What is silver nitrate?

Silver nitrate is an inorganic compound; its formula is AgNO₃. It is a caustic compound that can be produced by dissolving silver into nitric acid. Its appearance is a white crystalline solid. It is soluble in water and corrosive if ingested.⁴

Silver nitrate was discovered in the thirteenth century by Albertus Magnus in Germany, known as Doctor Universalis, one of the forward thinkers of the Middle Ages, who had interests in both science and theology.⁵ The product was named Lunar Caustic, because of silver's association with the moon at the time.⁶

Since as early as 4000 BC, the properties of silver have been understood. Yet, this was in a much less complex form than today. The King of Persia, Herodotus, said that ‘no King of Persia would carry water in anything but a silver jar’; it was thought that this would purify the water, perhaps because of its anti-bacterial and disinfectant properties.⁶

Although the creation of silver nitrate was not documented until the thirteenth century, it may have been used as early as 69 BC. An early pharmacopeia published from this time mentions its use.^{Reference Hill and Pillsbury7} The first official use of silver nitrate in medicine for wound healing was reported by Gabor in 702–705 AD.^{Reference Krishnaraj and Sani8}

In 1520, Paracelsus used silver nitrate as a caustic in wound treatment, an intervention that has continued to the modern day.^{Reference Alexander9} The next documented use of silver nitrate came in 1614, when the Italian physician Angelo Sala used it as a treatment for skin irritation, whilst also using it as a laxative and in the treatment of brain infection.^{Reference Alexander9} The Indian Army Officer James Abbott, in 1827, noted how he used silver nitrate in the wound of his arm after being bitten by a dog, in order to cauterise the wound and prevent rabies infection.¹⁰

The next involvement of silver nitrate in the development of medicine occurred in the 1880s. A German obstetrician named Credé used a 1 per cent silver nitrate solution as a prophylactic measure for gonorrhoeal ophthalmia in children.^{Reference Forbes and Forbes11} Following this, silver nitrate prophylaxis became mandatory across most of Europe and Northern America until the development of antibiotics.^{Reference Forbes and Forbes11}

Silver nitrate for epistaxis

Silver nitrate used for the cauterisation of bleeding was described as early as 1842, when Miller described various topical chemical pro-coagulants, but favoured silver nitrate for use in dental procedures.^{Reference Miller12}

The earliest evidence of silver nitrate being used in the nose was from Philadelphia in 1854.^{Reference Erichsen13} Management included ‘local application of injection of astringents, as a strong solution of the nitrate of silver applied by means of a camel's hairbrush’. The use of silver nitrate on this occasion, however, was to treat chronic inflammation of the mucous membranes of the nose. Treatment of epistaxis at this time included similar first aid advice to today, alongside ‘plugging’ of the nose.^{Reference Erichsen13} In 1894, Fullerton^{Reference Fullerton14} published perhaps the most comprehensive account of epistaxis management experience, which is remarkably similar to the modern management techniques suggested by Integrate (the National ENT Trainee Research Network).³ However, Fullerton found electrocautery to be superior to silver nitrate application.^{Reference Fullerton14} The electrocautery he described was in fact in the form of galvanocautery – the heating of a wire to a red heat over an electric coil which was then applied topically. If a coil was not available, he suggested using a spirit lamp instead.^{Reference Fullerton14}

In London in 1879, an epistaxis case was described in which haemorrhaging continued after the anterior nares plugging was removed. There was a small septal ulcer found upon inspection, to which a silver nitrate stick was applied to cease the haemorrhage.^{Reference Franks15} This demonstrates that silver nitrate sticks were in use as early as 1879. A similar case occurred in New York, in 1880,^{Reference Franks15} and in Pittsburgh, in 1884, wherein a silver nitrate stick was used alongside other astringents including salicylate of zinc, glycerol of tannic acid, chromic acid and tannate of iron.^{Reference Rankin16} This appears to be around the time that silver nitrate usage in epistaxis was becoming commonplace, as described in Prague, in 1887.^{Reference Bandler17}

A study by Stewart, which covered epistaxis management from 1912 to 1957, described the use of silver nitrate sticks in the cauterisation of active epistaxis at the Royal Infirmary Edinburgh; it was not utilised as a mainstay of treatment however.^{Reference Stewart18} The paper describes using a hot or cold saline douche, applied with a syringe, alongside ribbon gauze for packing, which was soaked in hydrogen peroxide for haemostasis, and the use of a ‘Rose-Cooper’ inflatable bag to exert pressure upon the bleeding point.^{Reference Stewart18} Stewart also makes reference to an epistaxis treatment, used in 1769, which involved immersing the genitalia into cold water, perhaps to promote vasoconstriction? Similar to this, there are reports of cold metal being placed over the cervical sympathetic ganglion.^{Reference Stewart18}

By 1974, silver nitrate cautery had established itself as a key part of epistaxis management. It was the fifth most used epistaxis treatment in a study of 1724 patients, behind anterior packing, posterior packing, blood transfusion and the Stevens balloon.^{Reference Juselius19} The Stevens Nasal Balloon seems to be similar to the Rapid Rhino^™ nasal tamponades that are used in practice today. Of interest, tamponading by means of a balloon was described as early as 1851.^{Reference Gabriel20} Posterior packing was repeatedly favoured in the late nineteenth century and was popularised with the use of a Belloq sound (an instrument used for plugging the nasal cavity) – debated to have been invented in the 1700s.^{Reference Feldmann21}

Silver nitrate concentration

In Philadelphia, 1895, epistaxis treatment with silver nitrate was described as a ‘5 to 10% solution of silver nitrate applied on a small swab to the bleeding surface and held in position’. This differs from the silver nitrate sticks used in practice today.^{Reference Vansant22}

Chemical cauterisation used today requires visualisation of the bleeding point.

Cocainisation was originally used as a vasoconstrictor, prior to the implementation of other methods such as silver nitrate.^{Reference Stephenson23} In the present day, adrenaline or xylometazoline are commonly used instead.

A step down to 4 per cent silver nitrate solution was noted in Atlanta, in 1933,^{Reference Roy24} a reduction from the 5–10 per cent aforementioned solutions used in 1895.^{Reference Vansant22} Silver nitrate solutions as high as 50 per cent were noted in the treatment of epistaxis.^{Reference Goodyear25} In 1932, 75 per cent silver nitrate sticks were available for use for epistaxis.^{Reference Littell26} Given the silver nitrate sticks used in today's practice, it is difficult to compare the current treatment with the historical version; however, it is suggested that a 75 per cent concentration is superior to a 95 per cent concentration, as it seems to be more effective in the early stages, whilst causing less pain and fewer side effects.^{Reference Glynn, Amin, Sheahan and McShane27,Reference Qureishi and Burton28} Nonetheless, despite best efforts, there does seem to be a gap in the literature regarding how we went from using silver nitrate solution at 4–50 per cent to routinely using 75 per cent silver nitrate sticks.

Interestingly, the British National Formulary does not list epistaxis as an indication for the use of silver nitrate. Furthermore, epistaxis treatment is not mentioned in the product information for the Avoca silver nitrate stick, a product available from the UK supplier Bray Healthcare (Oxford, UK).

Mechanism of action

As previously mentioned, silver nitrate has been used throughout history for a range of different pathologies, but the question remains, why? What properties of silver nitrate have made it a versatile treatment over the years, and why is it particularly useful in epistaxis management?

There seems to be a lack of clear research into the mechanism of action of silver nitrate in epistaxis. An interesting article response published in 2008 highlights this, even stating ‘we have hit a brick wall!’.^{Reference Persaud, Awad and Dhillon29} Some may argue that inductive reasoning should be sufficient over understanding the true action of the drug.^{Reference Persaud, Awad and Dhillon29,Reference Tanweer and Hanif30} Even the manufacturers of silver nitrate sticks (Bray Healthcare) have been unsure of how their product works.^{Reference Persaud, Awad and Dhillon29} For this reason, they cannot provide any evidence for the concentrations used for epistaxis either.

Although there is no direct research investigating the mechanism of action, there is no reason why we cannot hypothesise how silver nitrate exerts its effects in epistaxis. A leading theory is that silver nitrate acts as an oxidising agent. Ag(I) (the cation) reduces to Ag(O) (neutral silver metal); this then precipitates and leads to the release of free radicals. This free radical production results in oxidation of organic matter, which coagulates tissues and kills bacteria.^{Reference Hanif, Tasca, Frosh, Ghufoor and Stirling31} The tissue is effectively being burned in this process.^{Reference Bastianpillai, Saxby, Coyle, Armstrong, Mohamid and Mochloulis32}

As per Fullerton, other means of chemical cauterisation have been used over the years, such as chromic acid.^{Reference Fullerton14} Trichloroacetic acid was also used in the US army around 1954.^{Reference Erkenbeck33} This would support the idea that the acidic properties of silver nitrate are responsible for its effects in epistaxis management. Another hypothesis is that silver ions can react with proteins to form nitrites or ammonia, which leads to thrombosis and tissue denaturing.^{Reference Persaud, Awad and Dhillon29}

Although a tissue study has been performed fairly recently to assess the effects of silver nitrate on nasal septal cartilage, viable mucosa containing the offending vessels was not included.^{Reference Lloyd, Almeyda, Di Cuffa and Shah34}