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Effect of Antibiotic Lavage in Adhesion Prevention in Bacterial Peritonitis

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Effect of Antibiotic Lavage in Adhesion Prevention in Bacterial Peritonitis Turkish Journal of Trauma & Emergency Surgery Ulus Travma Acil Cerrahi Derg 2013;19 (3):189-194 Experimental Study Deneysel Çalışma doi: 10.5505/tjtes.2013.63444 Effect of antibiotic lavage in adhesion prevention in bacterial peritonitis Bakteriyel peritonitte antibiyotikle lavajın adezyonu önlemede etkisi Hüseyin Ayhan KAYAOĞLU,1 Namık ÖZKAN,1 Erdinç YENİDOĞAN,1 Reşid Doğan KÖSEOĞLU2 BACKGROUND AMAÇ Intra-abdominal adhesions remain a major clinical problem. Karıniçi yapışıklıklar halen ciddi bir problemdir. Geçmişte Previously, rifamycin lavage was used to prevent adhesion septik karında adezyon formasyonunu önlemek için sade- formation in the septic abdomen. The aim of our study was ce rifamisin lavajı denenmiştir. Bu çalışmanın amacı karın to test the effectiveness of intraperitoneal application of al- sepsis modelinde farklı antibiyotiklerin periton içine uygu- ternate antibiotics in an abdominal sepsis model. lamasının etkinliğini değerlendirmektir. METHODS GEREÇ VE YÖNTEM Sixty Wistar-albino rats were randomly divided into 6 Altmış adet Wistar-albino sıçan rastgele olacak şekilde 6 equal groups. Bacterial peritonitis was induced using cae- eşit gruba ayrıldı. Tüm gruplara çekal ligasyon ve puncture cal ligation and puncture model in all groups. Group 1 was modeli uygulanarak bakteriyel peritonit oluşturuldu. Grup an untreated control. The peritoneum was lavaged with iso- 1 kontrol grubuydu. Grup 2’ye izotonik salinle, grup 3’e tonic saline in Group 2, with imipenem in Group 3, with imipenemle, grup 4’e seftriaksonla, grup 5’e sefazolinle ve ceftriaxone in Group 4, with cefazolin in group 5 and with grup 6’ya metronidazolle periton lavajı yapıldı. Cerrahiden metronidazole in group 6. Four weeks after the surgery, 4 hafta sonra karıniçi yapışıklık değerlendirildi, yapışıklık- intra-abdominal adhesions were graded, tensile strength of ların gerginlik kuvveti ölçüldü ve histopatolojik değerlen- the adhesions was measured and histopathological exami- dirme yapıldı. nations were performed. BULGULAR RESULTS İmipenem, seftriakson ve sefazolin ile yapışıklık formas- Imipenem, ceftriaxone and cefazolin significantly reduced adhesion formation (p<0.001) with significantly reduced yonu anlamlı derecede azaldı (p<0,001) ve fibrozis skor- fibrosis scores (p=0.013). Adhesion formation was great- ları anlamlı derecede düşük olarak bulundu (p=0,013). En est in the metronidazole treatment group. The breaking kötü yapışıklık metronidazol grubunda izlendi. Yapışık- force of adhesions was significantly reduced in Groups 4 lık kopma kuvveti grup 4 ve 5’te anlamlı olarak düşüktü and 5 (p<0.001). Although, the inflammation scores were (p<0,001). Enflamasyon dağılım skorları benzer olmasına similar between groups (p=0.058), grade 3 inflammation rağmen (p=0,058) grade 3 enflamasyon skorları sadece scores were only seen in control, saline and metronidazole- kontrol, salin ve metronidazol grubunda gözlemlendi. treatment groups. SONUÇ CONCLUSION Bu veriler ışığında septik karında sefalosporinle peritoneal According to these data, cephalosporins may be effective in lavajın yapışıklığı önlenmede etkin olduğu ve sonuçların preventing adhesion formation in septic abdomens. These bir klinik çalışmada değerlendirilmesi gerektiği söylene- antibiotics need to be evaluated in a clinical trial. bilir. Key Words: Antibiotic; cefazolin; ceftriaxone; imipenem; intraab- Anahtar Sözcükler: Antibiyotik; sefazolin; seftriakson; imipe- dominal adhesion; metronidazole; peritoneal lavage. nem; karıniçi yapışıklık; metronidazol; peritoneal lavaj. Departments of 1General Surgery, 2Pathology, Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Gaziosmanpasa University, Faculty of Medicine, Tokat, Turkey. 1Genel Cerrahi Anabilim Dalı, 2Patoloji Anabilim Dalı, Tokat. Correspondence (İletişim): Hüseyin Ayhan Kayaoğlu, M.D. Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat, Turkey. Tel: +90 - 356 - 213 32 94 e-mail (e-posta): [email protected] 189 Ulus Travma Acil Cerrahi Derg Intra-abdominal adhesions occur in approximately Rats were sacrificed by high dose pentothal injection 95% of patients following abdominal surgery. Adhe- four weeks after the surgery. After performing a U-type sions cause serious problems including chronic ab- incision to the anterior abdominal wall, the adhesions dominal pain, intestinal obstructions, and female in- were evaluated. A numerical score described by Knight- fertility. Certain conditions, such as intra-abdominal ly et al.[11] was used to determine the adhesion grading infections, aggravate this condition. Infectious condi- by a surgeon unaware of the study groups (Table 1). tions are associated with fibrin deposits, which may After the grading of adhesions, the tensile strength of cause clinically significant adhesion and abscess adhesions between abdominal organs was measured by formation with mortality rates as high as 17 to 38%. the help of tensile testing equipment (Mark-10 Corpo- [1-4] Gram negative and anaerobic bacteria occur fre- ration, NY, USA), in which the test material was placed quently in intra-abdominal infections and abscesses. between a moveable arm over a stationary and a fixed Previously, systemic or local use of antibiotics have arm connected to the balance with metal clips, by the been evaluated for adhesion prevention properties.[5-8] same independent surgeon. By stretching the moveable However, only rifamisin has been studied in experi- arm gradually at speed of 10 mm/min, strength was ap- mental sepsis model.[9] plied and breaking force values at the time of disruption The aim of our study was to test the effectiveness were detected in Newtons (N). of intraperitoneal application of various antibiotics in Histopathology an experimental intra-abdominal sepsis model created Histopathological evaluations were performed by by cecal ligation and puncture. light microscopy with a magnification power of 100x MATERIALS AND METHODS and 400x. The resected adherent tissues were fixed in formaldehyde, embedded in paraffin blocks, and 4 µm Subjects and surgery sections were stained with haematoxylin and eosin After the approval of the institutional ethical com- (H&E). A pathologist, who was blind to the groups, mittee (approval code 03-GEKTIP-007), 60 adult, graded the extent of fibrosis and inflammation in each male, Wistar-albino rats (250-300 g) provided by the specimen with a semi-quantitative scoring system (Ta- Experimental Research Laboratory of the University bles 2 and 3).[12] under standard husbandry conditions, were randomly divided into 6 equal groups. Animals were operated on at a room temperature of 20°C under 75 mg/kg ket- Table 1. Adhesion grading scale[11] amine hydrochloride with 5 mg/kg xylazine anesthesia Score Adhesion was injected intramuscularly. After cleaning the skin, the anterior abdominal wall was shaved, treated with 0 No adhesions 10% povidon iodine, and a 3-cm median laparotomy 1 Filmy adhesions was performed. Bacterial peritonitis was induced us- 2 Definite localized adhesions ing a caecal ligation and puncture (CLP) model in all 3 Dense multiple visceral adhesions groups.[10] The cecum was punctured on the antimes- 4 Dense adhesions extending to abdominal wall enteric border with an 18-gauge needle after ligation below the ileocecal valve. Six hours later, following [12] repeat laparotomy, the caecum was resected and the Table 2. Fibrosis grading scale peritoneum was lavaged with isotonic saline (Medi- Score Amount of fibrosis flex; Eczacibasi-Baxter Hastane Urunleri, Ayazaga, 0 None Istanbul, Turkey) in Group 2, with 50mg/kg imipenem 1 Minimal, loose (Tienam 500 mg IV Flakon, Merck Sharp & Dohme 2 Moderate Ilac, Esentepe, Istanbul, Turkey) in Group 3, with 100 3 Florid, dense mg/kg ceftriaxone (Forsef Flakon; Bilim Ilac, Gebze, Kocaeli, Turkey) in Group 4, with 50 mg/kg cefazo- lin (Cefamezin Flakon; Eczacibasi Ilac, Luleburgaz, Table 3. Inflammation grading scale[12] Kırklareli, Turkey) in Group 5 and with 40 mg/kg met- ronidazole (Flagyl enjektabl solusyon 0.5%; Eczacibasi Score Amount of inflammation Ilac, Luleburgaz, Kırklareli, Turkey) in Group 6. These 0 None doses were chosen based on the manufacturer’s recom- 1 Giant cells, occasional lymphocytes, and mendation using the appropriate surface area-dosage plasma cells conversion factor of seven from man to rat. Group 1 2 Giant cells, plasma cells, eosinophils, served as control and peritoneal lavage was not per- neutrophils formed in this group. All animals were resuscitated 3 Many inflammatory cells, microabscesses with 10 ml saline subcutaneously in divided doses. 190 Mayıs - May 2013 Effect of antibiotic lavage in adhesion prevention in bacterial peritonitis mortalities were excluded while performing other 6 Knightly statistical analyses. Distribution of adhesion grad- 1.00 ing scores among groups was significantly different 5 2.00 3.00 (p<0.001, Fig. 1). Peritoneal lavage with imipenem, 4.00 ceftriaxone, and cefazolin significantly reduced adhe- 4 sion formation compared to the other groups. Control 3 and isotonic saline groups exhibited similar rates of Count adhesion formation. The most severe adhesions were 2 observed in the metronidazole group (Fig. 2). Mean and standard deviation values for the break- 1 ing force of adhesions between organs of the study groups are shown in Table 4. The differences were 0 Control Isotonic Imipenem Ceftriaxone Cefazolin metronidazole statistically significant (p<0.001). In paired compari- Fig. 1. Peritoneal lavage with imipenem, ceftriaxone and ce- sons of the groups, Groups
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