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Blood/Systemic Agents (Knockdown Toxidrome)

Blood/systemic agents are poisons that affect the body by being absorbed into the blood. Chemicals such as hydrogen cyanide, hydrogen sulfide, and phospine cause rapid loss of consciousness and collapsing, seizure, hypotension and cardiac arrest, also known as Knockdown Syndrome.

Concise toxidrome definition: Altered state of consciousness, progressing from fatigue and lightheadedness to coma, with possible seizures and cardiac signs, secondary to disrupted cellular oxygen delivery and/or utilization.

Rationale or reasoning for toxidrome decisions: The name was chosen based upon a unifying pathophysiological basis for all agents in this toxidrome for the initial presentation; however, some agents have specific treatments or antidotes that are accommodated in the second tier of this toxidrome.

Examples of names initially considered included: None.

Issues or concerns about this toxidrome: Branch groupings could be created based on latency from exposure. Possible subgroupings would be: a) Cellular asphyxiants, b) Simple asphyxiants, c) Hemoglobinopathies, and d) Anemias (including hemolysis).

Knockdown/Asphyxiant examples of industrial chemicals and potential chemical warfare/terrorism agents: a) Dysruption of cellular energetic - prevents intracellular oxygen utilization, causing anaerobic cell metabolism and cell death (e.g., cyanide and sodium azide), b) Hemoglobinopathies - Prevents red blood cells from carrying or delivering oxygen to tissues and cells. (e.g., carbon monoxide and aniline), c) Anemias - loss of red blood cell destruction (e.g., arsine), and d) Simple asphyxiants - physical oxygen deprivation (nitrogen)

The clinically relevant routes of exposure and types of sources: Inhalation and ingestion predominate.

The organ systems generally affected: Central nervous system (CNS) and cardiac.

The initial signs and symptoms: Altered state of consciousness, progressing from fatigue and lightheadedness to coma, with possible seizures and cardiac signs, secondary to disrupted cellular oxygen delivery and/or utilization.

A progression of signs and symptoms includes: 1) Inhalation exposure medical endpoints include: a) Mild to moderate exposure - flushing of the skin, fatigue and lightheadedness, b) Severe exposure - nausea, anxiety, and difficulty breathing, c) Life threatening exposure - convulsions and respiratory distress, and d) Fatal exposure - severe convulsions and irreversible respiratory distress, and 2) Ingestion exposure medical endpoints include: a) Mild to moderate exposure - vomiting, abdominal pain, fatigue, and lightheadedness, b) Severe exposure - gastrointestinal (GI) irritation, sedation, confusion, mild increased lactate, and seizures/convulsions, c) Life threatening exposure - hypotension, GI perforation, lactic acidosis apnea, coma, seizure, and hematemesis, and d) Fatal exposure - refractory hypotension, high lactate, and acidemia (metabolic and respiratory), and refractory bradycardia.

The underlying pathology, biological processes, or modes of action include: a) Dysruption of cellular energetic - prevents intracellular oxygen utilization, causing anaerobic cell metabolism and cell death (e.g., cyanide and sodium azide), b) Hemoglobinopathies - Prevents red blood cells from carrying or delivering oxygen to tissues and cells. (e.g., carbon monoxide and aniline), c) Anemias - loss of red blood cell destruction (e.g., arsine), and d) Simple asphyxiants - physical oxygen deprivation (nitrogen).

Common treatment protocol, specific antidotes and key supportive measures: Supportive care for all agents and rule out other diagnoses - oxygen. For cyanides - Cyano kits; for other agents, specific antidotes may be available (e.g., chelators for arsenic).

Source:
Report to the Toxic Chemical Syndrome Definitions and Nomenclature Workshop (PDF - 2.01 MB) (DHS, NLM, May, 2012)


Information from Other Resources


Resource Comparison Table of Resource Comparison
Information from CDC, WISER, and CAMEO
Emergency Response Safety and Health Database (CDC/NIOSH) arrow WISER (NIH/NLM) arrow CAMEO (EPA, NOAA) arrow Medical Management Guidelines for Acute Chemical Exposures (CDC/ATSDR) arrow Chemical Emergencies (CDC) arrow

Additional Resources:

ChemIDplus - Chemical dictionary, structures, and links to many Internet resources (NIH/NLM)
Arsine, Carbon Monoxide, Cyanide, Cyanogen Chloride, Hydrogen Cyanide, Potassium Cyanide, Sodium Fluoroacetate

Hazardous Substances Data Bank - Comprehensive, peer-reviewed toxicology data (NIH/NLM)
Arsine, Carbon Monoxide, Cyanogen Chloride, Hydrogen Cyanide, Potassium Cyanide, Sodium Cyanide, Sodium Fluoroacetate



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