Cyanide toxicity

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Background

  • 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 recommend hydroxocobalamin administration patients who have had known smoke inhalation in an enclosed space with any of the following:[1][2]

  1. Altered mental status
  2. Soot in the nares or mouth
  3. Full arrest without full body burns incompatible with life. They found 50% ROSC in fire victims in full arrest when hydroxycobalamin was administered.

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 weapons

Burns

Evaluation

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

Management

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

Cyanokit (Hydroxocobalamin)[3][4]

  • 1st line therapy
  • Give empirically if cyanide poisoning is suspected

Mechanism of action

Directly binds cyanide 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% sodium thiosulfate 1.65ml/kg IV (12.5g max dose) over 10min; may repeat at half 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[5]
OBTAIN Co-ox and labs prior to Hydroxocobalamin administration

Cyanide Antidote Package (Lilly kit)

Composed of two drugs(2 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[6]
  • 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 cyanide more avidly than cytochrome oxidase
    • Thiosulfate: donates its sulfur group to cyanide to form thiocyanate (less toxic than CN)

Warnings

  • Nitrites are relatively contraindicated in patients with concomitant CO toxicity
  • Induction of metHb further decreases O2 delivery
  • Avoid nitrites in presence of severe hypotension if diagnosis is unclear

Administration

  • Amyl nitrite
    • Inhaled by patient (only use if unavailable to obtain IV)
    • Hold under patient's nose for 30s of each minute, for 3 minutes
  • Sodium nitrite
    • 10mg/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 (Pediatric Dosing)

Hb Level (g/dL) Dose of 3% sodium nitrite (mL/kg)
7 0.19
8 0.22
9 0.25
10 0.27
11 0.30
12 0.33
13 0.36
14 0.39
^Max dose should not exceed 10mL
^Do not give faster than 5mL/min (to avoid hypotension)

Disposition

  • Admit all patients for observation

See Also

References

  1. Fortin JL, et al. Prehospital administration of Hydroxoco- balamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade. Clin Toxicol. 2006;44 Suppl 1:37-44. PMID: 16990192.
  2. Borron SW, et al. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007 Jun;49(6):794-801, e1-2. PMID: 17481777.
  3. 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.
  4. 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.
  5. 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.
  6. Hall AH, Saiers J, Baud F. Which cyanide antidote?. Crit Rev Toxicol. 2009;39(7):541-52.

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