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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)

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Information from Other Resources

Resource Comparison

Information from CDC, WISER, and CAMEO
Emergency Response Safety and Health Database (CDC/NIOSH) More Information Close ERSH-DB is a occupational safety and health database developed by NIOSH for the emergency response community. Contains high-priority agents in terrorist events Information includes: Agent characteristics Personal protective equipment Emergency response Signs/symptoms Decontamination First aid Long-term implications On-site fatalities Occupational exposure limits Acute expousre guidelines Decontamination (environmental and equipment) Agent properties Hazardous materials warning labels/placards Trade names and other synonyms Who to contact in an emergency Important notice Arsine (SA) Cyanogen Chloride (CK) Hydrogen Cyanide (AC) Potassium Cyanide Sodium Cyanide WISER (NIH/NLM) More Information Close WISER is a system designed to assist first responders in HAZMAT incidents. Data derived from HSDB and DOT Emergency Response Guidebook Information includes: Substance identification Protective equipment/clothing Protective distance Fire fighting procedures Reactivities/incompatibilities Treatment overview and many more... Arsine Carbon Monoxide Hydrogen Cyanide Potassium Cyanide Sodium Cyanide CAMEO (EPA, NOAA) More Information Close CAMEO is a database of response information for thousands of hazardous materials MyChemicals: build a customized list of chemicals Predicts reactivity of 2 chemicals Information includes: Chemical identifiers Hazards Response recommendations Physical properties Regulatory information Alternate chemical names Arsine Cyanide Solution, N.O.S Cyanogen Chloride, Inhibited Hydrocyanic Acid Solution, with >20% Hydrogen Cyanide Hydrocyanic Acid Solution, with ≤20% Hydrogen Cyanide Potassium Cyanide Sodium Cyanide Sodium Fluoroacetate	Medical Management Guidelines for Acute Chemical Exposures (CDC/ATSDR) More Information Close MMGs for Acute Chemical Exposures were developed by ATSDR to aid emergency department physicians and other emergency healthcare professionals. Guidelines for managing acute exposures resulting from chemical incidents Information includes: Basic chemical and exposure information Summary of potential health effects Prehospital management information Emergency department management information Information for the patient Arsine Hydrogen Cyanide Chemical Emergencies (CDC) More Information Close A collection of CDC resources for professionals, including: Case definition Toxic syndrome description Toxicology profiles Training First responders Medical management Emergency response cards Lab info Surveillance Preparation & planning Toxic Syndrome Description: Arsine or Stibine Poisoning (Signs and symptoms, differential diagnosis) Arsine (and Stibine) Carbon Monoxide Cyanide Sodium Monofluoroacetate

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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