Cyanide AntidotesPaul Jones

September 10, 2010

Objectives

To review the management decisions in a case of cyanide poisoning

Case presentation

Clinical question to consider

Case conclusion

Case Presentation

Patient brought in VSA to the ED by EMS Roommate found patient collapsed on the

floor and unresponsive – started CPR after calling EMS

No known medical conditions Works in chemistry research lab

Case Cont’d…

GCS 3 Pupils fixed and dilated ETT intubation by EMS PEA Bedside U/S shows no cardiac activity No signs of obvious injury

Case Cont’d… Ongoing CPR IV access obtained Femoral line inserted Blood drawn Epinephrine and atropine administered Sodium bicarbonate boluses given … EMS presents vial found beside patient

at the scene labelled NaCN

Cyanide: Background

Sources: industry, smoke inhalation

Cyanide: Clinical Presentation

Hypoxia and acidosis Coma, hemodynamic compromise,

seizures, apnea, cardiac arrest, death Acute cyanide toxicity: dizziness,

headache, weakness, flushing, diaphoresis, dyspnea, hyperventilation, hyperpnea

Labs: metabolic acidosis and elevated lactate, supranormal venous O2 content

Cyanide: Treatment GI Decontamination Supplemental O2

? Hyperbaric oxygen Antidotes:

Increase endogenous metabolism: ThiosulfateCyanide chelating: Hydroxocobalamin,

Dicobalt EDTAMethemoglobin generation: Nitrites, 4-DMAP

CAK = Amyl nitrite + Sodium nitrite + Sodium thiosulfate

Question to Consider?

Is hydroxocobalamin an effective and safe antidote to administer for suspected cyanide ingestion?

Evidence source:

PICO Analysis Patients

Patients with cyanide poisoning

Lethal threshold = 100 µmol/L

= patients found in Cardiac arrest

PICO Analysis Cont’d...

Interventions Retrospective chart review First-line treatment:

hydroxocobalamin Comparators/Confounders

Time between exposure and antidote administration

Environment/context in which cyanide poisoning occurs

Health/medical status of the patient

Adequacy of supportive measures

Outcomes of Interest Survival Post-treatment

neurological status Adverse events

Methodology

Strengths Measured blood

cyanide levels Pure cyanide

poisoning – eliminates other toxins present with smoke inhalation or co-ingestions

Weaknesses Retrospective study No comparison group Small, heterogenous

sample

Chart review of cases between 1988-2003 from toxicological ICU in France

Study Results…

Study Results… Adverse Events Caused by

Hydroxocobalamin: n = 8Chromaturia (red-colored

urine): n =5Pink-to-red skin discoloration:

n = 3 Increase in HR: n =1Elevated BP: n = 1

Borron et al. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation.

Uhl et al. Safety of Hydroxocobalamin in Healthy Volunteers in a RCT

Study Results…

Conclusions…

71% of patients survived potentially lethal cyanide poisoning after treatment with hydroxocobalamin

Need for rapid intervention Builds on previous case reports Risk-benefit profile supports empiric use in

both the pre-hospital and hospital settings Uhl et al. Safety of Hydroxocobalamin in Healthy Volunteers in a Randomized,

Placebo-Controlled Study

Case Conclusion… Cyanide Antidote Kit (CAK) retrieved Sodium nitrite and sodium thiosulfate

administered intravenously Further boluses of sodium bicarbonate given No cardiac activity seen on repeat bedside U/S Time of death called after over an hour of

resuscitation Suicide note and printout on cyanide poisoning

found in patients apartment

What Would Google Do?

Try it for yourself.

Ask a good question, get a good

answer!

References1. Borron SW, Baud FJ, Megarbane B and Bismuth C. Hydroxocobalamin for

severe acute cyanide poisoning by ingestion or inhalation. American Journal of Emergency Medicine (2007) 25, 551–558

2. Rodgers GC and Condurache CT. Antidotes and treatments for chemical warfare/terrorism agents: an evidence-based review. Clinical Pharmacology Therapeutics. 2010 Sep;88(3):318-27.

3. Gracia R and Shepherd G. Cyanide Poisoning and Its Treatment. Pharmacotherapy 2004;24(10):1306-1310.

4. Uhl W, Nolting A, Golor G, Rost KL and Kovar, A. Safety of Hydroxocobalamin in Healthy Volunteers in a Randomized, Placebo-Controlled Study. Clinical Toxicology, 44:17–28, 2006.

5. Alan H. Hall AH, Saiers J and Baud F. Which cyanide antidote? Critical Reviews in Toxicology, 2009; 39(7): 541–552.

Thank you…

“The true harvest of my life is intangible - a little star dust caught, a portion of the rainbow I have clutched”

Henry David Thoreau