East & South East England Specialist Pharmacy Services

East & South East England Specialist Pharmacy Services

East of England, London, South Central & South East Coast

Proflavine cream and acriflavine solution for wounds

Summary and Recommendations

·  Due to the lack of evidence supporting the use of proflavine cream and acriflavine solution, as well as the difficulty in obtaining the raw materials used to make these products, these should no longer be used.

·  Alternative wound care products are hydrofibre dressings, such as Aquacel ribbon or Kaltostat rope, or hydrogel sheets such as Gel FX.

·  If an antimicrobial dressing is required, one such as Aquacel Ag, Flaminal hydro or forte gels, honey wound gel or Prontosan wound gel can be used.

·  Hibitane obstetric cream can be used as an antiseptic and lubricant in obstetrics and gynaecology.

·  Advice should be sought from tissue viability clinical nurse specialists as necessary.

Background

Proflavine cream is an acridine derivative and acts as a slow-acting antiseptic.1 The acridine derivatives are bacteriostatic against many Gram-positive bacteria, but less effective against Gram-negative bacteria. Other acridine derivatives include acriflavine, but their use has been superseded by other antiseptics or suitable antibacterials.1 Antiseptic solutions such as proflavine and acriflavine, are used to cleanse or irrigate wounds, or incorporated into dressings to allow for a longer contact time with the wound, giving a prolonged antibacterial effect.2

The raw materials used to make proflavine cream and acriflavine solution are difficult to obtain, with no guarantee of availability in the future; manufacture of these products is now no longer deemed viable.3 Other wound management products should be used instead.

Evidence supporting the use of proflavine

There is no reliable evidence that proflavine-soaked gauze for wound packing is effective, or that it has any clinical benefits.2;4 Before the advent of moisture-retentive cavity dressings, cavity wounds were packed with gauze soaked in antiseptics such as proflavine.5 The theory was that this would keep the wound margins apart and allow the wound to granulate from the base upwards, but this has never been substantiated.5 Studies report pain associated with dressing changes, and no advantages over modern dressings have been demonstrated.4;6 It has been suggested that because the proflavine is not released from the cream into the wound, it actually has no effect on the bacteria.7

Evidence supporting the use of acriflavine

No evidence supporting the use of acriflavine in wound management was found in a literature search (Medline, Embase and Cinahl).

Cost-benefit analysis for proflavine

Traditional antiseptics have a low unit cost but many require frequent dressing changes and involve high costs with respect to nursing time.4;7

A randomised, controlled trial assessed patient pain levels and overall costs in a comparison of a modern hydrocolloid-fibrous (hydrofibre) dressing (Aquacel) were ribbon gauze soaked in proflavine, for the treatment of acute surgical wounds (abscesses and pilonidal sinuses) (n=40).8;9 All analyses were based on the total patient sample and one research nurse assessed dressing changes at 24 hours and 7 days post-surgery. Time to healing was not assessed. The study results indicated that a change in practice from using ribbon gauze soaked in proflavine to hydrofibre dressings would allow for surgery of open wounds to be conducted on a day-case basis, saving a substantial number of bed days each year. Consequently, ribbon gauze and proflavine dressings were withdrawn from the clinical areas. The results were:

·  Less pain experienced by patients when the hydrofibre dressings were first changed (60% vs. 0% experienced no pain, and 30% vs. 70% experienced moderate-severe pain, p=0.006). This may have been influenced by wound type, which in turn influences how ‘easy to remove’ the dressing is perceived to be: 19/20 dressings in the hydrofibre group and 11/20 in the ribbon gauze group (95% vs. 55%) were ‘easy to remove’ (p=0.01).8

·  More patients in the hydrofibre dressing group would prefer the first post-operative dressing change at home which would allow for a significant number of patients in this group to be treated as day cases, compared with the overnight stay required for the ribbon gauze/proflavine group (60% vs. 15%, p=0.02). Fourteen patients in the ribbon gauze group (70%) vs. two in the hydrofibre group (10%) reported pain as the main reason for requesting a dressing change in hospital.8

·  Nursing time to change the hydrofibre dressing was approximately half the time required in the ribbon gauze group, due to the fact that the hydrofibre dressing produced a moist environment for healing and could be easily lifted out, compared with the soaking in saline required for removal of the gauze.9 In addition, the hydrofibre dressing could be changed in alternate-days compared with daily changes for the ribbon gauze.9

·  No statistically significant between-group differences in the length of time of dressing change and the frequency of dressing change, but these did contribute to the overall cost of nursing time.9

·  The average cost per patient treated in the hydrofibre group was less than half than of the ribbon gauze group (£280 vs. £680) (p=0.01).9

There are limitations to this study. More patients randomised to ribbon gauze had wounds from which dressings were perceived to be ‘harder-to-remove’, no power calculation was carried out to ensure that the patient population was large enough to show that this difference was not due to chance, and the study was sponsored by ConvaTec, manufacturers of Aquacel.

Alternative products

Antiseptic products

Hibitane obstetric cream is used as an antiseptic and lubricant in obstetrics and gynaecology. 10 Tissue viability nurses11-16 have suggested a number of alternative products for other wounds, such as:

·  A hydrofibre containing silver, such as Aquacel Ag ribbon if an antimicrobial dressing is required for cavity wounds

·  Flaminal hydro or forte alginate gels. The forte gel is more absorbant and can be used in pilonidal sinus wounds and infected leg ulcers.

·  Honey wound gel

·  Prontosan wound gel (contains betaine surfactant and polihexanide)

Wound dressings

There are a wide number of wound dressing products available. Tissue viability nurses11-13;15;16 have suggested a number of alternative products, such as:

·  For cavity wounds would be a hydrofibre dressing such as Aquacel ribbon or an alginate dressing such as Kaltostat rope, or a hydrogel sheet dressing such as Gel FX.

·  Hydrofibre dressings resemble alginate dressings and because they are more absorptive are suitable for moderately to heavily exuding wounds.

Reference List

(1) Brayfield A (ed), Martindale: The Complete Drug Reference. [online] London: Pharmaceutical Press <http://www.medicinescomplete.com/> (accessed on 15/07/13).

(2) White RJ, Cooper R, Kingsley A. Wound colonization and infection: the role of topical antimicrobials. Br J Nurs 2001; 10(9):563-578.

(3) Personal Communication: Stephen Langford, Pharmacy Production Director, Calderdale & Huddersfield NHS Foundation Trust, Pharmacy Manufacturing Unit, 24/07/13.

(4) Scanlon E, Stubbs N. To use or not to use? The debate on the use of antiseptics in wound care. Wound Care 2002; September:8-20.

(5) Jones VJ. The use of gauze: will it ever change? International Wound Journal 2006; 3:79-86.

(6) Wound Healing and Management Node Group. Evidence summary: Wound management: dressings - alginate. Wound Practice and Research 2013; 21(1):23-25.

(7) Johnson M. Dressings in the management of open surgical wounds. British Journal of Perioperative Nursing 2004; 14(8):354-360.

(8) Foster L, Moore P. The application of a cellulose-based fibre dressing in surgical wounds. J Wound Care 1997; 6(10):469-473.

(9) Moore PJ, Foster L. Cost benefits of two dressings in the management of surgical wounds. Br J Nurs 2000; 9(17):1128-1132.

(10) British National Formulary, 65th edition. March - September 2013. Ed. Ryan RSM. British Medical Association and Royal Pharmaceutical Society of Great Britain. Accessed via: www.bnf.org.

(11) Personal Communication: Sean Connerty, Tissue Viability Nurse, North West London Hospitals NHS Trust. 18/07/13.

(12) Personal Communication: Hannah Patten, Clinical Nurse Specialist - Tissue Viability, North East London NHS Foundation Trust, 02/08/13.

(13) Personal Communication: Bernadette Byrne, Tissue Viability Nurse Specialist, Kings College Hospital, 15/08/13.

(14) Personal Communication: Debby Sinclair, Clinical Nurse Specialist - Paediatric Plastic Surgery, St George's Hospital, 19/08/13.

(15) Personal Communication: Wilma Williams-Kelly, Tissue Viability Clinical Lead - East, North East London Community Services, North East LondonNHS Foundation Trust, September 2013.

(16) Personal Communication: Beverley Wilson, Nurse Consultant Tissue Viability, Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust, September 2013.

Written by Alexandra Denby, London Medicines Information Service, August 2013. Updated September 2013. Comments to .

Medline: terms PROFLAVINE/ [limit to Human and English] = 80 hits

Medline: ACRIFLAVINE/ and [WOUND HEALING/ OR ANTI-INFECTIVE AGENTS, LOCAL/] [Limit to: English Language and Humans] – 27 hits

Embase: terms: PROFLAVINE/ [limit to Human and English] = 124 hits

Embase: terms: ACRIFLAVINE/ and [WOUND DRESSING/ OR WOUND HEALING/ OR WOUND HEALING PROMOTING AGENT/ OR WOUND INFECTION/] = 7 hits

CINAHL: terms: proflavine.af = 19 hits

CINAHL: terms: acriflavine.af = 10 hits

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