Normal Saline vs Povidone-iodine as Irrigation Solutions for Laceration Wounds

Dr. Julina Md Noor MBBCh (Wales)

A thesis submitted in partial fulfilment for the degree of Masters in Emergency Medicine 2006/2010

Department of Emergency Medicine Faculty of Medicine University Malaya

Acknowledgement
First and foremost, I thank God for letting me finish writing up this dissertation. This thesis would not have materialized without my supervisor, Prof David Choon Siew Kit, who has guided me through it all, and for that, I am eternally grateful. I would like to express my gratitude towards the staff nurses who have helped me in the data collection, namely SN Hasmah Binti Mohd Tahir and SN Zainun Binti Dollah. Thank you also to Prof Sazaly Bin Abu Bakar, Head of the Microbiology Department, who has allowed me to use his lab facilities. Special thanks to my dear friend, Dr Fadzilah Binti Mohd Nor, who has enlightened me about the world of microbiology. To Dr Mohd Idzwan Zakaria, thank you for being my teacher in emergency medicine, I am forever indebted. Lastly, to the special people in my life: My parents, who are responsible for where I am today. My husband, who had to put up with all my moans and groans, not to mention his unrelentless support in everything that I do. And my children, Muizz, Faizz and Syafa, who made it all worth while.

This study was funded by Postgraduate Research Fund, University Malaya.

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CONTENTS

List of figures List of tables Abstract Chapter 1: Introduction Chapter 2: Objectives Chapter 3: Literature reviews: Solutions for irrigation of 3.1 Povidone-iodine 3.1.1 History 3.1.2 Chemical property 3.1.3 Antimicrobial activity 3.1.4 Effect on wound healing 3.1.5 Toxicity 3.2 Normal Saline Chapter 4: Materials and methods 4.1 Study design 4.2 Setting 4.3 Materials 4.4 Methods 4.5 Inclusion and exclusion criteria 4.6 Statistitcal analysis

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Chapter 5: Results 5.1 Demographic 5.2 Bacterial growth 5.3 Type of organisms Chapter 6: Discussion 6.1 Limitations of study Chapter 7: Conclusion Chapter 8: References Appendix A 20 22 27 34 40 42 43 51

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LIST OF FIGURES
Figure 1: Bernard Courtois, discovered iodine Figure 2: Casamir Davain, French bacteriologist Figure 3: Normal saline and povidone-iodine solutions Figure 4: 1% lignocaine for local anaesthetic and nylon for suturing Figure 5: Suture set Figure 6: Strokes performed on the agar plate Figure 7: Percentage of patients in each group with degree of contamination Figure 8: Graph representing the grade of bacterial count before and after irrigation with normal saline for each individual patient. Figure 9: Graph representing the grade of bacterial count before and after irrigation with povidone-iodine for each individual patient Figure 10: Amount of bacteria before irrigation in both the normal saline and povidoneiodine group Figure 11: Amount of bacteria after irrigation in both the normal saline and povidoneiodine group Figure 12: Type of organism before and after treatment with saline Figure 13: Type of organism before and after treatment with povidone Figure 14: Type of organisms before treatment Figure 15: Type of organisms after irrigation

in

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LIST OF TABLES

Table 1: Summary of Organisms Susceptible to Povidone-Iodine Solutions Table 2: Demographic data and wound characteristics Table 3: Site of wound Table 4: Different type of organisms grown from the wound Table 5: P-value for reductions in grade of bacterial growth and type of organisms grown when povidone is compared with normal saline.

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ABSTRACT
Background: Traumatic laceration is a common presentation to A&E attendance as

pertain to trauma. Bacterial contamination and subsequent infection is the most common complication post surgical repair. Wound irrigation is a critical component in wound management, but there is no general agreement regarding the 'best' antiseptic solution, and the practice varies widely.

Objectives: This study aims to determine whether irrigation of traumatic wound - 1) has any effect on bacterial load, and 2) to determine the better solution for wound irrigation. In this study, povidone-iodine and normal saline was chosen as both are widely used and easily available in our hospital setting.

Methodology: This is a prospective randomized controlled study from August 2008 to February 2009. Patient age more than 18 years old who presented with traumatic simple laeration wound were enrolled in this study and randomized to have normal saline or povidone-iodine as irrigation solution. Wound swab were taken before and after irrigation and analyzed for semi-quantitative bacterial count, culture and sensitivity. Results were analyzed using chi squared analysis for non parametric categorical data.

Results: 101 patients were recruited for this study from the period of August 2008 to February 2009. There was 60 patients in the normal saline group and 40 patients in the povidone-iodine group. Both normal saline and povidone-iodine significantly reduce the bacterial count (p<0.001 for normal saline and p=0.004 for povidone-iodine) and significantly reduce the number of organisms (p<0.001 for normal saline, pO.OOl 1 for

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povidone-iodine). When normal saline is compared to povidone-iodine, it was found that povidone-iodine is more superior to normal saline in reducing the bacterial count (p=0.016).

Conclusion: Irrigating wound with either solution would reduce the bacterial load, but in this study, it was found that povidone-iodine is better than normal saline at reducing it. However, the relationship between the degree of bacterial load and rate of infection cannot be proven because this was not analyze in this study.

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CHAPTER 1: INTRODUCTION

Traumatic laceration is a common presentation to A&E attendance as pertain to trauma. In University Malaya Medical Centre (UMMC), it accounts for 3.2% of 96 000 patients that was seen annually . Bacterial contamination and subsequent infection is the most common complication post surgical repair. The incidence of infections is estimated at between 130% . There is a direct correlation between infection and bacterial counts of more than 105 per gram of tissue8'9.

Wound infection is associated with a variety of factors, e.g. timing of wound closure, presence of foreign bodies, mechanism of injury, host immune response, bacterial inoculums and presence of devitalized tissue. The principles of wound management are: 1) to prevent further bacterial inoculation 2) wound debridement. Wound irrigation is a critical component in wound management. Irrigation removes loose devitalized tissue, particulate matter, and possible infective bacterial inoculum from the wound10. Many studies were done on several aspects of debridement including the volume of fluid, pressure used, antiseptics used and prophylactic antibiotics.

Volume is an important factor; increased volume improves wound cleansing to a point, but the optimal volume is unknown11. Low pressure irrigation removes negligible small particles as well as large particulate matter such as devitalized tissue12. However, when irrigating solutions are applied to the wound bed at high pressure, destruction of vital tissue may occur, and end cosmetic results may be affected12'13. The amount of pressure needed for adequate wound irrigation with minimal damage to vital tissue is approximately 5 to 8

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psi of continuously applied pressure12"14. This is achieved by using 35-60 ml syringes with 19 gauge angiocatheter15.

The prophylactic use of systemic and topical antibiotics remains controversial. Numerous studies have demonstrated the futility of using prophylactic systemic antibiotics in the prevention of infection in accidental wounds2'4. Burke reported that parenteral antibiotics had no effect in preventing infection if administered more than three hours after contamination16.

There are a wide range of antiseptics available including alcohol, hydrogen peroxide, chlorhexidine, hypochlorite (bleach), povidone-iodine and phenols. This aims to kill

bacteria or inhif' their growth. Many of these cause damage to normal living cells. Chlorhexidine, a I guanide, is known to be less toxic to tissues and has high antibacterial activity against both gram positive and gram negative bacteria including some fungi and viruses 7. But it causes damage to new tissues and should not come in contact with the meninges and mucous membranes as this can cause permanent damage. It's antimicrobial efficacy is not total, as certain microbes like Pseudomonas aeruginosa and Proteus mirabilis are known to grow in the solution. Hydrogen peroxide, in 3% (10 volumes) solution is also quite popular. Its use in cleaning superficial trauma wounds has declined since the formation of air emboli was reported18, yet analysis of studies in animals and humans failed to find any negative effects on wound healing. At present there seems to be insufficient evidence to base definitive judgements about the merits of hydrogen peroxide on wound healing19.

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As yet there is no general agreement regarding the 'best' antiseptic solution, and the practice varies widely. Even so, povidone-iodine is possibly one of the antiseptic that is studied most. This may be due to the fact that it is fairly cheap, widely used, established broad spectrum antimicrobial activity, well known chemical and microbiological properties and it is also non-irritating.

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CHAPTER 2: OBJECTIVES

Despite the wide range of antiseptic solution available, povidone-iodine is regarded as the gold standard in our hospital setting. It is used regularly and extensively in the emergency department. The most common commercial form is a 10% solution in water yielding 1% available iodine. Povidone-iodine is available as a surgical scrub or skin cleanser with a detergent base (0.75% available iodine) or in other forms. Numerous studies have been

done on the efficacy of povidone-iodine in surgical wounds, open fractures as well as laceration wounds. Others have compared povidone-iodine with other solution, including normal saline, with conflicting results. Recently studies were done to compare between normal saline and tap water as irrigation solution, raising the question of whether the practice of using povidone-iodine should be abandoned. Since in our department, the use of povidone-iodine is still a standard procedure, we are interested to find out, at least in our setting, whether povidone-iodine has any benefit over normal saline in wound management, and proceed to carry out similar study by comparing povidone-iodine and normal saline.

The objectives of this study are: 1. To determine whether irrigation of traumatic wound has any effect on bacterial load. 2. To determine the better solution for wound irrigation. In this study, povidone-iodine and normal saline was chosen as both are easily available in our hospital setting.

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CHAPTER 3: LITERATURE REVIEWS

3.1 POVIDONE-IODINE

3.1.1 History

Iodine occurs in seaweed as well as various minerals. It was first discovered by 1811 by Bernard Courtois, a French chemist (figure 1). He observed the violet fumes of iodine when treating seaweed (a substitute of willow which had become unavailable during the naval blockade during the Napoleonic Wars) with sulphuric acid while attempting to isolate nitrates for the manufacture of explosives20. From this observations, Courtois suspected that this was a new element but lacked the money to pursue it . Joseph GayLussac than proved that iodine was an element.

Figure 1: Bernard Courtois, discovered iodine.

French physician Jean Lugol introduced an aqueous solution of in 1829, rendering the iodine sufficiently soluble by the additions of two parts potassium iodide for each of iodine22. In 1839, Davies, a physician in Hertford, used an iodine solution to disinfect

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wound,

purpose

for

which

it

was

later

employed

in

American Civil War23. Nevertheless, iodine disinfection failed to gain general acceptance until the 1870s, when the French bacteriologist Casamir Davaine (figure 2) confirmed that iodine solutions could kill a wide variety of microorganisms24.

Figure 2: Casamir Davain, French bacteriologist

Povidone (polyvinylpyrolidone) is a water soluble polymer of widely varying chain length that was developed by IG Farbenindustrie just before the Second World War as a volume expander for the emergency treatment of shock, both on account of its resemblance to bilirubin and its colloidal properties25. Following reports that povidone bound and

detoxified various drugs in a manner similar to that of plasma proteins, Shelanski and Shelanski at the Industrial Toxological Laboratories in Philadelphia investigated its effect on toxic inorganic materials. In the course of formulation with tincture of iodine, they found a unique complex was formed between iodine and povidone and that it was no longer necessary to add solvent or solubelisers in order to dissolve the iodine. In vitro test for antibacterial activity were done and it was noticed that the povidone treated iodine was less toxic to animals than was tincture of iodine. Skin test on volunteers and then test

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involving application to mucous membrane were followed by clinical trials, all of which confirmed the superiority of the product over other iodine formulations26. It was marketed in 1955 with approved name of povidone-iodine, since then it has become the universally preferred iodine disinfectant27.

3.1.2 Chemical property

Polyvinylpyrrolidone-iodine or povidone-iodine is a water soluble compound that results from the combination of molecular iodine and polyvinylpyrrolidone28. These solutions of complexed iodine is called iodophors26. The 10% polyvinylprrolidone-iodine solution generally contains 90% water, 8.5% polyvinylprrolidone, 1% available iodine, and iodide . The free iodine concentration in such a product is typically 1 part per million (ppm) or 0.0001%30. This solution is highly water soluble, has a reddish-brown colour with a pH of approximately 4.5. Since it contains very little free iodine, it is stable, nonstaining, and nonirritating26.

Polyvinylpyrrolidone is a polymer similar to dextran. The molecular weight utilized in povidone-iodine solution ranges from 10 000 to 40 000 daltons31. It is a flexible molecule that may be adequately excreted by the kidney even in high molecular weights, unlike protein of similar weight.

Iodine is complexed by polyvinylpyrrolidone and iodide through a hydrogen bond between two pyrroles32. Although most of the elemental iodine is complexed in association with polyvinylpyrrolidone and iodide, a small amount of free iodine is constantly released, 9

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remains in dynamic equilibrium with the complex, and undergoes the chemical reactions characteristic of iodine until the available iodine is exhausted. The free iodine level is dependent on the concentration of the solution and follows a bell-shaped curve, with levels of 1 ppm in 1 % and 10% polyvinylpyrrolidone-iodine solutions, and a maximum level of 24 ppm in a 0.7% solution31. Dilutions of less than 0.05% lose the polymer complex characteristics of polyvinylpyrrolidone and behave like aqueous iodine solutions . It is the level of free iodine that dictates the activity of the iodophore34.

3.1.3 Antimicrobial activity

Povidone-iodine is a microbicidal agent and acts on a wide variety of bacteria, including anaerobic and sporulated organisms, fungi, protozoa and viruses. Polyvinylpyrrolidone itself does not have any intrinsic antibacterial activity, but by virtue of its affinity to cell membranes, it delivers diatomic free iodine (I2) directly to the bacterial cell surfaces. Delivery of complexed iodine to the sensitive elements of cell membrane seems to be the crucial event of antibacterial action35. Iodine's targets are located in the bacterial cytoplasm and cytoplasmic membrane, and its killing action takes place in a matter of seconds34. In contact with polyvinylpyrrolidone-iodine, sulfhydryl compounds, peptides, proteins, enzymes, vitamin c, lipids, and cytosine are iodinated and oxidated by free iodine, resulting in inactivation of molecules that are essential for biologic viability .

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Table 1: Summary of Organisms Susceptible to Povidone-iodine Solutions'

Gram -ve Bacteria Enterobacter aerogenes Eschericia coli Haemophilus vaginalis Klebsiella pnemoniae Proteus mirabilis (all strain) Pseudomonas aeruginosa Pseudomonas pyocyanea Salmonella typhi Shigella dysenteriae Vibrio comma Gram +ve Bacteria Bacillus subtilis Clostridium perfringens Clostridium tetani Corynebacterium diphtheriae Diphtheroids Diplococcus pneumoniae Staphylococcus albus Staphylococcus aureus (haemolytic) Streptococcus faecalis Streptococcus pyogenes Fungi Aspergillus flavus Candida albicans Crptococcus neoformans Epidermophyton floccosum Nocardia asteroids Protozoa and Other Organisms Entomoeba histolytica Trichomonas vaginalis Treponema pallidum Chlamydia Trachomatis Mycoplasma hominis

Viruses Cytomegalovirus Influenza type A Polio type I, Mahoney and CHAT strains Herpes genitalis Herpes simplex type 1 Rabies Rubella Vaccinia

Acid Fast Bacteria Mycobacterium tuberculosis

Rodeheaver et al studied the bactericidal activity of povidone-iodine in vivo and concluded that though povidone-iodine did not enhance the rate of wound infection, it does not offer therapeutic benefit when compared with control wounds treated with saline solution34.

3.1.4 Effect on wound healing

When using povidone-iodine as irrigation solution, it is not only the bactericidal activity that is observed, but also the effect of povidone-iodine on the tissue itself. Various in vivo animal studies as well as on patients were done to assess this. Gilmore et al in 1977 assess 11

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wound healing macroscopically, histologically and mechanically in rats and found no different compared to the control groups38. They then proceed to clinical trial, using it on clean, non-abdominal operations just before the wound is closed and found no evidence that it caused either excoriation or irritation to the skin. Brennan and Leaper studied the effect of six different antiseptics on wound healing using the rabbi ear chamber39. They reported that povidone-iodine at 5% caused cessation of blood flow, but at a concentration of 1% povidone-iodine solution was innocuous. Viljanto also demonstrated that 5% solution of povidone-iodine interfered at a cellular level with healing, an caused an increased incidence of wound infections when the solutions was instilled as a surgical wound prophylactic40.

3.1.5 Toxicity

This could be local and/or systemic. It has been demonstrated that blastogenesis of human lymphocyte cultures and the viability of granulocytes and monocytes is inhibited by the addition of povidone-iodine41'42. It was also found that povidone-iodine inhibit

chemotaxis which could progress to total arrest of chemotaxis41'43. The toxicity of povidone-iodine at the cellular level is directly proportional to the concentration of the solution utilized40'44.

Systemic toxicity can result from any route. The amount of iodine absorbed will vary according to the concentration of the solution utilized, the number of applications, and the route of administration. The incidence of allergy and contact dermatitis is very low when applied locally on intact skin or mucosa, with 2 allergic reactions in 5000 patients 12

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recorded . In patients with known allergies to various substances including fish and iodine-containing compounds, the incidence of allergic reactions was 2 in 500 applications.

3.2 NORMAL SALINE

Saline is a general term referring to a sterile solution of sodium chloride (salt) in water. Normal saline is the commonly used term for solution of 0.91% w/v of NaCl, Less commonly, this solution is referred to as physiological saline or isotonic saline. The solution is 9 grams of sodium chloride (NaCl) dissolved in 1 litre of water. It contains 154 mEq/L of Na+ and CI", with an osmolarity of 308 mOsmol/L45.

Normal saline has several medical purposes such as intravenous therapy, fluid for bladder, rinse for contact lenses, as well as its use in wound care for irrigating, cleansing and hydrating wounds. It is widely recommended irrigating and wound dressing solution, as it is known to be compatible with human tissue17.

Normal saline does not burn or irritate a wound. It is safe, non-toxic, effective, readily available and inexpensive. It causes no damage to new tissue and does not affect the function of fibroblast and keratinocytes in healing wounds46. The only disadvantage is saline has no antimicrobial property.

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CHAPTER 4: MATERIALS AND METHODS

4.1 Study design

This is a prospective pseudo- randomized controlled study comparing normal saline and povidone-iodine as irrigation solution. The study was approved by the ethical committee of University Malaya Medical Centre. (20th Feb 2008, reference number 637.20).

4.2 Setting

This study was conducted in the Minor Operating Theatre, Emergency Department of University Malaya Medical Centre, an academic tertiary facility with an annual ED cencus of 96 000 patients. Patients age > 18 who presented to the ED with simple traumatic laceration, between August 2008 and February 2009 were enrolled in this study. They were randomised according to the month, alternating between 0.9% normal saline (control group) and 10% povidone-iodine. The procedures were performed by the on duty physicians and to

standardize the procedure, a standard protocol was made available in the minor operating theatre. The procedure was done under aseptic technique. Information was collected regarding patient demographics, site, size and nature of wound and these were recorded in a log book by the physician.

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4.3 Materials

The instruments used in the minor operating theatre for the procedure were as follows: 1. 10 % Povidone-iodine solution 2. 0.9% Normal saline solution 3. 1% Lignocaine solution as local anaesthetic agent 4. Toothed and non-toothed forceps 5. Small Metzenbaum scissors 6. Small artery forceps 7. Small towel clips 8. Small needle holder 9. Small suture scissors 10. Sterile disposable syringes - 5 ml and 50 ml 11. Sterile disposable 24 gauge needles 12. 19G catheter (attached to the 50 ml syringe for irrigation to generate a pressure of around 8 psi) 13. 3-0, 4-0 and 5-0 nylon sutures (depending on the site of laceration wound) 14. Sterile disposable drapes 15. Sterile disposable gauzes 16. Primapore dressing and crepe bandage

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Figure 3: Normal saline and povidone-iodine solutions.

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Figure 4:1% lignocaine for local anaesthetic and nylon for suturing.

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Figure 5: Suture set.

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4.4 Methods

The patient will be lying on the bed and positioned comfortably to get the maximum exposure of the laceration wound on the affected site. First the wound was classified according to the degree of contamination as described by Gravett et al47. 1. Clean - fresh wound without notable debris 2. Debris- contaminated, small amount of debris/dirt in and around the wound 3. Dirty - grossly contaminated older wounds, large amount of dirt and debris, or wounds occuring in a dirty environment. Then a swab sample was taken at the centre of the laceration wound. The wound and the surrounding area of the affected site were cleaned and draped. Local anaesthesia (1% lignocaine) was given until the patient was pain-free and according to the attending physician's judgement. The wound was then irrigated with at least 100ml of the studied solution. During the irrigation, any debris and devitalized tissues were removed. Once the physician was satisfied with the debridement, another swab sample was taken after the irrigation. The wound was closed with interrupted sutures using nylon. Dressing was done using a primapore dressing and crepe bandage if necessary. Aseptic technique was observed throughout the procedure.

All patients were discharged from the emergency department with oral analgesia (Paracetamol lgm QID or Diclofenac 75mg BD). The prescription of oral antibiotics (Cloxacillin 500mg QID) were up to the physician's jurisdiction. They were advised to go to the nearest clinic two days post-operatively for wound inspection and change of dressing. The sutures were removed between 7-14 days post-operatively at the nearest clinic depending on the site. 17

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The swab samples were sent to the microbiology laboratory in UMMC for semi quantitative assessment of the organism, as well as culture and sensitivities. The samples are cultured using blood and Mac Conkey Agar. It is incubated for 18-48 hours in 5% CO2 concentration48. The inoculum from the clinical material or another plate is first spread out in the form of a primary inoculum, seen in figure 6, which is also called as 'well-inoculum' or only 'well'. The successive series of strokes, B, C, D and E are made with the loop sterilized between each sequence. At each step the inoculum is derived from the most distal part of the immediately preceding strokes so as to gradually reduce the number of bacteria . This helps in obtaining isolated colonies.

Figure 6: Strokes performed on the agar plate .

After 48 hours, if there is no growth, it will be reported as nil. The amount of bacteria grown is base on how many streaks that have organism on them. Therefore, when reading the agar plate48: 1. Scanty growth, organism grown on B only 2. Moderate growth, organism grown on B and C 3. Heavy growth, where organism found on all 3 streaks.

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