Effect of frequent water immersion on the rate of tissue adhesive sloughing: a randomized study

EM Advances

CJEM 2005;7(6):391-395

Abstract

Résumé

Introduction

Cyanoacrylate tissue adhesives were developed by a German chemist in 1949¹ and first used clinically by a British plastic surgeon in 1959.² Butyl-cyanoacrylate has been available in Canada, Europe and Israel for over 4 decades. In 1993, Quinn and colleagues, from Ottawa, published the first randomized clinical trial comparing butyl-cyanoacrylate to sutures for repair of pediatric facial lacerations, showing that the adhesive was quicker and less painful than sutures and provided similar cosmetic results.³ Due to its inferior mechanical characteristics (relative weakness, low moisture resistance and brittleness) the use of butyl-cyanoacrylate never gained widespread use and was limited mostly to small simple wounds.⁴ During the last decade other investigators have shown that octylcyanoacrylate, a longer chain cyanoacrylate, has comparable efficacy to standard wound closure devices.^5,6 A recent report prepared by an independent marketing research company estimated that there are over 19 million lacerations per year worldwide, of which at least one-third could be closed using tissue adhesive.⁷

Existing recommendations for healing wounds, such as keeping the wound site clean and avoiding prolonged immersion in water, have been applied to skin adhesives, although these recommendations were derived from research on sutured lacerations, which are not water impermeable until 48 to 72 hours after repair.⁸ It has been suggested that, during the first 48–72 hours following wound repair, prolonged water immersion will saturate tissues and promote poor wound healing.^9,10 For wounds repaired using tissue adhesives, there is the added concern of premature adhesive sloughing and subsequent wound dehiscence. These concerns have prevented physician endorsement of prolonged bathing or swimming while the adhesive is affixed to the skin. This concern is especially pertinent in view of a recent Cochrane review, which suggests that traumatic lacerations repaired using tissue adhesives may have a slightly higher (statistically significant) rate of dehiscence, with a number needed to harm of 25.¹¹

We are unaware of any prior study evaluating the effects of water immersion on the sloughing characteristics of topical skin adhesives. Our objective was to compare the durability of low viscosity octylcyanoacrylate when applied to intact skin with and without frequent, controlled immersion in soapy water. We hypothesized that frequent exposure of the adhesive to soapy water would not result in accelerated sloughing of the adhesive.

Methods

Study design

This prospective, randomized, controlled, single-blind study compared time to complete sloughing of octylcyanoacrylate tissue adhesive with or without daily immersion in soapy water. Our Institutional Review Board approved this study, and all subjects or their guardians gave written, informed consent.

Setting and subjects

Our study was conducted in the emergency department at Stony Brook University Hospital, Stony Brook, NY, a university-based, tertiary care, Level 1 trauma centre with an affiliated residency in emergency medicine. Departmental faculty and their families, between the ages of 10 and 65 years, were eligible for enrollment in our study. Subjects with local dermatologic or systemic disorders and those with an allergy to the cyanoacrylates or formaldehyde were excluded from the study.

Study protocol

For each subject, an indelible marker was used to apply a 4-cm marking to intact skin on the volar surface of each forearm, 8–10 cm distal to the antecubital fossa, in the midline of the forearm, proximal to the volar wrist crease, and parallel to the arm’s long axis. Three layers of low viscosity octylcyanoacrylate (Dermabond™ Topical Skin Adhesive, Ethicon Products Worldwide, Somerville, NJ) were applied along the markings extending approximately 5 mm on either side of the marking. The individual layers of the adhesive were allowed to dry for 30 seconds between subsequent applications.

We randomized one forearm to daily 1-hour immersions in room temperature, soapy water, while the other forearm served as a control. Patients were allowed to shower or bathe briefly as per their standard daily routine. The order of treatment assignment was determined using a random numbers table. There were no restrictions to the allocation sequence and it was concealed until interventions were assigned by sealed, opaque envelopes that were prepared by a research nurse uninvolved in the study. Although the study subjects were not masked, the investigator measuring percent sloughing was blinded to treatment assignment. The success of blinding was not ascertained.

The immersion solution consisted of 3.8 L (1 gal) of tap water with 30 mL (2 tbsp) of Sunlight dishwashing detergent (Proctor and Gamble, Cincinnati). The detergent was placed in a 7.6 L (2-gal) rectangular plastic basin after the tap water had been added, and this mixture sat for 1/2 hour at room temperature. This allowed the water time to equilibrate with room temperature and to maximize study subject comfort. The solution was stirred 30 times over a 30-second period by one of the investigators. The participant immersed the experimental arm into the basin and was instructed to assure complete immersion of the tissue adhesive for 60 minutes. Following the 60-minute immersion period, the participants blotted the forearm dry.

The study took place during the winter, and subjects routinely wore long-sleeved clothing. The participants continued all other routine daily activities without attention to the study areas. All subjects were moderately active and showered daily. The adhesive was not covered by any dressing. The study subjects were instructed to avoid applying any topical creams or ointments to the study areas. The participants completed a daily inventory of all water-related and other relevant activities, and documented the number of times they showered or bathed and the amount of time spent in the shower or bathtub.

Every day for a 2-week period an investigator examined each forearm and documented the tissue adhesive properties of each side. Recorded data included length and width of the tissue adhesive, presence or absence of white flake or denuded segments, and the degree of adhesive sloughing expressed in percentages of the original area of the applied adhesive. The study was continued for 14 days or until all tissue adhesive had sloughed off. We chose to discontinue follow-up after 14 days because this is the maximum duration of acute wound care provided in the emergency department (i.e., the latest time at which sutures and staples are typically removed). We would expect tissue adhesive sloughing to be clinically unimportant after this time.

Outcomes and measures

Each day, the area of remaining adhesive was traced by an investigator onto a transparent film placed over the tissue adhesive on each forearm. The tracing was then scanned into a computer and the cross sectional area of the remaining adhesive was determined using Scion Imaging software (Scion Corporation, Frederick, Md.). The percent sloughing was calculated daily by subtracting the remaining adhesive area from the original adhesive area and dividing it by the original adhesive area multiplied by 100. The reliability of this measure was determined by having 2 investigators independently determine the percent sloughing on a subset of 10 subjects at Day 3. On this subset, inter-observer correlation was 0.90 using Cohen’s intra-class coefficient. Our main outcome was the rate at which the adhesive sloughed off. A secondary outcome was the number of days until the adhesive had completely sloughed off.

Data analysis

A Kaplan–Meier survival analysis using the log-rank test was used to compare complete sloughing times, with the end point defined as the time of 100% sloughing. Since the log-rank test does not take into account the paired sample design of this study, Wilcoxon’s signed-rank test was also used to compare the mean times to 100% sloughing between the immersed and control arms. A sample size of 20 paired wounds had 80% power to detect a difference of 2 days in time to complete sloughing (2-tailed α = 0.05).¹²

Results

We enrolled 20 subjects, including 12 females and 8 males, all white, with a mean age of 32 years (range 10–62 yr). Since each subject served as their own control, there were a total of 40 applications of skin adhesive. All of the subjects were right-hand dominant and half of the subjects had their dominant forearm exposed to the soapy water. Bathing was the only significant source of secondary water exposure, and there were no significant inter-subject differences in the amount of secondary water exposure.

The mean (± standard deviation) time to 100% sloughing was 4.2 (± 0.3) days for the immersed arms and 5.2 (± 0.6) days for the control arms (p = 0.07 [Fig. 1]). There was some loss of power for this test since the survival curves were compared without accounting for paired correlations between arms. The Wilcoxon’s test, which considers the paired nature of our design, suggested that time to complete sloughing was significantly shorter for the immersed arms, with a mean difference of 1.0 days (95% confidence interval, 0.2–1.8 d; p = 0.014).

Discussion

Our results suggest that 1 hour of daily immersion in soapy water leads to earlier tissue adhesive sloughing when applied to intact skin. These results are somewhat in contrast with those from a recent study of infants published by Ferlise and coworkers, in which 52 groin incisions closed with octylcyanoacrylate and exposed to bodily fluids under soiled diapers did not demonstrate any wound dehiscence or infection.¹³ This difference may be explained by the difference between painful incisions or wounds and normal skin. The fact that daily immersion of the adhesive in soapy water resulted in earlier sloughing in volunteers with intact skin may be due to the fact that the area was not guarded as well as a true laceration or incision would be.

Fig. 1. Kaplan–Meier survival curves for tissue adhesive.

It is also possible that tissue adhesive is less adherent to intact skin than to wounds. This possibility was raised by the fact that, in this study, 100% adhesive sloughing occurred in 4–5 days — more rapidly than we expected based on our familiarity with tissue adhesives. In fact, the mean sloughing by Day 2 was 20% (data not shown). Interestingly, the sloughing rate appears to be identical in both groups until about the 5th day. The differences between groups were greatest for the subjects in whom the adhesive lasted the longest (Fig. 1). Whether this rate of sloughing can be generalized to real wounds is unclear. However, it underscores the need for caution when considering the use of an adhesive for wounds subject to tension, especially in areas that require prolonged wound apposition. In these cases, the use of absorbable deep sutures and splinting might be indicated.¹⁴ Also, it is unclear how much intact adhesive is required to maintain the integrity of the wound closure. This makes extrapolation of our results to clinical practice somewhat problematic. In any event, our results suggest that daily soaking of real wounds that have been closed with a tissue adhesive may not be safe since it may result in earlier sloughing of the tissue adhesive and wound dehiscence.

One limitation of our study was that the adhesive was applied to intact skin. We chose to study an intact skin model because there are no data demonstrating the safety of daily soaks in soapy water, and an experiment involving real lacerations was deemed unethical. Data from the manufacturer of Dermabond suggest that the octylcyanoacrylate polymerization process may be different when it is applied to open wounds rather than intact skin (Joe Barefoot, Vice President of Regulatory Affairs and Quality Assurance, Ethicon, Inc.: personal communication, 2005); hence a study of real wounds exposed to daily soaks might provide different outcomes. In addition, the results from the forearm, a relatively dynamic area of the body, may not generalize to other locations such as the face. Also, rates of adhesive sloughing may be different with the more recently developed high viscosity octylcyanoacrylate and with other cyanoacrylate tissue adhesives than with the low viscosity octylcyanoacrylate we studied.

Our study had other limitations. It was conducted during the winter in a temperate climate. During these cold months, long-sleeved garments may irritate the skin adhesive and accelerate sloughing. Additionally, seasonal variation of moisture conditions could affect adhesive adherent properties. We also cannot exclude a recall bias with regard to subject recall and documentation of the amount of water exposure during the study period. This could lead to an underestimation or an overestimation of the importance of additional water exposure. We did not ascertain whether the investigator measuring the percent sloughing was truly masked to treatment assignments, which may have introduced observer bias. Finally, although the difference between the groups in rate of adhesive sloughing was statistically significant, the clinical significance of a 1-day difference in time to complete sloughing is unclear. Our study was not designed to translate the difference in time until sloughing to differences in wound dehiscence rates and ultimate scar appearance.

Conclusion

Our study demonstrates that the average time to complete sloughing of low viscosity octylcyanoacrylate applied to intact skin is 5 days and that this time is reduced by approximately 1 day by daily immersion in soapy water. The clinical applicability of these results remains to be determined. Future studies might include the use of an animal model to determine the sloughing characteristics from actual lacerations.

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