2001 OPEN FORUM Abstracts
EVALUTIONOF A NEW IN-LINE COLLAPSIBLE HOLDING CHAMBER (CHC) FOR DELIVERY OF INHALED MEDICATIONSTO THE MECHANICALLY VENTILATED PATIENT
Jolyon P. Mitchell, Sara-LouBates, Cathy C. Doyle, MarkW. Nagel, Robert W. Morton and James N. Schmidt Trudell Medical Aerosol Laboratory,London, Canada
Background: Delivery of medicationsfrom pressurized metered dose inhalers (pMDIs) to mechanically ventilated patientsis complicated by the presence of the endo-tracheal tube (ETT) as well as by?rain-out? of condensed water vapor, both of which make it more difficult todeliver the therapeutically beneficial portion of the dose contained in particles< 4.7 mm aerodynamic diameter to the patient. The AeroVent?-IIcollapsible holding chamber ((CHC), Monaghan Medical Corp., Plattsburgh, NY)has been re-designed to optimize transport of pMDI-delivered aerosols. It isintended to remain collapsed in-circuit when not in use, and is expanded whilstaerosol therapy is being delivered.
Methods: We compared thein vitro performance of a group of AeroVent?-II CHCs (n=5devices) for the delivery of a short-acting bronchodilator (Proventil?-HFA:108 mg albuterol sulfate ex actuator mouthpiece of the pMDI, Key Pharmaceuticals,Kenilworth, NJ) in both a dry (T=24C/RH=50%) and humidified (T=34C/RH=100%)adult ventilator circuit. Tidal breathing (750-ml) was simulated with inspiratory/expiratoryratio of 1:2 and rate ca. 15 breaths/min by means of an Infrasonics Adult Star®1500 ventilator. The CHC was located in the inspiratory limb of the ventilatorcircuit. Filter collection at the distal end of a 8-mm diameter endo-trachealtube was used to assess total emitted dose (TEDvent). In a parallelstudy conducted at room ambient conditions, the AeroVent?-II CHCswere connected directly to the induction port of an Andersen 8-stage cascadeimpactor operated in accordance with the US Pharmacopeia, in order to determinethe fine particle fraction (FPFimp, particles < 4.7 mm aerodynamicdiameter) leaving the CHC. Fine particle dose (FPDvent/imp) was thencalculated as the product of TDvent and FPFimp dividedby 100. Measurements of TDimp and FPDimp for the pMDIwithout CHC (n=5 canisters) were also undertaken by impactor to determine baselinedrug availability for this formulation.
Results: TEDvent(mean ± SD) with the AeroVent?-II CHCs in the dry ventilator circuitwas 54.0 ± 6.6 mg/dose, decreasing to 30.5 ± 4.0 mg when the circuit was humidified.FPFimp was 89.5 ± 1.3%. The absence of the ETT for the impactor measurementsis deemed unlikely to have had a significant effect on this parameter, sincethe coarse ballistic component of the aerosol had already been removed by theCHC. Fine particle dose (FPDvent/imp) ex AeroVent?-IICHCs was therefore estimated to be close to 48 mg (dry) and 27 mg (humidified).By comparison, TEDimp and FPDimp from the pMDI alone were79.1 ± 1.3 mg and 43.6 ± 1.7 mg respectively.
Conclusions: Under dryconditions, fine particle dose from the new AeroVent?-II CHCs wascomparable with that available from the pMDI alone. As expected, the presenceof a saturated environment in the humidified circuit reduced the delivery ofmedication. Nevertheless, fine particle dose was still almost 62% of that availablefrom the pMDI alone under ideal conditions (direct delivery ex actuator underdry conditions).