View source for Cyanide toxicity

==Background==
===Sources===
*Burning of nitrogen-containing polymers (plastics, wool, silk)
*Prolonged use of nitroprusside
*Pits of peaches, pears, apricots, crab apples
*Intentional poisoning

===Pathophysiology===
*Binds to cytochrome oxidase in mitochondria; leads to cessation of electron transport
**Causes switch from aerobic to anaerobic metabolism despite adequate O2

===Paris Fire Brigade Protocol===
{{Paris Fire Brigade Protocol}}

==Clinical Features==
===Acute Intoxication===
*Affected by dose, route, formulation and exposure pattern
**Inhaled toxins more rapid than ingested
***Inhalation exposure may cause syncope and death after only a few breaths
*'''Early signs'''
**CNS stimulation (Headache, anxiety, confusion)
**Tachycardia, palpitations and hypertension
**Tachypnea
**Cherry-red color (rarely seen)
*'''Late signs'''
**Nausea, Vomiting
**Bradycardia, hypotension, arrhythmias, asystole
**Coma, Seizures (rare), Mydiriasis
**Bradypnea and pulmonary edema (non-cardiogenic), apnea
**Renal Failure
**Hepatic Necrosis
**Cyanosis
**Rhabdo, bright red venules seen on fundoscopy

===Chronic===
*Retrobulbar Optic Atropy (proposed)
**Heavy smokers
*Ataxic peripheral neuropathy
*Konzo
**Spactic upper motor neuron paraparesis seen in chronic ingestion of inadequately cooked casava

==Differential Diagnosis==
{{Chemical weapon DDX}}

==Diagnosis==
===Work-Up===
*Lactate (normal lactate highly suggests another diagnosis)
*VBG and ABG (narrowing of the venous-arterial PO2 gradient, causes venous hyperoxemia/increased redness -- as does CO poisoning)
*Co-oximetry
*Chemistry (anion gap acidosis)
*RBC or Serum cyanide levels (unlikely to return in time to be clinically useful)

===Evaluation===
*Smell of bitter almonds (only 60-80% of population can detect this)
*Severe unexplained metabolic acidosis (lactic)
*PO2 of venous blood similar to arterial blood
*normal SpO2
*Cherry-red skin color is uncommon 

==Treatment==
*Supportive care
**O2 100% NRB
**IVF and vasopressors for hypotension
**Bicarb for acidemia (enchances of effect of nitrite and thiosulfate)
*Antidote

===Cyanokit (Hydroxocobalamin)<ref>Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. Jun 2007;25(5):551-8.</ref><ref>Bebarta VS, Tanen DA, Lairet J, Dixon PS, Valtier S, Bush A. Hydroxocobalamin and sodium thiosulfate versus sodium nitrite and sodium thiosulfate in the treatment of acute cyanide toxicity in a swine (Sus scrofa) model. Ann Emerg Med. 2010;55(4):345-51. </ref>===
1st line therapy
====Mechanism of action====
Directly binds CN forming cyanocobalamin which is readily excreted in the urine
====Administration====
*Give 70mg/kg IV over 15min (5g is standard adult dose); may repeat 5g once as needed
*Also give 25% Na thiosulfate  1.65ml/kg IV (12.5g max dose) over 10min; may repeat at 1/2 original dose if needed
====Adverse Effects====
*May cause temporary reddish discoloration of skin, plasma, urine, mucous membranes
*'''Interferes with colorimetric tests''' -- Pulse ox, Hemoglobin, Carboyxhemoglobin, methemeglobin, oxyhemoglobin, Serum Cr, AST/ALT, bilirubin, magnesium for 2-3 days<ref>Lee J, Mukai D, Kreuter K, et al. Potential interference by hydroxocobalamin on co-oximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med. 2007;49(6):802-805.</ref>
;OBTAIN Co-ox and labs prior to Hydroxocobalamin administration

===Cyanide Antidote Package (Lilly kit)===
Composed of two drugs( two nitrites and a thiosulfate). The nitrites convert the iron in hemoglobin from the ferrous to the ferric form, creating methemoglobinemia. The thiosulfate is a sulfate donor, which allows the enzyme rhodanese to convert the cyanide to a form that can be renally excreted.
*2nd line therapy - use if Cyanokit unavailable<ref>Hall AH, Saiers J, Baud F. Which cyanide antidote?. Crit Rev Toxicol. 2009;39(7):541-52.</ref>
*Consider using only Na thiosulfate (no nitrites) in cases where concern for CO poisoning since nitrate administration will severely decrease oxygen carrying capacity

====Mechanism of action====
*Nitrites: form metHb which binds CN more avidly than cytochrome oxidase
**Thiosulfate: donates its sulfur group to CN to form thiocyanate (less toxic than CN)

====Warnings====
*Nitrites are relatively contraindicated in pts w/ concomitant CO toxicity
*Induction of metHb further exacerbates O2 delivery
*Avoid nitrites in presence of severe hypotension if diagnosis is unclear

====Administration====
;Amyl nitrite
*Inhaled by pt (only use if unavailable to obtain IV)
*Hold under pt's nose for 30s of each minute, for 3 minutes
;Sodium nitrite 
*10 mg/kg IV over 5min (use instead of amyl nitrite if IV is available)
*Lack of measurable MetHb levels after administration confirms CN presence
*Monitor MetHb and keep level <30%
;Pediatric dosing is based on Hemoblogin (see Peds dosing below)
;25% Sodium thiosulfate 
*1.65ml/kg IV (12.5g max dose) over 10min
*may repeat at 1/2 original dose if needed

===Sodium Nitrite (Peds Dosing)===
*Max dose should not exceed 10mL
*Do not give faster than 5mL/min (to avoid hypotension)
*Hb 7 g/dL, dose is 0.19 mL/kg of 3% sodium nitrite
*Hb 8 g/dL, dose is 0.22 mL/kg of 3% sodium nitrite
*Hb 9 g/dL, dose is 0.25 mL/kg of 3% sodium nitrite
*Hb 10 g/dL, dose is 0.27 mL/kg of 3% sodium nitrite
*Hb 11 g/dL, dose is 0.30 mL/kg of 3% sodium nitrite
*Hb 12 g/dL, dose is 0.33 mL/kg of 3% sodium nitrite
*Hb 13 g/dL, dose is 0.36 mL/kg of 3% sodium nitrite
*Hb 14 g/dL, dose is 0.39 mL/kg of 3% sodium nitrite

==Disposition==
*Admit all patients for observation

==See Also==
*[[Carbon Monoxide (CO)]]
*[[Hydrogen Sulfide]]
*[[Burns]]
*[[Acrylonitrile]]

==References==
<references/>

==Video==
{{#widget:YouTube|id=vsA6_c-cbe4}}

[[Category:Toxicology]]