Cyanide Poisoning Daniel Shodell MD MPH Anne Arundel

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

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 2

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 3

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 4

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 5

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/fy 04 press/field/051104 dal_chemweapons. htm (2) CNN edition. cnn. com/2003/US/02/06/sprj. irq. alqaeda. links/index. html (3) CBWInfo www. cbwinfo. com/Chemical/Blood/AC. shtml Anne Arundel County DOH, 2004 6

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 7

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 8

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 9

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 10

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 11

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 p. O 2 may be elevated Anne Arundel County DOH, 2004 12

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 13

Treatment: overview 1) 2) 3) 4) 5) 6) 7) Activated charcoal Supplemental oxygen Supportive care / ACLS Sodium nitrite Amyl nitrite Sodium thiosulfate Hydroxocobalamin Anne Arundel County DOH, 2004 14

Treatment 1) Activated charcoal -For alert, asymptomatic patients following ingestion 2) Supplemental oxygen -100% for suspected exposure 3) Supportive care / ACLS Anne Arundel County DOH, 2004 15

Treatment 4) Sodium nitrite -Mechanism: forms methemoglobin, competes with cytochrome oxidase for free cyanide; combines with cyanide to form cyanmethemoglobin -Dose: Adults: 300 mg 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 16

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 firstline intervention -Dose: Adults: 12. 5 g IV over 10 -20 minutes following administration of sodium nitrite Children: 412. 5 mg 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 17

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 18

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 19

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 20

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 21

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 22

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 23

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 24

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): 897922 Anne Arundel County DOH, 2004 25

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/c yanide. pdf – The National Institute for Occupational Safety and Health, Online NIOSH Pocket Guide to Chemical Hazards http: //www. cdc. gov/niosh/npgd 0000. html – Agency for Toxic Substances and Disease Registry Public Health Statement for Cyanide http: //www. atsdr. cdc. gov/toxprofiles/phs 8. html – Agency for Toxic Substances and Disease Registry Medical Management Guidelines for Hydrogen Cyanide http: //www. atsdr. cdc. gov/MHMI/mmg 8. html – CBWInfo Factsheets on Chemical and Biological Warfare Agents, Hydrogen Cyanide http: //www. cbwinfo. com/Chemical/Blood/AC. shtml Anne Arundel County DOH, 2004 26