Rinsing of complex conduit geometries in implanted insulin infusion devices

Abstract

Implanted intra-peritoneal insulin infusion (‘i4’) devices administer insulin into the peritoneum of diabetic patients with extreme blood glucose swings, that are highly difficult to control. The flushing procedures of i4 devices to clear obstructions from its conduits caused by insulin degradation are not always fully effective. The goal of this research was to investigate how the flushing effectiveness can be increased by adapting conduit geometries and adapting the flush flow rate. It was hypothesized that flushing of conduits with complex geometries (featuring a.o. widened sections, or parallel flow paths) would be less effective than simple geometries, and that a higher flush flow rate would increase flushing effectiveness. An ex vivo laboratory experimental setup was created by producing polymethyl methacrylate (PMMA) test conduits of differing geometries that model the in vivo implanted intra-peritoneal insulin infusion (i4) device’s conduits, but are transparent to allow optical inspection. These test conduits were filled with acidified insulin, and precipitation thereof was artificially induced by heat incubation of the filled conduits, as a model for obstructed i4-device conduits. Experimental flushing procedures using sodium hydroxide (NaOH) as a flush liquid were performed on these test conduits at 2 different flush flow rates: 1.5mL/min, and at 20mL/min. After the flushing, the effectiveness of the procedure to clear the conduit of precipitates was evaluated by microscopically analysing the quantity of residual precipitates, and measuring Total Organic Carbon (TOC) of a liquid sample taken from the post-flushing conduit. All conduits with more complex geometries than straight tubes showed lower effectiveness of cleaning by flushing. The high flow rate showed an averaged 19% higher effectiveness of the flushing. In the sections of the conduits featuring widening, flushing often resulted in a narrow path being effectively cleaned, but significant regions of the conduit showed presence of residual precipitates. This research provides insight into the negative influence of complex geometries on effectiveness of flushing, and the positive influence of increased flush flow rate to improve effectiveness. Experimental repetition in this research is low, and the experimental methods were prone to much influence of material or measurement disturbances. This research merits elaboration and improvement of materials and methods to more precisely investigate the proposed relations. Outcomes suggest that future i4-devices should be designed to avoid complex conduit geometries as much as possible, and to be flushed with significantly higher flush flow rates than currently clinically applied.