Respimat Delivery of Tiotropium Through Mechanical Ventilation

Abstract

Background: The Global Initiative for Chronic Obstructive Lung Disease supports the daily use of long-acting muscarinic antagonists (LAMAs), such as tiotropium, for long-term treatment regimens. LAMA agents are primarily designed for patients with spontaneous breathing and, unfortunately, none exist for intubated patients. The optimal inhaled drug dose and method of connecting Respimat to the ventilator system is unknown. We aimed to evaluate Respimat delivery with different adaptors and timing of priming during mechanical ventilation. Methods: A Draeger V300 ventilator operated under volume control (500 mL, 15 breaths/min, PEEP 5 cm H₂O, T_I 1.3 s) with heated humidification at 37 ○C was connected to an endotracheal tube, with an inline collecting filter connected to a lung model (Michigan Instruments, Kentwood, MI). The tiotropium Respimat (2.5 mg, Boehringer Ingelheim) was connected as follows: 1) an inline adaptor (RTC 26-C, Instrumentation Industries Inc.) was placed between the Y-adaptor and the inspiratory limb, 2) a T-adaptor was placed between the Y-adaptor and the endotracheal tube, and 3) a T-adaptor was placed between the endotracheal tube and an Ambu bag. Four actuations of tiotropium were administered, synchronized with inspiration or expiration, according to the ventilation waveforms. The drug was administered only at the beginning of inspiration with the Ambu bag. To test the inhaled drug dose with spontaneous breathing in a control group, the Respimat was connected to a collecting filter and then to a breath simulator (500 mL, 15 breaths/min, ASL 5000; IngMar Medical). The collected drug dose was eluted with a salt-base solvent and analyzed using high-performance liquid chromatography. Results: The inhaled dose for the spontaneous breathing was 8.4 ± 1.2%. The average inhaled drug dose percent was 4.44 ± 0.8% for the RTC- at inspiration, 15.36 ± 2.0% for the RTC- at expiration, 2.4 ± 1.2% for the T-adaptor at inspiration, 2.04 ± 0.1% for the T-adaptor at expiration, and 5.6 ± 2.9% for the Ambu bag. The figure below compares the inhaled doses. The inhaled dose of RTC-expiration was significantly greater than the other four groups (P < .001), and the inhaled dose with the Ambu bag was significantly greater than that with the T-adaptor (P = .035). Conclusions: Respimat delivery of tiotropium led to a greater drug dose with the new RTC adaptor only with expiratory synchronization.

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Comparison delivered dose among 5 methods