Death By Smoke: Cyanide Poisoning & Cyanokits ® Amy Gutman MD EMS Medical Director prehospitalmd@gmail.com / www.TEAEMS.com

Introduction Review cyanide toxicity, assessment & emergency management A full presentation on the “Toxic Twins” of carbon monoxide and hydrogen cyanide is available for review as the lecture “Toxic Smoke” on www.TEAEMS.com, but is beyond the scope of this brief presentation

Rescuer Morbidity & Mortality 80% fire scene injuries due to smoke inhalation 50% firefighter line-of-duty deaths from cardiovascular stressors >4,000 fire-related deaths & >20,000 smoke inhalation injuries occur in the US annually Rescuers & fire victims have a high mortality from enclosed space burns due to the chemical composition of modern manufactured materials

Toxic Smoke Toxic smoke inhalation is a major cause of rescuer morbidity & mortality, causing acute critical injuries with long-term cardiovascular & neurological effects Many toxic products released during a typical building & contents fire Many toxins are difficult to rapidly detect, yet must be immediately treated based upon clinical exam and a high degree of suspicion

Toxic Smoke “Anatomy” Particulates (dust, soot) Irritants Hydrochloric acid Sulfur dioxide Nitrogen oxides Ammonia Formaldehyde Benzene Asphyxiants/Toxicants Carbon dioxide Hydrogen cyanide Carbon monoxide Hydrogen sulfide Acrolein Aldehyde Phosgene Structural fires often involve polyvinyl chloride, used to make upholstery, wire, pipes & wall coverings Burning pvc creates hydrogen chloride & phosgene Polyethylene & pvc more dangerous when smoldering than during the high heat of a working fire, emitting carbon monoxide, hydrogen cyanide, hydrochloric acid & other toxins

“Toxic Twins” Carbon monoxide (CO) & hydrogen cyanide (HCN) are "toxic twins" of smoke inhalation Released from rubber, plastics, synthetics, laminates & other materials with deadly synergistic effects HCN exposure compounds CO injuries Cyanide 35 times more toxic than CO Cyanide toxicity additive with CO as minimal levels often lethal causing rapid AMS, hemodynamic instability & death CO & HCN so rapidly lethal that other toxins rarely found on autopsy blood analysis

Cyanide Poisoning Accidental exposure Intentional exposure Inhalation (occupational, fire smoke) Ingestion (household products) Dermal (industrial materials) Intentional exposure Terrorism (Saddam Hussain) Intentional poisoning via suicide or tampering with commercial products (Tylenol in 1980s) Smoke inhalation is most common route exposure

Hydrogen Cyanide (HCN) Odorless, colorless Inhalation results in loss of consciousness in 30 secs, apnea in 3-5 mins, cardiac arrest in 5-8 mins In a low-O2 environment, cyanide 10 X more toxic In a closed room, cyanide released from combustion of one seat cushion can kill all occupants w/i minutes Prevents cells from using O2 in energy production causing acidosis, cell death & cardiopulmonary arrest As death occurs within minutess, there may be no other evidence of smoke inhalation

HCN Mechanism of Action Cyanide binds & deactivates mitochondrial cytochrome a3, inhibiting cellular O2 utilization No amount of supplemental oxygen can overcome this O2 deficit Inhibition of cellular respiration results in accumulation of toxic byproducts of anaerobic metabolism (i.e. lactic acid) & depletion of cellular adenosine triphosphate (ATP) Tissues with highest O2 requirements (brain & heart) rapidly affected

Acute Cyanide Poisoning HCN poisoning presumptive, (no rapid diagnostic test) Toxicity suggested by: AMS Dilated pupils (mydriasis) Bradypnea Hypotension, tachycardia Confirmed CO poisoning Holstege CP, et al. Goldfrank’s Toxicologic Emergencies. 8th ed.

HCN Poisoning Management Treatment decisions must be made immediately based upon history, SSX, exam & clinical suspicion Supportive care, rapid transport Establish airway, administer 100% O2 Cardiopulmonary resuscitation often necessary Administer Cyanokit antidote during resuscitation (carried by selective Region V / CIEMSS ALS ambulances) Additional management dependant on symptoms (i.e. anticonvulsants, antiarrhythmics) Clinical signs of HCN & CO toxicity similar Both have AMS, hypotension, confusion, anxiety, tachycardia, tachypnea, respiratory distress High suspicion for HCN poisoning if suspected CO poisoning or exposure to a closed space fire Oximetry may record normal SaO2 with CO poisoning

Hydroxycobalamin / Cyanokit ® Class:   Vitamin B complex Therapeutic Class:  Hematinic, vitamin Actions:   Cyanide rapidly binds with cytochrome c-a3 oxidase mitochondrial complex which inhibits cells from using O2 forcing anaerobic metabolism Results in rapid lactate production, cellular hypoxia, metabolic acidosis & cell death Effectiveness of hydroxycoblamin based on ability to bind cyanide ions to form cyanocobalamin which is harmlessly secreted in urine   

Hydroxycobalamin / Cyanokit ® Pharmacokinetics:  Each mL contains hydroxocobalamin acetate equivalent to 1000mcg hydroxocobalamin & inert preservatives including cobalt Appears as dark red needles or red powder Hygroscopic while anhydrous, moderately water-soluble, unstable in light Plasma-protein bound, stored in the liver, excreted in the bile after enterohepatic recycling 50% disappears from injection site in 2.5 hours; within 72 hrs 16-66% appears in the urine with the majority excreted within 24 hrs Indications:   Smoke inhalation, known / suspected cyanide poisoning Contraindications:   Hypersensitivity ro hydroxycobalamin or cyanocobalamin

Hydroxycobalamin / Cyanokit ® Precautions:   Rare allergic reactions Pregnancy category C Blunted therapeutic response due to infection, uremia, drugs having bone marrow suppressant properties such as chloramphenicol, and concurrent iron or folic acid deficiency. Side Effects: Transient HA, hypertention, chromoaturia, N/V erythema, rash, injection site reactions

Cyanokit® Only ancillary supply needed is sterile water for reconstitution Takes effect in minutes Is only FDA approved emergency antidote for treatment of known or suspected cyanide poisoning Side effects usually minimal & transient Allergic Reactions Transient elevation in blood pressure Photosensitivity Transient urine red-coloration

Cyanokit ® Step 1: Reconstitute Add 100cc of 0.9% saline to vial using sterile transfer spike LR & 5% dextrose also compatible Diluent not included in the kit Fill to line, which represents 100cc Keep vial in upright position Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

Cyanokit® Step 2: Mix Rock or rotate vial for 30 seconds to mix solution Do not shake

Cyanokit ® Step 3: Infuse 1st Vial Use vented IV tubing Hang & infuse over 7.5 – 15 minutes

Cyanokit® Step 4: Infuse 2nd Vial (Medical Control) EMS must call Medical Control for 2nd vial Repeat steps 1 & 2 before 2nd infusion Reconstitute Mix Use vented IV tubing Hang & infuse over 15-120 mins

Cyanokit® Considerations Inspect solution for particulate matter & color Discard if particulates present or solution not dark red Stored at 25°C (77°F) Use separate IV line for infusion as most resuscitation drugs incompatible with Cyanokit If administering other antidotes, do not use same IV line In addition to Cyanokit, HCN treatment includes aggressive airway management, cardiovascular support, & seizure management Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

References Cyanokit Project. California Department of Public Health, Emergency Preparedness Office. 2010. Eckstein M. JEMS. 2004;29:suppl 22-31 Guy JS, et al. Smoke inhalation injury. www.medscape.com. 2007 Lee-Chiong TL. Postgrad Med. 1999;105:55-62. Cyanide Poisoning Treatment Coalition. 2007 Alcorta R. JEMS. 2004;29:suppl 6-15; CDC. MMWR. 2003;52:906-908; RTI International. Clin Toxicol. 2006;44 Suppl 1:47-63 Guidotti T. Prehosp Disast Med. 2005;21:s40-s48. www.masimo.com www.Firerehab.com www.firegrantshelp.com www.emsgrantshelp.com www.naemse.org www.naemt.org www.iaff.org www.carbonmonoxidekills.com www.epa.gov/iaq/pubs/coftsht.html www.carbon-monoxide-poisoning.com www.cdc.gov www.nlm.nih.gov/medlineplus/carbonmonoxidepoisoning.html www.emedicinehealth.com/carbon_monoxide_poisoning/article_em.htm www.osha.gov/OshDoc/data_General_Facts/carbonmonoxide-factsheet.pdf www.postgradmed.com/issues/1999/01_99/tomaszewski.htm Goldfrank’s Toxicologic Emergencies. 8th ed. New York, NY: McGraw-Hill; 2006:1712 Meridian Medical Technologies Training Presentation. 2011 Alarie Y. “Toxicity of Fire Smoke,” Critical Reviews in Tox, 2002; 32(4):259-289 Guy JS. “Smoke Inhalation Injury: Pulmonary Implications,” MedGenMed, 1999; 1(3) Cone DC. “Threats to life in residential structure fires,” PEC. Jul 2008;12(3):297-301 Gilmer B. “Hyperbaric oxygen does not prevent neurologic sequelae after carbon monoxide poisoning,” AEM; 2002:9 (1), 1-8. Borron, S. Emergency physician’s role in appropriate treatment of cyanide poisoning in smoke inhalation. Oral presentation, Seattle, Wash., 10/09/2008. Tuovinen H. ”Modeling of Hydrogen Cyanide Formation in Room Fires.” SP Swedish National Testing and Research Institute, 2003 Griggs TR. “The role of exertion as a determinant of carboxyhemoglobin accumulation in firefighters,” Journal of Occupational Medicine; 1997 Nov:19(11):759-61 O’Brien D. “Cyanide Exposure, Smoke Inhalation, and Pre-Hospital Treatment: Recognizing the Signs and Symptoms and Available Treatment Options,” “Smoke, Cyanide and Carbon Monoxide, The Toxic Twins of Smoke Inhalation,” Cyanide Poisoning Treatment Coalition, Indianapolis, Ind, 2009, www.FireSmoke.org Baskin S. “Cyanide poisoning: Medical aspects of chemical and biological warfare,” Chapter 10. U.S. Army Medical Research Institute. 2000, 271-286 Baud FJ. “Elevated blood cyanide concentrations in victims of smoke inhalation,” NEJM. Dec 1991; 325(25):1761-1766 NIOSH Report. Career Lieutenant Dies in Residential Structure Fire. 2007 Hall G. Toxicology of smoke inhalation. Fire Engineering. 2009 Jon Marinaro, MD. Trauma-Surgical ICU Director. UNM Burn Center. Presentation 2010.

Summary prehospitalmd@gmail.com / www.TEAEMS.com Full presentation on “Toxic Smoke” including full review of CO & HCN poisoning available at www.TEAEMS.com With ANY suspicion of HCN poisoning, immediately start treatment as a few minute delay can be lethal Cyanokit simple & easy to use, easy to store with minimal side effects or contraindications