Friday March 20 2009
The larval therapy used maggots from the green bottle fly
Maggots are in the news today. Newspapers have taken slightly different angles on a study into the use of larval therapy for leg ulcers. The Daily Telegraph reported that “maggots are as successful at treating leg ulcers as standard dressings”. The BBC was less optimistic, saying that maggots may not have the miracle healing properties that have been claimed. Meanwhile, The Times pointed out that although maggots heal leg ulcers no quicker than the normal dressings (hydrogel), the maggots cleaned the wound five times faster.
These reports are based on a randomised controlled trial that compared loose larvae, bagged larvae and hydrogel in treating leg ulcers in 267 patients in the UK. This good-quality study found that there was no difference between larval treatment and hydrogel in healing ulcers. However, the larvae were better at debriding wounds (getting rid of dead tissue).
Questions about the use of maggots to heal wounds still remain unanswered, and further study is needed. The researchers say that “future treatment decisions should be fully informed by the finding that there is no evidence of an impact on healing time”.
Where did the story come from?
Dr Jo C. Dumville and colleagues from the University of York, the University of Warwick, Micropathology Ltd in Coventry and the University of Leeds carried out this study. The research was funded by the UK National Institute for Health’s Research Health Technology Assessment Programme. It was published in the peer-reviewed British Medical Journal.
What kind of scientific study was this?
This randomised controlled trial compared the treatment of leg ulcers with larvae from the green bottle fly (maggots) to hydrogel (a standard non-adherent, gel-like dressing). Venous and arterial ulcers result from poor blood circulation. Most leg ulcers are venous ulcers caused by faulty valves in superficial and deep veins. Due to the faulty valves, blood fails to flow out of the limb properly, which results in high venous pressure, oedema (collection of fluid in tissues) and damage to skin. This leads to ulceration. Arterial leg ulcers are different in that they are the result of a reduced blood supply from the heart to the tissues.
The treatment of leg ulcers usually involves cleaning them with saline or tap water followed by the application of a dressing. For venous leg ulcers, a compression bandage is also applied to improve blood flow from the lower limbs. The wound is cleaned and the dressing is changed regularly until healing is complete. There are several different types of dressing, including hydrogel dressings. The choice of dressing depends on the type of tissue in the wound, the presence of odour or infection, and the presence and type of exudate (fluid that oozes from blood vessels due to inflammation).
The study recruited people from 22 leg ulcer clinics across the UK. The participants all had venous leg ulcers or a mix of venous and arterial leg ulcers, with at least a quarter of the ulcer covered by necrotic tissue (dead tissue, also called slough). These are the types of wounds that larval therapy is used on. The ulcers were non-healing (no change in area in previous month), were 5cm2 or less in diameter, and they occurred and in people with more than one ulcer. The largest ulcer was chosen as the reference. Pregnant or lactating women were excluded, as were people who were allergic to hydrogel, and those who had “grossly oedematous legs” or who were taking anticoagulants (which would render larval therapy unsuitable).
There were 267 eligible patients, who were randomly allocated to receive either loose larvae, bagged larvae or hydrogel. These were applied in the debridement phase of the patient’s treatment (i.e. the phase when dead tissue is removed from the ulcer). Larvae were left on the wound for three to four days. After debridement, all patients had a standard dressing without compression. In this study, the compression aspect of treatment was not compromised and nurses used this as appropriate, although it could not be used when larvae were in place.
The researchers compared the time it took for the ulcer to completely heal between the three groups, as judged by two nurses. Photographs were taken every week for the first six months, and then monthly thereafter. These were used to independently assess healing by a third party, who was unaware of the treatment allocation. The researchers also assessed other outcomes, including the length of time until debridement, bacteria in wounds, quality of life, adverse events and pain.
What were the results of the study?
There was no difference between the three groups in the time that it took for the ulcers to heal. There was no significant difference in chance of healing between hydrogel and larval therapy (loose larvae and bagged larvae combined).
Loose larvae debrided the wounds quicker than either bagged larvae or hydrogel, but when the larval treatments were combined into one, there was no difference in time to debridement compared with hydrogel. However, the larval therapy debrided the patients' wounds twice as fast as hydrogel (HR 2.31, 95% CI 1.65 to 3.24).
The three groups showed no significant differences in bacteria levels in the wounds or in adverse events. Patients in the larval groups reported significantly more pain than those in the hydrogel groups.
What interpretations did the researchers draw from these results?
The researchers report that there is no evidence that larval therapy using loose or bagged larvae reduces the healing time of ulcers compared with hydrogel. However, their study does suggest that larvae are better at debridement than hydrogel. Although pain was greater in the larval therapy group, this was “probably transient”, and it did not have an affect on the regular quality-of-life measurements.
What does the NHS Knowledge Service make of this study?
This randomised controlled trial provides the strongest evidence to date about the effects of larval therapy on leg ulcer healing. It found that there was no difference in the healing of leg ulcers when larval therapy was used for debridement compared with using hydrogel dressings.
These results can be interpreted in different ways, as reflected in the newspaper headlines. No difference can be interpreted as ‘just as good as’ or ‘no better than’. The important points are:
- People receiving larval therapy reported more pain than those receiving hydrogel.
- There may be issues of acceptability with regards to larval therapy (some people might choose not to receive it).
- Larval therapy seems to improve wound debridement, and the researchers say that “if debridement is the goal of treatment, such as before skin grafting or other surgery, then larval therapy should be considered”.
- In spite of this recommendation, the researchers say that the role of debridement in managing leg ulcers is not clear. While it is viewed as an important part of wound healing, more research is needed to understand whether it is indeed beneficial for patients.
- A separate study concludes that, based on these results, larval therapy has “similar health benefits” and “similar costs” to hydrogel treatment.
- The findings of this study apply to people with quite serious wounds, i.e. those that hadn’t improved in the month before randomisation, and wounds that took about 240 days to completely heal.
The researchers highlight some limitations of their study, including the difficulty they had in recruiting enough people who met their criteria of “sloughy” ulcers (i.e. ones with sufficient dead tissue to indicate larval therapy as an option). As such, the study is likely to be underpowered, and there is a greater risk that positive results are false positives, or that the study misses true differences between treatment groups. The researchers also did not investigate debridement in the long term, i.e. whether wounds remained debrided. Another limitation is that they only measured total bacterial load in the wound and didn’t investigate particular types of bacteria (except MRSA).
There are still unanswered questions regarding larval therapy, and the researchers say that “future treatment decisions should be fully informed by the finding that there is no evidence of an impact on healing time”.