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Search for a nontoxic surgical scrub solution for periorbital lacerations
ORIGINAL CONTRIBUTION laceration, periorbital, cleansing agent; periorbital laceration, cleansing agent; surgical scrub, periorbital laceration
Search for a Nontoxic Surgical Scrub Solution for Periorbital Lacerations The purpose of this study was to identify a skin wound cleanser that could be used safely to cleanse lacerations of the periorbital region. The irritation and toxicity to the eye of the commercially available skin wound cleansers were quantitated using numerical values and weights for the ocular lesions in experimental animals. Shut Clens ® did not elicit lesions in experimental animals or in a series of 20 patients with periorbital lacerations. On the basis of this study, Shur Clens ® is recommended as a safe skin wound cleanser for periorbital lacerations. [Bryant CA, Rodeheaver GT,, Reem EM, Nichter LS, Kenney JG, Edlich RF: Search for a nontoxic surgical scrub solution for periorbital lacerations. Arm Emerg Med May 1984;13:317-321.]
INTRODUCTION Recommendations for immediate care of soft tissue injuries include cleansing the area surrounding the wound and the wound itself. Practices vary considerably in selection and use of the cleansing agent. Many emergency physicians use commercially available skin wound cleansers for cleansing the skin and the wound. Other physicians, suspicious about possibly deleterious effects exerted by these agents on the wound, use a cleanser for the skin and irrigate the wound using a high-pressure irrigation assembly. 1 In periorbital lacerations (ie, those of the forehead, eyebrow, eyelid), the physician usually protects the patient's eyes from contact with skin wound deansers because the cleansers may cause ocular lesions. In an effort to isolate the patient's eye from the skin wound cleansing agent, the physician may pay more attention to shielding the eyes than to cleansing the wound. The potential consequences of skin wound cleansers on the eye have never been studied. For that reason, we initiated an experimental and clinical study to quantitate the severity of ocular lesions resulting from skin wound cleansers. The study was expanded to search for new skin wound cleansers for use in contaminated wounds.
Carol A Bryant, MD George T Rodeheaver, PhD Evelyn M Reem Larry S Nichter, MD John G Kenney, MD Richard F Edlich, MD, PhD Charlottesville, Virginia From the Department of Plastic Surgery and the Emergency Medical Service, University of Virginia School of Medicine, Charlottesville, Virginia. Presented at the University Association for Emergency Medicine Annual Meeting in Boston, June 1983. Received for publication June 13, 1983. Revision received September 21, 1983. Accepted for publication November 8, 1983. Address for reprints: Richard F Edlich, MD, PhD, Department of Plastic and Maxillofacial Surgery, University of Virginia Medical Center, Box 376, Charlottesville, Virginia 22908.
MATERIALS AND METHODS A skin wound cleanser is designed to aid removal of bacteria and other contaminants from superficial wounds by its cleansing activity. Such a product contains a synthetic detergent, but may or may not contMn an antimicrobial agent. Four skin wound cleansers are commonly used by emergency physicians to cleanse lacerations. PHisoHex ® (Winthrop Laboratories) is an antibacterial sudsing emulsion. It contains a colloidal dispersion of hexachlorophene 3% {w/v) in a stable emulsion consisting of entsufon sodium, petrolatum, lanolin cholesterols, methylcelhilose, polyethylene glycol, polyethylene glycol monostearate, lauryl myristyl diethanolamide, sodium benzoate and water. Entsufon sodium is a synthetic detergent [sodium octylphenoxy-ethoxyethyl ether sulfonate). The antimicrobial properties of hexachlorophene are directed predominantly against Gram-positive bacteria; its effect on Gram-negative bacteria is weak. Hibiclens ® (Stuart Pharmaceuticals I contains 4% chlorhexidine gluconate and 4% isopropyl alcohol in a mild sudsing base {poloxamer) adjusted to pH 5.0 to 6.5. Its antiseptic activity is effective against a wide range of microorganisms, including Gram-positive bacteria and Gram-negative bacteria. A fragrance has also been added to this skin wound cleanser.
13:5 May 1984
Annals of Emergency Medicine
317/25
NONTOXIC SURGICAL SCRUB Edlich et al
Betadine ® (Purdue Frederick) surgical scrub solution contains 7.5% polyvinylpyrrolidone-iodine with 0.75 % free iodine as well as an anionic detergent. This combination of iodine and a solubilizing agent slowly liberates or releases free iodine when diluted w i t h water, and is called an iodophor (iodo-iodine, and phor-carrier). Iodine is essentially bactericidal over a wide pH range against a broad s p e c t r u m of pathogens, including most bacteria, fungi, viruses, protozoa, and even spores of bacteria and fungi. Shur Clens ® (Biosyntec, Inc) is a new skin wound cleanser that contams 20% poloxamer 188. This polyol contains 80% ethylene oxide content by weight with an average molecular weight of 8,350. It is a nonionic detergent that does not display antibacterial activity. The exact c o m p o s i t i o n and concentration of the components in Betadine ® surgical scrub solution, Hibiclens ®, and p H i s o H e x ® were not identified by the manufacturers because this information is considered to be proprietary. In the case of Shur Clens*, the manufacturer indicated that it contains 20% poloxamer 188 as its only ingredient. Due to the limited information regarding the composition of three of the surgical scrub solutions, they are referred to in the article by their trade names.
TABLE. Scale of weighted scores for grading the severity of ocular lesions Cornea
A
B
Score = A x B x 5
26/318
1 2 3 4 1 2 3 4
Total m a x i m u m = 80
Iris
A
Values Folds above normal, congestion, swelling, circumcorneal injection (any one or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) . . . . . . . . . . . . No reaction to light, hemorrhage; gross destruction (any one or all of these) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Score = A x 5
1 2
Total m a x i m u m = 10
Conjunctivae
A
B
Experimental Study A standard and easily reproducible quantitative objective test to measure the irritation and toxicity of substances applied to the mucous membranes of the eye of experimental animals was devised by Draize, Woodard, and Calvery.2 To transform qualitative observations of physiological effects to reasonably quantitative measurements, and to obtain data easily subjected to arithmetical interpretation, they assigned numerical values and weights to ocular lesions. Injuries to the cornea, conjunctival and palpebral mucosae, and the iris were scored separately. Fluorescein dye was used to detect epithelial injury to the cornea. In testing the surgical scrub solution, 0.2 mL of each solution was instilled separately into the conjunctival sacs of New Zealand white rabbits. Trained examiners, who were unaware of the treatments, examined the rabbits' eyes at 1, 24, and 48 hours alter instillation of the agents into the eye and graded the ocular lesions according to the scale outlined (Table). The
O p a c i t y - - Degree of Density (area that is most dense is taken for reading) Scattered or diffuse area, details of iris clearly visible . . . . . . . . . . . . . . Easily discernible translucent areas, details of iris slightly obscured . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Opalescent areas, no details of iris visible, size of pupil barely discernible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Opaque, iris visible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Area of Cornea Involved One quarter (or less) but not zero . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Greater than one quarter, less than one half . . . . . . . . . . . . . . . . . . . . . . Greater than one half, less than three quarters . . . . . . . . . . . . . . . . . . . . Greater than three quarters, up to whole area . . . . . . . . . . . . . . . . . . . . .
C
Redness (refers to palpebral conjunctivae only) Vessels definitely injected above normal . . . . . . . . . . . . . . . . . . . . . . . . . . More diffuse, deeper crimson red; individual vessels not easily discernible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diffuse beefy red . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 3
Chemosis A n y swelling above normal (includes nictitating membrane) . . . . . . . . . Obvious swelling with partial eversion of the lids . . . . . . . . . . . . . . . . . . Swelling with lids about half closed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Swelling with lids about half closed to completely closed . . . . . . . . . .
1 2 3 4
1
Discharge Any amount different from normal (does not include small amount observed in inner canthus of normal animals) . . . . . . . . . . . . Discharge with moistening of the lids and hairs just adjacent in the lids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discharge with moistening of the lids and considerable area around the eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Score = (A + B + C) x 2
statistical significance of the irritation scores for the different t r e a t m e n t groups was compared using the Student's t test. Clinical Study Twenty patients w i t h periorbital lacerations (ie, forehead, eyebrow, eyelid) were included in this study. Prior to wound cleansing, each wound was anesthetized with 1% lidocaine hydrochloride using infihration anesthesia. An Opripore ® sponge that was soaked in undiluted Shur Clens ~ was used to Annals of Emergency Medicine
1 2 3
Total m a x i m u m = 20
wash each wound to remove dirt and bacteria. This mechanical scrub usually lasted approximately three minutes. I n a d v e r t e n t spillage of Shut Clens ® into the eye was encountered in each patient. No effort was made to remove this surfactant from the patient's eye. The wound edges of the lacerations were approximated by interrupted monofilament 5'0 nylon sutures. The physician examined the patient's eyes for ocular lesions at 24 hours alter injury and at the time of suture removal using fluorescein dye 13:5 May 1984
Maximum Score Hours 110
89 86
100-
+ 4 +5
79 80 80 90-
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Shur Clens ®
Betadine ®
1
24 48
Hibiclens ®
1
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pHisoHex ®
Assessment of the Effect of Amphoteric Detergents on the Wound's Resistance to Infection
(S aureus 105) 0.9% Sodium Chloride Amphoteric Detergents Anion Basic Nitrogen Atom Dicarboxylate Carboxylate 100
P < .05
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13:5 May 1984
to demonstrate epithelial injury or denudation of the cornea.
Toxicity of Detergents in Shampoos
60-
0 Hours
Fig. 1. Severity of ocular lesions resulting from skin wound cleansers. Fig. 2. Amphoteric detergents potentiated the development of infection in contaminated wounds.
,xxx\\\\,
~ 75% ,~
Amphoteric Detergent
Control
Amphoteric Detergent 2
Annals of Emergency Medicine
The experimental study was expanded to search for a new skin wound cleanser for use in contaminated wounds. Because eye irritation appears to correlate with wound toxicity, several commercially available detergents in shampoos that are supposedly nonirritating to the eye were evaluated as skin wound cleansers. Claims of their innocuous effects on the eyes appear prominently on their bottles. This group of shampoos contains either anionic or amphoteric detergents. To test their potential as skin wound cleansers, we examined the effect of these detergents on the wound's ability to resist Lrdection in a standardized experimental model. 3 Male Hartley guinea pigs weighing between 300 g and 350 g were anesthetized using an intraperitoneal injection of sodium pentobarbital (33 mg/kg). The dorsal hair on each animal was clipped and the skin was depilated with Surgex ®. The skin was washed with water and treated with an iodophor solution followed by 70% ethyl alcohol. Two standardized paravertebral incisions were made in each guinea pig. The wounds, measuring 3 cm in length, extended through the panniculus camosus. All wounds in each animal were then contaminated with 0.1 mL of 0.9% sodium chloride containing l0 s Staphylococcus aureus (American Type Culture Collection 12,600, Rockville, MD). Five minutes after contamination, the animals were divided into four groups. One wound in each animal was subjected to 0.1 mL of either an amphoteric or an anionic detergent, while the contralatera~ wound was treated with 0.1 mL o f 0.9% saline serving as control. Five minutes later, the wounds were closed with microporous tape and the animals were bandaged. On the fourth postoperative day, the inflammatory responses of the wounds were measured. Each wound was opened and examined for evidence of purulent exudate. Bacteri319/27
NONTOXIC SURGICAL SCRUB Edlich et al
Fig. 3. The infection rate of contaminated wounds subjected to anionic detergents was significantly higher than that of the control wounds.
Assessment of the Effect of Anionic Detergents on the Wound's Resistance to Infection (S
ologic cultures of each wound were recorded. The statistical significance of the gross infection score was determined by the sign test. RESULTS Following topical application of the skin wound cleansers into the conjunctival sacs, the severity of injury to the cornea, conjunctival and palpebral mucosae, and iris were graded separately at 1, 24, and 48 hours using a scale of weighted scores. In this test, 110 is the maximum total score for the most severe ocular lesions; 0 is the lowest score (Figure 1). Within one hour after topical application of the skin wound cleansers to the conjunctival sac, Betadine ® surgical scrub solution, Hibiclens ®, and pHisoHex ® elicited irritation scores of 59 +- 3, 79 +- 7, and 75 -+ 5, respectively. For Betadine ® surgical scrub solution and Hibiclens ®, the irritation scores remained relatively constant for the duration of the experiment. In pHisoHex®-treated animals, the irritation score increased significantly, to 89 -+ 4 at 24 hours and 86 -+ 5 at 48 hours. In contrast, the irritation scores for Shut Clens ® were 0 throughout the study. At 1, 24, and 48 hours after exposure to Betadine ® surgical scrub solution, Hibiclens% and pHisoHex% fluorescein dye confirmed the evidence of epithelial injury to the cornea. In rabbit eyes exposed to Shur Clens ®, no corneal epithelial injury was detected with the fluorescein dye. Inadvertent spilling of Shur Clens ® into the eyes of 20 patients with periorbital lacerations did not result In an inflammatory response in any patient. When this nonionic surfactant gained access into the conjunctival sac, the solution did not elicit any symptoms. Consequently we made no attempt to remove the solution from the patient's eye. Twenty-four hours after exposure of the eye to Shut Clens ®, as well as at the time of suture removal, the patient had no sign of corneal lesions as evidenced by the fluorescein stain. Other surfactants that are considered to be innocuous to the mucous membranes of the eyes were found to damage wound defenses, inviting the development of infection. In contaminated w o u n d s subjected to either 28/320
aureus
105)
0.9% Sodium Chloride Anionic Detergents Hydrophilic Group
100 -
P < .01
Hydrophobic Group
[Na] +
[AIkyl Benzene Sulfonate]-
[Na] +
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60
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50
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\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \
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Anionic Detergent
amphoteric or anionic detergents, the incidence of infection was significandy greater than that of the contralateral control wound subjected to a similar level of bacterial contamination [Figures 2 and 3). The bacteria recovered from the infected wounds were the same as the original bacterial inocula.
DISCUSSION Shur C l e n s ® is a s k i n w o u n d cleanser that has been approved by the Food and Drug Administration for use in man. 4 Mechanical cleansing of contaminated wounds with an Optipore ® sponge soaked in this surfactant has been shown to prevent the developm e n t of infection, s Its therapeutic merit was associated with the absence of local and systemic toxic manifestation. Exposure of blood to Shut Clens ® did not alter its cellular components, s It is biologically inert, with more than 60% of the surfactant being excreted within one hour following intravenous administration. 6 Annals of Emergency Medicine
Control
Anionic Detergent
Furthermore, our clinical and experimental studies demonstrate that it did not elicit irritation to the eye. This finding suggests that it is an ideal skin wound cleanser for periorbital lacerations. In contrast, Betadine ® surgical scrub solution, Hibiclens ®, and pHisoHex ® elicited marked ocular lesions. These deleterious effects correlate with their damaging effects on wound resistance to infection as well as on the cellular components of blood.5, 7 On the basis of these findings, we recommend that these skin wound cleansers not be used in periorbital lacerations. In our search for new, safe skin wound cleansers, we investigated the potential toxicity of detergents used in shampoos that are considered to be harmless to the human eye. Our experimental study demonstrated that this group of amphoteric and anionic detergents damaged the host defenses and invited the development of infection. These findings were surprising in light of the advertising claims for 13:5 May 1984
these products. Even if their claims can be confirmed by carefully controlled e x p e r i m e n t a l studies, these suffactants have no potential therapeutic merit as skin wound cleansers. An alternate approach to cleansing periorbital lacerations is to e m p l o y high-pressure syringe irrigation with 0.9% sodium chloride. 1 T h e advantage of this technique is that it can successfully cleanse t h e w o u n d of small particulate matter, bacteria, and soil infection p o t e n t i a t i n g factors, thereby reducing the infection rate of experimentally contaminated wounds. During wound cleansing, inadvertent spilling of 0.9% sodium chloride into the eye does not cause ocular injuries. Despite these advantages of high-pressure syringe irrigation, several objections have been raised about its routine use in periorbital lacerations. First, the irrigant solution disseminates deeply into the pefiorbital tissue and causes considerable edema. Second, 0.9% saline is not a surfactant and cannot solubilize grease and oils in the periorbital region. Consequent-
13:5 May 1984
ly we prefer mechanical cleansing of periorbital lacerations with an Optipore ¢ sponge soaked in Shur Clens ®, rather than high-pressure syringe irrigation with 0.9% saline.
SUMMARY Shut Clens ® is a nonionic detergent that can be used safely to cleanse periorbital lacerations. Topical application of this skin cleanser to the eyes of experimental animals and h u m a n beings did not elicit ocular lesions. In contrast, Betadine ® surgical scrub solution, H i b i c l e n s ®, a n d p H i s o H e x ® caused marked irritation to the eyes of e x p e r i m e n t a l a n i m a l s and should, therefore, n o t be u s e d in h u m a n beings to cleanse pcriorbital lacerations.
REFERENCES 1. Stevenson TR, Thacker JG, Rodeheaver GT, et al: Cleansing the traumatic wound by high pressure syringe irrigation. JACEP 1976;5:17-21.
Annals of Emergency Medicine
2. Draize JH, Woodard G, Calvery HO: Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes, f Pharm Exp Ther 1944;82:377-390. 3. Edlich RE Tsung MS, Rogers W, ct al: Studies in the management of the contaminated wound. I. Techniques of closure of such wounds together with a note on a reproducible model. J Surg Res 1968~8:585-592. 4. O-T-C topical antimicrobial products: Over the counter drug generally recognized as safe, effective and not misbranded. Fed Reg 1978;43:1210-1249. 5. Rodeheaver GT, Kurtz L, Kircher BJ, et al: Pluronic F-68: A promising new skin wound cleanser. Ann Emerg Med 1980;9: 572-576. 6. Geyer RP: The biliary excretion of components of intravenous fat emulsions by the rat. A m J Clin Nutr 1965~16: 146-150. 7. Custer J, Edlich RF, Prusak M, et ah Studies in the management of the contaminated wound. V. An assessment of effectiveness of pHisoHex and Betadine surgical scrub solutions. A m J Surg 1971; 121:572-575.
321/29
Search for a Nontoxic Surgical Scrub Solution for Periorbital Lacerations The purpose of this study was to identify a skin wound cleanser that could be used safely to cleanse lacerations of the periorbital region. The irritation and toxicity to the eye of the commercially available skin wound cleansers were quantitated using numerical values and weights for the ocular lesions in experimental animals. Shut Clens ® did not elicit lesions in experimental animals or in a series of 20 patients with periorbital lacerations. On the basis of this study, Shur Clens ® is recommended as a safe skin wound cleanser for periorbital lacerations. [Bryant CA, Rodeheaver GT,, Reem EM, Nichter LS, Kenney JG, Edlich RF: Search for a nontoxic surgical scrub solution for periorbital lacerations. Arm Emerg Med May 1984;13:317-321.]
INTRODUCTION Recommendations for immediate care of soft tissue injuries include cleansing the area surrounding the wound and the wound itself. Practices vary considerably in selection and use of the cleansing agent. Many emergency physicians use commercially available skin wound cleansers for cleansing the skin and the wound. Other physicians, suspicious about possibly deleterious effects exerted by these agents on the wound, use a cleanser for the skin and irrigate the wound using a high-pressure irrigation assembly. 1 In periorbital lacerations (ie, those of the forehead, eyebrow, eyelid), the physician usually protects the patient's eyes from contact with skin wound deansers because the cleansers may cause ocular lesions. In an effort to isolate the patient's eye from the skin wound cleansing agent, the physician may pay more attention to shielding the eyes than to cleansing the wound. The potential consequences of skin wound cleansers on the eye have never been studied. For that reason, we initiated an experimental and clinical study to quantitate the severity of ocular lesions resulting from skin wound cleansers. The study was expanded to search for new skin wound cleansers for use in contaminated wounds.
Carol A Bryant, MD George T Rodeheaver, PhD Evelyn M Reem Larry S Nichter, MD John G Kenney, MD Richard F Edlich, MD, PhD Charlottesville, Virginia From the Department of Plastic Surgery and the Emergency Medical Service, University of Virginia School of Medicine, Charlottesville, Virginia. Presented at the University Association for Emergency Medicine Annual Meeting in Boston, June 1983. Received for publication June 13, 1983. Revision received September 21, 1983. Accepted for publication November 8, 1983. Address for reprints: Richard F Edlich, MD, PhD, Department of Plastic and Maxillofacial Surgery, University of Virginia Medical Center, Box 376, Charlottesville, Virginia 22908.
MATERIALS AND METHODS A skin wound cleanser is designed to aid removal of bacteria and other contaminants from superficial wounds by its cleansing activity. Such a product contains a synthetic detergent, but may or may not contMn an antimicrobial agent. Four skin wound cleansers are commonly used by emergency physicians to cleanse lacerations. PHisoHex ® (Winthrop Laboratories) is an antibacterial sudsing emulsion. It contains a colloidal dispersion of hexachlorophene 3% {w/v) in a stable emulsion consisting of entsufon sodium, petrolatum, lanolin cholesterols, methylcelhilose, polyethylene glycol, polyethylene glycol monostearate, lauryl myristyl diethanolamide, sodium benzoate and water. Entsufon sodium is a synthetic detergent [sodium octylphenoxy-ethoxyethyl ether sulfonate). The antimicrobial properties of hexachlorophene are directed predominantly against Gram-positive bacteria; its effect on Gram-negative bacteria is weak. Hibiclens ® (Stuart Pharmaceuticals I contains 4% chlorhexidine gluconate and 4% isopropyl alcohol in a mild sudsing base {poloxamer) adjusted to pH 5.0 to 6.5. Its antiseptic activity is effective against a wide range of microorganisms, including Gram-positive bacteria and Gram-negative bacteria. A fragrance has also been added to this skin wound cleanser.
13:5 May 1984
Annals of Emergency Medicine
317/25
NONTOXIC SURGICAL SCRUB Edlich et al
Betadine ® (Purdue Frederick) surgical scrub solution contains 7.5% polyvinylpyrrolidone-iodine with 0.75 % free iodine as well as an anionic detergent. This combination of iodine and a solubilizing agent slowly liberates or releases free iodine when diluted w i t h water, and is called an iodophor (iodo-iodine, and phor-carrier). Iodine is essentially bactericidal over a wide pH range against a broad s p e c t r u m of pathogens, including most bacteria, fungi, viruses, protozoa, and even spores of bacteria and fungi. Shur Clens ® (Biosyntec, Inc) is a new skin wound cleanser that contams 20% poloxamer 188. This polyol contains 80% ethylene oxide content by weight with an average molecular weight of 8,350. It is a nonionic detergent that does not display antibacterial activity. The exact c o m p o s i t i o n and concentration of the components in Betadine ® surgical scrub solution, Hibiclens ®, and p H i s o H e x ® were not identified by the manufacturers because this information is considered to be proprietary. In the case of Shur Clens*, the manufacturer indicated that it contains 20% poloxamer 188 as its only ingredient. Due to the limited information regarding the composition of three of the surgical scrub solutions, they are referred to in the article by their trade names.
TABLE. Scale of weighted scores for grading the severity of ocular lesions Cornea
A
B
Score = A x B x 5
26/318
1 2 3 4 1 2 3 4
Total m a x i m u m = 80
Iris
A
Values Folds above normal, congestion, swelling, circumcorneal injection (any one or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) . . . . . . . . . . . . No reaction to light, hemorrhage; gross destruction (any one or all of these) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Score = A x 5
1 2
Total m a x i m u m = 10
Conjunctivae
A
B
Experimental Study A standard and easily reproducible quantitative objective test to measure the irritation and toxicity of substances applied to the mucous membranes of the eye of experimental animals was devised by Draize, Woodard, and Calvery.2 To transform qualitative observations of physiological effects to reasonably quantitative measurements, and to obtain data easily subjected to arithmetical interpretation, they assigned numerical values and weights to ocular lesions. Injuries to the cornea, conjunctival and palpebral mucosae, and the iris were scored separately. Fluorescein dye was used to detect epithelial injury to the cornea. In testing the surgical scrub solution, 0.2 mL of each solution was instilled separately into the conjunctival sacs of New Zealand white rabbits. Trained examiners, who were unaware of the treatments, examined the rabbits' eyes at 1, 24, and 48 hours alter instillation of the agents into the eye and graded the ocular lesions according to the scale outlined (Table). The
O p a c i t y - - Degree of Density (area that is most dense is taken for reading) Scattered or diffuse area, details of iris clearly visible . . . . . . . . . . . . . . Easily discernible translucent areas, details of iris slightly obscured . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Opalescent areas, no details of iris visible, size of pupil barely discernible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Opaque, iris visible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Area of Cornea Involved One quarter (or less) but not zero . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Greater than one quarter, less than one half . . . . . . . . . . . . . . . . . . . . . . Greater than one half, less than three quarters . . . . . . . . . . . . . . . . . . . . Greater than three quarters, up to whole area . . . . . . . . . . . . . . . . . . . . .
C
Redness (refers to palpebral conjunctivae only) Vessels definitely injected above normal . . . . . . . . . . . . . . . . . . . . . . . . . . More diffuse, deeper crimson red; individual vessels not easily discernible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diffuse beefy red . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 3
Chemosis A n y swelling above normal (includes nictitating membrane) . . . . . . . . . Obvious swelling with partial eversion of the lids . . . . . . . . . . . . . . . . . . Swelling with lids about half closed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Swelling with lids about half closed to completely closed . . . . . . . . . .
1 2 3 4
1
Discharge Any amount different from normal (does not include small amount observed in inner canthus of normal animals) . . . . . . . . . . . . Discharge with moistening of the lids and hairs just adjacent in the lids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discharge with moistening of the lids and considerable area around the eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Score = (A + B + C) x 2
statistical significance of the irritation scores for the different t r e a t m e n t groups was compared using the Student's t test. Clinical Study Twenty patients w i t h periorbital lacerations (ie, forehead, eyebrow, eyelid) were included in this study. Prior to wound cleansing, each wound was anesthetized with 1% lidocaine hydrochloride using infihration anesthesia. An Opripore ® sponge that was soaked in undiluted Shur Clens ~ was used to Annals of Emergency Medicine
1 2 3
Total m a x i m u m = 20
wash each wound to remove dirt and bacteria. This mechanical scrub usually lasted approximately three minutes. I n a d v e r t e n t spillage of Shut Clens ® into the eye was encountered in each patient. No effort was made to remove this surfactant from the patient's eye. The wound edges of the lacerations were approximated by interrupted monofilament 5'0 nylon sutures. The physician examined the patient's eyes for ocular lesions at 24 hours alter injury and at the time of suture removal using fluorescein dye 13:5 May 1984
Maximum Score Hours 110
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Assessment of the Effect of Amphoteric Detergents on the Wound's Resistance to Infection
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13:5 May 1984
to demonstrate epithelial injury or denudation of the cornea.
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Fig. 1. Severity of ocular lesions resulting from skin wound cleansers. Fig. 2. Amphoteric detergents potentiated the development of infection in contaminated wounds.
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Annals of Emergency Medicine
The experimental study was expanded to search for a new skin wound cleanser for use in contaminated wounds. Because eye irritation appears to correlate with wound toxicity, several commercially available detergents in shampoos that are supposedly nonirritating to the eye were evaluated as skin wound cleansers. Claims of their innocuous effects on the eyes appear prominently on their bottles. This group of shampoos contains either anionic or amphoteric detergents. To test their potential as skin wound cleansers, we examined the effect of these detergents on the wound's ability to resist Lrdection in a standardized experimental model. 3 Male Hartley guinea pigs weighing between 300 g and 350 g were anesthetized using an intraperitoneal injection of sodium pentobarbital (33 mg/kg). The dorsal hair on each animal was clipped and the skin was depilated with Surgex ®. The skin was washed with water and treated with an iodophor solution followed by 70% ethyl alcohol. Two standardized paravertebral incisions were made in each guinea pig. The wounds, measuring 3 cm in length, extended through the panniculus camosus. All wounds in each animal were then contaminated with 0.1 mL of 0.9% sodium chloride containing l0 s Staphylococcus aureus (American Type Culture Collection 12,600, Rockville, MD). Five minutes after contamination, the animals were divided into four groups. One wound in each animal was subjected to 0.1 mL of either an amphoteric or an anionic detergent, while the contralatera~ wound was treated with 0.1 mL o f 0.9% saline serving as control. Five minutes later, the wounds were closed with microporous tape and the animals were bandaged. On the fourth postoperative day, the inflammatory responses of the wounds were measured. Each wound was opened and examined for evidence of purulent exudate. Bacteri319/27
NONTOXIC SURGICAL SCRUB Edlich et al
Fig. 3. The infection rate of contaminated wounds subjected to anionic detergents was significantly higher than that of the control wounds.
Assessment of the Effect of Anionic Detergents on the Wound's Resistance to Infection (S
ologic cultures of each wound were recorded. The statistical significance of the gross infection score was determined by the sign test. RESULTS Following topical application of the skin wound cleansers into the conjunctival sacs, the severity of injury to the cornea, conjunctival and palpebral mucosae, and iris were graded separately at 1, 24, and 48 hours using a scale of weighted scores. In this test, 110 is the maximum total score for the most severe ocular lesions; 0 is the lowest score (Figure 1). Within one hour after topical application of the skin wound cleansers to the conjunctival sac, Betadine ® surgical scrub solution, Hibiclens ®, and pHisoHex ® elicited irritation scores of 59 +- 3, 79 +- 7, and 75 -+ 5, respectively. For Betadine ® surgical scrub solution and Hibiclens ®, the irritation scores remained relatively constant for the duration of the experiment. In pHisoHex®-treated animals, the irritation score increased significantly, to 89 -+ 4 at 24 hours and 86 -+ 5 at 48 hours. In contrast, the irritation scores for Shut Clens ® were 0 throughout the study. At 1, 24, and 48 hours after exposure to Betadine ® surgical scrub solution, Hibiclens% and pHisoHex% fluorescein dye confirmed the evidence of epithelial injury to the cornea. In rabbit eyes exposed to Shur Clens ®, no corneal epithelial injury was detected with the fluorescein dye. Inadvertent spilling of Shur Clens ® into the eyes of 20 patients with periorbital lacerations did not result In an inflammatory response in any patient. When this nonionic surfactant gained access into the conjunctival sac, the solution did not elicit any symptoms. Consequently we made no attempt to remove the solution from the patient's eye. Twenty-four hours after exposure of the eye to Shut Clens ®, as well as at the time of suture removal, the patient had no sign of corneal lesions as evidenced by the fluorescein stain. Other surfactants that are considered to be innocuous to the mucous membranes of the eyes were found to damage wound defenses, inviting the development of infection. In contaminated w o u n d s subjected to either 28/320
aureus
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amphoteric or anionic detergents, the incidence of infection was significandy greater than that of the contralateral control wound subjected to a similar level of bacterial contamination [Figures 2 and 3). The bacteria recovered from the infected wounds were the same as the original bacterial inocula.
DISCUSSION Shur C l e n s ® is a s k i n w o u n d cleanser that has been approved by the Food and Drug Administration for use in man. 4 Mechanical cleansing of contaminated wounds with an Optipore ® sponge soaked in this surfactant has been shown to prevent the developm e n t of infection, s Its therapeutic merit was associated with the absence of local and systemic toxic manifestation. Exposure of blood to Shut Clens ® did not alter its cellular components, s It is biologically inert, with more than 60% of the surfactant being excreted within one hour following intravenous administration. 6 Annals of Emergency Medicine
Control
Anionic Detergent
Furthermore, our clinical and experimental studies demonstrate that it did not elicit irritation to the eye. This finding suggests that it is an ideal skin wound cleanser for periorbital lacerations. In contrast, Betadine ® surgical scrub solution, Hibiclens ®, and pHisoHex ® elicited marked ocular lesions. These deleterious effects correlate with their damaging effects on wound resistance to infection as well as on the cellular components of blood.5, 7 On the basis of these findings, we recommend that these skin wound cleansers not be used in periorbital lacerations. In our search for new, safe skin wound cleansers, we investigated the potential toxicity of detergents used in shampoos that are considered to be harmless to the human eye. Our experimental study demonstrated that this group of amphoteric and anionic detergents damaged the host defenses and invited the development of infection. These findings were surprising in light of the advertising claims for 13:5 May 1984
these products. Even if their claims can be confirmed by carefully controlled e x p e r i m e n t a l studies, these suffactants have no potential therapeutic merit as skin wound cleansers. An alternate approach to cleansing periorbital lacerations is to e m p l o y high-pressure syringe irrigation with 0.9% sodium chloride. 1 T h e advantage of this technique is that it can successfully cleanse t h e w o u n d of small particulate matter, bacteria, and soil infection p o t e n t i a t i n g factors, thereby reducing the infection rate of experimentally contaminated wounds. During wound cleansing, inadvertent spilling of 0.9% sodium chloride into the eye does not cause ocular injuries. Despite these advantages of high-pressure syringe irrigation, several objections have been raised about its routine use in periorbital lacerations. First, the irrigant solution disseminates deeply into the pefiorbital tissue and causes considerable edema. Second, 0.9% saline is not a surfactant and cannot solubilize grease and oils in the periorbital region. Consequent-
13:5 May 1984
ly we prefer mechanical cleansing of periorbital lacerations with an Optipore ¢ sponge soaked in Shur Clens ®, rather than high-pressure syringe irrigation with 0.9% saline.
SUMMARY Shut Clens ® is a nonionic detergent that can be used safely to cleanse periorbital lacerations. Topical application of this skin cleanser to the eyes of experimental animals and h u m a n beings did not elicit ocular lesions. In contrast, Betadine ® surgical scrub solution, H i b i c l e n s ®, a n d p H i s o H e x ® caused marked irritation to the eyes of e x p e r i m e n t a l a n i m a l s and should, therefore, n o t be u s e d in h u m a n beings to cleanse pcriorbital lacerations.
REFERENCES 1. Stevenson TR, Thacker JG, Rodeheaver GT, et al: Cleansing the traumatic wound by high pressure syringe irrigation. JACEP 1976;5:17-21.
Annals of Emergency Medicine
2. Draize JH, Woodard G, Calvery HO: Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes, f Pharm Exp Ther 1944;82:377-390. 3. Edlich RE Tsung MS, Rogers W, ct al: Studies in the management of the contaminated wound. I. Techniques of closure of such wounds together with a note on a reproducible model. J Surg Res 1968~8:585-592. 4. O-T-C topical antimicrobial products: Over the counter drug generally recognized as safe, effective and not misbranded. Fed Reg 1978;43:1210-1249. 5. Rodeheaver GT, Kurtz L, Kircher BJ, et al: Pluronic F-68: A promising new skin wound cleanser. Ann Emerg Med 1980;9: 572-576. 6. Geyer RP: The biliary excretion of components of intravenous fat emulsions by the rat. A m J Clin Nutr 1965~16: 146-150. 7. Custer J, Edlich RF, Prusak M, et ah Studies in the management of the contaminated wound. V. An assessment of effectiveness of pHisoHex and Betadine surgical scrub solutions. A m J Surg 1971; 121:572-575.
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