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Comparison between powdered gloves, powder-free gloves and hyaluronate/carboxymethylcellulose membrane on adhesion formation in a rat caecal serosal abrasion model

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Comparison Between Powdered Gloves, Powder-free

Gloves and Hyaluronate/Carboxymethylcellulose

Membrane on Adhesion Formation in a Rat

Caecal Serosal Abrasion Model

Varim Numanoglu, Alper Cihan,1Bülent Salman,2Bülent Hamdi Uçan,1Guldeniz Karadeniz Çakmak,1

Ali Cesur,1Hakan Balbaloglu1and Mustafa N. Ilhan,3Departments of Pediatric Surgery, and 1General Surgery, Medical Faculty of Zonguldak Karaelmas University, Zonguldak, Departments of 2General Surgery, and

3Public Health and Medical Statistics, Medical Faculty of Gazi University, Ankara, Turkey.

OBJECTIVE: Intraabdominal adhesion formation and prevention is one of the major conflicts of

modern surgery. We aimed to determine the effects of powdered gloves versus powder-free gloves and hyaluronate/carboxymethylcellulose membrane (H/CMCm) in a rat caecal serosal abrasion model.

METHODS: Sixty wistar albino rats were subjected to a standardized lesion by caecal abrasion model. In

group 1, the procedure was performed with sterile powdered gloves. In group 2, the procedure was per-formed with powder-free sterile gloves. The H/CMCm was applied directly to the abraded caecum in group 3. Formation of adhesions were determined on one half of the animals from each group on the 7th

post-operative day, and on the other half on the 15thpostoperative day.

RESULTS: There was a statistically significant difference between the adhesion scores on day 7 and 15 in

groups 1 and 2 (p= 0.005, p = 0.007). There was no significant difference in adhesion scores on day 7 and 15 in group 3 (p= 0.145). The mean adhesion score was significantly higher in group 1 (powdered glove group) than group 2 (powder-free glove group) and group 3 (powder-free glove plus H/CMCm) on post-operative day 7 (p= 0.001). However, no significant difference was found between groups regarding adhesion scores on postoperative day 15 (p= 0.607). The comparisons of group 2 versus group 3, both on postoperative day 7 (p= 0.051) was not statistically significant, whereas a significant difference was detected between group 1 versus group 2 and group 3 on postoperative day 7 (p= 0.013, p = 0.001).

CONCLUSION: Our experiment shows that the use of powder-free gloves may be as beneficial as

Seprafilm in preventing postoperative adhesion formation. [Asian J Surg 2007;30(2):96–101]

Key Words: adhesion, glove, hyaluronate/carboxymethylcellulose membrane, powdered, powder-free

First presented at the 40thCongress of the European Society for Surgical Research, 25–28 May 2005, Konya, Turkey.

Address correspondence and reprint requests to Dr Bülent Salman, Department of General Surgery, Gazi University Medical School, Bes¸evler 06500, Ankara, Turkey.

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Introduction

Intraabdominal adhesions are serious complications following abdominal and pelvic surgery, which remain a common circumstance resulting in enormous costs in terms of patient morbidity, mortality and medical expense.1

Adhesions are reported to be the reason for about 2% of all surgical admissions and 3% of all laparotomies in general surgery.2Previous intraperitoneal surgical

inter-ventions are known to be the most common cause of intra-abdominal adhesions with an approximate incidence of 80–90%. Inflammatory causes are responsible for 5–20% of adhesions and the only remaining 2–5% is considered to be congenital.3Postoperative adhesions are stated to

account for 40% of all cases of intestinal obstruction and are reported to be the most common cause of small intestinal obstruction with an incidence of 65–75%, which in turn is probably the most severe consequence of adhesions.4–6

Intraperitoneal surgery, and presumably its inherent mechanical or physical stimulus, is a well-known risk factor for the development of postoperative adhesions. However, in addition, intraabdominal surgery exposes patients’ viscera and peritoneum to varying degrees of contact with surgical gloves and their powders.7

Hyaluronate/carboxymethylcellulose membrane (H/ CMCm) is transformed within 1 day into a gel and offers a complete covering of a tissue surface for a minimum of 7 days, with slow decline in the following 28 days due to resorption. H/CMCm is neither toxic nor immunogenic, and thus, displays an optimal biocompatibility.8,9Rat

mod-els and human trials have shown that incidence, severity and extent of adhesions were reduced with H/CMCm.8,10,11 Surgical gloves were introduced in 1890 by William Halsted to protect the hands of his scrub nurse from harsh antiseptics with which she scrubbed her hands multiple times a day. The gloves were so satisfactory that soon all of his assistants were wearing them. The introduction of sur-gical gloves poses a great value in prevention of sursur-gical infections. They are now an essential and necessary com-ponent of all surgical procedures.7However, starch powder in surgical gloves was reported to have the ability to lead to serious complications such as granulomatous peritoni-tis, adhesion formation and potentiation of infection.12

The aim of the present study was to evaluate the effects of glove powder on peritoneal adhesion formation and compare the adhesion prevention effect of H/CMCm and powder-free gloves in a rat caecal abrasion model.

Materials and methods

Ethics

All surgical procedures were conducted in accordance with the regulations and approval of the Animal Ethics Review Committee of the Faculty of Medicine of Zonguldak Karaelmas University.

Animals

Animal rights oversight rules provided by Turkish Laws were followed in the study. Sixty male Wistar-Albino rats weighing 250–290 g were housed under constant temper-ature (22°C) and humidity with 12 hours dark/light cycles. They were housed according to standard guidelines. Animals were provided with standard laboratory rodent chow and water ad libitum pre- and postoperatively.

Experimental design

Three randomized groups that consisted of 20 rats each were subjected to a standardized lesion by caecal abrasion model. In group 1, the procedure was performed with ster-ile powdered gloves (Beybi, Istanbul, Turkey). In group 2, the procedure was performed with powder-free sterile gloves (Beybi, Istanbul, Turkey) and in addition, H/CMCm (Seprafilm®, Genzyme Biosurgery, Cambridge, MA, USA)

was applied directly to the abraded caecum in group 3.

Surgical procedure

All surgical procedures were performed using intramus-cular thiopental anaesthesia (50 mg/kg) under sterile con-ditions. The abdomen was shaved and prepared with povidone–iodine. All animals underwent a laparotomy through a 4 cm midline incision and the caecum was exte-riorized. One square centimetre area of caecal serosa was gently abraded until visibly damaged by scrubbing with a sterile surgical blade by the same surgeon. In group 1, all interventions were done with sterile powdered gloves. In groups 2 and 3, procedures were performed with powder-free sterile gloves. In addition, H/CMCm (Seprafilm®)

with a size of 2× 2 cm was applied directly to the abraded caecum before returning to its original location in group 3. Before abdominal closure, groups were intraperitoneally administered 3 mL of normal saline solution. The midline incision was closed in two layers of 3–0 silk sutures in all groups.

Relaparotomy and complete adhesiolysis were per-formed on one half of the animals in each group on the

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7th postoperative day; thereafter, identical procedures

were performed in the remainder of the animals on the 15thpostoperative day.

Measurement of adhesions

The surgeon of the operative procedures assessed the type, tenacity and extent of adhesion formation and the diffi-culty of adhesiolysis beginning from the incision using the adhesion scoring system shown in Table 1.13,14Total

adhesion scores were the sum of type, tenacity and extent scores of lesions.

Statistical analysis

Statistical analysis was performed using SPSS version 10.0 (SPSS Inc., Chicago, IL, USA) for Windows XP. Data were expressed as mean ± standard deviation values. The adhe-sion score of each rat was determined to calculate the group averages and standard deviations. The differences between adhesion scores were compared with the Kruskal–Wallis one-way analysis. Wilcoxon signed rank test was used in the comparison of adhesion scores in a group. Mann– Whitney U test and post-hoc Bonferroni test were used to assess the adhesion score difference between groups. P val-ues < 0.05 were considered to be statistically significant.

Results

None of the rats were found to have adhesions at the initial operation and no complications or deaths were observed. There was a statistically significant difference between the adhesion scores on day 7 and 15 in groups 1 and 2 (group 1, p= 0.005; group 2, p = 0.007). On the other hand, there was no significant difference in adhesion scores of day 7 and 15 in group 3 (p= 0.145). The mean

adhesion score was significantly higher in group 1 than group 2 (p=0.013) and group 3 on the 7thpostoperative day

(p= 0.001) (Figure 1). However, no statistically significant difference was found between groups regarding adhesion scores on postoperative day 15 (p= 0.607) (Figure 2).

The comparisons of group 2 versus group 3, both on postoperative day 7 (p= 0.051) was not statistically signif-icant. Whereas a significant difference was detected between group 1 versus group 2 and group 3 on postoperative day 7 (p= 0.013, p = 0.001, respectively). All results are presented in Table 2.

Total adhesion score

12 10 8 6 4 2 0 −2 Group 3 Group 2 Group 1

Figure 1.Comparison of adhesion scores between groups on the 7th postoperative day.

Table 1.Adhesion scoring system*

Score Type Tenacity Extent (%)

0 No adhesions – –

1 Filmy adhesions Easily fall apart 1–25 2 Firm adhesions Require traction 26–50 3 Require sharp Require sharp 51–75

dissection to be dissection separated

4 More More 76–100

*Total adhesion scores were the sum of type, tenacity and extent scores of lesions. T ot al adhesion scor e 10 8 6 4 2 0 −2 Group 3 (n = 10) Group 2 (n = 10) Group 1 (n = 10)

Figure 2.Comparison of adhesion scores between groups on the 15thpostoperative day.

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Discussion

The occurrence of intraperitoneal adhesions after abdomi-nal surgery is a well-known clinical problem. Postoperative peritoneal adhesions are a major cause of intestinal obstruc-tions. Postmortem evaluation of patients with prior sur-gical interventions has demonstrated adhesions in 67% of patients.15Menzies5and Menzies and Ellis16reported that the incidence of adhesions approaches 100% in patients with prior abdominal operations and/or prior intraabdom-inal infection. Intestintraabdom-inal obstruction, which is the most life-threatening adhesion-related complication, has a reported mortality rate of up to 15%.17,18It is well

estab-lished that any trauma to the peritoneum, for example, mechanical, physical, chemical or infective, causes a response on the peritoneal and serosal surfaces with sub-sequent adhesion formation. Although sophisticated min-imally invasive and laparoscopic techniques are used in most surgical procedures, iatrogenic surgical trauma can-not be avoided. Therefore, for prevention of adhesion formation, adjuvant treatment is necessary.

The pathogenesis of intraabdominal adhesion forma-tion is a complex process consisting of several factors that

control inflammation, cellular proliferation and migration, collagen and matrix synthesis, and interactions between various cell types, blood and matrix components.19Starch

powder of surgical glove is one of the most frequently accused agent for intraabdominal adhesions.

Since the introduction of surgical gloves powdered with starch particles, an increasing number of reports have indicated that postoperative inflammation and granu-loma formation may take place in the peritoneal cavity. Starch was introduced to eliminate the incidence of talc powder-related surgical complications, a goal only incom-pletely realized. Starch also absorbs latex proteins and thus provides a ready vehicle for aerosolization of latex proteins. However, the exact pathogenic mechanism respon-sible for these undesirable reactions to starch particles is not clear and may be diverse.20Nevertheless, starch is reported to be the main component of powdered gloves that promotes adhesion formation as a result of direct effects on the peritoneum.21

Many factors have been attributed to prevent or at least reduce adhesion formation in terms of surgical technique and adjuvant agents. Antiadhesive materials of different forms currently attract great attention. Various agents for

Table 2.Statistical analysis of the results

Group 3 Group 1 Group 2 (powder-free glove+

(powdered glove) (powder-free glove) Seprafilm®) p* ppp§

Rat 7thd 15thd 7thd 15thd 7thd 15thd 7thd 15thd I 6 3 6 5 3 1 II 7 0 4 1 1 3 III 7 4 3 1 0 0 IV 7 0 3 1 1 1 V 10 8 5 0 4 3 VI 8 0 8 3 5 3 0.001 0.607 0.013 0.001 0.051 VII 8 6 10 4 0 1 VIII 9 7 3 3 3 1 IX 6 0 3 0 3 0 X 7 4 3 0 4 3 Total 75 32 38 18 24 16 Mean ± SD 7.5 ± 1.3 3.2 ± 3.1 4.8 ± 2.5 1.8 ± 1.8 2.4 ± 1.8 1.6 ± 1.3 pⱍⱍ= 0.005 p= 0.007 p#= 0.145

*Kruskal–Wallis; †group 1 versus group 2 (Mann–Whitney U test–post-hoc Bonferroni test); group 1 versus group 3 (Mann–Whitney

U test–post-hoc Bonferroni test); §group 2 versus group 3 (Mann–Whitney U test–post-hoc Bonferroni test); ⱍⱍgroup 1, 7thday versus 15thday

(Wilcoxon signed rank test);¶group 2, 7thday versus 15thday (Wilcoxon signed rank test); #group 3, 7thday versus 15thday (Wilcoxon signed

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postsurgical adhesion prevention have been evaluated. To date, many clinical and animal trials have essayed multiple adjuvants, such as interleukins, corticosteroids, nonsteroidal anti-inflammatory drugs, lactated Ringer’s solution, dextran, antihistamines, saline, anticytokine agents, nitric oxide, hyaluronic acid, octreotide, platelet-activating factor receptor antagonists, polyanionic polysac-charides and physical barriers, to prevent intraabdominal adhesion formation.19,22,23 One of which is H/CMCm that is shown to reduce intraabdominal adhesions in both animals and humans.8,10

Our study demonstrated that H/CMCm, which was reported to be an effective antiadhesive agent, reduced adhesion formation in the first postoperative week on rat caecal abrasion model. Nevertheless, there was no statisti-cally significant difference in adhesions between groups on postoperative day 15. Results also showed that the presence of powder on surgical gloves promoted increased peritoneal adhesions on postoperative day 7. Compared with powdered gloves, adhesion formation was dimin-ished with the use of powder-free gloves. However, by postoperative day 15, there was no difference in adhesions between all groups. These findings may be related to adhesion formation/reformation duration. The most important step in this period is the inflammation phase that is seen in the first week. The inflammation phase due to neutrophil migration and fibrin formation on the damaged peritoneal surfaces affect adhesion formation in the first week.2If this can be controlled in the first week, then adhesion formation may be reduced. The for-mation of dense adhesions reduce in the second week due to migration of the macrophages and remodelling.2

Starch powder contact with damaged peritoneal surface increases inflammation and adhesion formation as seen in this study. However, H/CMCm blocks the connection of the damaged peritoneal surfaces and adhesion formation in the inflammation phase in the first week. This study showed that powder-free gloves may be as effective as H/CMCm under normal surgical conditions except for the increased adhesion formation in patients who have had repeated surgery, inflammation, infections and perforations. Our experiment also showed that the use of powder-free gloves may be as beneficial as Seprafilm in preventing postoperative adhesion formation. Since good powder-free alternatives are available, the use of powdered gloves during abdominal surgery needs to be justified.

References

1. Ray NF, Larsen JW Jr, Stillman RJ, Jacops RJ. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet 1993;176:271–6. 2. Dijkstra FR, Nieuwenhuijzen M, Rejinen MMP, van Goor H.

Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions. Scand

J Gastroenterol 2000;232(Suppl 35):52–9.

3. Menzies D. Peritoneal adhesions: incidence, cause, and prevention.

Surg Annu 1992;24 Pt 1:27–45.

4. Tulandi T. Salpingo-ovariolysis: a comparison between laser surgery and electrosurgery. Fertil Steril 1986;45:489–91.

5. Menzies D. Postoperative adhesions: their treatment and relevance in clinical practice. Ann R Coll Surg Engl 1993;75:147–53. 6. Ellis H. The magnitude of adhesion related problems. Ann Chir

Gynaecol 1998;87:9–11.

7. Dwivedi AJ, Kuwajerwala NK, Silva YJ, Tennenberg SD. Effects of surgical gloves on postoperative peritoneal adhesions and cytokine expression in a rat model. Am J Surg 2004;188: 491–4.

8. Medina M, Paddock HN, Connolly RJ, Schwaitzberg SD. Novel antiadhesion barrier does not prevent anastomotic healing in a rabbit model. J Invest Surg 1995;8:179–86.

9. Burns JW, Colt MJ, Burgees LS, Skinner KC. Preclinical evaluation of Seprafilm®bioresorbable membrane. Eur J Surg Suppl 1997;

577:40–8.

10. Szabo A, Haj M, Waxsman I, Eitan A. Evaluation of Seprafilm®

and amniotic membrane as adhesion prophylaxis in mesh repair of abdominal wall hernia in rats. Eur Surg Res 2000;32:125–8. 11. Kelekci S, Yilmaz B, Oguz S, et al. The efficacy of a hyaluronate/

carboxymethylcellulose membrane in prevention of postopera-tive adhesion in a rat uterine horn model. Tohoku J Exp Med 2004; 204:189–94.

12. Osman MO, Jensen SL. Surgical gloves: current problems. World

J Surg 1999;23:630–7.

13. Fiedler EP, Guzick DS, Guido R, et al. Adhesion formation from release of dermoid contents in the peritoneal cavity and effect of copious lavage: a prospective, randomised, blinded, controlled study in a rabbit model. Fertil Steril 1996;65:852–9.

14. Ornodez JL, Dominguez J, Evrard V. The effect of training and duration of surgery on adhesion formation in the rabbit model.

Hum Reprod 1997;12:2654–7.

15. Weibel MA, Mayno G. Peritoneal adhesions and their relation to abdominal surgery. Am J Surg 1972;126:345–53.

16. Menzies D, Ellis H. Intestinal obstruction from adhesions—how big is the problem? Ann R Coll Surg Engl 1990;72:60–3.

17. Wilson MS, Ellis H, Menzies D, et al. A review of the management of small bowel obstruction. Members of the surgical and clinical adhesions research study (SCAR). Ann R Coll Surg Engl 1999;81: 320–8.

18. Van Der Krabben AA, Dijkstra FR, Nieuwenhuijzen M, et al. Morbidity and mortality of inadvertent enterotomy during adhesiotomy. Br J Surg 2000;87:467–71.

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19. Chiang SC, Cheng CH, Moulton KS, et al. TNP-470 inhibits intra-abdominal adhesion formation. J Pediatr Surg 2000;35:189–96. 20. Van den Tol MP, Haverlag R, van Rossen ME, et al. Glove powder

promotes adhesion formation and facilitates tumour cell adhesion and growth. Br J Surg 2001;88:1258–63.

21. Hunt TK, Slavin JP, Goodson WH. Starch powder contamination of surgical wounds. Arch Surg 1994;129:825–8.

22. Reijnen MM, Skrabut EM, Postma VA, et al. Polyanionic polysaccharides reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model. J Surg Res 2001;101:248–3. 23. Oncel M, Remzi FH, Senagore AJ, et al. Comparison of a novel

liquid (Adcon-P) and a sodium hyaluronate and carboxymethyl-cellulose membrane (Seprafilm®) in postsurgical adhesion

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