86 Journal of Tissue Viability 1994 Vol4 No 3

What's New in Wound Treatment? -Not a Lot! John Topham Former Clinical Pharmacist, Main Hospital, Zanzibar, and Senior Lecturer in Pharmaceutical Technology Portsmouth University

Principles of wound treatment have changed little since Egyptian times. Many traditional wound treatment agents, especially sugar based materials, can be used to advantage today.

Introduction We are being bombarded with new dressings and wound treatments, which frequently cost more than the items they are supposed to replace. But is there any fundamental difference in the way wounds are treated nowadays compared with three millenia ago?

In Roman times they would cover the wound with lard containing a preservative such as benzoin (BenzoinatedLardBP 1948) and then wrap a cloth around. This kept the wound moist and, provided only a small quantity of lard was applied, the wound did not 'macerate', that is trap too much water so that micro-organisms could grow.

This treatment was not always successful for deep ulcers. The Egyptians, one and a half centuries earlier, had discovered that honey was a good treatment for such wounds 1• If a fanatical mob had not destroyed the Library in Alexandria in the early part of the Fourth Century AD, maybe we would now have some very interesting wound treatments from which to choose.

Conditions for Wound Healing What are the criteria for a good wound treatment? Most authorities are now agreed that the following conditions are needed for wounds to heal:

(i) A clean wound.

(ii) Sufficient moisture to encourage healing without encouraging bacterial or fungal growth.

(iii) Protection from mechanical damage.

(iv) Favourable pH- probably between pH3.5 and pH7.

(v) Favourable temperature- probably about 37°C.

(vi) Time to heal- minimum number of dressing changes.

Let us examine these requirements to see how we have improved on treatments used 3,500 years ago.

In olden days, once large foreign bodies had been taken out of the wound, the excess debris would be washed off with water or even wine to satisfy condition (i). Then honey would be poured into the wound, which would be covered with a cloth. Obviously ants and other insects had to be kept at bay. This

may have been achieved by covering the cloth dressing with oil, wax or embalming fluids. The Edwin Smith Papyrus (dated 1700BC) describes how gum was applied to linen strips to form a wound covering. These coverings would help to prevent wounds from drying, thus satisfying requirements (ii) and (iii).

The honey would keep the wound sterile as long as the exudate did not cause the water activity (aw) to rise above 0.85. This would occur when the total sugar concentration fell below 68%2

• If yeasts and moulds were absent, the wound would remain sterile until the water activity rose to 0.9, equivalent to a total sugar concentration of 60% (Table I).

Once granulation tissue had filled the wound cavity, the dressing would be removed and the wound surface would be covered with a thin layer of oil or fat until the epithelial tissue had covered the wound surface. Did this treatment meet our requirements (iv) a favourable pH, (v) favourable temperature and (vi) time to heal?

Thomas1 states that the pH of honey is 3.7. We assume that the coverings maintained the wound at a favourable temperature and, since valuable resources were used up at each dressing change, we may assume that they were carried out only when necessary. Hence the conditions (iv ), ( v) and (vi) were satisfied.

Nowadays wound dressings of honey or sugar pastes are changed either daily or on alternate days 3•

4·5 provided the wound

is clean. This satisfies the time to heal condition (vi). If sugar paste dressings are changed at more frequent intervals, bleeding will occur 6

• Furthermore Archer et al7 observed that sugar paste applied to wounds on a pig had a pH of5.5, which satisfies the favourable pH condition (iv).

Sugar pastes and Intrasite gel8 seem to be preferred to honey with the new hydrogel preparations starting to compete9

•10

•

Scherisorb was the precursor of Intrasite. This replaced the Starch Glycerin of the 1867 British Pharmacopoeia, which is said to have given a burning sensation when initially applied to a wound cavity. Even the hydrogel preparations cannot claim to be novel, because a gel obtained from the parenchymal cells of Aloe Vera leaves was used by the ancient Egyptians 11

•

Oiled silk has been used on wounds for more than a century. This gave us an almost non-porous dressing, allowing water

vapour to pass through. It has been replaced by plastic films. Although polyurethane films are popular12

, thin polythene sheet, such as freezer quality cling film is less expensive and probably just as good. Ordinary PVC cling film is used by ambulance workers 13 to wrap around serious wounds such as broken skulls and severe lacerations. There is a slight query concerning the use of PVC cling film in that it may contain a plasticiser, such as butyl phthalate, which is slightly toxic and may delay wound healing. The film permitted for wrapping cheese is suitable as a wound dressing material14

• Maybe a film made from the new genetically engineered spider's web silk will be the covering of the future, just as spiders' webs were used on facial cuts in the past.

From early times sailors have used sea water to wash wounds which were covered with seaweed. We now use a sterile saline solution15 and 'cleaned up' seaweed called alginate for similar purposes16

•

In bygone days, sometimes wounds were covered with animal skins. Skins are the source of gelatin (collagen) used in hydrocolloid dressings. Zinc Gelatin BPC 1907 -known as Unna' s Paste- could be called a hydrocolloid dressing according to today' s definition. The instructions for its use are as follows 17:

'The leg or foot (with varicose veins or similar indolent lesions) is thoroughly cleansed and a dusting powder applied.' (We would object to the use of those dusting powders nowadays because they contained talc.) 'The paste, previously melted and cooled, is applied with a brush to the affected part and the paste is covered with a gauze bandage. A total of four layers of paste are applied, each layer being covered with a gauze bandage. The dressing is left for three days to two weeks and removed by soaking in warm water.' So a form of four-layer bandaging has been around for some time ! Note the wound was given time to heal between dressing changes which meets condition (vi).

Apparently the offensive odour associated with dressings containing gelatin occurs with all so-classified hydrocolloid dressings. The word 'hydrocolloid' normally refers to water-liking substances with dimensions between 10·4mm and 1Q·6mm 18

· Besides gelatin some hydro gels fall into this category. So the present use of the word 'hydrocolloid' to describe a group of dressings, containing gelatin plus other hydrogels, seems to be a misnomer.

Since some of the olden methods were satisfactory wound treatments, is there any reason why we should discard them ?

Honey is still used19 but some honeys have been found to contain toxic materials20 which originated in the flowers from which the bees gathered nectar. Nevertheless most honeys are non-toxic and promote wound healing.

Debrideing Action of Sugar Castor or granulated sugar will destroy cells because it has a low water activity, see Table 1. Thus it can be used as a debrideing agent21 and may be superior to streptokinase (V arinase) which should not be used on patients at risk of

Journal of Tissue Viability 1994 Vol4 No 3 87

myocardial infarction22• When mixed with pawpaw (papai)

juice, sugar is claimed to be an even better debrideing agent because of the action of the proteolytic enzyme (papain) in the juice.

Water Sucrose Activity concn

Effect on microbiological activity

aw (approx)

0.9 0.85 0.80 0.75 0.55

60% 68% 75% 85% 93%

Lower limit for growth of most bacteria Lower limit for growth of most yeasts Lower limit for growth of most fungi Lower limit for halophilic bacteria Lower limit for life to continue DNA becomes disordered

Table 1 - Effect of Water Activity aw of various sugar concentrations on microbiological activity.

Loncin & Merson2, Chirife23

If there is copious exudate, pure sucrose (sugar) can also act as a wound healing agent. The reason for this is that the exudate will raise the level of water activity, aw, at the wound surface as the ratio:

vapour pressure at the wound surface vapour pressure of pure water at the wound surface temperature

increases23•

When 15% water is added to sugar, a paste is formed which will still have debrideing properties and will prevent bacterial and fungal growth (Table 1), yet encourage the formation of granulation tissue. Evidence for this is the work of Beyer and co-workers24 who showed that the presence of intralysosomal sucrose caused a considerable increase in postnatal human skin fibroblasts. The exact method by which granulation tissue is formed is complex and involves cell death, APOPTOSIS, as described by Kerr et al25 and explained genetically by Raff26•

Turner 27 described it in simpler terms.

Sugar/Water/Gum Combinations A paste consisting of 15% water in granulated sugar is runny and will seep out of the wound unless it is held in firmly by an adhesive film over the top of the wound. This seepage can be reduced by adding a gum (hydrogel) to the sugar paste. Examples of gums that can be used are:

Carboxymethylcellulose ( carmellose ),

Hydroxypropyl methylcellulose (hypromellose) and

other cellulose derivatives

Alginic acid and alginates

Pectin, polyvinylpyrrolidone (povidone)

Cross-linked pol:Yoxyethylene (macrogol) polymers

Sodium starch glycollate and other starch derivatives.

88 Journal of Tissue Viability 1994 Vol4 No 3

Callaghan et al28 list the equilibrium moisture contents of seven of these gums. This will help workers to anticipate the moisture uptake from wounds, when gums are present in dressings applied to them.

The presence of gums (hydro gels) will lower the water activity, aw, of the preparation with the result that more exudate will be absorbed before a dressing change is needed. This lowering of the water activity has the advantage that lower concentrations of sugar can be used, for example super-saturated sugar solutions29 or Syrup BP (which contains 66% sucrose). Since more exudate is taken up when gums are present in a sugar/ water mix, dressing changes can be made less frequently: this fulfils requirement (vi). Sugar also reduces the odour from wounds 7: this is another reason for using it as a wound dressing.

Rheology By altering the quantities of gum present in a sugar/water dressing the 'rheology' or flow properties of the dressing can be adjusted according to the type of wound to be treated. The sugar will act as a humectant, preventing drying of the dressing, which would cause it to be excessively adhesive30• Thus cavity wounds will require a preparation that flows more freely than the dressing for a surface wound. The 'rheology' of each preparation could be measured using a modification31 of the Plastometertest of the British Pharmacopoeia and its absorbancy determined by the weighing method described by Thomas and Loveless32

•

Advantages of Sugar/Gum Formulations Other advantages of sugar/gum preparations are:

1. Hypergranulation, associated with some sugar pastes, is unlikely to occur.

2. Wound healing rates are relatively rapid.

3. Contraction and scar tissue is non-existent in many cases.

4. Frequently the need for skin grafting is eliminated5•

In the treatment of wounds of diabetic patients it is natural to think that sugar should not be used. But sugar pastes have been used to successfully treat diabetic wounds 18

•33

•34

•35

• Furthermore it has been shown36 that sorbitol collects in diabetic wounds, not dextrose or sucrose.

Conclusion The way forward could be a combination of the old with the new. That is sugar with water (or honey) could be combined with the new gums (hydrogels) to make a range of products suitable for both deep and surface wounds which produce varying amounts of exudate. At the same time it is important to remember that wounds will not heal if the general health of the patient is poor. Good diet or dietary supplements containing essential minerals and vitarnins37 are necessary to ensure rapid, sustained wound healing.

Maybe the ancient physicians can still teach us a thing or two about wound healing.

Address for Correspondence Mr J Topham, 31 Elizabeth Gardens, Southsea, Hants P04 9QZ

References 1. Thomas S. WoundManagementandDressings. London:

The Pharmaceutical Press. 1990: 63. 2. Loncin R, Merson R L. Food Engineering. London:

Academic Press. 1979: 200. 3. Efem SEE. Clinical observations on the wound healing

properties of honey. Br J Surg. 1988; 75: 679-681. 4. Subrahmanyan M. Topical applications of honey in

treatment of bums. Br J Surg. 1991; 78: 497-8. Also: Honey impregnated gauze versus polyurethane film (Opsite) in the treatment of bums- a prospective randomised study. Br J Plast Surg. 1993; 46: 322-323.

5. Topham J D. Experience with sugar paste in Zanzibar. Dressing Times. 1991; 4(3): 3-4.

6. Seal D V, Middleton K. Healing of cavity wounds with sugar. Lancet. 1991; 338: 571-72.

7. Archer H G, et al. A controlled model of moist wound healing: between semi-permeable film, antiseptic and sugar paste. J Exp Path. 1990; 71: 155-170.

8. Thomas S. Comparing two dressings for wound debridement. J Wound Care. 1993; 2(5): 272-274.

9. Crane J. Extending the role of a new hydrogel. J Tiss Viab. 1993; 3(3): 98-99.

10. Shrivastava S, Grant H, Courtney J, Barbenel J. The in-vitro cellular response of mouse and human fibroblasts to collagen based wound dressings. J Tiss Viab. 1993; 3(3): 100-103.

11. Marshall J M. Aloe vera gel: what is the evidence ? Pharm J. 1990; 244: 360-361.

12. Morgan D. Formulary of Wound Management Products (Fifth Edition). Chichester: Media Medica Publications: 1992.

13. Personal Communication, Portsmouth Ambulance Service.

14. Plastic materials and articles in contact with food regulations. 1992. SI 1992, No. 3145 10/12/92.

15. Russell L. Healing alternatives. Nursing Times. 1993; 89: 42. 16. Attwood A I. Calcium alginate dressing accelerates split

skingraftdonorsitehealing.Br J Plast Surg.1993;43(4): 373-379.

17. Martindale. The Extra Pharmacopoeia (28th Edition). London: The Pharmaceuticiil Press. 1982:510.

18. Isaacs A. A Dictionary of Science (Fourth Edition). Harmondsworth, Middx. Penguin Books, 1971.

19. Tovey Fl. Honeyandhealing. JRoySocMed.1991;84:447. 20. Mirkin G. Side effects ofraw honey. JAM A. 1991;

266(19): 2766. 21. Trouillet J L, Chastre J, Fagon J Y, Pierre J, Domart Y,

Gilbert C. Use of granulated sugar in treatment of open mediastinitis after cardiac surgery. Lancet. 1985; 2: 180-184.

22. Green C. Antistreptokinase titres after topical streptokinase. Lancet. 1993; 341: 1602.

23. Chirife J, Scarmatto G, Herzage L. Scientific basis for the use of granulated sugar in the treatment of infected wound. Lancet. 1982; 1: 560-61.

24. BeyerEM,IvlevaTS,ArtykovaGT, WiederschainGY. Comparative studies of intracellular activity, secretion and multiple forms spectra of human skin fibroblast alpha-1-fucosidase in the normal and after sucrose load. Biochem Mol Biollnt. 1993; 30(2): 367-75.

25. Kerr J F R, Wyllie A, Currie. Apoptosis: a basic biological phenomenon. Br J of Cancer. 1972; 26: 239-57.

26. RaffM C. Social controls on cell survival and cell death. Nature. 1992; 356: 397-400.

27. TumerT. Thehealingprocess.PhannJ, 1993;250: 735-737. 28. Callaghan J C, Cleary G W, Elefant M, Caplan G,

Kensler T, Nash RA. Equilibrium moisture contents of pharmaceutical ingredients. Drug Dev Ind Phann. 1982; 8(3): 355-367.

29. Bhanaganada K, Kiettephongthavom V, Wilde H. The use of super-saturated sucrose solution for chronic skin ulcers. (Resurrection of an old remedy). J Med Assn Thailand. 1986; 69(7): 358-365.

30. Porter J M. A review of dressing material used for the

I

(

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treatment of raw areas in plastic surgery. J Tiss Viab. 1991; 1(2): 48-52.

31. Brown D T, Topham J D and MartinG P. A rational approach to the official BP test for determination of yield values of visco-elastic gels. J Phann Phannacol. 1984; 36:20.

32. Thomas S, Loveless P. A comparative study of the properties of six hydrocolloid dressings. Phann J. 1991; 247: 672-675.

33. TophamJD. Sugar paste in treatment of pressure sores, bums and wounds. Phann J. 1988; 240: 118-119.

34. Knutson R A, Merbitz LA, Creekmore A A, Snipes L G. Use of sugar and povidone iodine to enhance wound healing. Five years experience. South Med J. 1981; 74(11): 1329-35.

35. Quatraro A, Minei A, Donzella C, Caretta G, Guigliana D. Sugar and wound healing. Lancet. 1985; (2): 664.

36. Editorial. Diabetic neuropathy. Lancet. 1989; (1): 1113-4.

37. Department ofHealthreport on health and social subjects. 41-Dietary reference values for food energy and nutrients for the United Kingdom. London HMS0,1991.

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