Cyanide toxicity: Difference between revisions

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==Background==
==Background==
*Cyanide is formed when nitrogen-containing polymers are burned (plastics, wool, silk)
*Sources
*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)
*Newer CyanoKit safer (but very expensive) without significant adverse rxn
**Prolonged use of nitroprusside
**
*Pathophysiology
**Binds to cytochrome oxidase in mitochondria; leads to cessation of electron transport
***Causes switch from aerobic to anaerobic metabolism despite adequate O2
 
==Clinical Features==
#CNS
##Headache, anxiety, confusion, vertigo, coma, seizure
#Cardiovascular
##Tachycardia and hypertension initially, then bradycardia and hypotension
#Respiratory
##Tachypnea initially, then then bradypnea and pulmonary edema
#GI
##Vomiting, abdominal pain
#Skin
##Cherry-red color (rarely seen), cyanosis (late finding)
#Renal
##Renal failure
#Hepatic
##Hepatic necrosis
#Miscellaneous
##Rhabdo, bright red venules seen on fundoscopy


===Pathophysiology===
*glucose metabolized to pyruvate yields 2 ATP by anaerobic glycolysis.  No O2 needed.
* 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.
*cyanide, hydrogen sulfide and carbon monoxide  bind to and inhibit cytochrome part of electron xport chain.
*if pyruvate blocked from entering Krebs cycle, pyruvate metabolized to lactic acid- leads to lactic acidosis.


==Diagnosis==
==Diagnosis==
*PO2 of venous blood similar to arterial blood
#Smell of bitter almonds (only 60-80% of population can detect this)
**Venous (VBG) PO2 = Arterial (ABG) PO2
#Severe unexplained metabolic acidosis (lactic)
*Cyanide (CN) poisoning correlated with lactate level > 10mmol/L
#PO2 of venous blood similar to arterial blood
*nl SaO2
#normal SpO2
#Cherry-red skin color is uncommon
 
==Work-Up==
#Lactate
#VBG and ABG (narrowing of the venous-arterial PO2 gradient)
#Co-oximetry
#Chemistry (anion gap acidosis)


==Treatment==
==Treatment==
# Amyl nitrite inhaler
#Supportive care
# then, iv sodium nitrite
##O2 100% NRB
## 10cc of 3% over 2- 4 min (0.2cc/kg in peds)
##IVF and vasopressors for hypotension
###may cause hypotension if given too fast
##Bicarb for acidemia (enchances of effect of nitrite and thiosulfate)
###will generate methb level of 8%
#Antidote
####lack of measurable methb levels after administration confirms Cyanide presence
 
# then sodium thiosulfate 12.5 gm (50 cc of 25% soln of 5X vol of na nitrite)
===Antidote Kits===
##Sulfur will bind with CN to make thiocyanate which is nontoxic and renally excreted
#Cyanokit (Hydroxocobalamin) - 1st Line Therapy
#follow methemoglobn levels
##Mechanism of action
#If incomplete response, consider
###Directly binds CN forming cyanocobalamin which is readily excreted in the urine
##retreatment
##How to use:
##ongoing absorption (e.g. oral Cyanide poisoning)
###Give 70mg/kg IV over 15min (5g is standard adult dose); may repeat 5g once as needed
#using vit b12 hydroxycobalamin (to make cyanocobalamine)
###Also give Na thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed
##Side effects
###May cause temporary reddish discoloration of skin, plasma, urine, mucous membranes
###Interferes w/ co-oximetry measurements
#Cyanide Antidote Package - Use if Cyanokit unavailable
##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
##How to use:
###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 (use instead of amyl nitrite if IV is available)
####Lack of measurable MetHb levels after administration confirms CN presence


==CO/CN Combined Poisoning==
####Peds requires dosing based on Hb (see Peds dosing below)
*Can occur with closed-space [[Burns]]
###Sodium thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed
*if pt has CO poisoning already and is given Cyanide antidote can increase dyshemoglobins (cohb and methb) to further inhibit O2 carriage
 
 
===Sodium Thiosulfate (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


===Treatment===
#Sodium thiosulfate given alone (no alteration O2 carrying capacity)
##Consider emperic  tx (12.5 mg) for smoke inhalation victims with:
###Hypotension
###Acidosis
###CV collapse


==See Also==
==See Also==
[[Hydrogen Sulfide]]
*[[Carbon Monoxide]]
 
*[[Hydrogen Sulfide]]
[[Burns]]
*[[Burns]]


==Source==
==Source==
Pani
*Tintinalli
 
*UpToDate
8/07  DONLDSON (adapted from Sandness, Mistry)


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

Revision as of 04:06, 22 September 2011

Background

  • Sources
    • Burning of nitrogen-containing polymers (plastics, wool, silk)
    • Prolonged use of nitroprusside
  • Pathophysiology
    • Binds to cytochrome oxidase in mitochondria; leads to cessation of electron transport
      • Causes switch from aerobic to anaerobic metabolism despite adequate O2

Clinical Features

  1. CNS
    1. Headache, anxiety, confusion, vertigo, coma, seizure
  2. Cardiovascular
    1. Tachycardia and hypertension initially, then bradycardia and hypotension
  3. Respiratory
    1. Tachypnea initially, then then bradypnea and pulmonary edema
  4. GI
    1. Vomiting, abdominal pain
  5. Skin
    1. Cherry-red color (rarely seen), cyanosis (late finding)
  6. Renal
    1. Renal failure
  7. Hepatic
    1. Hepatic necrosis
  8. Miscellaneous
    1. Rhabdo, bright red venules seen on fundoscopy


Diagnosis

  1. Smell of bitter almonds (only 60-80% of population can detect this)
  2. Severe unexplained metabolic acidosis (lactic)
  3. PO2 of venous blood similar to arterial blood
  4. normal SpO2
  5. Cherry-red skin color is uncommon

Work-Up

  1. Lactate
  2. VBG and ABG (narrowing of the venous-arterial PO2 gradient)
  3. Co-oximetry
  4. Chemistry (anion gap acidosis)

Treatment

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

Antidote Kits

  1. Cyanokit (Hydroxocobalamin) - 1st Line Therapy
    1. Mechanism of action
      1. Directly binds CN forming cyanocobalamin which is readily excreted in the urine
    2. How to use:
      1. Give 70mg/kg IV over 15min (5g is standard adult dose); may repeat 5g once as needed
      2. Also give Na thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed
    3. Side effects
      1. May cause temporary reddish discoloration of skin, plasma, urine, mucous membranes
      2. Interferes w/ co-oximetry measurements
  2. Cyanide Antidote Package - Use if Cyanokit unavailable
    1. Mechanism of action
      1. Nitrites: form metHb which binds CN more avidly than cytochrome oxidase
      2. Thiosulfate: donates its sulfur group to CN to form thiocyanate (less toxic than CN)
    2. Warnings
      1. Nitrites are relatively contraindicated in pts w/ concomitant CO toxicity
        1. Induction of metHb further exacerbates O2 delivery
      2. Avoid nitrites in presence of severe hypotension if diagnosis is unclear
    3. How to use:
      1. Amyl nitrite inhaled by pt (only use if unavailable to obtain IV)
        1. Hold under pt's nose for 30s of each minute, for 3 minutes
      2. Sodium nitrite 10 mg/kg IV (use instead of amyl nitrite if IV is available)
        1. Lack of measurable MetHb levels after administration confirms CN presence
        1. Peds requires dosing based on Hb (see Peds dosing below)
      1. Sodium thiosulfate 12.5g over 10min; may repeat at 1/2 original dose if needed


Sodium Thiosulfate (Peds Dosing)

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


See Also

Source

  • Tintinalli
  • UpToDate