Burn 6. Cyanide Toxicity

Key points:

1.       Confined space burn victims with autonomic instability should be treated early with CyanoKit (ED Pyxis). If still unstable can repeat dose at 30 minutes.

2.       Thiosulfate as a second line agent.

3.       Everyone needs a carboxyhemoglobin. 

4.       Caution against empiric administration of Cyanokit for simple for smoke inhalation. There's no proven benefit and increased risk of AKI.

General:

·         The extent of poisoning caused by cyanide depends on concentration, route of exposure and length of exposure.

·         Cyanide gas is less dense than air, so it will rise.

·         Cyanide anion inhibits cytochrome c oxidase in the electron transport chain and thus disrupts ATP generation.

·         Cyanide is more harmful to the heart and brain than to other organs because the heart and brain are more metabolically active.

Immediate signs and symptoms of exposure to cyanide:

·         ·         Lab findings:

• Serum lactic acid > 10
• Arterialization of the venous blood gas (high PvO2, since oxygen extraction is impaired
• People exposed to a small amount of cyanide by breathing it, absorbing it through their skin, or eating foods that contain it may have some or all of the following signs and symptoms within minutes:

o    Dizziness

o    Headache

o    Nausea and vomiting

o    Rapid breathing

o    Rapid heart rate

o    Restlessness

o    Weakness

·         Exposure to a large amount of cyanide by any route may cause these other health effects as well:

o    Convulsions

o    Loss of consciousness

o    Low blood pressure

o    Lung injury

o    Respiratory failure leading to death

o    Slow heart rate

All burn patients get a CO (carbon monoxide) level.

Cyanide poisoning screening and treatment:

Suspect cyanide toxicity in all patients with elevated CO level.

CyanoKit (hydroxocobalamin):  These are stocked in the ER pyxis

Cyanide poisoning is treated with specific antidotes and supportive medical care in a hospital setting. Antidotes for cyanide poisoning are most useful if given as soon as possible after exposure. Clinicians should treat suspected cases accordingly and not wait for laboratory confirmation. The most important principle is for victims to seek medical treatment as soon as possible.

CDC Basic Cyanide facts.  (2013). Retrieved from www.cdc.gov/agent/cyanide/basics/facts.asp

 

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Cyanide is a highly toxic chemical with a variety of uses, including chemical synthesis, laboratory analysis, and metal plating. Aliphatic nitriles (acrylonitrile and propionitrile) used in plastics manufacturing are metabolized to cyanide. The vasodilator drug nitroprusside releases cyanide upon exposure to light or through metabolism. Natural sources of cyanide (amygdalin and many other cyanogenic glycosides) are found in apricot pits, cassava, and many other plants and seeds, some of which may be important, depending on ethnobotanical practices. Acetonitrile, a solvent that was a component of some artificial nail glue removers, has caused several pediatric deaths. 

Hydrogen cyanide is a gas easily generated by mixing acid with cyanide salts and also is a common combustion by-product of burning plastics, wool, and many other natural and synthetic products. Hydrogen cyanide poisoning is an important cause of death from structural fires, and deliberate cyanide exposure (through cyanide salts) remains an important instrument of homicide and suicide. Hydrogen cyanamide, an agricultural chemical used as a plant regulator, is a potent toxin that inhibits aldehyde dehydrogenase but does not act as a cyanide analog. 

Mechanism of toxicity 

Cyanide is a chemical asphyxiant; binding to cellular cytochrome oxidase, it blocks the aerobic utilization of oxygen. Unbound cyanide is detoxified by metabolism to thiocyanate, a much less toxic compound that is excreted in the urine. 

Toxic dose 

Exposure to hydrogen cyanide gas (HCN), even at low levels (150–200 ppm), can be fatal. The air level considered immediately dangerous to life or health (IDLH) is 50 ppm. The Occupational Safety & Health Administration (OSHA) legal permissible exposure limit (PEL) for HCN is 10 ppm. The recommended workplace ceiling limit (ACGIH TLV-C) is 4.7 ppm (5mg/m3 for cyanide salts). Cyanide in solution is well absorbed across the skin. Adult ingestion of as little as 200mg of sodium or potassium salt may be fatal. Solutions of cyanide salts can be absorbed through intact skin. 

Acute cyanide poisoning is relatively rare with nitroprusside infusion (at normal infusion rates) or after ingestion of amygdalin-containing seeds (unless they have been pulverized). 

Clinical Presentation 

Abrupt onset of profound toxic effects shortly after exposure is the hallmark of cyanide poisoning. Symptoms include headache, nausea, dyspnea, and confusion. Syncope, seizures, coma, agonal respirations, and cardiovascular collapse ensue rapidly after heavy exposure. 

A brief delay may occur if the cyanide is ingested as a salt, especially if it is in a capsule or if there is food in the stomach. 

Delayed onset (minutes to hours) also may occur after ingestion of nitriles and plant-derived cyanogenic glycosides because metabolism to cyanide is required. 

Chronic neurologic sequelae may follow severe cyanide poisoning, consistent with anoxic injury. 

 

Diagnosis  

Diagnosis is based on a history of exposure or the presence of rapidly progressive symptoms and signs. Severe lactic acidosis is usually present with significant exposure. The measured venous oxygen saturation may be elevated owing to blocked cellular oxygen consumption. The classic "bitter almond" odor of hydrogen cyanide may or may not be noted, in part because of genetic variability in the ability to detect the smell. 

Labs 

Cyanide determinations are rarely of use in emergency management because they cannot be performed rapidly enough to influence initial treatment. In addition, they must be interpreted with caution because of a variety of complicating technical factors. 

Whole-blood levels higher than 0.5–1 mg/L are considered toxic. Cigarette smokers may have levels of up to 0.1 mg/L. Rapid nitroprusside infusion may produce levels as high as 1 mg/L, accompanied by metabolic acidosis. 

Other useful laboratory studies include electrolytes, glucose, lactate, arterial blood gases, mixed venous oxygen saturation, and carboxyhemoglobin (via co-oximetry, if the patient experienced smoke inhalation exposure). 

 

Treatment 

Emergency and supportive measures. Treat all cyanide exposures as potentially lethal. 

1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. 

2. Treat coma, hypotension, and seizures if they occur. 

3. Start an IV line and monitor the patient's vital signs and ECG closely. 

Specific drugs and antidotes 

1. The conventional cyanide antidote package consists of amyl and sodium nitrites, which produce cyanide-scavenging methemoglobinemia, and sodium thiosulfate, which accelerates the conversion of cyanide to thiocyanate. 

a. Break a pearl of amyl nitrite under the nose of the victim and administer sodium nitrite, 300 mg IV (6 mg/kg for children, not to exceed 300 mg). Adjust the dose downward if anemia is present. Caution: Nitrite-induced methemoglobinemia can be extremely dangerous and even lethal. Nitrite should not be given if the symptoms are mild or if the diagnosis is uncertain, especially if concomitant carbon monoxide poisoning is suspected. 

b. Administer sodium thiosulfate, 12.5 g IV. Thiosulfate is relatively benign and may be given empirically even if the diagnosis is uncertain. It also may be useful in mitigating nitroprusside toxicity. 

2. The most promising alternative antidote is hydroxocobalamin. Long available in Europe, more recently it has become available in the United States as Cyanokit. 

a. In acute poisoning, give 5 g of hydroxocobalamin (children: 70 mg/kg) by IV infusion over 15 minutes. 

b. In severe cases, a second administration may be considered. 

c. For prophylaxis of cyanide toxicity from nitroprusside, recommended hydroxocabalamin dosing is 25 mg/h by IV infusion. 

3. Dicobalt edentate is also used outside the United States. 

4. Hyperbaric oxygen has no proven role in cyanide poisoning treatment. 

Decontamination  

Caution: Avoid contact with cyanide-containing salts or solutions and avoid inhaling vapors from vomitus (which may give off hydrogen cyanide gas). 

1. Inhalation. Remove victims from hydrogen cyanide exposure and give supplemental oxygen if available. Each rescuer should wear a positive-pressure, self-contained breathing apparatus and, if possible, chemical-protective clothing. 

2. Skin. Remove and isolate all contaminated clothing and wash affected areas with copious soap and water. 

3. Ingestion. Even though charcoal has a relatively low affinity for cyanide, it will effectively bind the doses typically ingested (eg, 100–500 mg). 

a. Prehospital. Immediately administer activated charcoal if it is available and the patient is alert. Do not induce vomiting unless the victim is more than 30 minutes from a medical facility and charcoal is not available. 

b. Hospital. Immediately place a gastric tube and administer activated charcoal, then perform gastric lavage. Give additional activated charcoal and a cathartic after the lavage. 

Enhanced elimination.  

There is no role for hemodialysis or hemoperfusion in cyanide poisoning treatment. Hemodialysis may be indicated in patients with renal insufficiency who develop high thiocyanate levels while on extended nitroprusside therapy.