Sodium nitrite and sodium thiosulphate

Why this drug is interesting

This is the antidote that treats one poisoning by causing another. Sodium nitrite oxidises haemoglobin to methaemoglobin, which cannot carry oxygen but binds cyanide with higher affinity than cytochrome oxidase does. Cyanide is pulled off the mitochondrial enzyme onto the methaemoglobin, forming cyanomethaemoglobin, and cellular respiration resumes. Sodium thiosulphate then donates sulphur to rhodanese, which converts cyanide to thiocyanate for renal excretion.

It is an elegant piece of nineteenth-century-style chemistry and it is genuinely effective. It is also, in the emergency department's commonest cyanide scenario — the patient pulled from a house fire — close to the worst thing you could give.

Pharmacology

Sodium nitrite

In the presence of nitrites, haemoglobin is converted to methaemoglobin, which has a higher binding affinity for cyanide than cytochrome oxidase. Cyanide preferentially binds methaemoglobin, forming non-toxic cyanomethaemoglobin, and is displaced from cytochrome oxidase so that aerobic metabolism resumes.¹²

Sodium nitrite is also a vasodilator, which is the source of its hypotension. Haemodynamics must be monitored during and after administration and the infusion rate slowed if the blood pressure falls. Use with caution alongside other drugs that lower blood pressure.¹

Sodium thiosulphate

Thiosulphate is a sulphur donor for the enzyme rhodanese, which transfers sulphur to cyanide to form thiocyanate, a far less toxic anion cleared by the kidney. It is given second, after a "fast-acting cyanide antidote such as sodium nitrite or hydroxocobalamin" — the label's phrase, which classes hydroxocobalamin as fast-acting too and never actually describes thiosulphate as slower.² That thiosulphate is the slower of the pair is the conventional reading, not a label statement.

Thiosulphate is well tolerated. Each 12.5 g dose contains roughly 3.6 g of sodium and 115 mg of potassium, and may contain trace sulphite impurities — the label states plainly that sulphite sensitivity should not deter administration in an emergency.¹

Dosing

Adults

10 mL (300 mg) of sodium nitrite intravenously at 2.5–5 mL/minute, immediately followed by 50 mL (12.5 g) of sodium thiosulphate at 5 mL/minute.¹²

Children (0–18 years)

0.2 mL/kg (6 mg/kg, or 6–8 mL/m² BSA) of sodium nitrite at 2.5–5 mL/min, not exceeding 10 mL, immediately followed by 1 mL/kg (250 mg/kg, or approximately 30–40 mL/m² BSA) of sodium thiosulphate, not exceeding 50 mL total.¹² The two labels give different paediatric thiosulphate rates — Nithiodote says 5 mL/min, the sodium thiosulphate label says 2.5–5 mL/min. Take the slower figure.

Repeat dosing

If no treatment response is observed within 30 to 60 minutes, or if signs of poisoning reappear, repeat treatment no sooner than 30 minutes after the initial administration, using one-half the original dose of both agents.² (The Nithiodote label carries the shorter form, with no timing at all — the 30-minute constraint is from the sodium thiosulphate label.)

The haemoglobin-adjusted nitrite dose

Anaemic patients form more methaemoglobin as a percentage of total haemoglobin, so the label reduces the nitrite dose in proportion to oxygen-carrying capacity. This table is the single most important dosing content in the label and is rarely reproduced:¹

Who should not receive sodium nitrite

The label does not use the word contraindication — the only formal contraindication is hypersensitivity — but section 4.4 identifies groups in whom "special consideration" should be given when the diagnosis is uncertain or the patient is not in extremis:¹

• Smoke inhalation victims
• Pre-existing anaemia
• Substantial blood loss
• Cardiac or respiratory compromise
• Congenital methaemoglobin reductase deficiency

G6PD deficiency

Use with caution alongside other drugs that cause methaemoglobinaemia, such as procaine and nitroprusside — noting that prolonged nitroprusside infusion is itself a cause of cyanide toxicity.¹

Combining with hydroxocobalamin

Thiosulphate is more flexible than nitrite. Its own SmPC licenses it "for sequential use with hydroxocobalamin or sodium nitrite", and gives the alternative adult regimen explicitly: 5 g hydroxocobalamin as an IV infusion over 15 minutes, followed by 50 mL (12.5 g) sodium thiosulphate at 5 mL/min. The paediatric equivalent is hydroxocobalamin 70 mg/kg, max 5 g, followed by thiosulphate 1 mL/kg, max 50 mL.²

Practical use in the ED

Everything on the hydroxocobalamin page about diagnosing cyanide poisoning applies here unchanged — the same signs, the same lactate thresholds, the same enclosed-space-fire triad, the same absence of a usable confirmatory test. This label repeats it verbatim. The difference is entirely in what you then give.

1. Support vital functions first. The label is emphatic that supportive care alone may be sufficient in many cases, particularly in conscious patients without severe toxicity, and that oxygen must not be delayed to give antidotes.¹
2. Establish whether there was fire smoke. If yes, this is not the drug.
3. Check the haemoglobin if you have any result at all, and use the dose table.
4. Give the nitrite slowly — 2.5–5 mL/min — with continuous blood pressure monitoring, and slow it further if hypotension develops.
5. Follow immediately with thiosulphate at 5 mL/min. Same line is acceptable, sequentially.
6. Monitor methaemoglobin and keep the oxygen running.
7. Reassess at 30–60 minutes; half doses if features recur.
8. Call NPIS on 0344 892 0111. Cyanide is a diagnosis where an expert on the phone changes management.

If methaemoglobin climbs

Pregnancy

"Based on human experience sodium nitrite is suspected to cause congenital malformations when administered during pregnancy. Nithiodote should not be used during pregnancy unless the clinical condition of the woman requires treatment."¹ One more reason the hydroxocobalamin-first approach has displaced this regimen.

Critical appraisal

As with every cyanide antidote, there is no randomised human evidence. The nitrite–thiosulphate combination has the longest clinical history of any of them, and its mechanism is well characterised in both directions — including the dose at which it stops working and starts harming.

Its displacement by hydroxocobalamin is not a case of a better molecule so much as a better risk profile against an unconfirmable diagnosis. When you cannot know whether the patient in front of you has the poisoning, the antidote with no contraindications wins on decision theory alone. Nitrite's role has narrowed to confirmed or near-confirmed cyanide exposure in a patient with adequate oxygen-carrying reserve, and to places where hydroxocobalamin is not stocked.

One thing this page cannot tell you is what your own department holds. Nithiodote is a combination pack; sodium thiosulphate is also available alone. Find out which, and where, before there is a fire.

References

1. 1
   Nithiodote (sodium nitrite 300 mg/10 mL and sodium thiosulfate 12.5 g/50 mL) — Summary of Product Characteristics, Hope Pharmaceuticals Ltd. electronic Medicines Compendium, product 7355. Sections 4.1–4.4, 6.2. Source of the adult and paediatric doses and rates, the death-at-under-twice-therapeutic statement, the 40% methaemoglobin ceiling and 58% report, the haemoglobin-adjusted dose tables, the smoke inhalation and G6PD warnings, the sodium and potassium content, and the hydroxocobalamin incompatibility. Verified 31 Aug 2026.
2. 2
   Sodium Thiosulfate Solution for Injection — Summary of Product Characteristics, Hope Pharmaceuticals Ltd. electronic Medicines Compendium, product 7354. Sections 4.1, 4.2, 5.1, 6.2. Source of the licensed sequential use with hydroxocobalamin or sodium nitrite, the alternative hydroxocobalamin-first regimen, the 30–60 minute reassessment and half-dose repeat, and the rhodanese mechanism. Verified 31 Aug 2026.
3. 3
   National Poisons Information Service. TOXBASE · NPIS telephone 0344 892 0111. The operational UK source for cyanide management and for what antidote is held where.