A Proof-of-Principle Setup for Delivery of Relenza® (Zanamivir) Inhalation Powder to Intubated Patients

J Aerosol Med Pulm Drug Deliv. 2016 Feb;29(1):30-35. doi: 10.1089/jamp.2014.1179. Epub 2015 May 14.

Abstract

Background: A fatal incident was reported when a mechanical ventilated patient received nebulization of a reconstituted Relenza® formulation. We propose a delivery system to introduce Relenza and other inhalation dry powders to intubated patients to avoid accidental fatalities in the future.

Methods: This is a bench study demonstrating the feasibility of a delivery system to introduce dry powder of Relenza to intubated patients. A dry powder inhaler placed within a delivery chamber was actuated by compressing a ventilation bag to disperse powder into a tracheal tube. The performance of two inhalers, a Diskhaler® and an Osmohaler, were compared. The effects of the length and size of the tracheal tube on the powder output and sizing of emitted powder were investigated using the more efficient Osmohaler.

Results: The efficiency of Osmohaler in delivering Relenza to the distal end [delivered dose=30.2±0.2% and fine particle fraction (FPF)=14.5±1.7%] was significantly higher than the Diskhaler (delivered dose=18.1±4.7% and FPF=3.4±2.1%). While no differences in the delivered dose and FPF were observed between the tracheostomy and endotracheal tubes of the same internal diameter, a larger endotracheal tube (9.0 mm internal diameter) gave a 6% higher FPF compared with the smaller counterpart (7.0 mm internal diameter).

Conclusion: The dry powder delivery system has been demonstrated to be capable of delivering Relenza formulation to the distal end of tracheal tubes with a reasonable delivered dose and FPF. It would be necessary for further investigation into incorporating the proposed powder delivery system within a mechanical ventilator, as well as animal and clinical studies to prove its applicability to deliver zanamivir dry powder to ventilated influenza patients in the intensive care setting.

Keywords: dry powder inhaler; endotracheal tube; influenza virus A (H1N1); tracheostomy tube; ventilated patients.