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Cyanide toxicity is a rare but often fatal poisoning that occurs through ingestion, inhalation, dermal absorption, or injection. Historically, cyanide toxicity has been used in mass suicides, individual murders, and chemical warfare. Ingestion and inhalation of toxic salts and gases are the most common sources of toxicity, respectively, though ingestion of plants, medications, and cyanogenic chemicals are alternative routes of exposure. Symptoms vary across organ systems, affecting the neurological, respiratory, cardiovascular, and gastrointestinal systems. Cyanide toxicity often goes unrecognized in the acute setting, and antidotes are subsequently underutilized. This course explores the challenges surrounding this condition, including the clinical diagnosis and treatment strategies. This activity for healthcare professionals is designed to enhance the learner's competence in identifying cyanide toxicity, performing the recommended evaluation, and implementing an appropriate interprofessional approach when managing this condition. Objectives: Identify the clinical features associated with cyanide toxicity. Identify patients at risk for cyanide exposure. Implement management of cyanide toxicity. Apply interprofessional team strategies to improve care coordination and outcomes in patients with cyanide toxicity. Access free multiple choice questions on this topic.

Cyanide toxicity is a rare, often fatal poisoning that patients are exposed to through various modes of entry and circumstances. It has been used historically in mass suicides such as the ingestions in the Jonestown mass suicide in 1978, as an agent for individual murders, and as a chemical weapon in gaseous form on battlefields and in the form of Zyklon B during the Holocaust.[1][2] Ingestion and inhalation of toxic salts and gases are the most common sources of toxicity, respectively, though ingestion of plants, medications, and cyanogenic chemicals are alternative routes of exposure.[3][4] Dermal absorption and injection are rare but possible sources of cyanide exposure. Ingestion is commonly found in suicide attempts, while inhalation exposures are often the result of structural fires. Cyanide salts, eg, potassium cyanide, are the most common type of cyanide ingestant, though exposure to cyanogenic glycosides in plants like cassava root can be fatal as well.[5] The combustion of synthetic plastics in structural fires releases hydrogen cyanide gas, making it the most common source of inhalation exposure.[6]

Individuals at Risk of Cyanide Exposure The most common cause of cyanide exposure is hydrogen cyanide gas exposure through inhalation, while the most common source of suicide attempts via cyanide is ingestion of cyanide salts, usually sodium or potassium cyanide. Hydrogen cyanide inhalation most commonly results from the burning of synthetic materials, such as plastics, in house fires.[7][8][9][10][11][12] Dermal exposure can occur in chemical spills of cyanide salts or liquids and in patients with improper clothing decontamination after exposure, such as when exposed to a house fire.[13] Ingestion of cyanide-containing foods is an additional route of exposure. Cassava root that has been improperly processed can cause cyanide toxicity, as occurred in Uganda in 2017, in which highly cyanogenic cassava flower was traced as the cause of illness in 33 individuals.[14] Cyanide can also be found in apple seeds, flax seeds, apricot pits, and bitter almonds.[15] Sodium nitroprusside, a vasodilating agent used in the treatment of severe hypertension, can occasionally cause cyanide toxicity as it contains several cyano groups. This generally only occurs after prolonged administration of the medication and is a rare complication. [16] In contrast, thiocyanate toxicity due to the accumulation of nitroprusside metabolites is more common, though typically less severe. Workers in industrial settings, eg, electroplating plants, have higher chronic exposure to cyanide. These individuals are at risk for acute cyanide toxicity in the event of industrial accidents and chronic toxicity from prolonged low-level occupational exposures.[17]

According to annual reports of the National Poison Data System, between 2019 and 2023, 853 exposures were reported, with 14 deaths and a 1.6% fatality rate. Adults accounted for 86.5% of the exposures, while 4.2% occurred in children under 5 years old. 7.6% of exposures were intentional self-harm attempts, and 68.2% were unintentional exposures.[7][9][10][11][12] Cyanide ingestions are predominately seen in male patients at a rate of 68%, with a mean age of 34.[4] A 2018 study that reviewed 49 years of cyanide exposures in 65 cases established that 84.3% of exposures were ingestions, 7.8% were inhalation, 1% dermal, and 1% intravenous.[8]

Cyanide toxicity is the result of cessation of aerobic respiration. Cyanide binds to copper and iron moieties in the electron transport chain, inhibiting cytochrome c oxidase activity, a mechanism similar to that of hydrogen sulfide and carbon monoxide. The resulting inhibition of oxidative phosphorylation prevents the production of adenosine triphosphate and redirects energy production to anaerobic respiration pathways, which are rapidly overwhelmed. The pathognomonic lactic acidosis of cyanide toxicity is a direct result of the arrest of aerobic respiration.[18]

Clinical History Proper treatment of cyanide exposure requires a thorough history and a complete physical exam. First, the treating team should determine the route of exposure, as this can predict the clinical course. The most common routes of exposure are ingestion and inhalation, while dermal exposure is less common. Additionally, the team should obtain information about how much cyanide salt the patient ingested or how long they were exposed to cyanide gas. Patients exposed to cyanide gas presenting with mild symptoms are less likely to progress to severe symptoms once they have been removed from the source of their exposure, while patients with cyanide ingestion are more likely to progress in symptom severity.[1] Patients exposed to cyanide gas present with their symptoms developing over seconds to minutes from the time of their initial exposure. Cyanide ingestion patients can have a longer arc of minutes to hours of symptom onset. Cases of cyanide toxicity can occur when eating cyanogenic glycosides, which are found in foods such as cassava root, peach pits, apricot pits, and bitter almonds. A careful dietary history should be included. Cyanide exposures present with broad, nonspecific findings across multiple organ systems. Neurologic symptoms include headache, confusion, and dizziness in milder exposures, while seizures and obtundation are observed in more severe exposures. Respiratory symptoms range from dyspnea and tachypnea to respiratory arrest. Gastrointestinal symptoms include abdominal cramping, nausea, and vomiting.[18] Physical Examination Findings Cardiovascular symptoms include tachycardia as well as ventricular dysrhythmias, including ventricular fibrillation and ventricular tachycardia. Patients may initially have hypertension and bradycardia before progressing to hypotension and eventual hemodynamic collapse.[18] Cherry red skin and bitter almond scent, classically taught as pathognomic of cyanide poisoning, are present in just 11% and 15% of cases, respectively.[8]

No single, readily available laboratory test has been identified to confirm cyanide poisoning; thus, diagnosis is primarily driven by clinical assessment. However, some laboratory findings are particularly suggestive of cyanide toxicity, which can support diagnosis. Due to inhibition of the electron transport chain, anaerobic respiration predominates, resulting in profound lactic acidosis. Serum lactate ≥8 mmol/L is both sensitive and specific for toxic cyanide serum concentrations in patients with suspected cyanide exposure.[24] Furthermore, peripheral oxygen delivery and utilization are impaired with the arrest of oxidative phosphorylation secondary to cyanide. The resulting arterialization of venous blood, in which the concentration of venous oxygen resembles that of arterial blood, is indicative of cyanide toxicity. A central venous oxygen saturation >90% is suggestive of cyanide toxicity but may also be present in both hydrogen sulfide and carbon monoxide toxicity.[25] Furthermore, venous blood may appear bright red, similar to arterial blood, due to the failure of peripheral oxygen utilization and the subsequent high oxygen content in venous blood. Carbon monoxide oximetry is also a valuable test to obtain in critically ill patients to narrow the differential, particularly given that patients may present with clinical features of both carbon monoxide toxicity and cyanide toxicity simultaneously. Given that patients often present with nonspecific symptoms initially, additional serum studies should be obtained, including a complete blood count, a basic metabolic panel, liver function tests, and cardiac biomarkers such as troponin.

Acute Stabilization The first step in the management of a patient with acute cyanide toxicity is an assessment of the patient’s airway, breathing, and circulation, as with other emergent conditions. Patients often present with central nervous system depression and with respiratory status ranging from labored tachypnea to apnea. If necessary, administration of 100% oxygen should be completed while preparations are made to secure the patient’s airway with endotracheal intubation. Patients with severe toxicity may also rapidly progress to hemodynamic collapse. Therefore, care teams should be prepared to administer intravenous fluids and vasopressors to support hemodynamics. Decontamination If a concern for dermal exposure is present, decontaminating the patient by removing clothing and washing with soap and water is appropriate. The administration of activated charcoal may also be provided for acute ingestions. Activated charcoal adsorbs 35 mg of cyanide for each 1 g of charcoal administered.[26][27] Patients with active vomiting or central nervous system depression should have a secure airway in place before administration of activated charcoal to reduce the risk of charcoal aspiration. Cyanide Antidotes In conjunction with the assessment of the airway, breathing, and circulation, the healthcare team should rapidly assess their suspicion of cyanide exposure and the need for an antidote. The first-line antidote in the United States is hydroxycobalamin, usually in the form of the Cyanokit. Standard dosing is 5 g administered intravenously over 15 minutes with an additional possible 5 g dose. This 10 g total dose is approximately 5,000 times the recommended daily dose of vitamin B12. Hydroxycobalamin is preferred over sodium thiosulfate and sodium nitrite due to its minimal side effect profile, which is typically limited to discoloration of the skin or urine, although it may also interfere with certain laboratory tests.[28]

In conjunction with the assessment of the airway, breathing, and circulation, the healthcare team should rapidly assess their suspicion of cyanide exposure and the need for an antidote. The first-line antidote in the United States is hydroxycobalamin, usually in the form of the Cyanokit. Standard dosing is 5 g administered intravenously over 15 minutes with an additional possible 5 g dose. This 10 g total dose is approximately 5,000 times the recommended daily dose of vitamin B12. Hydroxycobalamin is preferred over sodium thiosulfate and sodium nitrite due to its minimal side effect profile, which is typically limited to discoloration of the skin or urine, although it may also interfere with certain laboratory tests.[28] Additional cyanide antidotes include sodium nitrite and sodium thiosulfate, which are typically administered in tandem. These are less preferred for multiple reasons. Sodium nitrite produces hypotension as a side effect via vasodilatory-mediated action, which should be avoided in patients already at risk for hemodynamic collapse. Furthermore, sodium nitrite induces methemoglobin, a desired effect in the treatment of cyanide poisoning but with the associated risk of severe morbidity or mortality if high levels of methemoglobin are formed. Sodium thiosulfate has poor penetration to the brain, a location where cyanide is highly active and exerts significant damage on the basal ganglia.[19]

Acute cyanide exposure from inhalation often occurs concomitantly with carbon monoxide exposure in the setting of structural fires. Patients with carbon monoxide and cyanide toxicity alike can present with evidence of end-organ damage, hypoxia, hemodynamic instability, and altered mental status. Historically, a bitter almond scent and cherry-red skin were used as indicators of cyanide toxicity, but these are not reliable physical exam findings.[8] Hydrogen sulfide exposure exerts toxicity by a similar cellular mechanism to cyanide and should remain on the differential for undifferentiated patients with unexplained severe hemodynamic instability.

Patients with severe acute exposure requiring antidote administration and intensive care are more likely to experience long-term neurologic sequelae. Areas of the brain, such as the basal ganglia, that are highly metabolically active are more likely to experience damage. The result of this damage is a Parkinsonian-like syndrome, which includes bradykinesia, hypomimia, slowed speech, and slowed cognition.[29] A large review of cyanide ingestions determined roughly 26% of ingestions were fatal.[8] National Poison Data System data from 2019 to 2023 revealed a 1.6% overall fatality rate across all routes of exposure and intentional use.[7][9][10][11][12]

Potential complications of cyanide exposure include: Episodic memory loss Nausea Vomiting Tachypnea Dizziness Arrhythmia Respiratory Failure Hypotension Seizure Gait Instability Dystonia Parkinsonian symptoms [30][31]

A medical toxicologist or poison center should be consulted regarding the management of suspected cyanide toxicity. The expertise of medical toxicologists can help guide treatment strategies, including the use of antidotes and potential complications from their use. However, if cyanide poisoning is strongly suspected, consultation should not delay the administration of hydroxocobalamin.

Patients ingesting cyanide salts or other cyanogenic ingestants with self-harm intent should be appropriately medically treated and receive a psychiatric evaluation. Patients working in industrial settings with cyanogenic materials should be educated on the need for proper personal protective equipment and the symptoms of cyanide exposure. Patients with accidental ingestion and toxicity from plants or food should receive education on proper food processing to avoid repeat events. Patients treated for cyanide toxicity in the setting of structural fires should be educated on the treatment they received and the source of their symptoms. Smoke and carbon monoxide detectors should be encouraged in all patient homes.

Effective management of cyanide toxicity requires a well-coordinated, interprofessional approach to ensure timely recognition, treatment, and patient-centered care. Physicians, advanced practitioners, and nurses must maintain a high index of suspicion, particularly in patients presenting from structural fires or suicide attempts. Rapid assessment, history-taking, and symptom recognition are essential skills for preventing delays in treatment. Pharmacists play a crucial role in ensuring the availability and proper administration of antidotes, such as hydroxycobalamin. Poison control should be contacted immediately to provide expert guidance, and if available, medical toxicologists should be consulted to optimize patient management. Given the high rates of undertreatment, improved awareness and education among all healthcare professionals are necessary to enhance patient outcomes and safety. Care coordination among emergency clinicians, critical care teams, and support staff is essential for the effective management of severe cyanide toxicity cases. Nurses are responsible for continuous monitoring, ensuring the prompt administration of antidotes, and communicating any changes in patient status. Pharmacists assist in medication dosing and minimizing adverse effects, while respiratory therapists provide ventilatory support in patients with respiratory distress or failure. Psychiatric consultation should be considered early for patients with intentional ingestions once hemodynamic stability is achieved. Strong interprofessional communication and collaboration improve team performance, ensuring that all aspects of patient care, from diagnosis to treatment and long-term support, are effectively addressed.