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Cyanide Antidotes. Paul 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
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Cyanide Antidotes Paul 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: Thiosulfate • Cyanide chelating: Hydroxocobalamin, Dicobalt EDTA • Methemoglobin 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?
PICO Analysis Lethal threshold = 100 µmol/L = patients found in Cardiac arrest • Patients • Patients with cyanide poisoning
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
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 Methodology Chart review of cases between 1988-2003 from toxicological ICU in France
Study Results… 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 • Adverse Events Caused by Hydroxocobalamin: n = 8 • Chromaturia (red-colored urine): n =5 • Pink-to-red skin discoloration: n = 3 • Increase in HR: n =1 • Elevated BP: n = 1
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
Try it for yourself. Ask a good question, get a good answer!
References • 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 • 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. • Gracia R and Shepherd G. Cyanide Poisoning and Its Treatment. Pharmacotherapy 2004;24(10):1306-1310. • 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. • 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