Cyanide Poisoning

[Section Outline]

Description
Etiology

Author:

Kirk L.Cumpston

Description

Toxicity through inhalation, GI tract absorption, or injection
Intracellular toxin that inhibits aerobic metabolism through inhibition of oxidative phosphorylation:
- Leads to decreased O₂ utilization and ATP production
Intrinsic detoxification:
- Rhodanese: Hepatic mitochondrial enzyme responsible for the metabolism:
  - Combines cyanide (CN) with sulfur (rate-limiting step) covalently (irreversible) to form less toxic and water-soluble thiocyanate (T-CN)
  - Rate of CN removal requires adequate bioavailability of sulfur compounds (thiosulfate [TS])

Etiology

Fires:
- Combustion byproduct of natural and synthetic products
Industry:
- Metal plating, microchip manufacturing
- Chemical synthesis
- Plastic manufacturing
- Pesticides
Solvents:
- Artificial nail remover (Acetonitrile)
- Metal polishes
Byproduct of nitroprusside metabolism (nonenzymatic):
Amygdalin (converted by intestinal flora to CN), CN-containing plants (apricot and peach pits, apple and pear seeds, and cassava)
Jewelry making

Diagnosis ⬆ ⬇

[Section Outline]

Signs and Symptoms
Essential Workup
Diagnostic Tests & Interpretation
Differential Diagnosis

Signs and Symptoms

Heart and brain - most sensitive organs - first to show manifestation of toxicity
CNS:
- Headache
- Confusion
- Syncope
- Seizures
- Coma
Cardiovascular:
- Dysrhythmia
- Chest pain
- Cardiorespiratory collapse and death
Other:
- Nausea/vomiting
Oral exposure: Can be caustic, 50 mg has caused death
Inhalational exposure:
- 50 ppm causes anxiety, palpitations, dyspnea, headache
- 100-135 ppm <1 hr is lethal

Essential Workup

History of exposure:
- Smoke inhalation in a closed space
- Industrial exposure
- Intentional suicide
- Intentional homicide
Clinical clues:
- Peculiar odor of bitter almonds (variable perception)
- Bright red (arterialization) retinal vessels
- Abrupt onset and /or deteriorating toxic effects
- Lactic acidosis
- High venous O₂ saturation (secondary to blocked cellular O₂ consumption); arterialization of venous blood gases

Diagnostic Tests & Interpretation

Lab

CBC
Electrolytes, BUN, creatinine, glucose:
- Anion gap acidosis
Liver profile
Creatine phosphokinase (CPK)
Carboxyhemoglobin (COHgb) level
Methemoglobin (MH) level
CN level:
- Send out lab that is not usually available in a clinically relevant time period
- Levels >0.5-1 mg/L: Toxic
- Levels 2.5-3 mg/L: Fatal
Blood gas determinations:
- Decreased arteriovenous O₂ difference: AVO₂D (normal about 3-4.8 mL/dL)
Lactate level:
- An elevated lactate (>8 mmol/L) is a surrogate marker for the presence of CN with the appropriate history and physical exam

Imaging

CXR

Differential Diagnosis

Carbon monoxide
Hydrogen sulfide
Methemoglobinemia
Sulfhemoglobinemia
Simple asphyxiants
Other causes of high anion gap metabolic acidosis

Treatment ⬆ ⬇

[Section Outline]

Prehospital
Initial Stabilization/Therapy
ED Treatment/Procedures
Medication

Prehospital

Remove source of CN
Prevent others from becoming contaminated
If a liquid contamination, remove and bag all contaminated clothing and wash affected areas copiously with soap and water
If vapor contamination, removal of the patient from the CN environment may be all that is necessary

Initial Stabilization/Therapy

ABCs:
- Administer 100% oxygen
Gastric decontamination for oral ingestions if within 1 hr:
- Administer activated charcoal (AC) if ingestion of solid CN or CN-containing products and no contraindications
- Do not induce emesis
Dermal exposure: Stand ard decontamination

ED Treatment/Procedures

Hydroxocobalamin (B_12a) Cyanokit®:
- Administer if manifesting significant CN toxicity with persistent high anion gap metabolic acidosis and hyperlactatemia, with any syncope, seizures dysrhythmias, and hypotension
- Administration often instituted empirically; CN levels not immediately available
- Binds to CN:
  - Forms nontoxic cyanocobalamin (B₁₂); renally excreted
- Advantages:
  - No MH induction
  - Causes hypertension
  - Intracellular distribution
- Limitations:
  - Cost
- Incompatible in the same IV line with:
  - Diazepam
  - Dobutamine
  - Dopamine
  - Fentanyl
  - Nitroglycerin
  - Pentobarbital
  - Propofol
  - Sodium thiosulfate
  - Sodium nitrite
  - Ascorbic acid
  - Blood products
- Side effects of hydroxocobalamin:
  - HTN
  - Red skin and all secretions
  - Interference of colorimetric assays of COHgb, AST, ALT, total bilirubin, creatinine, Mg, iron
  - Hemodialysis failure due to detection of red color in machine
CN antidote kit:
- Administer if manifesting significant CN toxicity with persistent high anion gap metabolic acidosis, hyperlactatemia with any syncope, seizures dysrhythmias, and hypotension
- Administration often instituted empirically; CN levels not immediately available
- Contents: Amyl nitrite pearls, sodium nitrite, and sodium thiosulfate
- Amyl and sodium nitrite action:
  - Induce a CN-scavenging MH by oxidizing hemoglobin (Fe²⁺ to Fe³⁺), which attracts extracellular CN away from the mitochondria-forming CN-MH, which is less toxic
  - Do not administer empirically or prophylactically
- Sodium thiosulfate action:
  - Substrate for the enzyme rhodanese
  - Combines with CN to form a less toxic T-CN

Medication

AC: 1 g/kg PO

First Line

Hydroxocobalamin (B_12a):

70 mg/kg IV, or IO, max 5 g
The kit contains one 5 g/bottle. Administer the bottle
Reconstitute the powder by gently rolling the bottle after filling with 100 mL of 0.9% NS
One 5-g bottle over 15 min. The 5-g dose can be repeated

Consider adjunctive use of sodium thiosulfate

Second Line

CN antidote kit: Amyl nitrite, sodium nitrite, and sodium thiosulfate
Amyl nitrite pearls:
- Crush 1 or 2 amp in gauze and hold close to nose, in lip of face mask, or within Ambu bag
- Inhale for 30 s-1 min until IV access obtained
Sodium nitrite (NaNO₂): 10 mL (300 mg) (peds: 0.15-0.33 mL/kg) IV as 3% solution over 5-20 min
- May repeat once at half dose within 30-60 min
- Keep MH level <30%
- Dilute; infuse slowly if hypotensive
Sodium thiosulfate: 50 mL: 12.5 g (peds: 0.95-1.65 mL/kg) IV over 10-15 min of 25% solution:
- 1/2 initial dose may be given after 30-60 min

Pregnancy Prophylaxis
Hydroxocobalamin is class C Amyl nitrite is class X Sodium nitrite is unknown Sodium thiosulfate is class C

Geriatric Considerations

∼50 known or suspected CN victims aged 65 or older received hydroxocobalamin and it had similar safety and efficacy as younger patients
Hydroxocobalamin is renally excreted unchanged in the urine so renal impairment could prolong the elimination half-life
The safety and effectiveness of hydroxocobalamin is unknown in hepatic impairment
Sodium thiosulfate is metabolized in the liver and excreted by the kidney. Impairment in either organ may prolong elimination
The nitrites are short acting. Hepatic or renal impairment may prolong elimination

Pediatric Considerations
The safety and effectiveness of hydroxocobalamin has not been established in children, but the 70 mg/kg dose has been used

ALERT

Sodium nitrite has weight-based dosing for children
Sodium nitrite dosing can be based on serum hemoglobin when the clinical scenario does NOT require life-saving administration of the antidote before lab testing:
Hgb Nitrite (mg/kg) Nitrite (mL/kg)
7 5.8 0.19
8 6.6 0.22
9 7.5 0.25
10 8.3 0.27
11 9.1 0.30
12 10.0 0.33
13 10.8 0.36
14 11.6 0.39

Follow-Up ⬆ ⬇

Disposition

Admission Criteria

ICU admission of all symptomatic exposures

Discharge Criteria

Asymptomatic patients after at least 4 hr of observation
Survival after 4 hr of acute exposure usually associated with complete recovery

Issues for Referral

Psychiatry referral for intentional overdose and suicidal patients

Pearls and Pitfalls ⬆ ⬇

In a patient with hypotension, high-anion-gap metabolic acidosis, hyperlactatemia, seizures, syncope, altered mental status consider CN in the differential diagnosis and treat presumptively
Use serum lactate as a surrogate marker for CN exposure
Victims of smoke inhalation may have combination of:
- CN toxicity
- MH
- CO toxicity
- If the COHgb concentration is extremely elevated, considered a concomitant CN exposure as well
- To avoid further reduction in oxygen transport; initially treat with hydroxocobalamin or sodium thiosulfate, without sodium nitrite to avoid methemoglobinemia

Additional Reading ⬆ ⬇

DangT, NguyenC, TranPN. Physician beware: Severe cyanide toxicity from amygdalin tablets ingestion . Case Reports in Emergency Medicine. 2017:1-3.
ElliottA, DubePA, Cossette-CoteA, et al. Intraosseous administration of antidotes - A systematic review . Clin Toxicol (Phila). 2017;55(10): 1025-1054.
LimK, HeherE, SteeleD, et al. Hemodialysis failure secondary to hydroxocobalamin exposure . Baylor University Medical Center Proceedings. 2017;30(2):167-168.
PurvisMV, RooksH, YoungLJ, et al. Prehospital hydroxocobalamin for inhalation injury and cyanide toxicity in the United States - Analysis of a database and survey of EMS providers . Ann Burns Fire Disasters. 2017;30(2):126-128.

Codes ⬆

ICD9

987.7 Toxic effect of hydrocyanic acid gas
989.0 Toxic effect of hydrocyanic acid and cyanides

ICD10

T65.0X1A Toxic effect of cyanides, accidental (unintentional), initial encounter
T65.0X2A Toxic effect of cyanides, intentional self-harm, initial encounter
T65.0X4A Toxic effect of cyanides, undetermined, initial encounter
T57.3X1A Toxic effect of hydrogen cyanide, accidental (unintentional), initial encounter
T57.3X2A Toxic effect of hydrogen cyanide, intentional self-harm, initial encounter
T57.3X4A Toxic effect of hydrogen cyanide, undetermined, init encntr

SNOMED

66207005 Toxic effect of cyanide (disorder)
216740001 Accidental poisoning by cyanide (disorder)
16686005 Toxic effect of hydrocyanic acid

section name header

Basics ⬇

Diagnosis ⬆ ⬇

Lab

Imaging

Treatment ⬆ ⬇

First Line

Second Line

Pregnancy Prophylaxis

Geriatric Considerations

Pediatric Considerations

ALERT

Follow-Up ⬆ ⬇

Admission Criteria

Discharge Criteria

Issues for Referral

Pearls and Pitfalls ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆