Although it has been speculated that iodine delays healing and is cytotoxic, there is substantial evidence to suggest that the commonly-used low concentration, slow release iodophors improve healing rates and are effective as highly potent antimicrobials with a broad spectrum of activity, including antibiotic-resistant strains such as MRSA.

Authors: Sibbald RG, Leaper DJ, Queen D.
Full author details can be found on page 4.

What is iodine?
Iodine is a natural dark violet, non-metallic element that plays a key role in human metabolism. It is essential for the production of thyroid hormones and an iodine deficiency can result in hypothyroidism. Iodine occurs naturally in the form of iodide ions in sea water, fish, oysters and certain seaweeds[2]. It can also be found in vegetables grown in iodine-rich soil and dairy products. It has been described as 'the most potent antiseptic available'[3].


What is the history of iodine in wound healing?
In the 4th century BC, before iodine had been discovered, Theophrastus, a pupil of Aristotle, recorded that iodine-rich seaweeds could be used to reduce the pain of sunburn [4]. One of the first antiseptic iodine preparations to be used in wound care was Lugol's solution containing elemental iodine and potassium in water, which was developed in 1829[5]. This solution was also used to treat wounds in the American Civil War.

The antimicrobial properties of iodine were first demonstrated in 1882 by Davaine6. In the First World War, iodine was found by Alexander Fleming to reduce the incidence of gas gangrene in the wounds of soldiers when compared to carbolic acid [7].  Since the mid-19th century, iodine-based preparations have also had an important role in the prevention of surgical site infections. Povidone iodine preparations are popularly used as an antiseptic to prepare the patient's skin before surgery and are also used by surgeons and theatre staff as a skin cleanser and antiseptic in preoperative hand scrubs.

Early uses of iodine involved aqueous and alcoholic iodine preparations, which were associated with unpleasant side effects including pain, irritation and skin staining.

Why is iodine safer today?
Iodophors were developed in the 1950s to overcome the side effects associated with elemental iodine. These were found to be safer and less painful, but just as effective as elemental iodine, allowing widespread use.

Bonding iodine with another molecule makes it less toxic and instead of high concentrations of iodine being released in a single application, the iodine is slowly released from the reservoir carrier molecule over a sustained period of time.

Iodophors are preparations that bind iodine to a solubilising agent or carrier. The water-soluble complex allows the slow release of a low concentration of free iodine when the carrier comes into contact with wound exudate. This controlled release of low concentrations of iodine helps to minimise the negative side effects of using free elemental iodine.

Modern iodine preparations
The two most commonly used iodophors in modern wound dressings (Table 1) are:

• Povidone iodine (PVP-I): a chemical complex of polyvinylpyrrolidone (also known as povidone and PVP) and elemental iodine. Examples include dressings such as Inadine® (Systagenix) and solutions such as Betadine® (Purdue Products) and Braunol® (B Braun)
• Cadexomer iodine: an iodine and polysaccharide complex, such as Iodoflex® (Smith and Nephew) and Iodosorb® (Smith and Nephew), which can be used as antiseptic fillers, particularly in cavity wounds.  

Povidone iodine preparations were introduced in the 1960s and it is now the most common iodophor in clinical use. It is available in different formulations, including solution, cream, ointment, spray and wound dressings.


What is the evidence to support  iodine use?
There is extensive evidence to support the use of povidone iodine in wound healing [8] (Table 2), but its use is not without controversy due to perceived issues with toxicity, systemic absorption and delayed healing. It has been suggested that iodine has a negative impact on cells involved in the wound healing process and because of this its safety and efficacy have been questioned.

Some reviews have analysed the conflicting evidence and have found that studies based on animal models tend to support the argument for iodine's cytotoxicity, whereas human studies suggest that PVP-I can help the wound healing process by reducing bacterial load and decreasing infection rates [9,10]. One study demonstrated that not only does PVP-1 significantly improve the healing rates of chronic venous leg ulcers, but also that it lacks cytotoxicity in vivo [11].

The efficacy of cadexomer iodine has been demonstrated using both animal models and clinical studies. Cadexomer iodine was found to significantly reduce symptoms associated with infection (eg exudate, erythema, oedema and pain) in patients with pressure ulcers [12] and venous leg ulcers [13].

In addition to providing an antimicrobial effect, in vitro studies have reported a lack of toxicity for human fibroblast activity [14] and that cadexomer iodine may increase epithelialisation of chronic wounds [15,16]. However, its mode of action is not understood and further research is needed to determine whether wound aetiology has a contributory role [8].