Cyanide Poisoning, Emergency Medicine

Basics

Description

Toxicity through inhalation, or GI tract absorption
Intracellular toxin that inhibits aerobic metabolism through interruption of oxidative phosphorylation:
- Leads to decreased O2 utilization and ATP production
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)
  - Forms less toxic reversible cyanhemoglobin when combined with hemoglobin (Fe 3+)
  - Forms nontoxic cyanocobalamin (B12) when combined with hydroxocobalamin (B12a)
  - Rate of CN removal requires adequate bioavailability of sulfur compounds (thiosulfate [TS]).

Etiology

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

Diagnosis

Signs and Symptoms

Heart and brain-most sensitive organs-1st to show manifestation of toxicity
CNS:
- Headache
- Confusion
- Syncope
- Seizures
- Coma
Cardiovascular:
- Dyspnea
- 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
- Industrial exposure
- Intentional suicide
- Intentional homicide
Clinical clues (frequently absent):
- Peculiar odor of bitter almonds
- 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

Diagnosis Tests & Interpretation

Lab

CBC
Electrolytes, BUN, creatinine, glucose:
- Anion gap acidosis
Liver profile
Creatine phosphokinase (CPK)
Carboxyhemoglobin (CO) 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:
- Elevated mixed venous O2: MvO2 (normal about 35-40)
- Elevated mixed venous O2 saturation (co-oximeter): SmvO2 (normal about 75%)
- Decreased arteriovenous O2 difference: AVO2D (normal about 3-4.8 mL/dL)
Elevated lactate level >8 mmol/L:
- An elevated lactate 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
Inert gases "asphyxiants"�
Other causes of high anion gap metabolic acidosis

Treatment

Pre-Hospital

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

Initial Stabilization/Therapy

ABCs:
- Administer 100% oxygen:
  - Even in presence of normal PaO2
  - Acts synergistically with antidotes
Gastric decontamination for oral ingestions if within 1 hr:
- Perform gastric lavage and administer activated charcoal (AC) if ingestion of solid CN or CN-containing products and no contraindications.
- Do not induce emesis.
Dermal exposure: Standard decontamination

Ed Treatment/Procedures

Hydroxocobalamin (B12a) 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
  - Does not cause hypotension
  - 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 AST, ALT, total bilirubin, creatinine, Mg, iron
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
- 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
Hyperbaric oxygen therapy:
- Can be used to treat CN exposures
- Maximizes tissue oxygenation despite toxic MH level

Medication

AC: 1 g/kg PO �
First Line
Hydroxocobalamin (B12a): �

70 mg/kg IV, max. 5 g
The kit contains either two 2.5 grams/bottle or one 5 gram/bottle. The starting dose is 5 grams.
Reconstitute the powder by gently rolling the bottle after filling with 100 mL of 0.9% NS.
Infuse each 2.5 gram bottle over 7.5 minutes, or one 5 gram bottle over 15 minutes. The 5 gram 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 ampules in gauze and hold close to nose, in lip of face mask, or within Ambu bag.
- Inhale for 30 sec-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.

Hydroxocobalamin is class C.
Amyl nitrite is class X.
Sodium nitrite is unknown.
Sodium thiosulfate is class C.

~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.

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

Sodium nitrite has weight-based dosing for children.
Sodium nitrite dosing can be based on serum hemoglobin when the clinical scenario does NOT life-saving
administration of the antidote before lab testing:
�
View LargeHgbNitrite (mg/kg)Nitrite (mL/kg)75.80.1986.60.2297.50.25108.30.27119.10.301210.00.331310.80.361411.60.39

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

Borron �SW, Baud �FJ, Barriot �P, et al. Prospective study of hydroxycobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007;49(6):794-801.
Fortin �JL, Giocanti �JP, Ruttimann �M, et al. Prehospital administration of hydroxycobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris fire brigade. Clin Toxicol. 2006;44:37-44.
Handbook. 4th ed. Boca Raton, FL: Lexi-Comp; 2008:781-782, 830, 991, 1011.
Leikin �J, Paloucek �F. Cyanide, nitrites, sodium thiosulfate, sodium nitrite, hydroxycobalamin. In: Leikin �JB, Paloucek �F, eds. Leikin and Palouceks Poisoning and Toxicology
Thompson �JP, Marrs �TC. Hydroxocobalamin in cyanide poisoning. J Toxicol Clin Toxicol. 2012;50:875-885.

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

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