

A) COMA

1) Patients ingesting lethane 384 or thanite have developed coma or CNS depression (Hayes, 1982; Harrison, 1947; Guy, 1951; Coulter & Creery, 1953).

B) SEIZURE

1) Generalized seizure activity or muscular "twitching" have been noted in humans ingesting lethane 384 (Guy, 1951; Coulter & Creery, 1953). Exposed experimental animals develop convulsions (Cameron et al, 1939; von Oettingen et al, 1936).

Gastrointestinal

3.8.1)

3.8.2)

A) GASTRITIS

1) Esophageal erosions or petechial hemorrhages have been noted at autopsy following fatal thanite and lethane 384 ingestions (Hayes, 1982; Harrison, 1947).
2) Evidence of gastrointestinal tract mucosa irritation has been found in experimental animals given oral doses of lethane 384 (Cameron et al, 1939; von Oettingen et al, 1936).

B) ASCITES

1) Ascites has been reported at autopsy in one case of human thanite ingestion (Hayes, 1982).

C) NAUSEA AND VOMITING

1) Nausea and vomiting may be seen following ingestion (Sittig, 1991; Plunkett, 1976; Harrison, 1947).

Hepatic

3.9.1)

A) Liver injury may occur.

3.9.2)

A) LIVER DAMAGE

1) Liver injury may occur (EPA, 1985; Sittig, 1991).

Genitourinary

3.10.1)

A) Kidney injury may occur.

3.10.2)

A) KIDNEY DISEASE

1) Kidney injury may occur (EPA, 1985; Sittig, 1991).

Acid-Base

3.11.1)

3.11.2)

A) ACIDOSIS

1) While not reported in human exposures, the clinical presentation (coma, convulsions, circulatory compromise, and a possible cyanide poisoning component with inhibition of oxidative phosphorylation) of aliphatic thiocyanate poisoning would likely result in an elevated anion gap metabolic acidosis.

Dermatologic

3.14.1)

3.14.2)

A) SKIN IRRITATION

1) Severe dermal irritation has been noted in exposed experimental animals and in some human exposures (Cameron et al, 1939).
2) Patch tests with thanite in human volunteers did not show any sensitization to the material (Hayes, 1982).
3) Dermal application of lethane 384 in concentrations similar to those used as insecticides did not produce undue irritation in experimental animals (Cameron et al, 1939).

Reproductive

3.20.1)

3.20.2)

A) THYROID DISORDER

1) CYANIDE has been linked with congenital cretinism (deformities, dwarfism, and mental insufficiency) due to thyroid deficiency in regions of the world where cassava is a major part of the diet (Anon, 1972). The critical period is the first trimester, and damage can be prevented with iodine supplements (Anon, 1972).

B) ANIMAL STUDIES

1) LACK OF EFFECT

a) Lethane 384, a related compound, was not teratogenic in rats (Cameron et al, 1939).

1) Rats housed in special enclosures painted with diluted or undiluted lethane 384 delivered healthy litters which grew normally (Cameron et al, 1939).

2) CONGENITAL ANOMALY

a) Other compounds that release cyanide after absorption such as laetrile, cassava powder, acetonitrile, acrylonitrile, and propionitrile have caused teratogenic effects in the offspring of exposed experimental animals (Singh, 1981; Willhite, 1982) 1983; (Willhite et al, 1981).
b) Cyanide has also been teratogenic and has affected the fertility of laboratory animals. Chemicals which liberate cyanide are also known to be teratogenic in animals. This is especially true of the aliphatic nitriles (Willhite et al, 1981; Smith, 1981), including acrylonitrile (Buchter & Peter, 1984) and acetonitrile (Willhite, 1983).

3.20.3)

A) LACK OF INFORMATION

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.

3.20.4)

A) LACK OF INFORMATION

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.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS542-90-5 (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)

A) At the time of this review, no studies were found on possible carcinogenic effects of ethyl thiocyanate in humans.

3.21.3)

A) LACK OF INFORMATION

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

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) With current understanding of aliphatic thiocyanate poisoning, there is no value in measuring blood levels of these compounds.

B) Arterial blood gases and serum electrolytes are useful in the assessment of patients poisoned with cyanide.

1) A REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen.

C) Monitor methemoglobin levels during nitrite administration, especially if more than one dose is needed. Maintain methemoglobin levels below 30 percent.
D) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
E) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
F) Monitor the chest x-ray in patients with significant exposure.
G) MRI studies may be useful in identifying the location and extent of injury in patients with cyanide-induced Parkinsonian syndrome.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Blood levels of the aliphatic thiocyanate insecticides have not been reported in human poisoning cases and would be of undetermined value in assessing patients with exposure.
2) BLOOD CYANIDE LEVELS - Blood cyanide levels and associated symptoms in untreated patients (Graham et al, 1977)

No symptoms:  less than 0.2 mg/L (mcg/mL)
                        (0.02 mg%)
                        (SI = 7.7 mcmol/L)
Flushing and tachycardia:  0.5-1.0 mg/L (mcg/mL)
                           (0.05-0.1 mg%)
                           (SI = 19.2 to
                           38.5 mcmol/L)
Obtundation:  1.0-2.5 mg/L (mcg/mL)
              (0.1-0.25 mg%)
              (SI = 38.5 to
              96.1 mcmol/L)
Coma/Respiratory Depression:  greater than
                              2.5 mg/L (mcg/mL)
                              (0.25 mg%)
                              (SI = 96.1 mcmol/L)
Death:  greater than 3 mg/L (mcg/mL)
                     (0.3 mg%)
                     (SI = 115.4 mcmol/L)

3) Serum lactate levels may be useful in monitoring the severity of poisoning and the efficacy of treatment (Vogel et al, 1981).
4) 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.

B) ACID/BASE

1) SCREENING LABORATORY TESTS - 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 REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen (Graham et al, 1977; Paulet, 1955).

C) HEMATOLOGIC

1) Monitor methemoglobin levels during nitrite administration, especially if more than one dose is needed. Maintain methemoglobin levels below 30% (Hall & Rumack, 1986).

4.1.3)

A) URINALYSIS

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

4.1.4)

A) OTHER

1) MONITORING

a) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.

Radiographic Studies

1) Patients with significant inhalation exposure to aliphatic thiocyanates, respiratory tract irritation, or clinical suspicion of pulmonary edema should have a chest x-ray.
2) There is a large percentage of kerosene in many of these products. Patients who have aspirated these agents may have an initially normal chest x-ray. This examination should be repeated in six hours, or sooner if the patient develops symptoms or signs of hypoxemia or becomes febrile.

1) MRI studies may be useful in identifying the location and extent of injury in patients with cyanide-induced parkinsonian syndrome (Rosenberg et al, 1989; Carella et al, 1988).

Treatment

Life Support

Monitoring

1) A REDUCED ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE may be seen due to cellular inability to extract oxygen.

Oral Exposure

6.5.2)

A) MEDICAL FACILITY MANAGEMENT

1) LIFE SUPPORT: In severely symptomatic patients, skip these steps until other major emergency treatments including life support measures and administration of specific antidotes have been instituted.

B) EMESIS/NOT RECOMMENDED

1) Induced emesis should be avoided.

C) ACTIVATED CHARCOAL

1) 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.

2) 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).

D) GASTRIC LAVAGE

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).

a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2) 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.

3) 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.

4) 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).

5) 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.

6.5.3)

A) ABDOMINAL EXAMINATION FINDING

1) ABDOMINAL EXAMINATION: should be done in cases of aliphatic thiocyanate ingestion. Abdominal pain or tenderness, fever, hematemesis, or hematochezia should prompt an evaluation for gastrointestinal irritation, bleeding, ulceration, or perforation. In patients with esophageal symptoms, an esophagogram or esophagoscopy may be useful for evaluation.

B) MONITORING OF PATIENT

1) CHEST X-RAY: In cases of possible aspiration of aliphatic thiocyanate insecticides containing large percentages of kerosene, obtain a baseline chest x-ray. If the initial chest x-ray is normal, repeat the examination 6 hours later, or sooner if symptoms or signs of respiratory distress or fever are noted.
2) LABORATORY: Obtain blood for arterial blood gases, serum electrolytes, serum lactate, and whole blood cyanide.
3) INTERPRETATION OF LABORATORY VALUES

a) ARTERIAL PO2: Usually normal until the stage of hypoventilation or apnea. Usually remains normal until terminal stages of the poisoning if supplemental oxygen and assisted ventilation are provided.
b) SERUM ELECTROLYTES: Elevated anion gap (Na - (Cl + CO2)) (normals 12 to 16 milliequivalents/liter (12 to 16 millimoles/liter) or less) is present from the presence of unmeasured organic anions (usually lactate).
c) SERUM LACTATE: Elevated (normals 0.6 to 1.8 milliequivalents/liter) (0.6 to 1.8 millimoles/liter) due to anaerobic metabolism with excessive production of lactic acid.
d) ARTERIO-CENTRAL VENOUS MEASURED %O2 SATURATION DIFFERENCE: Due to cellular inability to extract and use oxygen, more is present on the venous side. The MEASURED values of arterial and central venous %O2 saturation approach each other with MEASURED central venous %O2 saturation greater than 70%.

C) OXYGEN

1) Administer 100% oxygen to maintain an elevated pO2. Oxygen may reverse the cyanide-cytochrome oxidase complex and facilitate the conversion to thiocyanate following thiosulfate administration (Graham et al, 1977). There is fairly good evidence that 100% oxygen, combined with traditional nitrite/thiosulfate therapy is better than thiosulfate alone (Litovitz et al, 1983; Way et al, 1972).
2) HYPERBARIC OXYGEN (HBO) THERAPY - is approved for cyanide poisoning as a category one condition (approved for third party reimbursement and known effective as treatment) by the Hyperbaric and Undersea Medical Society (Myers & Schnitzer, 1984). Hyperbaric oxygen has been suggested to improve clinical outcome, especially in those patients with CNS toxicity not responding to more traditional therapy. Animal studies have both confirmed and refuted this (Skene et al, 1966; Way et al, 1972; Takano et al, 1980).

a) Case reports suggest that HBO may be of value (Carden, 1970; Trapp, 1970). However, one patient treated with supportive therapy, antidotes, and HBO did not survive a serious poisoning (Litovitz et al, 1983). Hyperbaric oxygen should be reserved for those patients with significant symptoms (ie, coma, seizures, unstable vital signs) who do not respond to normal supportive and antidotal therapy, and for those poisoned with both cyanide and carbon monoxide secondary to smoke inhalation (Hart et al, 1985).

D) TOXIC EFFECT OF CYANIDE

1) IV ACCESS: Establish secure large bore IV 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)

a) ADULT DOSE: 5 g (two 2.5 g vials each reconstituted with 100 mL sterile 0.9% saline) administered as an intravenous infusion over 15 minutes. For severe poisoning, a second dose of 5 g may be infused intravenously over 15 minutes to 2 hours, depending on the patient's condition (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
b) PEDIATRIC DOSE: A dose of 70 mg/kg has been used in pediatric patients, based on limited post-marketing experience outside the US (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
c) INDICATIONS: Known or suspected cyanide poisoning.
d) ADVERSE EFFECTS: Transient hypertension, allergic reactions (including anaphylaxis), nausea, headache, rash. Hydroxocobalamin's deep red color causes red-colored urine in all patients, and erythema of the skin in most (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
e) LABORATORY INTERFERENCE: Because of its' color, hydroxocobalamin interferes with colorimetric determination of various laboratory parameters. It may artificially increase serum creatinine, bilirubin, triglycerides, cholesterol, total protein, glucose, albumin , alkaline phosphatase and hemoglobin. It may artificially decrease serum ALT and amylase. It may artificially increase urinary pH, glucose, protein, erythrocytes, leukocytes, ketones, bilirubin, urobilinogen, and nitrate (Prod Info CYANOKIT(R) 2.5g IV injection, 2006).
f) HEMODIALYSIS INTERFERENCE: Dialysis machines have a spectrophotometric safety measure that can shut down after detecting blood leaking across the dialysis membrane. Hydroxocobalamin has a deep red color and can permeate the dialysis membrane, coloring the dialysate and causing the hemodialysis machine to shut down erroneously. In one case report, a patient with cyanide poisoning underwent dialysis after receiving 5 g of IV hydroxocobalamin because of refractory acidemia, reduced kidney function and hyperkalemia. A blood leak alarm caused the dialysis machine to shut down erroneously, delaying therapy, and resulting in the death of the patient (Stellpflug et al, 2013).

4) CYANIDE ANTIDOTE KIT

a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT, consisting of sodium nitrite and sodium thiosulfate.

1) Antidotes should be used only in significantly symptomatic patients (ie, impaired consciousness, convulsions, acidosis, or unstable vital signs).
2) Even when patients are rendered comatose by the inhalation of hydrogen cyanide gas, antidotes may not be necessary if the exposure is rapidly terminated, the patient has regained consciousness on arrival at the medical facility, and there is no acidosis or abnormality of the vital signs (Peden et al, 1986).

5) SODIUM NITRITE

a) INDICATION

1) Sodium nitrite should be given initially and administered as soon as vascular access is established.
2) Further administration of sodium nitrite is dictated only by the clinical situation, provided no significant complications (hypotension, excessive methemoglobinemia) are present. Use with caution if carbon monoxide poisoning is also suspected.
3) The goal of nitrite therapy is to achieve a methemoglobin level of 20% to 30%. This level is not based on clinical data, but represents the tolerated concentration without significant adverse symptoms from methemoglobin in an otherwise healthy individual. Clinical response has been reported to occur with methemoglobin levels in the range of 3.6% to 9.2% (DiNapoli et al, 1989; Johnson et al, 1989; Johnson & Mellors, 1988).

b) ADULT DOSE

1) 10 mL of a 3% solution (300 mg) administered intravenously at a rate of 2.5 to 5 mL/minute (Prod Info NITHIODOTE intravenous injection solution, 2011). Frequent blood pressure monitoring must accompany sodium nitrite injection and the rate slowed if hypotension occurs.
2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011).

c) PEDIATRIC DOSE

1) The recommended pediatric sodium nitrite dose is 0.2 mL/kg of a 3% solution (6 mg/kg) administered intravenously at a rate of 2.5 to 5 mL/minute, not to exceed 10 mL (300 mg) (Prod Info NITHIODOTE intravenous injection solution, 2011).
2) If there is inadequate clinical response, an additional dose of sodium nitrite at half the amount of the initial dose may be administered 30 minutes following the first dose (Prod Info NITHIODOTE intravenous injection solution, 2011; Berlin, 1970a).
3) PRESENCE OF ANEMIA: If there is a reason to suspect the presence of anemia, the following initial sodium nitrite doses should be given, depending on the child's hemoglobin (sodium nitrite should not exceed the doses listed below; fatal methemoglobinemia may result) (Berlin, 1970a):

a) Hemoglobin: 8 g/dL - Initial 3% sodium nitrite dose: 0.22 mL/kg (6.6 mg/kg)
b) Hemoglobin: 10 g/dL - Initial 3% sodium nitrite dose: 0.27 mL/kg (8.7 mg/kg)
c) Hemoglobin: 12 g/dL (average child) - Initial 3% sodium nitrite dose: 0.33 mL/kg (10 mg/kg)
d) Hemoglobin: 14 g/dL - Initial 3% sodium nitrite dose: 0.39 mL/kg (11.6 mg/kg)

d) It is highly recommended that total hemoglobin and methemoglobin concentrations be rapidly measured (30 minutes after dose), when possible, before repeating a dose of sodium nitrite to be sure that dangerous methemoglobinemia will not occur, especially in the pediatric patient.
e) Monitor blood pressure frequently and treat hypotension by slowing infusion rate and giving crystalloids and vasopressors. Consider possible excessive methemoglobin formation if patient deteriorates during therapy.
f) Excessive methemoglobinemia and hypotension are potential complications of nitrite therapy.
g) In individuals with G6PD deficiency, therapy with methemoglobin-inducing agents is contraindicated because of the likelihood of serious hemolysis.

6) SODIUM THIOSULFATE

a) Sodium thiosulfate is the second component of the cyanide antidote kit. It is supplied as 50 mL of a 25% solution and it is administered intravenously. There are no adverse reactions to thiosulfate itself. The pediatric dose is adjusted for weight and not hemoglobin concentration.
b) Sodium thiosulfate supplies sulfur for the rhodanese reaction, and is recommended after sodium nitrite, hydroxocobalamin, or 4-DMAP (4-dimethylaminophenol) administration (Marrs, 1988; Hall & Rumack, 1987).
c) DOSE

1) Follow sodium nitrite with IV sodium thiosulfate. ADULT: Administer 50 mL (12.5 g) of a 25% solution IV; PEDIATRIC: 1 mL/kg of a 25% solution (250 mg/kg), not to exceed 50 mL (12.5 g) total dose (Prod Info NITHIODOTE intravenous injection solution, 2011).
2) A second dose, one-half of the first dose, may be administered if signs of cyanide toxicity reappear (Prod Info NITHIODOTE intravenous injection solution, 2011).
3) Sodium thiosulfate is usually used in combination with sodium nitrite but may be used alone (Prod Info sodium thiosulfate IV injection, 2003).
4) Sodium thiosulfate can be administered without sodium nitrite in patients at risk to develop further methemoglobinemia (ie excessive methemoglobinemia or hypotension after initial sodium nitrite administration or in the presence of methemoglobinemia or carboxyhemoglobin in patients with smoke inhalation due to fire). Sodium thiosulfate can also be used in combination with hydroxocobalamin to treat cyanide poisoning (Howland, 2011)
5) CONTINUOUS INFUSION: It has been suggested that a continuous infusion of sodium thiosulfate be given after the initial bolus to maintain high thiosulfate levels. Low sodium intravenous fluids are required to avoid sodium overload. If large amounts of sodium thiosulfate are required, hemodialysis may be necessary to maintain a physiologic serum sodium level (Turchen et al, 1991).
6) ADVERSE EVENTS: Sodium thiosulfate does not usually produce significant toxicity. Possible adverse events include hypotension, headache, nausea, vomiting, disorientation, and prolonged bleeding time (Prod Info NITHIODOTE intravenous injection solution, 2011).

E) ACIDOSIS

1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
2) Acidosis may be difficult to correct prior to administration of antidotes in serious cyanide poisoning cases (Hall & Rumack, 1986).

F) 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, 2010; 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).

G) METHEMOGLOBINEMIA

1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur in children receiving excessive nitrite doses.
2) If excessive methemoglobinemia occurs, some authors have suggested that methylene blue should not be used because it could cause the release of cyanide from the cyanmethemoglobin complex. Such authors have suggested that emergency exchange transfusion is the treatment of choice (Berlin, 1970). Hyperbaric oxygen therapy could be used to support the patient while preparations for exchange transfusion are being made.
3) However, methylene or toluidine blue have been used successfully in this setting without worsening the course of the cyanide poisoning (van Heijst et al, 1987). There is some controversy over whether or not the induction of methemoglobinemia is the sodium nitrite mechanism of action in cyanide poisoning. As long as intensive care monitoring and further antidote doses (if required) are available, methylene blue can most likely be safely administered in this setting.
4) SUMMARY

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

5) METHYLENE BLUE

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

H) ANTIDOTE

1) ALTERNATE ANTIDOTES

a) DICOBALT-EDTA (KELOCYANOR(R))

1) Dicobalt-EDTA (Kelocyanor(R)) is a highly effective cyanide chelating agent currently used in Europe and Australia. Significant toxicity from the antidote (severe hypertension or hypotension, cardiac ischemia or arrhythmias) may be seen in patients incorrectly diagnosed as being poisoned by cyanide and administered this antidote (Pronczuk de Garbino & Bismuth, 1981). Severe anaphylactoid reactions with airway compromise may also occur (Dodds & McKnight, 1985). Dicobalt-EDTA is not available in America.

b) 4-DIMETHYLAMINOPHENOL (4-DMAP)

1) 4-DMAP - is a methemoglobin inducing agent used in some European countries for the treatment of acute cyanide poisoning. Excessive methemoglobinemia may be a major complication following the use of this agent (van Dijk et al, 1986).

c) STROMA-FREE METHEMOGLOBIN SOLUTION

1) Stroma-free methemoglobin solution prepared from outdated human red blood cells by oxidation of the ferrous iron of hemoglobin to the ferric form in vitro has been studied in experimental animals and shows promise as a cyanide antidote (Ten Eyck et al, 1985). It has not been studied in human poisoning cases and is not available for human administration.

d) ALPHA-KETOGLUTARIC ACID

1) Alpha-ketoglutaric acid is also being tested as a replacement for sodium nitrite in combination with sodium thiosulfate in animal models where it has been efficacious in experimental cyanide poisoning (Moore et al, 1986). It has not been studied in human poisoning cases and is not available for human administration.

e) CHLORPROMAZINE

1) Chlorpromazine has been studied in various animal models as a possible cyanide antidote. Conflicting reports of efficacy have been published (Pettersen & Cohen, 1986). It has not been studied in human poisoning cases.

I) 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).

J) 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).

K) HOSPITAL ADMISSION

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

a) As delayed onset of serious toxicity may occur 6 to 12 hours following aliphatic thiocyanate exposure (Cameron et al, 1939), patients with any symptoms should be admitted. Whenever the cyanide antidote kit is used, patients should be admitted to the intensive care unit.

L) OBSERVATION REGIMES

1) Patients with a history of significant cyanide exposure but who are asymptomatic should be observed closely in the hospital with an IV in place and the drugs drawn up ready at the bedside. If they remain asymptomatic for a period of 12 hours, they may be released from the hospital.

a) As serious toxicity was sometimes delayed for 6 to 12 hours after administration (Cameron et al, 1939), initially asymptomatic patients should be observed in the ICU for at least 12 hours.

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) IRRITATION SYMPTOM

1) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
2) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.

B) MONITORING OF PATIENT

1) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
2) LABORATORY: Obtain blood for arterial blood gases, serum electrolytes, serum lactate, and whole blood cyanide.
3) INTERPRETATION OF LABORATORY VALUES

C) ACUTE LUNG INJURY

D) OXYGEN

1) Administer 100% oxygen to maintain an elevated pO2. Oxygen may reverse the cyanide-cytochrome oxidase complex and facilitate the conversion to thiocyanate following thiosulfate administration (Graham et al, 1977). There is fairly good evidence that 100% oxygen, combined with traditional nitrite/thiosulfate therapy is better than thiosulfate alone (Litovitz et al, 1983; Way et al, 1972).
2) HYPERBARIC OXYGEN (HBO) THERAPY is approved for cyanide poisoning as a category one condition (approved for third party reimbursement and known effective as treatment) by the Hyperbaric and Undersea Medical Society (Myers & Schnitzer, 1984). Hyperbaric oxygen has been suggested to improve clinical outcome, especially in those patients with CNS toxicity not responding to more traditional therapy. Animal studies have both confirmed and refuted this (Skene et al, 1966; Way et al, 1972; Takano et al, 1980).

a) Case reports suggest that HBO may be of value (Carden, 1970; Trapp, 1970). However, one patient treated with supportive therapy, antidotes, and HBO did not survive a serious poisoning (Litovitz et al, 1983). Hyperbaric oxygen should be reserved for those patients with significant symptoms (i.e., coma, seizures, unstable vital signs) who do not respond to normal supportive and antidotal therapy, and for those poisoned with both cyanide and carbon monoxide secondary to smoke inhalation (Hart et al, 1985).

E) TOXIC EFFECT OF CYANIDE

1) IV ACCESS: Establish secure large bore IV line access.
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

a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT, consisting of sodium nitrite and sodium thiosulfate.

5) SODIUM NITRITE

a) INDICATION

b) ADULT DOSE

c) PEDIATRIC DOSE

6) SODIUM THIOSULFATE

F) ACIDOSIS

G) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

H) METHEMOGLOBINEMIA

5) METHYLENE BLUE

6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

I) ANTIDOTE

1) ALTERNATE ANTIDOTES

a) DICOBALT-EDTA (KELOCYANOR(R))

b) 4-DIMETHYLAMINOPHENOL (4-DMAP)

1) 4-DMAP is a methemoglobin inducing agent used in some European countries for the treatment of acute cyanide poisoning. Excessive methemoglobinemia may be a major complication following the use of this agent (van Dijk et al, 1986).

c) STROMA-FREE METHEMOGLOBIN SOLUTION

d) ALPHA-KETOGLUTARIC ACID

e) CHLORPROMAZINE

J) HYPOTENSIVE EPISODE

1) SUMMARY

2) DOPAMINE

3) NOREPINEPHRINE

K) HOSPITAL ADMISSION

a) Patients with respiratory tract irritation or significant inhalation exposure to oxides of nitrogen or oxides of sulfur from thermal decomposition of aliphatic thiocyanates (Lewis, 1996) should be admitted for at least 24 hours of ICU observation (Kizer, 1984).

L) OBSERVATION REGIMES

M) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

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)

A) SUPPORT

1) SYSTEMIC CYANIDE POISONING from ocular exposure to aliphatic thiocyanate compounds has not been reported.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).

6.9.2)

A) SKIN ABSORPTION

1) Significant toxicity followed dermal exposure in experimental animals, and symptom onset was delayed for 6 to 12 hours in some cases (Cameron et al, 1939).

B) OXYGEN

1) Administer 100% oxygen to maintain an elevated pO2. Oxygen may reverse the cyanide-cytochrome oxidase complex and facilitate the conversion to thiocyanate following thiosulfate administration (Graham et al, 1977). There is fairly good evidence that 100% oxygen, combined with traditional nitrite/thiosulfate therapy is better than thiosulfate alone (Litovitz et al, 1983; Way et al, 1972).
2) HYPERBARIC OXYGEN (HBO) THERAPY is approved for cyanide poisoning as a category one condition (approved for third party reimbursement and known effective as treatment) by the Hyperbaric and Undersea Medical Society (Myers & Schnitzer, 1984). Hyperbaric oxygen has been suggested to improve clinical outcome, especially in those patients with CNS toxicity not responding to more traditional therapy. Animal studies have both confirmed and refuted this (Skene et al, 1966; Way et al, 1972; Takano et al, 1980).

a) Case reports suggest that HBO may be of value (Carden, 1970; Trapp, 1970). However, one patient treated with supportive therapy, antidotes, and HBO did not survive a serious poisoning (Litovitz et al, 1983). Hyperbaric oxygen should be reserved for those patients with significant symptoms (i.e., coma, seizures, unstable vital signs) who do not respond to normal supportive and antidotal therapy, and for those poisoned with both cyanide and carbon monoxide secondary to smoke inhalation (Hart et al, 1985).

C) TOXIC EFFECT OF CYANIDE

4) CYANIDE ANTIDOTE KIT

a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT, consisting of sodium nitrite and sodium thiosulfate.

5) SODIUM NITRITE

a) INDICATION

b) ADULT DOSE

c) PEDIATRIC DOSE

6) SODIUM THIOSULFATE

D) ACIDOSIS

E) MONITORING OF PATIENT

1) LABORATORY: Obtain blood for arterial blood gases, serum electrolytes, serum lactate, and whole blood cyanide.
2) INTERPRETATION OF LABORATORY VALUES

F) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

G) METHEMOGLOBINEMIA

5) METHYLENE BLUE

6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

H) ANTIDOTE

1) ALTERNATE ANTIDOTES

a) DICOBALT-EDTA (KELOCYANOR(R))

b) 4-DIMETHYLAMINOPHENOL (4-DMAP)

c) STROMA-FREE METHEMOGLOBIN SOLUTION

d) ALPHA-KETOGLUTARIC ACID

e) CHLORPROMAZINE

I) HYPOTENSIVE EPISODE

1) SUMMARY

2) DOPAMINE

3) NOREPINEPHRINE

J) ACUTE LUNG INJURY

K) HOSPITAL ADMISSION

L) OBSERVATION REGIMES

M) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) A successful suicidal adult has apparently ingested an estimated 0.07 milliliter/kilogram of 49 percent Lethane 384 (539 milligram/kilogram) and 0.206 milliliter/kilogram of 37.5 percent lauryl thiocyanate (412.5 milligram/kilogram) contained in Lethane hair oil (pediculoside) (Harrison, 1947).
2) A 23-month-old child died after ingesting an undetermined amount ("small quantity") of a similar preparation (Coulter & Creery, 1953).
3) The fatal dose of cyanide salts is estimated at 200 to 300 milligrams for an adult (Bonnichsen & Maely, 1966; Baselt & Cravey, 1989).

1) Inhalation of air concentrations of 0.2 to 0.3 milligrams per liter (200 to 300 parts per million) is rapidly fatal (ACGIH, 1986).

Maximum Tolerated Exposure

1) A 20-month-old child survived the ingestion of between 3.5 and 7 milliliters of a lethane hair oil (1,750 to 3,500 milligrams of lethane 384) (Guy, 1951).
2) CASE SERIES - 292 subjects exposed to a 5 percent solution of technical thanite in a refined kerosene vehicle as a dense fog with a thanite concentration of 60 milligrams/cubic meter developed only mild irritation of the nose, throat, and eyes that usually subsided immediately on termination of exposure (Hayes, 1982).

1) In the concentrations usually employed in agriculture, no dermal toxicity of the aliphatic thiocyanates have been observed in experimental animals (Cameron et al, 1939).
2) These agents are generally considered safe when used in these dilute concentrations (Gosselin et al, 1984), but care and dermal protection must be used when handling the concentrated materials (Cameron et al, 1939).
3) Patients have survived exposure to air concentrations of 500 milligrams per cubic meter (Bonsall, 1984), ingestions of one gram of potassium cyanide (Yacoub et al, 1974; Hall et al, 1987), and complete immersion in solutions of cyanide salts (Bismuth et al, 1984; Dodds & McKnight, 1985).

Workplace Standards

1) Not Listed

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

1) Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 1999

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 10 mg/kg

2) LD50- (SUBCUTANEOUS)MOUSE:

a) 70 mg/kg

Pharmacology Toxicology

Physicochemical

Physical Characteristics

Molecular Weight

Animal Toxicology

References

General Bibliography

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ETHYL THIOCYANATE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Dermatologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Life Support

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Physical Characteristics

Molecular Weight

General Bibliography