Introduction

Definition of cyanide poisoning

Cyanide is a potentially deadly chemical that is traditionally called a poison. It is a rapid-acting substance that disrupts the body’s ability to use oxygen and when a person is exposed to it, it can result in cyanide poisoning. Cyanide sometimes smells like bitter almond, but it does not always give off an odour, and not everyone can detect this scent.¹

Sources of cyanide

Cyanide is released by natural substances such as lima beans and almonds. It is also found in certain manufacturing and industrial sources including insecticides, jewellery cleaners, photographic solutions, and plastics manufacturing.² Cyanide is one of the most lethal poisons and can cause death within minutes to hours. As a result, understanding the sources of cyanide, its effects on humans, including symptoms and necessary treatments, is critical in preventing its harmful impact.

Types and sources of cyanide

Cyanide poisoning can be a result of different exposures, such as structural fires, industrial processes, medical exposures like sodium nitroprusside, and certain foods. According to the Toxic Exposure Surveillance System, of the 3,165 human exposures to cyanide between 1993-2002, 2.5% were fatal. However, in industrialised countries including the United States, fires have been the most common source of cyanide exposure.³

Types of cyanide

• Cyanogen chloride (CNCl) or hydrogen cyanide (HCN): In this form, cyanide exists as a colourless gas or liquid. It is used in manufacturing industries and is produced by combustion
• Potassium cyanide (KCN) or sodium cyanide (NaCN): Cyanide is present here in solid/crystal form and as a soluble compound. It is used in industries such as mining and metal processing

Natural sources

• Plants: Cyanogenic glycosides are found in plants such as cassava, almonds, and fruit seeds, including apricot, cherry, and peach pits

Industrial and chemical exposure

• Mining and metal processing: Cyanide is used in gold extraction and electroplating
• Chemical industries: It is used to develop photographs, produce pesticides, and remove vermin from ships and buildings
• Metallurgical industries: Cyanide is used for metal cleaning, electroplating, and removing gold from its ore
• Manufacturing: It is used to produce paper, textiles, and plastics 
• Smoke inhalation: Cyanide is also produced by burning materials like plastic, wool, and synthetic materials in house fires
• Chemical laboratories: Exposure to chemicals containing cyanide or its compounds can release cyanide gas
• Medical application: A medication named sodium nitroprusside is used for treatment in hypertensive emergencies. In patients, toxic levels of cyanide may develop if they receive prolonged infusions of sodium nitroprusside¹

Mechanism of action

Intake of cyanide intravenously or through inhalation leads to the onset of symptoms rapidly. It is faster than exposure using oral or transdermal (through the skin) route. This happens because the first two routes provide faster diffusion into the bloodstream (blood) than the later ones. It is common for humans to get exposed to cyanide by cyanogenic foods or artificial sources including cigarette smoke. But the concentration of cyanide released from these sources is very low and the internal mechanisms of our body detoxify it. 

There are various minor mechanisms to metabolise cyanide (or discard it from the body). In our body, the primary mechanism detoxifies cyanide by converting it into thiocyanate in the liver by rhodanese enzyme. Thiocyanate is a nontoxic compound which is removed by the kidneys. While a significant amount of cyanide if present, interrupts its detoxification mechanism and results in cyanide poisoning.^2,4

Interference with cellular respiration

Inhibition of cytochrome C oxidase

Cyanide poisoning is mainly related to the termination of aerobic cell metabolism (aerobic respiration) or inhibits the use of cellular oxygen (oxygen present in human cells). Cyanide reversibly attaches to the cytochrome oxidase within the mitochondria. This process blocks the conversion of oxygen to water thus halts cellular respiration.

Prevention of oxygen utilisation

Cyanide inhibits the oxidative phosphorylation mechanism, where oxygen is used to produce essential cellular energy in the form of ATP. In this, it binds to the enzyme cytochrome C oxidase in the mitochondria. Due to this cellular hypoxia (lack of oxygen in the body tissues) and the depletion of ATP takes place. This results in the use of oxygen by the tissues followed by damage to vital functions. 

Effect on vital organs

When hypoxia occurs, cells start anaerobic metabolism to generate ATP in the absence of oxygen and to maintain cellular function. Anaerobic metabolism produces only a small amount of ATP, and results in the development of lactic acidosis. Consequently, it leads to improper cell functioning, progressing to cell death and multisystem organ failure. The brain and heart are particularly affected due to their high oxygen demand, leading to neurological symptoms and cardiac arrest.

Symptoms

Cyanide absorbs rapidly through the gastrointestinal tract, mucous membranes, respiratory tract and the skin. The symptoms of poisoning begin when cyanide concentration is found above 0.51 mg/L of whole blood. The blood cyanide concentration of 0.5 mg/L is a threshold concentration to change blood chemistry. In addition to this, symptoms of cyanide poisoning which are given below occur above a concentration of 2 mg/L.^1,2

Acute symptoms

During or immediate exposure to small doses of cyanide may lead to the following signs and symptoms:

• Early signs: Dizziness, headache, nausea, shortness of breath, rapid or slow heart rate, restlessness, vomiting, eye pain or eye tearing, chest pain or chest tightness
• Severe symptoms: Seizures, loss of consciousness, cardiac arrest, respiratory failure, and death if untreated

Chronic symptoms due to low-level exposure

• Neurological and respiratory symptoms: Weakness, confusion, difficulty breathing, and ataxia
• Thyroid dysfunction: Long-term exposure may lead to hypothyroidism and nerve damage

Hypotension (low blood pressure) and bradycardia are common signs of cyanide poisoning. In cyanide poisoning, a patient's skin can have a normal or slightly ashen appearance in spite of tissue hypoxia. Patients affected with this may have a cherry red colour caused by excess oxygen present in the bloodstream. The symptoms in a patient can appear within a minute of inhalation and a few minutes of its ingestion, which aids in the diagnosis that is discussed ahead.

Diagnosis 

Cyanide is the most dangerous gas in enclosed places and contact with containing cyanide can expose people to it. If cyanide is present in the air, a person can be exposed through eye contact, skin, or breathing. The detection of early symptoms of cyanide poisoning saves lives but in prolonged exposure diagnosis requires following examinations.^5,6  

Clinical assessment

• Physical examination: Symptoms such as rapid breathing, low blood pressure, and altered mental status can suggest cyanide poisoning
• Cherry-red skin: Due to high levels of oxygen in the blood that cannot be used by the tissues
• Toxicology screen: Evaluate possible overdose or poisoning in the blood, urine, or other bodily fluids
• Other lab tests: Urinalysis, arterial blood gas, carboxyhemoglobin level (for fire incidents or smoke inhalation), chest x-ray, and electrocardiogram

Blood tests

• Blood cyanide levels: Direct measurement of cyanide in the blood through complete blood count (though rare in emergency settings)
• Metabolic acidosis: Elevated lactic acid levels due to anaerobic metabolism in the absence of oxygen utilisation

Pulse oximetry

• It is used to measure the oxygen level in the tissues
• May show normal oxygen levels even though tissues are starved of oxygen

Early treatment is essential in cyanide toxicity, but not accomplishing the early diagnosis in the course is the major problem. Some complications encountered by the survivors of severe cyanide poisoning include Parkinson’s disease or other forms of neurological problems. The measures taken for the treatment of a patient affected with cyanide poisoning are provided thereafter.

Treatment

Cyanide poisoning is treated by supportive medical care available in a hospital or by trained emergency personnel. Antidotes are most useful for cyanide poisoning when provided quickly after exposure. It is important for the victims to receive medical treatment as given below, soon after exposure to cyanide.^7,8

Immediate action

Decontamination is the most important part of the treatment of a patient exposed to cyanide through topical (direct contact with the body) and inhalation routes.

• Remove the person from the source: Quick removal from cyanide exposure is critical to prevent further poisoning
• Decontamination: Skin and clothing decontamination in cases of contact with liquid or powdered cyanide

Oxygen therapy

• In this, oxygen availability is increased to 100% and helpful in displacing cyanide from cells

Antidotes

Hydroxocobalamin is the antidote commonly used for acute cyanide poisoning, particularly when the patient has carbon monoxide poisoning with cyanide. Other antidotes impair the oxygen-carrying capacity and worsen cellular hypoxia and acidosis mechanisms. 

• Hydroxocobalamin (cyanokit): Binds cyanide to form cyanocobalamin (vitamin B12), which is excreted in the urine
• Sodium thiosulfate: Converts cyanide to a less toxic compound (thiocyanate), which is excreted by the kidneys
• Sodium nitrite: Induces methemoglobin formation, which binds to cyanide and removes it from cytochrome c oxidase

Supportive care

• Cardiac and respiratory support: Mechanical ventilation to stabilise the breathing of a patient and fluids to stabilise the cardiovascular system in severe cases

The treatment of poisoning should be initiated as soon as possible to reduce its effects. While it is better to prevent it through various measures which are discussed ahead.

Prevention 

The prevention of cyanide poisoning includes various safety measures for domestic, industrial and other workplaces which are mentioned here.^1,2

Safety Measures In Industrial Settings

• Proper handling and storage: Ensure appropriate ventilation, protective equipment, and storage of cyanide-containing substances
• Training and awareness: Educating workers on the risks and safety protocols associated with cyanide use

Household and fire safety

• Carbon monoxide detectors: Installing detectors in homes to prevent cyanide and carbon monoxide exposure from house fires
• Avoid consumption of toxic plants: Recognizing and avoiding consumption of seeds and parts of plants that may contain cyanogenic compounds

The release of cyanide in any form into water can be exposed to toxicity by touching or drinking that water. Food or drink exposed to cyanide can affect people and such contamination is likely caused by solid forms. If cyanide is ingested by someone, vomiting should not be induced.

Summary

Cyanide poisoning is a life-threatening condition that results from exposure to cyanide through various sources. A person can be exposed to it through plants and various manufacturing or industrial processes. Cyanide poisoning interferes with cellular respiration to prevent the use of oxygen by tissues and in critical cases may cause the failure of organs. Early recognition and treatment with antidotes and oxygen therapy are vital for survival. Cyanide can enter into the body through the skin so people working with cyanide-related chemicals must be aware of garments and other devices required while working there. Safety procedures with awareness related to cyanide exposure are necessary for both industrial settings and households to minimise its adverse effects.