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Cyanide Poisoning

Cyanide Poisoning. Daniel Shodell MD, MPH. Learning objectives. Describe the clinical syndrome, treatment, and epidemiology of cyanide Identify the key public health agency response in a cyanide chemical terrorism event. Overview / Background. Cyanide: recognized since antiquity

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Cyanide Poisoning

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  1. Cyanide Poisoning Daniel Shodell MD, MPH Anne Arundel County DOH, 2004

  2. Learning objectives • Describe the clinical syndrome, treatment, and epidemiology of cyanide • Identify the key public health agency response in a cyanide chemical terrorism event Anne Arundel County DOH, 2004

  3. Overview / Background • Cyanide: • recognized since antiquity • present in bitter almonds, cassava, and other foods • used extensively in industry for fumigation, electroplating, and mining activities Anne Arundel County DOH, 2004

  4. Overview / Background • Several forms exist; all may have an odor of bitter almonds, but this is not always detectable • Gas: colorless, dissipates rapidly • hydrogen cyanide [HCN] and cyanogen chloride [CNCl, also known as CK] • Liquid: ranges from blue to colorless, stable • hydrocyanic acid; an aqueous solution of HCN • Solid: white granular powder, stable • sodium, potassium, or calcium Anne Arundel County DOH, 2004

  5. Overview / Background • Tylenol tampering in 1982 • 7 deaths • subsequent events involved other over the counter medications and prepared foods • Easily available • cheap • plentiful supplies in industry • large scale contamination (eg. municipal water supplies) unlikely due to enormous quantity required to achieve toxic levels in a large body of water. • single or multiple local events are more likely Anne Arundel County DOH, 2004

  6. Overview / Background • Current threat is both domestic and international • 2003 search of a Texas property revealed cyanide salts that were possibly intended for use in domestic militia activities (1) • international terrorist groups have also been found to possess stores of cyanide (2, 3) Sources • ATF www.atf.gov/press/fy04press/field/051104dal_chemweapons.htm • CNN edition.cnn.com/2003/US/02/06/sprj.irq.alqaeda.links/index.html • CBWInfo www.cbwinfo.com/Chemical/Blood/AC.shtml Anne Arundel County DOH, 2004

  7. Epidemiology • Acute v. Chronic poisoning • Varying clinical presentation • This presentation will focus on acute intoxication, consistent with a terrorist event or industrial accident Anne Arundel County DOH, 2004

  8. Epidemiolgy - Routes of exposure • Gas: Inhalation • hydrogen cyanide • cyanogen chloride • Liquid: Inhalation (aerosol), ingestion, skin contact • hydrocyanic acid • Solid: Inhalation, ingestion, skin contact • cyanide salts Anne Arundel County DOH, 2004

  9. Clinical manifestations • Mechanism: • inhibits mitochondrial cytochrome oxidase • an “asphyxiating” agent • Primarily targets CNS and cardiac tissue, but multiple systems involved • Presentation depends on dose and route of exposure Anne Arundel County DOH, 2004

  10. Clinical manifestations • Common final pathway for cyanide intoxication is cellular hypoxia. Exposure to any form of cyanide: • Metabolic acidosis: nonspecific symptoms • CNS: dizziness, nausea, vomiting, drowsiness, tetany, trismus, hallucations • CV: arrhythmia, hypotension. Tachycardia and hypertension may occur transiently in early stages • Respiratory: dyspnea, initial hyperventilation followed by hypoventilation and pulmonary edema. Cyanosis not apparent, since blood is adequately oxygenated Anne Arundel County DOH, 2004

  11. Clinical manifestations • Time to onset of symptoms, as well as additional signs of exposure, depends on dose and route of exposure: • Inhalation • Rapid onset: seconds to minutes • Additional signs: Metallic taste; burning sensation in GI / respiratory tract • Ingestion • Delayed onset: 15 to 30 minutes • Additional signs: Sore throat; burning sensation in GI / respiratory tract; diarrhea • Skin contact • Delayed onset: 15 to 30 minutes • Additional signs: Erythema, pain at site of contact Anne Arundel County DOH, 2004

  12. Diagnosis Diagnosis is primarily made by index of suspicion and clinical judgement • Case history • suspicion of exposure • Clinical presentation • metabolic acidosis, multisystem involvement • odor of bitter almonds • Laboratory diagnosis • blood cyanide levels can be drawn, but empiric treatment is almost always required before lab results are available • high anion gap metabolic acidosis • arterial and venous pO2 may be elevated Anne Arundel County DOH, 2004

  13. Treatment • Treatment protocol differs between United States and other industrialized nations • Within the United States, new consensus is developing regarding best practices • Treatment regimen depends on severity of symptoms, route of exposure (to some extent), and what is available Anne Arundel County DOH, 2004

  14. Treatment: overview • Activated charcoal • Supplemental oxygen • Supportive care / ACLS • Sodium nitrite • Amyl nitrite • Sodium thiosulfate • Hydroxocobalamin Anne Arundel County DOH, 2004

  15. Treatment 1) Activated charcoal -For alert, asymptomatic patients following ingestion • Supplemental oxygen -100% for suspected exposure 3) Supportive care / ACLS Anne Arundel County DOH, 2004

  16. Treatment 4) Sodium nitrite -Mechanism: forms methemoglobin, competes with cytochrome oxidase for free cyanide; combines with cyanide to form cyanmethemoglobin -Dose: Adults: 300mg IV over 5 minutes; slower if hypotension develops Children: 0.12 to 0.33 mg/kg IV infused as above -Adverse reactions: Hypotension associated with rapid infusion, tachycardia, syncope, cyanosis due to methemoglobin formation, headache, dizziness, nausea, vomiting. Frequency of events is not clearly defined 5) Amyl nitrite -An inhaled drug, similar to sodium nitrite but with little systemic distribution: second line agent used when sodium nitrite is not avaialable Anne Arundel County DOH, 2004

  17. Treatment 6) Sodium thiosulfate -Mechanism: sulfur donor promotes rhodanase activity: detoxifies cyanide as it is released from cyanmethemoglobin. Directly detoxifies cyanide by conversion to thiocyanate; too slow to be useful as a first-line intervention -Dose: Adults: 12.5g IV over 10-20 minutes following administration of sodium nitrite Children: 412.5mg per kg IV over 10-20 minutes -Adverse reactions: Hypotension, CNS depression and coma due to thiocyanate intoxication, psychosis, confusion, weakness, tinnitus, contact dermatitis. Frequency of events is not clearly defined Anne Arundel County DOH, 2004

  18. Treatment 7) Hydroxocobalamin -Mechanism: direct binding agent, chelates cyanide -Dose: 4 to 5 g IV -Adverse reactions: minimal toxicity -Additional information: -not the drug of choice in the United States, in part due to its high cost; more common in Europe -other chelating agents, such as dicobalt edetate, are not generally used in the United States due to toxicity -not yet approved by FDA [Mokhlesi B, Leiken JB, Murray P, Corbridge TC. Adult toxicology in critical care: Part II: Specific poisonings. Chest. 2003 Mar;123(3):897-922] Anne Arundel County DOH, 2004

  19. Treatment • Typical cyanide treatment kit in the United States is stocked with: • Amyl nitrite ampules • Sodium nitrite solution • Sodium thiosulfate solution • Speed is critical for survival Anne Arundel County DOH, 2004

  20. Clinical outcomes • Without treatment: • Lethal exposure levels will result in rapid death • With supportive treatment and specific antidotes: • Lethal exposure levels can be survived with immediate medical management Anne Arundel County DOH, 2004

  21. Decontamination • Gas: • exposure does not require decontamination or contact precaution • Liquid or solid: • treatment team is at risk for contact exposure or inhalation of gas produced by significant quantities of remaining cyanide compounds • skin decontamination can be achieved using a rinse with dilute detergent • contaminated clothing should be removed, preferentially by the patient if alert and asymptomatic, and placed in sealed bags Anne Arundel County DOH, 2004

  22. Differential Diagnosis • Causes of anion gap metabolic acidosis: • “CATMUDPILES” • CO, CN • Alcoholic ketoacidosis • Toluene • Methanol • Uremia • DKA • Paraldehyde • Iron, INH • Lactic acidosis • Ethylene glycol • Salicylates Anne Arundel County DOH, 2004

  23. Public health response • Reporting • Critical for enabling surveillance: used to establish baselines that are used for comparison when analyzing a potential terrorist event • Reporting is the first step in coping with a covert chemical event • County or state Department of Health Anne Arundel County DOH, 2004

  24. Summary • Cyanide intoxication diagnosis and treatment has current bearing on clinical practice • terrorism • industrial accident • The hallmark of cyanide is asphyxiation and metabolic acidosis without cyanosis • Effective treatment is available • Both baseline and outbreak reporting are critical Anne Arundel County DOH, 2004

  25. Resources • Anne Arundel County physician link • Essential Reading • Cummings, TF. The treatment of cyanide poisoning. Occupational Medicine. 2004; 54:82-85 •  Additional Reading • Centers for Disease Control and Prevention. Recognition of illnesses associated with exposure to chemical agents – United States 2003. Morbidity and Mortality Weekly Report. 2003: 52(39);938-940 • Centers for Disease Control and Prevention. Biological and chemical terrorism: Strategic plan for preparedness and response. Morbidity and Mortality Weekly Report. 2000; 49(RR-4):1-14 • Mokhlesi B, Leiken JB, Murray P, Corbridge TC. Adult toxicology in critical care: Part II: Specific poisonings. Chest. 2003 Mar;123(3):897-922 Anne Arundel County DOH, 2004

  26. Resources • Web Resources • Centers for Disease Control and Prevention, Emergency Preparedness and Response www.bt.cdc.gov/agent/cyanide • Health Protection Agency Guidelines for Action in the Event of a Deliberate Release: Hydrogen Cyanide http://www.hpa.org.uk/infections/topics_az/deliberate_release/chemicals/cyanide.pdf • The National Institute for Occupational Safety and Health, Online NIOSH Pocket Guide to Chemical Hazards http://www.cdc.gov/niosh/npg/npgd0000.html • Agency for Toxic Substances and Disease Registry Public Health Statement for Cyanide http://www.atsdr.cdc.gov/toxprofiles/phs8.html • Agency for Toxic Substances and Disease Registry Medical Management Guidelines for Hydrogen Cyanide http://www.atsdr.cdc.gov/MHMI/mmg8.html • CBWInfo Factsheets on Chemical and Biological Warfare Agents, Hydrogen Cyanide http://www.cbwinfo.com/Chemical/Blood/AC.shtml Anne Arundel County DOH, 2004

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