EMS Subspecialty Certification Review Course 1.3.7.1.2 Cyanide Version Date: 9/5/2013 Rev 6/5/2015
Questions 1. Which of the following is true of CN poisoning? a. Interferes with cellular respiration by uncoupling phosphorylation b. Has multiple safe antidotes c. Renders cells less susceptible to oxidative stress d. Results in increases in GABA effects and decreased glutamate e. Hallmark is ongoing respiratory collapse despite oxygen therapy 2. T/F Best antidote for CN is Lilly Kit 3. T/F CN Toxicity can be mischaracterized as CO Toxicity 43 Learning Objectives Upon the completion of this program participants will be able to: 1. List the potential sources of cyanide exposure 2. Understand the pathophysiology of cyanide poisoning 3. List the signs and symptoms of cyanide exposure 4. Describe the treatment of cyanide poisoning 44 Chemistry of Cyanide Gas (hydrogen cyanide): Colorless with faint bitter almond smell Nearly 40% of the population cannot smell cyanide. Sodium cyanide (NaCN) and potassium cyanide (KCN) are both white powders.
Chemistry of Cyanide Molecule consists of one carbon atom joined to one nitrogen atom by a triple bond. Cyanide anion is extremely toxic. Cyanide Hydrogen cyanide is a product of combustion of certain materials. High in: Plastics Wool Silk Synthetic rubber Polyurethane Asphalt Pathophysiology Cyanide can be inhaled, ingested or absorbed (rarely). Ingestion more common with suicide/murder Don t let the enemy get the information out of you Toxicity depends on: Route Dose Duration of exposure
Cyanide Toxicity varies with chemical form. Hydrogen cyanide (HCN) gas at concentrations of 130 ppm can be fatal within an hour. OSHA permissible exposure levels are 10 ppm as an 8 hour time weighted average. Pathophysiology Cyanide stops aerobic production of ATP Cyanide poisoning is a form of histotoxic hypoxia because the cells of an organism are rendered unable to use oxygen Cyanide inhibits mitochondrial cytochrome(a3) oxidase of electron transport chain Oxidative phosphorylation inhibitor (Phenols uncouple ) Inhibits other enzymes leading to: Increased susceptibility to oxidative stress Increased glutamate and excitatory neurotoxicity Decreased GABA (inhibitory receptors) leading to seizures Tissues that primarily depend on aerobic respiration are particularly affected: Heart Central nervous system Signs and Symptoms Low levels Dyspnea Headache Nausea Anxiety Altered mental status High levels Hyperpnea Loss of consciousness Seizures Apnea Death within minutes High oxygen consumption tissues are most susceptible 51
Consider CN Toxicity At various stages, the symptoms of CN poisoning are similar to those experienced when hiking or climbing at altitudes Classic scenario is hemodynamic and respiratory compromise not responsive to oxygen despite expectation History is key: Suspect co inhalation with any smoke inhalation Markedly elevated lactate Some suggest > 10 Unreliable indicators: Cherry red skin/flushing Bright red venous blood 52 Antidotes available: Cyanide Antidote Kit:* Amyl nitrite Sodium nitrite Sodium thiosulfate Hydroxycobalamin Cyanide Treament Review this for historical interest Cyanide Antidote Kit Nitrites administered to form methemoglobin. Cyanide has a greater affinity for methemoglobin (MET Hb) and frees cytochrome oxidase Amyl nitrite (inhaled q 30s); Sodium nitrite (300mg IV) Sodium thiosulfate (12.5g IV) binds cyanide and forms thiocyanate. Thiocyanate much less toxic than cyanide anion and excreted through the kidneys
Cyanide Antidote Kit Problems (related to nitrites): MET Hb does not transport O 2. The conversion of HB to MET Hb changes the state of the heme molecule where O 2 binds. MET Hb has heme in the ferric (Fe 3+ ) state and not the ferrous state (Fe 2+ ). O 2 can only bind to heme when in the Fe 2+ state. Cyanide Treatment Caveat Concomitant CO and CN poisoning is more common than once thought CO Hb and CN treatment induced MET HB reduce the O 2 carrying capacity of the blood. Children are particularly at risk for hypotension and adverse effects from methemoglobinemia. Once useable Hgb reaches crucial level CV Collapse 20% CO-Hb 20% MET-Hb O 2 -carrying capacity nearly halved! 100% Hb Hydroxocobalamin Precursor to cyanocobalamin (a form of Vitamin B 12 ). Hydroxocobalamin combines with cyanide forming renally excreted cyanocobalamin Does not inhibit Hgb function Minimal side effect profile Reddish skin and urine Allergic reaction Hypertension Prohibitively expensive for some systems Especially to replace multiple expired doses
CO and Cyanide Poisoning Parts of cyanide antidote kit (amyl nitrite, sodium nitrite) induce methemogloninemia. Cyanide antidotes and CO poisoning can lead to elevated CO Hb and MET Hb significantly reducing O 2 capacity of blood. Sodium nitrite should be avoided for combination cyanide/co poisonings when SpCO >10%. Hydroxycobalamin converts cyanide to cyanocobalamin (Vitamin B 12 ) which is renally cleared. Hydroxycobalamin is the antidote of choice for mixed CO and cyanide poisoning. Take Home Points Cyanide is a cellular poison which blocks cellular respiration via inhibition of Cytochrome Cyanide exposure usually leads to rapid loss of conscious, respiratory failure and cardiovascular collapse Nitrite based antidotes are contraindicated in the presence of hypoxia and concomitant CO poisoning Important to consider CN in smoke exposure 59 Carbon Monoxide and Cyanide Cyanide more common in fires than once thought. CO and CN often released in structure fires from burning plastic materials resulting in severe toxicity Symptoms of cyanide toxicity often attributed to CO because of lack of a high index of suspicion. Cyanide and CO both primarily affect the heart and CNS thus multiplying the ill effects The effects of CO and cyanide are cumulative.
Cyanide Poisoning Amyl nitrite is administered via inhalation or ventilation. Sodium nitrite is administered intravenously. Sodium thiosulfate is administered intravenously. Cyanide Treatment Concomitant CO and CN poisoning therapy can significantly decrease the O 2 carrying capacity of the blood. Combination of CO Hb and MET HB can significantly reduce the O 2 carrying capacity of the blood. Children are particularly at risk for hypotension and adverse effects from methemoglobinemia. Cyanide Treatment 20% CO-Hb 20% MET-Hb O 2 -carrying capacity nearly halved! 100% Hb
Cyanide Treatment Hydroxycobalamin Precursor to cyanocobalamin (Vitamin B 12 ). Hydroxycobalamin combines with cyanide to form cyanocobalamin which is excreted through the kidneys. FDA approval in US obtained in December 2006. Marketed as Cyanokit.