Antidotes
There are no clear diagnostic markers of cyanide poisoning, so early discussion with a clinical toxicologist is essential to determine whether to use antidotal therapy. If antidotal therapy is indicated, administer it early.
A number of antidotes are available for cyanide poisoning, but they all have disadvantages, including risk of significant adverse effects, high cost or limited availability. See Practical information on the use of antidotes for cyanide poisoning for practical information on the use of antidotes for cyanide poisoning.
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Hydroxocobalamin | |
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mechanism of action |
rapidly reacts with cyanide to create nontoxic cyanocobalamin ions that are renally excreted |
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practical points on use |
use empirically easily administered by intravenous injection may be given in both the prehospital and hospital settings the safest antidote for cyanide poisoning |
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disadvantages |
not universally available [NB1] |
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Sodium thiosulfate | |
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mechanism of action |
used by the intracellular enzyme, rhodanese, to metabolise cyanide to thiocyanate ions and liberate sulfate ions. Thiocyanate ions are renally excreted |
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practical points on use |
use empirically |
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disadvantages |
metabolism of cyanide is not as rapid as that seen with hydroxocobalamin |
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Sodium nitrite | |
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mechanism of action |
induces methaemoglobinaemia as a temporising measure while waiting for sodium thiosulfate to take effect. Cyanide avidly binds to methaemoglobin to form cyanomethaemoglobin, which may prevent cyanide from binding to cellular cytochromes |
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practical points on use |
use as a cotherapy before administration of sodium thiosulfate in suspected cyanide poisoning target methaemoglobin fraction is 30 to 40% |
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disadvantages |
avoid after smoke inhalation; methaemoglobinaemia reduces the oxygen-carrying capacity of haemoglobin, which may compound hypoxia, especially in concurrent carbon monoxide poisoning causes vasodilation (hypotension) |
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Dicobalt edetate | |
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mechanism of action |
cyanide combines with cobalt ions to form cobalt cyanide conjugates that are renally excreted |
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practical points on use |
only indicated if there is evidence of cyanide poisoning in a critically ill patient and hydroxocobalamin is not available |
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disadvantages |
only use when there is a high suspicion of cyanide poisoning cobalt is toxic and in the absence of cyanide, may cause systemic toxicity including: vomiting, urticaria, life-threatening hypotension, anaphylaxis and ventricular arrhythmias |
Note:
NB1: Hydroxocobalamin 5 g vials are not registered for use in Australia but are available via the Special access scheme (SAS). Pharmacists or emergency staff should also check the emergency and life-saving drugs register for their state. This register lists hospitals that hold specific SAS drugs that may be borrowed in an emergency. | |
The approach to antidotal therapy depends on the severity of cyanide poisoning, which is based on the results of blood gas analysis (severity of acidaemia and hypoxaemia) and history of the exposure.
For mild cyanide poisoning, in adults, use:
1 hydroxocobalamin 5 g diluted in sodium chloride 0.9% 200 mL intravenously, over 15 minutes; repeat after 30 to 60 minutes if there is no clinical improvement1 cyanide poisoning hydroxocobalamin
OR
2 sodium thiosulfate 25% 50 mL (12.5 g) intravenously, over 10 minutes; repeat half of this dose after 30 to 60 minutes if there is no clinical improvement. cyanide poisoning
For mild cyanide poisoning, in children, use:
1 hydroxocobalamin 70 mg/kg up to 5 g2 diluted in sodium chloride 0.9% 2.8 mL/kg up to 200 mL intravenously, over 15 minutes; repeat after 30 to 60 minutes if there is no clinical improvement1 hydroxocobalamin
OR
2 sodium thiosulfate 25% 1.6 mL/kg up to 50 mL (400 mg/kg up to 12.5 g) intravenously, over 10 minutes; repeat half of this dose after 30 to 60 minutes if there is no clinical improvement.
For moderate to severe cyanide poisoning, in adults, use the combination of:
hydroxocobalamin 5 g diluted in sodium chloride 0.9% 200 mL intravenously, over 15 minutes; repeat after 30 to 60 minutes if there is no clinical improvement1 hydroxocobalamin
PLUS
sodium thiosulfate 25% 50 mL (12.5 g) intravenously, over 10 minutes; repeat half of this dose 30 to 60 minutes after the second dose of hydroxocobalamin if there is still no clinical improvement.
For moderate to severe cyanide poisoning, in children, use the combination of:
hydroxocobalamin 70 mg/kg up to 5 g2 diluted in sodium chloride 0.9% 2.8 mL/kg up to 200 mL intravenously, over 15 minutes; repeat after 30 to 60 minutes if there is no clinical improvement1 hydroxocobalamin
PLUS
sodium thiosulfate 25% 1.6 mL/kg up to 50 mL (400 mg/kg up to 12.5 g) intravenously, over 10 minutes; repeat half of this dose 30 to 60 minutes after the second dose of hydroxocobalamin if there is still no clinical improvement.
If hydroxocobalamin is not available, for moderate to severe cyanide poisoning, except in the setting of smoke inhalation3, in adults, use:
sodium nitrite 3% 10 mL (300 mg) intravenously, over 5 minutes; repeat half of this dose after 30 minutes if there is no clinical improvement cyanide poisoning
PLUS
sodium thiosulfate 25% 50 mL (12.5 g) intravenously, over 10 minutes; repeat half of this dose after 30 to 60 minutes if there is no clinical improvement.
If hydroxocobalamin is not available, for moderate to severe cyanide poisoning, except in the setting of smoke inhalation3, in children, use:
sodium nitrite 3% 0.13 to 0.33 mL/kg up to 10 mL (4 to 10 mg/kg up to 300 mg) intravenously, over 5 minutes; repeat half of this dose after 30 minutes if there is no clinical improvement
PLUS
sodium thiosulfate 25% 1.6 mL/kg up to 50 mL (400 mg/kg up to 12.5 g) intravenously, over 10 minutes; repeat half of this dose after 30 to 60 minutes if there is no clinical improvement.
If the antidotes above are not available, for severe cyanide poisoning, in adults, use:
dicobalt edetate 1.5% 20 mL (300 mg) intravenously, over 1 minute cyanide poisoning
FOLLOWED IMMEDIATELY BY
glucose 50% 50 mL intravenously, by slow injection, via a large peripheral vein. cyanide poisoning
If the antidotes above are not available, for severe cyanide poisoning, in children, use:
dicobalt edetate 1.5% 0.5 mL/kg up to 20 mL (7.5 mg/kg up to 300 mg) intravenously, over 1 minute
FOLLOWED IMMEDIATELY BY
glucose 10% 2.5 mL/kg intravenously, by slow injection, via a large peripheral vein. cyanide poisoning