1. Death By Smoke: Cyanide Poisoning & Cyanokits ®
Amy Gutman MD
EMS Medical Director /

2. 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 but is beyond the scope of this brief presentation

3. 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

4. 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

5. 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

6. “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

7. 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

8. 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

9. 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

10. 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.

11. 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

12. 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   

13. 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

14. 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

15. 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

16. 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.

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

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

19. 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 mins

20. 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.

21. References
Cyanokit Project. California Department of Public Health, Emergency Preparedness Office
Eckstein M. JEMS. 2004;29:suppl 22-31
Guy JS, et al. Smoke inhalation injury
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: ;
RTI International. Clin Toxicol. 2006;44 Suppl 1:47-63
Guidotti T. Prehosp Disast Med. 2005;21:s40-s48.
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):
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):
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,
Baskin S. “Cyanide poisoning: Medical aspects of chemical and biological warfare,” Chapter 10. U.S. Army Medical Research Institute. 2000,
Baud FJ. “Elevated blood cyanide concentrations in victims of smoke inhalation,” NEJM. Dec 1991; 325(25):
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.

22. Summary prehospitalmd@gmail.com / www.TEAEMS.com
Full presentation on “Toxic Smoke” including full review of CO & HCN poisoning available at
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