Top

Surgical Endoscopy

Published in:

01-12-2013

The role of aerosolized intraperitoneal heparin and hyaluronic acid in the prevention of postoperative abdominal adhesions

Authors: Nawar A. Alkhamesi, Christopher M. Schlachta

Published in: Surgical Endoscopy | Issue 12/2013

Abstract

Introduction

Intraperitoneal adhesions are a common and serious problem following abdominal surgery. Significant research has been performed to investigate the mechanisms involved; however, this has not influenced the incidence; it is still the leading cause of intestinal obstruction, pelvic pain, and infertility in women. The purpose of this study was to evaluate the ability of aerosolized heparin and hyaluronic acid for the prevention of postoperative adhesions.

Materials and Methods

A survival pig model was employed (N = 40). The pigs underwent laparoscopic insertion of polypropylene mesh to create intraperitoneal adhesions. The animals were randomized into four groups: control (n = 10), aerosolized heparin (n = 10), aerosolized hyaluronic acid (n = 10), and aerosolized mixture of both agents (n = 10). After a 2-week recovery period, the animals were killed and intraperitoneal adhesions were assessed.

Results

All of the animals in the control group suffered postoperative adhesions (10/10) compared with three in the heparin group, two in the hyaluronic group, and one in the mixed group. The number of adhesions per animal and the severity was higher in the control group compared with the therapeutic groups. The mean number of adhesions in the affected pigs also was higher in the control group compared with the therapeutic groups: 3.3 versus 0.4 in heparin group (range 0–2) versus 0.3 in hyaluronic acid group versus 0.1 in the mixed group (p = 0.002).

Conclusions

This study has shown that aerosolised heparin and hyaluronic acid is an effective method to prevent postoperative adhesions whether they were used independently or in synergism. However, the best result was when both agents mixed together compared with the control. A human-based study will be the next step to confirm the success of these agents.

Holmdahl L, Risberg B (1997) Adhesions: prevention and complications in general surgery. Eur J Surg 163:169–174PubMed

Ray NF, Larsen JW Jr, Stillman RJ, Jacobs RJ (1993) Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet 176:271–276PubMed

Saed GM, Zhang W, Diamond MP (2001) Molecular characterization of fibroblasts isolated from human peritoneum and adhesions. Fertil Steril 75:763–768PubMedCrossRef

Saed GM, Diamond MP (2003) Modulation of the expression of tissue plasminogen activator and its inhibitor by hypoxia in human peritoneal and adhesion fibroblasts. Fertil Steril 79:164–168PubMedCrossRef

Holmdahl L, Eriksson E, al Jabreen M, Risberg B (1996) Fibrinolysis in human peritoneum during operation. Surgery 119:701–705PubMedCrossRef

Holmdahl L, Falkenberg M, Ivarsson ML, Risberg B (1997) Plasminogen activators and inhibitors in peritoneal tissue. APMIS 105:25–30PubMedCrossRef

Ivarsson ML, Falk P, Holmdahl L (2001) Response of visceral peritoneum to abdominal surgery. Br J Surg 88:148–151PubMedCrossRef

Scott-Coombes D, Whawell S, Vipond MN, Thompson J (1995) Human intraperitoneal fibrinolytic response to elective surgery. Br J Surg 82:414–417PubMedCrossRef

Scott-Coombes DM, Whawell SA, Thompson JN (1995) The operative peritoneal fibrinolytic response to abdominal operation. Eur J Surg 161:395–399PubMed

10.

Raftery AT (1981) Effect of peritoneal trauma on peritoneal fibrinolytic activity and intraperitoneal adhesion formation. An experimental study in the rat. Eur Surg Res 13:397–401PubMedCrossRef

11.

Whawell SA, Scott-Coombes DM, Vipond MN et al (1994) Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells. Br J Surg 81:214–216PubMedCrossRef

12.

Whawell SA, Thompson JN (1995) Cytokine-induced release of plasminogen activator inhibitor-1 by human mesothelial cells. Eur J Surg 161:315–318PubMed

13.

Ambler DR, Fletcher NM, Diamond MP, Saed GM (2012) Effects of hypoxia on the expression of inflammatory markers IL-6 and TNF-α in human normal peritoneal and adhesion fibroblasts. Syst Biol Reprod Med 58:324–329PubMedCrossRef

14.

Arung W, Meurisse M, Detry O (2011) Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol 17:4545–4553PubMedCrossRef

15.

Arung W, Drion P, Cheramy JP et al (2012) Intraperitoneal adhesions after open or laparoscopic abdominal procedure: an experimental study in the rat. J Laparoendosc Adv Surg Tech A 22:651–657PubMedCrossRef

16.

Nwokoma NJ, Hassett S, Tsang TT (2009) Trocar site adhesions after laparoscopic surgery in children. Surg Laparosc Endosc Percutan Tech 19:511–513PubMedCrossRef

17.

Gago LA, Saed GM, Chauhan S et al (2003) Seprafilm (modified hyaluronic acid and ) acts as a physical barrier. Fertil Steril 80:612–616PubMedCrossRef

18.

Hosie K, Gilbert JA, Kerr D et al (2001) Fluid dynamics in man of an intraperitoneal drug delivery solution: 4% icodextrin. Drug Deliv 8:9–12PubMedCrossRef

19.

Khaitan E, Scholz S, Richards WO (2002) Laparoscopic adhesiolysis and placement of Seprafilm: a new technique and novel approach to patients with intractable abdominal pain. J Laparoendosc Adv Surg Tech A 12:241–247PubMedCrossRef

20.

Oncel M, Remzi FH, Senagore AJ et al (2003) Comparison of a novel liquid (Adcon-P) and a sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) in postsurgical adhesion formation in a murine model. Dis Colon Rectum 46:187–191PubMedCrossRef

21.

Vrijland WW, Tseng LN, Eijkman HJ et al (2002) Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial. Ann Surg 235:193–199PubMedCrossRef

22.

Yagmurlu A, Barlas M, Gursel I, Gokcora IH (2003) Reduction of surgery-induced peritoneal adhesions by continuous release of streptokinase from a drug delivery system. Eur Surg Res 35:46–49PubMedCrossRef

23.

Yoldemir T, Sagol S, Adakan S et al (2002) Comparison of the reduction of postoperative adhesions by two barriers, one solution, and two pharmacologic agents in the rat uterine model. Fertil Steril 78:335–339PubMedCrossRef

24.

Nadig C, Binswanger U, von Felten A (1997) Is heparin therapy necessary in CAPD peritonitis? Perit Dial Int 17:493–496PubMed

25.

Pawlaczyk K, Kuzlan-Pawlaczyk M, Anderstam B et al (2001) Effects of intraperitoneal heparin on peritoneal transport in a chronic animal model of peritoneal dialysis. Nephrol Dial Transplant 16:669–671PubMedCrossRef

26.

Al Chalabi HA, Otubo JA (1987) Value of a single intraperitoneal dose of heparin in prevention of adhesion formation: an experimental evaluation in rats. Int J Fertil 32:332–335PubMed

27.

Fukasawa M, Girgis W, diZerega GS (1991) Inhibition of postsurgical adhesions in a standardized rabbit model: II. Intraperitoneal treatment with heparin. Int J Fertil 36:296–301PubMed

28.

Turkcapar AG, Ozarslan C, Erdem E et al (1995) The effectiveness of low molecular weight heparin on adhesion formation in experimental rat model. Int Surg 80:92–94PubMed

29.

Vela AR, Littleton JC, O’Leary JP (1999) The effects of minidose heparin and low molecular weight heparin on peritonitis in the rat. Am Surg 65:473–477PubMed

30.

Alkhamesi NA, Ridgway PF, Ramwell A et al (2005) Peritoneal nebulizer: a novel technique for delivering intraperitoneal therapeutics in laparoscopic surgery to prevent locoregional recurrence. Surg Endosc 19:1142–1146PubMedCrossRef

31.

Alkhamesi NA, Peck DH, Lomax D, Darzi AW (2007) Intraperitoneal aerosolization of bupivacaine reduces postoperative pain in laparoscopic surgery: a randomized prospective controlled double-blinded clinical trial. Surg Endosc 21:602–606PubMedCrossRef

32.

Krahenbuhl L, Schafer M, Kuzinkovas V et al (1998) Experimental study of adhesion formation in open and laparoscopic fundoplication. Br J Surg 85:826–830PubMedCrossRef

33.

Mazuji MK, Kalambaheti K, Pawar B (1964) Prevention of adhesions with polyvinylpyrrolidone. Preliminary report. Arch Surg 89:1011–1015PubMedCrossRef

34.

Menzies D (1993) Postoperative adhesions: their treatment and relevance in clinical practice. Ann R Coll Surg Engl 75:147–153PubMed

35.

Monk BJ, Berman ML, Montz FJ (1994) Adhesions after extensive gynecologic surgery: clinical significance, etiology, and prevention. Am J Obstet Gynecol 170:1396–1403PubMedCrossRef

36.

Hirschelmann A, Tchartchian G, Wallwiener M et al (2012) A review of the problematic adhesion prophylaxis in gynaecological surgery. Arch Gynecol Obstet 285:1089–1097PubMedCrossRef

37.

Ouaissi M, Gaujoux S, Veyrie N et al (2012) Postoperative adhesions after digestive surgery: their incidence and prevention: review of the literature. J Visc Surg 149:e104–e114PubMedCrossRef

38.

Ten Broek RP, Strik C, Issa Y et al (2012) Adhesiolysis-related morbidity in abdominal surgery. Ann Surg 258(1):98–106CrossRef

39.

Ray NF, Denton WG, Thamer M et al (1998) Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994. J Am Coll Surg 186:1–9PubMedCrossRef

40.

De Wilde RL, Brolmann H, Koninckx PR et al (2012) Prevention of adhesions in gynaecological surgery: the 2012 European field guideline. Gynecol Surg 9:365–368PubMedCrossRef

41.

Cohen Z, Senagore AJ, Dayton MT et al (2005) Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium hyaluronate/carboxymethylcellulose-based bioresorbable membrane: a prospective, randomized, evaluator-blinded multicenter study. Dis Colon Rectum 48:1130–1139PubMedCrossRef

42.

Kim T, Ahn KH, Choi DS et al (2012) A randomized, multi-center, clinical trial to assess the efficacy and safety of alginate carboxymethylcellulose hyaluronic Acid compared to carboxymethylcellulose hyaluronic acid to prevent postoperative intrauterine adhesion. J Minim Invasive Gynecol 19:731–736PubMedCrossRef

43.

Catena F, Ansaloni L, Di Saverio S, Pinna AD (2012) P.O.P.A. study: prevention of postoperative abdominal adhesions by icodextrin 4% solution after laparotomy for adhesive small bowel obstruction. A prospective randomized controlled trial. J Gastrointest Surg 16:382–388PubMedCrossRef

44.

Ditzel M, Deerenberg EB, Komen N et al (2012) Postoperative adhesion prevention with a new barrier: an experimental study. Eur Surg Res 48:187–193PubMedCrossRef

45.

Hermans MH, Brown L, Darmoc M (2012) Adhesion prevention in an intraperitoneal wound model: performance of two resorbable hemostats in a controlled study in rabbits. J Biomed Mater Res B Appl Biomater 100:1621–1626PubMed

46.

Shimi SM, Loudon MA (2012) Pumactant in the prevention of postoperative adhesions: a randomized trial. J Surg Res 178:677–684PubMedCrossRef

47.

Yigitler C, Karakas DO, Kucukodaci Z et al (2012) Adhesion-preventing properties of 4% icodextrin and canola oil: a comparative experimental study. Clinics (Sao Paulo) 67:1303–1308CrossRef

48.

Yilmaz Y, Celik IH, Pampal A et al (2012) Effects of different pulmonary surfactants in the prevention of postoperative intraabdominal adhesion formation. J Pediatr Surg 47:1560–1565PubMedCrossRef

49.

Boztosun A, Ozer H, Altun A et al (2012) The effect of sorafenib in postoperative adhesion formation in a rat uterine horn model. Clin Exp Obstet Gynecol 39:351–355PubMed

50.

Parker JE, Fibini SL, Car BD, Erb HN (1987) Prevention of intraabdominal adhesions in ponies by low-dose heparin therapy. Vet Surg 16:459–462PubMedCrossRef

51.

Tayyar M, Basbug M (1999) The effects of intraperitoneal piroxicam and low molecular weight heparin in prevention of adhesion reformation in rat uterine horn. Res Exp Med (Berl) 198:269–275CrossRef

Title: The role of aerosolized intraperitoneal heparin and hyaluronic acid in the prevention of postoperative abdominal adhesions
Authors: Nawar A. Alkhamesi
Christopher M. Schlachta
Publication date: 01-12-2013
Publisher: Springer US
Published in: Surgical Endoscopy / Issue 12/2013
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-013-3102-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The role of aerosolized intraperitoneal heparin and hyaluronic acid in the prevention of postoperative abdominal adhesions

Abstract

Introduction

Materials and Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Materials and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2013

Transanal minimally invasive surgery (TAMIS) versus transanal endoscopic microsurgery (TEM): Is one better than the other?

Diaphragmatic relaxing incisions during laparoscopic paraesophageal hernia repair

Critical appraisal of learning curve for single incision laparoscopic right colectomy

Is the routine use of intraoperative cholangiography during laparoscopic cholecystectomy really the key to lowering bile duct injuries?

Patient-centered outcomes after laparoscopic cholecystectomy

Endoscopic submucosal dissection for early gastric cancer with undifferentiated histology: could we extend the criteria beyond?