Development of an ex-vivo porcine lower urinary tract model to evaluate the performance of urinary catheters

Abstract

Intermittent catheterization is the gold standard method for bladder management in individuals with urinary retention and/or incontinence. It is therefore important to understand the performance of urinary catheters, especially on parameters associated to risks of developing urinary tract infections, and that may impact the quality of life for urinary catheter users. Examples of such parameters include, urine flowrate, occurrence of flow-stops, and residual urine left in the bladder after flow-stop. Reliable in-vitro and/or ex-vivo laboratory models represent a strong asset to assess the performance of urinary catheters, preceding and guiding in-vivo animal studies and/or human clinical studies. Existing laboratory models are generally simplified, covering only portions of the catheterization process, or poorly reflect clinical procedures. In this work, we developed an ex-vivo porcine lower urinary tract model that better reflects the catheterization procedure in humans and allows to investigate the performance of standard of care catheters. The performance of three standard of care catheters was investigated in the developed model showing significant differences in terms of flowrate. No differences were detected in terms of residual volume in the bladder at first flow-stop also when tuning the abdominal pressure to mimic a sitting down and standing up position. A newly discovered phenomenon named hammering was detected and measured. Lastly, mucosal suction was observed and measured in all standard of care catheters, raising the concern for microtrauma during catheterization and a need for new and improved urinary catheter designs. Results obtained with the ex-vivo model were compared to in-vivo studies, highlighting similar concerns.

Figure 1

Example of a freshly retrieved male porcine LUT (a), and of a male porcine LUT prepared after trimming off the excess fat and placing of the fittings (b). In this specific example, a needle was punched through the bladder wall to access the bladder lumen (b); this additional access point was never used in the tests described in this manuscript.

Figure 2

Example of a filled male porcine LUT inside the pressurized tank. The porcine LUT is pinned to the silicone mold (in pink) and connected to the tank via the urethral and ureteral fittings. (a) lateral view, (b) frontal view.

Figure 3

Schematic representation of the ex-vivo porcine LUT model setup. (1) Pressurized tank, (2) silicone mold to mimic the pelvic floor, (3) porcine LUT, (4) porcine urethra, (5) catheter inserted in the bladder through the urethra, (6) reservoir used to fill the bladder through one of the two ureters, (7) peristaltic pump, (8) adjustable water column to apply the desired abdominal pressure in the tank “1”, (9) vessel to collect the volume emptied from the bladder, (10) waste, (11) pressure sensor, (12) weighing scale, (13) ON/OFF valve, (14) ureters, (15) syringe used to add additional solutions/suspensions in the bladder through the second available ureter (can also be used as an access point for an endoscope), (16) LUT model support allowing for the vertical movement of both the tank “1” and the water column “8”, (17) computer collecting data from the pressure sensor “11” and the weighing scale “12”.

Figure 4

Workflow of an IC. The figure shows the possible events during intermittent catheterization.

Figure 5

Performance of three standard of care catheters: (a) flowrate (mL·s^-1), calculated in the first 5 s of voiding, (b) residual volume (mL), calculated as the difference between the total volume in the porcine bladder and the volume emptied at the first flow-stop, (c) mucosal suction perceived by the operator during the first flow-stop, and (d) hammering perceived by operator during the whole catheterization. For all Brands, a total of 3 catheters were tested, each catheter was used 5 times and a total of 3 porcine LUTs were used to take the biological variation into account. Significant differences were calculated using a t-test with Welch correction when appropriate.

Figure 6

Endoscopic investigation in the ex-vivo porcine LUT model. The (a) series depicts the phenomenon of mucosal suction from outside the Brand A catheter (CH12). The (b) series depicts, instead, the phenomenon of mucosal suction from inside the Brand A catheter (CH16). (6a1 and 6b1): the eyelet is not blocked, and bladder voiding is continuing. (6a2 and 6b2): the bladder mucosa is approaching the open eyelet, in “6b2” the eyelet further away from the endoscope already shows tissue pulled into the catheter, bladder voiding is continuing. (6a3 and 6b3): Mucosal suction, flow-stop and repositioning is required.

Figure 7

Endoscopic investigation in the ex-vivo porcine LUT model. The (a) series depicts the phenomenon of mucosal suction from outside the Brand B catheter (CH12). The (b) series depicts, instead, the phenomenon of mucosal suction from inside the Brand B catheter (CH16). Arrows are used in picture 7a2 and 7a3 to guide the reader in visualizing the eyelet. (7a1 and 7b1): the eyelet is visible and bladder emptying is continuing. (7a2): the bladder mucosa is approaching the open eyelet. Flow through the catheter is continuing. (7a3 and 7b2): Mucosal suction, flow-stop, and repositioning is required.

Figure 8

Endoscopic investigation in the ex-vivo porcine LUT model. The (a) series depicts the phenomenon of mucosal suction from outside the Brand C catheter (CH12). The (b) series depicts, instead, the phenomenon of mucosal suction from inside the Brand C catheter (CH18). (8a1 and 8b1): the eyelet is visible and bladder emptying is continuing. (8a2): the bladder mucosa is approaching the open eyelet, bladder emptying continues. (8a3 and 8b2-3): Mucosal suction, flow-stop and repositioning is required.

Figure 9

Effect of the abdominal pressure on the performances of three standard of care catheters: (a) flowrate (mL·s^–1), calculated in the first 5 s of voiding, (b) residual volume (mL), calculated as the difference between the total volume in the porcine bladder and the volume emptied at the first flow-stop, (c) mucosal suction perceived by the operator during the first flow-stop, and (d) hammering perceived by operator during the whole catheterization. For all Brands, a total of 3 catheters were tested, each catheter was used 5 times in a total of 3 porcine LUTs to take the biological variation into account (N = 15, SD). The sample size for the flowrate calculation was between 10 and 15 for all brands at both abdominal pressures tested. Significant differences were calculated using a t-test with Welch correction when appropriate.

Figure 10

Examples of intra-catheter pressure sensor measurements. (a) Brand A, (b) Brand B, and (c) Brand C. The numbers on the figures represent specific events during IC: (1) insertion of the catheter through the sphincter and into the bladder, emptying starts; (2) flow-stop with an associated mucosal suction; (3) series of mucosal suction events during repositioning; (4) withdrawal of the catheter out of the bladder. The first mucosal suction pressure drop for each example, as indicated by the numbers “2” is zoomed in next to the pressure profile. In the zoomed in picture, the measured profile is shown in blue whereas a gaussian fitting is depicted in red. Brand A, B, and C were tested 5 times in 3 different porcine LUTs (N = 15, SD). An abdominal pressure of 50 cmH₂O was used.

Figure 11

Pressures measured with the intra-catheter pressure sensor at first flow-stop. The test was performed at both 20 and 50 cmH₂O of abdominal pressure. Each Brand was tested 5 times in 3 different porcine LUTs. The same porcine LUTs where used at both abdominal pressures. Results are reported as individual values, mean and standard deviation. Statistical analysis was performed by means of t-test using Welch’s correction when appropriate.

Figure 12

Comparison between the pressure at first flow-stop recorded with the intra-catheter pressure sensor. The results are divided according to whether the mucosal suction phenomenon was perceived by the operator during catheterization, or not. Results are reported as individual values (N = 15, SD). Statistical analysis was performed by means of t-test using Welch’s correction when appropriate.

Figure 13

Example of hammering measured with the intra-catheter pressure sensor (Brand C, 20 cmH₂O).

Figure 14

Endoscope investigation in the in-vivo porcine studies. The pictures are snapshot of a video recorded during the catheterization in a pig with a SOC catheter (Brand A, CH16). Tissue from the bladder mucosa progressively closes in towards the catheter eyelet as emptying continues (a), the mucosal tissue then begins to be sucked inside the catheter lumen (b) when suddenly mucosal suction happens (c), the suction increases blood flow on the tissue pulled inside the catheter (d), repositioning begins (e), after which tissue residues (pointed at with arrows) can be seen on the eyelet sides, probably as a consequence to scraping (f).

Figure 15

In-vivo in-catheter pressure analysis. The pressure drop visible after the 150 s mark corresponds to the perceived mucosal suction phenomenon.