Comparative Analysis of Nebulizers in Clinical use for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Abstract

Objective: Technical ex-vivo comparison of commercial nebulizer nozzles used for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Methods: The performance of four different commercial nebulizer nozzles (Nebulizer; HurriChem; MCR-4 TOPOL; QuattroJet) was analysed concerning: i) technical design and principle of operation, ii) operational pressure as function of the liquid flow rate, iii) droplet size distribution via laser diffraction spectrometry, iv) spray cone angle, spray cone form as well as horizontal drug deposition by image-metric analyses and v) chemical resistance via exposing to a cytostatic solution and chemical composition by means of spark optical emission spectral analysis. Results: The Nebulizer shows quasi an identical technical design and thus also a similar performance (e.g., mass median droplet size of 29 micrometer) as the original PIPAC nozzles (MIP/ CapnoPen). All other nozzles show more or less a performance deviation to the original PIPAC nozzles. The HurriChem has a similar design and principle of operation as the Nebulizer, but provides a finer aerosol (22 micrometer). The principle of operation of MCR-4 TOPOL and QuattroJet differ significantly from that of the original PIPAC nozzle technology. The MCR-4 TOPOL offers a hollow spray cone with significantly larger droplets (50 micrometer) than the original PIPAC nozzles. The QuattroJet generates an aerosol (22 micrometer) similar to that of the HurriChem but with improved spatial drug distribution. Conclusion: The availability of new PIPAC nozzles is encouraging but can also have a negative impact if their performance and efficacy is unknown. It is recommended that PIPAC nozzles that deviate from the current standard should be subject to bioequivalence testing and implementation in accordance with the IDEAL-D framework prior to routine clinical use.

Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)

“…In practice this pressure operating window corresponds to the liquid volume flowrate of 1.2 ml/s - 1.6 ml/s. [2]. Accordingly, these operating parameters were stored in the high-pressure injector as a separate MDN-PIPAC working programme.…”

“…To optimize spatial aerosol distribution during MDN-PIPAC, the spraying distance between the nozzle orifice and the peritoneum should be as large as possible [2, 7]. Periumbilical, perpendicular placement of the MDN is therefore ideal, if surgically possible (Figure 2A).…”

“…Such a large database could provide insight into the role of different nebulizers used on oncological outcome. Prior standard PIPAC applications before MDP-PIPAC (median, range) 1 (1)(2)(3)(4) Ongoing systemic chemotherapy between MDN-PIPAC procedures (n) 14…”

“…However, all nebulizers are based on the same/similar design as the standard technology. Therefore, the problem of local chemotherapy accumulation and inhomogeneous drug distribution pattern in the peritoneal cavity remains unresolved [2], which may affect the oncological efficacy of PIPAC [23]. Therefore, the optimal position of the standard PIPAC nozzle has been investigated in recent years in order to optimize the spatial distribution of chemotherapy [14, 24, 25].…”

“…However, for such reasons, PIPAC nebulizer technology has been extended by integrating three additional atomizer units into the nebulizer head in the horizontal plane at a distance of 6 120 degrees. Initial ex-vivo data from such multi-directional nebulizer (MDN) report an improved spatial drug distribution [2,9].…”