icodextrin and Peritoneal-Diseases

Pelvic adhesion can form as a result of inflammation, endometriosis or surgical trauma. Most surgical procedures performed by obstetrician-gynecologists are associated with pelvic adhesions that may cause subsequent serious sequelae, including small bowel obstruction, infertility, chronic pelvic pain, and difficulty in postoperative treatment, including complexity during subsequent surgical procedures. An increasing number of adhesion reduction agents, in the form of site-specific and broad-coverage barriers and solutions, are becoming available to surgical teams. The most widely studied strategies include placing synthetic barrier agents between the pelvic structures. Most of the adhesions in the barrier-treated patients develop in uncovered areas in the abdomen. This fact suggests that the application of liquid or gel anti-adhesive agents to cover all potential peritoneal lesions, together with the use of barrier agents, may reduce the formation of postoperative adhesions. This article introduces the topical choices available for adhesion prevention mentioned in preliminary clinical applications and animal models. To date there is no substantial evidence that their use reduces the incidence of postoperative adhesions. In combination with good surgical techniques, these non-barrier agents may play an important role in adhesion reduction.

Topics: Acetamides; Antioxidants; Collagen Type I; Female; Fibrin; Glucans; Glucose; Honey; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Icodextrin; Inflammation; Linezolid; Melatonin; Oxazolidinones; Pain, Postoperative; Pelvic Pain; Pelvis; Peritoneal Diseases; Phosphatidylcholines; Postoperative Complications; Tissue Adhesions; Treatment Outcome

Adhesive small bowel obstruction (ASBO) is an important cause of hospital admission, is associated with significant morbidity and mortality, and therefore is a substantial burden for healthcare systems worldwide. Icodextrin 4% solution (Adept, Shire Pharmaceuticals, UK) is a high-molecular-weight a-1,4 glucose polymer approved in Europe for use as intraoperative lavage and postoperative instillation to reduce the occurrence of post-surgery intra-abdominal adhesions. The present clinical study aimed to evaluate the safety and effectiveness of icodextrin 4% in decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASBO.. The study was a single-center prospective, randomized investigation. The study is designed and conducted in compliance with the principles of Good Clinical Practice regulations. Safety and efficacy of icodextrin 4% in the study group are compared to no anti-adhesion treatment in a parallel control group with blinded evaluation of primary endpoints. Primary endpoints are the evaluation of the therapeutic role of icodextrin 4% in reducing ASBO recurrence incidence and the need of laparotomies for ASBO recurrence, as well as adhesion formation (with evaluation of their incidence, extent, and severity). A sum of 181 patients with ASBO and surgical indication to laparotomy were enrolled and randomized in two groups. Patients were submitted to adhesiolysis with bowel resection if required with or without anastomosis. The first group received traditional treatment (control group), whereas the second group was treated with the addition of icodextrin 4% solution before the abdominal closure.. Ninety-one patients were randomized to have icodextrin 4% solution administered intraperitoneally, and 90 patients were randomized to have the traditional treatment. The two study groups were homogeneous regarding their baseline characteristics. The ASBO recurrence rate was 2.19% (2/91) in the icodextrin groups vs 11.11% (10/90) in the control group after a mean follow-up period of 41.4 months (p < 0.05). No differences were found in the need of laparotomies for ASBO recurrence in the studied groups. The adhesion severity score seems lower in the group treated with the addition of icodextrin (p = n.s.).. The data resulting from this RCT showed that the use of icodextrin 4% solution in ASBO is safe and reduces intra-abdominal adhesion formation and the risk of re-obstruction.

Topics: Aged; Female; Follow-Up Studies; Glucans; Glucose; Humans; Icodextrin; Intestinal Obstruction; Laparotomy; Male; Middle Aged; Peritoneal Diseases; Postoperative Complications; Prospective Studies; Secondary Prevention; Single-Blind Method; Tissue Adhesions; Treatment Outcome

A pilot randomized controlled clinical multicentre trail was established to compare intraperitoneal 4% icodextrin (ID) solution with lactated Ringer's solution (LRS) on adhesion formation after Hartmann's procedure. The adhesiolysis surgery time during Hartman's reversal was used as a marker of the severity of adhesions.. Patients scheduled for Hartmann's resection were randomized at surgery to either of the two study solutions used as an irrigant during the operation and instilled (1000 ml) at the end of surgery. During the reversal procedure, the time for small bowel adhesiolysis was recorded.. On completion of 17 eligible patients, an interim analysis was performed. There were no complications following the use of 4% ID solution. The mean (SD) total adhesiolysis times in patients treated with 4% ID solution and LRS were 30.8 (18.0) min and 47.6 (45.7) min, respectively. The mean reduction of 16.8 min, although greater than expected, was not statistically significant (P = 0.33) because of the large variance in adhesiolysis times. Further statistical analysis showed that to achieve significance for the observed differences and variance, a minimum of 240 patients in each group would be required.. Icodextrin treatment resulted in a decreasing trend in adhesiolysis time. The use of 4% ID solution in peritonitis patients seemed to be safe. Because of larger than expected variations in adhesiolysis times, this pilot study was underpowered to meet the study end-point and further statistical modelling estimated that significance cannot be reached within a reasonable time scale. Other models should be used to evaluate the efficacy of anti-adhesive agents.

Topics: Aged; Aged, 80 and over; Colostomy; Female; Follow-Up Studies; Glucans; Glucose; Humans; Icodextrin; Isotonic Solutions; Male; Middle Aged; Peritoneal Diseases; Ringer's Lactate; Therapeutic Irrigation; Tissue Adhesions

Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an alpha-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery.. Women aged > or = 18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6-12 weeks. Procedures were video-taped for third party, blinded assessment.. Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance.. In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.

Topics: Adult; Female; Glucans; Glucose; Gynecologic Surgical Procedures; Humans; Icodextrin; Laparoscopy; Middle Aged; Peritoneal Diseases; Pilot Projects; Safety; Single-Blind Method; Solutions; Tissue Adhesions; Treatment Outcome

To assess the value of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) as prognostic serum markers for intraperitoneal adhesions.. Postoperative adhesions are associated with serious complications responsible for increased patient's morbidity.. Forty-eight rabbits were used and randomized into groups A, B, C, and D. Abdominal laparotomy and experimental adhesion formation model was carried out. In group A, 60 mL of N/S 0.9% were instilled intraperitoneally, in group B 60 mL of icodextrin 4% were instilled intraperitoneally, in group C 0.1 mL/kg of dimetindene maleate were administered intravenously, and in group D both agents were administered. Prior to euthanasia 0.5 mL of blood was obtained. The type, the surface area of adhesions, and serum concentration of MMPs were assessed.. The mean surface area and Zuhlke classification of adhesions of groups B, C, and D has been proved to be significantly lower compared to group A. Serum MMP-2 levels were significantly higher in groups B and D than in group A, while group D was higher when compared to group C. Serum MMP-9 levels were significantly higher in group D compared to groups A, B, and C. Serum MMP-9 was the most accurate test to differentiate between animals with and without adhesions with a sensitivity of 81.8% and a specificity of 100% at a cut-off point of 21.5 (AUC = 0.934).. The administration of icodextrin 4% and dimetindene maleate seems to prevent postoperative adhesion formation. Serum levels of MMP-2 and MMP-9 may serve as prognostic markers to identify postoperative adhesions.

Topics: Animals; Biomarkers; Dimethindene; Female; Glucans; Glucose; Icodextrin; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Peritoneal Diseases; Postoperative Complications; Prognosis; Rabbits; Tissue Adhesions

Postoperative peritoneal adhesion formation following abdominal surgery remains a relevant surgical problem. The application of soluble physico-chemical barriers like 4% icodextrin is one approach to protect the peritoneal surface from getting linked to adhesive scar. The aim of this study was to investigate the influence of 4% icodextrin on peritoneal tissue response both of visceral and parietal peritoneum, adhesion formation and wound healing.. 40 rats were divided into two groups. After creation of an intraabdominal defect, either 4% icodextrin (Adept®) or sodium chloride was applied. Animals were sacrificed after 7 and 21 days. Adhesions were scored by an adhesion score. Furthermore, immunohistochemical investigations were conducted to determine the discrete influence of icodextrin on the parietal and visceral peritoneal tissue responses (CD68+ macrophages, CD3+ T-lymphocytes, vimentin for mesenchymal cells, HBME-1 for mesothelial cells, and as components of wound healing COX-2, C-myc, catenin).. Postoperative peritoneal adhesions were predominantly present in the sodium chloride group as compared to the icodextrin group (14/19 (74%) vs. 9/19 (47%); p = 0.048). The adhesion score however did not reveal any significant differences, (p = 0.614). Furthermore, the expression of vimentin in both the parietal and visceral peritoneum after 21 days was significantly lower in the icodextrin group than in the sodium chloride group (p = 0.038 and p = 0.028, respectively). No significant differences were observed for macrophages, lymphocytes, reperitonealisation or the expression of COX-2, C-myc or Catenin.. The intraperitoneal application of 4% icodextrin reduces adhesion formation in comparison to sodium chloride. 4% icodextrin solution reduces the inflammatory and mesenchymal infiltrate in the wounded area, thus improving the ratio of mesothel cells to mesenchymal infiltrate. As demonstrated, icodextrin is able to ameliorate the local tissue response. Further experimental studies would be done to elaborate the impact on the early response of the adaptive immune system, which may then trigger the subsequent wound healing and tissue repair.

Topics: Abdominal Wound Closure Techniques; Administration, Topical; Animals; Biomarkers; Glucans; Glucose; Icodextrin; Immunohistochemistry; Male; Peritoneal Diseases; Peritoneum; Postoperative Complications; Protective Agents; Random Allocation; Rats; Rats, Wistar; Severity of Illness Index; Tissue Adhesions

Postsurgical abdominal adhesions are common, serious postoperative complications. The present study compared the usefulness of 4% icodextrin and canola oil in preventing postoperative peritoneal adhesions.. Twenty-four Wistar albino rats were divided into three groups. Following a laparotomy, a serosal abrasion was made by brushing the cecum, and 3 mL of 0.9% NaCl, 4% icodextrin, or 3 mL of canola oil were intraperitoneally administered for the control, icodextrin, and canola oil groups, respectively. The abdomen was then closed. All of the rats were sacrificed at day 10. Macroscopic, histopathological, and biochemical evaluations were performed. The results were statistically analyzed using Kruskal-Wallis and ANOVA tests.. Macroscopic analyses revealed that both canola oil and 4% icodextrin reduced adhesion formation, but the difference was not statistically significant (p = 0.17). The histopathological examinations revealed no significant differences in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM1, or PECAM1 scores. However, both canola oil and 4% icodextrin significantly reduced fibrosis (p = 0.025). In the canola oil group, the histiocytic reactions were significantly increased (p = 0.001), and the hydroxyproline levels were significantly lower than those in the other groups (p = 0.034).. In the present study, canola oil was determined to be superior to 4% icodextrin in lowering hydroxyproline levels and increasing histiocytic reactions. Considering these results, we believe that canola oil is a promising agent for preventing adhesion formation.

Topics: Animals; Fatty Acids, Monounsaturated; Female; Glucans; Glucose; Icodextrin; Peritoneal Diseases; Peritoneum; Rapeseed Oil; Rats; Rats, Wistar; Reproducibility of Results; Tissue Adhesions; Treatment Outcome

Topics: Animals; Dimethindene; Drug Combinations; Drug Interactions; Glucans; Glucose; Icodextrin; Peritoneal Diseases; Rabbits; Sample Size; Tissue Adhesions

Peritoneal adhesions are a well-known and frequently occurring postoperative complication. Many published studies have looked into the prophylaxis of adhesions following abdominal surgery, but only few clinically relevant agents have been reported. Most publications refer to adult patients and not to paediatric patient collectives. This experimental study in a rat model compares the effect of perfluorocarbons as adhesion prophylaxis with those of a well-known anti-adhesive agent Adept and with an untreated control group. We hypothesized that PFC might have a double effect: initially it could suppress the accumulation of monocytes and neutrophilic granulocytes, and subsequently it would work as a barrier to prevent contact between the visceral and parietal layers of the peritoneum. After a standardised operation, PFC was injected into the abdominal cavity of rats in the study group. Macroscopically, the PFC group did not fare significantly better, but nevertheless a clear tendency towards fewer adhesions after the application of PFC could be ascertained.

Topics: Animals; Disease Models, Animal; Fluorocarbons; Glucans; Glucose; Icodextrin; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Treatment Outcome

To date, no single method has been successful in eliminating peritoneal adhesion formation after major abdominal surgery. This study evaluated the individual and possible synergistic effect of a local intraperitoneal barrier, 4 per cent icodextrin, and an intravenously administered antihistamine drug, dimetindene maleate, in the prevention of adhesion development following surgical trauma.. De novo experimental adhesions were induced by standardized trauma of the peritoneum and large bowel in 120 New Zealand White rabbits. The animals were randomized into four groups receiving intraperitoneal saline, intraperitoneal 4 per cent icodextrin (60 ml), intravenous dimetindene maleate (0.1 mg/kg) and 4 per cent icodextrin-dimetindene in combination (n = 30 per group). Ten days later, adhesion scores and incidence were assessed by two independent surgeons. and surface area by computer-aided planimetry.. Treatment with either icodextrin or dimetindene maleate significantly reduced adhesion scores and increased the incidence of adhesion-free animals in an equipotent manner. The effect of combined treatment on severity, incidence and surface area of adhesions was more pronounced than that of each drug administered separately.. Combined administration of 4 per cent icodextrin and dimetindene maleate may be used safely and efficaciously to prevent surgically induced adhesions.

Topics: Animals; Dimethindene; Drug Combinations; Female; Glucans; Glucose; Icodextrin; Observer Variation; Peritoneal Diseases; Rabbits; Random Allocation; Tissue Adhesions

Important progress has been made in the field of post-surgical adhesion prevention with the development of consensus statements in gynaecology from the United Kingdom, Germany, the European Society of Gynaecological Endoscopy, Call for Action in Colorectal Surgery and a recent Technical Bulletin from The Practice Committee of the American Society of Reproductive Medicine. These reports suggest that the application of adhesion reduction devices together with the use of microsurgical principles reduces the formation of post-operative adhesions. This commentary provides additional information to assist gynaecologists in making surgical decisions. However, variation in adhesion classifications, mode of device application, lack of uniformity in surgical approaches and variations in interpretation of results make comparative assessment of the efficacy of adhesion reduction devices and surgical techniques difficult. Considering the choice of an adhesion-reduction device, one has to evaluate the cost and its clinical impact carefully. This is particularly important if one were to support routine, prophylactic use of adhesion-reduction devices. Healthcare providers should take into account the needs of individual patients, available resources, and institutional or clinical practice limitations. Good surgical technique and perhaps the use of approved devices for adhesion reduction would give patients the best chance to benefit from reproductive and gynaecological surgery.

Topics: Abdomen; Cellulose, Oxidized; Female; Gastrointestinal Diseases; Glucans; Glucose; Gynecologic Surgical Procedures; Humans; Hyaluronic Acid; Icodextrin; Peritoneal Diseases; Postoperative Complications; Practice Guidelines as Topic; Tissue Adhesions

Peritoneal sclerosis (PS) is a severe complication of long-term peritoneal dialysis (PD). We therefore investigated whether longitudinal analysis of solute and fluid transport preceding a diagnosis of PS could predict its development. We reviewed all standard peritoneal permeability analyses (SPAs) performed with 3.86% glucose and completed before a diagnosis of PS in all patients (n = 11) in whom that diagnosis was made in our center between 1995 and 2006. Most patients had 4 SPAs available. A linear mixed-model procedure was used to analyze the trends. Transport of small-solutes showed significant inverse U-shaped trends before a diagnosis of PS. This trend held for the mass transport area coefficients of creatinine, urea, and urate (all p < 0.05) and for their dialysate-to-plasma ratios (all p < 0. 001). Net ultrafiltration and free water transport at 60 minutes showed significant downward linear trends (both p < or = 0. 01). This U-shaped trend in small-solute transport combined with an ongoing decrease in net ultrafiltration and free water transport might be a warning sign of the development of PS. It underlines the importance of regular assessment of peritoneal function with 3.86% peritoneal equilibration tests in every PD patient-not only those at risk for peritoneal membrane failure.

Topics: Adolescent; Adult; Aged; Biological Transport; Creatinine; Glucans; Glucose; Hemodialysis Solutions; Humans; Icodextrin; Middle Aged; Peritoneal Dialysis; Peritoneal Diseases; Peritoneum; Permeability; Sclerosis; Urea; Uric Acid

Phospholipids and icodextrin reduce peritoneal adhesions resulting from general peritonitis without promoting abscess formation.. Evaluation of adhesion reduction fluids in a randomized animal study using a standardized peritonitis model.. Experimental animal model in a university laboratory.. In 60 rats, experimental peritonitis was induced using the cecal ligation and puncture model. On day 1, the abdominal cavity was rinsed with 10 mL of isotonic sodium chloride solution and the cecum was resected. Animals were randomly assigned to 3 groups: the RL group, which received Ringer lactate intraperitoneally; the PL group, which received phospholipids intraperitoneally; and the ID group, which received icodextrin intraperitoneally. In each group, 50% of the animals were humanely killed at day 11 and 50% at day 21.. The areas of adhesions were measured and the abscess formation was scored according to location and size. Abscesses, abdominal fluid, and blood were sampled for microbiologic workup.. The median area of adhesions was significantly lower in the PL groups (PL(11), 43.7 mm(2); PL(21), 20.4 mm( 2)) than in the RL groups (RL(11), 163.8 mm(2); RL( 21), 120.9 mm(2)) and ID groups (ID(11), 418.5 mm( 2); ID(21), 218.6 mm(2)). Abscess formation was increased by icodextrin but not influenced by phospholipids, whereas microbiologic investigations did not reveal any differences among these 3 groups.. In this model of general peritonitis, phospholipids significantly reduced adhesion formation without promoting septic complications. Icodextrin enhanced adhesion and abscess formation in this peritonitis model. Phospholipids may be beneficial for adhesion control in general peritonitis.

Topics: Abdominal Abscess; Animals; Female; Glucans; Glucose; Icodextrin; Peritoneal Diseases; Peritonitis; Phospholipids; Random Allocation; Rats; Rats, Sprague-Dawley; Tissue Adhesions

Two controlled in vivo studies in rats have investigated the effect of icodextrin solution on intraperitoneal chemotherapy-induced adhesion formation. The first study evaluated the effect of three concentrations of icodextrin (4, 15, 20% w/v) in comparison to a phosphate-buffered saline (PBS) control in response to intraperitoneal doxorubicin (n = 40). The second study compared the effect of 4% icodextrin to Ringers' lactate solution (RLS) control in response to intraperitoneal bleomycin (n = 30).. Doxorubicin and bleomycin were administered via a continuous pump and as a single bolus (bleomycin only). Doxorubicin 2 ml (23.2 microg/ml) was delivered via pump in conjunction with 20 ml of 4, 15, or 20% icodextrin or PBS (n = 10 per group). In the bleomycin experiments rats received either 2 ml (0.77 U/ml) bleomycin delivered via pump in conjunction with 15 ml 4% icodextrin or RLS, or 0.77 or 0.077 U bleomycin delivered in 15 ml 4% icodextrin or RLS administered as a bolus injection (n = 5 per group). Seven days after the initiation of doxorubicin treatment and 9 days after initiation of bleomycin treatment, the rats were euthanized by CO(2) and the extent of peritoneal adhesion formation was evaluated using an 8-point scoring system.. When icodextrin was administered in conjunction with doxorubicin there was a reduction in the formation of adhesions compared to PBS. Efficacy increased with the concentration of icodextrin used. The lowest dose of bleomycin (0.077 U) caused very few adhesions. Results with bleomycin 0.77 U/ml (pump) and 0.77 U (bolus) showed that 4% icodextrin was significantly more effective than RLS at preventing adhesion formation, irrespective of the dosing regimen.. These studies suggest that 4% icodextrin may reduce adhesion formation caused by intraperitoneal chemotherapy.

Topics: Animals; Antineoplastic Agents; Bleomycin; Dose-Response Relationship, Drug; Doxorubicin; Female; Glucans; Glucose; Icodextrin; Infusions, Parenteral; Peritoneal Diseases; Rats; Rats, Sprague-Dawley; Tissue Adhesions

Peri-operative lavage and postoperative instillation of a 4% icodextrin solution reduces de novo formation and reformation of peritoneal adhesions following abdominal surgery. This experimental study evaluated the effects of 4% icodextrin treatment on the healing of bowel anastomoses and laparotomy incisions.. Female New Zealand White rabbits (weight 2.21-2.77 kg) were randomised by ascending weight to one of 3 surgical treatments, each with 2 termination points (6 groups of 8 animals). The treatments were anastomotic bowel surgery alone or with lavage and postoperative instillation of either 4% icodextrin solution or Lactated Ringer's Solution (LRS). The solutions were coded A and B by the supplier, so that the study personnel were blinded to their identity. After the abdomen was opened, 30 ml of solution A or B was instilled and removed by aspiration prior to surgery. The ascending colon was then transected 5 cm aboral to the ileocaecal junction and the ends anastomosed. During surgery, 5 ml of the solution was applied 4 times at the surgical site, and a further 30 ml was administered and aspirated as a postoperative lavage. Just prior to closure of the abdominal wall, 50 ml of the solution was administered as a postoperative instillate. Duplicate treatment groups were terminated 7 and 21 days after surgery and the anastomotic sites inspected for adhesion and/or abscess formation. In 6 animals per group, an 8-12 cm length of colon including the anastomotic site was removed for measurement of bursting pressure, and a section of the abdominal wall including the incision line was tested for breaking strength. The other 2 animals per group provided tissue for histological analysis of wound healing at the bowel and incision sites.. There was no significant difference between the 3 treatment groups for any parameter (P > 0.05). Compared with the surgical control at either day 7 or 21 after surgery, the administration of solutions A or B did not affect the formation of abscesses or adhesions, the bursting strength of the bowel, or the tear strength of the abdominal wall incision. Histological assessment of the quality of wound healing showed no differences between treatment groups in inflammatory cell infiltration, fibroblast density, blood vessel formation or collagen maturity.. The use of a 4% icodextrin solution for peri-operative lavage and postoperative instillation in a rabbit model of bowel anastomotic healing did not result in any difference from either LRS treated or untreated surgical controls.

Topics: Anastomosis, Surgical; Animals; Female; Glucans; Glucose; Icodextrin; Instillation, Drug; Models, Animal; Peritoneal Diseases; Rabbits; Random Allocation; Therapeutic Irrigation; Tissue Adhesions; Wound Healing