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Cyanide Poisoning, Emergency Medicine

Basics

Description

- Industry: - Metal plating, microchip manufacturing - Chemical synthesis - Plastic manufacturing - Pesticides

- Cardiovascular: - Dyspnea - Chest pain - Cardiorespiratory collapse and death

- 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

- ABCs: - Administer 100% oxygen: - Even in presence of normal PaO2 - Acts synergistically with antidotes

- Advantages: - No MH induction - Does not cause hypotension - Intracellular distribution

- Side effects of hydroxocobalamin: - HTN - Red skin and all secretions - Interference of colorimetric assays of AST, ALT, total bilirubin, creatinine, Mg, iron

  • 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 manufacturingChemical synthesisPlastic manufacturingPesticides
  • Solvents:Artificial nail removerMetal 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:HeadacheConfusionSyncopeSeizuresComa
  • Cardiovascular:DyspneaChest painCardiorespiratory collapse and death
  • Other:
  • 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 inhalationIndustrial exposureIntentional suicideIntentional homicide
  • Clinical clues (frequently absent):Peculiar odor of bitter almondsBright red (arterialization) retinal vesselsAbrupt onset and/or deteriorating toxic effectsLactic acidosisHigh venous O2 saturation (secondary to blocked cellular O2 consumption); arterialization of venous blood gases

Diagnosis Tests & Interpretation

Lab

  • CBC
  • Electrolytes, BUN, creatinine, glucose:
  • 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: ToxicLevels 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 пїЅ

Differential Diagnosis

  • Carbon monoxide
  • Hydrogen sulfide
  • Methemoglobinemia
  • Sulfhemoglobinemia
  • Inert gases "asphyxiants"пїЅ
  • 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 PaO2Acts 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 пїЅ: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 availableBinds to CN:Forms nontoxic cyanocobalamin (B12); renally excretedAdvantages:No MH inductionDoes not cause hypotensionIntracellular distributionLimitations:Incompatible in the same IV line with:DiazepamDobutamineDopamineFentanylNitroglycerinPentobarbitalPropofolSodium thiosulfateSodium nitriteAscorbic acidBlood productsSide effects of hydroxocobalamin:HTNRed skin and all secretionsInterference 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 availableContents: Amyl nitrite pearls, sodium nitrite, and sodium thiosulfateNitrite 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 rhodaneseCombines with CN to form a less toxic T-CN
  • Hyperbaric oxygen therapy:Can be used to treat CN exposuresMaximizes tissue oxygenation despite toxic MH level

Medication

AC: 1 g/kg PO пїЅ

First Line

Hydroxocobalamin (B12a): пїЅ

  • 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 пїЅ

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 minKeep 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. пїЅ

  • 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: пїЅ 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 пїЅ

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 пїЅ

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 toxicityMHCO toxicityIf the COHgb concentration is extremely elevated, considered a concomitant CN exposure as wellTo avoid further reduction in oxygen transport; initially treat with hydroxocobalamin or sodium thiosulfate, without sodium nitrite to avoid methemoglobinemia.

Additional Reading

  • Borron пїЅSW, Baud пїЅFJ, Barriot пїЅP, et al. Prospective study of hydroxycobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007;49(6):794-801.
  • Fortin пїЅJL, Giocanti пїЅJP, Ruttimann пїЅM, 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 пїЅJ, Paloucek пїЅF. Cyanide, nitrites, sodium thiosulfate, sodium nitrite, hydroxycobalamin. In: Leikin пїЅJB, Paloucek пїЅF, eds. Leikin and Palouceks Poisoning and Toxicology
  • Thompson пїЅJP, Marrs пїЅTC. 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