Controlling Drug Delivery During Mechanical Ventilation: Breath-Enhanced Jet Nebulization

Abstract

Background:

Nebulized aerosol delivery during mechanical ventilation results in profound unregulated aerosol losses, which are a strong function of duty cycle or I/E ratio, bias flow and humidification. The present study describes a novel nebulizer and ventilator circuit that minimizes these influences by utilizing a design that results in aerosol generation primarily during inspiration (breath enhancement) and minimizes expiratory losses (breath actuation). The circuit facilitates control of supplemental humidification and functions independently of the brand of ventilator.

Methods:

The novel device may be operated continuously or via a stand-alone breath-actuated circuit. During a treatment, a 3-way valve directs all ventilator flow to the nebulizer resulting in aerosol generation primarily during inspiration. Special connections in the ventilator circuit bypass the effects of supplemental humidification and allow nebulizer removal for servicing without breaking the circuit. This combination results in controlled drug delivery of bronchodilators and other potent drugs over all ventilator settings without any electrical support. The addition of a pressure sensitive breath-actuated electrical circuit further increases efficiency affording the potential to deliver higher doses of less potent drugs such as antibiotics. The nebulizer is powered independently of the ventilator by wall gases at 50 PSIG. Nebulizer flows of 2 L/m in the continuous mode and 3.5 L/m during breath actuation were used. In vitro testing was performed on several commonly used ventilators over a wide range of breathing patterns, duty cycles and ventilator modes. The nebulizer was charged with radiolabeled saline and filled to 3 or 6 mL. Inhaled mass (IM) and mass balance were measured.

Results:

IM (% neb charge) mean ± SE, breath-enhanced 11.4 ± 0.9; breath-enhanced and breath actuated 27.2 ± 0.8.

Conclusions:

During jet nebulization, breath enhancement overcomes much of the variability in aerosol delivery introduced by the ventilator circuit providing a predictable delivered dose to the patient at any ventilator setting. The addition of breath actuation further enhances aerosol delivery for specialized drugs requiring high doses. The use of wall gases and stand-alone breath actuation standardizes conditions driving the nebulizer independent of ventilator design. Circuit design eliminates variation in humidification effects and allows nebulizer servicing without circuit interruption.