What Is Non-PVC (Polyvinyl Chloride) Infusion Set?

The Rationale for using PVC in the infusion set

Non-PVC (Polyvinyl Chloride) Infusion Set is the infusion set made of Non-PVC materials. Non-PVC (polyvinyl chloride) infusion sets have some advantages that PVC infusion sets do not have. However, producers prefer to use PVC because it provides the following:

1. High strength and flexibility (if plasticized).
2. Transparency and ease of sealing.
3. Good resistance to sterilization procedures.
4. Lesser expenditures or costs.

The addition of bis(2-Ethylhexyl)phthalate (DEHP) makes the PVC-based infusion devices flexible. The DEHP, however, is not chemically bonded to PVC; hence, it can leach into the drug solutions, especially those containing non-aqueous components such as fats or surfactants. Based on research findings, DEHP inflicts adverse health effects on patients who receive the infusion. Thus, PVC in infusion sets is discouraged if not allowed. This reservation of using PVC gives birth to the non-PVC infusion set.

Meaning of Non-PVC infusion set

Non-PVC infusion set means the use of other materials aside from PVC. In other saying, designers need to replace the PVC with alternative materials. In most instances, manufacturers use polyurethane (PU) and polyolefin (PO) instead of PVC.

Advantages of Non-PVC infusion sets

• Non-PVC-based tube lowers the drug sorption. Based on the study titled “Evaluation of drug sorption to PVC- and non-PVC-based tubes in administration sets using a pump” by Su-Eon Jin et al., the PVC-based tubes showed high sorption levels for many drugs such as diazepam, tacrolimus, nitroglycerin, and cyclosporine A. There are several approaches to lowering drug sorption: (1) using alternative materials or polymeric combinations and (2) using layer-by-layer designs. Under using alternative materials, a non-PVC-based tube lowers the drug sorption;

• Non-PVC infusion sets do not carry the DEHP molecules, which cause adverse health effects; The leached DEHP molecules from the PVC tube during intravenous infusion of aqueous drug solutions cause several toxic health effects, including but not limited to a disturbance in human metabolism.

• Non-PVC tube retains and maintains the stability of the anti-cancer drug docetaxel in solution. Based on the study by Kang Hoon Park and Dong June Chung published in 2015 and titled “Stability study of docetaxel solution (0.9%, saline) using non-PVC and PVC tubes for intravenous administration”, they found out that the docetaxel solution passing through the non-PVC (polyolefin) tube was more stable than the solution coursing through the PVC tube, with high DEHP content. As mentioned in the preceding, the DEHP molecules leaching and coming from the PVC tube dissolve themselves in the solution. Then, these molecules interact with the surfactants of anti-cancer drugs, such as docetaxel, which reduces the solubility of docetaxel in an aqueous solution during anti-cancer drug administration.

Surfactants, such as polysorbate 80 and polyethoxylated castor oil, enhance the solubility of anti-cancer drugs in the solution. When the leached DEHP molecules interact with the surfactants, the solubility of the anti-cancer drug wanes, and the precipitation of the anti-cancer drug molecules leads to a reduction in drug efficacy.

Alternative materials to PVC 

If PVC possesses several shortcomings as a material for infusion sets, then search for alternatives started in manufacturing. Based on the paper titled “Impact of alternative materials to plasticized PVC infusion tubings on drug sorption and plasticizer release”, written by N. Tokhadze et al. and published in December 2019, three drugs—namely, diazepam, insulin, and paracetamol—were tested on five possible materials for infusion sets. The study aimed to assess the interactions between the said drugs to the five alternative materials in terms of drug sorption and plasticizer release.

Researchers tested the following five alternative materials:

The study found out that PVC coextruded with PE, thermoplastic elastomers alone, or coextruded with PVC could be exciting alternatives to PVC infusion sets to prevent sorption and plasticizer release phenomena.

Non-DEHP PVC

One of the drawbacks of using PVC in the infusion set is the leaching of the DEHP, which has several toxicity effects on humans. Thus, researchers propose that DEHP, as a plasticizer for PVC, be replaced as a second option when PVC’s replacement cannot be implemented in full.

In line with this, researchers propose eight to nine other plasticizers that could be used in PVC. However, the consensus seems to have been built around four in particular: di-octyl terephthalate (DOTP), trioctyl trimellitate (TOTM), acetyl tributyl citrate (ATBC), and di-isononyl cyclohexane (DINCH). The researchers based their consensus on cost, performance, and chemical compatibility, which are very much related to the use of PVC as part of infusion sets.

Researchers ranked the possible replacements for DEHP in terms of efficiency factor, relative cost, compatibility, chemical resistance, long-term aging, migration, and red blood cell (RBC) hemolysis. The following table summarizes the different properties versus the plasticizer type, with the DEHP as the standard. The table aims to serve as the basis of comparison, with (1) being the best and (7) being the worst. If two items are considered equivalent, they have the same ranking. 

Based on Table 1, TOTM appears to be the plasticizer of choice for drug infusion or chemotherapy because of its significant chemical resistance. Designers could consider DOTP because of its low costs. However, it failed in efficiency factors, migration, and RBC hemolysis.

ATBC and BTHC are bio-based plasticizers. In terms of sustainability, they are the best plasticizers on the list, and they are both biodegradable. Both plasticizers show excellent toxicological and eco-toxicological properties. ATBC is the common plasticizer for gastrointestinal tract applications. In contrast, medical workers often use the BTHC for blood storage bags and catheters. BTHC, however, is a very expensive plasticizer.

DOA or dioctyl adipate shows the best efficiency among the common plasticizers. It demonstrates, by far, the best low-temperature properties. Its biggest drawback is the tendency to migrate easily to the surface of the tubing, which can cause other problems.

Finally, to store blood, wherein the use of PVC applies most of the time,  DINCH works best as an alternative to DEHP to avoid the hemolysis of blood cells. However, despite some recent licensing arrangements and expansion, the problem of supply limitations remains.

Future trends in non-PVC infusion sets

With the drawbacks of PVC infusion sets as enumerated and discussed in the preceding, the search for possible replacement of PVC as the primary material for infusion sets needs to be started soonest. There have been attempts to search for potential substitutes for PVC. Still, if these efforts will not suffice, the search for possible replacements of DEHP as a plasticizer of PVC needs to be started. However, based on the initial steps toward finding new plasticizers, the choice of plasticizers will vary from one indication to another. It may be more complicated and taxing, but researchers in the manufacturing industry need to do it to avoid the health complications of PVC with DEHP.