Cyanide stability can be maximised at -20 o C.
4mL EDTA tube should be frozen as early as possible (preferred). Do not spin.
Emergency - transport to lab rapidly on ice. Pre-warn Biochemistry department of sample. Freeze on arrival if not already frozen.
Gastric aspirate testing is no longer available.
Method/ Principle: Microdiffusion/ Colorimetric
Units: umol/L
Uncertainty of Measurement: 20%
Conversion Factor: umol/L x 0.04 = mg/L
Blood Reference interval (also see section on diagnostic use):
|
< 8 umol/L in smokers. Lower in non-smokers. 10 - 20 umol/L - Confusion and dysphonia 20 - 30 umol/L - Dyspnoea and convulsions > 40 umol/L - significant toxicity with a considerable risk of fatality > 100 umol/L - generally fatal |
Ideally samples are analysed within 24 hours.
Please contact the on-call Chemical Pathologist for unusual requests (e.g. multiple patients, nitroprusside related toxicity), urgent cases or those that may benefit from additional monitoring such as thiocyanate testing.
Background:
Acute cyanide poisoning can occur in fire smoke inhalation. Other forms of cyanide exposure include: industrial processes such as electroplating jewellery, metal cleaning, precious metal extraction, laboratory assays, photographic processes or chemical warfare (hydrogen cyanide or cyanogen chloride). Some compounds such as nitroprusside may release cyanide during metabolism.
Cyanide causes tissue hypoxia by binding mitochondrial cytochrome C oxidase, thus disrupting the electron transport chain and utilisation of oxygen in aerobic metabolism. The binding of cyanide to cytochrome oxidase can be reversed by the enzyme rhodanese present in muscle and liver. This enzyme converts cyanide to less toxic thiocyanate, a potential marker of chronic exposure (see below).
Acute Exposure:
The half-life of cyanide is estimated at 1 hour in patients presenting with smoke inhalation. Testing of specimens closest to time of exposure is preferable. Whole blood cyanide is a manual method that requires several hours or longer to perform. Therefore, the decision to administer specific antidotes such hydroxycobalamin should be made on clinical grounds. Once a diagnosis is confirmed, repeat cyanide testing is usually not necessary.
Clinical features may include slow ideation/confusion/amnesia/loss of consciousness, presence of soot in the mouth or nose, hypotension/cardiac arrest or a cherry red appearance to the skin or retinal arteries/veins. Approximately 40-60% of patients exposed to cyanide will have an odour of bitter almonds. In the setting of fire smoke inhalation, a high anion gap is typically observed and a plasma lactate concentration of >8 umol/L carries a sensitivity of 94% and a specificity of 70% in patients with significant toxicity (9>40 umol/L).
Other possible laboratory features include narrowing of the arterial/venous PO2 gradient due to mitochondrial dysfunction; or a high carbon monoxide (detected by raised carboxyhaemoglobin) which may support smoke inhalation.
Treatment with amyl or sodium nitrate leads to the formation of methaemoglobin which binds to excess toxic cyanide to form cyanomethaemoglobin. Repeat monitoring by measuring whole cyanide is not helpful in this instance, as this method measures both toxic (free) cyanide and cyanide bound to methaemoglobin. The proportion of methaemoglobin can be a useful marker to monitor treatment in these patients (see https://fda.report/DailyMed/41e11afb-5fa4-4212-889d-1092dbd0702a for further information).
Treatment with hydroxocobalamin leads to the binding of toxic cyanide to form cyanocobalamin. In this scenario, measurements of methaemoglobin would not be beneficial.
Treatment with thiosulphate leads to the conversion of toxic cyanide to thiocyanate (which is a less toxic compound than cyanide, but may cause secondary thiocyanate toxicity). Request for urine or plasma thiocyanate may be helpful in these instances if secondary toxicity is a concern.
Chronic Exposure:
Chronic exposure to cyanide such as cigarette smoking may lead to increases in whole blood cyanide (<8 umol/L). However due to the short half-life and stability of whole blood cyanide, concentrations can be variable. Safe Work Australia suggests the testing of the metabolite thiocyanate for chronic exposure to cyanide. The apparent half-life in urine is approximately 4-6 days. Testing for thiocyanate is not available at LabPlus but can be requested by special arrangement by calling the on-call chemical pathologist.
References:
1. https://emergency.cdc.gov/agent/cyanide/basics/casedef.asp as retrieved on 07/10/2021
2. Hall AH. Cyanide and related compounds (chapter 88) in Haddad and Winchesters Clinical Management of Poisoning and Drug overdose (2007, 4th edition) Shannon MW, Borron SW, Burns MJ (eds) Saunders Elsevier, Philadelphia
3. Agency for toxic substances and disease registry. Cyanide toxicity. American Family Physician 1993; 48(1): 107-114
4. Baud FJ, Borron SW, Megarbane B, Trout H, Lapostolle F, Vicaut E, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Critical care medicine. 2002;30(9):2044-50.
5. Baud FJ, Barriot P, Toffis V, Riou B, Vicaut E, Lecarpentier Y, et al. Elevated Blood Cyanide Concentrations in Victims of Smoke Inhalation. New England Journal of Medicine. 1991;325(25):1761-6.
6. Safe Work Australia. Guide for preventing and responding to cyanide poisoning in the workplace. April 2013.
7. Geldner G, Koch EM, Gottwald-Hostalek U, Baud F, Burillo G, Fauville JP, et al. Report on a study of fires with smoke gas development: determination of blood cyanide levels, clinical signs and laboratory values in victims. Anaesthetist. 2013;62(8):609-16.
8. https://emedicine.medscape.com/article/814287-overview as retrieved on 07/10/2021
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427
| 5ml EDTA Blood. Do not Spin |
The sample should be analysed within 24 hours
Within Auckland send refrigerated (2-8 degrees)
From outside of Auckland send frozen - changes in Cyanide can be minimised by storage at -20 o C