1) Cyanide poisoning from smoke inhalation is a serious threat, as cyanide prevents cells from using oxygen and can be fatal even with high oxygen levels. Hydroxocobalamin (Cyanokit) binds to cyanide and allows cells to use oxygen again, and is the only approved cyanide antidote for smoke inhalation. 2) Cyanokit comes in a single 5g vial and is administered by reconstituting with saline and infusing over 15 minutes as a starting dose for cyanide poisoning. Additional doses may be given if needed. 3) Cyanokit turns the skin and urine red but has few other side effects, and is safer than other options for treating

1. Cyanokit
Administration
Dr. Amy Gutman
AHMD Tobey Hospital
EMS Officer Rob Sanders
Harwich Fire Dept.

2. Combating Another Side of Smoke
Cyanide Poisoning and How to Treat It
Using the Single-Vial CYANOKIT® 5 g (hydroxocobalamin for injection)
Full Starting Dose
in a Single Vial

5. RAE
Atmospheric Monitors

6. IFSTA
NFPA
DOT
Boston EMS
N. Las Vegas FD
Houston FD

7. CDC, Textbook on CBREN
Events, 2010
Brigham & Women’s Hospital
MA OEMS Medical Treatment
Protocols

10. The “Toxic Twins”
• CO & HCN dubbed the "toxic twins" of smoke
inhalation
Released from rubber, plastics, synthetics,
laminates & other materials found in modern-
day residential structures with deadly
synergistic effects
• HCN exposure compounds carbon monoxide
injuries
– Cyanide 35 times more toxic than CO
– Cyanide toxicity additive with CO as even
minimal levels are often lethal

12. Anatomy and Physiology
• Oxygen is
transported across
the alveolar
membrane.
• It then attaches to
HEMOGLOBIN in
RED BLODD CELLS
for transport to the
rest of the body.

14. • CO displaces O2 from hemoglobin
binding sites (4)
• CO prevents O2 from binding
• COHb increases O2 affinity,
interfering with normal release

15. Hydrogen Cyanide (CN)
• TOXIC GAS!!!!!!:
–Colorless or pale blue
–Faint bitter almond
odor*
–Irritating
–Burning taste
• Physical Properties:
–Vapor Density = 0.94
–LEL/UEL = 5.6 – 40%
–IDLH = 50 ppm
*Up to 40% of population unable to detect HCN odor

16. HCN Mechanism of Action
• Cyanide binds & deactivates mitochondrial
cytochrome a3, effectively inhibiting
cellular utilization of oxygen
• 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) most affected

17. 17
How Cyanide Affects
Cellular Respiration
1. Cyanokit (single 5-g vial) [package
insert]. Columbia, MD: Meridian Medical
Technologies, Inc.; 2011. 2. Schnepp R.
Where there's fire—there's smoke! In:
Smoke: Cyanide and Carbon Monoxide:
The Toxic Twins of Smoke Inhalation.
Indianapolis, IN: Cyanide Poisoning
Treatment Coalition; 2009:3-8.
Cyanide may disable the body’s
ability to use oxygen so it can be
fatal despite the amount of oxygen
available to the body.1,2

22. Cyanide in Fire Smoke
Natural
Substances:
• Wool
• Silk
• Cotton
• Paper
Synthetic Substances:
Plastics
Nylons
Styrofoam
Polyurethane foam

23. Hydrogen Cyanide (HCN)
• HCN forms from burning materials
containing nitrile or cyano group (bonded
carbon & nitrogen molecules)
• Plastics (polyurethane foam, melamine,
nylon, PVC) all release cyanide
• In a closed room, cyanide released from
combustion of one seat cushion can kill all
occupants w/i minutes

25. Hydrogen Cyanide (HCN)
• Greatest in fires with low-heat & low-O2 levels
– Odorless & colorless
• When inhaled in a low-O2 environment,
cyanide becomes 10 X more toxic
• Inhalation results in the loss of
consciousness within 30 secs, apnea in 3-5
mins, & cardiac arrest in 5-8 mins
• Affects cells by preventing the use of O2 in
energy production causing acidosis, cell
death, respiratory depression & arrest
• As death occurs within mins, there may be no
other evidence of smoke inhalation

26. Trends in Construction
Shift from wood & natural to lightweight materials (read
synthetics and petroleum based products) =
– Burn 2 – 3 times hotter and ignite 2 – 3 times
faster
– Emit significant HCN during pyrolysis
1. Less time to escape (shorter time to
flashover)
2. Toxic gases incapacitate!!!!!!!!!!
3. Increased risk of injury (thermal, inhalation)

27. CN & CO: Exposure in Fire Deaths
COHb, carboxyhemoglobin; FFS, Foundation for Fire Safety.
Adapted from Alarie Y. Crit Rev Toxicol. 2002;32:259-289.
48%
87% 87%
34% 33% 35%
5%
98%
21%
58%
49% 47%
0%
20%
40%
60%
80%
100%
Dupont Plaza
Hotel (n=97)
Happy Land
Social Club
(n=87)
Manchester
aircraft fire
(n=54)
Maryland fire
deaths (n=530)
FFS fire deaths
(n=129)
Glasgow fire
deaths (n=199)
Elevated cyanide (≥1 mg/L)
Elevated carbon monoxide (≥50% COHb)
Percentageoffiredeaths

28. The crowd at the station should have been able to evacuate in 200
seconds. But, from his examination of the videotape, he estimates that
once patrons reacted to the reality of the fire, they had just 43
seconds to get out before the main door was blocked.
Feb. 20 2003 The Station Nightclub fire which killed 100, injured nearly 200

29. Station Nightclub Fire - RI
• Feb 2003 band pyrotechnics ignite
polyurethane foam lining stage walls
• 440 people, 100 deaths

30. Simulation of
platform area
60 seconds - flashover
90 seconds – CO, CN, O2
incompatible with life

31. INHALATION INJURY
COMPLEX
Injuries Resulting From
Products of
Combustion

32. INHALATION INJURY
COMPLEX
•“Toxic Twins”
CO/HCN
• Heat Injury
• Other Toxic Gases

33. GENERAL TREATMENT
INHALATION INJURIES
• REMOVE FROM ENVIRONMENT!
• HIGH FLOW O2!
Non-Rebreather
BVM (positive pressure)
ETT (positive pressure)
? Hyperbaric Medicine
• ? Neb Treatment, ? “Cyanokit”

34. HIGH FLOW
OXYGEN !!!!!!!!
• CO reduced 50% every
30 min if 100% O2 used
*PO unreliable until Co
treated!!!!!!!!
*RAD 57 to measure % C0

36. Acute Cyanide Poisoning
• HCN poisoning
presumptive, as there is
no rapid diagnostic test
• Toxicity suggested by
ALTERED MENTAL STATUS!!!!!!!!
– Dilated pupils
– Low respiratory rate
– Low systolic blood pressure
with increased heart rate
– Nausea/vomiting
– Confirmed CO poisoning
SIGNS/SYMPTOMS
CO and HCN
VERY SIMILAR
Holstege CP, et al. Goldfrank’s Toxicologic Emergencies. 8th ed.

37. TREATMENT
HYDROGEN CYANIDE GAS
•Hydroxocobalamin
“CYANOKIT”
• FDA approved 2006
• Binds to form B12
• MA DPH approved Pre-Hospital
• No known major side
effects/toxicities

38. CYANOKIT® 5 g
(hydroxocobalamin for injection)
FDA-approved for the treatment of known or
suspected cyanide poisoning.
Click for Table of Contents
Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.

40. Paris Fire Brigade Protocol
1. Known smoke
exposure in
enclosed space
2. Altered mental
status
3. Soot in nares or
mouth

43. 43
How Cyanide Affects
Cellular Respiration
1. Cyanokit (single 5-g vial) [package
insert]. Columbia, MD: Meridian Medical
Technologies, Inc.; 2011. 2. Schnepp R.
Where there's fire—there's smoke! In:
Smoke: Cyanide and Carbon Monoxide:
The Toxic Twins of Smoke Inhalation.
Indianapolis, IN: Cyanide Poisoning
Treatment Coalition; 2009:3-8.
Cyanide may disable the body’s
ability to use oxygen so it can be
fatal despite the amount of oxygen
available to the body.1,2

44. 44
How Hydroxocobalamin
Interacts With Cyanide
1. Cyanokit (single 5-g vial) [package
insert]. Columbia, MD: Meridian Medical
Technologies, Inc.; 2011. 2. Schnepp R.
Where there's fire—there's smoke! In:
Smoke: Cyanide and Carbon Monoxide:
The Toxic Twins of Smoke Inhalation.
Indianapolis, IN: Cyanide Poisoning
Treatment Coalition; 2009:3-8.
CYANOKIT® 5 g
(hydroxocobalamin for injection)
is the only cyanide antidote that
contains hydroxocobalamin,
which binds to cyanide, allowing
the body to use oxygen again.1,2

45. Paris Fire Brigade Protocol
ROSC = 50%

46. HCN Poisoning Treatment
• France has Cyanokits on
every ambulance
• In the United States
– 21% of ALS providers have
cyanide treatment kits
– 36% of ALS providers stock
large cache of kits as part of a
disaster response plan
• In a 2008 California survey
only 38 hospitals carried
Cyanokits
– Does your closest hospital?

47. HCN Poisoning Management
• All persons from a closed space fire are
considered to have smoke inhalation until
proven otherwise
• Administer CYANOKIT during resuscitation
• Supportive treatment urgently required including fluid
resuscitation, aggressive pulmonary care & early
wound management
• Supportive care with rapid transport!!!!!!!!!!!
– Establish patent airway & administer 100% oxygen
– Cardiopulmonary resuscitation often necessary
• Additional management depends on symptoms (i.e.
anticonvulsants, antiarrhythmics)

48. Hydroxocobalamin: Characteristics
Risk:benefit ratio
renders it suitable
for prehospital
empiric use and
use in smoke-
inhalation victims
Does not reduce oxygen-carrying capacity of
blood !!!!!!!!!!!!!!!!!!!
Does not cause hemodynamic instability
Transient side effects:
Red discoloration of urine, skin, and mucous
membranes
Transient increases in blood pressure
Interference with colorimetric laboratory tests
AST, total bilirubin, creatinine, glucose
Mg2+, Fe2+, creatinine kinase, phosphorus
Flomenbaum NE, et al. Goldfrank’s Toxicologic Emergencies. McGraw-Hill. 2006.
Megarbane B, et al. J Chin Med Assoc. 2003;66:193-203.

49. Cyanokit® (hydroxocobalamin)
Vitamin B12 precursor
Binds with cyanide in blood, forms cyanocobalamin
(vitamin B12)
Cyanocobalamin is not toxic and is excreted in
the urine!!!!!!!
Side effects:
Turns mucosa, skin & urine red
Transient hypertension
Interferes with colorimetric lab values
No other cyanide antidote is safe
for FIRE SMOKE INHALATION!!!!!
Sauer SW, Keim ME. Ann Emerg Med 2001;37:635-641.

50. Skin Redness in Healthy Volunteers
After 10 g treatment, photos on Day 1 and on Day 8.
Day 1*
Day 8†
*No flash photography. †Flash photography used.
OHCo, hydroxocobalamin. Uhl W, et al. Clin Toxicol. 2006;44:17-28.

51. 51
Contents of Single-Vial CYANOKIT® 5 g
(hydroxocobalamin for injection)1
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

52. 52
Step 1: RECONSTITUTE1
• Place the vial in an upright position
• Add 200 mL of 0.9% Sodium Chloride Injection to the
vial using the sterile transfer spike. Fill to the line.
– 0.9% Sodium Chloride Injection is the
recommended diluent
– Diluent is not included in the kit
– Lactated Ringer's Solution and 5% Dextrose Injection
have also been found to be compatible with
hydroxocobalamin
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

53. 53
Step 2: MIX1
• The vial should be repeatedly
inverted or rocked, not shaken, for at
least
60 seconds prior to infusion
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

54. 54
Step 3: INFUSE VIAL1
• Use vented intravenous tubing
• Hang and infuse over 15 minutes
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.
One 5-g vial is a complete starting dose.

55. Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.
Storage of Lyophilized Form1
• CYANOKIT® 5 g (hydroxocobalamin for injection) should be stored
at 25°C (77°F)
– Excursions are permitted to 15° to 30°C (59° to 86°F)
• CYANOKIT® may be exposed, during short periods, to temperature variations of usual
transport, transport in the desert, and freezing/defrosting cycles
– Usual transport defined as 15 days subjected to temperatures
ranging from 5° to 40°C (41° to 104°F)
– Transport in the desert defined as 4 days subjected to temperatures
ranging from 5° to 60°C (41° to 140°F)
– Freezing/defrosting cycles defined as 15 days subjected to temperatures
ranging from –20° to 40°C (–4° to 104°F)
55
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

56. Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.
Recommended Dosing1
• The starting dose of CYANOKIT® 5 g (hydroxocobalamin for injection)
for adults is 5 g over 15 min (Pedi 70mg/kg over 15 min; chart
available)
– One 5-g vial
– Administer by intravenous (IV) infusion over 15 minutes
• Depending upon the severity of the poisoning and the clinical response, a second dose
of 5 g may be administered by IV infusion up to a total dose of 10 g
– The rate of infusion for a potential second dose may range from 15 minutes (for patients in
extremis) to 2 hours, as clinically indicated
56
Important Safety Information
Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin
or cyanocobalamin. Allergic reactions may include anaphylaxis, chest tightness, edema, urticaria,
pruritus, dyspnea, rash, and angioneurotic edema. Substantial increases in blood pressure may occur
following treatment with CYANOKIT®.
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

57. Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.
Storage of Reconstituted Drug Product1
• CYANOKIT® 5 g (hydroxocobalamin for injection) may be kept up to 6 hours at a
temperature not exceeding 40°C (104°F)
• Do not freeze
• Product not used by 6 hours should be discarded
57
1. Cyanokit (single 5-g vial) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

58. Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.
Grant Eligibility
• CYANOKIT® 5 g (hydroxocobalamin for injection) is approved on the Department of
Homeland Security's Authorized Equipment List (AEL), making it eligible for the following
grant programs1:
– State Homeland Security Program (SHSP)
– Urban Area Security Initiative (UASI)
– Metropolitan Medical Response System (MMRS)
– Transit Security Grant Program (TSGP)
• Additional grant information and resources can be found at:
– emsgrantshelp.com
– firegrantshelp.com
– usfa.dhs.gov/grants
– fema.gov/firegrants/
– usfa.dhs.gov/fireservice/grants/afgp
58
1. Department of Homeland Security. Authorized equipment list. https://www.rkb.us/mel.cfm?subtypeid=549. Accessed September 2, 2011.
These Web sites are neither owned nor controlled by Meridian. Meridian is not responsible for the content or services of these sites.

59. OEMS Protocols-2013
(CYANOKIT)
• Hydroxocobalamin listed as a
Medical Control Item in 3.13
Toxicology/Posioning/Abuse/OD
(Burn protocol also notes
CYANOKIT and refers to 3.13)
1-Known exposure to HCN*
2-Altered Mental Status*
* IF BOTH PRESENT REQUEST
ORDERS FOR ADMIN OF CYANOKIT

60. Thank You and
Stay Safe!
Rob Sanders, FF/Paramedic
EMS Officer Harwich Fire Dept.
Instructor Cape & Islands EMS
r.sanders@harwichfire.com