- 1 - Welcome to the third edition of the Dressings Times which, by popular request consists primarily of a review of the use of antiseptics and wound cleansing solutions. Although wide- ly used, the irritant nature and cytotoxic properties of some of these materials have led some workers to recommend that they should no longer be used for routine wound manage- ment. In this issue some of the more commonly used solu- tions are described and their applications discussed in the light of published literature. Hypochlorite solutions. Hypochlorite solutions have been known for over two hundred years. Eau de Javelle a solution of potassium hypochlorite, was first used as a bleaching agent in 1782 and a solution of sodium hypochlorite (known as eau de Labbaraque) was used as a disinfectant as early as 1820. Similar solutions were later used to great effect by Sammelweiss in preventing the spread of puerperal sepsis. Chemically, hypochlorite solutions are highly reactive, combining rapidly with =NH groups on proteins bringing about chlorination, oxidation and hydrolysis of nitrogenous mate- rial.1 It is this interaction with protein that gives hypochlorites their antimicrobial activity and leads to their use as disinfectants, lavatory cleaners and water pu- rification agents. Hypochlorite solutions even at very low concentrations have a marked inhibitory effect on enzyme systems and because they react with all forms of protein, they are rapidly inac- tivated by the presence of pus, serum and other organic mat- ter. Solutions of sodium hypochlorite are very alkaline (pH 11) and are consequently irritant to the skin. This problem was recognised by Dakin who in 1915 described a buffered hypochlorite solution which stills bears his name.2 Both the biological activity and the stability of sodium hypochlorite solutions are pH dependent. When stored cor- rectly, a solution of sodium hypochlorite at pH 11 is stable for several months but at lower pH values the stability is reduced dramatically. Unfortunately, the undissociated hypochlorous acid, the chemically active form, reaches a maximum concentration around pH 5.5 at which point the solu- tion is at its most unstable.1 Under these conditions decom- position will be very rapid. For this reason, solutions of hypochlorites used in wound management are sometimes buffered to a point somewhere between these two values in order to reduce their irritant effect and achieve a compro- mise between effective biological activity and chemical sta- bility. A brief description of some of the commonly used solutions is given below. Dakin's solution (Surgical Chlorinated Soda Solution B.P.C.) contains 0.5% w/v available chlorine and is buffered with boric acid to a final pH of 9.5. The solution has to be freshly prepared and is only stable for a period of 2-3 weeks. Eusol is a solution of calcium hypochlorite containing not less than 0.25% w/v of available chlorine buffered with boric acid to a pH of 7.5 - 8.5. Like Dakin's solution, Eu- sol has to be freshly prepared and is only stable for about 2 weeks when stored in a full, tightly closed bottle. Because of the stability problems associated with the two solutions described above, many pharmacies now supply an al- ternative product which is a dilution of Milton Milton solution (Richardson Merrell Ltd.) is a commercially available product containing 1% sodium hypochlorite and 16.5% sodium chloride. It is widely used as a 1 in 80 dilu- tion to sterilise babies feeding utensils and a 1 in 20 so- lution is isotonic with body fluids. For wound management applications, a 1 in 4 dilution of Milton is generally used. This contains 0.25% w/v available chlorine and has a pH of 10.5-11.2. Despite the difference in the pH of the two solu- tions, this dilution of Milton is often supplied as a Eusol equivalent. Because of its high pH, the diluted solution is stable for several months in unopened containers. Chlorasol (Seton-Prebbles) consists of a solution of sodium hypochlorite containing 0.3 to 0.4% available chlorine, pre- sented in clear 25ml disposable sachets. An unbuffered solu- tion it is stable for eighteen months and has a pH of 11-11.5. Chloramine (B.P.C.) is an organic derivative of chlorine with a bactericidal activity similar to that of the inorgan- ic hypochlorite solutions. It is sometimes used as a 2% so- lution for irrigating wounds and is said to be relatively non-irritant. Chloramine is stable at an alkaline pH but is much more active under acid conditions. A comprehensive study on the stability and irritant proper- ties of a number of hypochlorite solutions has been pub- lished previously.3 Clinical usage of hypochlorites Solutions such as those described above were originally in- troduced for the treatment of infected wounds before antibi- otics or antiseptic agents such as cetrimide and chlorhexi- dine were available. They were used extensively during the first world war and were claimed by Dakin to have a dramatic effect in reducing wound sepsis. However in order to be ef- fective, they had to be used in large volumes. As much as two litres of solution per day were used in some instances, applied either by frequent or continuous irrigation.2 It was noted that when used in this way, hypochlorites had the ad- ditional property of bringing about the rapid dissolution of necrosed tissue - an observation which was confirmed experi- mentally in studies involving necrotic wounds produced on the ears of rabbits.4 It was found that if the affected ears were immersed in a solution of hypochlorite, it was able to remove eschar, secretions and pus. This activity coincided with a loss of available chlorine from the solution. It was also noted that the ears of healthy animals when treated in an similar fashion became intensely inflamed with marked congestion. In this test, Chloramine was found to be markedly less effective than the hypochlorites in removing necrotic material but showed less tendency to cause irrita- tion. With the development of antibiotics and newer and more ef- fective antiseptic solutions, the importance of the hypochlorites was reduced but they continue to be used in the form of packs and wet dressings for their supposed de- briding properties. Laboratory studies carried out on slough and necrotic tissue removed from a pressure sore showed that a single gram of soft slough required in the order of 100ml of a solution containing 0.25% available chlorine to bring about complete dissolution. However, no solubilising activ- ity was detected when a piece of necrotic epidermis was sim- ilarly tested,5 suggesting that hypochlorites will totally ineffective if applied to wounds covered with intact necrot- ic epidermis. A simple calculation will demonstrate that the volume of hypochlorite which would be required to debride a large ul- cer or pressure sore containing several hundred grams of slough would be far in excess of that which can be delivered by the application of wet gauze packs. In order to achieve any significant solubilising effect, it would be necessary to irrigate such a wound with large volumes of solution as recommended by Dakin in 1915. "Sister asked if you have finished with the Eusol, as she is waiting to do the dressings" In recent times it has been demonstrated that dressings such as the hydrocolloids or hydrogels can enhance wound de- bridement.6,7,8 It is thought that they do this by increas- ing the hydration of slough or necrotic tissue which is then removed by autolysis, a process which takes place at the in- terface between the slough and the healthy tissue beneath. It is highly likely that this simple rehydration mechanism is responsible for much of the success claimed for the de- briding action of the hypochlorites solutions rather than any direct chemical action upon the slough itself.5,8 If this is the case, it is probable that simple saline soaks would be almost equally as effective at cleaning the wound, without causing irritation either of the wound itself or of the surrounding skin. At the present time, the author is unaware of any published data which confirms the value of hypochlorite solutions used in the form of wet dressings or packs and anecdotal evidence is all that can be found in their favour. Indeed in one prospective study it was shown that pressure sores treated with with a hypochlorite solution healed significantly more slowly than a matched group of wounds dressed with a hydro- colloid dressing.9 On the negative side however, a number of papers have been published which demonstrate that in in-vitro studies 10,11,12 using cell culture systems and in-vivo experiments with experimental animals,13,14 hypochlorites have a marked and in some cases irreversible effect upon the viability of the test system used. In one study, biochemical and histo- logical examination of the wound site revealed that compared with saline controls, wounds treated with hypochlorite showed an increased inflammatory response and inhibition of collagen development. In a much quoted publication on the management and preven- tion of pressure sores, Barton and Barton 15 have suggested that the use of hypochlorites in common with other antisep- tics and antibiotics used topically can cause the release of endotoxins and other toxic materials from bacteria present in pressure sores which in turn can cause acute oliguric re- nal failure. Fortunately additional reports of this effect are hard to find. In the light of all the available evidence it is difficult to justify the continued use of hypochlorites in wound man- agement save in exceptional circumstances and the burden of proof of its effectiveness must now surely rest with those who wish to continue with its use rather than those who wish to see it discontinued. Hydrogen Peroxide. Hydrogen Peroxide Solution B.P. contains between 5-7% w/v of hydrogen peroxide. This is sometimes known as twenty volume solution as it liberates twenty times its own volume of oxy- gen upon decomposition. Used as a mild cleansing solution, hydrogen peroxide has very limited antibacterial properties in vivo as it is rapidly broken down by the enzyme `cata- lase' which is present in all living tissue. Hydrogen perox- ide appears to be relatively non toxic in animal studies and may be of value in cleansing dirty wounds due to the effer- vescent activity which results from its decomposition. Hy- drogen peroxide solutions should not be used to irrigate closed cavities as there is a danger that oxygen will pass into the blood stream and cause a life threatening embo- lus.16,17 Proflavine. Proflavine is an acridine derivative possessing mild bacte- riostatic activity against Gram-positive organisms but which is almost totally ineffective against Gram-negative bacteria such as Proteus, Pseudomonas and Escherichia coli. Proflavine is generally supplied as a simple solution (Proflavine Solution B.N.F.) or in the form of a water in oil cream (Proflavine Cream B.P.C.) which is often used in conjunction with ribbon gauze for packing wounds. It has been shown in laboratory studies that because of the nature of the formulation, the proflavine, which is concentrated in the aqueous phase of the cream, is not available to exert any significant antimicrobial activity. Also as the cream contains wool fat, a known sensitising agent, there is a possibility that a skin reaction may develop in response to the use of this particular preparation.17 All these facts suggest that proflavine is probably of lim- ited value in wound management and will be unlikely to have any significant beneficial effect upon an infected wound. Cetrimide Cetrimide B.P. is a quaternary ammonium compound, very solu- ble in water, which has the properties and uses which are typical of cationic surfactants. Solutions have pronounced emulsifying and detergent properties and have bactericidal activity against Gram-positive and some Gram-negative organ- isms.19 The combined detergent and antibacterial properties of Cetrimide are of value in solutions used for cleaning dirty or infected wounds and burns where they may be used alone or in combination with chlorhexidine (see below). Cetrimide in solution even in very low concentrations has a marked effect upon fibroblast cells in culture,11 and as a consequence should probably not be used for the routine and repeated cleansing of non infected wounds. Chlorhexidine Chlorhexidine (Hibitane ICI Ltd.) is available in the sever- al forms, but the most commonly used salt is the gluconate which forms the basis of a range of antiseptic solutions. It is active against a wide range of micro-organisms including both Gram-positive and Gram-negative bacteria. Probably the most familiar preparation containing chlorhexidine is Savlon (ICI Ltd) which also contains cetrimide. Savlon is available as a concentrate which is diluted before use containing chlorhexidine gluconate 1.5% w/v and cetrimide 15% w/v. A 1 in 30 dilution is sometimes used in first aid when a wound is physically contaminated with gravel, oil or other foreign material. In these situations the detergent proper- ties of the cetrimide are of great value and assist in the cleansing process. In other wound management situations, sachets containing a 1 in 100 dilution of Savlon are often used. These may be useful when cleansing dirty sloughy ulcers for example. If a wound is clean and granulating with no evidence of infec- tion, the cetrimide may not be required at all and it may be preferable to use a solution of chlorhexidine alone. This is also available in sterile sachets. Alternatively, it might be considered more appropriate to use a sterile solu- tion of isotonic saline for gentle cleaning between dressing changes. The selection of the most appropriate antiseptic or wound cleansing solution for use in any given situation must ulti- mately be the responsibility of the medical and nursing con- cerned, taking account of local wound management policies and recommendations. However it is hoped that these brief notes may be of help when formulating such policies. References 1. An introduction to Milton sterilizing fluid and its use. Richardson-Merrell Ltd. 2. Dakin H.D., On the use of certain antiseptic substances in the treatment of infected wounds, Br. Med. J., 1915, (ii); 318-320. 3. Bloomfield S.F. and Sizer T.J., Eusol BPC and other hypochlorite formulations used in hospitals, Pharm. J. 1985, 235; 153-157. 4. Taylor H.D. and Austin J.H., The solvent action of anti- septics on necrotic tissue, J. Exp. Med., 1918, 27; 155-164. 5. Thomas S, Milton and the treatment of burns,(letter) Pharm. J. 1986, 236; 128-129. 6. Tudhope M., Management of pressure ulcers with a hydro- colloid occlusive dressing; Results in twenty three pa- tients, J. Enterostomal. Ther., 1984, 11; 102-105. 7. Johnson A., Towards rapid tissue healing, Nursing Times, 1984, Nov, 39-43. 8. Thomas S., Pressure points, Community Outlook Suppl., Nursing Times, 1988, 84; 20-22. 9. Gorse G.J. and Messner R.L., Improved pressure sore healing with hydrocolloid dressings, Arch. Dermatol., 1987, 123; 766-771. 10. Brennan S.S. et al., Antiseptic toxicity in wounds healing by secondary intention, J. Hosp. Infec., 1986, 8; 263-267. 11. Thomas S. and Hay N.P., Wound cleansing,(letter) Pharm. J., 1985, 235; 206. 12. Kozol R.A., et al., Effects of sodium hypochlorite (Dakin's Solution on cells of the wound module, Arch. Surg., 1988, 123; 420-423. 13. Brennan S.S. and Leaper D.J., The effect of antiseptics on the healing wound; a study using the the rabbit ear cham- ber, Br. J. Surg., 1985, 72; 780-782. 14. Brennan S.S., et al., Antiseptic toxicity in wounds healing by secondary intention, J. Hosp. Infect., 1986, 8; 263-267. 15. Barton A. and Barton M,. The management and prevention of pressure sores, 1981, Faber and Faber, London. 16. Bassan M.M. et al., Near fatal systemic oxygen embolism due to wound irrigation with hydrogen peroxide, Postgrad. Med. J. 1982, 58; 448-451. 17. Sleigh J.W. and Linter S.P.K., Hazards of hydrogen per- oxide, Brit. Med. J. 1985, 291; 1706. 18. Martindale, The Extra Pharmacopoeia, 27th edition, 1978, Pharmaceutical Press, London. 19. ICI Antiseptics in Practice, ICI Ltd. 1978. Editor's note The views expressed in this review are those of the author based upon a review of the literature together with personal experience of the products concerned but there will doubt- less be others who hold different or contradictory views. Any correspondence on this or any other issue related to wound management would be welcomed and reproduced in the next edition of the `Dressings Times' The Dressings Times is produced by the Welsh Centre for the Quality Control of Sur- gical Dressings, East Glamorgan Hospital, Church Village, Pontypridd, Mid Glamorgan. Telephone No. (0443) 202641.