Cyanide toxicity: Difference between revisions

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==Background==
==Background==
Older cyanide kit with potential to cause metHgb which potentially problem as patient may have CO as well
*Burning of nitrogen-containing polymers (plastics, wool, silk)
*Gaseous [[chemical weapon]] known as prussic acid, hydrogen cyanide, or hydrocyanic acid
*Prolonged use of [[nitroprusside]]
*Pits of peaches, pears, apricots, crab apples
*Intentional poisoning


Newer CyanoKit safer (but very expensive) without significant adverse rxn
===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 [[hypotension]]
**Tachypnea
**Cherry-red color (rarely seen)
*'''Late signs'''
**[[Nausea]], vomiting
**[[Bradycardia]], hypotension, [[arrhythmias]], asystole
**[[Coma]], [[seizures]] (rare), Mydriasis
**Bradypnea and [[pulmonary edema]] (non-cardiogenic), apnea
**[[Renal failure]]
**Hepatic Necrosis
**Cyanosis
**[[Rhabdo]], bright red venules seen on fundoscopy


===Pathophysiology===
===Chronic===
-glucose metabolized to pyruvate yields 2 ATP by anaerobic glycolysis.  No O2 needed.
*Retrobulbar Optic Atropy (proposed)
**Heavy smokers
*Ataxic peripheral neuropathy
*Konzo
**Spastic upper motor neuron paraparesis seen in chronic ingestion of inadequately cooked casava


- pyruvate then enters  Kreb cycle and with O2, yields 36 more ATP.  Requires function of mitochondrial electron xport system, the last step of which transfers electrons to oxygen to form water.
==Differential Diagnosis==
{{Chemical weapon DDX}}
{{Toxic gas exposure DDX}}
{{Burn DDX}}


- cyanide, hydrogen sulfide and carbon monoxide  bind to and inhibit cytochrome part of electron xport chain.
==Evaluation==
===Work-Up===
*[[Lactate]] (normal lactate highly suggests another diagnosis)
**Serum lactate >8 mmol/L has 94% sensitivity
*[[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)


- if pyruvate blocked from entering Krebs cycle, pyruvate metabolized to lactic acid- leads to lactic acidosis.
===Diagnosis===
*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 (same as CO poisoning)
*Cherry-red skin color is uncommon


==Diagnosis==
==Management==
-cn and h2s pts can’t extract o2 from blood.  Po2 of venous blood similar to arterial blood.  May diagnose cn poisoning by similar mixed venous o2 and arterial o2- get arterial and venous blood gases ana compare O2
*Supportive care
**[[O2]] 100% NRB
**[[IVF]] and vasopressors for hypotension
**Bicarb for acidemia (enchances of effect of nitrite and thiosulfate)
*Antidote


- Venous PO2 = Arterial PO2
===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
*Give empirically if cyanide poisoning is suspected
====Mechanism of action====
Directly binds cyanide forming cyanocobalamin which is readily excreted in the urine


-  lactic acidosis
====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


- nl SaO2
====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


==Treatment==
===Cyanide Antidote Package (Lilly kit)===
# goal is to remove cn from cytochrome enzyme and bind cn to something else
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 thiocyanate that can be renally excreted.
# give amyl nitrite inhaler followed by iv sodium nitrite to make MetHb- methb bind to  cn and pulls cn out of tissue into blood to make cyanomethemoglobin.
*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>
# dose of  sodium nitrite is  10cc of 3% soln over  2- 4 min. Ped dose is 0.2cc.kg.  May cause hypotension if given too fast.  Will generate methb level of 8%.
*Consider using only Na thiosulfate (no nitrites) in cases where concern for CO poisoning since nitrate administration will severely decrease oxygen carrying capacity
# if cn present, will rapidlly be converted to cnmethb.  Lack of measurable methb levels p iv Na nitrite confirms cn presence.
# once cnmethb in blood, give sodium thiosulfate 12.5 gm (50 cc of 25% soln of 5X vol of na nitrite).  Sulfur will bind with cn to make thiocyanate which is nontoxic and renally excreted.
#consider retreatment of incomplete response or oral cn poisoning with ongoing absorption.
# can also use vit b12 hydroxycobalamin to make cyanocobalamine


===TREATMENT===
====Mechanism of action====
# amyl nitrite inhaler
*Nitrites: form metHb which binds cyanide more avidly than cytochrome oxidase
# then iv sodium nitrite
**Thiosulfate: donates its sulfur group to cyanide to form thiocyanate (less toxic than CN)
##  10cc of 3% over  2- 4 min.(0.2cc/kg in peds)
# then sodium thiosulfate 12.5 gm (50 cc of 25% soln of 5X vol of na nitrite)
#follow methemoglobn levels
# also consider hydroxycobalamin


==CO/CN Combined Poisoning==
====Warnings====
#if pt has co poisoning already and is given cn antidote and methb make, two dyshemoglobins cohb and methb will further inhibit o2 carriage.
*Nitrites are relatively contraindicated in patients with concomitant CO toxicity
# cn poisoning correlated with lactate level > 10mmol/L
*Induction of metHb further decreases O2 delivery
# sodium thiosulfate given alone is safe without alteration of o2 carrying capacity of nitrites.  Consider emperic  tx c 12.5 mg to all smoke inhalation victims with hypotension, acidosis, or CV collapse.
*Avoid nitrites in presence of severe hypotension if diagnosis is unclear


===CO/CN COMBINED POISONING===
====Administration====
# sodium thiosulfate given alone (no alteration O2 carrying capacity)
*[[Amyl nitrite]]
## consider emperic  tx (12.5 mg) for smoke inhalation victims with
**Inhaled by patient (only use if unavailable to obtain IV)
#hypotension, acidosis, or CV collapse
**Hold under patient's nose for 30s of each minute, for 3 minutes
## See also [[Burns (Severe)]]
*[[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


==See Also==
{{Sodium Nitrite Peds Dosing}}
[[Hydrogen Sulfide]]


[[Burns (Severe)]]
==Disposition==
*Admit all patients for observation


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


8/07  DONLDSON (adapted from Sandness, Mistry)
==References==
<references/>


[[Category:Tox]]
[[Category:Toxicology]]

Latest revision as of 20:10, 17 April 2024

Background

  • Burning of nitrogen-containing polymers (plastics, wool, silk)
  • Gaseous chemical weapon known as prussic acid, hydrogen cyanide, or hydrocyanic acid
  • 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

Chronic

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

Differential Diagnosis

Chemical weapons

Toxic gas exposure

Burns

Evaluation

Work-Up

  • Lactate (normal lactate highly suggests another diagnosis)
    • Serum lactate >8 mmol/L has 94% sensitivity
  • 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)

Diagnosis

  • 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 (same as CO poisoning)
  • 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 thiocyanate 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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