Cyanide toxicity
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]
- Altered mental status
- Soot in the nares or mouth
- 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
- 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
- Inhaled toxins more rapid than ingested
- 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
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
- Blister chemical agents (Vesicants)
- Lewisite (L)
- Sulfur mustard (H)
- Phosgene oxime (CX)
- Pulmonary chemical agents (Choking agents)
- Incendiary agents
- Cyanide chemical weapon agents (Blood agents)
- Prussic acid (AKA hydrogen cyanide, hydrocyanic acid, or formonitrile)
- Nerve Agents (organophosphates)
- Acetylcholinesterase inhibitors
- Household and commercial pesticides (diazinon and parathion)
- G-series (sarin, tabun, soman)
- V-series (VX)
- Lacrimating or riot-control agents
- Pepper spray
- Chloroacetophenone
- CS
Toxic gas exposure
- Carbon monoxide toxicity
- Chemical weapons
- Cyanide toxicity
- Hydrocarbon toxicity
- Hydrogen sulfide toxicity
- Inhalant abuse
- Methane toxicity
- Smoke inhalation injury
- Ethylene dibromide toxicity
Burns
- Smoke inhalation injury (airway compromise)
- Chemical injury
- Acrolein
- Hydrochloric acid
- Tuolene diisocyanate
- Nitrogen dioxide
- Systemic chemical injury
- Specific types of burns
- Associated toxicities
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
- 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
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Hall AH, Saiers J, Baud F. Which cyanide antidote?. Crit Rev Toxicol. 2009;39(7):541-52.