POTASSIUM CYANIDE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1.2.1) MOLECULAR FORMULA
1) CKN
2) C-K-N
3) CN.K
4) C-N.K
5) KCN

Available Forms Sources

1) Potassium cyanide can be produced by combining potassium hydroxide and hydrogen cyanide (salt formation) (Ashford, 1994a).

1) Potassium cyanide is used to extract gold and silver from ores. It also is used in electroplating and as an insecticide, a fumigant, and a reagent in analytical chemistry (Lewis, 1997a).
2) The compound is used as a benzoin condensation catalyst, a component in metal surface hardening salts, in metal cleaning, and as a raw material in the manufacture of pigments, nylon, dyes, and chelating agents (ACGIH, 1991a; Ashford, 1994a).

Overview

Life Support

Clinical Effects

0.2.1)

A) Potassium cyanide is an alkaline cyanide salt compound. It is decomposed by water (slowly) and by acids (rapidly) releasing flammable and highly toxic HYDROGEN CYANIDE gas.

1) In water of neutral pH, not enough hydrogen cyanide gas is released to be dangerous, except in enclosed spaces. However, if the water is acidic, significant amounts of hydrogen cyanide gas may be released. While potassium cyanide is not volatile, reaction of suspended dust particles with moisture and carbon dioxide in the air can result in release of some hydrogen cyanide.

B) Dermal contact with the moist solid material can result in skin irritation or ulceration. Chronic occupational cyanide exposure has been associated with a variety of dermal and mucous membrane irritant complaints, usually attributed to exposure to highly alkaline aerosols or solutions of cyanide salts.
C) True chronic cyanide toxicity in humans is rare, although a variety of complaints including goiter, subclinical thyroid dysfunction, B12 and folate abnormalities, headaches, vertigo, chest discomfort, palpitations, eye and respiratory irritation, dermatitis, fatigue, poor appetite and sleeping, and epistaxis have been recorded in cyanide-exposed workers.

1) Functional changes in hearing, loss of appetite, headache, weakness, nausea, dizziness, upper respiratory tract irritation, and dermatoses have been described in chronically exposed workers.

D) Potassium cyanide exposure may produce death within minutes. IMMEDIATELY BEGIN ADMINISTERING 100% OXYGEN. OBTAIN THE CYANIDE ANTIDOTE KIT AND PREPARE IT FOR USE.

1) Lesser exposures may produce nausea, vomiting, palpitations, confusion, hyperventilation, anxiety, and vertigo. Severe hypoxic signs in the absence of cyanosis suggest the diagnosis. Patients have survived potentially lethal ingestions with supportive care only, and the absence of a rapidly deteriorating course does not exclude the diagnosis.
2) Cyanosis is generally a late finding and does not occur until the stage of circulatory collapse and apnea. Initially the patient may experience flushing, tachycardia, tachypnea, headache, and dizziness. This may progress to agitation, stupor, coma, apnea, generalized convulsions, pulmonary edema, bradycardia, hypotension, and death.

E) Percutaneous absorption has been rarely said to result in systemic toxicity, although most such cases have involved either complete immersion in cyanide-salt solutions or large-area burns with molten cyanide.

0.2.3)

A) The initial presentation of cyanide poisoning may include hyperpnea and tachypnea. Hypoventilation progressing to apnea may be seen in the later phases of cyanide poisoning and is a major cause of death.
B) Tachycardia and hypertension may be seen in the initial phases of cyanide poisoning. Bradycardia and hypotension are seen in the late phases of cyanide poisoning.

0.2.4)

A) Dilated pupils are common. Corneal edema may be seen. Retinal arteries and veins that appear equally red on funduscopic examination suggest the diagnosis. A burning sensation in the mouth and throat may occur following ingestion.
B) Accidental eye contamination with cyanide compounds may produce systemic symptoms.

0.2.5)

A) Tachycardia and hypertension may be seen in the initial phases of cyanide poisoning. Bradycardia and hypotension are seen in the late phases of cyanide poisoning.
B) Erratic atrial and ventricular cardiac rhythms with varying degrees of atrioventricular block followed by asystole may be seen; ST-T segment elevation or depression may be noted.

0.2.6)

A) Hyperpnea and tachypnea may be noted initially. Hypoventilation progressing to apnea may be seen in the later phases and is a major cause of death.
B) Acute lung injury (noncardiogenic pulmonary edema) has been reported in cases of acute cyanide poisoning, even following ingestion. Cyanosis is a late finding and does not occur until the stage of apnea and circulatory collapse.

0.2.7)

A) Headache, CNS stimulation with anxiety, agitation, and combative behavior, coma, and seizures may be seen. Opisthotonos, trismus, and paralysis were reported in one case of cyanide poisoning.
B) Most victims of acute poisoning either die acutely or fully recover, but rare cases of neurological sequelae such as personality changes, memory deficits, and extrapyramidal (Parkinsonian-like) syndromes have been reported.

0.2.8)

A) Nausea, vomiting, and abdominal pain may occur, especially after ingestion. Ingestion of cyanide salts can cause irritation or corrosion of the esophageal or gastric mucosa.

0.2.11)

A) Elevated anion gap metabolic acidosis and elevated serum lactate levels may be found.

0.2.12)

A) An elevated anion gap metabolic acidosis is seen in cyanide poisoning, largely from excess production of lactic acid.

0.2.14)

A) Direct dermal contact with moist potassium cyanide can cause skin irritation or ulceration.
B) Cyanide has been said to be absorbed through intact skin and carries a "skin" designation for workplace exposures.
C) However, most cases of toxicity from dermal exposure have been due to industrial accidents with immersion in vats of cyanide solutions or severe, large total body area burns with molten cyanide.

0.2.16)

A) Insulin resistance was noted in a severely cyanide poisoned patient.

0.2.17)

A) Subclinical derangements of B12 and folate metabolism were noted in a group of chronically exposed cyanide workers.

0.2.20)

A) POTASSIUM CYANIDE - Fetotoxicity has been noted in the offspring of rats and domestic animals administered potassium cyanide. However, some rat studies have been negative for teratogenicity.
B) RELATED COMPOUNDS - Sodium cyanide, acetonitrile, acrylonitrile, propionitrile, and laetrile caused resorptions or malformations in the offspring of hamsters. Cassava was teratogenic in rats.
C) Subchronic dosing (12 mg of potassium cyanide injected subcutaneously for 28 doses during 6 weeks) caused degenerative changes in the testes of rats.

0.2.21)

A) POTASSIUM CYANIDE - There are no reports of carcinogenicity in humans or experimental animals due to potassium cyanide itself.
B) RELATED COMPOUNDS - Acrylonitrile has carcinogenic properties in some species of experimental animals and has been suggested to be associated with a slight increase in deaths from lung cancer and other malignancies in humans. Whether the metabolic release of cyanide plays any role in this carcinogenesis is unknown.

0.2.22)

A) Patients with cyanide poisoning characteristically have an odor of bitter almonds in gastric contents or expired breath. However, up to 50% of the population is genetically unable to detect this odor.

Laboratory Monitoring

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) Perform gastric lavage with a large bore tube after endotracheal intubation.

1) 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.

B) Administer 100% oxygen and establish a secure large-bore IV access.
C) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
D) 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.
E) The Cyanide Antidote Kit is administered as follows:

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.

F) SODIUM BICARBONATE: Administer 1 mEq/kg IV to acidotic patients.
G) 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.

H) METHEMOGLOBINEMIA

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 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.

I) HYPERBARIC OXYGEN and HEMODIALYSIS: May be useful in severe cases not responsive to other therapy.
J) 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.
K) ALTERNATE ANTIDOTES

1) Kelocyanor(R) (dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are alternate cyanide antidotes in clinical use in various countries outside the US. See TREATMENT SECTION in the main body of this document for more information.

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) 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.
C) 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.
D) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
E) 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.
F) 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.

G) Administer 100% oxygen. HYPERBARIC OXYGEN may be useful in severe cases not responsive to supportive and antidotal therapy.
H) Establish a secure large-bore IV access.
I) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
J) 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.
K) The Cyanide Antidote Kit is administered as follows:

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

N) METHEMOGLOBINEMIA

1) Rarely, clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy. Some authors have suggested that methylene blue should not be used in this setting, 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 blue or toluidine blue have been used successfully in this setting without worsening the clinical course of cyanide poisoning. There is some controversy over whether or not the induction of methemoglobinemia is the sodium nitrite mechanism action in cyanide poison. 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.

O) 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.
P) 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.
Q) 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) Experimental animals have developed serious systemic cyanide poisoning following ocular exposure. Human poisoning cases have not been reported due to eye exposure only. If systemic cyanide poisoning is suspected following eye exposure, REFER to TREATMENT RECOMMENDATIONS in the INHALATION EXPOSURE section above.

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) While cyanide can be absorbed through intact skin, most reported cases have involved whole-body immersion in cyanide solutions or large-area burns with molten cyanide solutions. Most nitrile compounds are well absorbed through intact skin, and may cause delayed onset of symptoms following exposure by this route.
3) Administer 100% oxygen and establish a secure large-bore IV access.
4) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
5) 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.
6) The Cyanide Antidote Kit is administered as follows:

a) 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).
b) 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.
c) 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.

7) SODIUM BICARBONATE: Administer 1 mEq/kg IV to severely acidotic patients.
8) 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.

9) METHEMOGLOBINEMIA

a) 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 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.

10) HYPERBARIC OXYGEN and HEMODIALYSIS may be useful in severe cases not responsive to supportive and antidotal therapy.
11) 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.
12) 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.
13) ALTERNATE ANTIDOTES: Kelocyanor(R) (dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are alternate cyanide antidotes in clinical use in various countries outside the US. See TREATMENT SECTION in the main body of this document for more information.

Range Of Toxicity

1) Death may result from a few minutes exposure to 300 ppm of hydrogen cyanide. Air concentrations of 200 to 300 parts per million are rapidly fatal. Patients have survived exposure to hydrogen cyanide air concentrations of 500 mg/m(3).

Clinical Effects

Summary Of Exposure

1) Functional changes in hearing, loss of appetite, headache, weakness, nausea, dizziness, upper respiratory tract irritation, and dermatoses have been described in chronically exposed workers.

Vital Signs

3.3.1)

3.3.2)

A) The initial presentation of cyanide poisoning may include hyperpnea and tachypnea (Hall & Rumack, 1986).
B) Hypoventilation progressing to apnea may be seen in the later phases of cyanide poisoning and is a major cause of death (Vogel et al, 1981).

3.3.4)

A) Tachycardia and hypertension may be seen in the initial phases of cyanide poisoning (Vogel et al, 1981).
B) Bradycardia and hypotension are seen in the late phases of cyanide poisoning (Hall & Rumack, 1986).

3.3.5)

Heent

3.4.1)

3.4.3)

A) MYDRIASIS - Dilated pupils are common in severe poisoning (Vogel et al, 1981).
B) FUNDUSCOPIC EXAMINATION - Retinal arteries and veins that appear equally red on funduscopic examination suggest the diagnosis (Buchanan et al, 1976).
C) CYANIDE - When solid particles or concentrated solutions of NaCN, KCN or HCN were instilled into rabbit eyes, the product was rapidly absorbed, producing systemic toxicity and death. Accidental eye contamination with industrial chemicals may produce systemic symptoms (Ballantyne, 1983).
D) CORNEAL EDEMA - One case of corneal edema from exposure to hydrocyanic acid vapors has been reported (Grant, 1993).
E) OPTIC NEURITIS - Chronic exposure to low levels of cyanide such as result from cigarette smoking coupled with either a defective rhodanese enzyme or protein-calorie malnutrition with decreased sulfur-containing amino acids intake have been postulated to lead to retrobulbar optic neuritis in certain cases (Grant, 1986).
F) IRRITATION - Eye irritation has been described in workers chronically exposed to cyanide (Hathaway et al, 1996).

3.4.4)

A) Functional hearing changes were described in a group of workers chronically exposed to cyanide (Saia et al, 1970).

3.4.5)

A) EPISTAXIS - Frequent nosebleeds have been described in workers chronically exposed to cyanide (Proctor et al, 1988; HSDB , 1998).

3.4.6)

A) BURNING SENSATION - A burning sensation in the mouth and throat may occur following ingestion of cyanide salts (Vogel et al, 1981).

Cardiovascular

3.5.1)

3.5.2)

A) TACHYARRHYTHMIA

1) Tachycardia and hypertension may be seen in the initial phases of cyanide poisoning (Vogel et al, 1981).

B) BRADYCARDIA

1) Bradycardia and hypotension are seen in the late phases of cyanide poisoning (Hall & Rumack, 1986).

C) ELECTROCARDIOGRAM ABNORMAL

1) Erratic atrial and ventricular cardiac rhythms with varying degrees of atrioventricular block followed by asystole may be seen in severe cyanide poisoning (Hall & Rumack, 1986). ST-T segment elevation or depression may be noted (Cope, 1961).

Respiratory

3.6.1)

3.6.2)

A) HYPERVENTILATION

1) The initial presentation of cyanide poisoning may include hyperpnea and tachypnea (Hall & Rumack, 1986).

B) APNEA

1) Hypoventilation progressing to apnea may be seen in the later phases of cyanide poisoning and is a major cause of death (Vogel et al, 1981; HSDB , 1998).

C) ACUTE LUNG INJURY

1) Acute lung injury (noncardiogenic pulmonary edema) has been reported in cases of acute cyanide poisoning, even following ingestion (Graham et al, 1977).

D) CYANOSIS

1) Cyanosis is a late finding in cyanide poisoning and does not occur until the stage of apnea and circulatory collapse (Hall & Rumack, 1986).

Neurologic

3.7.1)

3.7.2)

A) HEADACHE

1) Headache may be an early sign of cyanide poisoning (Vogel et al, 1981; Sittig, 1991).

B) CENTRAL STIMULANT ADVERSE REACTION

1) CNS stimulation with varied presentations from anxiety to agitation and combative behavior may be seen in the early stages of cyanide poisoning (Vogel et al, 1981).

C) COMA

1) Coma is common in severe poisoning (Hall & Rumack, 1986; Vogel et al, 1981; Sittig, 1991).

D) SEIZURE

1) Convulsions are common in severe cyanide poisoning (Hall & Rumack, 1986; Sittig, 1991).

E) PARALYSIS

1) Opisthotonos, trismus, and paralysis were reported in one case of cyanide poisoning (De Busk & Seidl, 1969).

F) SEQUELA

1) Most victims of acute poisoning either die acutely or fully recover, but rare cases of neurological sequelae such as personality changes, memory deficits, and extrapyramidal syndromes have been reported (Jouglard et al, 1971; Jouglard et al, 1974).
2) An 18-year-old patient who ingested between 975 and 1,300 mg of potassium cyanide developed a Parkinsonian syndrome with rigidity and akinesis (Uitti et al, 1985).
3) Parkinsonism developed progressively over 3 weeks after acute ingestion of 1,500 mg of potassium cyanide. Slowed gait, masked facies, hypophonia, mild rigidity, and minimal tremor were noted. Damage was permanent, and although not evident on CT or MRI scan at 6 months, was noted on MRI at 12 months postingestion. There was no improvement with levodopa therapy (Rosenberg et al, 1989).
4) Progressive parkinsonism was reported after acute cyanide poisoning over a five-year period in a 46-year-old woman. Drooling and dysphagia increased over this time, and marked tongue and mouth dystonia developed. Apraxia of eyelid opening was also marked (Carella et al, 1988). Some improvement was noted with trihexyphenidyl treatment.

G) NEUROLOGICAL FINDING

1) WITH POISONING/EXPOSURE

a) CASE REPORT - After drinking a beverage laced with potassium cyanide prepared by another individual, a 17-year-old boy developed profound coma and died 4 days later. The neuropathological findings showed acute hypoxic-ischemic encephalopathy with edema, narrowing of the sulci and flattening of the gyri, autolysis of basal ganglia, and pseudolaminar cortical necrosis (Riudavets et al, 2005).

H) EXTRAPYRAMIDAL DISEASE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - After ingesting potassium cyanide in a suicide attempt, a 35-year-old woman survived following antidote therapy and supportive care. On day 5, she developed agitation, choreoathetotic involuntary stereotypical movements of the upper and lower extremities and the trunk for several days. It was followed by akinetic mutism and buccofacial and ideomotoric aphasia. She also experienced severe rigid-akinetic syndrome, dysarthria, dysphagia and generalized dystonia several weeks later. MRI showed lesions in the caudate and lentiform nuclei, precentral cortex and cerebellum with a cortical precentral perfusion defect consistent with pseudolaminar cortical necrosis. On two occasions, a progressive loss of dopamine transporter suggestive of nigral neuronal apoptosis was observed by SPECT with beta-CIT (SPECT by [I-123] 2 beta-carbomethoxy-3-beta-(4-iodophenyl)-Tropan). FDG-PET and HMPAO SPECT showed striatal and frontal hypometabolism and hypoperfusion (Zaknun et al, 2005).

Gastrointestinal

3.8.1)

A) Nausea, vomiting, and abdominal pain may occur, especially after ingestion. Ingestion of cyanide salts can cause irritation or corrosion of the esophageal or gastric mucosa.

3.8.2)

A) NAUSEA AND VOMITING

1) Nausea, vomiting, and abdominal pain may occur, especially after ingestion of cyanide salts (Hall & Rumack, 1986; Singh et al, 1989; Vogel et al, 1981).

B) GASTRITIS

1) Ingestion of cyanide salts can cause irritation or corrosion of the esophageal or gastric mucosa (HSDB , 1998; Jouglard et al, 1974).

Acid-Base

3.11.1)

A) Elevated anion gap metabolic acidosis and elevated serum lactate levels may be found.

3.11.2)

A) ACIDOSIS

1) Elevated anion gap metabolic acidosis and elevated serum lactate levels are frequently found cyanide poisoning (Hall & Rumack, 1986; Vogel et al, 1981; Singh et al, 1989).

Dermatologic

3.14.1)

3.14.2)

A) SKIN IRRITATION

1) Direct dermal contact with potassium cyanide can cause skin irritation (CHRIS , 1998).

B) SKIN ULCER

1) Direct dermal contact with potassium cyanide can cause skin ulceration (CHRIS , 1998).

C) SKIN ABSORPTION

1) Cyanide has been said to be absorbed through intact skin and carries a "skin" designation for workplace exposures (ACGIH, 1991).

a) However, most cases of toxicity from dermal exposure have been due to industrial accidents with immersion in vats of cyanide solutions (Bismuth et al, 1984; Dodds & McKnight, 1985) or severe, large total body area burns with molten cyanide (Bourrelier & Paulet, 1971).

Endocrine

3.16.1)

A) Insulin resistance was noted in a severely cyanide poisoned patient.

3.16.2)

A) HYPERGLYCEMIA

1) Insulin resistance was noted in a severely cyanide poisoned patient (Singh et al, 1989).

Reproductive

3.20.1)

3.20.2)

A) ANIMAL STUDIES

1) FETOTOXICITY

a) POTASSIUM CYANIDE - Fetotoxicity has been noted in the offspring of rats and domestic animals administered potassium cyanide (RTECS , 1998). However, some rat studies have been negative for teratogenicity (Schardein, 1993).

2) RELATED COMPOUNDS

a) HAMSTERS - Sodium cyanide solution delivered by constant infusion to pregnant Golden Hamsters at doses from 0.126 to 0.1295 mmol/kg/hour between days 6 and 9 of gestation caused a high incidence of both resorptions and malformations in the offspring (Doherty et al, 1982).
b) Neural tube defects (exencephaly, encephalocele) were the most common malformations. Hydropericardium and crooked tails were also noted (Doherty et al, 1982).
c) Concomitant infusion of sodium thiosulfate prevented both maternal signs of toxicity and the teratogenic effects of the sodium cyanide infusion (Doherty et al, 1982).

3) ACETONITRILE -

a) HAMSTERS - Pregnant hamsters exposed by either inhalation of 5000 to 8000 ppm or given 100 to 400 mg/kg oral or intraperitoneal doses of acetonitrile delivered offspring with severe axial skeletal disorders (Willhite, 1983).
b) Injections of sodium thiosulfate antagonized the teratogenic effects. Elevated cyanide and thiocyanate levels were found in all tissues studied 2.5 hours after oral or intraperitoneal dosing, and suggested that the in vivo liberation of cyanide from acetonitrile was responsible for the observed teratogenic effects (Willhite, 1983).

4) ACRYLONITRILE/PROPIONITRILE -

a) HAMSTERS - Intraperitoneal injections of acrylonitrile or propionitrile to hamsters on day 8 of gestation resulted in exencephaly, encephaloceles, and rib abnormalities in the offspring (Willhite et al, 1981).
b) Sodium thiosulfate injections protected the fetus from these effects, except at larger nitrile doses where thiosulfate protected the dam against overt poisoning but did not protect the fetus against malformations. The teratogenic effects of both nitriles may be related to the metabolic release of cyanide after absorption (Willhite et al, 1981).

5) LAETRILE -

a) HAMSTERS - Laetrile given orally to pregnant hamsters produced skeletal malformations in the offspring and increased levels of tissue cyanide. Intravenous administration of laetrile (which does not result in cyanide release) produced neither effect (Willhite, 1982).
b) Sodium thiosulfate administration protected the fetus from teratogenic effects. These data suggested that the teratogenic effects were due to cyanide released in vivo from oral laetrile dosing (Willhite, 1982).

6) CASSAVA -

a) RATS - Rats fed cassava powder (containing high concentrations of a cyanogenic glycoside) as 50 to 80% of their diet during the first 5 days of pregnancy showed a small increase in the incidence of limb defects, open eye defects, microcephaly, and fetal growth retardation in fetuses collected on day 20 of pregnancy (Singh, 1981).

3.20.3)

A) ANIMAL STUDIES

1) FETOTOXICITY

a) Fetotoxicity has been noted in the offspring of rats and domestic animals administered potassium cyanide (RTECS , 1998).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS151-50-8 (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)

3.21.3)

A) ANIMAL STUDIES

1) RELATED COMPOUNDS

a) Acrylonitrile has carcinogenic properties in some species of experimental animals and has been suggested to be associated with a slight increase in deaths from lung cancer and other malignancies in humans (Buchter & Peter, 1984; Geiger et al, 1983).
b) Whether the metabolic release of cyanide after acrylonitrile absorption plays any role in this carcinogenesis is unknown. In isolated cell preparations, the release of cyanide from acrylonitrile does not appear to play a role in cell death (Geiger et al, 1983).

B) LACK OF EFFECT

1) POTASSIUM CYANIDE - There are no reports of carcinogenicity in humans or experimental animals due to potassium cyanide itself.

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Cyanide can be measured chemically by several methods, but the results cannot be obtained rapidly enough to assist in emergent diagnosis or treatment decisions; initial therapy should be based on clinical examination.
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%.
D) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
E) Monitor the chest x-ray in patients with significant exposure.
F) 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 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)

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

B) ACID/BASE

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 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).

4.1.4)

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) Monitor the chest x-ray in patients with significant exposure.

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

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) All patients with cyanide 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.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) 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 two hours, they may be released from the hospital.

6.3.3)

6.3.3.1) ADMISSION CRITERIA/INHALATION

A) All patients with cyanide 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.

6.3.3.5) OBSERVATION CRITERIA/INHALATION

A) 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 two hours, they may be released from the hospital.

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) SUMMARY

1) 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) 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.

C) ACTIVATED CHARCOAL

1) The usefulness of activated charcoal may be questionable.

a) 1 gram of activated charcoal may adsorb 35 mg of potassium cyanide (Anderson, 1946) but this is a low percentage.
b) The absorption of cyanide is so rapid that charcoal may be of little use unless administered immediately after ingestion of cyanide.
c) Immediate administration of a large dose of superactivated charcoal (4 grams/kg) to rats given an oral lethal dose of potassium cyanide (35 to 40 mg/kg) prevented lethality. Eight of 26 treated animals died compared to 25 of 26 untreated animals (Lambert et al, 1988).

2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) OXYGEN

1) Administer 100% oxygen to maintain an elevated PO2.

a) Oxygen may reverse the cyanide-cytochrome oxidase complex and facilitate the conversion to thiocyanate following thiosulfate administration (Graham et al, 1977).
b) 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).

B) HYPERBARIC OXYGEN THERAPY

1) 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 Undersea Medical Society (Myers & Schnitzer, 1984).
2) Hyperbaric oxygen has been suggested to improve clinical outcome, especially in those patients with CNS toxicity not responding to more traditional therapy.
3) Animal studies have both confirmed and refuted this (Skene et al, 1966; Way et al, 1972; Takano et al, 1980).
4) 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).
5) Hyperbaric oxygen should be reserved for those patients with significant symptoms (ie, coma, seizures) who do not respond to normal supportive and antidotal therapy, and for those patients poisoned by both cyanide and carbon monoxide secondary to smoke inhalation (Hart et al, 1985).

C) FLUID/ELECTROLYTE BALANCE REGULATION

1) Establish secure large bore IV line.

D) CYANIDE ANTIDOTE

1) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
2) 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).
g) In a study of heavy smokers, a group given hydroxocobalamin alone in a dose of 5 grams IV showed a decrease in whole blood cyanide of 59%. A group given 5 grams hydroxocobalamin followed with 12.5 grams sodium thiosulfate showed an 87% decrease in whole blood cyanide (Forsyth et al, 1993).
h) Hydroxocobalamin has been shown to be effective in treating cyanide poisoned animals and has the advantage of neither producing methemoglobinemia nor hypotension as does sodium nitrite (Forsyth et al, 1993).

3) CYANIDE ANTIDOTE KIT

a) OBTAIN AND PREPARE for administration a CYANIDE ANTIDOTE KIT, consisting of sodium nitrite and sodium thiosulfate.
b) Antidotes should be administered in patients who are clinically symptomatic (i.e., unstable vital signs, acidosis, impaired consciousness, seizures, or coma).
c) SODIUM NITRITE

1) INDICATION

a) Sodium nitrite should be given initially and administered as soon as vascular access is established.
b) 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.
c) 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).

2) ADULT DOSE

a) 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.
b) 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).

3) PEDIATRIC DOSE

a) 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).
b) 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).
c) 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):

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

4) 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.
5) 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.
6) Excessive methemoglobinemia and hypotension are potential complications of nitrite therapy.
7) In individuals with G6PD deficiency, therapy with methemoglobin-inducing agents is contraindicated because of the likelihood of serious hemolysis.

d) SODIUM THIOSULFATE

1) 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.
2) Sodium thiosulfate supplies sulfur for the rhodanese reaction, and is recommended after sodium nitrite, hydroxocobalamin, or 4-DMAP (4-dimethylaminophenol) administration (Marrs, 1988a; Hall & Rumack, 1987).
3) DOSE

a) 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).
b) 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).
c) Sodium thiosulfate is usually used in combination with sodium nitrite but may be used alone (Prod Info sodium thiosulfate IV injection, 2003).
d) 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)
e) 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).
f) 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) MONITORING OF PATIENT

1) Obtain blood for arterial blood gases, venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, and whole blood cyanide levels.

F) 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).
3) The following set of laboratory values suggest poisoning with an agent that inhibits oxidative phosphorylation (ie, cyanide, hydrogen sulfide) (Hall & Rumack, 1986).

1) Normals have been reported as 12 plus or minus 4 mEq/L, but vary depending on the laboratory used. The range for a normal anion gap reported in some laboratories is 7 plus or minus 4 mEq/L (Hoffman, 1994).

c) Serum Lactate: Elevated (normals 0.6 to 1.8 mEq/L (0.6 to 1.8 mmol/L)) 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%.

1) Arteriolization of venous blood gases (elevated venous pO2 or measured venous %O2 saturation) may serve as an early clue in the diagnosis of cyanide poisoning (Hall & Rumack, 1986; Johnson & Mellors, 1988).

4) 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 most likely do no harm to a hydrogen sulfide poisoned patient.

G) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

H) METHEMOGLOBINEMIA

1) CAUSE

a) The goal of nitrite therapy has been 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) Clinically significant excessive methemoglobinemia has rarely occurred following sodium nitrite therapy for cyanide poisoning. It usually occurs in children receiving excessive nitrite doses. Intravenous sodium nitrite administered as a 3% solution over 15 to 20 minutes induces approximately 7% to 14% methemoglobin (Kirk et al, 1993).

2) TREATMENT

a) 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.
b) 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.
c) SUMMARY

1) 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

1) 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).
2) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
3) 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).
4) 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).

e) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

1) 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).
2) 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).
3) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

I) DICOBALT EDETATE

1) Kelocyanor(R) (dicobalt-EDTA) is a highly effective cyanide chelating agent currently used clinically in Europe, Israel, and Australia (Davison, 1969; Hillman et al, 1974). It is not available in the US.
2) PRECAUTIONS

a) Significant toxicity from the antidote (severe hypertension or hypotension, cardiac ischemia or arrhythmias) may be seen in patients incorrectly diagnosed as being poisoned with cyanide and administered this antidote (Pronczuk de Garbino & Bismuth, 1981; Tyrer, 1981). Therefore, KELOCYANOR(R) should NOT be used in cases of MILD CYANIDE POISONING or DIAGNOSTIC UNCERTAINTY (Peden et al, 1986; Tyrer, 1981).
b) Severe anaphylactoid reactions with periorbital and massive facial edema, and airway compromise may also occur (Dodds & McKnight, 1985; Wright & Vesey, 1986).
c) ADVERSE EFFECTS: can include nausea, vomiting, tachycardia, hypotension, hypertension, anaphylactic reactions, facial and neck edema, chest pain, diaphoresis, nervousness, tremulousness, gastrointestinal hemorrhages, seizures, cardiac irregularities, and rashes (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969; Tyrer, 1981; Hillman et al, 1974).
d) Cobalt edetate has been shown to significantly increase plasma catecholamine levels which probably accounts for the cardiac effects of this drug. Vasodilator activities appear to be associated with cobalt edetate and it may induce a metabolic acidosis (Riou et al, 1993).

3) DOSE

a) ADULTS: One to two 20 mL ampules (300 to 600 mg) injected intravenously over about 1 to 5 minutes (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969).

1) A third 20 mL ampule (300 mg) can be injected intravenously over about 1 to 5 minutes, 5 minutes after the first 1 to 2 ampules if there is not sufficient clinical improvement (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969).
2) Manufacturers recommend following the Kelocyanor(R) injection with intravenous injection of 50 mL of 50% dextrose in water (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987).
3) Kelocyanor(R) can be used with other standard cyanide antidotes (Prod Info, 1978).

b) CHILDREN: Pediatric doses have not been established by manufacturers. A suggested dose used in Israel for children is 0.5 mL/kg (not to exceed 20 mL) (Personal Communication, Uri Taitelman, MD, 1963).

a) Kelocyanor(R) is supplied in 20 mL ampules containing 300 mg of dicobalt-EDTA and 4 grams of dextrose in water for injection (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987).

J) 4-DIMETHYLAMINOPHENOL HYDROCHLORIDE

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). Hemolysis may occur with therapeutic doses (van Heijst et al, 1987).

K) EXPERIMENTAL THERAPY

1) STROMA-FREE METHEMOGLOBIN SOLUTION: 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 used in experimental animals as a cyanide antidote (Ten Eyck et al, 1985).

a) By virtue of its in vitro production, stroma-free methemoglobin solution has the advantage of sparing the oxygen-carrying capacity of the blood (Marrs, 1988).
b) It has not been studied in human poisoning cases and is not available for human administration.

2) ALPHA-KETOGLUTARIC ACID: 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).

a) In vitro and animal studies show that alpha-ketoglutaric acid binds with cyanide and thereby antagonizes cyanide-induced inhibition of brain cytochrome oxidase (Norris et al, 1990).
b) Alpha-ketoglutaric acid administered with sodium thiosulfate abolished the cyanide-induced decrease in brain gamma-aminobutyric acid in mice (Yamamoto, 1990).
c) Oral administration of alpha-ketoglutarate was effective as pretreatment only when given between 10 and 30 minutes prior to cyanide exposure in rats. In combination with N-acetylcysteine, it improved the protective effect but did not alter the time course for protection (Dulaney et al, 1991).
d) It has not been studied in human poisoning cases and is not available for human administration.

3) CHLORPROMAZINE: Chlorpromazine has been studied in various animal models as a possible cyanide antidote. Conflicting reports of efficacy have been published (Pettersen & Cohen, 1985).

a) Animal and in vitro studies show that chlorpromazine can decrease peroxidation of lipid membranes and prevent cyanide-induced calcium influx believed to be responsible for neurotoxicity (Johnson et al, 1986; Maduh et al, 1988).
b) It has not been studied in human poisoning cases.

4) OTHER INVESTIGATIONAL ANTIDOTES: Animal studies to identify alternate cyanide antidotes have tested phenoxybenzamine, centrophenoxine, naloxone hydrochloride, etomidate, para-aminopropiophenone, hydroxylamine, and calcium-ion-channel blockers (Amery et al, 1981; Ashton et al, 1980; Bright & Marrs, 1987; Burrows & Way, 1976; Dubinsky et al, 1984; Johnson et al, 1986; Leung et al, 1984; Bright & Marrs, 1987; Marrs, 1988; Rump & Edelwijn, 1968; Vick & Froehlich, 1985) (Vick & Froehlick, 1991).

L) 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).

M) 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).

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) TOXIC EFFECT OF CYANIDE

1) HYDROGEN CYANIDE gas may be released from potassium cyanide on contact with acid (CHRIS , 1990) (Budavari, 1989).
2) In cases where patients are rendered comatose by the inhalation of hydrogen cyanide gas, 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, administering antidotes may not be necessary (Peden et al, 1986).

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.

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 (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).

E) FLUID/ELECTROLYTE BALANCE REGULATION

1) Establish secure large bore IV line.

F) CYANIDE ANTIDOTE

1) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
2) HYDROXOCOBALAMIN - CYANOKIT(R)

3) CYANIDE ANTIDOTE KIT

1) 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.
2) 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.
3) Excessive methemoglobinemia and hypotension are potential complications of nitrite therapy.
4) In individuals with G6PD deficiency, therapy with methemoglobin-inducing agents is contraindicated because of the likelihood of serious hemolysis.
5) INDICATION

6) ADULT DOSE

7) PEDIATRIC DOSE

d) SODIUM THIOSULFATE

G) ACIDOSIS

H) MONITORING OF PATIENT

1) Obtain blood for arterial blood gases, serum electrolytes, serum lactate, and whole blood cyanide.
2) 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 mEq/L (12 to 16 mmol/L) or less) is present from the presence of unmeasured organic anions (usually lactate).
c) Serum Lactate: Elevated (normals 0.6 to 1.8 mEq/L) (0.6 to 1.8 mmol/L) 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%.

I) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

J) METHEMOGLOBINEMIA

1) While clinically significant excessive methemoglobinemia has occurred following sodium nitrite therapy for cyanide poisoning, such instances are rare and usually occur in children receiving excessive nitrite doses.

a) Inducing a "therapeutic methemoglobin level" of 25% is unnecessary to insure satisfactory clinical outcome (Johnson et al, 1989).

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

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

5) METHYLENE BLUE

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

6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

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

K) DICOBALT EDETATE

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.

L) 4-DIMETHYLAMINOPHENOL HYDROCHLORIDE

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).

M) EXPERIMENTAL THERAPY

1) STROMA-FREE METHEMOGLOBIN SOLUTION

a) 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.

2) ALPHA-KETOGLUTARIC ACID

a) 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.

3) CHLORPROMAZINE

a) 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.

N) HYPOTENSIVE EPISODE

1) SUMMARY

2) DOPAMINE

3) NOREPINEPHRINE

O) 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) OCULAR ABSORPTION

1) There are no reports of systemic poisoning in humans exposed to cyanide by the ocular route; however, deaths in experimental animals have followed ocular exposure (Ballantyne, 1983).
2) Patients exposed by this route should be observed for several hours in a controlled setting for the possible development of symptoms of systemic cyanide poisoning.

B) SUPPORT

1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

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

Dermal Exposure

6.9.1)

A) 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).

6.9.2)

A) SKIN ABSORPTION

1) Cyanide can be absorbed and cause systemic cyanide poisoning by the dermal route, usually only following severe burns from molten material (Bourrelier & Paulet, 1971) or total immersion in cyanide solution (Bismuth et al, 1984; Dodds & McKnight, 1985).

B) OXYGEN

1) Administer 100% oxygen to maintain an elevated PO2.

C) HYPERBARIC OXYGEN THERAPY

D) FLUID/ELECTROLYTE BALANCE REGULATION

1) Establish secure large bore IV line.

E) CYANIDE ANTIDOTE

1) A cyanide antidote, either hydroxocobalamin OR the sodium nitrite/sodium thiosulfate kit, should be administered to patients with symptomatic poisoning.
2) 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).
g) In a controlled pilot study of male smokers, administration of 5 grams of IV 5% hydroxocobalamin significantly decreased whole blood cyanide levels (Forsyth et al, 1992).

3) CYANIDE ANTIDOTE KIT

6) ADULT DOSE

7) PEDIATRIC DOSE

d) SODIUM THIOSULFATE

F) MONITORING OF PATIENT

1) Obtain blood for arterial blood gases with venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, and whole blood cyanide levels.
2) The following set of laboratory values suggest poisoning with an agent that inhibits oxidative phosphorylation (ie, cyanide, hydrogen sulfide) (Hall & Rumack, 1986).

a) Arterial pO2: Usually normal until the stage of 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 - (C1 + CO2)) (normals 12 to 16 mEq/L (12 to 16 mmol/L) or less) is present from the presence of unmeasured organic anions (usually lactate).
c) Serum Lactate: Elevated (normals 0.6 to 1.8 mEq/L) (0.6 to 1.8 mmol/L) 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%.

3) 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 most likely do no harm to a hydrogen sulfide poisoned patient.

G) ACIDOSIS

H) SEIZURE

1) SUMMARY

2) DIAZEPAM

3) NO INTRAVENOUS ACCESS

4) LORAZEPAM

5) PHENOBARBITAL

6) OTHER AGENTS

I) METHEMOGLOBINEMIA

a) Inducing a "therapeutic methemoglobin level" of 25% is unnecessary to insure satisfactory clinical outcome (Johnson et al, 1989).

5) METHYLENE BLUE

6) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

J) DICOBALT EDETATE

a) Significant toxicity from the antidote (severe hypertension or hypotension, cardiac ischemia or arrhythmias) may be seen in patients incorrectly diagnosed as being poisoned with cyanide and administered this antidote (Pronczuk de Garbino & Bismuth, 1981; Tyrer, 1981). Therefore, KELOCYANOR(R) should NOT be use in cases of MILD CYANIDE POISONING or DIAGNOSTIC UNCERTAINTY (Peden et al, 1986; Tyrer, 1981).
b) Severe anaphylactoid reactions with periorbital and massive facial edema and airway compromise may also occur (Dodds & McKnight, 1985; Wright & Vesey, 1986).
c) ADVERSE EFFECTS can include nausea, vomiting, tachycardia, hypotension, hypertension, anaphylactic reactions, facial and neck edema, chest pain, diaphoresis, nervousness, tremulousness, gastrointestinal hemorrhages, convulsions, cardiac irregularities, and rashes (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969; Tyrer, 1981; Hillman et al, 1974).

3) DOSE

a) ADULTS: One to two 20 mL ampules (300 to 600 mg) injected intravenously over about 1 to 5 minutes (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969).

1) A third 20 mL ampule (300 mg) can be injected intravenously over about 1 to 5 minutes, 5 minutes after the first 1 to 2 ampules if there is not sufficient clinical improvement (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987) (Davison, 1969).
2) Manufacturers recommend following the Kelocyanor(R) injection with intravenous injection of 50 mL of 50% dextrose in water (Prod Info, 1978; Prod Info, 1986; Prod Info, 1987).
3) Kelocyanor(R) can be used with other standard cyanide antidotes (Prod Info, 1978).

4) Kelocyanor(R) is supplied in 20 mL ampules containing 300 mg of dicobalt-EDTA and 4 grams of dextrose in water for injection (Prod Info, 1978) (Prod Info, 1986) (Prod Info, 1987).

K) 4-DIMETHYLAMINOPHENOL HYDROCHLORIDE

L) EXPERIMENTAL THERAPY

1) STROMA-FREE METHEMOGLOBIN SOLUTION: 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; Breen et al, 1996).

2) ALPHA-KETOGLUTARIC ACID

a) 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; Dulaney et al, 1991).
b) In vitro and animal studies show that alpha-ketoglutaric acid binds with cyanide and thereby antagonizes cyanide-induced inhibition of brain cytochrome oxidase (Norris et al, 1990).
c) Alpha-ketoglutaric acid administered with sodium thiosulfate abolished the cyanide-induced decrease in brain gamma-aminobutyric acid in mice (Yamamoto, 1990).
d) It has not been studied in human poisoning cases and is not available for human administration.

3) CHLORPROMAZINE

a) Chlorpromazine has been studied in various animal models as a possible cyanide antidote. Conflicting reports of efficacy have been published (Pettersen & Cohen, 1986).
b) Animal and in vitro studies show that chlorpromazine can decrease peroxidation of lipid membranes and prevent cyanide-induced calcium influx believed to be responsible for neurotoxicity (Johnson et al, 1986; Maduh et al, 1988).
c) It has not been studied in human poisoning cases.

4) OTHER INVESTIGATIONAL ANTIDOTES: Animal studies to identify alternate cyanide antidotes have tested phenoxybenzamine, centrophenoxine, naloxone hydrochloride, etomidate, para-aminopropiophenone, hydroxylamine, and calcium-ion-channel blockers (Amery et al, 1981; Ashton et al, 1980; Bright & Marrs, 1987; Burrows & Way, 1976; Dubinsky et al, 1984; Johnson et al, 1986; Leung et al, 1984; Marrs & Bright, 1987; Marrs, 1988; Rump & Edelwijn, 1968; Vick & Froehlich, 1985; Vick & Froehlick, 1991).

M) HYPOTENSIVE EPISODE

1) SUMMARY

N) ACUTE LUNG INJURY

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

Enhanced Elimination

1) Hemodialysis may be an effective adjunct by correcting resistant acidemia and by increasing thiocyanate clearance, thereby favoring thiosulfate-cyanide reaction to thiocyanate (Wesson et al, 1985).
2) 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).
3) Limited animal studies, using historical controls and only a few animals, have so far shown some potential effectiveness of hemodialysis when combined with thiosulfate infusion (Gonzales & Sabatini, 1989).
4) Hemodialysis cannot be considered standard therapy for cyanide poisoning at this time.

1) CASE REPORT: Charcoal hemoperfusion has also been used in one reported case of cyanide poisoning (Kreig & Saxena, 1987).
2) This patient also received supportive measures and sodium nitrite/thiosulfate antidotes.
3) The outcome in this case was no different from that of other patients treated similarly without hemoperfusion.
4) Hemoperfusion cannot be considered standard therapy for cyanide poisoning at this time.

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Hydrogen cyanide and cyanide salts, as CN; cyanide salts

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling: 5 mg/m(3)

b) Notations and Endnotes:

1) Carcinogenicity Category: Not Listed
2) Codes: Skin
3) Definitions:

a) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): URT irr; headache; nausea; thyroid eff
d) Molecular Weight: Varies

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS151-50-8 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Potassium cyanide (as CN)
2) REL:

a) TWA:
b) STEL:
c) Ceiling: 5 mg/m(3) (4.7 ppm) [10-minute]
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s): [*Note: The REL and PEL also applies to other cyanides (as CN) except Hydrogen cyanide.]

3) IDLH: Not Listed

C) Carcinogenicity Ratings for CAS151-50-8 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Hydrogen cyanide and cyanide salts, as CN; cyanide salts
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Potassium cyanide
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 ; Listed as: Potassium cyanide (as CN)
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS151-50-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Not Listed

Toxicity Information

7.7.1)

A) Reference: Budavari, 1996; Clayton & Clayton, 1994; ITI, 1995 Lewis, 1996 RTECS, 1998

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 5991 mcg/kg

2) LD50- (ORAL)MOUSE:

a) 8500 mcg/kg
b) 8500 mcg/kg
c) 6.02 plus or minus 3.3 mg/kg at 23-25 degrees C
d) 2.86 plus or minus 1.6 mg/kg at 40 degrees C

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 6500 mcg/kg
b) 6 mg/kg

4) LD50- (INTRAPERITONEAL)RAT:

a) 4 mg/kg

5) LD50- (ORAL)RAT:

a) 5 mg/kg
b) 10 mg/kg

6) LD50- (SUBCUTANEOUS)RAT:

a) 7814 mcg/kg
b) 9 mg/kg

Pharmacology Toxicology

Physicochemical

Physical Characteristics

Ph

Molecular Weight

Animal Toxicology

References

General Bibliography

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POTASSIUM CYANIDE

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

Acid-Base

Dermatologic

Endocrine

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Physical Characteristics

Ph

Molecular Weight

General Bibliography