1. Anne Arundel County DOH, 20041 Cyanide Poisoning Daniel Shodell MD, MPH

2. Anne Arundel County DOH, 20042 Learning objectives Describe the clinical syndrome, treatment, and epidemiology of cyanide Identify the key public health agency response in a cyanide chemical terrorism event

3. Anne Arundel County DOH, 20043 Overview / Background Cyanide: –recognized since antiquity –present in bitter almonds, cassava, and other foods –used extensively in industry for fumigation, electroplating, and mining activities

4. Anne Arundel County DOH, 20044 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

5. Anne Arundel County DOH, 20045 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

6. Anne Arundel County DOH, 20046 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 (1)ATF www.atf.gov/press/fy04press/field/051104dal_chemweapons.htmwww.atf.gov/press/fy04press/field/051104dal_chemweapons.htm (2)CNN edition.cnn.com/2003/US/02/06/sprj.irq.alqaeda.links/index.htmledition.cnn.com/2003/US/02/06/sprj.irq.alqaeda.links/index.html (3)CBWInfo www.cbwinfo.com/Chemical/Blood/AC.shtmlwww.cbwinfo.com/Chemical/Blood/AC.shtml

7. Anne Arundel County DOH, 20047 Epidemiology Acute v. Chronic poisoning –Varying clinical presentation –This presentation will focus on acute intoxication, consistent with a terrorist event or industrial accident

8. Anne Arundel County DOH, 20048 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

9. Anne Arundel County DOH, 20049 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

10. Anne Arundel County DOH, 200410 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

11. Anne Arundel County DOH, 200411 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

12. Anne Arundel County DOH, 200412 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

13. Anne Arundel County DOH, 200413 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

14. Anne Arundel County DOH, 200414 Treatment: overview 1)Activated charcoal 2)Supplemental oxygen 3)Supportive care / ACLS 4)Sodium nitrite 5)Amyl nitrite 6)Sodium thiosulfate 7)Hydroxocobalamin

15. Anne Arundel County DOH, 200415 Treatment 1) Activated charcoal -For alert, asymptomatic patients following ingestion 2)Supplemental oxygen -100% for suspected exposure 3) Supportive care / ACLS

16. Anne Arundel County DOH, 200416 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

17. Anne Arundel County DOH, 200417 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

18. Anne Arundel County DOH, 200418 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]

19. Anne Arundel County DOH, 200419 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

20. Anne Arundel County DOH, 200420 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

21. Anne Arundel County DOH, 200421 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

22. Anne Arundel County DOH, 200422 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

23. Anne Arundel County DOH, 200423 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

24. Anne Arundel County DOH, 200424 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

25. Anne Arundel County DOH, 200425 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

26. Anne Arundel County DOH, 200426 Resources Web Resources –Centers for Disease Control and Prevention, Emergency Preparedness and Response www.bt.cdc.gov/agent/cyanidewww.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/c yanide.pdf http://www.hpa.org.uk/infections/topics_az/deliberate_release/chemicals/c yanide.pdf –The National Institute for Occupational Safety and Health, Online NIOSH Pocket Guide to Chemical Hazards http://www.cdc.gov/niosh/npg/npgd0000.html 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.htmlhttp://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 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.shtmlhttp://www.cbwinfo.com/Chemical/Blood/AC.shtml