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PubMedDate not supplied

Stability of cefazolin sodium in four heparinized and non-heparinized dialysate solutions at 38 degrees C.

BACKGROUND: Intraperitoneal administration of antibiotics is often required in the treatment of peritoneal dialysis-associated peritonitis. Extended use and heating may affect drug stability. The objective of our study was to determine the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non-heparinized dextrosecontaining peritoneal dialysis solution (Dianeal PD-2; Baxter Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose, or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38 degrees C for 4 days. METHODS: Three poly-vinyl chloride containers of each dialysis fluid were stored at 38 degrees C for 4 days. Samples were taken after the bags were mixed and allowed to stand for 2 minutes. Two 500-microL samples were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96. Samples were then analyzed by high-performance liquid chromatography (HPLC) in our laboratory. In order to establish the stability-indicating nature of the method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH) hydrolysis, oxidation (H(2)O(2) 0.3%), and heat at 80 degrees C. Samples were analyzed every 30 minutes until approximately 25% of the drug's peak disappeared. The drug was considered stable if its concentration exceeded 90% of the original. RESULTS: For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%, and 4.25% dextrose, cefazolin sodium was considered stable at 38 degrees C for 60 hours at low cefazolin concentrations (125 mg/L), both with and without heparin, and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 48 hours at low cefazolin concentrations in heparinized and non-heparinized solutions, and at high concentrations only in non-heparinized dialysate, not in heparinized dialysate. Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 60 hours at high concentrations when heparinized. CONCLUSION: Cefazolin sodium was stable in all four nonheparinized dialysate fluids for at least 48 hours at 38 degrees C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium were not stable for extended periods of time. Extended use and heating of dialysate containing cefazolin may adversely affect patient outcome.

Cefazolin↗
PubMed2005

Adhesion prevention comparing liquid and solid barriers in the rabbit uterine horn model.

OBJECTIVE: The purpose of this study was to assess the ability of four different either solid or fluid barriers to reduce adhesions in an established model of gynecological surgery. STUDY DESIGN: 50 Chinchilla rabbits underwent bilateral deperitonealization and devascularization of the uterine horns (DUH). Afterwards solid membranes of either hyaluronic acid-carboxymethylcellulose (HA-CMC) or lactide-caprolactone-copolymer (LCC) were placed around the injured uterine horns or fluids (icodextrin (ID) or phospholipids (PL)) were intraperitonealy administered. The control group went without protection. After 10 days, adhesions were measured by planimetry. RESULTS: Phospholipids (median 49.8 mm2) significantly reduced adhesion areas in comparison to all other groups: surgical controls (median 230.6 mm2), HA-CMC (median 194.9 mm2), LCC (median 327.1 mm2), and icodextrin (median 242.1 mm2). CONCLUSIONS: These results prove the efficacy of phospholipids to reduce primary adhesion formation in the Chinchilla double uterine horn model compared to HA-CMC, LCC and icodextrin. Future clinical studies are recommended.

Animals↗
PubMed2000

Transperitoneal transport of glucose in vitro.

The effect of fluid mixing intensification, damage of mesothelial cells, gentamicin, and icodextrin on the diffusive glucose transport across the peritoneal membrane were evaluated in in vitro studies. A mathematical model of mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient (P). In the control conditions, the rate of glucose transfer from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) remained constant, and the P value at mean was 2,731 +/- 1,493 x 10-4 (cm x s-1). The change of the stirring rate from 5.5 to 11 ml/min increased P values by about 74% for transport direction I-->M and 58% for M-->I, and the change from 11 to 22 ml/min enhanced P at mean by about 42% for both directions. The damage of the mesothelial layer, using sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial to the mesothelial side of the peritoneum by 41% and to the opposite direction by 70%. Addition of icodextrin to the glucose solution increased glucose bidirectional transport at mean by about 14% for I-->M and 24% for M-->I. Furthermore, gentamicin did not change the I-->M transfer, but diminished M-->I transport by about 12%. In conclusion, the reduction of unstirred fluid layers at the mesothelium and the interstitium-fluid interfaces, removal of mesothelium, and addition of icodextrin increased the diffusive glucose transport in vitro; unstirred fluid layers restricted glucose transfer (I-->M) more than the mesothelium; and peritoneal glucose transport, directed from the mesothelial to the interstitial side of the peritoneum, decreased slightly after the addition of gentamicin.

Algorithms↗
PubMedDate not supplied

Effects of peritoneal dialysis solutions on the secretion of growth factors and extracellular matrix proteins by human peritoneal mesothelial cells.

OBJECTIVE: To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGFbeta1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC). DESIGN: Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFbeta1 1 ng/mL, or different concentrations of icodextrin. VEGF, TGFbeta1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay. RESULTS: Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFbeta1 secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFbeta1 secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFbeta1 1 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. CONCLUSIONS: The present study provides direct evidence that HPMC can secrete VEGF, TGFbeta1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.

Bicarbonates↗
PubMedDate not supplied

Sodium removal in patients undergoing CAPD and automated peritoneal dialysis.

OBJECTIVES: To compare sodium removal in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) patients, and to identify the main factors that modify Na removal in clinical practice in these patients. DESIGN: Study in three steps. Cross-sectional observational (Study A), and longitudinal interventional (Studies B and C). PATIENTS AND METHODS: First (Study A) we carried out a cross-sectional survey of Na removal in 63 patients on CAPD and 78 patients on APD. Second (Study B), we studied Na removal in 32 patients before and after changing from CAPD to APD therapy. Finally (Study C), we analyzed the impact on Na removal of introducing icodextrin for the long dwell in 16 patients undergoing CAPD or APD. RESULTS: In Study A, total Na removal averaged 210 mmol/day for CAPD patients and 91 mmol/day for APD patients (p < 0.001); Na removal was < 100 mmol/day in 7.1% of CAPD patients and 56.4% of APD patients. Multivariate analysis identified ultrafiltration [B = 125 mmol/day, 95% confidence interval (CI) 110,140], CAPD therapy (B = 60 mmol/day, 95%CI 37, 83), and residual diuresis (B = 51 mmol/L, 95%CI 34, 69) as independent predictors of Na removal (adjusted r2 = 0.76). For APD patients, longer nocturnal dwell times and performing a supplementary diurnal exchange were also independently associated with higher Na removal rates. In Study B, Na removal decreased from 192 to 92 mmol/day (median) after the change to APD (p = 0.02). In Study C, peritoneal Na removal increased from 98 to 148 mmol/day (median) (p = 0.04) after introducing icodextrin. CONCLUSIONS: Standard APD schedules are frequently associated with poor Na removal rates. For any degree of ultrafiltration, Na removal is better in CAPD than in APD. Icodextrin, supplementary diurnal exchanges, and longer nocturnal dwell times improve Na removal in APD. Sodium removal can be estimated from ultrafiltration in patients on CAPD, but must be specifically monitored in patients on APD.

Adult↗
PubMedDate not supplied

Evaluation of intraperitoneal pressure and the effect of different osmotic agents on intraperitoneal pressure in children.

OBJECTIVES: To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell. DESIGN: IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2 with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m2 and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated. PATIENTS: IPP was established in 30 patients with median age of 4.5 years (range 1.0 - 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 - 10.9 years) and median treatment period of 12 months (range 5.6 - 122.3 months). RESULTS: Mean IPP was 12.0 +/- 6.5 cm H2O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin. CONCLUSIONS: IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.

Adolescent↗
PubMed2006

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Steroids, antihistamines and heparin were amongst the first substances to be advocated for adhesion prevention. More recently icodextrin 4%, hyaluronic acid agents and SprayGel have been used. This review aims to evaluate the role of fluid and pharmacological agents in the prevention of adhesions in fertility-conserving gynaecological surgery. OBJECTIVES: To investigate fluid and pharmacological agents for adhesion prevention when used as adjuvants during pelvic surgery. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Menstrual Disorders and Subfertility Group. The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesion formation after fertility-conserving gynaecological surgery. DATA COLLECTION AND ANALYSIS: Data extraction and analysis was performed independently by two authors (Metwally M and Watson A). Two-by-two tables were generated for dichotomous outcomes and expressed as odds ratios (OR) with 95% confidence intervals (CI). For continuous outcomes a standardised mean difference was used. MAIN RESULTS: There is no evidence of benefit from the use of steroids, dextran or other pharmacological agents in any of the outcomes. The use of hyaluronic acid agents may decrease adhesion formation (OR 0.31, 95% CI 0.19 to 0.51) and prevent the deterioration of pre-existing adhesions (OR 0.28 (95% CI 0.12 to 0.66). There is insufficient evidence for the use of icodextrin 4% or SprayGel as adhesion-preventing agents. None of the studied agents has been shown to improve the pregnancy rate when used as an adjunct during pelvic surgery. AUTHORS' CONCLUSIONS: The current evidence for the use of fluid and pharmacological agents for the prevention of adhesions is limited. There is no evidence on any benefit for improving pregnancy outcomes when pharmacological and fluid agents are used as an adjunct during pelvic surgery. There is insufficient evidence for the use of the following agents: steroids, icodextrin 4%, SprayGel and dextran in improving adhesions following surgery. There is some evidence that hyaluronic acid agents may decrease the proportion of adhesions and prevent the deterioration of pre existing adhesions. However, due to the limited number of studies available, this evidence should be interpreted with caution and further studies are needed.

Anticoagulants↗
PubMed2001

Impact of carrier solutions on pharmacokinetics of intraperitoneal chemotherapy.

PURPOSE: In the treatment of gastrointestinal malignancies with dissemination to peritoneal surfaces the principal advantage of intraperitoneal chemotherapy over intravenous chemotherapy is the high drug concentration achieved locally with low systemic toxicity. This advantage can be optimized by maintaining a large area of contact between the chemotherapy solution and the surfaces within the abdomen and pelvis over a prolonged time period. Using a rat model we compared the pharmacokinetics of two drugs infused intraperitoneally, 5-fluorouracil and gemcitabine, in five different carrier solutions. METHODS: A total of 120 Sprague Dawley rats were randomized into groups according to the carrier solution and the drug administered. Rats were given a single dose of intraperitoneal 5-fluorouracil (20 mg/kg) or gemcitabine (12.5 mg/kg) in 0.1 ml/g body weight of each carrier solution. The carrier solutions used varied in their tonicity (0.3%, 0.9% or 3% sodium chloride), or were isotonic and varied in molecular weight (0.9% sodium chloride, 4% icodextrin and 6% hetastarch). With the hypotonic, isotonic and hypertonic sodium chloride solutions, only 5-fluorouracil was used. Each group was further randomized according to the intraperitoneal dwell period (1, 3 or 6 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the blood was sampled using a standardized protocol. The volume of the peritoneal fluid was recorded, and the drug concentrations in the peritoneal fluid and plasma were determined by high-performance liquid chromatography. RESULTS: Measurements of peritoneal fluid volume showed a more rapid clearance of hypotonic and isotonic sodium chloride solutions from the peritoneal cavity as compared to hypertonic sodium chloride and high molecular weight solutions. When comparing the remaining intraperitoneal volumes at 6 h, the differences were statistically significant for both 5-fluorouracil and gemcitabine when hetastarch (P < 0.0001 and P = 0.0004) and icodextrin (P = 0.002 and 0.008) were compared with isotonic sodium chloride solution. Similarly, there was a significant difference in the volumes recorded at 6 h when hypotonic (P < 0.0001) and isotonic sodium chloride solutions (P = 0.0002) were compared with hypertonic sodium chloride solution. The concentrations of chemotherapy in the different carrier solutions varied little. The total amount of drug in the peritoneal cavity decreased with all solutions and more quickly with 5-fluorouracil than with gemcitabine. There was a significant difference in the total intraperitoneal 5-fluorouracil between hypotonic and isotonic sodium chloride solutions at 1 h (P = 0.0003) and 3 h (P = 0.0043), as well as between the isotonic and hypertonic sodium chloride solutions at 1 h (P = 0.03) and 3 h (P < 0.0001). Similarly, there was a significant difference in the total peritoneal gemcitabine at 6 h between icodextrin and isotonic sodium chloride solution (P = 0.01) and between hetastarch and isotonic sodium chloride solution (P = 0.05). There were no significant differences in plasma 5-fluorouracil and plasma gemcitabine concentrations obtained with the five solutions. CONCLUSIONS: These findings show that the clearance of 5-fluorouracil and gemcitabine from the peritoneal cavity can be significantly modified by varying the tonicity or the molecular weight of the carrier solution. Peritoneal fluid clearance was slower with hypertonic sodium chloride and high molecular weight solutions and this resulted in a reduced clearance of chemotherapy. By using a high molecular weight carrier solution the exposure of intraperitoneal cancer cells to gemcitabine was prolonged and drug availability at the peritoneal surface was increased. Similarly, by using a hypertonic carrier solution the exposure to 5-fluorouracil was prolonged and drug availability at the peritoneal surface was also increased.

Animals↗
PubMed2002

Impact of chronic renal failure and peritoneal dialysis fluids on advanced glycation end product and iNOS levels in penile tissue: an experimental study.

OBJECTIVES: To investigate the impact of chronic renal failure (CRF) on advanced glycation end product and inducible nitric oxide synthase (iNOS) in penile tissue, we examined the advanced glycation end product 5-hydroxy methyl furfural (5-HMF) content and iNOS expression in rats in which uremia had been produced by greater than 85% nephrectomy. In addition, the contribution of peritoneal dialysis (PD) fluids to the elevation of penile tissue 5-HMF levels and iNOS staining scores has been investigated. METHODS: Adult male Wistar rats, aged between 10 and 12 weeks and weighing 200 to 330 g, were divided into five groups that each included 6 animals. The first group served as a control group. In the second group, CRF was induced and a peritoneal catheter was implanted, but PD was not performed. In group 3, CRF was induced and PD was performed using dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF was also induced and PD was performed using 3.86% glucose and icodextrin. Finally, in group 5, without CRF, an indwelling catheter was implanted, and the PD procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin. RESULTS: The elevation in 5-HMF levels and iNOS staining scores in penile tissue from groups 2, 3, 4, and 5 was significant compared with group 1 (P <0.05). The elevation in 5-HMF levels and iNOS staining scores was also significant between groups 2 and 3, 2 and 4, 3 and 4, 3 and 5, and 4 and 5 (P <0.05). Moreover, the correlation between the 5-HMF levels and iNOS staining scores was statistically significant (r = 0.525, P = 0.003). CONCLUSIONS: In the present experimental study, we found that 5-HMF levels and iNOS staining scores were significantly elevated in rat penile tissue in which uremia had been produced compared with the groups without CRF. Additionally, PD fluids containing glucose had an effect on the elevation of penile tissue 5-HMF levels and iNOS staining scores.

Animals↗
PubMed2004

Survey among members of the roman group of gynecologic endoscopy on the use of agents for postoperative adhesion prevention.

STUDY OBJECTIVE: To evaluate patterns of use of agents for postoperative adhesion prevention. DESIGN: Mail survey. SETTING: Departments of Obstetrics and Gynecology, university-affiliated and public hospitals, Rome, Italy. PARTICIPANTS: Members of the Roman Group of Gynecologic Endoscopy. INTERVENTION: Evaluation of forms returned. MEASUREMENTS AND MAIN RESULTS: The response rate to either electronic or regular mailing was 31%, for a total of 42 forms evaluated. For laparoscopy, the perceived postoperative de novo adhesion formation rate was 0%-25%, whereas the adhesion reformation rate was 26%-75%; for laparotomy, the rates were 26%-75% and >75%, respectively. Sixty-five percent of the respondents were using at least one method for postoperative adhesion prevention during laparoscopy, and 68% during laparotomy. The most frequently used method during laparoscopy was Ringer's lactate (77% of the respondents), followed by ferric hyaluronate gel (46% of the respondents), and 4% icodextrin (39% of respondents). During laparotomy, the most frequently used methods were Ringer's lactate (28%), normal saline (20%), and 4% icodextrin (20%). Antibiotic prophylaxis was used by 87.5% of respondents. CONCLUSION: Postoperative adhesion formation, and especially reformation, are perceived as significant problems. Sixty-five percent of the respondents used some method for adhesion prevention after operative laparoscopy, with Ringer's lactate, ferric hyaluronate gel, and 4% icodextrin being the most frequently used.

Ferric Compounds↗
PubMed1994

Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.

Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.

Colorectal Neoplasms↗
PubMed2004

The triggering of human peritoneal mesothelial cell apoptosis and oncosis by glucose and glycoxydation products.

BACKGROUND: Peritoneal dialysis fluids (PDFs) have been shown to alter mesothelial cell functions. To further determine the mechanisms involved, we investigated the effects of glucose, glucose degradation products (GDPs) and advanced glycation end products (AGEs) on the inhibition of human peritoneal mesothelial cell (HPMC) proliferation and the induction of apoptosis and oncosis. METHODS: Four PDF solutions, heat-sterilized dextrose-lactate, filtered dextrose-lactate and heat-sterilized dextrose-bicarbonate-lactate, each containing 15 or 45 g/l glucose, and heat-sterilized icodextrin-lactate, containing 75 g/l icodextrin, were tested. In addition, we analysed the independent and synergistic effects of two glucose compounds, i.e. 3-deoxyglucosone (3-DG), a major GDP, and Nepsilon-(carboxymethyl)-lysine (CML), a high-affinity AGE receptor (RAGE) ligand on HPMC viability. Cell proliferation was measured by methyl-[(3)H]thymidine incorporation. Oncosis was quantified by nuclear propidium iodide (PI) DNA-intercalating capability, and apoptosis by the decrease in mitochondrial transmembrane potential ( triangle up psim). RESULTS: It was found that heat-sterilized dextrose-lactate inhibited HPMC proliferation to a greater extent than filtered dextrose-lactate, heat-sterilized dextrose-bicarbonate-lactate, or heat-sterilized icodextrin-lactate (P<0.001). Compared to filtered dextrose-lactate, heat-sterilized dextrose-lactate induced a significantly greater degree of apoptosis (P<0.05) and oncosis (P<0.01). Glucose-induced cell death and antiproliferative activity were significantly potentiated by the action of 3-DG or CML-albumin. By blocking the AGE-RAGE interaction recombinant soluble-RAGE reduced the PDF-induced inhibitory effect on cell proliferation (P<0.001) and apoptosis (P<0.05). CONCLUSION: Heat-sterilized PDFs that contain high glucose concentrations and GDPs, which are AGE precursors, reduce cell proliferation, induce mesothelial cell apoptosis and oncosis, and may be involved in peritoneal damage. PDFs containing lower glucose derivative products are more biocompatible.

Apoptosis↗
PubMed2005

Efficacy of three adhesion-preventing agents in reducing severe peritoneal trauma induced by bipolar coagulation in a laparoscopic rat model.

OBJECTIVE: To compare the antiadhesion efficacy of three agents (4% icodextrin, ferric hyaluronate gel, and Ringer's lactate) in severe peritoneal trauma caused by bipolar coagulation in a laparoscopic rat model. DESIGN: Prospective, randomized, blinded experimental study. SETTING: International Laparoscopic Surgery Centre, Clermont-Ferrand, France. ANIMAL(S): Female Sprague-Dawley rats. INTERVENTIONS: Animals were prospectively randomized to receive one of the three agents or to be controls. Coagulation of the parietal peritoneum was performed using a bipolar 40-W current followed by administration of an antiadhesion agent. Postoperative adhesion assessment was carried out on day 7 in 42 rats. MAIN OUTCOME MEASURE(S): Adhesions were scored according to their extent and severity. RESULT(S): Adhesions occurred in all rats, however, adhesion and vascular adhesion rate scores were significantly higher in controls compared with treated groups. Adhesions were more likely to be filmy and easily separable in the 4% icodextrin group compared with the Ringer's lactate solution group. CONCLUSION(S): Adhesion scores were decreased by the use of antiadherent agents. However, no rats were found to be free of adhesions after severe peritoneal trauma induced by 40-W bipolar coagulation of the peritoneum.

Animals↗
PubMed2006

Three-year analysis of microbial aetiology and antimicrobial susceptibilities of PD peritonitis.

The first-line antibiotic treatment of peritoneal dialysis (PD) peritonitis has to cover the most common causative microorganisms. Our aim was to analyse antimicrobial sensitivities of different empirical protocols for initial therapy of PD peritonitis. We analysed the aetiological microorganisms of PD peritonitis and their antimicrobial sensitivities during a 36-month period. Clinical characteristics of the cases were recorded. Altogether 86 PD peritonitides were diagnosed during the study period. In 58 cases, microbial cultures were positive with 72 different causative agents. 28 cases (33%) were culture-negative. Over-representation of icodextrin users was noted among the culture-negative cases. Staphylococcus aureus was the most frequent causative agent, often leading to severe course of illness. Of antimicrobial protocols for initial treatment of peritonitis tested in vitro, the combination of a first-generation cephalosporin and an aminoglycoside was superior to the combination of a first-generation cephalosporin and ceftazidime as well as to fluoroquinolone monotherapy but similar to the combination of vancomycin and ceftazidime. Based on antimicrobial sensitivities we continue using an aminoglycoside in the empirical treatment of PD peritonitis. In the present material, users of icodextrin PD fluid were over-represented among patients with culture-negative peritonitis.

Aged↗
PubMed2003

Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model.

OBJECTIVE: To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh. SUMMARY BACKGROUND DATA: Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas. METHODS: In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy. RESULTS: Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%). CONCLUSIONS: Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model.

Animals↗
PubMed2005

Occult hypoglycemia in a diabetic patient on peritoneal dialysis.

In a patient with diabetes mellitus undergoing icodextrin continuous ambulatory peritoneal dialysis, the interference caused by icodextrin metabolites in bedside glucose analyzers led to an overestimation of capillary glucose levels and the potential for inappropriate therapy. We report this case to raise an awareness of this among emergency care providers who are at the front-line treating diabetes emergencies.

Aged↗
PubMedDate not supplied

Metabolic consequences of peritoneal dialysis.

Optimization of the peritoneal dialysis (PD) prescription includes attempts to normalize the patient's blood pressure and extracellular volume. To do so, one must utilize crystalloid or colloid osmotic agents to achieve ultrafiltration. These osmotic agents are systemically absorbed and thus have both potential benefits and adverse effects. With glucose-based dialysate solutions, the average patient absorbs 300-450 kcal of glucose per day on either continuous ambulatory peritoneal dialysis (CAPD) or the cycler. The amount of glucose absorbed varies based on peritoneal transport characteristics, prescription, and tonicity of fluids used. Alternative osmotic agents such as amino acids and macromolecular solutions, including polypeptides and polyglucose (icodextrin) solutions, have a different rate of systemic absorption and thus a different caloric load profile. In addition, there are protein losses that average about 10 g/day with glucose-based solutions and glucose losses with either amino acid or icodextrin dialysate solutions. There are also potential advantages of these alternative solutions with regard to ultrafiltration. Glucose-based solutions require the development of significant crystalloid osmotic forces, which are dissipated as glucose is absorbed systemically. In contrast, macromolecular solutions achieve ultrafiltration via differences in colloid osmotic pressure, and the absorption of these agents is of a lesser magnitude than glucose-based solutions. Further research is needed to determine other potential risks and benefits of these alternative dialysate solutions.

Amino Acids↗
PubMedDate not supplied

Peritoneal dialysis: a primary care perspective.

As the population of chronic kidney disease (CKD) and end-stage renal disease (ESRD) grows at an alarming rate, primary care physicians will increasingly be involved in the management of these patients. Early recognition of CKD and timely referral to a nephrologist when glomerular filtration rate approaches 30 mL/min/1.73 m(2) is extremely important to improve ESRD outcome and appropriate selection of dialysis modality. Peritoneal dialysis (PD) remains a viable treatment option for ESRD patients. PD is less expensive dialysis modality and may provide a survival advantages over hemodialysis in first 2 to 4 years of treatment. Preserving residual renal function (RRF) is of paramount importance to prolong the survival outcomes in PD patients. Thus preservation of RRF is an important goal in the management of PD patients. Every effort should be made to avoid nephrotoxic drugs like aminoglycosides and nonsteroidal anti-inflammatory drugs, and limit the use of radiocontrast agents in PD patients with RRF. Judicious use of prophylactic antibiotics to prevent peritonitis would further help to reduce morbidity from PD. Protecting peritoneal membrane from long-term toxic and metabolic effects of the conventional glucose-based solutions is another objective to further improve PD outcome. Development of new, more biocompatible PD solutions holds promise for the future. One such solution, icodextrin, is now approved for use in the United States. Although extremely safe to use, it is associated with unique metabolic effects that may concern primary care physicians. They include false elevation of blood glucose, a reversible increase in serum alkaline phosphatase and a false decline in serum amylase. Monitoring of glycemia by assays that use glucose dehydrogenase pyrroloquinoline quinone enzymes should be avoided and serum amylase alone should not be relied on in diagnosing pancreatitis in patients on icodextrin.

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