Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model.

Abstract

Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated, mechanically ventilated patients requires adequate delivery of aerosol to the lower respiratory tract. We determined the effect of ventilator mode, inspiratory flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery in a model of the trachea and bronchi. The model was ventilated through an endotracheal tube during controlled mechanical ventilation (CMV), assist control (AC), pressure support (PS), and continuous positive airway pressure (CPAP), separately with a dry and humidified ventilator circuit. Delivery of albuterol administered by a MDI and spacer on filter placed at the ends of the bronchi was measured by spectrophotometry (246 nm). Under dry conditions and with a frequency of 10 breaths/min, albuterol delivery with CMV (VT, 800 ml; 30.3 +/- 3.4%), AC (VT, 800 ml; 31.9 +/- 1.3%), PS 10 cm H2O (VT, 700 ml; 28.8 +/- 4.5%), or PS 20 cm H2O (VT, 800 ml; 30.9 +/- 1.8%) was lower than that observed with simulated spontaneous breaths with CPAP (VT, 800 ml; 39.2 +/- 1.4%) (p < 0.01 for all modes). Delivery was greater under dry (28.8 to 39%) than under humidified conditions (15.9 to 20.2%) (p < 0.005 in all modes). Albuterol delivery showed a linear correlation with both inspiratory time and duty cycle (r > 0.91). Lower respiratory tract delivery of aerosol from a MDI varied from 4.9 to 39.2%. We conclude that in addition to other known factors such as dose, type of spacer, and its position the technique of administering MDIs in mechanically ventilated patients markedly influences lower respiratory tract aerosol delivery.

Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of flow pattern

“…It has been shown, in an in vitro model of mechanical ventilation, that salbutamol delivery with a decelerating inspiratory flow pattern profile was increased by 20% from that given with a square wave [12]. Thus, although drug delivery to the lower respiratory tract was not measured in the present study, it is likely that the administration of salbutamol with pressure control is associated with increased drug delivery.…”

“…The use of low inspiratory flow, high VT (> 500 mL), high duty cycle, decelerating rather than square-wave inspiratory/time profile and 3±5 s end-inspiratory pause has been suggested to increase the effectiveness of MDI therapy [4,5,11,12]. However.…”

“…these recommendations are based mainly on aerosol delivery data [11,12], which may not reflect drug bronchodilator effect. Indeed, in recent studies, it was shown that neither application of a 5 s end-inspiratory pause nor increasing the VT, strategies which probably enhanced drug delivery [4,5,11,12], augmented the bronchodilator effect of six puffs salbutamol [13,14]. The current study demonstrated that, at constant VT and inspiratory time, changing the inspiratory flow/time profile did not have any effect on salbutamol-induced bronchodilation, given via MDI and spacer.…”

“…The timing of drug delivery and ventilator parameters during the administration of bronchodilators, such as the tidal volume (VT), inspiratory flow/time profile and end-inspiratory pause (breath-hold), have been suggested to influence drug delivery to target sites and, thus, bronchodilation [4,5,11,12]. These suggestions, however, are based on in vitro studies using models of mechanical ventilation.…”

Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients

“…When radioactive materials are employed to assess aerosol deposition, the type of radioactive label used may influence the findings [18]. Direct assay of the active drug in the MDI formulation is a simple, inexpensive and reliable method of measuring aerosol deposition [19][20][21].…”