Capacity of Infusion Lines for Insulin Adsorption: Effect of Flow Rate on Total Adsorption

Abstract

Background: Insulin adsorption to clinical materials has been well observed, but not well quantified. Insulin adsorption reduces expected and actual insulin delivery and is unaccounted for in insulin therapy or glycemic control. It may thus contribute to poor control and high glycemic variability. This research quantifies the problem in the context of clinical use. Method: Experimental insulin adsorption data from literature is used to calculate insulin delivery and total insulin adsorption capacities for polyethylene (PE) and polyvinal chloride (PVC) lines at clinically relevant flow rates and concentrations. Results: Insulin adsorption capacity decreased hyperbolically with flow rate for both PE and PVC, where low flow scenarios result in greater insulin adherence to infusion lines. When the infusion flow rate was halved from 1 to 0.5 mL/h, twice as much insulin adsorbed to the line. Insulin loss to adsorption resulted in up to ~50% of intended insulin not delivered over 24 hours in a low flow and low concentration context. Conclusion: Material capacity for insulin adsorption is not constant, but increases with decreasing flow. Different materials have different adsorption capacities. In low flow and low concentration contexts, such as in neonatal or pediatric intensive care, insulin loss to adsorption represents a significant proportion of daily insulin delivery, which needs to be accounted for.

Clinical Recommendations for Managing the Impact of Insulin Adsorptive Loss in Hospital and Diabetes Care

“…In the case of very low flow pump infusions (of the order of μL/h), reflecting significant extrapolation of the relationship in Figure 1, adsorptive capacity is constrained to 500 U/m 2 , which is approximately twice the maximum observed across both materials in Ref. 24…”

“…For this analysis, all lines are assumed to be PE or PE-lined, as the most conservative case, since PE adsorbs less insulin than PVC. 24 A model-based analysis (see Appendix 1 for model) is carried out to assess the impact of adsorption at three different concentrations: 0.2, 1.0, and 100 U/mL. The model in Appendix 1 is used to calculate time-dependent insulin concentration at the infusion line outlet, representing the time profile of insulin delivered to the patient.…”

“…Appendix 2 translates concentrations and flow rates in mL/h to U/kg/h, for comparison across different ICU contexts. The material's total capacity for insulin adsorption (U/m 2 ) is assumed hyperbolic, based on relationships observed in previous work, 24 and the resulting equation in Figure 1 is used. In the case of very low flow pump infusions (of the order of μL/h), reflecting significant extrapolation of the relationship in Figure 1, adsorptive capacity is constrained to 500 U/m 2 , which is approximately twice the maximum observed across both materials in Ref.…”

“…As these infusion rates are of the order of μL/h rather than mL/h, the adsorptive capacity of the material is constrained to a maximum of 500 U/m 2 , as in Figure 1. The upper limit on adsorptive capacity of 500 U/m 2 was chosen as being similar or greater than the maximum adsorptive capacities seen in PE and PVC, 24 presenting the clinically conservative case of the maximal possible adsorptive loss.…”

“…Adsorptive capacity is limited to a maximum 500 U/m 2 , based on previous observations. 24 Clinical takeaway. Total adsorption to insulin lines is currently difficult to estimate due to uncertainties in dynamics at low flow rates and no reported test data.…”