rella cyanide 9.16
DESCRIPTION
rellaTRANSCRIPT
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MEMC V:Cyanide Toxicity from Common Housefires
Joseph Rella, MDAssistant Professor, Emergency MedicineNew Jersey Medical School2009
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Environmental Emergencies
Chemistry of CN
Various salts pKa ~ 9.2 Na-, K-, Ca-
Various routes of access Often a massive poisoning Ingestion, inhalation, transdermal
Cellular inhibition CN readily complexes with metals Cytochrome oxidase complex (4) (myoglobin, nitrate
reductase)
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Oxidative Phosphorylation
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Intermembranespace
Matrix
I
II
Q III IV
ATP synthase
SuccinateFumarateNADH NAD + H+
4 H+ 4 H+ 2 H+
pH pH pH pH and
H+
ADP + Pi
ATP
e-
e-e-
e-cyto C
O2
+ 2 H+ H2O
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Environmental Emergencies
Intermembranespace
Matrix (pyruvate dehydrogenase and Krebs cycle stop as well!)
I
II
Q III
ATP synthase
SuccinateNADH+
Pyruvate
pH pH pH pH and
H+
ADP + Pi
e-
e-
cyto C
O2
+ 2 H+
CN
Lactate
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Inhibitors of the System
Electron transport inhibitors CN (azide, CO) binds to Cu ligands in complex IV
Uncouplers Some dissipate
Energy transfer inhibitors Inhibitory uncouplers
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Physical effects of CN
A potent neurotoxin White matter is the more sensitive tissue Histotoxic anoxia Sudden loss of electrical activity in brain
Inhibits glutamate decarboxylase! Severe metabolic acidosis Clinical effects:
Headache, agitation, confusion, dyspnea, seizures, cardiovascular collapse - arrest
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Clinical symptoms among 36 cyanide intoxications
228Respiratory arrest
176Psychomotor retardation
145Post-anoxic coma and death
5018Metabolic acidosis
176Convulsions
3613Coma
2810Cardiovascular collapse
228Asymptomatic% of totalnSymptom
Boron SW, Baud FJ. Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment. Arh hig rada toksikol 1996;47:307
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Sources of CN
Industrial/laboratory reagents Plastics, electroplating, mining, photography,
precious metal reclamation Fumigants
And
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Combustion!
Silk, wool, nylon, polyurethane, melamine, polyacetonitrile,polyamide plastics
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The Part CN Plays in Housefires
Product of combustion Acts as a knockdown agent
Decreases patients ability to evacuate Now more vulnerable to flame, CO, smoke,
etc.
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Supporting Data of the Risk Symington I Lancet 1978 Clark CJ Lancet 1981 Birky MM Bull NY Acad Med 1981 Silverman SH J Trauma 1988 Baud FJ NEJM 1991 Jones J Am J Emerg Med 1987 Kulig K NEJM 1991 Chaturvedi AK J Appl Toxicol 1995 Shusterman D J Toxicol Clin Toxicol 1996 Ferrari L Forensic Sci Int 2001 Alarie Y Crit Rev Toxicol 2002 Yeoh M J Toxicol Clin Toxicol 2004 Borron SW NEJM 2004
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The Controversy: How good are the data?
Varied exposures Complicated sampling, storage, analysis Animal models of smoke inhalation
Years of relying on CO and MetHbmeasurements
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Evaluation of Potentially Exposed Patients
Clinically: comatose patients are easy to identify Be suspicious of awake, confused/agitated patients BP < 100mmHg without trauma
Emergency laboratory testing: Save blood in a heparinized tube at 4C for later an alysis Elevated lactate is the best we have for now
Baud FJ, et al. Crit Care Med 2002;30:2044
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Antidotal Therapies
Taylor kit
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Taylor Kit
Amyl nitrite / Sodium nitrite Cyanomethemoglobin outcompetes CN for Cyto aa3 to
restore function MetHb lags toxicity resolution Works despite methylene blue Possibly due to vasodilation, NO Some side effects
Sodium thiosulfate Sulfur supplier for sulfurtransferase transformation and
detoxification Very safe to give
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Hydroxycobalamin
Actively complexes cyanide Directly detoxifies
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(Fe) Cyto aa3CN
Nitrites
Cyanomethemoglobin
OxyHb
MetHb CN CN
CN
S2O32-
SCN- + SO32-
Rhodanese
Hydroxycobalamine
Cyanocobalamine
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Environmental Emergencies
Summary
CN is a potent, rapid acting toxin CN is commonly found in victims of
housefires Be suspicious that seemingly mildly ill
persons may be toxic Save blood, get lactate Taylor or Hydroxycobalamine Good supportive care