The University of Vermont Research Protections Office determined that this project was exempt from review by the Institutional Review Board.
The University of Vermont and the University of Vermont Medical Center protocols governing the use of cadavers in research were followed in all cases. The first three cadavers came from the University of Vermont Anatomy Department, through the Anatomical Gift Program. This program has a robust registration process, which includes the consent of the live donor to comply with their wishes to allow the University of Vermont to use their body for teaching and research, including the development of new and innovative techniques and devices. The Anatomical Gift Program maintains a file of these signed consent and registration documents. The fourth cadaver was procured through the University of Vermont Medical Center Department of Pathology, after obtaining written consent from the next of kin prior to expiration, in keeping with the patient’s wishes. This consent form is on record at the University of Vermont Medical Center.
All methods and experiments were carried out accordance with relevant guidelines and regulations (Declaration of Helsinki).
Benchtop in vitro study
Test devices were created under sanitary conditions by inserting five 4mm diameter tungsten-carbide ball (ACER Racing, Los Angeles, CA) into the center of 4cm long sections of Silastic tubing, four with medical grade tubing (Merit Medical, South Jordan, UT) and two with laboratory grade tubing (Tri-anim Health Services, Dublin, OH).(Fig. 1A) The ends of each column of tungsten-carbide balls were bordered by two 4mm in diameter stainless steel balls (VXB, Anaheim, CA), which were secured with 0 Prolene sutures to create a water-tight fit.
A single 4cm long section of medical grade Silastic tubing was filled with 1% methylene blue and sealed at both ends with 4mm in diameter stainless steel balls and 0 Prolene sutures to create a water-tight fit.
Eight Erlenmeyer flasks were filled with 500ml of medical grade normal saline and A) normal saline negative control, B) 0.1ml of 1% methylene blue for a concentration of 0.02% as a positive control, C) Five 4mm in diameter tungsten-carbide and two 4mm in stainless steel balls as a positive control, D) the methylene blue device, E) one test device, F) one test device, G) two test devices, and H) two test devices. The flasks were stored in the dark at room temperature for 21 months.(Fig. 1B) Two ml effluent saline samples were drawn from each flask at the following time points: 1 day, 14 days, 3 months, 6 months, 9 months, and 21 months. Samples A, B, and D were tested for methylene blue (668 nm) by ultraviolet visible photometry. Samples A, C, E, F, G, H, I, and J were digested with 0.280ml of nitric acid (TraceMetal Grade, Thermo Fisher Scientific, Waltham, MA) and then analyzed for tungsten, iron, cobalt, and chromium (6, 9, and 21 month measurements) by inductively coupled plasma mass spectrometry (ICP-MS) by the Meadowlands Environmental Research Institute (Rutgers University, Newark, NJ).
10 test devices of varying designs (flexible straight, segmented, and curled), lengths (8 to 16cm), and weights (10.5 to 20.6g) were attached to the terminal coiled ends of 8 Merit (Merit Medical, South Jordan, UT) and 2 Swan Neck Missouri Covidien (Covidien LLC, Mansfield, MA) curled PD catheters using 0 Prolene sutures.(Fig. 2) The devices were created by inserting multiple 4mm diameter tungsten-carbide balls into the center of medical grade Silastic tubing, with a 4mm in diameter stainless steel ball bordering each end. The ends were tied securely with 0 Prolene sutures. This created a water-tight attribute of each device, which remained intact throughout the study.
Four non-embalmed male cadavers were used within 24 hours from the time of expiration. Percutaneous insertion of all PD catheters and devices were successfully accomplished using the following percutaneous image guided technique. A needle was used with ultrasound guidance to enter the peritoneal cavity through the anterior abdominal wall and rectus muscle. A fluoroscopic and digital acquisition peritoneogram was obtained to ensure an intraperitoneal position and to delineate the retrovesical space. A 0.035-inch diameter guide wire was advanced into the peritoneal space and the needle was removed. Then, a 4-French angled angiographic catheter was used with the guide wire, to enter the retrovesical space. A 0.035-inch guide wire was coiled in the retrovesical space, the 4-French angiographic catheter was removed, and an 18-French peel away sheath (6.5mm outside diameter) was directed into the retrovesical space. The guide wire was removed and the PD catheter with attached device was pushed through the peel away sheath and into the retrovesical space. The peel away sheath was removed and the PD catheter was attached to the skin without creating a subcutaneous tunnel.
For each cadaver, one liter of normal saline was attempted to be infused and drained through each PD catheter via gravity. Flow rates and volumes were recorded. Table (Philips Allura table level at -9cm for infusion, +18 cm for drainage, and +6cm for cone beam CT), infusion pole (normal saline bag 6 feet above floor), and drainage bag (bag placed on floor) heights were standardized and consistent for all cadavers and all infusions and drainages. Between infusions and drainages for each PD catheter, each cadaver was manually rolled 360 degrees around the vertical axis to provoke migration. Peritoneograms in multiple 3-dimentional projections, as well as axial cone beam CT scanning (XperCT, Philips Medical Systems, The Netherlands) were obtained before and after each roll to detect migration. Images were recorded and archived.
Finally, each PD catheter and device were removed percutaneously. Each catheter and device were examined for tears and ruptures, and any breach in integrity was noted.
Statistical analysis for benchtop in vitro and cadaver studies
Comparisons of tungsten concentrations between the normal saline negative controls and the devices made of medical grade silastic tubing, as well as between the medical device made with laboratory grade silastic tubing and the devices made with medical grade silastic tubing, were performed with repeated measures mixed model analyses of variance. All effluent metal data was log transformed for normality. Comparison of the positive methylene blue control to the saline effluent of the methylene blue device was done using the Wilcoxon rank sum test. Cadaver study catheter flow rate comparisons were done using repeated measures mixed model analyses of variance. P-values < 0.05 were considered to be statistically significant. All statistical analyses were performed using SAS version 9.4 statistical analysis software (SAS Institute, Inc., Cary, NC).